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In the fourth edition of Small Animal Internal Medicine, we The section focusing on immune-mediated disorders has
have retained our original goal of creating a practical text been reorganized to include chapters on:
with a strong clinical slant that is useful for both practition Current recommendations and interpretation of diag
ers and students. We have continued to limit authorship, nostic tests
with each author selected for clinical expertise in his or her A n overview of c o m m o n l y used drugs for treating
respective field, to ensure as much consistency as possible immune-mediated disorders
within and among sections of the book. We have continued Treatment protocols for managing c o m m o n immune-
to focus on the clinically relevant aspects of the most c o m m o n mediated disorders
problems i n internal medicine, presenting information i n a Hundreds of new clinical photographs, the majority in
concise, understandable, and logical format. Extensive use of full color
tables, algorithms, cross-referencing within and among sec Algorithms throughout the text to aid readers in the
tions, and a comprehensive index help make Small Animal decision-making process
Internal Medicine a quick, easy-to-use reference textbook. Extensive cross-referencing to other chapters and dis
cussions, providing a helpful "road map" and reducing
ORGANIZATION redundancy within the book
Hundreds of functionally color-coded summary tables
The book contains 14 sections organized by organ systems and boxes to draw the reader's eye to quickly accessible
(e.g., cardiology, respiratory) or when multiple systems are information, such as:
involved, by discipline (e.g., oncology, infectious diseases,
immune-mediated disorders). Each section, when possible,
begins with a chapter on clinical signs and differential diag Etiology
noses and is followed by chapters on indications, techniques,
and interpretation of diagnostic tests; general therapeutic
principles; specific diseases; and finally a table listing recom Differential diagnoses
mended drug dosages for drugs commonly used to treat
disorders within the appropriate organ system or discipline.
Each section is supported extensively by tables, photographs, Drugs (appearing within chapters)
and schematic illustrations, including many algorithms,
which address clinical presentations, differential diagnoses,
diagnostic approaches, and treatment recommendations. D r u g formularies (appearing at the end of each
Selected references and recommended readings are provided section)
under the heading "Suggested Readings" at the end of each
chapter. In addition, specific studies are cited i n the text by
author name and year of publication and are included in the Treatment
Suggested Readings.
KEY FEATURES OF THE FOURTH EDITION General information (e.g., formulas, clinical
pathology values, manufacturer information,
We have retained all of the features that were popular in the breed predispositions)
first three editions, and have significantly updated and
expanded the new fourth edition. New features include:
Finally, we are grateful to the many practitioners, faculty, and
Thoroughly revised and updated content, with expanded students worldwide who provided constructive comments
coverage of hundreds of topics throughout the text on the first three editions, thereby making it possible to
The expertise of three new authors for the sections dealing design an even stronger fourth edition. We believe the
with hepatobiliary and exocrine pancreatic disorders, expanded content, features, and visual presentation will be
metabolic and electrolyte disorders, and immune- positively received and will continue to make this book a
mediated disorders valuable, user-friendly resource for all readers.
New, separate sections and expanded focus on hematol RICHARD W . NELSON
ogy and immunology C . GUILLERMO C O U T O
Acknowledgements
We w o u l d like to extend our sincerest thanks to Greg, Eleanor, Cheri, Michael, Sue, Wendy, and
M i k e for their continued dedication and hard work to this project; to Catharine, Penny, and Sean
for their willingness to become involved i n this project; and to Tony W i n k e l , Maureen Slaten,
Celeste Clingan, and many others at M o s b y for their commitment and latitude in developing this
text.
Contents
C H A P T E R 1
Clinical Manifestations
of Cardiac Disease
Hypoglycemia
Hypoadrenocorticism
Electrolyte i m b a l a n c e (especially p o t a s s i u m , calcium)
Anemia
Sudden hemorrhage
Neurologic Causes
Cerebrovascular accident
Brain tumor
(Seizures)
Neuromuscular Disease
Important H i s t o r i c Information
usually assessed, but caudal mucous membranes (prepuce or Injected, Brick-Red Membranes
vagina) also can be evaluated. The C R T is assessed by apply
Polycythemia (erythrocytosis)
ing digital pressure to blanch the membrane; color should
Sepsis
return within 2 seconds. Slower refill times occur as a result
Excitement
of dehydration and other causes of decreased cardiac output Other causes of peripheral vasodilation
because of high peripheral sympathetic tone and vasocon
striction. Pale mucous membranes result from anemia or Cyanotic Mucous Membranes*
membranes should be compared with that of the oral m e m Right-to-left shunting congenital cardiac defect
Hypoventilation
branes i n polycythemic cats and dogs for evidence of dif
Shock
ferential cyanosis. If the oral membranes are pigmented, the
Cold exposure
ocular conjunctiva can be evaluated. Box 1-4 outlines causes
Methemoglobinemia
for abnormal mucous membrane color. Petechiae i n the
mucous membranes may be noticed i n dogs and cats w i t h Differential Cyanosis
platelet disorders (see Chapter 87). In addition, oral and Reversed patent ductus arteriosus (head and forelimbs
ocular mucous membranes are often areas where icterus receive normally oxygenated blood, but caudal part of
(jaundice) is first detected. A yellowish cast to these m e m body receives desaturated blood via the ductus, which
branes should prompt further evaluation for hemolysis (see arises from the descending aorta)
Chapter 83) or hepatobiliary disease (see Chapter 35).
Icteric Mucous Membranes
A b n o r m a l Arterial Pulses
Weak Pulses
Dilated c a r d i o m y o p a t h y
(Sub)aortic stenosis
Pulmonic stenosis
Shock
Dehydration
Strong Pulses
Excitement
Hyperthyroidism
Fever
Hypertrophic cardiomyopathy
known as a precordial thrill. This feels like a buzzing sensa cultation. The animal should be standing, i f possible, so that
tion on the hand. A precordial thrill is usually localized to the heart is i n its normal position. Panting i n dogs is discour
the area of maximal intensity of the murmur. aged by holding the animal's m o u t h shut. Respiratory noise
can be decreased further by placing a finger over one or both
EVALUATION FOR FLUID nostrils for a short time. Purring i n cats may be stopped by
ACCUMULATION holding a finger over one or both nostrils (Fig. 1-7), waving
Right-sided C H F promotes abnormal fluid accumulation an alcohol-soaked cotton ball near the cat's nose, or turning
within body cavities (Fig. 1-6; see also Fig. 9-3) or, usually on a water faucet near the animal. Various other artifacts can
less noticeably, i n the subcutis of dependent areas. Palpation interfere with auscultation, including respiratory clicks, air
and ballottement of the abdomen, palpation of dependent movement sounds, shivering, muscle twitching, hair rubbing
areas, and percussion of the chest i n the standing animal are against the stethoscope (crackling sounds), gastrointestinal
used to detect effusions and subcutaneous edema. F l u i d sounds, and extraneous r o o m noises.
accumulation secondary to right-sided heart failure is usually The traditional stethoscope has both a stiff, flat diaphragm
accompanied by abnormal jugular vein distention and/or and a bell on the chestpiece. The diaphragm, when applied
pulsations, unless the animal's circulating blood volume is firmly to the chest wall, allows better auscultation of higher-
diminished by diuretic use or other cause. Hepatomegaly frequency heart sounds than those of low frequency. The
and/or splenomegaly may also be noted in cats and dogs bell, applied lightly to the chest wall, facilitates auscultation
with right-sided heart failure. of lower-frequency sounds such as S and S (see the follow
3 4
of sound: frequency (pitch), amplitude of vibrations (inten for timing abnormal sounds. The point of maximal intensity
sity/loudness), duration, and quality (timbre). Sound quality ( P M I ) of any abnormal sounds should be located. The exam
is affected by the physical characteristics of the vibrating iner should focus o n cardiac auscultation separately from
structures. pulmonary auscultation because full assimilation of sounds
Because many heart sounds are difficult to hear, a coop from both systems simultaneously is unlikely. Pulmonary
erative animal and a quiet r o o m are important during aus- auscultation is described further i n Chapter 20.
Transient Heart Sounds dia, systemic arterial hypertension, or shortened P R inter
The heart sounds normally heard i n dogs and cats are S 1 vals. A muffled S can result from obesity, pericardial effusion,
1
(associated w i t h closure and tensing of the A V valves and diaphragmatic hernia, dilated cardiomyopathy, hypovole
associated structures at the onset of systole) and S (associ 2 mia/poor ventricular filling, or pleural effusion. A split or
ated with closure of the aortic and pulmonic valves following sloppy-sounding S may be normal, especially i n large dogs,
1
events of the cardiac cycle with the E C G and timing of the increased by pulmonary hypertension (for example, from
heart sounds. It is important to understand these events and heartworm disease, a congenital shunt with Eisenmenger's
identify the t i m i n g of systole (between S and S ) and diastole
1 2 physiology, or cor pulmonale). Cardiac arrhythmias often
(after S until the next S ) i n the animal. The precordial
2 1 cause variation i n the intensity (or even absence) of heart
impulse occurs just after S (systole), and the arterial pulse
1 sounds.
between S and S .
1 2 N o r m a l physiologic splitting of S can be heard in some 2
Gallop Sounds
The third (S ) and fourth (S ) heart sounds occur during
3 4
diastole (see Fig. 1-10) and are not normally audible in dogs
and cats. W h e n an S or S sound is heard, the heart may
3 4
a l i g n m e n t with the c l i n i c i a n ' s e a r c a n a l s (Top of picture is ferentiation of S from S is difficult. If both sounds are
3 4
rostral). The flat d i a p h r a g m of the c h e s t p i e c e is f a c i n g left, present, they may be superimposed, which is called a sum
a n d the c o n c a v e bell is f a c i n g right. mation gallop.
FIG 1 - 9
A p p r o x i m a t e locations of v a r i o u s v a l v e a r e a s o n chest w a l l . T, T r i c u s p i d ; P, p u l m o n i c ; A,
a o r t i c ; M, mitral.
TABLE 1-1
Grading of Heart M u r m u r s
GRADE MURMUR
best over the mitral valve area. These sounds have been asso
ciated with degenerative valvular disease (endocardiosis),
mitral valve prolapse, and congenital mitral dysplasia; a con
current mitral insufficiency m u r m u r may be present. In dogs
with degenerative valvular disease, a mitral click may be the
first abnormal sound noted, with a m u r m u r developing over
time. A n early systolic, high-pitched ejection sound at the
left base may occur i n animals with valvular pulmonic ste
nosis or other diseases that cause dilation of a great artery.
The sound is thought to arise from either the sudden check
FIG 1 - 1 0 ing of a fused p u l m o n i c valve or the rapid filling of a dilated
C a r d i a c c y c l e d i a g r a m d e p i c t i n g relationships a m o n g g r e a t vessel during ejection. Rarely, restrictive pericardial disease
vessel, ventricular a n d atrial pressures, ventricular v o l u m e , causes an audible pericardial knock. This diastolic sound is
heart sounds, a n d electrical a c t i v a t i o n . AP, A o r t i c pressure; caused by sudden checking of ventricular filling by the
ECG, e l e c t r o c a r d i o g r a m ; IC, isovolumic c o n t r a c t i o n ; IR, restrictive pericardium; its timing is similar to the S . 3
isovolumic r e l a x a t i o n ; LVP, left ventricular pressure; LAP, left
atrial pressure; LVV, left ventricular v o l u m e .
Cardiac Murmurs
Cardiac murmurs are described by their timing within the
cardiac cycle (systolic or diastolic, or portions thereof),
The S , also k n o w n as an S gallop or ventricular gallop, is
3 3 intensity, P M I o n the precordium, radiation over the chest
associated with low-frequency vibrations at the end of the wall, quality, and pitch. Systolic murmurs can occur in early
rapid ventricular filling phase. A n audible S in the dog or 3 (protosystolic), middle (mesosystolic), or late (telesystolic)
cat usually indicates ventricular dilation with myocardial systole or throughout systole (holosystolic). Diastolic
failure. The extra sound can be fairly l o u d or very subtle and murmurs generally occur in early diastole (protodiastolic) or
is heard best over the cardiac apex. It may be the only aus throughout diastole (holodiastolic). M u r m u r s at the very
cultable abnormality i n an animal with dilated cardiomy end of diastole are termed presystolic. Continuous murmurs
opathy. A n S gallop may also be audible i n dogs with
3 begin i n systole and extend through S into all or part of 2
advanced valvular heart disease and congestive failure. diastole. M u r m u r intensity is arbitrarily graded o n a I to V I
The S gallop, also called an atrial or presystolic gallop, is
4 scale (Table 1-1). The P M I is usually indicated by the hemi
associated with low-frequency vibrations induced by blood thorax (right or left) and intercostal space or valve area
flow into the ventricles during atrial contraction (just after where it is located, or by the terms apex or base. Because
the P wave of the E C G ) . A n audible S i n the dog or cat is
4 murmurs can radiate extensively, the entire thorax, thoracic
usually associated with increased ventricular stiffness and inlet, and carotid artery areas should be auscultated. The
hypertrophy, as with hypertrophic cardiomyopathy or hyper pitch and quality of a m u r m u r relate to its frequency and
thyroidism i n cats. A transient S gallop of u n k n o w n sig
4 subjective assessment. "Noisy" or "harsh" murmurs contain
nificance is sometimes heard in stressed or anemic cats. mixed frequencies. "Musical" murmurs are of essentially one
frequency with its overtones.
Other Transient Sounds M u r m u r s are also described by phonocardiographic con
Other brief abnormal sounds are sometimes audible. Systolic figuration (Fig. 1-11). A holosystolic (plateau-shaped)
clicks are mid-to-late systolic sounds that are usually heard m u r m u r begins at the time of S and is of fairly uniform
1
intensity throughout systole. L o u d holosystolic murmurs before and after the murmur. This type is also called an ejec
may mask the S and S sounds. A V valve insufficiency and
1 2 tion murmur because it occurs during blood ejection, usually
interventricular septal defects c o m m o n l y cause this type of because of ventricular outflow obstruction. A decrescendo
m u r m u r because turbulent blood flour occurs throughout m u r m u r tapers from its initial intensity over time; it may
ventricular systole. A crescendo-decrescendo or diamond- occur in systole or diastole. Continuous (machinery) mur
shaped m u r m u r starts softly, builds intensity i n midsystole, murs occur throughout systole and diastole.
and then diminishes; S and S can usually be heard clearly
1 2 S y s t o l i c m u r m u r s . Systolic murmurs can be decre
scendo, holosystolic (plateau-shaped), or ejection (cre
scendo-decrescendo) i n configuration. It can be difficult to
differentiate these by auscultation alone. But the most
important steps toward diagnosis include establishing that a
m u r m u r occurs i n systole (rather than diastole), determin
ing its P M I , and grading its intensity. Fig. 1-12 depicts the
typical P M I of various murmurs over the chest wall.
Functional murmurs usually are heard best over the left
heartbase. They are usually soft to moderate in intensity and
of decrescendo (or crescendo-decrescendo) configuration.
Functional murmurs may have no apparent cardiovascular
cause (e.g., "innocent" puppy murmurs) or can result from
an altered physiologic state (physiologic murmurs). Inno
cent puppy murmurs generally disappear by the time
the animal is approximately 6 months of age. Physiologic
murmurs have been associated with anemia, fever, high sym
pathetic tone, hyperthyroidism, marked bradycardia, periph
eral arteriovenous fistulae, hypoproteinemia, and athletic
FIG 1 - 1 1
The p h o n o c a r d i o g r a p h i c s h a p e (configuration) a s w e l l a s hearts. Aortic dilation (e.g., with hypertension) and dynamic
the timing of different murmurs a r e illustrated in this right ventricular outflow obstruction are other conditions
diagram. associated with systolic murmurs in cats.
FIG 1 - 1 2
The usual point of m a x i m a l intensity (PMI) a n d c o n f i g u r a t i o n for murmurs t y p i c a l of various
c o n g e n i t a l a n d a c q u i r e d c a u s e s a r e d e p i c t e d o n left (A) a n d right (B) chest w a l l s . AS,
aortic (valvular) stenosis; MVI, mitral v a l v e insufficiency; PDA, patent ductus arteriosus; PS,
p u l m o n i c stenosis; SAS, s u b a o r t i c stenosis; TVI, tricuspid v a l v e insufficiency; VSD, ventricu
lar septal defect. (From B o n a g u r a J D , Berkwitt L: C a r d i o v a s c u l a r a n d p u l m o n a r y disorders.
In Fenner W , e d i t o r : Quick reference to veterinary medicine, e d 2, P h i l a d e l p h i a , 1 9 9 1 , JB
Lippincott.)
The m u r m u r of mitral insufficiency is heard best at the (vessels). The m u r m u r is not interrupted at the time of
left apex, i n the area of the mitral valve. It radiates well dor- S ; instead, its intensity is often greater at that time. The
2
sally and often to the left base and right chest wall. M i t r a l m u r m u r becomes softer toward the end of diastole, and
insufficiency characteristically causes a plateau-shaped at slow heart rates it can become inaudible. Patent ductus
m u r m u r (holosystolic timing), but i n its early stages the arteriosus ( P D A ) is by far the most c o m m o n cause of a
m u r m u r may be protosystolic, tapering to a decrescendo continuous murmur. The P D A m u r m u r is loudest high
configuration. Occasionally this m u r m u r has a musical or at the left base above the pulmonic valve area; it tends to
"whoop-like" quality. W i t h degenerative mitral valve disease, radiate cranially, ventrally, and to the right. The systolic com
murmur intensity is related to disease severity. ponent is usually louder and heard well all over the chest.
Systolic ejection murmurs are most often heard at the left The diastolic component is more localized to the left base
base and are caused by ventricular outflow obstruction, in many cases. The diastolic component (and the correct
usually from a fixed narrowing (e.g., subaortic or p u l m o n i c diagnosis) may be missed i f only the cardiac apical area is
valve stenosis) or dynamic muscular obstruction. Ejection auscultated.
murmurs become louder as cardiac output or contractile Continuous murmurs can be confused with concurrent
strength increases. The subaortic stenosis m u r m u r is heard systolic ejection and diastolic decrescendo murmurs. But
well at the low left base and also at the right base because the with these so-called "to-and-fro" murmurs, the ejection (sys
murmur radiates up the aortic arch, which curves toward the tolic) component tapers i n late systole and the S can be 2
right. This m u r m u r also radiates up the carotid arteries and heard as a distinct sound. The most c o m m o n cause of to-
occasionally can be heard o n the calvarium. Soft (grade and-fro murmurs is the combination of subaortic stenosis
I-II/VI), nonpathologic systolic ejection (physiologic) with aortic insufficiency. Rarely, stenosis and insufficiency of
murmurs are c o m m o n i n sight hounds and certain other the pulmonic valve cause this type of murmur. Likewise,
large breeds; these can be related to a large stroke volume both holosystolic and diastolic decrescendo murmurs occur
(relative aortic stenosis), as well as breed-related left ven occasionally (e.g., with a ventricular septal defect and aortic
tricular outflow tract characteristics. The m u r m u r of pul insufficiency from loss of aortic root support). This also is
monic stenosis is best heard high at the left base. Relative not considered a true "continuous" murmur.
pulmonic stenosis occurs with greatly increased flow through
a structurally normal valve (e.g., with a large left-to-right Suggested Readings
shunting atrial or ventricular septal defect).
Braunwald E, Perloff JK: Physical examination of the heart and
Most murmurs heard o n the right chest wall are holosys circulation. In Zipes DP et al, editors: Brannwald's heart disease:
tolic, plateau-shaped murmurs, except for the subaortic ste a textbook of cardiovascular medicine, ed 7, Philadelphia, 2005,
nosis m u r m u r (above). The tricuspid insufficiency m u r m u r W B Saunders, pp 77-106.
is loudest at the right apex over the tricuspid valve. Its pitch Davidow EB, Woodfield )A: Syncope: pathophysiology and differ
or quality may be noticeably different from a concurrent ential diagnosis, Compend Contin Educ 23:608, 2001.
mitral insufficiency murmur, and it often is accompanied by Fabrizio F et al: Left basilar systolic murmur in retired racing grey
jugular pulsations. Ventricular septal defects also cause holo hounds, / Vet Intern Med 20:78, 2006.
systolic murmurs. The P M I is usually at the right sternal Haggstrom J, Kvart C, Hansson K: Heart sounds and murmurs:
border, reflecting the direction of the intracardiac shunt. A changes related to severity of chronic valvular disease in the
Cavalier King Charles Spaniel, / Vet Intern Med 9:75, 1995.
large ventricular septal defect may also cause the m u r m u r of
Hamlin RL: Normal cardiovascular physiology. In Fox PR, Sisson
relative pulmonic stenosis.
DD, Moise NS, editors: Canine and feline cardiology, ed 2, New
Diastolic m u r m u r s . Diastolic murmurs are u n c o m m o n York, 1999, W B Saunders, pp 25-37.
in dogs and cats. Aortic insufficiency from bacterial endo Kienle R: Pulse alterations. In Ettinger SJ, Feldman EC, editors:
carditis is the most c o m m o n cause, although congenital mal Textbook of veterinary internal medicine, ed 6, Philadelphia, 2005,
formation or degenerative aortic valve disease occasionally WB Saunders, pp 200-204.
occurs. Clinically relevant pulmonic insufficiency is rare but Koplitz SL, Meurs K M , Bonagura JD: Echocardiographic assess
would be more likely in the face of pulmonary hypertension. ment of the left ventricular outflow tract in the Boxer, / Vet Intern
These diastolic murmurs begin at the time of S and are 2
Med 20:904, 2006.
heard best at the left base. They are decrescendo i n configu Pedersen H D et al: Auscultation in mild mitral regurgitation in
dogs: observer variation, effects of physical maneuvers, and
ration and extend a variable time into diastole, depending
agreement with color Doppler echocardiography and phonocar
on the pressure difference between the associated great vessel
diography, / Vet Intern Med 13:56, 1999.
and ventricle. Some aortic insufficiency murmurs have a
Prosek R: Abnormal heart sounds and heart murmurs. In Ettinger
musical quality. SJ, Feldman EC, editors: Textbook of veterinary internal medicine,
C o n t i n u o u s m u r m u r s . As implied by the name, con ed 6, Philadelphia, 2005, WB Saunders, pp 195-200.
tinuous (machinery) murmurs occur throughout the Rishniw M , Thomas WP: Dynamic right ventricular outflow
cardiac cycle. They indicate that a substantial pressure obstruction: a new cause of systolic murmurs in cats, / Vet Intern
gradient exists continuously between two connecting areas Med 16:547, 2002.
C H A P T E R 2
FIG 2 - 2
C o m m o n r a d i o g r a p h i c e n l a r g e m e n t patterns. D i a g r a m s i n d i c a t i n g direction of e n l a r g e m e n t
of c a r d i a c c h a m b e r s a n d great vessels in the dorsoventral (A) a n d lateral (B) v i e w s . Ao,
A o r t a ( d e s c e n d i n g ) ; LA, left atrium; LAu, left a u r i c l e ; LV, left ventricle; MPA, m a i n pulmo
n a r y artery; RA, right atrium; RAu, right a u r i c l e ; RV, right ventricle. ( M o d i f i e d from
B o n a g u r a J D , Berkwitt L: C a r d i o v a s c u l a r a n d p u l m o n a r y d i s o r d e r s . In Fenner W , editor:
Quick reference to veterinary medicine, e d 3 , P h i l a d e l p h i a , 2 0 0 0 , JB Lippincott.)
the dorsocaudal heart border, w i t h elevation o f the m a i n - (Fig. 2-3). L A size is influenced by the pressure or volume
stem bronchi. O n D V or V D view, the mainstem b r o n c h i are load imposed, as well as the length of time the overload has
pushed laterally and curve slightly around a markedly been present. For example, m i t r a l regurgitation of slowly
enlarged L A (sometimes referred to as the "bowed-legged increasing severity may cause massive L A enlargement
cowboy sign"). A bulge i n the 2- to 3-o'clock position o f the without p u l m o n a r y edema i f the chamber has had time to
cardiac silhouette is c o m m o n i n cats and dogs w i t h concur dilate at relatively l o w pressures. Conversely, rupture of
rent left auricular enlargement. Massive L A enlargement chordae tendinae causes acute valvular regurgitation; there
sometimes appears as a large, rounded soft tissue opacity can be p u l m o n a r y edema w i t h relatively n o r m a l L A size
superimposed over the L V apical area o n D V ( V D ) view because atrial pressure rises quickly.
FIG 2 - 3
Lateral (A) a n d d o r s o v e n t r a l (B) v i e w s from a d o g with c h r o n i c mitral r e g u r g i t a t i o n .
M a r k e d left ventricular a n d atrial e n l a r g e m e n t a r e evident. D o r s a l d i s p l a c e m e n t of the
c a r i n a is seen in A ; the c a u d a l e d g e of the left atrium (arrows), s u p e r i m p o s e d over the
ventricular s h a d o w , a n d a p r o m i n e n t left a u r i c u l a r b u l g e (arrowhead) are seen in B .
N o r m a l Cardiac Waveforms
WAVEFORM EVENT
P A c t i v a t i o n of atrial muscle; n o r m a l l y is
positive in l e a d s II a n d aV F
AV, Atrioventricular.
BOX 2-2
V , r V (CV RL)
1 2 5 Fifth right ICS n e a r sternum
V (CV LL)
2 6 Sixth left ICS near sternum
V 3 Sixth left I C S , equidistant between V 2
and V 4
l o c a t e d near seventh d o r s a l s p i n o u s p r o c e s s .
Orthogonal Leads
RA, Right arm; LA, left arm; LL, left leg; ICS, intercostal space.
perpendicular to the torso. Other body positions may change A deflection from baseline (up or down) o f 10 small boxes
various waveform amplitudes and affect the calculated mean (1 cm) equals 1 m V at standard calibration. E C G reference
electrical axis ( M E A ) . However, if only heart rate and rhythm ranges for cats and dogs (Table 2-2) are representative o f
are desired, any recording position can be used. Front l i m b most n o r m a l animals, although complex measurements for
electrodes are placed at the elbows or slightly below, not some subpopulations can fall outside these ranges. For
touching the chest wall or each other. Rear l i m b electrodes example, endurance-trained dogs can have E C G measure
are placed at the stifles or hocks. W i t h alligator clip or ments that exceed the " n o r m a l " range, probably reflecting
button/plate electrodes, copious E C G paste or (less ideally) the training effects o n heart size. Such changes i n nontrained
alcohol is used to ensure good contact. C o m m u n i c a t i o n dogs suggest pathologic cardiac enlargement. M a n u a l fre
between two electrodes via a bridge o f paste or alcohol or by quency filters, available o n many E C G machines, can mark
physical contact should be avoided. The animal is gently edly attenuate the recorded voltages o f some waveforms
restrained i n position to m i n i m i z e movement artifacts. A when activated, although baseline artifact is reduced. The
relaxed and quiet patient produces a better quality tracing. effects o f filtering o n Q R S amplitude may complicate the
Holding the mouth shut to discourage panting or placing a assessment for E C G chamber enlargement criteria.
hand on the chest o f a trembling animal may be helpful.
A good E C G recording produces m i n i m a l artifact from SINUS RHYTHMS
patient movement, no electrical interference, and a clean The n o r m a l cardiac rhythm originates i n the sinus node and
baseline. The E C G complexes should be centered and totally produces the P - Q R S - T waveforms previously described. The
contained within the background gridwork so that neither P waves are positive i n caudal leads (II and aVF) and the P Q
the top nor bottom of the Q R S complex is clipped off. If (or P R ) intervals are consistent. Regular sinus rhythm is
the complexes are too large to fit entirely w i t h i n the grid, characterized by less than 10% variation i n the t i m i n g o f the
the calibration should be adjusted (e.g., from standard Q R S to Q R S (or R to R) intervals. N o r m a l l y the Q R S c o m
| [1 cm = 1 m V ] to 1/2 standard [0.5 c m = 1 m V ] ) . The cali plexes are narrow and upright i n leads II and aVF. However,
bration used during the recording must be k n o w n to an intraventricular conduction disturbance or ventricular
accurately measure waveform amplitude. A calibration enlargement pattern may cause them to be wide or abnor
square wave (1 m V amplitude) can be inscribed manually mally shaped.
during the recording i f this is not done automatically. The Sinus arrhythmia is characterized by cyclic slowing and
paper speed and lead(s) recorded also must be evident for speeding o f the sinus rate. This is usually associated with
interpretation. respiration; the sinus rate tends to increase on inspiration
A consistent approach to E C G interpretation is recom and decrease with expiration as a result o f fluctuations i n
mended. First the paper speed, lead(s) used, and calibration vagal tone. There may also be a cyclic change i n P-wave
are identified. Then the heart rate, heart rhythm, and M E A configuration ("wandering pacemaker"), with the P waves
are determined. Finally, individual waveforms are measured. becoming taller and spiked during inspiration and flatter i n
The heart rate is the number o f complexes (or beats) per expiration. Sinus arrhythmia is a c o m m o n and n o r m a l
minute. This can be calculated by counting the number o f rhythm variation i n dogs. It occurs i n resting cats but is not
complexes i n 3 or 6 seconds and then multiplying by 20 or often seen clinically. Pronounced sinus arrhythmia is associ
10, respectively. If the heart rhythm is regular, 3000 divided ated w i t h chronic p u l m o n a r y disease i n some dogs.
by the number o f small boxes (at paper speed 50 mm/sec) "Brady-" and "tachy-" are modifying terms that describe
between successive R R intervals equals the instantaneous abnormally slow or fast rhythms, respectively, without iden
heart rate. Because variations i n heart rate are so c o m m o n tifying intracardiac origin. Both sinus bradycardia and sinus
(in dogs especially), determining an estimated heart rate tachycardia are rhythms that originate i n the sinus node and
over several seconds is usually more accurate and practical are conducted normally; however, the rate o f sinus bradycar
than calculating an instantaneous heart rate. dia is slower than n o r m a l for the species, whereas that o f
Heart rhythm is assessed by scanning the E C G for irregu sinus tachycardia is faster than normal. Some causes o f sinus
larities and identifying individual waveforms. The presence bradycardia and tachycardia are listed i n B o x 2-3.
and pattern of P waves and Q R S - T complexes are deter Sinus arrest is absence o f sinus activity lasting at least
mined. The relationship between the P waves and QRS-Ts is twice as long as the animal's longest expected Q R S to Q R S
then evaluated. Calipers are often useful for evaluating the interval. A n escape complex usually interrupts the resulting
regularity and interrelationships o f the waveforms. Estima pause i f sinus activity does not resume i n time. Long pauses
tion of M E A is described o n p. 28. can cause fainting or weakness. Sinus arrest cannot be dif
Individual waveforms and intervals are usually measured ferentiated with certainty from sinoatrial (SA) block by the
using lead II. Amplitudes are recorded i n millivolts and surface E C G . Fig. 2-8 illustrates various sinus rhythms.
durations i n seconds. O n l y one thickness o f the inscribed
pen line should be included for each measurement. A t ECTOPIC RHYTHMS
25 mm/sec paper speed, each small (1 m m ) box o n the E C G Impulses originating from outside the sinus node (ectopic
gridwork is 0.04 seconds i n duration (from left to right). A t impulses) are abnormal and create an arrhythmia (dysrhyth
50 mm/sec paper speed, each small box equals 0.02 seconds. mia). Ectopic impulses are described o n the basis o f their
TABLE 2-2
Heart Rate
0.4 mV 0.2 mV
PR interval
2.5 mV (small breeds) 0.9 mV in any lead; Q R S total in any lead <1.2 mV
3 mV (large breeds)
ST segment deviation
T wave
Normally <25% of R wave height; can be positive, Maximum 0.3 mV; can be positive (most common), negative,
negative, or biphasic or biphasic
QT interval duration
0.15-0.25 (to 0.27) sec; varies inversely with heart rate 0.12 to 0.18 (range 0 . 0 7 to 0.2) sec; varies inversely with
heart rate
Chest Leads
V ; rV : positive T wave
1 2
R wave 1.0 mV maximum
V : S wave 0.8 mV maximum; R wave
2
2.5 mV maximum
V : S wave 0 . 7 mV maximum; R wave
4
3 mV maximum
V : negative Q R S ; negative T wave (except Chihuahua)
10
R / Q <1.0; negative T wave
Each small box on the E C G paper grid is 0.02 second wide at 50 mm/sec paper speed, 0.04 second wide at 25 mm/sec, and 0.1 mV high
at a calibration of 1 cm = 1 mV.
* Range may extend lower for large breeds and higher for toy breeds.
May be greater in young (under 2 years old), thin, deep-chested dogs.
general site o f o r i g i n (atrial, junctional, supraventricular, heart. Premature ectopic impulses (complexes) occur singly
ventricular) and their t i m i n g (Fig. 2-9). Timing refers to or i n multiples; groups o f three or more constitute an episode
whether the impulse occurs earlier than the next expected of tachycardia. Episodes o f tachycardia can be brief (parox
sinus impulse (premature) or after a longer pause (late or ysmal tachycardia) or quite prolonged (sustained tachycar
escape). Escape complexes represent activation o f a subsid dia). W h e n one premature complex follows each n o r m a l
iary pacemaker and function as a rescue mechanism for the Q R S , a bigeminal pattern exists; the origin of the premature
BOX 2-3
Sinus Tachycardia
Hyperthermia/fever
Hyperthyroidism
FIG 2 - 8
Sinus rhythms. A , Sinus rhythm in n o r m a l cat. Lead II, 2 5 m m / s e c . B , Sinus a r r h y t h m i a
with w a n d e r i n g p a c e m a k e r in a d o g . N o t e g r a d u a l v a r i a t i o n in P-wave height a s s o c i a t e d
with respiratory c h a n g e s in heart rate; this v a r i a t i o n is n o r m a l in the d o g . Lead a V F ,
2 5 m m / s e c . C , Sinus b r a d y c a r d i a . L e a d II, 2 5 m m / s e c , d o g .
FIG 2 - 9
Diagrams illustrating the appearance of ectopic complexes. Abnormal impulses can origi
nate (A) above the AV node (supraventricular) or from within the ventricles (ventricular).
Supraventricular ectopic complexes have a normal-appearing Q R S . A n abnormal P wave
usually precedes a complex originating in atrial tissue; no P wave (or a retrograde P wave
in the ST segmentnot shown) is common with an impulse originating from the AV junction.
Ventricular-origin QRS complexes have a different configuration from the normal sinus QRS.
The timing (B) of ectopic complexes refers to whether they appear before the next expected
sinus complex (premature or early) or after a longer than expected pause (escape or late).
fusion complexes helps i n differentiating ventricular tachy activity i n the ventricles; the E C G consists of an irregularly
cardia from S V T with abnormal (aberrant) intraventricular undulating baseline (Fig. 2-12). The ventricles cannot func
conduction. tion as a p u m p because coordinated mechanical activity
Polymorphic ventricular tachycardia is characterized by cannot occur i n the presence of incoordinated electrical acti
QRS complexes that vary i n size, polarity, and often rate; vation. Ventricular flutter, w h i c h appears as rapid sine-wave
sometimes the Q R S configuration appears as i f it were rotat activity o n the E C G , may precede fibrillation. "Course" ven
ing around the isoelectric baseline. Torsades de pointes is a tricular fibrillation ( V F ) has larger E C G oscillations than
specific form of polymorphic ventricular tachycardia associ "fine"VF.
ated with Q - T interval prolongation.
Escape Complexes
Accelerated Ventricular Rhythm Ventricular asystole is the absence of ventricular electrical
Also called idioventricular tachycardia, accelerated ventricu (and mechanical) activity. Escape complexes and escape
lar rhythm is a ventricular-origin rhythm with a rate of rhythms are a protective mechanism. A n escape complex
about 60 to 100 beats/min i n the dog (perhaps somewhat occurs after a pause i n the dominant (usually sinus) rhythm.
faster in the cat). Because the rate is slower than true ven If the dominant rhythm does not resume, the escape focus
tricular tachycardia, it is usually a less serious rhythm dis continues to discharge at its o w n intrinsic rate. Escape
turbance. A n accelerated ventricular rhythm may appear rhythms are usually regular. Escape activity originates from
intermittently during sinus arrhythmia, as the sinus rate automatic cells w i t h i n the atria, the A V junction, or the ven
decreases; the ventricular rhythm is often suppressed as the tricles (see Fig. 2-10, G). Ventricular escape rhythms (idio
sinus rate increases. This is c o m m o n i n dogs recovering from ventricular rhythms) usually have an intrinsic rate less than
motor vehicle trauma. Often this rhythm disturbance has no 40 to 50 beats/min i n the dog and 100 beats/min i n the cat,
deleterious effects, although it could progress to ventricular although higher ventricular escape rates can occur. Junc
tachycardia, especially i n clinically unstable patients. tional escape rhythms usually range from 40 to 60 beats/min
in the dog, w i t h a faster rate expected i n the cat. It is impor
Ventricular Fibrillation tant to differentiate escape from premature complexes.
Ventricular fibrillation is a lethal rhythm that is character Escape activity should never be suppressed w i t h antiarrhyth
ized by multiple reentrant circuits causing chaotic electrical mic drugs.
FIG 2 - 1 2
Ventricular fibrillation. N o t e c h a o t i c b a s e l i n e motion a n d a b s e n c e of o r g a n i z e d w a v e
forms. A , C o a r s e fibrillation; B , fine fibrillation. Lead II, 2 5 m m / s e c , d o g .
left anterior fascicular block (LAFB) pattern is c o m m o n i n the A V node (extranodal) and allows early depolarization
cats with hypertrophic cardiomyopathy. (represented by the delta wave) of a part o f the ventricle
distant to where normal ventricular activation begins. Other
Ventricular Preexcitation accessory pathways connect the atria or dorsal areas of the
Early activation (preexcitation) of part of the ventricular A V node directly to the bundle of H i s . These cause a short
myocardium can occur when there is an accessory conduc P R interval without early Q R S widening. Preexcitation can
tion pathway that bypasses the normal slow-conducting A V be intermittent or concealed (not evident on E C G ) . The
nodal pathway. Several types of preexcitation and accessory danger with preexcitation is that a reentrant supraventricu
pathways have been described. Most cause a shortened P R lar tachycardia can occur using the accessory pathway and
interval. Wolff-Parkinson-White ( W P W ) preexcitation is A V node (also called AV reciprocating tachycardia). Usually
also characterized by early widening and slurring of the Q R S the tachycardia impulses travel into the ventricles via the A V
by a so-called delta wave (Fig. 2-15). This pattern occurs node (antegrade or orthodromic conduction) and then back
because the accessory pathway (Kent's bundle) lies outside to the atria via the accessory pathway, but sometimes the
FIG 2 - 1 4
E C G from a d o g that d e v e l o p e d right b u n d l e b r a n c h b l o c k a n d first-degree A V block after
d o x o r u b i c i n therapy. Sinus a r r h y t h m i a , Leads I a n d II, 2 5 m m / s e c , 1 c m = 1 mV.
FIG 2 - 1 5
Ventricular p r e e x c i t a t i o n in a cat. N o t e s l o w e d Q R S upstroke (delta w a v e ; arrows)
i m m e d i a t e l y f o l l o w i n g e a c h P w a v e . L e a d II, 5 0 m m / s e c , 1 c m = 1 mV.
direction is reversed. Rapid A V reciprocating tachycardia can 2. F i n d the lead (I, II, III, a V R , a V L , or aVF) with the
cause weakness, syncope, congestive heart failure, and death. most isoelectric Q R S (positive and negative deflections
The presence o f the W P W pattern o n E C G i n conjunction are about equal). Then identify the lead perpendicular
with reentrant supraventricular tachycardia that causes clin to this lead o n the hexaxial lead diagram (see Fig. 2-6).
ical signs characterizes the W P W syndrome. If the Q R S i n this perpendicular lead is mostly positive,
the M E A is toward the positive pole of this lead. If the
MEAN ELECTRICAL AXIS Q R S i n the perpendicular lead is mostly negative, the
The mean electrical axis ( M E A ) describes the average direc M E A is oriented toward the negative pole. If all leads
tion of the ventricular depolarization process i n the frontal appear isoelectric, the frontal axis is indeterminate.
plane. It represents the summation of the various instanta Fig. 2-6 shows the normal M E A range for dogs and
neous vectors that occur from the beginning until the end cats.
of ventricular muscle activation. Major intraventricular con
duction disturbances and/or ventricular enlargement pat CHAMBER ENLARGEMENT AND BUNDLE
terns can shift the average direction of ventricular activation BRANCH BLOCK PATTERNS
and therefore the M E A . O n l y the six frontal plane leads are Changes i n the E C G waveforms can suggest enlargement or
used to determine M E A . Either o f the following methods can abnormal conduction w i t h i n a particular cardiac chamber.
be used: However, enlargement does not always produce these
changes. A widened P wave has been associated with L A
1. Find the lead (I, II, III, a V R , a V L , or aVF) with the enlargement (p mitrale); sometimes the P wave is notched
largest R wave (note: the R wave is a positive deflec as well as wide. Tall, spiked P waves (p pulmonale) can
tion). The positive electrode of this lead is the approx accompany R A enlargement. W i t h atrial enlargement, the
imate orientation of the M E A . usually obscure atrial repolarization (T ) wave may be
a
evident as a baseline shift i n the opposite direction of the Other QRS Abnormalities
P wave. Small-voltage Q R S complexes sometimes occur. Causes of
A right-axis deviation and an S wave i n lead I are strong reduced Q R S amplitude include pleural or pericardial effu
criteria for R V enlargement (or R B B B ) . Other E C G changes sions, obesity, intrathoracic mass lesions, hypovolemia, and
can usually be found as well. Three or more of the criteria hypothyroidism. Small complexes are occasionally seen i n
listed i n Box 2-4 are generally present when right ventricular dogs without identifiable abnormalities.
enlargement exists. R V enlargement (dilation or hypertro Electrical alternans is an every-other-beat recurring
phy) is usually pronounced i f it is evident o n the E C G alteration i n Q R S complex size or configuration. This is
because L V activation forces are normally so dominant. L V most often seen with large volume pericardial effusions (see
dilation and eccentric hypertrophy (see Chapter 3) often Chapter 9).
increase R-wave voltage i n the caudal leads (II and aVF) and
widen the Q R S . L V concentric hypertrophy inconsistently ST-T ABNORMALITIES
produces a left-axis deviation. The ST segment extends from the end of the Q R S complex
Conduction block i n the major ventricular conduction (also called the J-point) to the onset of the T wave. In dogs
pathways disturbs the normal activation process and alters
QRS configuration. Electrical activation of ventricular
muscle regions served by a diseased bundle branch occurs
late and progresses slowly. This widens the Q R S complex and BOX 2-4
shifts the terminal Q R S orientation toward the area of
Ventricular Chamber Enlargement and Conduction
delayed activation. Box 2-4 and Fig. 2-16 summarize E C G
Abnormality Patterns
patterns associated with ventricular enlargement or conduc
tion delay. Box 2-5 lists c o m m o n clinical associations. Normal
Right-axis deviation
S wave present in lead I
S wave in V 2-3 larger than R wave or >0.8 mV
Q-S (W shape) in V10
Left-axis deviation
R wave in lead I taller than R wave in leads II or aV F
N o S wave in lead I
fascicular block; LV, left ventricular; RVE, right ventricular (incomplete LBBB)
enlargement; RBBB, right bundle branch block.
BOX 2-5 BOX 2-6
C l i n i c a l Associations of E C G Enlargement Patterns Causes of ST Segment, T Wave, and Q T Abnormalities
Left Atrial Enlargement Depression of J Point/ST Segment
Mitral insufficiency (acquired or congenital) Myocardial ischemia
Cardiomyopathies Myocardial infarction/injury (subendocardial)
Patent ductus arteriosus Hyperkalemia or hypokalemia
Subaortic stenosis Cardiac trauma
Ventricular septal defect Secondary change (ventricular hypertrophy, conduction
disturbance, VPCs)
Right Atrial Enlargement
Digitalis ("sagging" appearance)
Tricuspid insufficiency (acquired or congenital) Pseudodepression (prominent T ) a
Hypocalcemia
Left Ventricular Enlargement (Hypertrophy)
Hypokalemia
Hypertrophic cardiomyopathy Quinidine toxicity
Subaortic stenosis Ethylene glycol poisoning
Secondary to prolonged QRS
Right Ventricular Enlargement
Hypothermia
Pulmonic stenosis Central nervous system abnormalities
Tetralogy of Fallot
Tricuspid insufficiency (acquired or congenital) Shortening of QT Interval
Severe heartworm disease Hypercalcemia
Severe pulmonary hypertension (of other cause) Hyperkalemia
Digitalis toxicity
Large T Waves
Myocardial hypoxia
and cats this segment tends to slope into the following Ventricular enlargement
T-wave, so clear demarcation is u n c o m m o n . A b n o r m a l ele Intraventricular conduction abnormalities
vation (>0.15 m V in dogs or 0.1 m V i n cats) or depression Hyperkalemia
(>0.2 m V in dogs or >0.1 m V i n cats) of the J point and ST Metabolic or respiratory diseases
segment i n leads I, II, or a V F may be significant and can be Normal variation
caused by ischemia and other types of myocardial injury.
Tented T Waves
Atrial enlargement or tachycardia can cause pseudode
pression of the ST segment because of prominent T waves. Hyperkalemia
a
BOX 2-7
ECG Changes Associated With Electrolyte Imbalance and Selected Drug Adverse Effects/Toxicity
AV, Atrioventricular.
(except swimming), strenuous exercise, and sleep. This is
useful for detecting and quantifying intermittent cardiac
arrhythmias and therefore helps identify cardiac causes of
syncope and episodic weakness. Holter monitoring is also
used to assess the efficacy o f antiarrhythmic drug therapy
and to screen for arrhythmias associated with cardiomyopa
thy or other diseases. The Holter monitor is a small battery-
powered digital or analog tape recorder worn by the patient,
typically for 24 hours. Two or three E C G channels are
recorded from modified chest leads using adhesive patch
electrodes. D u r i n g the recording period, the animal's activi
ties are noted i n a patient diary for later correlation with
simultaneous E C G events. A n event button on the Holter
recorder can be pressed to mark the time a syncopal or other
episode is witnessed.
The digitized recording is analyzed using computer algo
rithms that classify the recorded complexes. Evaluation and
editing by a trained Holter technician experienced with vet
erinary recordings are important for accurate analysis. Fully
automated computer analysis can result i n significant mis-
classification of Q R S complexes and artifacts from dog and
cat recordings. A summary report and selected portions of
FIG 2 - 1 7
the recording are enlarged and printed for examination by
Progressive E C G c h a n g e s that d e v e l o p with w o r s e n i n g the clinician. Evaluation of a full disclosure print-out o f the
+
h y p e r k a l e m i a (scale represents serum K c o n c e n t r a t i o n in entire recording is also helpful when compared with the
m E q / L ) . A l t h o u g h E C G c h a n g e s c o r r e l a t e p o o r l y with serum selected E C G strips and the times of clinical signs and/or
+
K c o n c e n t r a t i o n , they a c c u r a t e l y reflect c a r d i a c electrophys activities noted i n the patient diary (see Suggested Readings
iologic changes.
for more information). A Holter monitor, hook-up supplies,
and analysis can be obtained from some commercial human
Holter scanning services, as well as many veterinary teaching
hospitals and cardiology referral centers.
whereas hypercalcemia and hypernatremia tend to coun Wide variation i n heart rate is seen throughout the day
teract them. i n n o r m a l animals. In dogs m a x i m u m heart rates o f up to
M a r k e d E C G changes caused by other electrolyte distur 300 beats/min have been recorded with excitement or activ
bances are u n c o m m o n . Severe hypercalcemia or hypocalce ity. Episodes o f bradycardia (<50 beats/min) are common,
mia could have noticeable effects (Table 2-3 on p. 34), but especially during quiet periods and sleep. Sinus arrhythmia,
this is rarely seen clinically. Hypomagnesemia has no reported sinus pauses (sometimes for more than 5 seconds), and occa
effects o n the E C G , but it can predispose to digoxin toxicity sional second-degree A V block are apparently c o m m o n in
and exaggerate the effects o f hypocalcemia. dogs, especially at times when mean heart rate is lower. In
normal cats heart rates also vary widely over 24 hours (e.g.
COMMON ARTIFACTS from ~70 to ~290 beats/minute. Regular sinus rhythm pre
Fig. 2-19 o n p. 35 illustrates some c o m m o n E C G artifacts. dominates i n n o r m a l cats, and sinus arrhythmia is evident
Electrical interference can be m i n i m i z e d or eliminated by at slower heart rates. Ventricular premature complexes occur
properly grounding the E C G machine; turning off other only sporadically i n n o r m a l dogs and cats; their prevalence
electrical equipment or lights o n the same circuit or having likely increases only slightly with age.
a different person restrain the animal may also help. Other
artifacts are sometimes confused with arrhythmias; how Event Recording
ever, artifacts do not disturb the underlying cardiac rhythm. Cardiac event recorders are smaller than typical Holter units
Conversely, ectopic complexes often disrupt the underlying and contain a microprocessor with a memory loop that can
rhythm and are followed by a T wave. Careful examination store a brief period o f a single modified chest lead E C G . The
for these characteristics usually allows differentiation event recorder can be w o r n for periods of a week or so, but
between intermittent artifacts and arrhythmias. it cannot store prolonged, continuous E C G activity. Event
recorders are used most often to determine whether episodic
AMBULATORY ELECTROCARDIOGRAPHY weakness or syncope is caused by a cardiac arrhythmia.
Holter Monitoring W h e n an episode is observed, the owner activates the
Holter monitoring allows the continuous recording o f recorder, which then stores the E C G from a predetermined
cardiac electrical activity during n o r m a l daily activities time frame (e.g., from 30 seconds before activation to 30
FIG 2 - 1 8
+
E C G s r e c o r d e d in a f e m a l e P o o d l e with A d d i s o n ' s d i s e a s e at presentation (A), (K =
+ + +
1 0 . 2 ; N a = 1 3 2 m E q / L ) , a n d 2 d a y s later after treatment (B), (K = 3 . 5 ; N a =
1 4 4 m E q / L ) . N o t e a b s e n c e of P w a v e s , a c c e n t u a t e d a n d tented T w a v e s (especially in
chest leads), shortened Q T interval, a n d slightly w i d e n e d Q R S c o m p l e x e s in A c o m p a r e d
with B. Leads a s m a r k e d , 2 5 m m / s e c , 1 c m = 1 mV.
seconds after) for later retrieval and analysis. Implantable cator o f autonomic function, and possibly o f prognosis, for
(subcutaneous) recording devices have also been used i n veterinary patients is being explored (see Suggested Readings).
some veterinary patients and can allow intermittent E C G
monitoring over an extended time frame. Signal-Averaged
Electrocardiography (SAECG)
OTHER METHODS OF ECG ASSESSMENT Digital signal averaging o f the E C G provides a means of
Heart Rate Variability (HRV) enhancing E C G signal resolution by discarding random
Phasic fluctuations i n vagal and sympathetic tone during the components (noise) so that small-voltage potentials that
respiratory cycle, and also during slower periodic oscillations may occur at the end o f the Q R S complex and into the early
of arterial blood pressure, influence the variation i n time ST segment can be detected. These so-called ventricular late
between consecutive heartbeats. HRV refers to the fluctua potentials can be found i n patients with injured myocar
tion of beat-to-beat time intervals around their mean value. dium; they indicate the presence of conditions that predis
H R V is influenced by baroreceptor function as well as by the pose to reentrant ventricular tachyarrhythmias. The presence
respiratory cycle and sympathetic/parasympathetic balance. of late potentials on S A E C G has been identified i n some
The degree of H R V decreases with severe myocardial dys D o b e r m a n Pinschers w i t h ventricular tachycardia and sig
function and heart failure, as well as other causes of increased nificant ventricular dysfunction, but the sensitivity for pre
sympathetic tone. The variation i n instantaneous heart rate dicting risk o f ventricular tachycardia is unclear (see
(R-to-R intervals) can be evaluated as a function of time Suggested Readings).
(time-domain analysis) as well as i n terms of the frequency
and amplitude o f its summed oscillatory components (fre
quency-domain or power spectral analysis). Frequency- ECHOCARDIOGRAPHY
domain analysis allows assessment o f the balance between
sympathetic and vagal modulation o f the cardiovascular Echocardiography (cardiac ultrasonography) is an impor
system. The potential clinical usefulness o f H R V as an i n d i tant noninvasive tool for imaging the heart and surrounding
TABLE 2-3
Miniature
(Morrison '92)
20 3 (1.4-9) 20 (16-28) 10 (8-16) 5(4-6) 8 (6-10) - - 47 (35-57) 12 (8-18) 10 (8-13) 1.2
Poodle
(CRIPPA '92)
Beagle 20 8.9 1.5 26.3 (19.5-33.1) 15.7 (8.9-22.5) 8.2 (4.4-12) 11.4 (7.6-15.2) 6.7 (4.5-8.9) 9.6 (6.6-12.6) 40 (22-58)
West Highland White 34 9.4 2.4 27.2 (21.6-32.8) 16.8 (12.8-20.8) 6.7 (4.7-8.7) 9.8 (6.8-12.8) 7.2 (4.6-9.8) 9.7 (7.1-12.3) 36 (2646)
(Boode '02)
Terrier
English Cocker
(Gooding '86)
12 12.2 2 . 2 5 33.8 (27.240.4] 22.2 (16.6-27.8) 7.9 (5.7-10.1) - - - 34.3 (25.3-43.3)
Spaniel
Welsh Corgie (Morrison '92)
20 15 (8-19] 32 (28-40) 19 (12-23) 8 (6-10) 12 (8-13) - 44 (33-57) 21 (12-24) 18 (15-22) 1.17
(Sisson '91)
English Pointer 16 19.2 2 . 8 39.2 (34.4-44) 25.3 (20.5-30.1) 7.1 (5.7-8.5) 11.5 (8.9-14.1) 6.9 (4.7-9.1) 10.6 (8.6-12.6) 35.5 (27.5-43.5) 22.6 (18.6-22.6) 24.1 (20.7-27.5) 0.94 (0.8-1.08)
Afghan Hound (Morrison '92)
20 23 (17-36) 42 (33-52) 28 (20-37) 9 (7-11) 12 (9-18) - - 33 (2448) 26 (18-35) 26 (20-34) 1.0
(Page '93)
Greyhound 16 26.6 3.5 44.1 (28.1-50.1) 32.5 (25.5-39.5] 12.1 (8.7-15.5) 15.3 (10.9-19.7) 10.6 (7.2-14) 13.4 (8.2-18.6) 25.3 (12.7-37.9)
(Herrtage '94)
Boxer 30 28 7 . 1 40 (30-50) 26.8 10 (6-14) 15 (11-19) 9 (5-13) 13 (9-17) 33 (17-49) 23 (19-27) 22 (18-26) 1.06 (1.04-1.08)
(Snyder '95)
Greyhound 11 29.1 3 . 7 46.9 (40.7-53.1] 33.3 (28.1-38.5) 11.6 (8.2-15) 13.4 (10-16.8) 28.8 (20.4-37.2)
Golden 20 32 (23-41) 45 (37-51) 27 (18-35) 10 (8-12)
-15 (10-19)
- 39 (27-55) 27 (16-32) 24 (14-27)
Retriever (Morrison '92)
- - 1.13
thickness in systole; IVS = interventricular septal thickness in diastole; IVS = interventricular septal thickness in systole; FS = left ventricular fractional shortening.
d S
FIG 2 - 1 9
C o m m o n E C G artifacts. A , 6 0 H z electrical interference; Lead III, 2 5 m m / s e c , d o g .
B, Baseline movement c a u s e d by p a n t i n g ; Lead II, 2 5 m m / s e c , d o g . C , R e s p i r a t o r y
motion artifact; Lead V , 5 0 m m / s e c , d o g . D , S e v e r e muscle tremor artifact; Lead V ,
3 3
Structures. Anatomic relationships as well as cardiac func Like other diagnostic modalities, echocardiography is
tion can be assessed by evaluating cardiac chamber size, wall best used w i t h i n the context o f a thorough history, cardio
thickness, wall motion, valve configuration and m o t i o n , and vascular examination, and other appropriate tests. Technical
proximal great vessels and other parameters. Pericardial and expertise is essential to adequately perform and interpret the
pleural fluid are easily detected, and mass lesions w i t h i n and echocardiographic examination. The importance o f the
adjacent to the heart can be identified. Echocardiographic echocardiographer's skill and understanding o f n o r m a l and
examination can usually be performed w i t h m i n i m a l or no abnormal cardiovascular anatomy and physiology cannot be
chemical restraint. overemphasized. The ultrasound equipment used as well as
individual patient characteristics also affect the quality of animal's dependent side. Some animals can be adequately
images obtained. Sound waves do not travel well though imaged while standing. Shaving a small area of hair over the
bone (e.g., ribs) and air (lungs); these structures may pre transducer placement site can improve skin contact and
clude good visualization of the entire heart. image clarity Coupling gel is applied to produce air-free
contact between skin and transducer. The transducer is
BASIC PRINCIPLES placed over the area of the precordial impulse (or other
Echocardiography uses pulsed, high-frequency sound waves appropriate site), and its position is adjusted to find a good
that are reflected, refracted, and absorbed by body tissue "acoustic w i n d o w " that allows clear visualization of the
interfaces. O n l y the reflected portion can be received and heart. The right and left parasternal transducer positions are
processed for display. Transducer frequency, power output, used most often. M i n o r adjustment of the animal's forelimb
and various processing controls influence the intensity and or torso position may be required to obtain a good acoustic
clarity of the displayed echo images. Three echo modalities window. Once the heart is located, the transducer is angled
are used clinically: M - m o d e , two-dimensional (2-D, real or rotated and the echocardiograph's controls for factors
time), and Doppler. Each has important applications such as beam strength, focus, and postprocessing parameters
(described i n the subsequent sections). are adjusted as necessary to optimize the image. Optimal
Sound waves are propagated through soft tissue at a char visualization generally is achieved for 2-D and M - m o d e
acteristic speed (~1540 m/sec), so the thickness, size, and studies when the ultrasound beam is perpendicular to the
location of various structures i n relation to the origin of the cardiac structures and endocardial surfaces of interest. Image
ultrasound beam can be determined at any point i n time. artifacts are c o m m o n and can m i m i c a cardiac abnormality.
Because the intensity of the ultrasound beam decreases as it If the suspected lesion can be visualized i n more than one
penetrates into the body (because of beam divergence, imaging plane, it is more likely to be real.
absorption, scatter, and reflection of wave energy at tissue The echocardiographic examination includes carefully
interfaces), echoes returning from deeper structures tend to obtained M - m o d e measurements and all standard 2-D
be weaker. W h e n the ultrasound beam (2-D and M - m o d e ) imaging planes from both sides of the chest, as well as any
is perpendicular to the imaged structure, stronger echos are other views needed to further evaluate specific lesions.
returned. Also, greater mismatch i n acoustic impedance Doppler evaluation provides important additional informa
(which is related to tissue density) between two adjacent tion (discussed i n more detail later). The complete examina
tissues produces a more reflective boundary, and stronger tion can be quite time consuming in some patients. Light
echoes result. Very reflective interfaces such as bone/tissue or sedation is helpful i f the animal does not lie quietly.
air/tissue interfere with imaging of weaker echos from deeper Buprenorphine (0.0075 to 0.01 mg/kg IV) with aceproma
tissue interfaces. zine (0.03 mg/kg IV) usually works well for dogs. Butorpha
Higher frequency ultrasound permits better resolution of nol (0.2 mg/kg I M ) with acepromazine (0.1 mg/kg I M ) is
small structures because of the beam characteristics of longer adequate for many cats, although some require more intense
near field and lesser far field divergence. However, higher sedation. Acepromazine (0.1 mg/kg I M ) followed in 15
frequencies have less penetrating ability as more energy minutes by ketamine (2 mg/kg IV) can be used in cats, but
is absorbed and scattered by the soft tissues. Conversely, a this regimen can increase heart rate undesirably.
transducer that produces lower frequencies provides greater
penetration depth but less well-defined images. Frequencies TWO-DIMENSIONAL
generally used for small animal echocardiography range ECHOCARDIOGRAPHY
from about 3.5 M H z (for large dogs) to >10 M H z (for cats A plane of tissue (both depth and width) is displayed using
and small dogs). A megahertz ( M H z ) represents 1,000,000 2-D echocardiography. The anatomic changes resulting from
cycles/sec. various diseases or congenital defects are evident, although
Strongly reflective tissues are referred to as being hyper- actual b l o o d flow is not usually visualized with 2-D or M -
echoic or of increased echogenicity. Poorly reflecting tissues mode imaging alone.
are hypoechoic; fluid, which does not reflect sound, is
anechoic or sonolucent. Tissue behind an area of sonolu Common 2-D Echocardiographic Views
cency appears hyperechoic because of acoustic enhancement. A variety of planes can be imaged from several chest wall
O n the other hand, through-transmission of the ultrasound locations. M o s t standard views are obtained from either
beam is blocked by a strongly hyperechoic object (such as a the right or left parasternal positions (directly over the
rib), and an acoustic shadow (where no image appears) is heart and close to the sternum). Images are occasionally
cast behind the object. obtained from subxiphoid (subcostal) or thoracic inlet
For most echocardiographic examinations, the animal is (suprasternal) positions. Long-axis views are obtained
gently restrained i n lateral recumbency; better-quality images with the imaging plane parallel to the long axis of the heart;
are usually obtained when the heart is imaged from the short-axis views are perpendicular to this plane (Figs. 2-20
recumbent side. For this the animal is placed on a table or to 2-25). Images are described by the location of the trans
platform with an edge cutout, which allows the echocardiog ducer and the imaging plane used (e.g., right parasternal
rapher to position and manipulate the transducer from the short-axis view, left cranial parasternal long-axis view). 2-D
FIG 2-20
T w o - d i m e n s i o n a l short-axis e c h o c a r d i o g r a p h i c v i e w s from the right p a r a s t e r n a l p o s i t i o n .
The center d i a g r a m i n d i c a t e s the orientation of the ultrasound b e a m used to i m a g e
c a r d i a c structures at the six levels s h o w n . S e v e r a l of these positions g u i d e M - m o d e b e a m
p l a c e m e n t as w e l l as D o p p l e r e v a l u a t i o n of tricuspid a n d p u l m o n a r y f l o w s . C o r r e s p o n d i n g
echo images a r e shown c l o c k w i s e from the bottom. A , A p e x . B , Papillary muscle. C , C h o r d a e
t e n d i n e a e . D , M i t r a l v a l v e . E, A o r t i c v a l v e . F, P u l m o n a r y artery. AMV, A n t e r i o r (septal)
mitral v a l v e c u s p ; AO, a o r t a ; APM, anterior p a p i l l a r y muscle; CaVC, c a u d a l v e n a c a v a ;
CH, c h o r d a e t e n d i n e a e ; LA, left atrium; LPA, left p u l m o n a r y artery; LV, left ventricle; LVO,
left ventricular outflow tract; PA, p u l m o n a r y artery; PM, p a p i l l a r y m u s c l e ; PMV, posterior
mitral v a l v e c u s p ; PPM, posterior p a p i l l a r y muscle; PV, p u l m o n a r y v a l v e ; RA, right a t r i u m ;
RAu, right a u r i c l e ; RC, LC, NC, right, left, a n d n o n c o r o n a r y cusps of aortic v a l v e ; RPA, right
p u l m o n a r y artery; RV, right ventricle; RVO, right ventricular outflow tract; TV, tricuspid
v a l v e . (From T h o m a s W P et a l : R e c o m m e n d a t i o n s for s t a n d a r d s in transthoracic
2-dimensi onal e c h o c a r d i o g r a p h y in the d o g a n d cat, J Vet Intern Med 7:247, 1 9 9 3 . )
imaging allows an overall assessment of cardiac chamber appropriately timed 2-D frames can also be used. Several
orientation, size and wall thickness. The R V wall is usually methods can be used to estimate L V volume and wall mass.
about one third of the thickness of the L V free wall and L A size is better assessed using 2-D rather than M - m o d e .
should be no greater than half its thickness. The size of the Several methods for measuring L A size have been described.
right atrial and ventricular chambers is subjectively com One is to measure the cranial-caudal diameter (top-to-
pared with that of the left atrium and ventricle; the right bottom on screen) at end-systole using a right parasternal
parasternal long axis and left apical 4 chamber views are long axis four-chamber view. In cats this L A dimension nor
useful for this. A l l valves and related structures as well as the mally is <16 m m ; a diameter >19 m m may indicate greater
great vessels are systematically examined. A n y suspected risk for thromboembolism. Because of greater body size
abnormality is scanned in multiple planes to further verify variation i n dogs, L A dimension is usually compared with
and delineate it. the 2-D aortic root diameter measured across the sinuses of
End diastolic and systolic L V internal dimensions and Valsalva. A 2-D maximal L A diameter: aortic root ratio
wall thickness are usually obtained using M - m o d e , but between 1.7 to 1.9 is considered normal.
FIG 2 - 2 1
T w o - d i m e n s i o n a l long-axis e c h o c a r d i o g r a p h i c v i e w s from
right p a r a s t e r n a l p o s i t i o n . E a c h d i a g r a m o n the left indi
cates the l o c a t i o n of the ultrasound b e a m a s it transects the
FIG 2 - 2 2
heart from the right s i d e , resulting in the c o r r e s p o n d i n g
Left c a u d a l (apical) parasternal position. Four-chamber v i e w
e c h o i m a g e o n the right. Long-axis f o u r - c h a m b e r (left
o p t i m i z e d for ventricular inflow is a b o v e . Five-chamber v i e w
ventricular inflow) v i e w is a b o v e . Long-axis v i e w of the left
o p t i m i z e d for left ventricular outflow is b e l o w . These v i e w s
ventricular o u t f l o w r e g i o n is b e l o w . AO, A o r t a ; CH,
p r o v i d e g o o d D o p p l e r velocity signals from mitral a n d
c h o r d a e t e n d i n a e ; LA, left a t r i u m ; LC, left c o r o n a r y c u s p of
aortic v a l v e r e g i o n s . AO, A o r t a ; AS, interatrial septum; LA,
aortic v a l v e ; LV, left ventricle; LVW, left ventricular w a l l ;
left a t r i u m ; LV, left ventricle; RA, right atrium; RV, right
MV, mitral v a l v e ; PM, p a p i l l a r y m u s c l e ; RA, right a t r i u m ;
ventricle. (From T h o m a s W P et a l : R e c o m m e n d a t i o n s for
RPA, right p u l m o n a r y a r t e r y ; RV, right ventricle; TV, tricuspid
v a l v e ; VS, interventricular septum. (From T h o m a s W P et a l : s t a n d a r d s in transthoracic 2 - d i m e n s i o n a l e c h o c a r d i o g r a p h y
R e c o m m e n d a t i o n s for s t a n d a r d s in transthoracic 2 - d i m e n - in the d o g a n d c a t , J Vet Intern Med 7 : 2 4 7 , 1 9 9 3 . )
s i o n a l e c h o c a r d i o g r a p h y in the d o g a n d c a t , J Vet Intern
Med 7 : 2 4 7 , 1 9 9 3 . )
especially when coupled with a simultaneously recorded
E C G (or phonocardiogram). Difficulty i n achieving consis
tent and accurate beam placement for standard measure
M-MODE ECHOCARDIOGRAPHY ments and calculations can be a limitation.
This modality provides a one-dimensional view (depth) into
the heart. M - m o d e images represent echos from various M-Mode Views
tissue interfaces along the axis o f the beam (displayed verti Standard M - m o d e views are obtained from the right para
cally on the screen). These echos, which move during the sternal transducer position. The M - m o d e cursor is posi
cardiac cycle, are displayed against time (on the horizontal tioned with 2 - D guidance using the right parasternal
axis). Thus the "wavy" lines that are seen on these recordings short-axis view. Precise positioning o f the ultrasound beam
correspond to the positions o f particular structures in rela within the heart (perpendicular to the structures to be mea
tion to the transducer as well as to each other at any point sured) and clear endocardial images are essential for accurate
i n time. Accurate placement o f the M - m o d e beam using a M - m o d e measurements and calculations. For example, pap
moveable cursor line superimposed on an appropriate 2 - D illary muscles within the left ventricle must be avoided when
(real-time) image is important. M - m o d e images usually measuring free-wall thickness. Fig. 2-26 illustrates standard
provide cleaner resolution o f cardiac borders than 2-D M - m o d e views. In cases in which the M - m o d e cursor cannot
because o f higher sampling rate. Measurements o f cardiac be optimally aligned (e.g., in animals with focal or asym
dimensions and m o t i o n throughout the cardiac cycle are metric hypertrophy), wall thickness measurements from 2-D
often more accurately obtained from M - m o d e tracings, images are preferred.
FIG 2 - 2 3
Left c a u d a l (apical) p a r a s t e r n a l 2 - d i m e n s i o n a l v i e w s
o p t i m i z e d for left ventricular inflow a n d left a u r i c l e (above)
a n d left ventricular outflow (below). AMV, A n t e r i o r (septal)
mitral v a l v e c u s p ; AO, a o r t a ; LA, left atrium; LAu, left
a u r i c l e ; LV, left ventricle; PMV, posterior mitral v a l v e c u s p ;
RC, NC, right a n d n o n c o r o n a r y cusps of aortic v a l v e ; RVO,
right ventricular outflow tract. (From T h o m a s W P et a l :
R e c o m m e n d a t i o n s for s t a n d a r d s in transthoracic 2-dimen FIG 2 - 2 5
sional e c h o c a r d i o g r a p h y in the d o g a n d cat, J Vet Intern Left c r a n i a l p a r a s t e r n a l long-axis v i e w s o p t i m i z e d for aortic
Med 7 : 2 4 7 , 1 9 9 3 . ) root (above), right atrium a n d a u r i c l e (middle), a n d right
ventricular o u t f l o w a n d m a i n p u l m o n a r y artery (below).
These v i e w s a r e u s e d to e v a l u a t e the heart b a s e a n d c a n
p r o v i d e g o o d D o p p l e r s i g n a l s for tricuspid a n d p u l m o n a r y
flows. AO, A o r t a ; CaVC, c a u d a l v e n a c a v a ; LA, left atrium;
LV, left ventricle; PA, p u l m o n a r y a r t e r y ; PV, p u l m o n a r y
v a l v e ; RA, right atrium; RAu, right a u r i c l e ; RC, NC, right
a n d n o n c o r o n a r y cusps of a o r t i c v a l v e ; RV, right ventricle;
RVO, right ventricular o u t f l o w tract. (From T h o m a s W P et a l :
R e c o m m e n d a t i o n s for s t a n d a r d s in t r a n s t h o r a c i c 2-dimen
s i o n a l e c h o c a r d i o g r a p h y in the d o g a n d cat, J Vet Intern
Med 7 : 2 4 7 , 1 9 9 3 . )
TABLE 2-4
LVID D (mm) LVID S (mm) LVW D (mm) LVW S (mm) IVS D (mm) IVS S (mm) L A (mm) A O (mm)
FS 35%-65%
EPSS 4 mm
LVID , Left ventricular internal diameter at end diastole; LVID , left ventricular internal diameter at end systole; LVW , left ventricular wall at end
d S d
diastole; L V W , left ventricular wall at end systole; IVS , interventricular septum at end diastole; IVS , interventricular septum at end systole; LA,
S d S
left atrium (systole); Ao, aortic root; FS, fractional shortening; EPSS, mitral E-point septal separation.
* These values are based on the author's experience and compilation of published studies. Ketamine increases heart rate and decreases LVID . d
CONTRAST ECHOCARDIOGRAPHY
This technique, often called a "bubble study," uses rapid
injection of a substance containing "microbubbles" either
into a peripheral vein or selectively into the heart. These
microbubbles generate tiny pinpoint echos that temporarily
opacify the b l o o d pool being imaged (Fig. 2-29). The micro-
bubbles appear as bright sparkles moving with the blood
flow. Agitated saline solution, a mixture of saline and the
patient's blood, and other substances can be used as echo-
contrast material. Injection into a peripheral vein opacifies
FIG 2 - 2 7
the right heart chambers; bubbles seen in the left heart or
C o l o r f l o w D o p p l e r i m a g e of a n aortic regurgitation jet
aorta indicate a right-to-left shunt. Saline microbubbles do
a n g l e d t o w a r d a n d a l o n g the anterior leaflet of the mitral
v a l v e in a 2-year-old Rottweiler with aortic v a l v e e n d o c a r d i not pass through the pulmonary capillaries (although some
tis. The regurgitant jet c a u s e s the mitral leaflet to flutter in commercially available echo-contrast agents do), so echo-
d i a s t o l e a s seen in F i g . 2 - 2 8 . I m a g e d from the right contrast injection via selective left-sided heart catheteriza
p a r a s t e r n a l long a x i s p o s i t i o n . Ao, A o r t a ; LA, left a t r i u m ; tion is required to visualize intracardiac left-to-right shunts
LV, left ventricle; RV, right ventricle. or mitral regurgitation. Doppler echocardiography has
largely replaced echocontrast studies, but they are still a
useful tool in some cases.
be seen when an aortic insufficiency jet causes the leaflet to
vibrate (Figures 2-27 and 2-28). DOPPLER ECHOCARDIOGRAPHY
The diameter o f the aortic root and sometimes its m o t i o n Blood flow direction and velocity are imaged with Doppler
are measured with M - m o d e . The parallel walls of the aortic echocardiography. Several types o f Doppler echocardiogra
root shift rightward i n systole. D u r i n g diastole one or two phy are used clinically: pulsed-wave ( P W ) , continuous-wave
aortic valve cusps may be seen as a straight line parallel to ( C W ) , and color flow (CF) mapping. Important clinical
and centered between the aortic wall echoes. At the onset o f applications relate to identifying abnormal flow direction or
ejection, the cusps separate toward the walls o f the aortic turbulence and increased flow velocity. This allows detection
root and then come together again at the end o f ejection. and quantification of valvular insufficiency, obstructive
The shape of these echoes (two cusps) has been described as lesions, and cardiac shunts. Cardiac output and other indica
a train o f boxcars or little rectangular boxes attached together tors of systolic function can be assessed, and there is much
by a string. Aortic diameter is measured at end diastole. The interest in Doppler-derived indices o f diastolic function in
amplitude o f posterior-to-anterior m o t i o n o f the aortic root patients with cardiac disease (see Suggested Readings). Ade
is often decreased in animals with poor cardiac output. The quate Doppler examinations are technically demanding.
L A dimension (behind the aortic root) is measured at They are often very time consuming and require a good
maximal systolic excursion. In n o r m a l cats and dogs, the understanding o f hemodynamic principles and cardiac
(M-mode) ratio o f L A to aortic root diameters is about 1 to anatomy.
1. However, L A size is underestimated with this M - m o d e The Doppler modality is based on detecting frequency
view because (especially in dogs) the M - m o d e cursor usually shifts between the emitted ultrasound energy and echoes
transects the L A close to the left auricle, not at its maximal reflected from m o v i n g b l o o d cells (the Doppler shift*).
dimension. In cats the M - m o d e beam is more likely to cross Echoes returning from cells moving away from the trans
the body o f the L A , but its orientation can be inconsistent. ducer are o f lower frequency, and those from cells moving
Echo beam placement may be difficult i n some animals, and toward the transducer are of higher frequency. The higher
the pulmonary artery can be inadvertently imaged instead.
Therefore L A size assessment is best done from 2 - D
images. * V = C( f/2f cos)
0
to estimate cardiac function, but they are influenced by quency; 6, intercept angle (between u l t r a s o u n d beam a n d b l o o d flow
cardiac filling and afterload. These intervals can be calcu direction).
FIG 3 - 2 8
C o l o r M - m o d e (A) a n d s t a n d a r d M - m o d e (B) i m a g e s of the mitral v a l v e from the d o g in
F i g . 2 - 2 7 . The disturbed f l o w from aortic r e g u r g i t a t i o n is seen as the c o l o r s a l o n g the
anterior leaflet in the left ventricular outflow r e g i o n . Fine fluttering of the anterior mitral
leaflet is seen in B; the leaflet a p p e a r s w i d e a n d " f u z z y " c o m p a r e d with the thin, discrete
posterior leaflet.
the velocity of the cells, the greater the frequency shift. ducer. Higher velocities are displayed farther from baseline.
Optimal blood flow profiles and calculation of maximal Other flow characteristics (e.g., turbulence) also affect the
blood flow velocity are possible when the ultrasound beam Doppler spectral display.
is aligned parallel to the flow. This is in contrast to the per
pendicular beam orientation needed for optimal M - m o d e Pulsed Wave Doppler
and 2-D imaging. W i t h Doppler, calculated blood flow veloc Pulsed wave ( P W ) Doppler uses short bursts of ultrasound
ity diminishes as the angle of incidence between ultrasound to analyze echoes returned from a specified area (designated
beam and direction of blood flow diverges from 0 degrees. the sample volume) along the Doppler cursor line. The
This is because the calculated flow velocity is inversely related advantage of P W Doppler is that blood flow velocity, direc
to the cosine of this angle (cosine 0 degrees = 1). As long as tion, and spectral characteristics can be calculated from a
the angle between the ultrasound beam and path of blood specific location i n the heart or blood vessel. The main dis
flow is less than 20 degrees, maximal flow velocity can be advantage is that the m a x i m u m measurable velocity is
estimated with reasonable accuracy. As this angle of inci limited. The pulse repetition frequency (time required to
dence increases, the calculated velocity decreases. At an angle send, receive, and process returning echoes), as well as the
of 90 degrees, the calculated velocity is 0 (cosine 90 degrees transmitted frequency and the distance of the sample volume
= 0); therefore no flow signal is recorded when the ultra from the transducer determine the m a x i m u m measurable
sound beam is perpendicular to blood flow. Flow signals are velocity (called the Nyquist limit). The Nyquist limit is
usually displayed with time on the x axis and velocity (scaled defined by two times the pulse repetition frequency. Lower
in m/sec) on the y axis. A zero baseline demarcates flow away frequency transducers and closer sample volume placement
from (below baseline) or toward (above baseline) the trans increase the Nyquist limit. W h e n blood flow velocity is
higher than the Nyquist limit, "aliasing" or velocity ambigu
ity occurs. This is displayed as a band of velocity signals
extending above and below ("wrapped around") the base
line, so neither velocity nor direction is measurable (Fig.
2-30). The velocity spectrum displayed with P W Doppler
when blood cells in the sample volume are moving in the
same direction and at the same velocity is relatively thin
(tight). Variation i n velocity causes spectral broadening
(widening).
Characteristic blood flow patterns are obtained from the
different valve areas. Flow across both A V valves has a similar
pattern; likewise, flow patterns across the semilunar valve
areas are similar. N o r m a l diastolic flow across the mitral
valve (Fig. 2-31) and tricuspid valve consists of an initial
higher velocity signal during the rapid ventricular filling
phase (E wave), which is followed by a smaller velocity signal
associated with atrial contraction (A wave). Breed, age, and
body weight appear to have little influence on normal
Doppler measurements. Peak velocities are normally higher
across the mitral (peak E usually 0.9 to 1.0 m/sec; peak A
usually 0.6 to 0.7 m/sec) compared with the tricuspid valve
(peak E usually 0.8 to 0.9 m/sec; peak A usually 0.5 to
FIG 2-29 0.6 m/sec). The four-chamber left apical view usually pro
E c h o " b u b b l e " study in a d o g with p u l m o n a r y h y p e r t e n s i o n . vides optimal alignment for assessing mitral inflow veloci
Bright speckles fill the R A a n d RV c h a m b e r s after a n
ties; the left cranial short axis view is usually best for
injection of a g i t a t e d s a l i n e into a p e r i p h e r a l v e i n . B e c a u s e
tricuspid inflow, although several other imaging planes may
there w a s no i n t r a c a r d i a c shunt in this d o g , no " b u b b l e s "
a r e seen in the left heart c h a m b e r s , despite a b n o r m a l l y h i g h
provide adequate alignment. Doppler-derived diastolic func
right heart pressures. V i e w from left a p i c a l p o s i t i o n ; A o , tion indices include the isovolumic relaxation time, mitral
a o r t a ; LA, left a t r i u m ; LV, left ventricle; RA, right a t r i u m ; RV, valve E / A ratio, and others.
right ventricle. Flow across the pulmonary and aortic valves (Fig. 2-32)
accelerates rapidly during ejection, with more gradual decel-
FIG 2 - 3 0
M i t r a l d i a s t o l i c i n f l o w a n d systolic regurgitant f l o w in a d o g with d e g e n e r a t i v e mitral valve
d i s e a s e r e c o r d e d with P W D o p p l e r from left c a u d a l p a r a s t e r n a l p o s i t i o n . The d i r e c t i o n of mitral
regurgitant f l o w is a w a y from the transducer ( b e l o w b a s e l i n e ) ; h o w e v e r , this direction c a n n o t b e
d i s c e r n e d with P W b e c a u s e the f l o w v e l o c i t y is too h i g h . The s i g n a l is instead " w r a p p e d
a r o u n d " the b a s e l i n e (aliased).
FIG 2 - 3 1
N o r m a l mitral v a l v e i n f l o w r e c o r d e d with P W D o p p l e r from left c a u d a l p a r a s t e r n a l
position in a d o g . The f l o w s i g n a l ( a b o v e baseline) f o l l o w i n g the Q R S - T of the E C G
represents e a r l y diastolic f l o w into the ventricle (E); the s e c o n d , smaller p e a k after the P
w a v e represents inflow from atrial c o n t r a c t i o n (A). Velocity s c a l e in m e t e r s / s e c o n d is o n
the left.
eration. Peak systolic pulmonary velocity is 1.4 to 1.5 m/sec Pressure Gradient Estimation
in most normal dogs. The left cranial views usually provide Doppler estimation of pressure gradients is used in combi
better flow alignment. Sample volume placement is at or just nation with M - m o d e and 2 - D imaging to assess the severity
distal to the valve. Peak aortic velocity is usually 1 . 6 to of congenital or acquired flow obstructions. In addition,
1.7 m/sec, although some normal dogs have peak aortic regurgitant jet maximal velocity estimates the peak pressure
velocities above 2 m/sec related to increased stroke volume gradient across the regurgitant valve. The instantaneous
or high sympathetic tone, especially i f unsedated. Ventricular pressure gradient across a stenotic or regurgitant valve is
outflow obstruction causes more rapid flow acceleration, estimated using the maximal measured velocity of the flow
increased peak velocity, and turbulence. In general, aortic jet. C F Doppler is useful to depict jet orientation. Careful
velocities over 2.2 (-2.4) m/sec are suggestive o f outflow Doppler beam alignment is essential in order to measure
obstruction. Between 1.7 and ~2.2 m/sec lies a "grey zone" m a x i m u m velocity. C W Doppler is employed i f aliasing
where mild LV outflow obstruction (e.g., some cases o f sub occurs with P W Doppler. A modification o f the Bernoulli
aortic stenosis) cannot be differentiated with certainty from equation is used to estimate pressure gradient:
normal but vigorous left ventricular ejection. M a x i m a l 2
Pressure gradient = 4 ( m a x i m u m velocity)
aortic/LV outflow velocities are obtained in most dogs from
the subcostal (subxiphoid) position; however, in some dogs Other factors involved in this relationship are usually of
the left apical view provides higher velocity recordings. The m i n i m a l clinical importance and are generally ignored.
LV outflow region should be interrogated from both views Pulmonary arterial systolic pressure can be estimated (if
and the greater maximal velocity value used. there is no p u l m o n i c stenosis) by using the maximal tricus
pid regurgitation jet velocity (TRmax). The calculated sys
Continuous Wave Doppler tolic pressure gradient plus about 8 to 10 m m H g (or the
Continuous wave ( C W ) Doppler employs continuous and measured central venous pressure) equals the peak right ven
simultaneous ultrasound transmission and reception along tricular systolic pressure, which approximates pulmonary
the line of interrogation. Theoretically, there is no m a x i m u m artery systolic pressure. Pulmonary hypertension ( P H ) is
velocity limit with C W Doppler, so high-velocity flows can associated when T R m a x exceeds 2.8 m/s. The severity o f P H
be measured (Fig. 2-33). The disadvantage o f C W Doppler is often categorized as m i l d (~35-50 m m H g ; T R m a x 2.9-
is that sampling of blood flow velocity and direction occurs 3.5 m/s), moderate (~51-75 m m H g ; T R m a x 3.6-4.3 m/s),
all along the ultrasound beam, not i n a specified area (so- or severe (>75 m m H g ; T R m a x >4.3 m/s). Likewise, p u l m o
called range ambiguity). nary diastolic pressure can be estimated from pulmonary
FIG 2-32
N o r m a l p u l m o n a r y f l o w r e c o r d e d with P W D o p p l e r from left c r a n i a l short-axis position in
a d o g . There is r a p i d b l o o d a c c e l e r a t i o n ( b e l o w baseline) into the p u l m o n a r y artery, with
a p e a k velocity of a b o u t 1.0 m / s e c . Velocity s c a l e in meters per s e c o n d is on the left.
FIG 2-33
C W D o p p l e r r e c o r d i n g of high-velocity aortic outflow in a d o g with severe subaortic
stenosis, i m a g e d from the subcostal p o s i t i o n . Estimated systolic pressure g r a d i e n t a c r o s s
the outflow r e g i o n is 1 6 9 mm H g b a s e d o n a p e a k velocity of 6 . 5 m / s e c . Velocity s c a l e
in m e t e r s / s e c o n d is o n the left.
regurgitant (PR) jet velocity at end-diastole. The calculated Color Flow Mapping
end-diastolic pressure gradient between the pulmonary C o l o r flow (CF) mapping is a form of P W Doppler that
artery and the right ventricle, plus the estimated right ven combines the M - m o d e or 2-D modality with blood flow
tricular diastolic pressure, represents pulmonary arterial dia imaging. However, instead of one sample volume along
stolic pressure. Pulmonary hypertension is also suggested by one scan line, many sample volumes are analyzed along
a peak PR velocity of >2.2 m/s. multiple scan lines. The mean frequency shifts obtained
FIG 2 - 3 4 FIG 2 - 3 5
E x a m p l e of c o l o r f l o w a l i a s i n g in a d o g with mitral v a l v e Systolic frame s h o w i n g turbulent r e g u r g i t a n t f l o w into the
stenosis a n d atrial fibrillation. Diastolic f l o w t o w a r d the e n l a r g e d LA of a d o g with c h r o n i c mitral v a l v e d i s e a s e . The
n a r r o w e d mitral orifice (arrow) a c c e l e r a t e s b e y o n d the regurgitant jet curves a r o u n d the d o r s a l a s p e c t of the LA.
N y q u i s t limit, c a u s i n g r e d - c o d e d f l o w ( b l o o d m o v i n g t o w a r d I m a g e d from the right p a r a s t e r n a l long a x i s , four c h a m b e r
transducer) to a l i a s to blue, then a g a i n to r e d , a n d o n c e v i e w . LA, left a t r i u m ; LV, left ventricle; RA, right a t r i u m ; RV,
more to blue. Turbulent f l o w is seen within the left ventricle right ventricle.
at the top of the 2-D i m a g e .
from multiple sample volumes are color-coded for direction Doppler Tissue Imaging
(in relation to the transducer) and velocity. Most systems Doppler tissue imaging (DTI) is a modality used to assess
code blood flow toward the transducer as red and b l o o d the m o t i o n o f tissue, rather than b l o o d cells, by altering the
flow away from the transducer as blue. Zero velocity is i n d i signal processing and filtering o f returning echoes. Myocar
cated by black, meaning either no flow or flow that is dial velocity patterns can be assessed with color flow and
perpendicular to the angle o f incidence. Differences i n rela pulsed wave spectral D T I techniques. Spectral D T I provides
tive velocity o f flow can be accentuated, and the presence o f greater temporal resolution and quantifies velocity o f myo
multiple velocities and directions o f flow (turbulence) can cardial m o t i o n at specific locations, such as the lateral or
be indicated by different display maps that use variations septal aspects o f the mitral annulus (Fig. 2-36). C o l o r D T I
in brightness and color. Aliasing occurs often, even with methods display mean myocardial velocities from different
normal blood flows, because o f low Nyquist limits. Signal regions. Other techniques used to assess regional myocardial
aliasing is displayed as a reversal o f color (e.g., red shifting function and synchrony are derived from D T I methods;
to blue; Fig. 2-34). Turbulence produces multiple velocities these include myocardial velocity gradients, myocardial
and directions o f flow in an area, resulting in a mixing of strain, strain rate, and velocity vector imaging.
color; this display can be enhanced using a variance map,
which adds shades o f yellow or green to the red/blue display TRANSESOPHAGEAL
(Fig. 2-35). ECHOCARDIOGRAPHY
The severity o f valve regurgitation is sometimes estim Transesophageal echocardiography (TEE) uses specialized
ated by the size and shape o f the regurgitant jet during C F transducers mounted on a flexible, steerable endoscope tip
imaging. Although technical and hemodynamic factors to image cardiac structures through the esophageal wall. T E E
confound the accuracy o f such assessment, wide and long can provide clearer images o f some cardiac structures (espe
regurgitant jets are generally associated with more severe cially those at or above the A V junction) compared with
regurgitation than narrow jets. Other methods for quantify transthoracic echocardiography because chest wall and lung
ing valve regurgitation have been described as well. M a x i m u m interference is avoided. This technique can be particularly
regurgitant jet velocity is not a good indicator o f severity, useful for defining some congenital cardiac defects and
especially with mitral regurgitation. Changes i n chamber identifying thrombi, tumors, or endocarditis lesions, as well
size provide a better indication of severity with chronic as guiding cardiac interventional procedures (Fig. 2-37).
regurgitation. The need for general anesthesia and the expense o f the
endoscopic transducers are the main disadvantages of T E E .
Complications related to the endoscopy procedure appear to
be m i n i m a l .
THREE-DIMENSIONAL
ECHOCARDIOGRAPHY
The ability to generate and manipulate 3-dimensional (3-D)
images of the heart and other structures is a promising new
way to evaluate cardiac structure and function. Anatomic
and blood flow abnormalities can be viewed from any angle
by rotating or bisecting the 3-D images. Current technology
requires several cardiac cycles in order to acquire sufficient
data for 3-D reconstruction of the entire heart, although true
"real time" 3-D echocardiography will soon be available.
OTHER TECHNIQUES
CENTRAL VENOUS PRESSURE
FIG 2-36
P W D o p p l e r tissue i m a g e from a cat. The mitral annulus
MEASUREMENT
moves t o w a r d the left a p e x (and transducer) in systole (S). Central venous pressure ( C V P ) is influenced by intravascu
Early d i a s t o l i c filling (Ea) shifts the annulus a w a y from the lar volume, venous compliance, and cardiac function. C V P
a p e x a s the LV e x p a n d s . A d d i t i o n a l motion o c c u r s with late measurement helps i n differentiating high right heart filling
diastolic filling from atrial contraction (Aa). pressure (as from right heart failure or pericardial disease)
from other causes of pleural or peritoneal effusion. But it is
important to note that pleural effusion itself can increase
intrapleural pressure enough to impair cardiac filling; this
FIG 2-37
A , T w o - d i m e n s i o n a l t r a n s e s o p h a g e a l e c h o (TEE) i m a g e at the h e a r t b a s e from a 5-year-old
English S p r i n g e r S p a n i e l s h o w s a patent ductus arteriosus (arrow) b e t w e e n the d e s c e n d i n g
a o r t a (D Ao) a n d p u l m o n a r y artery (PA). B , C o l o r f l o w D o p p l e r i m a g e in d i a s t o l e from the
s a m e orientation demonstrates f l o w a c c e l e r a t i o n t o w a r d the ductal o p e n i n g in the D A o
a n d the turbulent d u c t a l f l o w into the PA.
can raise C V P even i n the absence o f cardiac disease. There cTnT. H u m a n assays for c T n l and c T n T can be used i n dogs
fore C V P should be measured after thoracocentesis i n and cats, but because methodology is not standardized
patients with moderate- to large-volume pleural effusion. among various c T n l assays, the cut-off values for n o r m a l
C V P is sometimes used to monitor critical patients receiving may vary. Furthermore, c T n values that indicate clinically
large intravenous fluid infusions. However, C V P is not an relevant myocardial disease or damage i n animals are
accurate reflection of left heart filling pressure and thus unclear.
is not a reliable way to monitor for cardiogenic p u l The natriuretic peptides, A N P , B N P , and their precursors,
monary edema. The C V P in normal dogs and cats usually are other potentially useful biomarkers for assessing the
ranges from 0 to 8 (up to 10) c m H O . Fluctuations i n C V P
2 presence and possibly prognosis o f heart failure. Circulating
that parallel those o f intrapleural pressure occur during natriuretic peptide concentrations increase i n association
respiration. w i t h vascular volume expansion and decreased renal clear
C V P is measured via a large-bore jugular catheter that ance and when their production is stimulated (e.g., with
extends into or close to the right atrium. The catheter is ventricular strain and hypertrophy, hypoxia, or tachycardia).
placed aseptically and connected by extension tubing and a The natriuretic peptides should be used as functional markers
three-way stopcock to a fluid administration set. A water of cardiac disease rather than o f specific pathology. Issues
manometer is attached to the stopcock and positioned verti of standardization among different commercial assays and
cally, with the stopcock (representing 0 c m H O ) placed at
2
methodologies and lack o f universal reference values are
the same horizontal level as the patient's right atrium. The limitations. The N - t e r m i n a l fragments ( N T - p r o A N P and
stopcock is turned off to the animal, allowing the m a n o m N T - p r o B N P ) o f the natriuretic peptide precursor molecules
eter to fill with crystalloid fluid; then the stopcock is turned remain i n circulation longer and reach higher plasma con
off to the fluid reservoir so that the fluid c o l u m n i n the centrations than the active hormone molecules. Because
manometer equilibrates with the animal's C V P . Repeated A N P and N T - p r o A N P amino acid sequences are highly con
measurements are more consistent when taken w i t h the served among people, dogs, and cats, h u m a n assays may be
animal and manometer in the same position and during used. Canine and feline B N P are similar, but differences from
the expiratory phase of respiration. Small fluctuations i n the people preclude the use o f most human B N P assays. Canine
manometer's fluid meniscus occur w i t h the heartbeat, and and feline N T - p r o B N P measurement is commercially avail
slightly larger movement is associated w i t h respiration. able, although questions regarding interpretation o f results
Marked change in the height of the fluid c o l u m n associated remain. Plasma B N P and N T - p r o B N P are sensitive and spe
with the heartbeat suggests either severe tricuspid insuffi cific markers for chronic L V dysfunction i n people, and high
ciency or that the catheter tip is within the right ventricle. concentrations are negatively correlated w i t h prognosis.
B N P as well as N T - p r o A N P are high i n most cats w i t h hyper
BIOCHEMICAL MARKERS trophic cardiomyopathy. Elevated concentrations are also
A number of specific biochemical markers are being evalu seen i n dogs w i t h heart disease and heart failure, but overlap
ated for their diagnostic and prognostic potential. Cardiac i n these concentrations compared w i t h those o f some dogs
troponins are more sensitive for detecting myocardial injury without heart disease is o f concern. Studies are ongoing to
than cardiac-specific creatine kinase ( C K - M B ) and other clarify the potential usefulness o f plasma natriuretic peptides
biochemical markers of muscle damage. In dogs the C K - M B i n dogs w i t h cardiac disease.
isoform comprises only a m i n o r i t y of total cardiac C K , and Other biomarkers are currently being evaluated. The
it is also present in noncardiac tissues. Cardiac troponins are endothelin (ET) system is activated i n dogs and cats w i t h
regulatory proteins associated with cardiac actin (thin) con heart failure and i n those w i t h p u l m o n a r y hypertension, so
tractile filaments. Circulating concentrations of cardiac tro assays for plasma E T - l i k e immunoreactivity may be useful.
ponin I (cTnl) and cardiac troponin T (cTnT) provide a Tumor necrosis factor ( T N F ) may also be a useful marker
a
specific indicator o f myocardial injury or necrosis. The of cardiac disease progression, but it is not cardiac specific.
pattern and degree of their release can depend o n the type
and severity o f myocyte injury. A l t h o u g h there is an associa ANGIOCARDIOGRAPHY
tion between acute injury and the degree o f increase i n Nonselective angiocardiography can be used to diagnose
serum troponin concentration, this relationship is less clear several acquired and congenital diseases, including cardio
in patients with chronic disease. After acute myocyte damage, myopathy and heartworm disease i n cats, severe p u l m o n i c
serum c T n concentration increases within a few hours, peaks or (sub)aortic stenosis, patent ductus arteriosus, and tetral
in 12 to 24 hours, and then declines over the next few weeks. ogy o f Fallot. Intracardiac septal defects and valvular regur
Myocardial inflammation, trauma, congestive heart failure, gitation cannot be reliably identified. The quality o f such
hypertrophic cardiomyopathy, and gastric dilatation/volvu studies is higher with rapid injection o f radiopaque agents
lus have been associated with increased cardiac toponin via a large-bore catheter and w i t h smaller patient size.
concentrations. In dogs with congestive heart failure or In most cases, echocardiography provides similar infor
hypertrophic cardiomyopathy, this probably relates to con mation more safely However, evaluation o f the pulmonary
tinued myocardial remodeling, not just acute damage from vasculature is better accomplished using nonselective
myocardial infarction. cTnI appears to be more specific than angiocardiography.
Selective angiocardiography is performed by advancing tissue. Because cardiac movement during the imaging
cardiac catheters into specific areas of the heart or great sequence reduces image quality, some type of physiologic
vessels. Injection o f contrast material is generally preceded ( E C G ) gating, as well as rapid image acquisition, are needed.
by the measurement o f pressures and oxygen saturations. Identification of pathologic morphology is a major applica
This technique allows identification o f anatomic abnormal tion, although myocardial function, perfusion, and blood
ities and the path of blood flow. Doppler echocardiography flow studies may be done depending on the technical capa
may provide comparable diagnostic information noninva bility of the equipment. Novel M R techniques also allow
sively. However, selective angiography is a necessary compo noninvasive evaluation of blood vessels, including calcula
nent of many cardiac interventional procedures. tion of peripheral resistance.
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Schober KE et al: Pulmonary venous flow characteristics as assessed DeFrancesco TC et al: Prospective clinical evaluation of an ELISA
by transthoracic pulsed Doppler echocardiography in normal B-type natriuretic peptide assay in the diagnosis of congestive
dogs, Vet Radiol Ultrasound 39:33, 1998. heart failure in dogs presenting with cough or dyspnea, / Vet
Schober KE, Luis Fuentes V, Bonagura JD: Comparison between Intern Med 21:243, 2007.
invasive hemodynamic measurements and noninvasive assess Gookin JL, Atkins CE: Evaluation of the effect of pleural effusion
ment of left ventricular diastolic function by use of Doppler on central venous pressure in cats, / Vet Intern Med 13:561,
echocardiography in healthy anesthetized cats, Am J Vet Res 1999.
64:93, 2003. Herndon W E et al: Cardiac troponin I in feline hypertrophic car
Schober KE, Maerz I: Assessment of left atrial appendage flow diomyopathy, / Vet Intern Med 16:558, 2002.
velocity and its relation to spontaneous echocardiographic con MacDonald K A et al: Brain natriuretic peptide concentration in
trast in 89 cats with myocardial disease, / Vet Intern Med 20:120, dogs with heart disease and congestive heart failure, / Vet Intern
2006. Med 17:172, 2003.
Sisson D D et al: Plasma taurine concentrations and M-mode echo Oakley RE et al: Experimental evaluation of central venous
cardiographic measures in healthy cats and in cats with dilated pressure monitoring in the dog, J Am Anim Hosp Assoc 33:77-82,
cardiomyopathy, / Vet Intern Med 5:232, 1991. 1997.
Sisson D, Schaeffer D: Changes in linear dimensions of the heart, Oyama M A , Sisson D: Cardiac troponin-I concentration in dogs
relative body weight as measured by M-mode echocardiography with cardiac disease, / Vet Intern Med 18:831, 2004.
in growing dogs. Am J Vet Res 52:1591-1596, 1991. Prosek R et al: Distinguishing cardiac and noncardiac dyspnea in
Snyder PS, Sato T, Atkins CE: A comparison of echocardiographic 48 dogs using plasma atrial natriuretic factor, B-type natriuretic
indices of the non-racing, healthy greyhound to reference values factor, endothelin, and cardiac troponin-I, / Vet Intern Med
from other breeds, Vet Radiol Ultrasound 36:387, 1995. 21:238, 2007.
Stepien RL et al: Effect of endurance training on cardiac morphol Schober KE: Biochemical markers of cardiovascular disease. In
ogy in Alaskan sled dogs, J Appl Physiol 85:1368, 1998. Ettinger SJ, Feldman EC, editors: Textbook of veterinary internal
Thomas W P et al: Recommendations for standards in transthoracic medicine, ed 6, Philadelphia, 2005, WB Saunders, pp 940-948,
two-dimensional echocardiography in the dog and cat, / Vet 2005.
Intern Med 7:247-252, 1993. Shaw SP, Rozanski EA, Rush JE: Cardiac troponins I and T in dogs
Vollmar AC: Echocardiographic measurements in the Irish Wolf with pericardial effusion, / Vet Intern Med 18:322, 2004.
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35:271, 1999. North Am: Small Anim Pract 34:1105, 2004.
Sleeper M M , Clifford C A , Laster LL: Cardiac troponin I in the
O T H E R TECHNIQUES normal dog and cat, / Vet Intern Med 15:501, 2001.
Adin DB et al: Comparison of canine cardiac troponin I concentra Spratt DP et al: Cardiac troponin I: evaluation of a biomarker for
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2006. 46:139, 2005.
C H A P T E R 3
Management of
Heart Failure
O V E R V I E W O F H E A R T FAILURE
CARDIAC RESPONSES
Cardiac Responses
Cardiac remodeling refers to the changes in myocardial
Systemic Responses
size, shape, and stiffness that occur in response to various
General Causes of Heart Failure
mechanical, biochemical, and molecular signals induced
Approach to Treating Heart Failure
by the underlying injury or stress. These changes include
TREATMENT FOR A C U T E C O N G E S T I V E
myocardial cell hypertrophy, cardiac cell drop-out or self-
H E A R T FAILURE
destruction (apoptosis), excessive interstitial matrix forma
General Considerations
tion, fibrosis, and destruction of normal collagen binding
Supplemental Oxygen
between individual myocytes. The latter, resulting from
Drug Therapy
effects of myocardial collagenases or matrix metalloprotein
Heart Failure Caused by Diastolic Dysfunction
ases, can cause dilation or distortion of the ventricle from
Monitoring and Follow-Up
myocyte slippage. Stimuli for remodeling include mechani
M A N A G E M E N T O F C H R O N I C H E A R T FAILURE
cal forces (e.g., increased wall stress from volume or pressure
General Considerations
overload) and also various neurohormones (e.g., angioten
Diuretics
sin II, norepinephrine, endothelin, aldosterone) and cyto
Angiotensin Converting Enzyme Inhibitors
kines (e.g., tumor necrosis factor [TNF] -alpha). Contributing
Positive Inotropic Agents
biochemical abnormalities related to cellular energy produc
Other Vasodilators
tion, calcium fluxes, protein synthesis, and catecholamine
Dietary Considerations
metabolism have been variably identified in different models
Chronic Diastolic Dysfunction
of heart failure and in clinical patients. Myocyte hypertrophy
Reevaluation and M o n i t o r i n g
and reactive fibrosis increase total cardiac mass by eccentric
Strategies for Refractory Congestive Heart Failure
and, in some cases, concentric patterns of hypertrophy. Ven
tricular hypertrophy can increase chamber stiffness, impair
relaxation, and increase filling pressures; these abnormalities
OVERVIEW OF HEART FAILURE of diastolic function can also contribute to systolic failure.
Ventricular remodeling also promotes the development of
Heart failure entails abnormalities of cardiac systolic or dia arrhythmias. The initiating stimulus underlying chronic
stolic function, or both. These can occur without evidence cardiac remodeling may occur years before clinical evidence
of abnormal fluid accumulation (congestion), especially in of heart failure appears.
the initial stages of disease. Congestive heart failure ( C H F ) Acute increases in ventricular filling (preload) induce
is characterized by high cardiac filling pressure, which leads greater contraction force and blood ejection. This response,
to venous congestion and tissue fluid accumulation. It is a known as the Frank-Starling mechanism, allows beat-to-beat
complex clinical syndrome rather than a specific etiologic adjustments that balance the output of the two ventricles
diagnosis. The pathophysiology of heart failure is complex. and increase overall cardiac output i n response to acute
It involves structural and functional changes within the heart increases i n hemodynamic load. The Frank-Starling effect
and vasculature as well as other organs. The process of pro helps normalize cardiac output under conditions of increased
gressive cardiac remodeling inherent to heart failure can pressure and/or volume loading, but these conditions also
develop secondary to cardiac injury or stress from valvular increase ventricular wall stress and oxygen consumption.
Ventricular wall stress is directly related to ventricular activation o f the renin-angiotensin-aldosterone system, and
pressure and internal dimensions and inversely related to release o f antidiuretic hormone (ADH-vasopressin). These
wall thickness (Laplace's law). Myocardial hypertrophy can neurohormonal systems work independently and together to
reduce wall stress. The pattern o f hypertrophy that develops increase vascular volume (by sodium and water retention
depends on the underlying disease. A ventricular systolic and increased thirst) and vascular tone (Fig. 3-1). Excessive
pressure load induces "concentric" hypertrophy; myocardial volume retention results i n edema and effusions. Prolonged
fibers and ventricular walls thicken as contractile units are systemic vasoconstriction increases the workload on the
added i n parallel. A volume load causes "eccentric" hyper heart, can reduce forward cardiac output, and may exacer
trophy; myocardial fiber elongation and chamber dilation bate valvular regurgitation. The extent to which these mech
occur as new sarcomeres are laid d o w n i n series. Compensa anisms are activated varies with the severity and etiology of
tory hypertrophy lessens the importance o f the Frank-Star heart failure. In general, as failure worsens, neurohormonal
ling mechanism i n stable, chronic heart failure. A l t h o u g h activation increases. Increased production of endothelins
volume loads are better tolerated because myocardial oxygen and proinflammatory cytokines, as well as altered expression
demand is not as severe, both abnormal pressure and volume of vasodilatory and natriuretic factors, also contribute to the
loading impair cardiac performance over time. Eventually, complex interplay among these N H mechanisms and their
decompensation and myocardial failure develop. In patients consequences.
with p r i m a r y myocardial diseases, initial cardiac pressure The effects o f sympathetic stimulation (e.g., increased
and volume loads are normal, but intrinsic defects o f the contractility, heart rate, and venous return) can increase
heart muscle lead to the hypertrophy and dilation observed. cardiac output initially, but over time these effects become
Cardiac hypertrophy and other remodeling begin long detrimental by increasing afterload stress and myocardial
before heart failure becomes manifest. In addition to myocyte oxygen requirements, contributing to cellular damage and
hypertrophy, cardiac remodeling can include cell loss or self- myocardial fibrosis, and enhancing the potential for cardiac
destruction (apoptosis), excessive interstitial matrix for arrhythmias. N o r m a l feedback regulation of sympathetic
mation, and loss o f n o r m a l collagen binding. Myocyte nervous and hormonal systems depends on arterial and
hypertrophy and reactive fibrosis increase total cardiac mass atrial baroreceptor function. Baroreceptor responsiveness
as well as ventricular stiffness. This promotes elevated filling becomes attenuated in chronic heart failure, which contrib
pressures and predisposes the patient to ischemia. Increased utes to sustained sympathetic and hormonal activation and
chamber size increases wall stress and myocardial O demand.
2 reduced inhibitory vagal effects. Baroreceptor function can
Biochemical abnormalities involving cell energy production, improve with reversal of heart failure, increased myocardial
calcium fluxes, and contractile protein function can develop. contractility, decreased cardiac loading conditions, or inhibi
Clinical heart failure can be considered a state of decompen tion of angiotensin II (which directly attenuates barorecep
sated hypertrophy; ventricular function progressively dete tor sensitivity). Digoxin has a positive effect on baroreceptor
riorates as contractility and relaxation become more deranged. sensitivity.
C o n t i n u e d exposure to increased sympathetic stimula The renin-angiotensin system has far-reaching effects.
tion reduces cardiac sensitivity to catecholamines. D o w n - Whether systemic renin-angiotensin-aldosterone activation
regulation (reduced number) o f myocardial -receptors
1 always occurs before overt congestive failure is unclear, and
and other changes i n cellular signaling may help protect the may depend on the underlying etiology. Renin release from
myocardium against the cardiotoxic and arrhythmogenic the renal juxtaglomerular apparatus occurs secondary to low
effects o f catecholamines. Beta-blocking agents can reverse renal artery perfusion pressure, renal (-adrenergic receptor
+
(3 -receptor down-regulation but may worsen heart failure.
21 stimulation, and reduced N a delivery to the macula densa
Cardiac ( - and -receptors are also present but are not
2 1 of the distal renal tubule. Stringent dietary salt restriction
down-regulated; these are thought to contribute to myocar and diuretic or vasodilator therapy can promote renin
dial remodeling and arrhythmogenesis. Another cardiac release. Renin facilitates conversion o f the precursor peptide
receptor subtype ( -receptors) may promote myocardial
3 angiotensinogen to angiotensin I (an inactive form). Angio
function deterioration through a negative inotropic effect. tensin-converting enzyme ( A C E ) , found in the lung and
elsewhere, converts angiotensin I to the active angiotensin
SYSTEMIC RESPONSES II and is involved in the degradation of certain vasodi
Neurohormonal Mechanisms lator kinins. There are also other pathways that generate
Neurohormonal ( N H ) responses contribute to cardiac angiotensin II.
remodeling and also have more far-reaching effects. Over Angiotensin II has several important effects, including
time, excessive activation o f neurohormonal "compensa potent vasoconstriction and stimulation of aldosterone
tory" mechanisms leads to the clinical syndrome of C H E release from the adrenal cortex. Additional effects of angio
Although these mechanisms support circulation i n the face tensin II include increased thirst and salt appetite, facilita
of acute hypotension and hypovolemia, their chronic activa tion of neuronal norepinephrine synthesis and release,
tion accelerates further deterioration o f cardiac function. blockade o f neuronal norepinephrine reuptake, stimulation
Major neurohormonal changes i n heart failure include of antidiuretic hormone (vasopressin) release, and increased
increases i n sympathetic nervous tone, attenuated vagal tone, adrenal epinephrine secretion. Inhibition of A C E can reduce
FIG 3-1
Major neurohormonal mechanisms leading to volume retention and increased afterload in
congestive heart failure. ACE, Angiotensin-converting enzyme; AT, angiotensin; EPI,
epinephrine; HF, heart failure; NE, norepinephrine.
N H activation and promote vasodilation and diuresis. Local baroreceptor function. Aldosterone is also produced locally
production o f angiotensin II also occurs in the heart, vascu in the cardiovascular system and mediates inflammation and
lature, adrenal glands, and other tissues. Local activity affects fibrosis. C h r o n i c exposure can be detrimental to ventricular
cardiovascular structure and function by enhancing sympa function and contribute to pathologic remodeling and myo
thetic effects and promoting tissue remodeling that can cardial fibrosis.
include hypertrophy, inflammation, and fibrosis. Antidiuretic hormone is released from the posterior pitu
Aldosterone promotes sodium and chloride reabsorption itary gland. This hormone directly causes vasoconstriction
as well as potassium and hydrogen i o n secretion i n the renal and also promotes free water reabsorption i n the distal neph
collecting tubules; the concurrent water reabsorption aug rons. Although increased plasma osmolality or reduced blood
ments vascular volume. Increased aldosterone concentration volume are the n o r m a l stimuli for A D H release, reduced
can promote hypokalemia, hypomagnesemia, and impaired effective circulating volume and other nonosmotic stimuli
cause continued release o f A D H in patients with heart motes sodium and water retention. Continued activation of
failure. The continued release o f A D H contributes to the these mechanisms leads to clinical edema and effusions.
dilutional hyponatremia sometimes found i n patients with Afferent arteriolar vasodilation mediated by endogenous
heart failure. prostaglandins and natriuretic peptides can partially offset
Increased circulating concentrations o f other substances the effects o f efferent vasoconstriction, but progressive
that play a role in abnormal myocardial hypertrophy and/or impairment o f renal b l o o d flow leads to renal insufficiency.
fibrosis, including cytokines (e.g., T N F ) and endothelins,
a Diuretics not only can magnify azotemia and electrolyte loss
have also been detected in animals with severe heart failure. but can further reduce cardiac output and activate the neu
Endothelin production is stimulated by hypoxia and vascu rohormonal mechanisms.
lar mechanical factors but also by angiotensin II, A D H , nor
epinephrine, cytokines (including T N F and interleukin-I),
a
Other Effects
and other factors. Reduced exercise capacity, along with skeletal muscle atrophy,
Endogenous mechanisms that oppose the vasoconstrictor occurs in patients with heart failure. Poor diastolic filling,
responses also are activated. These include natriuretic pep inadequate forward output, and pulmonary edema or pleural
tides, nitric oxide, and vasodilator prostaglandins. Normally, effusion can interfere with exercise ability Furthermore,
a balance between vasodilator and vasoconstrictor effects impaired peripheral vasodilation during exercise contributes
maintains circulatory homeostasis as well as renal solute to inadequate skeletal muscle perfusion and fatigue. Exces
excretion. As heart failure progresses, the influence o f the sive peripheral sympathetic tone, angiotensin II (both circu
vasoconstrictor mechanisms predominates despite increased lating and locally produced), and vasopressin can contribute
activation o f vasodilator mechanisms. to impaired skeletal muscle vasodilatory capacity i n patients
Natriuretic peptides are synthesized i n the heart and play with CHF. Increased vascular wall sodium content and inter
an important role in regulation o f b l o o d volume and pres stitial fluid pressure stiffen and compress vessels. Other
sure. Atrial natriuretic peptide ( A N P ) is synthesized by atrial mechanisms can include impaired endothelium-dependent
myocytes as a prohormone, w h i c h is then cleaved to the relaxation, increased endothelin concentration, and vascular
active peptide after release stimulated by mechanical stretch wall changes induced by the growth factor effects o f various
of the atrial wall. Brain natriuretic peptide ( B N P ) is also neurohormonal vasoconstrictors. A C E inhibitor therapy,
synthesized i n the heart, mainly by the ventricles i n response with or without spironolactone, may improve endothelial
to myocardial dysfunction or ischemia. Natriuretic peptides vasomotor function and exercise capacity. Pulmonary endo
cause diuresis, natriuresis, and peripheral vasodilation. They thelial function is improved by A C E inhibitors in dogs with
act to antagonize the effects o f the renin-angiotensin system CHF.
and can also alter vascular permeability and inhibit growth
of smooth muscle cells. Natriuretic peptides are degraded by GENERAL CAUSES OF HEART FAILURE
neutral endopeptidases. Circulating concentrations o f A N P The causes o f heart failure are quite diverse; it can be useful
and B N P increase in patients with heart failure. This increase to think o f them in terms o f underlying pathophysiology. In
has been correlated with pulmonary capillary wedge pres most cases o f heart failure, the major initiating abnormality
sure and severity o f heart failure i n both dogs and people. is myocardial (systolic pump) failure, systolic pressure over
N i t r i c oxide ( N O ) , produced i n vascular endothelium i n load, volume overload, or reduced ventricular compliance
response to endothelial-nitric oxide synthetase ( N O S ) , is a (impaired filling). Nevertheless, several pathophysiologic
functional antagonist o f endothelin and angiotensin II. This abnormalities often coexist; both systolic and diastolic func
response is impaired i n patients with heart failure. At tion abnormalities are c o m m o n in patients with advanced
the same time, myocardial i n d u c i b l e - N O S expression is failure.
enhanced; myocardial N O release has negative effects on Myocardial failure is characterized by poor ventricular
myocyte function. Intrarenal vasodilator prostaglandins contractile function, and it is most commonly secondary to
oppose the action o f angiotensin II on the renal vasculature. idiopathic dilated cardiomyopathy; valvular insufficiency
The use o f prostaglandin synthesis inhibitors i n dogs or cats may or may not be present initially but usually develops as
with severe heart failure could potentially reduce glomerular the affected ventricle dilates. Persistent tachyarrhythmias,
filtration (by increasing afferent arteriolar resistance) and some nutritional deficiencies, and other cardiac insults also
enhance sodium retention. can lead to myocardial failure (see Chapters 7 and 8). Dis
eases that cause a volume or flow overload to the heart
Renal Effects usually involve a primary "plumbing" problem (e.g., a leaky
Renal efferent glomerular arteriolar constriction, mediated valve or abnormal systemic-to-pulmonary connection).
by sympathetic stimulation and angiotensin II, helps main Cardiac p u m p function is often maintained at a near-normal
tain glomerular filtration i n the face o f reduced cardiac level for a prolonged time, but myocardial contractility
output and renal b l o o d flow. Higher oncotic and lower does eventually deteriorate (see Chapters 5 and 6). Pressure
hydrostatic pressures develop i n the peritubular capillaries, overload results when the ventricle must generate higher-
enhancing the reabsorption o f tubular fluid and sodium. than-normal systolic pressure to eject blood. Concentric
Angiotensin II-mediated aldosterone release further pro hypertrophy increases ventricular wall thickness and stiff-
ness and predisposes the patient to ischemia. Excessive APPROACH TO TREATING
pressure loads eventually lead to a decline i n myocardial HEART FAILURE
contractility. Myocardial pressure overload results from con M o s t current treatment strategies are aimed at modifying
genital ventricular outflow obstruction and systemic or pul either the results of N H activation (i.e., sodium and water
monary hypertension (see Chapters 5, 10, and 11). Diseases retention) or the activation process itself (e.g., A C E i n h i b i
that restrict ventricular filling impair diastolic function. tion). In most cases, therapy centers o n controlling edema
These include hypertrophic and restrictive myocardial and effusions, improving cardiac output, reducing cardiac
disease and pericardial disease (see Chapters 8 and 9). C o n workload, supporting myocardial function, and managing
tractile ability is usually normal initially, but high filling concurrent arrhythmias. The approach to these goals varies
pressure leads to congestion behind the ventricle(s) and may somewhat w i t h different diseases, most notably those causing
diminish cardiac output. Examples of c o m m o n diseases are restriction to ventricular filling.
listed in Table 3-1 according to their main initiating patho The evolving perspective o n C H F management is based
physiology and typical clinical manifestation of C H F signs. on blocking excessive N H activation and preventing progres
sion of myocardial remodeling and dysfunction, with diuret
ics being used to control signs of congestion. Future strategies
may also involve drugs that block cytokines, antagonize
TABLE 3-1
endothelins, and enhance atrial peptides, as well as other
Common Causes of Congestive Heart Failure (CHF) strategies to block the effects of N H activation.
TYPICAL CHF
Classification of Severity
MAJOR PATHOPHYSIOLOGY MANIFESTATION*
Guidelines for clinical staging of heart failure (based on the
Myocardial Failure
American Heart Association and American College of Cardi
ology [ A H A / A C C ] system) are being increasingly applied to
Idiopathic dilated cardiomyopathy Either L- or R-CHF
veterinary patients (Table 3-2). These describe disease pro
Myocardial ischemia/infarction L-CHF
gression through four stages over time. This staging system
Drug toxicities (e.g., doxorubicin) L-CHF
Infective myocarditis Either L- or R-CHF
emphasizes the importance of early diagnosis and evidence-
based management of heart dysfunction. It also deemphasizes
Volume-Flow Overload the term "congestive" in congestive heartfailure because volume
Mitral valve regurgitation L-CHF overload is not consistently present at all stages. Nevertheless,
(degenerative, congenital, attention to the patient's fluid status is highly important.
infective) The clinical severity of heart failure is also sometimes
Aortic regurgitation (infective L-CHF described according to a modified N e w York Heart Associa
endocarditis, congenital) tion ( N Y H A ) classification scheme or the International
Ventricular septal defect L-CHF
Small A n i m a l Cardiac Health C o u n c i l ( I S A C H C ) criteria.
Patent ductus arteriosus L-CHF
These systems group patients into functional categories on
Tricuspid valve regurgitation R-CHF
the basis of clinical observations rather than underlying
(degenerative, congenital,
infective)
cardiac disease or myocardial function. Such classification
Tricuspid endocarditis R-CHF can be helpful conceptually and for categorizing study
Chronic anemia Either L- or R-CHF patients. Forrester's classification is another method of
Thyrotoxicosis Either L- or R-CHF grouping heart failure patients. Dogs with chronic mitral
regurgitation often fall into group II; severe dilated car
Pressure Overload
diomyopathy is the most c o m m o n diagnosis in group IV.
(Sub)aortic stenosis L-CHF Diseases causing group III heart failure are rare i n dogs and
Systemic hypertension L-CHF (rare) cats. Regardless of the clinical classification scheme, identify
Pulmonic stenosis R-CHF
ing the underlying etiology and pathophysiology, as well as
Heartworm disease R-CHF
the clinical severity, is important for individualized therapy.
Pulmonary hypertension R-CHF
A Patient "at risk" for the development of heart failure, but apparent cardiac structural abnormality
not yet identified
B Structural cardiac abnormality is evident, but no clinical signs of heart failure
C Structural cardiac abnormality, with past or present clinical signs of heart failure
D Persistent or end-stage heart failure signs, refractory to standard therapy
I Heart disease is present but no evidence of heart failure or exercise intolerance; cardiomegaly is
minimal to absent
II Signs of heart disease with evidence of exercise intolerance; radiographic cardiomegaly is present
III Signs of heart failure with normal activity or at night (e.g., cough, orthopnea); radiographic signs of
significant cardiomegaly and pulmonary edema or pleural/abdominal effusion
IV Severe heart failure with clinical signs at rest or with minimal activity; marked radiographic signs of
C H F and cardiomegaly
I Asymptomatic patient
la Signs of heart disease without cardiomegaly
lb Signs of heart disease and evidence of compensation (cardiomegaly)
II Mild to moderate heart failure. Clinical signs of failure evident at rest or with mild exercise, and
adversely affect quality of life
III Advanced heart failure. Clinical signs of C H F are immediately obvious
IlIa Home care is possible
llIb Hospitalization recommended (cardiogenic shock, life-threatening edema, large pleural effusion,
refractory ascites)
AHA/ACC, American Heart Association and American College of Cardiology; CHF, congestive heart failure.
be performed expediently i f marked pleural effusion exists. usually adequate. Concentrations of 50% to 100% oxygen
Likewise, large-volume ascites should be drained to improve may be needed initially, but this should be reduced within a
ventilation. Animals w i t h severe C H F are greatly stressed. few hours to 40% to avoid lung injury. When a nasal tube is
Physical activity must be maximally curtailed to reduce total used, humidified O is delivered at a rate of 50 to 100 ml/kg/
2
oxygen consumption; cage confinement is preferred. E n v i m i n . Extremely severe pulmonary edema with respiratory
ronmental stresses such as excess heat and humidity or failure may respond to endotracheal or tracheotomy tube
extreme cold should be avoided. W h e n transported, the placement, airway suctioning, and mechanical ventilation.
animal should be placed on a cart or carried. Unnecessary Positive end-expiratory pressure helps clear small airways
handling of the patient and administration of oral medica and expand alveoli. Positive airway pressures can adversely
tions should be avoided, when possible. affect hemodynamics, however, and chronic high oxygen
concentrations (>70%) can injure lung tissue (see Suggested
SUPPLEMENTAL OXYGEN Readings for more information). Continuous monitoring is
Oxygen administered by face mask or improvised hood, essential for intubated animals.
nasal catheter, endotracheal tube, or oxygen cage is beneficial
as long as the method chosen does not increase the patient's DRUG THERAPY
distress. A n oxygen cage with temperature and humidity Diuresis
controls is preferred, and a setting of 65 F is recommended Rapid diuresis can be achieved with I V furosemide; effects
for normothermic animals. Oxygen flow o f 6 to 10 L / m i n is begin within 5 minutes, peak by 30 minutes, and last about
BOX 3-1
* Dilution of 250 mg dobutamine into 500 ml of D W or lactated Ringer's solution yields a solution of 500 g/ml; CRI of 0.6 ml/kg/hr
5
provides 5 g/kg/min.
Dilution of 40 mg of dopamine into 500 ml of D W or lactated Ringer's solution yields a solution of 80 g/ml; a volume of 0.75 ml/kg/hr
5
provides 1 g/kg/min.
ACE, Angiotensin-converting enzyme; CRI, constant rate infusion; D W, 5% dextrose in water. 5
2 hours. This route also provides a m i l d venodilating effect. or electrolyte depletion. A n ancillary approach that has been
Some patients require aggressive initial doses or cumulative described for patients w i t h fulminant cardiogenic edema is
doses administered at frequent intervals (see Box 3-1). F u r o phlebotomy (up to 25% of total b l o o d volume), but this is
semide can be given by constant rate infusion ( C R I ) , which not generally done.
may provide greater diuresis than bolus injection. The vet
erinary formulation (50 mg/ml) can be diluted to 10 m g / m l Vasodilation
for C R I using 5% dextrose in water ( D W ) , lactated Ringer's
5 Vasodilator drugs can reduce p u l m o n a r y edema by increas
solution (LRS), or sterile water. D i l u t i o n to 5 m g / m l i n D W 5 ing systemic venous capacitance, lowering pulmonary
or sterile water is also described. The patient's respiratory venous pressure, and reducing systemic arterial resis
rate, as well as other parameters (discussed i n more detail tance. A l t h o u g h A C E inhibitors are a mainstay o f C H F
later), guide the intensity of continued furosemide therapy. management, more immediate afterload reduction is des
Once diuresis has begun and respiration improves, the irable for animals w i t h acute p u l m o n a r y edema. Arterio
dosage is reduced to prevent excessive volume contraction lar vasodilation is not recommended for heart failure
caused by diastolic dysfunction or ventricular outflow away from the lungs via dilation of capacitance vessels. M o r
obstruction. phine is contraindicated i n dogs with neurogenic edema
S o d i u m nitroprusside is a potent arteriolar and venous because it can raise intracranial pressure. M o r p h i n e is not
dilator, with direct action o n vascular smooth muscle. It is used i n cats.
given by I V infusion because o f its short duration o f action.
Blood pressure must be closely monitored when using this Inotropic Support
drug. The dose is titrated to maintain mean arterial pressure Positive inotropic therapy is indicated when heart failure is
at about 80 m m H g (at least >70 m m Hg) or systolic b l o o d caused by poor myocardial contractility. Oral therapy with
pressure between 90 and 110 m m H g . Nitroprusside C R I is pimobendan or digoxin can be started as soon as practical
usually continued for 12 to 24 hours. Dosage adjustments for animals needing chronic inotropic support (see Table
may be needed because drug tolerance develops rapidly. Pro 3-3 and p. 65). Treatment for one to three days with an I V
found hypotension is the major adverse effect. Cyanide tox sympathomimetic (catecholamine) or phosphodiesterase
icity can result from excessive or prolonged use (e.g., longer (PDE) inhibitor drug can help support arterial pressure,
than 48 hours). Nitroprusside should not be infused with forward cardiac output, and organ perfusion when myocar
other drugs, and should be protected from light. dial failure or hypotension is severe.
Hydralazine, a pure arteriolar dilator, is an alternative to Catecholamines enhance contractility via a cAMP-medi
nitroprusside. It is useful for refractory pulmonary edema ated increase i n intracellular Ca++. They can provoke arrhyth
caused by mitral regurgitation (and sometimes dilated car mias and increase pulmonary and systemic vascular resistance
diomyopathy) because it can reduce regurgitant flow and (potentially exacerbating edema formation). Their short
lower left atrial pressure. A n initial dose o f 0.75 to 1 mg/kg half-life (<2 minutes) and extensive hepatic metabolism
is given orally, followed by repeated doses every 2 to 3 hours necessitate constant I V infusion. Dobutamine (a synthetic
until the systolic blood pressure is between 90 and 110 m m H g analog o f dopamine) has lesser effect on heart rate and after-
or clinical improvement is obvious. If b l o o d pressure cannot load and is preferred over dopamine. Dobutamine stimulates
be monitored, an initial dose o f 1 mg/kg is repeated i n 2 to ( -receptors, w i t h only weak action on ( - and -receptors.
1 2
4 hours i f sufficient clinical improvement has not been Lower doses (e.g., 3 to 7 g/kg/min) have m i n i m a l effects on
observed. The addition o f 2% nitroglycerin ointment may heart rate and b l o o d pressure. The initial infusion rate should
provide beneficial venodilating effects. be low; this can be gradually increased over hours to achieve
A n A C E inhibitor or amlodipine, with or without nitro greater inotropic effect and maintain systolic arterial pres
glycerin ointment, is an alternative to hydralazine/nitroglyc sure between 90 and 120 m m H g . Heart rate, rhythm, and
erine. The onset o f action is slower and the effects are less b l o o d pressure must be monitored closely. Although dobu
pronounced, but this regimen can still be helpful. tamine is less arrhythmogenic than other catecholamines,
Nitroglycerin (and other orally or transcutaneously higher infusion rates (e.g., 10 to 20 g/kg/min) can precipi
administered nitrates) act mainly o n venous smooth muscle tate supraventricular and ventricular arrhythmias. Adverse
to increase venous capacitance and reduce cardiac filling effects are more likely i n cats; these include seizures at rela
pressure. The major indication for nitroglycerin is acute car tively low doses.
diogenic pulmonary edema. Nitroglycerin ointment (2%) is Dopamine at l o w doses (<2-5 g/kg/minute) also stimu
usually applied to the skin o f the groin, axillary area, or ear lates vasodilator dopaminergic receptors i n some regional
pinna, although the efficacy o f this i n heart failure is unclear. circulations. Low-to-moderate doses enhance contractility
A n application paper or glove is used to avoid skin contact and cardiac output, but high doses (10-15 g/kg/minute)
by the person applying the drug. cause peripheral vasoconstriction and increase heart rate, O 2
Diuretics
ACE Inhibitors
Positive Inotropes
there is little veterinary data with the I V form. A P D E likely to increase the ventricular response rate by enhancing
inhibitor can be used concurrently with digoxin and a atrioventricular (AV) conduction. If dobutamine or dopa-
catecholamine. mine is deemed necessary for such a case, diltiazem (admin-
Digoxin is generally not used intravenously except for istered rapidly by m o u t h or cautiously by IV) is used to
some supraventricular tachyarrhythmias when other acute reduce the heart rate. Digoxin, administered either by mouth
therapy is unavailable or ineffective (see Chapter 4). Acidosis (loading) or cautiously by IV, is an alternative.
and hypoxemia associated with severe p u l m o n a r y edema can
increase myocardial sensitivity to digitalis-induced arrhyth- HEART FAILURE CAUSED BY
mias. If digoxin is used intravenously, it must be given slowly DIASTOLIC DYSFUNCTION
(over at least 15 minutes); rapid injection causes peripheral W h e n acute C H F is caused by hypertrophic cardiomyopathy,
vasoconstriction. The calculated dose is usually divided, and thoracocentesis (if needed), diuretics, and oxygen therapy
boluses of one fourth the dose are given slowly over several are given as outlined previously. Cutaneous nitroglycerin can
hours. also be used. Diltiazem or a 1-blocker such as atenolol can
If arrhythmias develop during I V inotropic therapy, the be given to slow heart rate and increase ventricular filling
infusion rate is reduced or the drug is discontinued. In time once severe dyspnea has abated; alternatively, I V admin
animals with atrial fibrillation, catecholamine infusion is istration of diltiazem or esmolol could be used. Propranolol
(or other nonselective -blockers) is generally avoided In most patients with decompensated C H F , the smallest
in patients with fulminant pulmonary edema because (2- fluid volume possible should be used to deliver drugs by
blockade could induce bronchoconstriction. C R I . Careful monitoring and continued diuretic use is
Arteriolar vasodilators can be detrimental i f dynamic important to prevent recurrent pulmonary edema. W h e n
left ventricular (LV) outflow obstruction coexists, because additional fluid therapy is necessary, D W or a reduced
5
afterload reduction provokes greater systolic obstruction sodium fluid (e.g., 0.45% N a C l with 2.5% dextrose) with
(see Chapter 8). A C E inhibitors at standard doses do not added KC1 is administered at a conservative rate (e.g., 15 to
appear to worsen the LV outflow gradient. Addition of an 30 ml/kg/day I V ) . Alternatively, 0.45% NaCl with 2.5%
A C E inhibitor is recommended as soon as oral therapy is dextrose or lactated Ringer's solution can be administered
possible. subcutaneously.
Potassium supplementation at a maintenance rate is pro
MONITORING AND FOLLOW-UP vided by 0.05 to 0.1 mEq/kg/hour (or more conservatively,
Repeated assessment is important to monitor the effective 0.5 to 2.0 mEq/kg/day). For animals with hypokalemia,
+
ness o f therapy and to prevent hypotension or severe azote higher rates are used: 0.15 to 0.2 mEq/kg/hour for mild K
mia caused by excessive diuresis. M i l d azotemia c o m m o n l y deficiency; 0.25 to 0.3 mEq/kg/hour for moderate deficiency;
occurs. Hypokalemia and metabolic alkalosis can occur after and 0.4 to 0.5 mEq/kg/hour for severe deficiency. Measuring
+
aggressive diuresis. A serum potassium concentration w i t h i n serum K concentration in 4 to 6 hours is advised when
the m i d - to high-normal range is especially important for supplementing for moderate to severe deficiency. Hypona
animals with arrhythmias. Serum biochemical testing every tremia and worsened fluid retention can develop after using
24 to 48 hours is advised until the patient is eating and low-sodium IV solutions in some patients. These require a
drinking well. more balanced crystalloid solution. Other supportive thera
Arterial blood pressure can be monitored indirectly or pies for C H F and any underlying disease(s) depend on indi
directly, but gaining arterial access can increase patient vidual patient needs. Parenteral fluid administration is
stress. Indirect measures of organ perfusion such as capillary tapered off as the animal is able to resume oral food and
refill time, mucous membrane color, urine output, toe-web water intake.
temperature, and mentation can also be useful. Body weight
should be monitored, especially with aggressive diuretic
therapy. MANAGEMENT OF CHRONIC
Central venous pressure ( C V P ) does not adequately HEART FAILURE
reflect left heart filling pressures. It should not be used to
guide diuretic or f l u i d therapy in patients with cardiogenic GENERAL CONSIDERATIONS
pulmonary edema. Although pulmonary capillary wedge A general approach to chronic heart failure therapy is pre
pressure can reliably guide therapy, the placement and care sented in this section. Additional information is found in the
of an indwelling pulmonary artery catheter require meticu chapters describing different diseases. Therapy is tailored to
lous attention to asepsis and close monitoring. the individual animal's needs by adjusting dosages, adding
Pulse oximetry is a helpful noninvasive means of m o n i or substituting drugs, and modifying lifestyle or diet. Pleural
toring oxygen saturation (SpO ). Supplemental O should be
2 2 effusion and large-volume ascites that accumulate despite
given if SpO is <90%; mechanical ventilation is indicated i f
2 medical therapy should be drained to facilitate respiration.
S p O is <80% despite O therapy. Arterial sampling for blood
2 2 Likewise, pericardial effusion that compromises cardiac
gas analysis is more accurate but is stressful for the patient. filling must be drained. As heart disease progresses, more
Resolution o f radiographic evidence for pulmonary edema aggressive therapy is usually needed. Support of cardiac
usually lags behind clinical improvement by a day or two. function with digoxin or pimobendan is often indicated in
After respiratory signs begin to abate and diuresis is dogs and sometimes in cats.
evident, low-sodium water is offered. Fluid administration Exercise restriction helps reduce cardiac workload regard
(either subcutaneously or intravenously) is generally not less o f heart failure etiology. Strenuous exercise can provoke
advised i n patients with fulminant C H F . In most cases, dyspnea and potentially serious cardiac arrhythmias even in
gradual rehydration by free choice (low sodium) water intake animals with compensated C H F . Chronic heart failure is
is preferred even after aggressive diuretic therapy. However, associated with skeletal muscle changes that lead to fatigue
fluid therapy may be necessary for patients with heart failure and dyspnea. Physical training can improve cardiopulmo
and renal failure, marked hypokalemia, hypotension, digoxin nary function and quality o f life in patients with chronic
toxicity, persistent anorexia, or other serious systemic disease. heart failure. This is partly mediated by improvement in
Some animals require relatively high cardiac filling pressure vascular endothelial function and restoration of flow-depen
to maintain cardiac output, especially those with myocardial dent vasodilation. Although it is difficult to know how much
failure or markedly reduced ventricular compliance (e.g., exercise is best, regular (not sporadic) mild to moderate
from hypertrophic cardiomyopathy or pericardial disease). activity is encouraged, as long as excessive respiratory effort
Diuresis and vasodilation in such cases can cause inadequate is not induced. Bursts of strenuous activity should be avoided.
cardiac output and hypotension. Dietary salt restriction and other nutritional issues are also
important in the management o f patients w i t h chronic heart effects are also thought to be important locally within the
failure. heart. Spironolactone is a competitive antagonist o f aldoste
+ +
rone. It promotes N a loss and K retention in the distal renal
DIURETICS tubule and can reduce the renal potassium wasting o f furo
Diuretic therapy is indicated for controlling cardiogenic p u l semide and other diuretics, especially when circulating aldo
monary edema and effusions. Diuretics remain fundamental sterone concentration is high. But its diuretic effect in n o r m a l
to the management of C H F because o f their ability to dogs is questionable. Spironolactone's onset of action is
decrease venous congestion and fluid accumulation (see slow; peak effect occurs w i t h i n 2 to 3 days.
Table 3-3). Agents that interfere with i o n transport in the Aldosterone release can occur despite the use of an A C E
loop of Henle (e.g., furosemide) have potent ability to inhibitor (so-called aldosterone escape); this may involve
promote both salt and water loss. Diuretics o f other classes, reduced hepatic clearance, increased release stimulated by K +
is ineffective, phenytoin (diphenylhydantoin) is the second (from a free-flowing jugular vein) is the suggested therapeu
drug of choice in dogs; its effects are similar to those o f tic goal for dosage titration. Systolic pressures o f less than 90
lidocaine. I V administration o f phenytoin must be slow to to 100 m m H g should be avoided. Clinical signs o f drug-
prevent hypotension and myocardial depression caused induced hypotension include weakness, lethargy, tachycar
by the propylene glycol vehicle. Phenytoin has occasionally dia, and poor peripheral perfusion. The vasodilator dose can
been used orally to treat or prevent ventricular tachyarrhyth be titrated upward, i f necessary, while m o n i t o r i n g for hypo
mias caused by digitalis. tension with each increase i n dose.
Other measures are also helpful for digoxin toxicity, Venodilators relax systemic veins, increase venous capac
including I V potassium supplementation i f the serum potas itance, decrease cardiac filling pressures (preload), and
sium concentration is <4 m E q / L (see p. 62). Magnesium reduce pulmonary congestion. Goals o f venodilator therapy
supplementation may also be effective in suppressing are to maintain central venous pressure at 5 to 10 c m
arrhythmias; M g S O has been used at 25 to 40 mg/kg via
4 H O and pulmonary capillary wedge pressure at 12 to
2
I
Amlodipine tion is recommended to help control fluid accumulation and
This dihydropyridine L-type Ca++ channel blocker causes reduce necessary drug therapy. Chloride restriction also
peripheral vasodilation as its major action, which tends to appears important. However, very low salt intake can increase
offsets any negative inotropic effect. A m l o d i p i n e has little rennin-angiotension system activation. It is unclear whether
effect on A V conduction. Besides being used to treat hyper a reduced-salt diet is necessary before overt C H F develops,
tension i n cats and sometimes dogs (see Chapter 11), it is an but refraining from feeding the patient high-salt table scraps
adjunctive therapy for refractory C H F . In dogs that cannot or treats w o u l d appear prudent. High-salt foods include pro
tolerate ACEIs, amlodipine could be used i n combination cessed meats; liver and kidney; canned fish; cheese, marga
w i t h a nitrate. rine, or butter; canned vegetables; breads; potato chips,
Amlodipine's oral bioavailability is good. It has a long pretzels, and other processed snack foods; and dog treats
duration o f action (at least 24 hours i n dogs). Plasma con such as rawhide and biscuits.
centration peaks i n 3 to 8 hours; half-life is about 30 hours. Moderate salt restriction is advised when clinical heart
Plasma concentrations increase with long-term therapy. failure develops. This represents a sodium intake of about
M a x i m a l effect develops over 4 to 7 days after therapy is 30 mg/kg/day (about 0.06% sodium for canned food or 210
begun in dogs. The drug is metabolized i n the liver. E l i m i n a to 240 mg/100 g o f dry food). Diets for senior animals or
tion is through the urine and feces. Because o f the delay i n those w i t h renal disease usually provide this level o f salt.
achieving m a x i m u m effect, l o w initial doses and weekly Prescription cardiac diets usually have greater sodium
b l o o d pressure monitoring during slow up-titration are restriction (e.g., 13 m g sodium/kg/day, or about 90 to 100 mg
recommended. sodium/100 g o f dry food, or 0.025% sodium i n a canned
food) and can be helpful i n patients with advanced heart
Prazosin failure. Severe sodium restriction (e.g., 7 mg/kg/day) can
Prazosin selectively blocks -receptors i n both arterial and
1 exacerbate N H activation and contribute to hyponatremia.
venous walls. It is not often used for chronic C H F manage A well-balanced diet and adequate caloric and protein intake
ment because drug tolerance can develop over time and the are important. Recipes for homemade low-salt diets are
capsule dose-size is inconvenient i n small animals. In addi available, but providing balanced vitamin and mineral
tion, controlled clinical studies i n dogs are lacking. Hypoten content may be difficult. D r i n k i n g water in some areas can
sion is the most c o m m o n adverse effect, especially after the contain high sodium concentrations. Nonsoftened water or
first dose. Tachycardia should occur less frequently than w i t h (where water from the public water supply contains more
hydralazine because presynaptic -receptors, important i n
2 than 150 p p m o f sodium), distilled water can be recom
the feedback control o f norepinephrine release, are not mended to further decrease salt intake. Supplementation of
blocked. specific nutrients is important i n some cases (discussed in
more detail later i n this section).
Nitrates Inappetence is c o m m o n i n dogs and cats with advanced
Nitrates act as venodilators. They are metabolized i n vascu heart failure. However, more calories may be needed because
lar smooth muscle to produce N O , w h i c h indirectly mediates of increased cardiopulmonary energy consumption or stress.
vasodilation. Nitroglycerin ointment or isosorbide dinitrate Malaise, increased respiratory effort, azotemia, digoxin
are used occasionally i n the management of chronic C H F , toxicity, and adverse effects o f other medications all can
either combined w i t h standard therapy for refractory C H F contribute to poor appetite. Meanwhile, poor splanchnic
or with hydralazine or amlodipine i n animals that cannot perfusion, bowel and pancreatic edema, and secondary intes
tolerate ACEIs. Nitrates effect b l o o d redistribution i n people, tinal lymphangiectasia may reduce nutrient absorption and
but there are few studies involving dogs, especially using the promote protein loss. Hypoalbuminemia and reduced
oral route for C H F management. There is extensive first-pass i m m u n e function may develop. Such factors, as well as renal
hepatic metabolism, and the efficacy o f oral nitrates is ques or hepatic dysfunction, also can alter the pharmacokinetics
tionable. Nitroglycerine ointment (2%) is usually applied of certain drugs.
cutaneously (see p. 60). Self-adhesive, sustained-release Strategies that sometimes help improve appetite include
preparations may be useful, but they have not been system warming the food to enhance its flavor, adding small amounts
atically evaluated i n small animals. Transdermal patches, of very palatable human foods (e.g., nonsalted meats or
5 m g , applied for 12 hours per day, have been used w i t h gravy, low-sodium soup), using a salt substitute (KC1) or
anecdotal success i n large dogs. Large doses, frequent appli garlic powder, handfeeding, and providing small quantities
cation, or long-acting formulations are most likely to be of the diet several times a day. If a change in diet is i n d i
associated with drug tolerance. Whether intermittent treat cated, a gradual switch improves acceptance (e.g., mixing
ment (with drug-free intervals) w i l l prevent nitrate tolerance the new w i t h the old diet i n a 1:3 ratio for several days, then
from developing in dogs and cats is u n k n o w n . 1:1 for several days, then 3:1, and finally the new diet
alone).
DIETARY CONSIDERATIONS Cardiac cachexia is the syndrome o f muscle wasting and
Heart failure can interfere with the kidney's ability to excrete fat loss associated with some cases of chronic C H F . Loss of
sodium and water loads. Therefore dietary s o d i u m restric muscle over the spine and gluteal region is usually noted
first. Weakness and fatigue are seen w i t h loss of lean body ation by echocardiogram is done to assess L V functional
mass; cardiac mass also can be affected. Cardiac cachexia is improvement. Dogs treated w i t h carnitine supplementation
thought to be a predictor of poor survival, and it is associated may give off a peculiar odor.
with reduced immune function i n people. The pathogenesis The m i n i m u m effective dose of L-carnitine is not k n o w n ;
of cardiac cachexia involves multiple factors, including pro it may vary with the type of deficiency, i f present at all.
inflammatory cytokines, T N F , and interleukin-1. These
a Several dose ranges have been suggested, including 50 to
substances suppress appetite and promote hypercatabolism. 100 mg/kg every 8 to 12 hours for systemic deficiency or
Dietary supplementation with fish oils, which are high i n 200 mg/kg every 8 hours for myopathic deficiency. Others
omega-3 fatty acids (eicosapentaenoic [EPA] and docosa use 1 g of oral L-carnitine every 8 hours for dogs <25 kg and
hexaenoic [ D H A ] acids) can reduce cytokine production a dose of 2 g every 12 hours for dogs between 25 and 40 kg.
and may improve endothelial function, among other benefi A b o u t teaspoonful of pure L-carnitine powder is the
cial effects. Approximate doses of 27 mg/kg/day E P A and equivalent o f 1 g. Both taurine and L-carnitine can be mixed
18 mg/kg/day D H A produced improvement i n cachexia and w i t h food for easier administration.
lower interleukin-1 levels i n dogs with dilated cardiomyopa
thy, although there was no effect of fish oil o n overall mortal Other Supplements
ity (Freeman, 1998). Whether higher E P A and D H A doses The role of other dietary supplements is unclear. Oxidative
would provide added benefit is not known; 30 to 40 mg/kg/ stress and free-radical damage probably play a role i n the
day E P A and 20 to 25 mg/kg/day D H A orally have been pathogenesis of myocardial dysfunction. Cytokines such as
recommended. T N F , shown to increase i n the circulation i n heart failure,
Grossly overweight pets with heart disease may benefit can promote oxidative stress. In people v i t a m i n C supple
from a weight-reducing diet. Obesity increases metabolic mentation has a beneficial effect o n endothelial function,
demands on the heart and expands b l o o d volume. This cardiac morbidity, and mortality. But the role of supplemen
Could increase cardiac filling and stimulate hypertrophy, tal antioxidant vitamins i n C H F is unclear, especially i n
increase venous pressure, and predispose the patient to animals. Whether coenzyme Q-10 provides any measurable
arrhythmias as well as alter cardiac metabolism. Mechanical benefit is controversial.
interference with respiration promotes hypoventilation; this
can contribute to cor pulmonale and complicate preexisting Beta-Blockers in Patients With
heart disease. Heart Failure
-blockers must be used cautiously, especially i n animals
Taurine with myocardial failure, because of their negative inotropic
Taurine is an essential nutrient for cats. Prolonged deficiency effects. A n important role is i n the management of certain
causes myocardial failure as well as other abnormalities (see arrhythmias, such as atrial fibrillation, and some ventricular
p. 151). Most commercial and prescription cat foods are well tachyarrhythmias (see Chapter 4). Another potential role for
supplemented with taurine, which has markedly reduced the some -blockers is i n modulating the processes that lead to
prevalence of taurine-responsive dilated cardiomyopathy i n pathologic cardiac remodeling i n patients w i t h heart failure.
cats. But taurine concentrations should be measured i n cats It is well k n o w n that certain agents, i n people, can improve
diagnosed with dilated cardiomyopathy, because the diet of cardiac function, reverse pathologic ventricular remodeling,
some cats may still be deficient. Taurine-deficient cats are and reduce mortality w i t h chronic therapy. Carvedilol (a
given oral supplements of taurine (250 to 500 mg) twice third-generation -blocker) appears to be most effective i n
daily. this regard, but some second-generation -blockers (e.g.,
Some dogs with dilated cardiomyopathy appear deficient metoprolol) also show a survival benefit. It is possible that
in taurine and/or L-carnitine, most notably American Cocker carvedilol or metoprolol might play a similar beneficial role
Spaniels but also others (see p. 136). Dogs fed protein- in dogs, especially those w i t h dilated cardiomyopathy, but
testricted diets can become taurine deficient, and some the clinical efficacy of this i n dogs (and cats) is presently not
develop evidence of dilated cardiomyopathy. Taurine supple known.
mentation for dogs <25 kg is 500 to 1000 m g every 8 hours; Carvedilol blocks , - , and -adrenergic receptors
1 2 1
for dogs 25 to 40 kg the dose is 1 to 2 g every 8 to 12 hours. but is without intrinsic sympathomimetic activity. It has
Although not all taurine-deficient American Cocker Spaniels antioxidant effects, reduces endothelin release, has some
heed both taurine and L-carnitine, most appear to. Ca++ blocking effect, and also is thought to promote vasodi
lation by affecting either N O or prostaglandin mechanisms.
L-carnitine Peak plasma concentrations appear to be quite variable after
Although L-carnitine deficiency has been identified i n Boxers oral administration. The drug is eliminated mainly through
and Doberman Pinschers with dilated cardiomyopathy, its hepatic metabolism. The half-life is short (<2 hours) i n dogs;
prevalence is thought to be low and the number of affected an active metabolite is thought to account for the nonselec
dogs responsive to L-carnitine supplementation even lower. tive -blocking effect, which lasts for 12 to 24 hours. Some
[Nevertheless, a trial period of supplementation (at a higher experimental evidence suggests that metoprolol also may
dosage) may be worthwhile. After at least 4 months, reevalu produce beneficial effects o n myocardial function i n dogs,
but ability to improve function and survival i n clinical cases pulmonary edema increases lung stiffness, which induces
is u n k n o w n . faster, more shallow respiration. Likewise, a persistent
Dogs w i t h occult myocardial dysfunction, stable compen increase i n resting heart rate accompanies the heightened
sated C H F (e.g., no evidence o f congestion for at least a week sympathetic tone o f decompensating failure.
or more) caused by cardiomyopathy, or chronic mitral regur A thorough physical examination, with emphasis on the
gitation that show signs o f myocardial dysfunction (and cardiovascular system (see Chapter 1), is important at each
compensated C H F ) are likely good candidates for carvedilol evaluation. Depending on the patient's status, clinical tests
(or metoprolol) therapy. There are presently no definitive might include a resting electrocardiogram ( E C G ) or ambu
guidelines. Initially, very low doses are used, along w i t h con latory monitoring, thoracic radiographs, serum biochemis
ventional C H F therapy as indicated. -blocker up-titration try analyses, an echocardiogram, serum digoxin concentration,
is done slowly. The dosage is increased every 1 to 2 weeks, i f or others. Periodic measurement o f serum electrolyte and
possible, over a 2-month period, to a target dose or as toler creatinine or B U N concentrations is recommended. Electro
ated. Anecdotal experience suggests a starting dose o f 0.05 lyte imbalance (especially hypokalemia or hyperkalemia,
to 0.1 mg/kg every 24 hours for carvedilol, w i t h an eventual hypomagnesemia, and sometimes hyponatremia) can occur
target o f 0.2 to 0.3 mg/kg every 12 hours (or higher) i f toler from the use o f diuretics, ACEIs, and salt restriction. Pro
ated. A n initial metoprolol dose might be 0.1 to 0.2 mg/kg/ longed anorexia can contribute to hypokalemia, but potas
day, w i t h an eventual target o f 1 mg/kg (if tolerated). Careful sium supplementation should not be used without
monitoring is important because C H F decompensation, documenting hypokalemia, especially when ACEIs and spi
bradycardia, and hypotension can occur. ronolactone are prescribed. Serum magnesium concentra
tion does not accurately reflect total body stores; however,
CHRONIC DIASTOLIC DYSFUNCTION supplementation may be especially beneficial i n animals that
Furosemide is continued orally i n patients that have devel develop ventricular arrhythmias while receiving furosemide
oped C H F from hypertrophic cardiomyopathy and other and digoxin.
causes o f diastolic dysfunction. Gradual reduction to the M a n y factors can exacerbate the signs o f heart failure,
lowest dosage level and frequency that are effective for con including physical exertion, infection, anemia, exogenous
trolling edema is the aim. A -blocker or diltiazem has tra fluid administration (excess volume or sodium load), high-
ditionally also been used, but the efficacy o f this i n cats w i t h salt diet or dietary indiscretion, erratic administration of
chronic C H F from hypertrophic cardiomyopathy is unclear. medication, inappropriate medication dosage for the level o f
A n A C E I i n such cases is thought to be beneficial, unless it disease, development of cardiac arrhythmias, environmental
provokes hypotension, particularly i n cats w i t h dynamic L V stress (e.g., heat, humidity, cold, smoke), development or
outflow obstruction (see Chapter 8). Spironolactone can also worsening of concurrent extracardiac disease, and progres
be useful as an adjunct therapy, especially for cases w i t h sion o f underlying heart disease (e.g., ruptured chordae ten
recurrent pleural effusion. dineae, left atrial tear, secondary right heart failure). Repeated
episodes o f acute, decompensated congestive failure that
REEVALUATION AND MONITORING may require hospitalization and intensive diuresis are rela
Client education is important when managing dogs and cats tively c o m m o n in patients with chronic progressive heart
with chronic heart failure. A good understanding o f the pet's failure.
underlying disease, the signs of heart failure, and the purpose
and potential adverse effects o f each medication make early STRATEGIES FOR REFRACTORY
identification o f complications more likely. Frequent reeval CONGESTIVE HEART FAILURE
uation is important i n patients with chronic heart failure Recurrent C H F while o n initial therapy with furosemide and
because underlying diseases progress and complications an A C E I is usually first handled by increasing the dose o f
often develop. The time frame for recheck visits may vary furosemide and/or maximizing the A C E I dose. Pimobendan
from weekly to every 6 months or so, depending on the or digoxin, i f not previously used, is added i f inotropic
severity o f heart disease and the clinical stability o f the support is indicated. Other ancillary therapy could include
patient. an additional diuretic or vasodilator. Spironolactone is rec
Medications and dosage schedules should be reviewed at ommended because o f its action as an aldosterone antago
each visit, and problems with drug administration or signs nist and its likely cardioprotective effects. Because its benefits
of adverse effects ascertained. H o w well the animal has are thought to extend beyond additional diuresis, use o f
responded to medications, the diet and appetite level, activ spironolactone earlier i n the course of therapy may be
ity level, and any other concerns should also be discussed. It advantageous. Some animals benefit from the addition o f a
is helpful to have owners m o n i t o r their pet's respiratory thiazide diuretic as failure becomes more refractory.
(and, i f possible, heart) rate when the animal is asleep or L o w doses o f an arteriolar vasodilator to further reduce
resting at home. Resting respiratory rates for n o r m a l animals afterload (e.g., amlodipine or hydralazine) can further inten
i n the home environment are usually <30 breaths/minute. A sify therapy for dogs with C H F caused by mitral regurgita
persistent increase (of >20%) i n resting respiratory rate is tion or dilated cardiomyopathy. Blood pressure should be
often an early sign o f worsening heart failure. This is because monitored. A n arteriolar vasodilator is not recommended
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C H A P T E R 4
Atrial Arrhythmias
Degenerative valvular disease with myocardial fibrosis
Cardiac
Ischemia
Mitral or tricuspid insufficiency Trauma
Dilated cardiomyopathy Cardiac neoplasia
Hypertrophic cardiomyopathy Heartworm disease
Restrictive cardiomyopathy Congenital heart disease
Cardiac neoplasia Ventricular dilation
Congenital malformation Mechanical stimulation (intracardiac catheter, pacing wire)
Accessory AV nodal bypass tract(s)
Myocardial fibrosis Extracardiac
High sympathetic tone Hypoxia
ischemia Electrolyte imbalances (especially K )+
include chronic mitral or tricuspid valve degeneration with Because some drugs can provoke arrhythmias, reducing
regurgitation, dilated cardiomyopathy, congenital malfor dosage or discontinuing the medication may be useful.
mations, and cardiac neoplasia. Other factors also may pre
dispose to atrial tachyarrhythmias (Box 4-2). CLINICAL PRESENTATION
Ventricular premature contractions (VPCs) occur i n Box 4-3 lists c o m m o n arrhythmias according to a clinical
association with disorders that affect cardiac tissue directly description of the heartbeat.
or indirectly through neurohormonal effects (see Box 4-2).
For instance, disorders of the central nervous system can TACHYARRHYTNMIAS
produce abnormal neural effects on the heart that cause Rapid Irregular Rhythms
ventricular or supraventricular arrhythmias (brain-heart Irregular heart rhythms are c o m m o n , and the E C G is impor
syndrome). When V P C s are infrequent or underlying cardiac tant for differentiating abnormal rhythms as well as sinus
function is normal, adverse hemodynamic effects may arrhythmia. Pulse deficits (see p. 6) and an irregular, weak
be negligible. However, hemodynamic impairment can be pulse with heart sounds of varying intensity and regularity
severe in dogs or cats with underlying heart disease, rapid may be detected on physical examination. Premature con
ventricular rates, or myocardial depression stemming from tractions interrupt ventricular filling and reduce stroke
a systemic disease. volume, sometimes to the extent that there is no ejection at
Factors such as underlying hypoxia, electrolyte or acid- all for that cycle (Fig. 4-1). Rapid atrial fibrillation (AF) and
base imbalances, and abnormal hormone concentrations premature contractions o f any origin often cause pulse defi
(e.g., thyroid) can exacerbate arrhythmias. Therefore cor cits. Ventricular premature complexes can cause audible
recting these is usually important for arrhythmia control. splitting of the heart sounds because of asynchronous ven-
tion disturbance is present, S V T may resemble ventricular
BOX 4-3 tachycardia. A vagal maneuver can be useful i n differentiat
ing among narrow Q R S complex tachycardias.
Clinical Characterization of Common Heart Rate and
Sustained, rapid arrhythmias lead to decrease i n cardiac
Rhythm Disturbances
output, arterial blood pressure, and coronary perfusion.
Fast, Irregular Rhythms C H F eventually may result. Signs o f poor cardiac output and
A t r i a l or s u p r a v e n t r i c u l a r premature contractions hypotension include weakness, depression, pallor, prolonged
P a r o x y s m a l atrial or supraventricular t a c h y c a r d i a capillary refill time, exercise intolerance, syncope, dyspnea,
A t r i a l flutter o r fibrillation prerenal azotemia, worsening rhythm disturbances, and
Ventricular p r e m a t u r e contractions sometimes altered mentation, seizure activity, and sudden
P a r o x y s m a l ventricular t a c h y c a r d i a death.
FIG 4 - 2
A therapeutic a p p r o a c h to supraventricular t a c h y a r r h y t h m i a s . S e e Table 4-2 for d r u g
d o s e s a n d text for more information. APCs, A t r i a l premature contractions; BP, b l o o d
pressure; CHF, c o n g e s t i v e heart failure; HCM, h y p e r t r o p h i c c a r d i o m y o p a t h y ; HF, heart
failure or m y o c a r d i a l d y s f u n c t i o n ; SVT, supraventricular t a c h y c a r d i a .
alternative agent i n refractory cases. Sotalol or a class I A or ful, repeating the vagal maneuver after antiarrhythmic drug
IC drug might be tried i f the arrhythmia is unremitting. injection may be useful, -blockers, Ca++ entry-blockers,
Adenosine appears to be ineffective in dogs for terminating digoxin, and other agents can increase the effectiveness of
SVTs. Further cardiac diagnostic tests are indicated once vagal maneuvers. The vagal maneuver can be further poten
conversion is achieved or the ventricular rate has decreased tiated i n dogs by administering intramuscular (IM) mor
to <200 beats/min. Once the rhythm is better controlled, oral phine sulfate (0.2 mg/kg) or I V edrophonium chloride (1 to
diltiazem, digoxin, amiodarone, or -blockers are options 4 m g ; atropine and an endotracheal tube should be readily
for chronic therapy; combinations of these agents can be available).
used.
Paroxysmal A V reciprocating tachycardia is a reentrant Ventricular Tachyarrhythmias
tachycardia involving an accessory pathway and the A V node Occasional V P C s i n an otherwise asymptomatic animal
(see p. 27). It is interrupted by slowing conduction or pro should not be treated. Moderately frequent single V P C s of
longing the refractory period of either or both tissues. A uniform configuration may not require antiarrhythmic drug
vagal maneuver may slow A V conduction enough to termi treatment either, especially if underlying heart function is
nate the rhythm. Diltiazem and -blockers slow A V conduc normal. Nevertheless, guidelines as to whether, when, and
tion and increase refractoriness. Another approach is I V how best to treat intermittent ventricular tachyarrhythmias
amiodarone or procainamide. Digoxin slows A V conduction remain undefined. Besides being expensive, antiarrhythmic
but has variable effects o n the accessory pathway; its use is drugs can have serious adverse effects, can provoke addi
usually discouraged i n people with preexcitation syndromes. tional arrhythmias (proarrhythmic effects), and may not be
Procainamide and quinidine may prevent A V reciprocating efficacious. Pretreatment and posttreatment 24- to 48-hour
tachycardia because they lengthen the refractory period ambulatory E C G recordings showing at least a 70% to 80%
of the accessory pathway. High-dose procainamide, with or reduction i n arrhythmia frequency provide the best indica
without a -blocker or diltiazem, has been successful in pre tor o f drug arrhythmia-suppression efficacy. Intermittent
venting the recurrence o f tachycardia i n some cases. Intra E C G recordings cannot truly differentiate between drug
cardiac electrophysiologic mapping with radiofrequency effect (or lack thereof) and the spontaneous, marked vari
catheter ablation o f accessory pathways has been used suc ability o f arrhythmia frequency that occurs i n any individual.
cessfully to abolish refractory S V T associated with preexcita However, in-hospital E C G recordings o f 15 seconds to several
tion in dogs, although this technique is not widely available minutes in duration are often the most practical attempt to
yet. monitor arrhythmias.
Atrial tachycardia caused by a persistent automatic ectopic Several factors influence the decision to use ventricular
focus may be particularly difficult to suppress. W h e n the antiarrhythmic drug therapy. These factors include the
antiarrhythmic strategies outlined in the preceding para nature of the animal's underlying disease, the perceived
graphs are unsuccessful, the goal o f therapy shifts to ven severity o f the arrhythmia, and the presence or absence of
tricular rate control. By prolonging A V conduction time and hemodynamic compromise. Diseases such as dilated cardio
refractoriness, fewer atrial impulses are then conducted and myopathy, arrhythmogenic right ventricular cardiomyopa
ventricular rate is slowed (and usually irregular). Therapy thy in Boxers, hypertrophic cardiomyopathy, and subaortic
with combinations o f diltiazem or a -blocker and digoxin, stenosis, among others, are frequently associated with sudden
sotalol, or amiodarone can be effective. The animal w i t h death from arrhythmias. Therefore ventricular antiarrhyth
persistent automatic atrial tachycardia could be a candidate mic therapy w o u l d appear most urgent in animals with these
for intracardiac electrophysiologic mapping and catheter diseases. However, the efficacy of a particular therapy to
ablation when such tools are available. Alternatively, heart prolong survival as well as suppress the arrhythmia is diffi
rate control could be achieved by A V node ablation with cult to accurately assess. Traditional guidelines for instituting
permanent pacemaker implantation. ventricular antiarrhythmic therapy have been based on fre
V a g a l m a n e u v e r . A vagal maneuver can help the c l i n i quency, prematurity, and variability of the Q R S configura
cian differentiate among tachycardias caused by an ectopic tion o f the arrhythmia. Characteristics thought to imply
automatic focus, those dependent on a reentrant circuit increased electrical instability include rapid paroxysmal or
involving the A V node, or excessively rapid sinus node acti sustained ventricular tachycardia (e.g., >130 beats/min),
vation. The vagal maneuver may transiently slow or inter multiform (polymorphic) V P C configuration, or close cou
mittently block A V conduction, exposing abnormal atrial P ' pling of V P C s to preceding complexes (R-on-T phenome
waves, and allow an ectopic atrial focus to be identified. Vagal non). However, clear evidence that these guidelines predict
maneuvers can terminate reentrant SVTs involving the A V greater risk o f sudden death i n all patients is lacking. It is
node by interrupting the reentrant circuit. The maneuver probably more important to consider the animal's underly
tends to temporarily slow the rate o f sinus tachycardia. ing heart disease and whether the arrhythmia is causing
Vagal maneuvers are performed by massaging the area signs o f hypotension or low cardiac output. Animals that
over the carotid sinuses (below the mandible i n the jugular are hemodynamically unstable or have a disease associated
furrows) or by applying firm bilateral ocular pressure for 15 with sudden cardiac death are treated earlier and more
to 20 seconds. A l t h o u g h initial attempts are often unsuccess aggressively.
A c u t e t h e r a p y f o r v e n t r i c u l a r t a c h y c a r d i a . Sus Cats with frequent ventricular tachyarrhythmias are
tained ventricular tachycardia is treated aggressively because usually given a -blocker first. Alternatively, low doses o f
it can result in marked decreases i n arterial b l o o d pressure, lidocaine can be administered. However, cats, especially if
especially at faster rates. Lidocaine (IV) is usually the first- not anesthetized, can be quite sensitive to the neurotoxic
choice drug for controlling serious ventricular tachyarrhyth effects o f this drug. Procainamide or sotalol can also be
mias i n hospitalized dogs. It is effective against arrhythmias used.
of several underlying mechanisms and has m i n i m a l adverse Digoxin is not used specifically for treating ventricular
hemodynamic effects. Because the effects o f I V boluses last tachyarrhythmias, although it may be indicated for patients
only about 10 to 15 minutes, a constant rate infusion (CRI) with concurrent heart failure and supraventricular arrhy
is warranted if the drug is effective. Small supplemental IV thmias. Digoxin can also predispose to the development
boluses can be given i n addition to the C R I to maintain of ventricular arrhythmias. Another antiarrhythmic drug
therapeutic drug concentrations until a steady state is may be necessary i n animals with preexisting frequent
achieved. IV infusion can be continued for several days, i f or repetitive V P C s . Phenytoin is used only i n dogs for digi
needed. If lidocaine is ineffective after maximal recom talis-induced ventricular tachyarrhythmias that are refrac
mended doses, several other strategies can be tried (Fig. 4-3). tory to lidocaine. Ancillary KC1 supplementation (if serum
+
IV amiodarone or oral mexiletine or sotalol can be more K 4 m E q / L ) with or without M g S O can increase antiar
4
FIG 4 - 3
A therapeutic a p p r o a c h to ventricular t a c h y a r r h y t h m i a s . S e e Table 4-2 for d r u g d o s e s
a n d text for more i n f o r m a t i o n . CRI, Constant-rate infusion; Dx, d i a g n o s i s ; ECG,
electrocardiogram.
1. Reevaluate the E C G c o u l d the rhythm have been incor effects than the Class I drugs. Concurrent disease should be
rectly diagnosed initially? For example, S V T with an treated i f possible. It is likely that animals with arrhythmias
intraventricular conduction disturbance can m i m i c ven associated with underlying heart disease also benefit from
tricular tachycardia. In such cases, I V diltiazem is usually the use o f -blockers, A C E inhibitors, and some other ther
more effective than lidocaine. apies, as do people. However, -blockers alone do not appear
+
2. Reevaluate the serum K (and M g ) concentration. + +
effective i n suppressing ventricular tachyarrhythmias in
Hypokalemia reduces the efficacy of class I antiarrhyth Doberman Pinschers with cardiomyopathy.
mic drugs (e.g., lidocaine, procainamide, quinidine) and Several strategies are available for long-term oral therapy
can predispose to the development of arrhythmias. If the of patients with ventricular tachyarrhythmias:
+
serum K concentration is <3 m E q / L , KC1 can be infused
+
at 0.5 mEq/kg/hr; for serum K between 3 to 3.5 m E q / L , 1. A Class I agent alone: sustained-release procainamide,
+
KC1 can be infused at 0.25 mEq/kg/hr. A serum K con mexiletine, (or possibly tocainide); occasionally a class IA
centration i n the high n o r m a l range is the goal. If the and IB drug are used together. However, Class I drugs
++
serum Mg concentration is <1.0 mg/dl, M g S O or 4 provide questionable protection from V F .
M g C l , diluted in D W , can be administered at 0.75 to
2 5 2. A Class I agent combined with a -blocker (Class II)
1.0 mEq/kg/day by C R I . agent: sustained release procainamide or mexiletine and
3. Maximize the dose o f the conventional antiarrhythmic atenolol or propranolol. -Blockers can be useful for both
drug having the greatest effect. ventricular and supraventricular arrhythmias that are
4. Try amiodarone (IV), sotalol (oral), or a -blocker i n provoked by sympathetic stimulation or release of
conjunction with a class I drug (e.g., propranolol, esmolol, catecholamines. -Blockers may confer some protection
or atenolol w i t h procainamide or lidocaine) or a class I A against V F .
drug with a IB drug (e.g., procainamide with lidocaine or 3. A Class III agent: sotalol or amiodarone. These drugs may
mexiletine). provide greater antifibrillatory protection, but they also
5. Consider the possibility that the drug therapy is exacer have potentially serious adverse effects.
bating the rhythm disturbance (a proarrhythmic effect).
Polymorphous ventricular tachycardia (torsades de Presently, the three most favored options are sotalol; ami
pointes) has been associated with quinidine, procain odarone; or mexiletine or sustained-release procainamide
amide, and other drug toxicities. with atenolol, because they are likely to provide a greater
6. M g S O may be effective i n animals w i t h ventricular
4 antifibrillatory effect.
tachyarrhythmias associated with digoxin toxicity or with Frequent reevaluation is important for patients o n long-
suspected polymorphous ventricular tachycardia (tors term antiarrhythmic therapy (for any rhythm disturbance).
ades de pointes). A slowly administered I V bolus o f 25 to Patients' owners can be shown how to use a stethoscope or
40 mg/kg, diluted i n D W , followed by an infusion o f the
5 palpate the chest wall to count the number of "skipped" beats
same dose over 12 to 24 hours, has been suggested. Given per minute at home; this may yield an approximation o f the
that M g S O contains 8.13 m E q magnesium per gram, a
4 frequency o f arrhythmic events (either single or paroxysms).
similar magnesium dose is provided by calculating 0.15 However, continuous 24- to 48-hour ambulatory E C G
to 0.3 m E q / k g . recordings are more accurate. The decision to continue or
7. If the animal is tolerating the arrhythmia well, continue discontinue successful antiarrhythmic therapy is also based
supportive care, correct other abnormalities as possible, on consideration o f the clinical situation and any underlying
and continue cardiovascular monitoring alone or w i t h cardiac disease.
the most effective antiarrhythmic drug.
8. Direct current ( D C ) cardioversion or ventricular pacing Atrial Fibrillation
may be available at a referral center; ECG-synchronized A F most often develops when there is marked atrial enlar
equipment and anesthesia or sedation are required. H i g h - gement. It is a serious arrhythmia, especially when the
energy, nonsynchronized shock (defibrillation) can be ventricular response rate is high. Predisposing conditions
used for rapid polymorphic ventricular tachycardia or include dilated cardiomyopathy, chronic degenerative A V
flutter degenerating into fibrillation. valve disease, congenital malformations that cause atrial
Chronic oral therapy for ventricular tachyar enlargement, and hypertrophic or restrictive cardiomyopa
r h y t h m i a s . The same drug that was most effective during thy i n cats. Clinical heart failure is c o m m o n in these animals.
acute therapy, or a similar one, is often continued orally A F is characterized by an irregular and usually rapid ven
when long-term therapy is thought to be needed. A l t h o u g h tricular response rate. W h e n little time is available for ven
suppression of ventricular ectopy is one aim, reducing the tricular filling, stroke volume is compromised. Furthermore,
risk o f sudden arrhythmic death is the real issue for long- atrial contraction (the "atrial kick"), which is especially
term therapy. Whereas the Class IB drugs (lidocaine and important to ventricular filling at faster heart rates, is lost.
mexiletine) appear to raise the fibrillation threshold more Cardiac output tends to decrease considerably when A F
than the Class I A agents (procainamide and quinidine), develops; poor myocardial function exacerbates this
Class III agents appear to have m u c h greater antifibrillatory decrease.
FIG 4 - 4
A therapeutic a p p r o a c h to atrial fibrillation. S e e Table 4-2 for d r u g d o s e s a n d text for
more i n f o r m a t i o n . AF, atrial fibrillation; CHF, c o n g e s t i v e heart f a i l u r e ; HCM, h y p e r t r o p h i c
c a r d i o m y o p a t h y ; HR, heart rate.
Long-lasting conversion to sinus rhythm is rare in the face conduction and ventricular rate. Because o f their potential
of marked underlying cardiac disease, even after successful to depress myocardial function, the agent chosen is usually
electrical cardioversion. Therefore treatment in most cases is added 1 to 2 days after starting oral digoxin i n most patients
directed at reducing the ventricular response rate by slowing with reduced myocardial contractililty. A m i o d a r o n e can be
AV conduction (Fig. 4-4). A slower heart rate allows more added (or substituted) for additional rate control. A n occa
time for ventricular filling and lessens the relative impor sional dog w i l l revert to sinus rhythm i n response to diltia
tance o f atrial contraction. In-hospital heart rates <150 (or zem or amiodarone therapy. Digoxin is not used in cats with
180 in cats) beats/min are desirable. Heart rate should be hypertrophic cardiomyopathy that develop A F ; a -blocker
documented by E C G ; counting the ventricular rate by aus or diltiazem is used instead.
cultation or palpation is often highly inaccurate. Resting W h e n A F develops i n patients that also have ventricular
heart rate at home, which can be monitored by the owner, is preexcitation, A V nodal blocking drugs (Ca++ blockers,
a better indicator o f drug effectiveness. Heart rates o f 70 to digoxin, and possibly -blockers) should not be used because
120 beats/min in dogs and 80 to 140 beats/min in cats are they can paradoxically increase the ventricular response rate.
probably acceptable. Amiodarone is recommended i n these cases. Sotalol or pro
T h e r a p y f o r a t r i a l f i b r i l l a t i o n . The oral drug o f first cainamide can also be used.
choice for most dogs with A F is digoxin (see Table 3-3). If Electrical cardioversion o f A F has been o f limited success
the heart rate exceeds 200 to 220 beats/min at rest, twice the i n animals; most revert to A F . Newer methods, including
eventual oral maintenance dosage can be given for 1 to 2 biphasic current delivery combined with amiodarone (or
days. W h e n more immediate heart rate reduction is i n d i other drug) therapy, may be more successful. Nevertheless,
cated, IV diltiazem is recommended. This has less negative experience with A F in people suggests that heart rate control
inotropic effect than verapamil or an I V -blocker, although provides similar survival benefit (and fewer adverse effects)
esmolol could be cautiously tried because o f its short half- than conversion to sinus rhythm.
life. If dobutamine or dopamine infusion is needed to
support myocardial function (see p. 60 and Box 3-1), I V Lone atrial fibrillation
diltiazem or an IV loading dose o f digoxin (cautiously) can A F sometimes develops in large or giant-breed dogs without
be used, but a -blocker should be avoided. cardiomegaly or other evidence o f structural heart disease.
Digoxin alone does not adequately reduce the heart rate This can occur transiently, usually i n association with trauma
in many animals. Increases i n sympathetic tone from C H F , or surgery. A F with a slow ventricular response rate can also
exercise, or excitement can override the vagal effect of digoxin be an incidental finding i n such dogs. This is k n o w n as "lone
on A V conduction. Either a -blocker or diltiazem can be AF". Acute A F without signs o f heart disease or failure may
added and titrated upward as needed to further slow A V convert to sinus rhythm spontaneously or i n response to
drug therapy, such as with diltiazem (e.g. P O for ~3 days),
amiodarone, or possibly sotalol or other Class III or IC
agents. Acute onset A F associated with high vagal tone may
convert with I V lidocaine. Q u i n i d i n e P O or I M has been
used for acute A F conversion i n large dogs without signs of
heart disease; but adverse effects can include increased ven
tricular response rate from the drug's vagolytic effects, ataxia,
and most seriously, seizures or polymorphic ventricular
tachycardia. If effective, the drug is discontinued after sinus
rhythm is achieved. Dogs that do not convert to sinus rhythm
are either given digoxin or continued on diltiazem for rate
control. Alternatively, i f the ventricular rate is consistently
low at rest, dogs can be monitored periodically without
therapy; but rapid heart rates still are likely with exercise or
FIG 4 - 5
excitement.
A therapeutic a p p r o a c h to m a n a g i n g symptomatic bradyar
rhythmias. S e e B o x 3-1 a n d Table 4-2 a n d text for more
BRADYARRHYTHMIAS information.
Sinus Bradycardia
Slow sinus rhythm (or arrhythmia) can be a n o r m a l finding,
especially in athletic dogs. Sinus bradycardia has also been different regions, but the syndrome is also seen in Dachs
associated with the administration of various drugs (e.g., hunds, Cocker Spaniels, Pugs, and mixed-breed dogs.
xylazine, thorazine tranquilizers, some anesthetic agents, Affected dogs have episodes of marked sinus bradycardia
medetomidine, digoxin, calcium entry blockers, -blockers, with sinus arrest (or sinoatrial block). Sick sinus syndrome
parasympathomimetic drugs), trauma or diseases of the is extremely rare in cats.
central nervous system, organic disease of the sinus node, Abnormalities of the A V conduction system may coexist,
hypothermia, hyperkalemia, and hypothyroidism, among causing the activity of subsidiary pacemakers to be depressed
other disorders. Conditions that increase vagal tone (e.g., and leading to prolonged periods of asystole. Some affected
respiratory or gastrointestinal tract disease or a mass involv dogs also have paroxysmal SVTs, prompting the name bra
ing the vagosympathetic trunk) may induce sinus bradycar dycardia-tachycardia syndrome (Fig. 4-6). Premature com
dia. C h r o n i c pulmonary disease often is associated with plexes may be followed by long pauses before sinus node
pronounced respiratory sinus arrhythmia. activity resumes, indicating a prolonged sinus node recovery
In most cases o f sinus bradycardia, the heart rate increases time. Intermittent periods of accelerated junctional rhythms
in response to exercise or atropine administration, and no and variable junctional or ventricular escape rhythms may
clinical signs are associated with the slow heart rate. Symp also occur.
tomatic dogs usually have a heart rate slower than 50 beats/ Clinical signs can result from bradycardia and sinus arrest,
m i n and/or pronounced underlying disease. Because sinus paroxysmal tachycardia, or both. Signs can mimic seizures
bradycardia and sinus bradyarrhythmia are extremely rare stemming from neurologic or metabolic disorders. Concur
in cats, a search for underlying cardiac or systemic disease rent degenerative A V valve disease is also often present. Some
(e.g., hyperkalemia) is warranted i n any cat with a slow heart dogs have evidence of C H F , usually secondary to A V valve
rate. regurgitation, although the arrhythmias may be a complicat
W h e n sinus bradycardia is associated with signs of weak ing factor.
ness, exercise intolerance, syncope, or worsening underlying E C G abnormalities are frequently pronounced in dogs
disease, an anticholinergic (or adrenergic) agent is given with long-standing sick sinus syndrome. Nevertheless, some
(Fig. 4-5). If sinus bradycardia is the result of a drug effect, dogs have one or more normal resting ECGs. Prolonged
discontinuation, dosage reduction, or other therapy should visual E C G monitoring or 24-hour ambulatory E C G can
be used, as appropriate (e.g., reversal of anesthesia or medeto help establish a definitive diagnosis. A n atropine challenge
midine, calcium salts for calcium entry blocker overdose, test is done i n dogs with persistent bradycardia (see p. 93).
dopamine or atropine for -blocker toxicity). If there is The normal response is an increase in the heart rate of 150%
inadequate increase in heart rate with medical therapy, tem or to > 130 to 150 beats/min. Dogs with sick sinus syndrome
porary or permanent pacing is indicated (see Suggested generally have a subnormal response.
Readings). Therapy with an anticholinergic agent, methylxanthine
bronchodilator, or terbutaline given orally may temporarily
Sick Sinus Syndrome help some animals that have a positive response to atropine
Sick sinus syndrome is a condition of erratic sinoatrial func challenge. However, anticholinergic or sympathomimetic
tion characterized by episodic weakness, syncope, and drugs used to accelerate the sinus rate can also exacerbate
Stokes-Adams seizures. Older female Miniature Schnauzers tachyarrhythmias. Conversely, drugs used to suppress these
and West H i g h l a n d White Terriers are c o m m o n l y affected in supraventricular tachyarrhythmias can magnify the brady-
FIG 4 - 6
C o n t i n u o u s e l e c t r o c a r d i o g r a m from a n 111-year-oldf e m a l e M i n i a t u r e S c h n a u z e r with sick
sinus s y n d r o m e , illustrating a c o m b i n a t i o n of b r a d y c a r d i a a n d t a c h y c a r d i a . The top
portion s h o w s persistent sinus arrest with three different e s c a p e c o m p l e x e s , f o l l o w e d b y a n
atrial premature c o m p l e x . There is a 1-mV c a l i b r a t i o n mark in the m i d d l e of the top strip.
The b r a d y c a r d i a is interrupted b y a run of atrial t a c h y c a r d i a at a rate of 2 5 0 b e a t s / m i n ,
with 1 :1 atrioventricular c o n d u c t i o n initially; but starting in the m i d d l e of the bottom strip,
e v e r y other P' w a v e is b l o c k e d ( 2 : 1 atrioventricular c o n d u c t i o n ) .
cardia, although digoxin or diltiazem is helpful i n some dogs escape focus, as well as the tachyarrhythmia. Permanent
if used cautiously. Sick sinus syndrome with frequent or pacemaker implantation is the treatment o f choice, although
severe clinical signs is best managed by permanent artificial the prognosis is poor i n dogs w i t h concurrent ventricular
pacing. The Suggested Readings list includes sources of myocardial dysfunction.
further details on pacing. Dogs that remain symptomatic Hyperkalemia should be ruled out in animals without P
because of paroxysmal SVTs can safely be given appropriate waves. The apparent lack o f atrial electrical and mechanical
antiarrhythmic therapy once a normally functioning pace activity ("silent atrium") caused by hyperkalemia w i l l resolve
maker is in place. with treatment. Sinus node activity (and P waves) become
+
evident as the serum K concentration returns to normal.
Atrial Standstill
Persistent atrial standstill is a rhythm disturbance character Atrioventricular Conduction Block
ized by lack o f effective atrial electrical activity (i.e., no P Second-degree, or intermittent, A V block usually causes
waves and a flat baseline) in which a junctional or ventricu an irregular heartbeat. In contrast, the ventricular escape
lar escape rhythm controls the heart. This bradyarrhythmia rhythm that occurs w i t h a third-degree, or complete, A V
is rare in dogs and extremely rare i n cats; most cases have block is regular, although premature contractions or shifts
occurred i n English Springer Spaniels with muscular dystro i n the escape focus may cause some irregularities. A V con
phy o f the fascioscapulohumeral type, although infiltrative duction disturbances may result from therapy with certain
and inflammatory diseases of the atrial myocardium can also drugs (e.g., agonists, opioids, digoxin), high vagal tone, or
2
result in atrial standstill. Because organic disease o f the atrial organic disease o f the A V node. Diseases that have been
myocardium may also involve the ventricular myocardium, associated with A V conduction disturbances include bacte
persistent atrial standstill may be a harbinger o f a serious rial endocarditis (of the aortic valve), hypertrophic cardio
and progressive cardiac disorder. myopathy, infiltrative myocardial disease, and myocarditis.
Medical treatment for persistent atrial standstill is rarely Idiopathic heart block may occur i n middle-aged to older
rewarding; however, an anticholinergic drug or an infusion dogs; congenital third-degree heart block has also been seen
of dopamine or isoproterenol can sometimes temporarily i n dogs. Symptomatic heart block is less c o m m o n in cats, but
accelerate the escape rhythm. If ventricular tachyarrhyth evidence o f any A V conduction disturbance should prompt
mias result from this treatment, the drug should be discon further diagnostic evaluation. Most cases have been associ
tinued or the dose reduced. Oral terbutaline may also have ated with hypertrophic cardiomyopathy. Heart block is occa
some beneficial effect. Antiarrhythmic agents are contrain sionally found in old cats without detectable organic heart
dicated in these animals because they may suppress the disease.
Type I second-degree A V block and first-degree A V block
BOX 4-4
are frequently associated w i t h high vagal tone or drug effects
in dogs. These animals are often asymptomatic; exercise or Formulas to Calculate Constant-Rate Infusion
injection of an anticholinergic drug (atropine or glycopyr
Method 1
rolate) usually abolishes the conduction disturbance. H i g h -
grade (many blocked P waves) second-degree A V block and (Allows for "fine-tuning" fluid as well as drug administration
complete heart block usually cause lethargy, exercise intoler rate)
ance, weakness, syncope, and other signs of low cardiac Determine desired drug infusion rate: g/kg/min x kg
body weight = g/min (A)
output. These signs become severe when the heart rate is
Determine desired fluid infusion rate: ml/hour 60 = m l /
consistently <40 beats/min. C H F develops secondary to
min (B)
chronic bradycardia i n some dogs, especially i f other cardiac
(A) (B) = g/min ml/min = g drug/ml of fluid
disease is present. Convert from g to mg of drug needed (1 g =
A n atropine challenge test (p. 93) is used to determine the 0.001 mg)
degree o f vagal influence on the A V block. Long-term oral M g drug/ml fluid x ml of fluid in bag (or bottle, etc) = mg
anticholinergic therapy (e.g., propantheline bromide) can be of drug to a d d to the fluid container
attempted in symptomatic animals that are atropine-respon
Method 2
sive (see Fig. 4-5). Atropine or subsequent oral anticholiner
gic therapy is often ineffective, however, so artificial pacing (For total dose over a 6-hour period, must also calculate
fluid volume and administration rate)
is usually indicated. A n emergency infusion o f dopamine
Total dose in mg to infuse over a 6-hour period = Body
(see Box 3-1) or isoproterenol may increase the ventricular
weight (kg) x dose (g/kg/min) x 0.36
escape rate i n animals with high-grade second- or third-
degree block, although ventricular tachyarrhythmias may Method 3 (for Lidocaine)
also be provoked. O r a l isoproterenol is usually ineffective. A (Faster but less helpful if fluid rate is important or fine drug-
thorough cardiac workup is indicated before permanent dosage adjustments are needed)
artificial pacemaker implantation because some underlying For CRI of 4 4 g/kg/min of lidocaine, add 25 ml of 2%
diseases (e.g., myocardial disease, endocarditis) are associ lidocaine to 2 5 0 ml of D W 5
ated with a poor prognosis, even after pacing. Temporary Infuse at 0.25 m l / 2 5 lb of body weight/min
transvenous pacing is sometimes used for 1 to 2 days to
assess the animal's response to a n o r m a l heart rate before
permanent pacemaker surgery is performed.
venting VF. Class I V drugs are the calcium entry blockers;
ventricular arrhythmias are usually not responsive to these
ANTIARRHYTHMIC AGENTS agents, but they are important against supraventricular
tachyarrhythmias. Antiarrhythmic agents within this classi
Antiarrhythmic drugs can act by slowing the rate o f a tachy fication scheme are contraindicated i n animals with com
cardia, terminating a reentrant arrhythmia, or preventing plete heart block and should be used only cautiously in
abnormal impulse formation or conduction. These effects animals with sinus bradycardia, sick sinus syndrome, and
occur through modulation o f tissue electrophysiologic prop first- or second-degree A V block.
erties and/or autonomic nervous system effects. The tradi
tional (Vaughan-Williams) antiarrhythmic drugs are CLASS I ANTIARRHYTHMIC DRUGS
+
classified according to their m a i n electrophysiologic effects Class I antiarrhythmic drugs block membrane N a channels
o n cardiac cells (Table 4-1). Although this classification and depress the action potential upstroke (phase 0), which
system has several shortcomings (e.g., some drugs having slows conduction velocity along the cardiac cells. They have
antiarrhythmic effects are excluded, several drugs have the been subclassified according to differences in other electro
multiclass effects, and focus o n i o n channel mechanisms is physiologic characteristics. These differences (see Table 4-1)
lacking), clinical reference to this classification persists. See may influence their efficacy against particular arrhythmias.
+
Table 4-2 and Box 4-4 for antiarrhythmic drug dosages and Most o f the Class I agents depend on extracellular K con
C R I calculation methods. centration for their effects, and they lose effectiveness i n
Class I agents tend to slow conduction and decrease auto patients with hypokalemia.
maticity and excitability by means o f their membrane-stabi
lizing effects; traditional ventricular antiarrhythmic drugs Lidocaine
belong to this class. Class II drugs include the (-adrenergic Lidocaine HC1 is usually the first-choice I V ventricular anti
antagonists (-blockers), w h i c h act by inhibiting the effects arrhythmic agent i n dogs. It is often ineffective against
of catecholamines o n the heart. Class III drugs prolong supraventricular arrhythmias. It has little effect on sinus
the effective refractory period o f cardiac action potentials node rate, A V conduction rate, and refractoriness. Lidocaine
without decreasing conduction velocity; they may be most suppresses automaticity i n normal Purkinje fibers and dis
effective in suppressing reentrant arrhythmias and in pre- eased myocardial tissue, slows conduction, and reduces the
TABLE 4-1
+
Class I Decreases fast inward N a current; membrane-stabilizing effects (decreased
conductivity, excitability, and automaticity)
IA Quinidine Moderately decreases conductivity, increases action potential duration; can
Procainamide prolong Q R S complex and Q-T interval
Disopyramide
IB Lidocaine Little change in conductivity, decreases action potential duration; QRS
Mexiletine complex and Q-T interval unchanged
Phenytoin
IC Flecainide Markedly decreases conductivity without change in action potential duration
Encainide
Propafenone
Class II Propranolol -adrenergic blockadereduces effects of sympathetic stimulation (no direct
Atenolol myocardial effects at clinical doses)
Esmolol
Metoprolol
Carvedilol
Others
Class III Sotalol Selectively prolongs action potential duration and refractory period;
Amiodarone antiadrenergic effects; Q-T interval prolonged
Ibutilide
Dofetilide
Others
Class IV Verapamil Decreases slow inward Ca++ current (greatest effects on sinoatrial and AV
Diltiazem nodes)
Others
Other Antiarrhythmic Digoxin Antiarrhythmic action results mainly from indirect autonomic effects
Agents (especially increased vagal tone)
Atropine Anticholinergic agents oppose vagal effects on S A and AV nodes
Glycopyrrolate (glycopyrrolate and other drugs also have this effect)
Others
+ ++
Adenosine Briefly opens K channels and indirectly slows Ca current (greatest effects on
sinoatrial and AV nodes); may transiently block AV conduction, but
ineffective in dogs
supernormal period (during which the cell can be reexcited complete first-pass hepatic elimination. I V administration,
before complete repolarization occurs). It has greater effects usually as slow boluses followed by C R I , is most effective.
on diseased and hypoxic cardiac cells and at faster stimula Antiarrhythmic effects after I V bolus occur w i t h i n 2 minutes
tion rates. The electrophysiologic effects of lidocaine are and abate w i t h i n 10 to 20 minutes. C R I without a loading
dependent on the extracellular potassium concentration. dose produces steady-state concentrations i n 4 to 6 hours.
Hypokalemia may render the drug ineffective, but hyperka The half-life is <1 hour i n the dog. A n initial bolus of 2 mg/
lemia intensifies its depressant effects on cardiac membranes. kg is used in dogs and can be repeated two to three times i f
Lidocaine produces little or no depression of contractility at necessary. Lower doses should be used in cats to avoid toxic
therapeutic doses when administered slowly IV; this is useful ity (loading dose of 0.25 to 0.5 mg/kg). The half-life i n cats
in dogs with heart failure. The lidocaine congeners tocainide is 1 to 2 hours. Therapeutic plasma concentrations are
and mexiletine similarly produce m i n i m a l negative inotropic thought to range from 1.5 to 6 g/ml in dogs. O n l y lidocaine
and hypotensive effects. Toxic concentrations o f lidocaine without epinephrine should be used for antiarrhythmic
can cause hypotension. therapy. If I V access is not possible, I M administration could
Lidocaine undergoes rapid hepatic metabolism; some be used, but I V is m u c h preferred.
metabolites may contribute to its antiarrhythmic and toxic The most c o m m o n toxic effect of lidocaine is central
effects. Lidocaine is not effective orally because of its almost nervous system excitation. Signs include agitation,
TABLE 4-2
Dosage o f A n t i a r r h y t h m i c Drugs
AGENT DOSAGE
Class I
Class II
Atenolol D o g : 0 . 2 - 1 . 0 m g / k g b y mouth q 1 2 - 2 4 h
Cat: 6 . 2 5 - 1 2 . 5 m g / c a t b y mouth q ( 1 2 - ) 2 4 h
Propranolol Dog: 0 . 0 2 m g / k g initial bolus s l o w l y IV (up to m a x i m u m of 0.1 m g / k g ) ; initial d o s e , 0 . 1 - 0 . 2 m g / k g
by mouth q 8 h , u p to 1 m g / k g q 8 h
Cat: S a m e IV instructions; 2 . 5 u p to 1 0 m g / c a t b y mouth q 8 - 1 2 h
Esmolol Dog: 0 . 1 - 0 . 5 m g / k g IV over 1 minute ( l o a d i n g d o s e ) , f o l l o w e d b y infusion of 0 . 0 2 5 - 0 . 2 m g / k g / m i n
Cat: same
Metoprolol Dog: initial d o s e , 0 . 2 m g / k g b y mouth q 8 h , u p to 1 m g / k g q8(-12)h
Cat: -
Class III
Class IV
Dosage o f A n t i a r r h y t h m i c Drugscont'd
AGENT DOSAGE
Anticholinergic
Sympathomimetic
Isoproterenol D o g : 0 . 0 4 5 - 0 . 0 9 g / k g / m i n CRI
Cat: same
Terbutaline D o g : 2 . 5 - 5 m g / d o g b y mouth q 8 - 1 2 h
C a t : 1 . 2 5 m g / c a t b y mouth q 1 2 h
Other Agents
CRI, Constant rate infusion; CPR, cardiopulmonary resuscitation; , effective dosage not known.
disorientation, muscle twitches, nystagmus, and generalized premature ventricular (and sometimes atrial) depolariza
seizures. The latter may require diazepam (0.25 to 0.5 mg/kg tions and tachycardias. It is less effective than quinidine i n
IV) or a short-acting barbiturate. Nausea can also occur. managing atrial arrhythmias and is usually not effective i n
Worsening of arrhythmias (a proarrhythmic effect) is seen converting chronic atrial flutter-fibrillation to sinus rhythm.
occasionally, as it is with any drug having cardiac electro Procainamide should be used only with caution i n animals
physiologic effects. Cats are particularly sensitive to the with hypotension.
drug's toxic effects and may undergo respiratory arrest along Orally administered procainamide is well absorbed i n the
with seizures. In the event o f toxicity, lidocaine should be dog but has a half-life of only 2.5 to 4 hours. The sustained-
discontinued until the signs o f toxicity disappear; a lower release preparation has a slightly longer half-life o f 3 to 6
infusion rate may then be instituted. IV diazepam (0.25 to hours. Food may delay the absorption o f procainamide. The
0.5 mg/kg) is used to control lidocaine-induced seizures. drug undergoes hepatic metabolism and renal excretion i n
There are anecdotal reports o f respiratory depression and proportion to the creatinine clearance. The metabolite N -
arrest after the administration of lidocaine i n unconscious acetylprocainamide is not clinically important i n dogs and
dogs and cats. Propranolol, cimetidine, and other drugs that cats. Procainamide can be given orally or intramuscularly
decrease liver blood flow slow the metabolism o f lidocaine without marked hemodynamic effects, but rapid I V injec
and predispose to the development o f toxicity. Animals with tion can cause hypotension and cardiac depression, although
heart failure may also have reduced hepatic b l o o d flow and to a m u c h lesser degree than I V quinidine. Administration
may require a lower dosage of the drug. Hepatic disease can by C R I can be useful i f the arrhythmia responds to an I V
delay elimination as well. bolus; a steady state is reached i n 12 to 22 hours. Therapeu
tic plasma concentrations are thought to be 4 to 10 g/ml.
Procainamide The toxic effects o f procainamide are similar to those of
Procainamide HC1 has electrophysiologic effects similar to quinidine (discussed i n the following section) but are usually
those o f quinidine. Procainamide has both direct and indi milder. Gastrointestinal upset and prolongation o f the Q R S
rect (vagolytic) effects; it is indicated for the treatment o f or Q T intervals may occur. Procainamide can enhance the
ventricular response rate to A F i f used without digoxin Q u i n i d i n e toxicity occurs as an extension o f the drug's
or a - or Ca++ blocker. M o r e serious toxic effects include electrophysiologic and hemodynamic actions. As the plasma
hypotension, depressed A V conduction (sometimes causing concentration increases, the P R interval and Q R S duration
second- or third-degree heart block), and proarrhythmia. lengthen. M a r k e d Q T prolongation, right bundle-branch
The latter can cause syncope or V F . Hypotension responds block, or Q R S widening >25% of pretreatment value sug
to I V fluids, catecholamines, or calcium-containing solu gests drug toxicity; various conduction blocks and ventricu
tions. Gastrointestinal signs associated with oral therapy may lar tachyarrhythmias are other manifestations. Marked Q T
respond to dosage reduction. High-dose oral procainamide prolongation implies increased temporal dispersion of myo
therapy i n people has been associated w i t h a reversible lupus cardial refractoriness; this predisposes to torsades de pointes
like syndrome characterized by neutropenia, fever, depres (see p. 25) and V F . Transient episodes o f these serious
sion, and hepatomegaly, but this has not been documented arrhythmias can be a cause of syncopal attacks in people
in dogs. Long-term use can cause brown discoloration o f the taking quinidine. Lethargy, weakness, and C H F can result
haircoat i n black Doberman Pinschers. from the negative inotropic and vasodilatory effects of the
drug and subsequent hypotension. Cardiotoxicity and hypo
Quinidine tension can be partially reversed by sodium bicarbonate
+
Q u i n i d i n e has been used to treat ventricular and, occasion (1 m E q / k g I V ) , w h i c h temporarily decreases serum K con
ally, supraventricular tachyarrhythmias. In large dogs with centration, enhances quinidine's binding to albumin, and
recent-onset A F and n o r m a l ventricular function, quinidine reduces its cardiac electrophysiologic effects. Gastrointesti
may cause conversion to sinus rhythm. This drug must be nal signs (e.g., nausea, vomiting, diarrhea) are c o m m o n with
used cautiously i n animals with heart failure or hyperkale orally administered quinidine. Thrombocytopenia (revers
mia. The characteristic electrophysiologic effects o f q u i n i ible after quinidine discontinuation) can occur in people and
dine are depression o f automaticity and conduction velocity possibly i n dogs and cats.
and prolongation o f the effective refractory period. Corre
sponding dose-dependent E C G changes (e.g., PR, Q R S , and Mexiletine
Q T prolongation) result from direct electrophysiologic and Mexiletine HC1 is similar to lidocaine i n its electrophysio
vagolytic effects. A t low doses, quinidine's vagolytic effects logic, hemodynamic, toxic, and antiarrhythmic properties. It
may increase the sinus rate or the ventricular response rate can be effective i n suppressing ventricular tachyarrhythmias
to A F by antagonizing the drug's direct effects. As w i t h other i n dogs. The combination o f a -blocker (or procainamide
class I agents, hypokalemia reduces quinidine's antiarrhyth or quinidine) w i t h mexiletine may be more efficacious and
mic effectiveness. associated with fewer adverse effects than mexiletine alone.
The drug is well-absorbed orally but has fallen out o f The drug is easily absorbed when administered orally, but
favor for chronic oral therapy because o f its frequent adverse antacids, cimetidine, and narcotics reportedly slow its
effects and its interference w i t h digoxin pharmacokinetics. absorption i n people. Mexiletine undergoes hepatic metabo
Q u i n i d i n e is metabolized extensively by the liver, with little lism (influenced by liver b l o o d flow) and some renal excre
dependence o n liver b l o o d flow. The half-life is about 6 tion (which is slower if the urine is alkaline). Hepatic
hours i n dogs and 2 hours i n cats. Q u i n i d i n e is highly microsomal enzyme inducers may accelerate its clearance.
protein-bound; severe hypoalbuminemia can predispose to The half-life i n dogs is from 4.5 to 7 hours (depending to
toxicity. Cimetidine can also predispose to toxicity by slowing some degree o n the urine p H ) . Approximately 70% of the
the drug's elimination. Q u i n i d i n e can precipitate digoxin drug is protein bound. The therapeutic serum concentration
toxicity (when used concurrently) by displacing digoxin is thought to range from 0.5 to 2.0 g/ml (as in people). The
from skeletal muscle b i n d i n g sites and reducing its renal effects o f this drug in cats are not k n o w n . Adverse effects
clearance. Anticonvulsants and other drugs that induce have included vomiting, anorexia, tremor, disorientation,
hepatic microsomal enzymes can speed quinidine's metabo sinus bradycardia, and thrombocytopenia. Overall, mexi
lism. I V administration is not recommended because o f letine appears to produce fewer adverse effects than
quinidine's propensity to cause vasodilation (by means o f tocainide.
nonspecific -adrenergic receptor blockade), cardiac depres
sion, and hypotension. The oral and I M routes usually do Phenytoin
not cause adverse hemodynamic effects, but close monitor Phenytoin's electrophysiologic effects are similar to those of
ing is warranted initially, especially i n animals with underly lidocaine. It also has some slow-calcium channel inhibitory
ing cardiac disease. Therapeutic b l o o d concentrations are and central nervous system effects that may contribute to its
thought to be 2.5 to 5 g/ml and are usually achieved i n 12 effectiveness against digitalis-induced arrhythmias. This
to 24 hours after oral and I M administration. Slow-release drug is currently used only for digitalis-induced ventricular
sulfate (83% active drug), gluconate (62% active drug), and arrhythmias that have not responded to lidocaine in dogs.
polygalacturonate (80% active drug) salts o f quinidine Its contraindications are the same as for lidocaine. Slow IV
prolong the drug's absorption and elimination. The sulfate infusion and oral administration do not cause relevant
salt is more rapidly absorbed than the gluconate; peak effect hemodynamic disturbances; however, the oral bioavailability
is usually achieved 1 to 2 hours after oral administration. of phenytoin is poor. Rapid I V injection should be avoided
because the propylene glycol vehicle can depress myocardial CLASS II ANTIARRHYTHMIC DRUGS:
contractility, exacerbate arrhythmias, and cause vasodila -ADRENERGIC BLOCKERS
tion, hypotension, or respiratory arrest. The half-life o f phe Class II antiarrhythmic drugs act by blocking catecholamine
nytoin in the dog is about 3 hours. The drug is metabolized effects. They slow heart rate, reduce myocardial O demand, 2
in the liver, and it may speed up its own elimination by and increase A V conduction time and refractoriness. The
stimulating hepatic microsomal enzymes. Co-administra antiarrhythmic effect of -blockers relates to 1-receptor
tion of cimetidine, chloramphenicol, and other drugs that blockade rather than direct electrophysiologic effects. They
inhibit microsomal enzyme activity increases phenytoin's are often used i n combination with a class I agent (e.g., pro
serum concentration. The I V administration of phenytoin cainamide or mexiletine), although their negative inotropic
has been associated with bradycardia, A V blocks, ventricular effect demands caution when used i n animals with myocar
tachycardia, and cardiac arrest. Other manifestations of phe dial failure. -receptor blockers are used i n animals with
nytoin toxicity include central nervous system signs (e.g., hypertrophic cardiomyopathy, certain congenital and
depression, nystagmus, disorientation, ataxia). The drug is acquired ventricular outflow obstructions, systemic hyper
not used i n cats because its half-life is >40 hours, and even tension, hyperthyroid heart disease, supraventricular and
low doses produce toxic serum concentrations i n this ventricular tachyarrhythmias (especially those induced by
species. enhanced sympathetic tone), and other diseases or toxicities
that cause excessive sympathetic stimulation. A -blocker is
Other Class I Agents often used i n conjunction with digoxin to slow the ventricu
Disopyramide is similar to quinidine and procainamide elec lar response rate to AF. A -blocker such as propranolol or
trophysiologically. It has a very short half-life i n the dog (<2 atenolol is considered the first-line antiarrhythmic agent in
hours), as well as marked depressive effects o n the canine cats for the treatment of both supraventricular and ven
myocardium. Tocainide, a class IB agent similar to lidocaine, tricular tachyarrhythmias. In people with stable heart failure,
is no longer available i n the United States. Flecainide and long-term therapy with certain -blockers improves cardiac
propafenone are class I C agents. They produce marked function and prolongs survival in those who tolerate the
reduction in cardiac conduction velocity but have little effect drug (see p. 69).
on sinus rate or refractoriness. H i g h doses depress automa -adrenergic receptors have been classified into subtypes.
ticity in the sinus node and specialized conducting tissues. -receptors are located primarily i n the myocardium and
1
Vasodilation and myocardial depression can result i n severe mediate increases i n contractility, heart rate, A V conduction
hypotension after I V injection, especially i n animals with velocity, and automaticity i n specialized fibers. Extracardiac
underlying cardiac disease. Proarrhythmia is a serious poten -receptors mediate bronchodilation and vasodilation, as
2
tial adverse effect of these agents. Bradycardia, intraventricu well as renin and insulin release. There are also some - as 2
lar conduction disturbance, and consistent (although transient) well as -receptors in the heart. "Nonselective" -blockers
3
hypotension, as well as nausea, vomiting, and anorexia, have inhibit catecholamine binding to both - and -adrenergic
1 2
occurred in dogs. Flecainide (and encainide) have been asso receptors. Other -blockers are more selective; they antago
ciated with increased mortality in people. These agents are nize mainly one or the other receptor subtype (Table 4-3).
rarely (and cautiously) used for treating life-threatening ven The first-generation -blockers (e.g., propranolol) have
tricular arrhythmias refractory to other therapy. nonselective -blocking effects. Second-generation agents
TABLE 4-3
Characteristics of Selected -Blockers
DRUG ADRENERGIC RECEPTOR SELECTIVITY LIPID SOLUBILITY M A I N ROUTE O F ELIMINATION
Atenolol 1 0 RE
Carvedilol 1, 2, 1 + HM
Esmolol 1 0 BE
Labetalol 1, 2, 1 ++ HM
Metoprolol 1 ++ HM
Nadolol 1, 2 0 RE
Pindolol* 1, 2 ++ B
Propranolol 1, 2 ++ HM
Sotalol** 1, 2 0 RE
Timolol 1, 2 0 RE
Propranolol Esmolol
Propranolol HC1 is a nonselective -blocker that was widely Esmolol HCl is an ultra-short acting -selective agent.
1
used i n dogs and cats, although atenolol is used more often It is rapidly metabolized by blood esterases and has a
now. Propranolol is not recommended for patients w i t h p u l half-life o f <10 minutes. Steady state occurs i n 5 minutes
monary edema because o f the potential for bronchoconstric after a loading dose or 30 minutes without. Esmolol's
tion caused by -receptor antagonism. The -receptor
2 2 effects are gone w i t h i n 10 to 20 minutes after infusion
blocking effects of propranolol also make it relatively con is terminated. This drug is used for acute therapy o f
traindicated i n patients w i t h asthma or chronic small airway tachyarrhythmias and feline hypertrophic obstructive
disease. cardiomyopathy.
Propranolol undergoes extensive first-pass hepatic metab
olism, so oral bioavailability is low; but with time and use o f Other -Blockers
higher doses hepatic enzymes become saturated and bio M a n y other -blocking drugs are available. Their receptor
availability increases. Propranolol reduces hepatic b l o o d selectivity as well as their pharmacologic characteristic vary.
flow, which prolongs its elimination as well as that of other Certain -blockers may prove useful in patients with chronic,
drugs dependent o n liver b l o o d flow for their metabolism stable myocardial failure by reducing the cardiotoxic effects
(e.g., lidocaine). Feeding delays oral absorption and increases of excessive sympathetic stimulation, improving cardiac
drug clearance after I V dosing (by increasing hepatic b l o o d function, promoting upregulation o f cardiac -receptors,
flow). The half-life o f propranolol i n the dog is only about and increasing survival time (see p. 69). The third-genera
1.5 hours (0.5 to 4.2 hours i n cats). Active metabolites tion -blocker, carvedilol, and the second-generation agent,
exist and dosing every 8 hours appears to be adequate i n metoprolol, are effective i n this regard. Nonselective (first-
both species. I V propranolol is used mainly for refractory generation) agents, such as propranolol, and some later-gen
ventricular tachycardia (in conjunction w i t h a class I eration agents do not appear to confer these survival benefits.
Agents with intrinsic sympathomimetic activity appear to amiodarone include refractory atrial and ventricular tachyar
have deleterious effects. rhythmias, especially reentrant arrhythmias using an acces
sory pathway. The I V form is used i n people w i t h A F ,
CLASS III ANTIARRHYTHMIC DRUGS ventricular tachycardia, and during cardiopulmonary resus
C o m m o n features o f class III drugs include prolongation o f citation from recurrent ventricular tachycardia and fibrilla
the cardiac action potential and effective refractory period tion; similar applications are expected in dogs. However,
without a decrease i n conduction velocity. Their effects are conservative dosing w i t h slow injection over 10 to 20 minutes
mediated by inhibition o f potassium channels responsible is recommended, because I V use can cause hypotension and
for repolarization (delayed rectifier current). These agents bradycardia. The drug is also given by C R I in people; 10 to
are useful for ventricular arrhythmias, especially those caused 15 mg/kg/day has been used i n children.
by reentry. Class III drugs have antifibrillatory effects as well. The pharmacokinetics o f amiodarone are complex.
They share some characteristics o f other antiarrhythmic C h r o n i c oral use is associated with a prolonged time to
drug classes in addition to their class III effects. steady state (of several weeks), concentration o f drug in
myocardial and other tissues, and accumulation of an active
Sotalol metabolite (desethylamiodarone). Therapeutic serum con
Sotalol HC1 is a nonselective -blocker that has Class III centration is thought to be 1 to 2.5 g/ml. A m i o d a r o n e may
effects at higher doses. Its oral bioavailability is high, although have less o f a proarrhythmic effect than other agents and
absorption is reduced when given with food. Sotalol's half- may reduce the risk o f sudden death because of uniform
life is about 5 hours in dogs. It is eliminated unchanged by prolongation o f repolarization throughout the ventricles, as
the kidneys, and renal dysfunction prolongs elimination. well as suppression o f Purkinje fiber automaticity. In normal
Sotalol's -blocking effect outlasts its plasma half-life. The dogs I V amiodarone does not adversely affect contractility
drug has m i n i m a l hemodynamic effects, although it can at cumulative doses less than 12.5 to 15 mg/kg. However, the
cause slowed sinus rate, first-degree A V block, and hypoten potential exists for more profound cardiac depression and
sion. Proarrhythmia can occur (as with all antiarrhythmic hypotension i n dogs w i t h myocardial disease. Amiodarone
agents), including torsades de pointes. Sotalol's class III use is not described i n cats.
effects occur at higher doses i n dogs than i n people. Doses Long-term amiodarone is associated w i t h many potential
used clinically in dogs may be producing primarily -block adverse effects, including depressed appetite, gastrointestinal
ing effects. O n the other hand, a high incidence o f proar upset, pneumonitis leading to p u l m o n a r y fibrosis, hepatop
rhythmia (especially torsades de pointes), o f concern in athy, thyroid dysfunction, positive C o o m b s test, thrombo
people taking sotalol, has not been reported clinically cytopenia, and neutropenia. Occasional hypersensitivity
in dogs. Experimentally, i n dogs with hypokalemia, co reactions (with acute angioedema formation) or o f tremors
administration o f mexiletine reduced the proarrhythmic have occurred i n dogs. Other adverse effects observed
potential. i n people have included corneal microdeposits, photosen
Sotalol may worsen heart failure in animals w i t h dilated sitivity, bluish skin discoloration, and peripheral neuro
cardiomyopathy. However, sotalol is thought to have less pathy. Amiodarone can increase the serum concentration
negative inotropic effect than propranolol. Other adverse of digoxin, diltiazem, and possibly procainamide and
effects of sotalol have included hypotension, depression, quinidine.
nausea, vomiting, diarrhea, and bradycardia. There are occa
sional anecdotal reports o f aggression that resolved after Other Class III Agents
sotalol was discontinued. Ibutilide fumarate is somewhat effective for converting
recent-onset A F i n people, but there is little veterinary expe
Amiodarone rience w i t h this drug. In experimental rapid-pacing-induced
Amiodarone HC1 is thought to produce its antiarrhythmic cardiomyopathy i n dogs, ibutilide caused episodes o f tors
effects by prolonging the action potential duration and effec ades de pointes.
tive refractory period i n both atrial and ventricular tissues. Dofetilide is another drug that selectively blocks the rapid
+
Although considered a class III agent, it shares properties component o f the K current responsible for repolarization.
with all three other antiarrhythmic drug classes. A m i o It too is used i n people for the conversion o f A F and to
darone is an iodinated c o m p o u n d that also has n o n maintain sinus rhythm. Its efficacy for this appears to be
competitive - and -blocking effects, as well as Ca++
1 comparable to that o f other class III drugs, and it does not
channel-blocking effects. The -blocking effects occur soon exacerbate left ventricular dysfunction. Bretylium tosylate is
after administration, but maximal class III effects (and pro no longer available i n the United States.
longation o f action potential duration and Q T interval) are
not achieved for weeks with chronic administration. Its Ca++ CLASS IV ANTIARRHYTHMIC DRUGS:
blocking effects may inhibit triggered arrhythmias by reduc CALCIUM ENTRY BLOCKERS
++
ing afterdepolarizations. Therapeutic doses slow the sinus The Ca entry blockers are a diverse group o f drugs that
++
rate, decrease A V conduction velocity, and minimally depress have the c o m m o n property o f decreasing cellular Ca influx
myocardial contractility and b l o o d pressure. Indications for by blocking transmembrane L-type calcium channels. As a
group, these drugs can cause coronary and systemic vasodi this is given once daily. Diltiazem X R is another sustained-
lation, enhance myocardial relaxation, and reduce cardiac release diltiazem preparation. The 240-mg capsule contains
contractility. Some calcium entry blockers have antiarrhyth four 60-mg tablets. There is m u c h intercat variability in
m i c effects, especially o n tissues dependent on the slow pharmacokinetics with this form. Higher doses are more
++
inward Ca current, such as the sinus and A V nodes. Other likely to be associated with anorexia and other gastrointesti
conditions for which calcium entry blockers are potentially nal signs.
useful include hypertrophic cardiomyopathy, myocardial Adverse effects o f diltiazem are u n c o m m o n at therapeutic
ischemia, and hypertension. doses, although anorexia, nausea, and bradycardia may
Possible adverse effects o f these agents include reduced occur. Rarely, other gastrointestinal, cardiac, and neurologic
contractility, vasodilation, hypotension, depression, anorexia, adverse effects develop. H i g h liver enzyme activities and
lethargy, bradycardia, and A V block. L o w initial doses are anorexia occur sporadically i n cats. Some cats have become
used and increased as needed to effect or to maximal recom aggressive or shown other personality change when treated
++
mended dose. Contraindications to Ca channel blocker use with diltiazem.
include sinus bradycardia, A V block, sick sinus syndrome,
digoxin toxicity, and myocardial failure (for agents with pro Verapamil
nounced negative inotropic effect). They are usually not pre Verapamil H C 1 is a phenylalkylamine and has the most
scribed i n patients receiving a -blocker because o f additive potent cardiac effects o f the Ca++-blockers used clinically.
negative effects on contractility, A V conduction, and heart The drug increases the refractory period o f nodal tissues and
rate. A n overdose or exaggerated response to a Ca++ blocker can abolish reentrant S V T as well as slow the ventricular
is treated with supportive care, including atropine for bra response rate i n AF. Verapamil causes dose-related slowing
dycardia or A V block, dopamine or dobutamine (see Box of the sinus rate and A V conduction. It is sometimes used
3-1) and furosemide for heart failure, and dopamine or I V for supraventricular and atrial tachycardias i n animals
calcium salts for hypotension. without heart failure. Verapamil's half-life in dogs is about
2.5 hours. It is poorly absorbed and undergoes first-pass
Diltiazem hepatic metabolism, resulting i n low bioavailability with oral
++
Diltiazem HCl is a benzothiazepine Ca channel blocker. It use. The pharmacokinetics i n cats are similar to those of
slows A V conduction, causes potent coronary and m i l d dogs.
peripheral vasodilation, and has a lesser negative inotropic The drug has important negative inotropic and some
effect than the prototypical calcium entry blocker, verapamil. vasodilatory effects that can cause cardiac decompensation,
Diltiazem is often combined w i t h digoxin to further slow the hypotension, and even death i n the presence o f underlying
ventricular response rate to A F i n dogs. It is indicated for myocardial disease. A n initially low I V dose is given very
other supraventricular tachyarrhythmias as well. Diltiazem slowly; this can be repeated at 5- (or more) minute intervals
is often used i n cats with hypertrophic cardiomyopathy; its if no adverse effects have occurred and the arrhythmia per
beneficial effects can include enhanced myocardial relax sists. B l o o d pressure monitoring is advisable because o f the
ation and perfusion, as well as a m i l d decrease i n heart rate, potential for hypotension. As discussed above, verapamil is
contractility, and myocardial oxygen demand (see Chapter not recommended for use i n animals with heart failure. The
8). C h r o n i c diltiazem therapy may be associated with a toxic effects o f verapamil include sinus bradycardia, A V
decrease i n left ventricular wall and septal thickness i n cats block, hypotension, reduced myocardial contractility, and
w i t h hypertrophic cardiomyopathy. cardiogenic shock. Verapamil reduces the renal clearance o f
Peak effects are seen w i t h i n 2 hours o f oral dosing, and digoxin.
the effects last at least 6 hours i n dogs. Extensive first-pass
effect limits bioavailability, especially i n dogs. The half-life Other Calcium Channel Blockers
of diltiazem i n the dog is just over 2 hours, but chronic A number o f other Ca++-blockers are available. Most (dihy
oral treatment prolongs it because of enterohepatic circula dropyridine group) are used as antihypertensives. A m l o d i p
tion. In cats plasma diltiazem concentration peaks i n 30 ine besylate is recommended as the first-line antihypertensive
minutes, and the effects last for 8 hours. The therapeutic agent i n cats and is also used i n some hypertensive dogs (see
range is 50 to 300 n g / m l . Diltiazem is metabolized i n the Chapter 11). A m l o d i p i n e is also used in the treatment o f
liver; active metabolites exist. Drugs that inhibit hepatic chronic refractory heart failure i n some dogs (see Table 3-3).
enzyme systems (e.g., cimetidine) decrease the metabolism The drug is not useful as an antiarrhythmic agent. Nifedipine
of diltiazem. Propranolol and diltiazem reduce each other's is another potent vasodilator without antiarrhythmic
clearance when used simultaneously. A sustained-release effects.
preparation ( C a r d i z e m - C D ) , at 10 mg/kg daily i n cats,
produces plasma concentrations that peak i n 6 hours and ANTICHOLINERGIC DRUGS
remain i n the therapeutic range for 24 hours. A dose of Atropine and Glycopyrrolate
45 m g per cat is approximately equal to 105 m g o f Cardizem- Anticholinergic drugs increase sinus node rate and A V con
C D (or the amount that fits into the small end o f a N o . 4 duction when vagal tone is increased (see Table 4-2). Paren
gelatin capsule; a 300-mg capsule provides about 6.5 doses); teral atropine or glycopyrrolate is indicated for bradycardia
or A V block induced by anesthesia, central nervous system mias. Oral administration is not effective because of marked
lesions, and certain other diseases or toxicities. Atropine is first-pass hepatic metabolism.
a competitive muscarinic receptor antagonist that is used Terbutaline sulfate is a -receptor agonist that may have
2
to determine whether excess vagal tone is responsible a m i l d stimulatory effect o n heart rate when given orally.
for arrhythmias attributed to sinus and/or A V nodal dys Methylxanthine bronchodilators (e.g., aminophylline and
function. This is k n o w n as the atropine challenge test (or theophylline) increase heart rate i n some dogs with sick
atropine response test). Response to atropine challenge is sinus syndrome when used at higher doses.
most consistent with I V administration of 0.04 mg/kg. A n
E C G is recorded within 5 to 10 minutes after atropine injec OTHER DRUGS
tion. If the heart rate has not increased by at least 150%, the E d r o p h o n i u m chloride is a short-acting anticholinesterase
E C G is repeated 15 (to 20) minutes after atropine injection; with nicotinic and muscarinic effects. A l t h o u g h mainly used
sometimes, an initial vagomimetic effect on the A V node for diagnosing myasthenia gravis, it slows A V conduction,
lasts longer than 5 minutes. The normal sinus node response which can help i n the diagnosis and resolution of some cases
is a rate increase to 150 to 160 beats/minute (or >135 beats/ of acute SVT. The drug's effect begins within 1 minute and
minute). A positive response may not predict response to lasts up to 10 minutes after I V injection. Adverse effects
oral anticholinergic therapy. Atropine has little to no effect are primarily cholinergic and include gastrointestinal (e.g.,
on bradyarrhythmias caused by intrinsic disease of the sinus vomiting, diarrhea, salivation), respiratory (e.g., broncho-
or A V node. spasm, respiratory paralysis, edema), cardiovascular (e.g.,
Atropine given by any parenteral route can transiently bradycardia, hypotension, cardiac arrest), and muscular
exacerbate vagally mediated A V block when the atrial rate (e.g., twitching, weakness) signs. Atropine and supportive
increases faster than A V conduction can respond. However, care are used i f necessary.
IV administration causes the fastest and most consistent Phenylephrine HC1 is an -adrenergic agonist that
onset and resolution of the exacerbated block, as well as the increases b l o o d pressure by peripheral vasoconstriction. A
most rapid postbradycardia heart rates, compared with the baroreflex-mediated increase i n vagal tone slows A V conduc
I M and subcutaneous routes. Unlike atropine, glycopyrrolate tion and is thought to underlie its effects on SVT. Phenyl
does not have centrally mediated effects, and its effects are ephrine's pressor effect begins rapidly after I V injection and
longer-lasting than those of atropine. persists for up to 20 minutes. The drug is contraindicated
in patients with hypertension or ventricular tachycardia.
Oral Anticholinergic Drugs Extravasation can cause ischemic necrosis of surrounding
Some animals that respond to parenteral atropine or glyco tissue.
pyrrolate will also respond to an oral anticholinergic agent.
Clinical signs may be relieved i n these animals, at least for a Suggested Readings
time. Nevertheless, animals with symptomatic bradyarrhyth ARRHYTHMIAS AND ANTIARRHYTHMIC DRUGS
mias usually require permanent pacemaker implantation to Awaji T, Wu ZJ, Hashimoto K: Acute antiarrhythmic effects of intra
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hyoscyamine sulfate are c o m m o n l y used, but other oral anti arrhythmias, / Cardiovasc Pharmacol 26:869, 1995.
cholinergic agents are also available. Individual dosage is Baty CI, Sweet D C , Keene BK: Torsades de pointes-like polymor
adjusted to effect. Oral absorption of propantheline is vari phic ventricular tachycardia in a dog, / Vet Intern Med 8:439,
1994.
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Bicer S et al: Hemodynamic and electrocardiographic effects of
Vagolytic drugs can aggravate paroxysmal supraventricu
graded doses of amiodarone in healthy dogs anesthetized with
lar tachyarrhythmias (as i n sick sinus syndrome) and should
morphine/alpha chloralose, / Vet Intern Med 14:90, 2000.
be used only cautiously as chronic therapy i n those patients. Bicer S et al: Effects of chronic, oral amiodarone on left ventricular
Other adverse effects of anticholinergic therapy include pressure, electrocardiograms, and action potentials from myo
vomiting, dry mouth, constipation, keratoconjunctivitis cardium in vivo and from Purkinje fibers in vitro, Vet Therap
sicca, increased intraocular pressure, and drying of respira 2:325, 2001.
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Vet Cardiol 7:121,2005.
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Calvert CA, Brown I: Influence of antiarrhythmia therapy on sur
atropine, although electrical pacing is safer and more effec
vival times of 19 clinically healthy Doberman Pinschers with
tive. It also can be effective for torsades de pointes. Because dilated cardiomyopathy that experienced syncope, ventricular
of its affinity for -receptors, isoproterenol can cause hypo
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C H A P T E R 5
Congenital Cardiac
Disease
some of the following: a high V S D , a low A S D , and malfor caused by an aorticopulmonary w i n d o w (a communication
mations of one or both A V valves. The most c o m m o n mal between the ascending aorta and pulmonary artery) or some
formations in cats are A V valve dysplasias and atrial or other functionally similar communication in the hilar region.
ventricular septal defects; other lesions include SAS, P D A , T
of F, and PS. Endocardial fibroelastosis, mainly i n Burmese PATENT DUCTUS ARTERIOSUS
and Siamese cats, also has been reported. Congenital mal
formations are more prevalent i n male than female cats. Etiology and Pathophysiology
Congenital malformations i n both species can occur as iso Functional closure o f the ductus arteriosus normally occurs
lated defects, which is most often the case, or i n various w i t h i n hours after birth and is followed by structural changes
combinations. that occur over several months, which cause permanent
The prevalence o f congenital defects is higher i n purebred closure. The ductal wall i n animals w i t h an inherited P D A is
animals than in mixed-breed animals. In some studies a histologically abnormal and unable to constrict. W h e n the
polygenic inheritance pattern has been suggested, although ductus fails to close, b l o o d shunts through it from the
there is more recent focus on a single major gene effect descending aorta into the pulmonary artery. Shunting occurs
influenced by other modifying genes. Recognized breed pre during both systole and diastole because aortic pressure nor
dispositions are listed i n Table 5-1; animals o f other breeds mally is higher than p u l m o n i c pressure throughout the
can also be affected with any of these defects as well. cardiac cycle. This left-to-right shunt causes a volume over
load o f the pulmonary circulation, left atrium ( L A ) , and left
ventricle (LV). The shunt volume is directly related to the
EXTRACARDIAC ARTERIOVENOUS pressure difference (gradient) between the two circulations
SHUNT and the diameter o f the ductus.
Hyperkinetic arterial pulses are characteristic o f P D A .
The most c o m m o n congenital arteriovenous shunt is P D A . B l o o d runoff from the aorta into the pulmonary system
Rarely, similar hemodynamic and clinical abnormalities are allows diastolic aortic pressure to decrease below normal.
TABLE 5-1
Patent ductus arteriosus Maltese, Pomeranian, Shetland Sheepdog, English Springer Spaniel, Keeshond, Bichon
Frise, Toy and Miniature Poodles, Yorkshire Terrier, Collie, Cocker Spaniel, German
Shepherd D o g ; Chihuahua, Kerry Blue Terrier, Labrador Retriever, Newfoundland; female
> male
Subaortic stenosis Newfoundland, Golden Retriever, Rottweiler, Boxer, German Shepherd Dog, English
Bulldog, Great Dane, German Short-Haired Pointer, Bouvier des Flandres, Samoyed
Pulmonic stenosis Bulldog (male > female), Mastiff, Samoyed, Miniature Schnauzer, West Highland White
Terrier, Cocker Spaniel, Beagle, Airedale Terrier, Boykin Spaniel, Chihuahua, Scottish
Terrier, Boxer, Fox Terrier(?)
Ventricular septal defect English Bulldog, English Springer Spaniel, Keeshond; cats
Atrial septal defect Samoyed, Doberman Pinscher, Boxer
Tricuspid dysplasia Labrador Retriever, German Shepherd Dog, Boxer, Weimaraner, Great Dane, O l d English
Sheepdog, Golden Retriever; other large breeds; (male > female?)
Mitral dysplasia Bull Terrier, German Shepherd Dog, Great Dane, Golden Retriever, Newfoundland, Mastiff,
Rottweiler(?); cats; (male > female)
Tetralogy of Fallot Keeshond, English Bulldog
Persistent right aortic arch German Shepherd Dog, Great Dane, Irish Setter
FI6 5 - 2
Continuous femoral artery pressure recording during surgical ligation of a patent ductus
arteriosus in a Poodle. The wide pulse pressure (left side of trace) narrows as the ductus is
closed (right side of trace). Diastolic arterial pressure rises because blood runoff into the
pulmonary artery is curtailed. (Courtesy Dr. Dean Riedesel.)
The widened pulse pressure (systolic minus diastolic pres stemming from the chronic volume overload, and arrhyth
sure) causes palpably stronger arterial pulses (Fig. 5-2). mias contribute to the development of congestive heart
Compensatory mechanisms (e.g., increased heart rate, failure ( C H F ) .
volume retention) maintain adequate systemic blood In some cases, excessive p u l m o n a r y b l o o d flow leads to
flow. However, the L V is subjected to a great h e m o d y n a m i c p u l m o n a r y vascular changes, increased resistance, and p u l
burden, especially when the ductus is large, because the m o n a r y hypertension (see p. 109). If p u l m o n a r y artery pres
increased stoke volume is p u m p e d into the relatively h i g h sure rises to equal aortic pressure, very little b l o o d shunting
pressure aorta. L V and m i t r a l annulus dilation i n t u r n occurs. However, i f p u l m o n a r y artery pressure exceeds aortic
cause m i t r a l regurgitation and further volume overload. pressure, shunt reversal (right-to-left flow) occurs. A p p r o x i
Excess fluid retention, declining myocardial contractility mately 15% o f dogs w i t h inherited P D A develop a reversed
shunt; female Cocker Spaniels may be at increased risk for to L V enlargement may occur. However, the E C G is normal
reversed P D A . i n some animals w i t h P D A .
Echocardiography also shows left heart enlargement
Clinical Features and pulmonary trunk dilation. L V fractional shortening can
A left-to-right shunting P D A (discussed here) is by far the be n o r m a l or decreased, and the E point-septal separation is
most c o m m o n form; clinical features of reversed P D A are often increased. The ductus itself may be difficult to visualize
described on p. 110. The prevalence of P D A is higher i n because of its location between the descending aorta and
certain breeds of dogs, and a polygenic inheritance pattern pulmonary artery. Views from the cranial left parasternal
is thought to be responsible. The prevalence is approximately position are useful. Doppler interrogation documents con
three times greater in female than male dogs. Reduced exer tinuous, turbulent flow into the p u l m o n a r y artery (Fig. 5-4).
cise ability, tachypnea, or cough is present i n some cases, but The m a x i m u m aortic-to-pulmonary artery pressure gradi
many animals are asymptomatic when first diagnosed. ent should be estimated. Cardiac catheterization is generally
Typical findings include a continuous m u r m u r heard best unnecessary for diagnosis, although it is important during
high at the left base (see p. 9), often w i t h a precordial thrill, interventional procedures. Catheterization findings include
hyperkinetic (bounding, "waterhammer") arterial pulses, higher oxygen content i n the pulmonary artery compared
and pink mucous membranes. w i t h the right ventricle (oxygen "step-up") and a wide aortic
pressure pulse. Angiocardiography shows left-to-right shunt
Diagnosis ing through the ductus (see Fig. 5-3, C ) .
Radiographs usually show cardiac elongation (left heart dila
tion), left atrial and auricular enlargement, and pulmonary Treatment and Prognosis
overcirculation (Table 5-2). A bulge often is evident i n the Closure of the left-to-right ductus, usually performed as
descending aorta ("ductus bump") or main pulmonary soon as is feasible, is recommended by either a transcatheter
trunk, or both (Fig. 5-3). The triad of all three bulges (i.e., or surgical occlusion method. Surgical ligation is successful
pulmonary trunk, aorta, and left auricle), located i n that i n most cases, although a perioperative mortality of about
order from the 1 to 3 o'clock position on a dorsoventral 10% has been reported. Patient age or weight does not appear
(DV) radiograph, is a classic finding but not always seen. to affect the outcome of surgery. Several methods of trans-
There is also evidence of pulmonary edema i n animals with catheter P D A occlusion are available. These involve placing
left-sided heart failure. Characteristic E C G findings include a vascular occluding device (e.g., the Amplatz canine ductal
wide P waves, tall R waves, and often deep Q waves i n leads occluder) or wire coils w i t h attached thrombogenic tufts
II, aVF, and C V L L . Changes i n the ST-T segment secondary
6 w i t h i n the ductus. Vascular access is usually via the femoral
TABLE 5-2
PDA LAE, LVE; left auricular bulge; Overcirculated Bulge(s) in descending aorta + pulmonary
increased cardiac width trunk; pulmonary edema
SAS LAE, LVE Normal W i d e cranial cardiac waist (dilated
ascending aorta)
PS RAE, RVE; reverse D Normal to undercirculated Pulmonary trunk bulge
VSD LAE, LVE; RVE Overcirculated Pulmonary edema; pulmonary trunk
bulge (large shunts)
ASD RAE, RVE Overcirculated Pulmonary trunk bulge
T dys RAE, RVE; globoid shape Normal Caudal cava dilation; pleural effusion,
ascites, hepatomegaly
M dys LAE, LVE Venous hypertension Pulmonary edema
T of F RVE, RAE; reverse D Undercirculated; prominent Normal to small pulmonary trunk; cranial
bronchial vessels aortic bulge on lateral view
PRAA Normal Normal Focal leftward and ventral tracheal
deviation narrowing cranial to heart;
wide cranial mediastinum;
megaesophagus; ( aspiration
pneumonia)
ASD, Atrial septal defect; LAE, left atrial enlargement; LVE, left ventricular enlargement; M dys, mitral dysplasia; PDA, patent ductus arteriosus;
PS, pulmonic stenosis; RVE, right ventricular enlargement; RAE, right atrial enlargement; SAS, subaortic stenosis; T dys, tricuspid dysplasia;
T of F, tetralogy of Fallot; VSD, ventricular septal defect.
FIG 5 - 3
Lateral (A) a n d d o r s o v e n t r a l (DV) (B) r a d i o g r a p h s from a d o g with a patent ductus
arteriosus. N o t e the l a r g e a n d e l o n g a t e d heart a n d prominent p u l m o n a r y vasculature.
A l a r g e b u l g e is seen in the d e s c e n d i n g a o r t a o n the D V v i e w (arrowheads in B).
C , A n g i o c a r d i o g r a m o b t a i n e d using a left ventricular injection outlines the left ventricle,
a o r t a , patent ductus (arrowheads), a n d p u l m o n a r y artery.
artery, although some have used a venous approach to eventual outcome for most patients that do not undergo
the ductus. Where available, transcatheter P D A occlusion ductal closure. More than 50% o f affected dogs die within
offers a m u c h less invasive alternative to surgical ligation. the first year. In animals with pulmonary hypertension and
Complications can occur (including aberrant coil emboliza shunt reversal, ductal closure is contraindicated because
tion and residual ductal flow, among others), and not all the ductus acts as a "pop-off" valve for the high right-sided
cases are suitable for transcatheter occlusion. A normal life pressures. Ductal ligation in animals with reversed P D A
span can be expected after uncomplicated ductal closure. produces no improvement and can lead to right ventricular
The concurrent mitral regurgitation usually resolves after (RV) failure.
ductus ligation or occlusion if the valve is structurally normal.
Animals with C H F are treated with furosemide, an angio
tensin-converting enzyme inhibitor (ACEI), rest, and dietary VENTRICULAR OUTFLOW OBSTRUCTION
sodium restriction (see Chapter 3). Because contractility
tends to decline over time, pimobendan or digoxin may be Ventricular outflow obstruction can occur at the semilunar
indicated as well. Arrhythmias are treated as necessary. valve, just below the valve (subvalvular), or above the valve
If the ductus is not closed, prognosis depends on its size in the proximal great vessel (supravalvular). SAS and PS are
and the level o f pulmonary vascular resistance. C H F is the most c o m m o n in dogs and cats. Stenotic lesions impose a
failure results when ventricular diastolic and atrial pressures
are elevated. Cardiac arrhythmias can contribute to the onset
of C H F . Furthermore, the combination o f outflow obstruc
tion, paroxysmal arrhythmias, and/or inappropriate bra
dycardia reflexly triggered by ventricular baroreceptor
stimulation can result in signs o f low cardiac output. These
are often associated with severe outflow tract obstruction
and include exercise intolerance, syncope, and sudden death.
SUBAORTIC STENOSIS
Clinical Features
Historical signs of fatigue, exercise intolerance or exertional
weakness, syncope, or sudden death occur in about a third
of dogs with SAS. Low-output signs can result from severe
outflow obstruction, tachyarrhythmias or sudden reflex bra
dycardia, and hypotension resulting from the activation of
ventricular mechanoreceptors. Left-sided C H F can develop,
usually in conjunction with concurrent mitral or aortic
regurgitation, other cardiac malformations, or acquired
endocarditis. Dyspnea is the most c o m m o n l y reported sign
in cats with SAS.
Characteristic physical examination findings in dogs with
moderate-to-severe stenosis include weak and late-rising
femoral pulses (pulsus parvus et tardus) and a precordial
thrill low at the left heartbase. A harsh systolic ejection
m u r m u r is heard at or below the aortic valve area on the left
hemithorax. This m u r m u r often radiates equally or more FIG 5 - 5
loudly to the right heartbase because of the orientation of E c h o c a r d i o g r a m from a 6-month-old G e r m a n S h e p h e r d D o g
with severe s u b a o r t i c stenosis. N o t e the discrete r i d g e of
the aortic arch. The m u r m u r frequently is heard over the
tissue (arrow) b e l o w the aortic v a l v e , c r e a t i n g a fixed
carotid arteries, and it may even radiate to the calvarium. In
outflow tract o b s t r u c t i o n . A, A o r t a ; LV, left ventricle; RV,
m i l d cases a soft, poorly radiating ejection m u r m u r at the right ventricle.
left and sometimes right heartbase may be the only abnor
mality found on physical examination. Functional aortic
stenosis murmurs that are not associated with SAS are
c o m m o n in Greyhounds and other sight hounds. Aortic
regurgitation can produce a diastolic m u r m u r at the left base
or may be inaudible. Severe aortic regurgitation can increase
the arterial pulse strength. There may be evidence of p u l m o
nary edema or arrhythmias.
Diagnosis
Radiographic abnormalities (see Table 5-2) can be subtle,
especially i n dogs and cats with m i l d SAS. The LV can appear
normal or enlarged. Poststenotic dilation i n the ascending
aorta can cause a prominent cranial waist i n the cardiac
silhouette (especially on a lateral view) and cranial medias
tinal widening. The E C G is often normal, although evidence
of LV hypertrophy (left axis deviation) or enlargement (tall
complexes) can be present. Depression of the ST segment in
leads II and a V F can occur from secondary myocardial isch
FIG 5 - 6
emia or to hypertrophy; exercise induces further ischemic
C o l o r f l o w D o p p l e r f r a m e of the left ventricular outflow
ST-segment changes i n some animals. Ventricular tachyar r e g i o n in systole from a 2-year-old f e m a l e Rottweiler with
rhythmias are c o m m o n . severe subaortic stenosis. N o t e the turbulent f l o w pattern
Echocardiography reveals the extent of L V hypertrophy o r i g i n a t i n g b e l o w the aortic v a l v e , as w e l l as the thickened
and subaortic narrowing. A discrete tissue ridge below the septum, p a p i l l a r y muscle, a n d left ventricular free w a l l . Right
aortic valve is evident in many animals with moderate-to- p a r a s t e r n a l l o n g a x i s v i e w ; Ao, a o r t a ; L A , left atrium; LV,
left ventricle; RA, right atrium.
severe disease (Fig. 5-5). Premature closure of the aortic
valve, systolic anterior m o t i o n of the anterior mitral leaflet,
and increased L V subendocardial echogenicity (probably turbulence originating below the aortic valve and extending
from fibrosis) are c o m m o n i n animals with severe obstruc into the aorta, as well as high peak systolic outflow velocity
tion. Ascending aorta dilation, aortic valve thickening, and (Fig. 5-6). Some degree of aortic or mitral regurgitation is
L A enlargement with hypertrophy may also be seen. In c o m m o n . Spectral Doppler studies are used to estimate the
mildly affected animals 2 - D and M - m o d e findings may be stenosis severity. Doppler-estimated systolic pressure gradi
unremarkable. Doppler echocardiography reveals systolic ents i n unanesthetized animals are usually 40% to 50%
higher than those recorded during cardiac catheterization ent >100-125 m m Hg) is guarded. M o r e than half o f dogs
under anesthesia. Severe SAS is associated with peak esti with severe SAS die suddenly within their first 3 years. The
mated gradients >100 to 125 m m H g . The L V outflow tract overall prevalence of sudden death i n dogs with SAS appears
should be interrogated from more than one position to to be just over 20%. Infective endocarditis and C H F may be
achieve the best possible alignment with b l o o d flow. The more likely to develop after 3 years o f age. Atrial and ven
subcostal (subxiphoid) position usually yields the highest- tricular arrhythmias and worsened mitral regurgitation are
velocity signals, although the left apical position is optimal complicating factors. Dogs w i t h m i l d stenosis (e.g., catheter
in some animals. The Doppler-estimated aortic outflow ization gradient <35 m m H g or Doppler gradient <60-
velocity may be only equivocally high i n animals w i t h m i l d 70 m m Hg) are more likely to survive longer and without
SAS, especially with suboptimal Doppler beam alignment. clinical signs.
W i t h optimal alignment, aortic root velocities of <1.7 m/sec
are typical i n normal unsedated dogs; velocities over ~2.25 m / PULMONIC STENOSIS
sec are generally considered abnormal. Peak velocities i n the
equivocal range between these values may indicate the pres Etiology and Pathophysiology
ence of m i l d SAS, especially i f there is other evidence o f PS is more c o m m o n i n small breeds o f dogs. Some cases o f
disease, such as disturbed flow i n the outflow tract or ascend valvular PS result from simple fusion o f the valve cusps, but
ing aorta and aortic regurgitation. This is mainly o f concern valve dysplasia is more c o m m o n . Dysplastic valve leaflets are
when selecting animals for breeding. In some breeds (e.g., variably thickened, asymmetric, and partially fused, w i t h a
Greyhound, Boxer, Golden Retriever), outflow velocities i n hypoplastic valve annulus. Right ventricular pressure over
this equivocal range (1.8-2.25 m/sec) are c o m m o n . This may load produces right ventricle (RV) hypertrophy as well as
reflect breed-specific variation i n LV outflow tract anatomy secondary dilation. Severe ventricular hypertrophy promotes
or response to sympathetic stimulation, rather than SAS. A myocardial ischemia and its sequelae. Excessive muscular
limitation o f using the estimated pressure gradient to assess hypertrophy below the valve (infundibular area) can create
outflow obstruction severity is that this gradient depends o n a dynamic subvalvular component to the stenosis. Other
blood flow. Factors causing sympathetic stimulation and variants o f PS, including supravalvular stenosis and R V mus
increased cardiac output (e.g., excitement, exercise, fever) cular partition (double chamber R V ) occur rarely.
will increase outflow velocities, whereas myocardial failure, High-velocity b l o o d flow across the stenotic orifice creates
cardiodepressant drugs, and other causes o f reduced stroke turbulence leading to poststenotic dilation i n the m a i n p u l
volume will decrease recorded velocities. Cardiac catheter monary trunk. Right atrial dilation from secondary tricuspid
ization and angiocardiography are rarely used n o w to diag insufficiency and high R V filling pressure predisposes to
nose or quantify SAS, except i n conjunction with balloon atrial tachyarrhythmias and C H F . The combination of PS
dilation of the stenotic area. and a patent foramen ovale or A S D can allow right-to-left
shunting at the atrial level, but this is rare i n dogs and cats.
Treatment and Prognosis A single anomalous coronary artery has been described
Several palliative surgical techniques have been used i n in some Bulldogs and Boxers with PS and is thought to
dogs with severe SAS, with limited success. C a r d i o p u l m o contribute to the outflow obstruction. In such cases, pallia
nary bypass and open-heart surgery are necessary to reach tive surgical procedures and balloon valvuloplasty may cause
the lesion directly. Although resection of the stenotic area death secondary to transection or avulsion o f the major left
can significantly reduce the LV systolic pressure gradient and coronary branch.
possibly improve exercise ability, a long-term survival advan
tage appears lacking. Transvascular balloon dilation o f the Clinical Features
stenotic area reduces the measured gradient i n some dogs, M a n y dogs with PS are asymptomatic when diagnosed,
although narrowing may partially recur. Likewise, no sur although right-sided C H F or a history of exercise intolerance
vival benefit has been documented with this procedure. or syncope may exist. Clinical signs may not develop until
Medical therapy with a -blocker is advocated i n patients the animal is several years o l d , even i n those w i t h severe
with moderate to severe SAS to reduce myocardial oxygen stenosis. Physical examination findings characteristic of
demand and minimize the frequency and severity o f arrhyth moderate-to-severe stenosis include a prominent right pre
mias. Animals with a high pressure gradient, marked ST- cordial impulse; a thrill high at the left base; n o r m a l to
segment depression, frequent ventricular premature beats, slightly diminished femoral pulses; p i n k mucous m e m
or a history of syncope may be more likely to benefit from branes; and, i n some cases, jugular pulses. A systolic ejection
this therapy. Whether -blockers prolong survival is unclear. m u r m u r is heard best high at the left base on auscultation.
Exercise restriction is advised for animals with moderate-to- The m u r m u r can radiate cranioventrally and to the right i n
severe SAS. Prophylactic antibiotic therapy is recommended some cases but usually is not heard over the carotid arteries.
for animals with SAS before the performance o f any proce A n early systolic click is sometimes identified; this probably
dures with the potential to cause bacteremia (e.g., dentistry). is caused by abrupt checking o f a fused valve at the onset o f
The prognosis i n dogs and cats with severe stenosis (cath ejection. A m u r m u r o f tricuspid insufficiency or arrhyth
eterization pressure gradient >80 m m H g or Doppler gradi mias can be heard i n some cases.
Diagnosis diographic findings characteristic of moderate-to-severe
Radiographic findings typically seen in animals with PS are stenosis include R V hypertrophy and enlargement. The
outlined in Table 5-2. M a r k e d R V hypertrophy shifts the interventricular septum often appears flattened as high R V
cardiac apex dorsally and to the left. The heart may appear pressure pushes it toward the left (Figure 5-8, A). R A enlarge
as a "reverse D " shape on a D V or ventrodorsal ( V D ) view. ment is often seen as well. A thickened, asymmetrical, or
A variably sized pulmonary trunk bulge (poststenotic dila otherwise malformed pulmonic valve usually can be identi
tion) is best seen at the 1 o'clock position on a D V or V D fied (Fig. 5-8, B), although the outflow area may be narrow
view (Fig. 5-7). The size of the poststenotic dilation does not and difficult to visualize clearly. Poststenotic dilation of the
correlate with the severity of the pressure gradient. A dilated main pulmonary trunk is expected. Pleural effusion and
caudal vena cava is also seen in some animals. marked right heart dilation often accompany secondary
E C G changes are more c o m m o n in patients with moder C H F . Paradoxical septal m o t i o n is likely in such cases as well.
ate to severe stenosis. These include an R V hypertrophy Doppler evaluation along with anatomic findings provides
pattern, right axis deviation, and sometimes an R A enlarge an estimate of PS severity. Cardiac catheterization and angio
ment pattern (P pulmonale) or tachyarrhythmias. Echocar cardiography also can be used to assess the pressure gradient
FIG 5 - 7
Lateral (A) a n d d o r s o v e n t r a l (DV) (B) r a d i o g r a p h s from a d o g with p u l m o n i c stenosis,
s h o w i n g right ventricular e n l a r g e m e n t ( a p e x e l e v a t i o n o n lateral v i e w [arrowhead in A]
a n d reverse D c o n f i g u r a t i o n o n D V view) a l o n g with a p u l m o n a r y trunk b u l g e [arrowheads
in B) seen o n a D V v i e w . C , A n g i o c a r d i o g r a m using a selective right ventricular injection
demonstrates poststenotic d i l a t i o n of the m a i n p u l m o n a r y trunk a n d p u l m o n a r y arteries.
The t h i c k e n e d p u l m o n i c v a l v e is c l o s e d in this diastolic f r a m e .
FIG 5 - 8
E c h o c a r d i o g r a m s from t w o d o g s with severe p u l m o n i c stenosis. (A) Right p a r a s t e r n a l short-
a x i s v i e w at the ventricular level in a 4-month-old m a l e S a m o y e d s h o w s right ventricular
h y p e r t r o p h y (arrows) a n d e n l a r g e m e n t ; high right ventricular pressure flattens the septum
t o w a r d the left in this diastolic f r a m e . (B) T h i c k e n e d , p a r t i a l l y fused leaflets of the mal
f o r m e d p u l m o n a r y v a l v e (arrows) a r e seen in a 5-month-old m a l e P o m e r a n i a n . Ao, A o r t i c
root; LA, left atrium; RVOT, right ventricular outflow tract; RVW, right ventricular w a l l .
across the stenotic valve, the right heart filling pressure, and Exercise restriction is generally advised for animals with
other anatomic features. Doppler-estimated systolic pressure moderate-to-severe stenosis. A -blocker may be helpful,
gradients i n unanesthetized animals are usually 40% to 50% especially i n those with prominent R V infundibular hyper
higher than those recorded during cardiac catheterization. trophy. Signs o f C H F are managed medically (see Chapter
PS is generally considered m i l d i f the Doppler-derived gradi 3). The prognosis i n patients with PS is variable and depends
ent is <50 m m H g and severe i f it is >80 to 100 m m H g . on the severity o f the lesion. Life span can be normal in those
with m i l d PS, whereas animals with severe PS often die
Treatment a n d Prognosis within 3 years o f diagnosis. Sudden death or the onset o f
Balloon valvuloplasty is recommended for palliation of C H F is c o m m o n . The prognosis is considerably worse i n
severe (and sometimes moderate) stenosis, especially i f animals with tricuspid regurgitation, atrial fibrillation or
infundibular hypertrophy is not excessive. This procedure other tachyarrhythmias, or C H F .
reduces or eliminates clinical signs and appears to improve
long-term survival in severely affected animals. Balloon val
vuloplasty, done in conjunction with cardiac catheterization, INTRACARDIAC SHUNT
involves passing a specially designed balloon catheter across
the valve and inflating the balloon to enlarge the stenotic Blood flow volume across an intracardiac shunt depends
orifice. The procedure is most successful in dogs with simple on the size of the defect and the pressure gradient across
fusion of the pulmonic valve cusps. Dysplastic valves are it. In most cases, flow direction is from left to right, causing
more difficult to dilate effectively, but good results are pos pulmonary overcirculation. Compensatory increases i n
sible in some cases. Various surgical procedures also have blood volume and cardiac output occur in response to the
been used to palliate moderate-to-severe PS i n dogs. Balloon partial diversion o f blood away from the systemic circula
valvuloplasty generally is attempted before a surgical proce tion. A volume overload is imposed on the side o f the
dure because it is less risky. Animals with a single anomalous heart doing the most work. If right heart pressures increase
coronary artery should not undergo balloon or surgical dila as a result o f pulmonary hypertension or a concurrent
tion procedures. Coronary anatomy can be verified using PS, shunt flow may equilibrate or reverse (i.e., become
echocardiography or angiography. right-to-left).
VENTRICULAR SEPTAL DEFECT
Etiology and Pathophysiology
Most V S D s are located i n the membranous part o f the
septum, just below the aortic valve and beneath the septal
tricuspid leaflet. V S D s sporadically occur i n other septal
locations also. A V S D may be accompanied by other A V
septal (endocardial cushion) malformations, especially i n
cats. Usually, V S D s produce a volume overload o n the lungs,
L A , LV, and R V outflow tract. Small defects may be clinically
unimportant. Moderate-to-large defects tend to cause left
heart dilation and can lead to left-sided C H F . A very large
V S D causes both ventricles to function as a c o m m o n chamber
and induces R V dilation and hypertrophy. Pulmonary hyper
tension secondary to overcirculation is more likely to develop
i n animals with a large shunt. Some animals with V S D also
have aortic regurgitation, w i t h diastolic prolapse o f a valve
leaflet. Presumably this occurs because the deformed septum
provides inadequate anatomic support for the aortic root.
Aortic regurgitation places an additional volume load o n the FIG 5 - 9
C o l o r f l o w D o p p l e r f r a m e in systole s h o w i n g turbulent f l o w
LV.
(from left to right) through a small m e m b r a n o u s ventricular
septal defect just b e l o w the aortic root in a 1-year-old male
Clinical Features
terrier. Right p a r a s t e r n a l long a x i s v i e w ; AO, aortic root;
The most c o m m o n clinical manifestations o f V S D are exer LV, left ventricle.
cise intolerance and signs o f left-sided C H F . M a n y animals
are asymptomatic at the time o f diagnosis. The characteristic
auscultatory finding is a holosystolic murmur, heard loudest
at the cranial right sternal border (which corresponds to the more than one plane. Supporting clinical evidence and a
direction o f shunt flow). A large shunt volume can produce m u r m u r typical o f a V S D also should be present before the
a m u r m u r o f relative or functional PS (systolic ejection diagnosis is made. Doppler (or echo-contrast) studies usually
m u r m u r at the left base). W i t h concurrent aortic regurgita demonstrate the shunt flow (Fig. 5-9).
tion, the corresponding diastolic decrescendo m u r m u r is Cardiac catheterization, oximetry, and angiocardiogra
heard at the left base. phy allow measurement o f intracardiac pressures, indicate
the presence of an oxygen step-up at the level o f the R V
Diagnosis outflow tract, and show the pathway o f abnormal blood
Radiographic findings associated w i t h V S D vary with flow.
thesize o f the defect and the shunt volume (see Table 5-2).
Large shunts cause left heart enlargement and pulmonary Treatment and Prognosis
overcirculation. However, large shunts that increase p u l m o A small-to-moderate defect usually allows a relatively normal
nary vascular resistance and pressure lead to R V enlarge life span. In some cases, the defect closes spontaneously
ment. A large shunt volume (with or without pulmonary within the first 2 years of life. Closure can result from myo
hypertension) also can increase m a i n pulmonary trunk cardial hypertrophy around the V S D or a seal formed by the
size. septal tricuspid leaflet or a prolapsed aortic leaflet. Left-sided
The E C G may be n o r m a l or suggest L A or L V enlarge C H F is more likely i n animals with a large septal defect,
ment. In some cases, disturbed intraventricular conduction although pulmonary hypertension with shunt reversal devel
is suggested by "fractionated" or splintered Q R S complexes. ops in some instead, usually at an early age.
A n R V enlargement pattern usually indicates a very large Definitive therapy for V S D usually requires cardiopul
defect, pulmonary hypertension, or a concurrent R V outflow monary bypass or hypothermia and intracardiac surgery,
tract obstruction, although sometimes a right bundle-branch although transcatheter delivery o f an occlusion device may
block causes this pattern. be possible i n some cases. Large left-to-right shunts are
Echocardiography reveals left heart dilation (with or sometimes palliated by surgically placing a constrictive band
without R V dilation) when the shunt is large. The defect around the pulmonary trunk to create a m i l d supravalvular
often can be visualized just below the aortic valve in the right PS. This raises R V systolic pressure in response to the
parasternal long-axis L V outflow view. The septal tricuspid increased outflow resistance. Consequently, less b l o o d shunts
leaflet is located to the right o f the defect. Because echo from L V to RV. A n excessively tight band can cause right-to-
"dropout" at the thin membranous septum can m i m i c a left shunting (functionally analogous to a T o f F), however.
V S D , the area o f a suspected defect should be visualized in Left-sided C H F is managed medically. Palliative surgery
should not be attempted i n the presence o f pulmonary ATRIOVENTRICULAR VALVE
hypertension and shunt reversal. MALFORMATION
ATRIAL SEPTAL DEFECT MITRAL DYSPLASIA
Congenital malformations o f the mitral valve apparatus
Etiology and Pathophysiology include shortened or overly elongated chordae tendineae,
Several types of A S D exist. Those located i n the region o f the direct attachment of the valve cusp to a papillary muscle,
fossa ovalis (ostium secundum defects) are more c o m m o n thickened or cleft or shortened valve cusps, prolapse o f valve
in dogs. A n A S D i n the lower interatrial septum (ostium leaflets, upwardly displaced or malformed papillary muscles,
p r i m u m defect) is likely to be part o f the A V septal (endo and excessive dilation o f the valve annulus. M i t r a l valve dys
cardial cushion or c o m m o n A V canal) defect complex, espe plasia ( M D ) is most c o m m o n i n large-breed dogs and also
cially in cats. Sinus venosus-type defects are rare; these are occurs i n cats. Valvular regurgitation is the predominant
located high in the atrial septum near the entry of the cranial functional abnormality, and it may be severe; the patho
vena cava. Animals with A S D c o m m o n l y have other cardiac physiology and sequelae resemble those o f acquired mitral
malformations as well. In most cases o f A S D , b l o o d shunts regurgitation (see p. 121). M i t r a l valve stenosis is u n c o m
from L A to R A and results in a volume overload to the right m o n . Obstruction to ventricular filling increases L A pressure
heart. However, i f PS or pulmonary hypertension is present, and can precipitate the development o f pulmonary edema.
right-to-left shunting and cyanosis may occur. M i t r a l regurgitation usually accompanies stenosis.
The clinical signs seen i n patients w i t h M D are similar to
Clinical Features those in dogs w i t h degenerative mitral valve disease, except
The clinical history i n animals with an A S D is usually rather for the younger patient age. Reduced exercise tolerance,
nonspecific. Physical examination findings associated with respiratory signs o f left-sided C H F , inappetence, and atrial
an isolated A S D are often unremarkable, although large left- arrhythmias (especially atrial fibrillation) are c o m m o n in
to-right shunts can cause a m u r m u r of relative PS. Fixed affected animals. M i t r a l regurgitation typically causes a sys
splitting (i.e., with no respiratory variation) o f the second tolic m u r m u r heard best at the left apex.
heart sound (S ) is the classic auscultatory finding. Rarely, a
2 The radiographic, E C G , echocardiographic, and catheter
soft diastolic m u r m u r of relative tricuspid stenosis might be ization findings are similar to those found in patients with
audible. acquired mitral insufficiency. Echocardiography can depict
the specific mitral apparatus malformations as well as the
Diagnosis degree o f chamber enlargement and functional changes.
Right heart enlargement, with or without pulmonary trunk Therapy consists o f medical management for C H F .
dilation, is found radiographically i n patients with severe Animals w i t h m i l d to moderate mitral valve dysfunction
shunts (see Table 5-2). The pulmonary circulation may may do well clinically for years. However, for those w i t h
appear to be increased unless pulmonary hypertension has severe mitral regurgitation or stenosis, the prognosis is poor.
developed. Left heart enlargement is not seen unless another Surgical valve reconstruction or replacement may be possible
defect, such as mitral insufficiency, is present. The E C G may i n some cases.
be normal or show evidence o f R V and R A enlargement. Cats
with an AV septal defect may have R V enlargement and a left TRICUSPID DYSPLASIA
axis deviation. Animals with tricuspid dysplasia ( T D ) have malformations
Echocardiography is likely to show R A and R V dilation, of the tricuspid valve and related structures that are similar
with or without paradoxical interventricular septal m o t i o n . to those of M D . The tricuspid valve can be displaced ven
Large ASDs can be visualized. Care must be taken not to trally into the ventricle (an Ebsteinlike anomaly) i n some
confuse the thinner fossa ovalis region of the interatrial cases; ventricular preexcitation may be more likely i n these
septum with an A S D because echo dropout also occurs here. animals. Tricuspid dysplasia is identified most frequently i n
Doppler echocardiography allows identification of smaller large-breed dogs, particularly in Labrador Retrievers, and i n
shunts that cannot be clearly visualized o n 2-D exam, but males.
venous inflow streams may complicate this. Cardiac cathe The pathophysiologic features o f T D are the same as
terization shows an oxygen step-up at the level o f the R A . those o f acquired tricuspid regurgitation. Severe cases result
Abnormal flow through the shunt may be evident after the i n marked enlargement o f the right heart chambers. Progres
injection of contrast material into the pulmonary artery. sive increase in R A and R V end-diastolic pressures eventually
result in right-sided C H F . Tricuspid stenosis is rare.
Treatment and Prognosis The historical signs and clinical findings likewise are
Large shunts can be treated surgically, similarly to V S D s . similar to those o f degenerative tricuspid disease. Initially,
Otherwise, animals are managed medically i f C H F develops. the animal may be asymptomatic or mildly exercise intoler
The prognosis is variable and depends o n shunt size, con ant. However, exercise intolerance, abdominal distention
current defects, and the level of pulmonary vascular resulting from ascites, dyspnea resulting from pleural effu
resistance. sion, anorexia, and cardiac cachexia often develop. The
FIG 5 - 1 0
Right p a r a s t e r n a l long-axis e c h o i m a g e s from a 1-year-old m a l e L a b r a d o r Retriever with
tricuspid v a l v e d y s p l a s i a in d i a s t o l e (A) a n d systole (B). The v a l v e annulus a p p e a r s to be
ventrally d i s p l a c e d ; the leaflet tips a r e tethered to a m a l f o r m e d , w i d e p a p i l l a r y muscle
[arrows in A ) . W i d e leaflet tip s e p a r a t i o n in systole (B) c a u s e d severe tricuspid regurgita
tion a n d c l i n i c a l c o n g e s t i v e heart failure. LA, Left a t r i u m ; LV, left ventricle; RA, right atrium;
RV, right ventricle.
breath, syncope (especially in association with exercise or Thoracic radiographs typically reveal right heart enlarge
excitement), seizures, and sudden death are c o m m o n . Cough ment; a prominent pulmonary trunk; and tortuous, proxi
and hemoptysis may also occur. Cyanosis may be evident mally widened pulmonary arteries. A bulge in the descending
FIG 5 - 1 1
A n g i o c a r d i o g r a m s from a n 8-month-old f e m a l e C o c k e r S p a n i e l with patent ductus arterio
sus, p u l m o n a r y h y p e r t e n s i o n , a n d shunt reversal. Left ventricular injection (A) s h o w s d o r s a l
d i s p l a c e m e n t of the left ventricle b y the e n l a r g e d right ventricle. N o t e the dilution of
r a d i o g r a p h i c contrast solution in the d e s c e n d i n g a o r t a (from m i x i n g with n o n o p a c i f i e d
b l o o d from the ductus) a n d the p r o m i n e n t right c o r o n a r y artery. Right ventricular injection
(B) illustrates right ventricular h y p e r t r o p h y a n d p u l m o n a r y trunk d i l a t i o n s e c o n d a r y to
severe p u l m o n a r y h y p e r t e n s i o n . O p a c i f i e d b l o o d courses through the l a r g e ductus into the
descending aorta.
aorta may be seen in dogs with reversed P D A . The left heart clinical signs and exercise tolerance i n some dogs with pul
in animals with a reversed P D A or V S D may be enlarged monary hypertension, although experience in animals is
as well. The E C G usually suggests R V and sometimes R A limited. Doses o f 0.5 to 2(or 3) mg/kg q l 2 h or q8h seem to
enlargement, with a right axis deviation. be well-tolerated and produce some reduction i n Doppler-
Echocardiography reveals the R V hypertrophy and intra estimated pulmonary artery pressure. Lower initial doses are
cardiac anatomic defects (and sometimes a large ductus), as suggested, w i t h gradual up-titration. Adverse effects o f silde
well as pulmonary trunk dilation. Doppler or echo-contrast nafil can include possible nasal congestion, hypotension, or
study can confirm an intracardiac right-to-left shunt. sexual adverse effects, especially i n intact animals. Other
Reversed P D A flow can be shown by imaging the abdominal vasodilator drugs tend to produce systemic effects that are
aorta during venous echocontrast injection. Peak R V (and i n similar to or greater than those o n the pulmonary vascula
the absence of PS, pulmonary artery) pressure can be esti ture; therefore they are o f little benefit and possibly detri
mated by measuring the peak velocity o f a tricuspid regur mental. Low-dose aspirin (e.g., 5 mg/kg) therapy may also
gitation jet. Pulmonary insufficiency flow can be used to be useful i n animals w i t h pulmonary hypertension and
estimate diastolic pulmonary artery pressure. Cardiac cath reversed shunt, but this is not well-studied.
eterization also can confirm the diagnosis and quantify the
pulmonary hypertension and systemic hypoxemia.
OTHER CARDIOVASCULAR ANOMALIES
Treatment a n d Prognosis
114
tricle and atrium, diminishing the forward flow to the aorta. tion can reduce ventricular filling time and cardiac output,
Compensatory mechanisms augment b l o o d volume to meet increase myocardial oxygen needs, and worsen p u l m o n a r y
the circulatory needs o f the body (see Chapter 3), including congestion and edema. Ventricular tachyarrhythmias also
increased sympathetic activity, attenuated vagal tone, and occur but are less c o m m o n .
renin-angiotensin-aldosterone system (RAAS) activation. Sudden rupture o f diseased chordae tendineae acutely
Natriuretic peptide release occurs; higher atrial natriuretic increases regurgitant volume and can precipitate fulminant
peptide concentrations have been associated with marked pulmonary edema w i t h i n hours in previously compensated
left atrium (LA) enlargement and severe congestive heart or even asymptomatic dogs. Signs of low cardiac output may
failure ( C H F ) . The affected ventricle and atrium dilate to also occur. Sometimes, ruptured chordae tendineae are an
accept the growing regurgitant volume and the required incidental finding (on an echocardiogram or at necropsy),
forward stroke volume; eccentric myocardial hypertrophy especially i f second- or third-order chordae are involved.
develops i n an attempt to normalize the resulting increase i n Massive L A enlargement itself can result i n compression
wall stress. of the left mainstem bronchus and stimulate persistent
These compensatory changes i n heart size and b l o o d coughing, even i n the absence o f C H F . Furthermore, massive
volume allow most dogs to remain asymptomatic for a pro left (or right) atrial distention can result i n partial- or full-
longed period. Massive L A enlargement may develop before thickness tearing. Atrial wall rupture usually causes acute
any signs o f heart failure appear, and some dogs never show cardiac tamponade; there appears to be a higher prevalence
clinical signs o f heart failure. The rate at which the regurgi
tation worsens, as well as the degree o f atrial distensibility
and ventricular contractility, influence how well the disease
BOX 6-
is tolerated. A gradual increase i n atrial, pulmonary venous, Potential Complications of Chronic Atrioventricular
and capillary hydrostatic pressures stimulates compensatory
Valve Disease
increases in pulmonary lymphatic flow. Overt pulmonary
edema develops when the capacity of the pulmonary l y m Causes of Acutely Worsened Pulmonary Edema
phatic system is exceeded. Tricuspid insufficiency may be Arrhythmias
severe enough to cause right-sided C H F . Increased p u l m o Frequent atrial premature complexes
nary vascular pressure secondary to chronic left-sided C H F Paroxysmal atrial/supraventricular tachycardia
may also contribute to the development o f right-sided heart Atrial fibrillation
failure. Frequent ventricular tachyarrhythmias
Rule out drug toxicity (e.g., digoxin)
Ventricular p u m p function is maintained fairly well until
Ruptured chordae tendineae
late in the disease in many dogs, even i n the face o f severe
Iatrogenic volume overload
congestive signs. Nevertheless, chronic volume overload
Excessive volumes of IV fluids or blood
eventually reduces myocyte contractility. The mechanism o f High-sodium fluids
myocardial dysfunction may involve damage from oxygen Erratic or improper medication administration
free radicals as well as neurohormonal activation. Reduced Insufficient medication for stage of disease
contractility exacerbates ventricular dilation and valve regur Increased cardiac workload
gitation and therefore can worsen C H F . Assessment o f left Physical exertion
ventricular (LV) contractility i n animals with M R is c o m p l i Anemia
cated by the fact that the most commonly used clinical Infections/sepsis
indices (e.g., echocardiographic fractional shortening, ejec Hypertension
Disease of other organ systems (e.g., pulmonary, renal,
tion fraction) overestimate contractility because they are
liver, endocrine)
obtained during ejection and are therefore affected by the
Hot, humid environment
reduced ventricular afterload caused by M R . The echocar
Excessively cold environment
diographic estimation of the end-systolic volume index may Other environmental stresses
be useful (see p. 41). This index suggests that myocardial High salt intake
function is normal to mildly depressed i n most dogs with Myocardial degeneration and poor contractility
chronic mitral degeneration. A number of other echo/
Causes of Reduced Cardiac Output or Weakness
Doppler indices can also help assess L V systolic and diastolic
function. Arrhythmias (see above)
Ruptured chordae tendineae
Complicating Factors Cough-syncope
Left atrial tear
Although this disease usually progresses slowly, certain c o m
Intrapericardial bleeding
plicating events can precipitate acute clinical signs i n dogs
Cardiac tamponade
with previously compensated disease (Box 6-1). For example,
Increased cardiac workload (see above)
tachyarrhythmias may be severe enough to cause decompen Secondary right-sided heart failure
sated C H F , syncope, or both. Frequent atrial premature Myocardial degeneration and poor contractility
contractions, paroxysmal atrial tachycardia, or atrial fibrilla
of this complication i n male Miniature Poodles, Cocker marked sinus arrhythmia and a normal heart rate. Pleural
Spaniels, and Dachshunds. In most o f these cases, severe effusion causes diminished pulmonary sounds ventrally.
valve disease; marked atrial enlargement; atrial jet lesions; Other physical examination findings may be normal or
and, often, ruptured first-order chordae tendineae are noncontributory. Peripheral capillary perfusion and arterial
present. pulse strength are usually good, although pulse deficits may
be present in dogs with tachyarrhythmias. A palpable pre
Clinical Features cordial thrill accompanies l o u d (grade 5-6/6) murmurs.
Degenerative A V valve disease may cause no clinical signs for Jugular vein distention and pulsations are not expected in
years, and some dogs never develop signs o f heart failure. In dogs with M R alone. In animals with T R , jugular pulses
those that do, the signs usually relate to decreased exercise occur during ventricular systole; these are more evident after
tolerance and manifestations o f pulmonary congestion and exercise or i n association with excitement. Jugular venous
edema. D i m i n i s h e d exercise capacity and cough or tachy distention results from elevated right heart filling pressures.
pnea with exertion are c o m m o n initial owner complaints. Jugular pulsations and distention are more evident with
As pulmonary congestion and interstitial edema worsen, the cranial abdominal compression (positive hepatojugular
resting respiratory rate increases. C o u g h i n g tends to occur reflux). Ascites or hepatomegaly may be evident in dogs with
at night and early m o r n i n g , as well as i n association w i t h right-sided C H F .
activity. Severe edema results i n obvious respiratory distress
and usually a moist cough. Signs o f severe pulmonary edema Diagnosis
can develop gradually or acutely. Intermittent episodes o f
symptomatic pulmonary edema interspersed with periods o f RADIOGRAPHY
compensated heart failure occurring over months to years Thoracic radiographs typically show some degree of L A and
are also c o m m o n . Episodes o f transient weakness or acute LV enlargement (see p. 13), which progresses over months
collapse (syncope) can occur secondary to arrhythmias, to years (Fig. 6-1). As L A size increases, dorsal main bron
coughing, or an atrial tear. Signs o f tricuspid regurgitation chus displacement occurs. Severe L A enlargement causes
(TR) are often overshadowed by those o f M R but include compression o f the left mainstem bronchus. Fluoroscopy
ascites; respiratory distress from pleural effusion; and, rarely, may demonstrate dynamic main bronchus collapse during
subcutaneous edema. Splanchnic congestion may precipitate coughing or even quiet breathing i n such animals. Extreme
gastrointestinal signs. The cough caused by m a i n bronchus dilation o f the L A can result over time, even without clinical
compression often is described as "honking." heart failure. Variable right heart enlargement occurs with
A holosystolic m u r m u r heard best i n the area o f the left chronic T R , but this may be masked by left heart and pul
apex (left fourth to sixth intercostal space) is typical i n monary changes associated with concurrent M V D .
patients with M R . The m u r m u r can radiate i n any direction. Pulmonary venous congestion and interstitial edema
M i l d regurgitation may be inaudible or cause a m u r m u r only occur with the onset o f left-sided C H F ; progressive intersti
in early systole (protosystolic). Exercise and excitement often tial and alveolar pulmonary edema may follow. Although
increase the intensity of soft M R murmurs. Louder murmurs cardiogenic pulmonary edema in dogs typically has a hilar,
have been associated with more advanced disease, but i n dorsocaudal, and bilaterally symmetric pattern, an asym
dogs with massive regurgitation and severe heart failure, the metric distribution is seen in some dogs. The presence and
m u r m u r can be soft or even inaudible. Occasionally, the severity o f pulmonary edema do not necessarily correlate
m u r m u r sounds like a musical tone or whoop. Some dogs with the degree o f cardiomegaly. Acute, severe M R (e.g., with
with chronic mitral disease have a m i d - to late-systolic click, rupture o f the chordae tendineae) can cause severe edema in
w i t h or without a murmur. A n S gallop may be audible at
3 the presence o f m i n i m a l L A enlargement. Conversely, slowly
the left apex i n dogs with advanced disease. T R typically worsening M R can produce massive L A enlargement with no
causes a holosystolic m u r m u r best heard at the right apex. evidence o f C H F . Early signs of right-sided heart failure
Features that aid i n differentiating a T R m u r m u r from radi include caudal vena caval distention, pleural fissure lines,
ation o f an M R m u r m u r to the right chest wall include and hepatomegaly. Overt pleural effusion and ascites occur
jugular vein pulsations, a precordial thrill over the right apex, with advanced failure.
and a different quality to the m u r m u r heard over the tricus
p i d region. ELECTROCARDOGRAPHY
Pulmonary sounds can be n o r m a l or abnormal. Accentu The electrocardiogram ( E C G ) may suggest L A or biatrial
ated, harsh breath sounds and end-inspiratory crackles enlargement and L V dilation (see p. 28), although the tracing
(especially i n ventral lung fields) develop as pulmonary is often normal. A n R V enlargement pattern is occasionally
edema worsens. Fulminant pulmonary edema causes wide seen in dogs w i t h severe T R . Arrhythmias, especially sinus
spread inspiratory as well as expiratory crackles and wheezes. tachycardia, supraventricular premature complexes, parox
Some dogs with chronic M R have abnormal lung sounds ysmal or sustained supraventricular tachycardias, ventricular
caused by underlying p u l m o n a r y or airway disease rather premature complexes, and atrial fibrillation are c o m m o n in
than C H F . Dogs w i t h C H F tend to have sinus tachycardia; dogs with advanced disease. These arrhythmias may be asso
those with chronic pulmonary disease frequently have ciated with decompensated C H F , weakness, or syncope.
FIG 6-1
Lateral (A) a n d d o r s o v e n t r a l (B) r a d i o g r a p h s from a P o o d l e with a d v a n c e d mitral v a l v e
insufficiency. N o t e m a r k e d left ventricular a n d atrial e n l a r g e m e n t a n d n a r r o w i n g of left
mainstem b r o n c h u s [arrowheads in A ) .
ECHOCARDIOGRAPHY
Echocardiography shows the atrial and ventricular chamber
dilation secondary to chronic A V valve insufficiency. Depend
ing on the degree of volume overload, this enlargement can
be severe. Vigorous LV wall and septal m o t i o n are seen with
M R when contractility is normal (Fig. 6-2); fractional short
ening is high, and there is little to no E point-septal separa
tion. Although ventricular diastolic dimension is increased,
systolic dimension is normal until myocardial failure ensues.
Calculation of end-systolic volume index may help in assess
ing myocardial function. Ventricular wall thickness is typi
cally normal in dogs with chronic A V valve disease. W i t h
severe T R , paradoxical septal motion may occur along with
the right ventricular (RV) and right atrial (RA) dilation.
Pericardial fluid (blood) is seen after an L A tear, and evi FIG 6 - 2
dence for cardiac tamponade may be evident. M i l d pericar S a m p l e M - m o d e e c h o c a r d i o g r a m from m a l e M a l t e s e with
a d v a n c e d mitral v a l v e insufficiency a n d left-sided heart
dial effusion may also accompany signs of right-sided C H F .
failure. N o t e a c c e n t u a t e d septal a n d left ventricular poste
Affected valve cusps are thickened and may appear
rior w a l l motion (fractional shortening = 5 0 % ) a n d lack of
knobby. Smooth thickening is characteristic of degenerative mitral v a l v e E p o i n t - s e p t a l s e p a r a t i o n (arrows).
disease (endocardiosis). Conversely, rough and irregular veg
etative valve lesions are characteristic of bacterial endo
carditis; however, clear differentiation between these by flow area provides a rough estimate of regurgitation severity,
echocardiography alone may be impossible. Systolic prolapse there are technical limitations with this. The proximal
involving one or both valve leaflets is c o m m o n with degen isovelocity surface area (PISA) method is considered by
erative A V valve disease (Fig. 6-3, A). A ruptured chorda some to be a more accurate way to estimate M R severity.
tendinea or leaflet tip sometimes is seen flailing into the Other Doppler techniques can be used to evaluate systolic
atrium during systole (Figure 6-3, B). The direction and and diastolic ventricular function. M a x i m a l T R jet velocity
extent of flow disturbance can be seen with color-flow indicates whether pulmonary hypertension is present and its
Doppler (see Figure 2-35). Although the size of the disturbed severity.
FIG 6 - 3
A , Thick, mildly p r o l a p s i n g mitral v a l v e a n d LA e n l a r g e m e n t a r e seen from the left a p i c a l
position in a n o l d e r D a c h s h u n d with severe d e g e n e r a t i v e A V v a l v e d i s e a s e . The tricuspid
v a l v e is also thick. B , C h o r d a t e n d i n e a e rupture is e v i d e n t b y the flail segment (arrow)
seen in the e n l a r g e d LA of a n o l d e r m i x e d b r e e d d o g . C , A l a r g e jet of mitral regurgita
tion c a u s e s a w i d e a r e a of f l o w d i s t u r b a n c e in a n o t h e r m i x e d b r e e d d o g o n c o l o r f l o w
e c h o . N o t e the LA a n d LV e n l a r g e m e n t . LA, Left a t r i u m ; LV, left ventricle; RA, right atrium.
* S e e Tables 3-2, 3-3, and Box 3-1 for further details and doses.
in dogs o n long-term C H F therapy often can be successfully delays time to C H F onset i n asymptomatic dogs is presently
managed. Therapy must be guided by the patient's clinical lacking. Whether dogs w i t h marked cardiomegaly might
status and the nature o f complicating factors. Surgical pro benefit from therapy to modulate pathologic remodeling is
cedures such as m i t r a l annuloplasty, other valve repair tech unclear.
niques, and mitral valve replacement may be treatment Client education about the disease process and early signs
options i n some patients but are not widely available. of C H F is important. It is probably prudent to discourage
high-salt foods, pursue weight reduction for obese dogs, and
Asymptomatic Atrioventricular avoid prolonged strenuous exercise. A diet moderately
Valve Regurgitation reduced i n salt may be helpful. Periodic reevaluation (e.g.,
Dogs that have shown no clinical signs o f disease are gener every 6 to 12 months) o f cardiac size and function as well
ally not given drug therapy. C o n v i n c i n g evidence that angio as b l o o d pressure is advised. Other disease conditions are
tensin-converting enzyme inhibitor (ACEI) or other therapy managed as appropriate.
Mild to Moderate Congestive Heart Failure Severe Congestive Heart Failure
When clinical signs occur i n association w i t h exercise or Severe p u l m o n a r y edema and shortness of breath at rest
activity, several treatment modalities are instituted (see Box require urgent treatment (see Box 3-1). Aggressive diuresis
6-2 and Tables 3-3 and Box 3-1). The severity o f clinical signs with parenteral furosemide (e.g., 2 to 4 mg/kg q l - 4 h IV,
and the nature o f any complicating factors influence the initially), supplemental oxygen, and cage rest are instituted
aggressiveness o f therapy. W h e n it is unclear whether respi as soon as possible. Gentle handling is important because
ratory signs are caused by early C H F or a noncardiac cause, added stress may precipitate cardiopulmonary arrest. Tho
a therapeutic trial o f furosemide (e.g., 1 to 2 mg/kg by m o u t h racic radiographs and other diagnostic procedures are post
q8-12h) is indicated. Cardiogenic p u l m o n a r y edema usually poned until the animal's respiratory condition is more
responds rapidly. stable.
Furosemide is used for dogs with radiographic evidence Vasodilator therapy is also indicated. If adequate m o n i
of p u l m o n a r y edema and/or more severe clinical signs. toring facilities are available, intravenous (IV) nitroprusside
Higher and more frequent doses are used when edema is may be used for rapid arteriolar and venous dilation; however,
severe. After signs o f failure are controlled, the dose and blood pressure must be closely monitored to prevent hypo
frequency o f furosemide administration are gradually tension. Another approach for acute therapy is oral hydrala
reduced to the lowest effective levels for chronic therapy. zine. Its direct and rapid arteriolar vasodilating effect
Furosemide alone (e.g., without an A C E I or other agent) is increases forward flow and decreases regurgitation; however,
not recommended for the long-term treatment o f heart oral administration can be stressful. A reduced dose is used
failure. in animals already o n an A C E I . A m l o d i p i n e is an alternative
A n A C E I is generally recommended for dogs with early arteriolar vasodilator, but it has a m u c h slower onset of
signs o f failure (see Chapter 3). The ability o f these agents action. Topical nitroglycerin also can be used in an attempt
to modulate neurohormonal responses to heart failure to reduce pulmonary venous pressure by direct venodilation.
is thought to be their m a i n advantage. C h r o n i c A C E I W h e n positive inotropic therapy is indicated, pimoben
therapy can improve exercise tolerance, cough, and respira dan (or digoxin) may be initiated (or continued i f previously
tory effort, although the issue o f enhanced survival is prescribed) once acute dyspnea subsides. Paroxysmal atrial
unclear. tachycardia or atrial fibrillation may respond to digoxin.
Pimobendan also is being used increasingly for the man Although several days are needed to achieve a therapeutic
agement o f moderate to advanced C H F (see Chapter 3). This blood concentration w i t h oral maintenance doses, I V digi
drug has positive inotropic, vasodilator, and other actions. talization is generally not recommended. Diltiazem or a
Its beneficial effects may exceed those o f ACEIs, although -blocker (see Table 4-2) can be used instead o f or in addi
they are often used together. Digoxin, with or without p i m o tion to digoxin i f supraventricular tachyarrhythmias require
bendan, is often added to the chronic therapy o f C H F treatment (see Chapter 4). Dogs that need more intense
resulting from advanced A V valve insufficiency. Digoxin's inotropic support or that have persistent hypotension can be
sensitizing effect o n baroreceptors may be more advanta given an IV agent (e.g., dobutamine, dopamine, amrinone;
geous than its modest positive inotropic effect (see Chapter see Box 3-1).
3). M a r k e d L V dilation, evidence for reduced myocardial Ancillary therapy often includes m i l d sedation to reduce
contractility, or recurrent episodes o f p u l m o n a r y edema anxiety (e.g., butorphanol or morphine). A bronchodilator
despite furosemide and other treatment are indications for (e.g., theophylline, aminophylline) may be useful if broncho-
adding digoxin. D i g o x i n also is indicated for heart rate spasm is induced by severe pulmonary edema; although effi
control i n dogs with atrial fibrillation and for its antiarrhyth cacy for this is unclear, these agents may help support
mic effect i n some cases o f frequent atrial premature beats respiratory muscle function.
or supraventricular tachycardia. Conservative doses and Thoracocentesis is indicated i n dogs with moderate- to
measurement o f serum concentrations are recommended to large-volume pleural effusion to improve pulmonary func
prevent toxicity (see p. 66). tion. Ascites that impedes respiration also should be drained.
Moderate dietary salt restriction (e.g., diets formulated Therapy for ventricular tachyarrhythmias is warranted
for dogs with kidney disease or for senior dogs) is recom in some cases. Close monitoring is important for titrating
mended initially. Further salt restriction may be achieved therapy and identifying drug toxicities or adverse effects
with diets formulated for patients w i t h heart failure. Exercise (e.g., azotemia, electrolyte abnormalities, hypotension,
restriction is important when signs o f C H F exist. M i l d to arrhythmias).
moderate, regular activity (not causing undue respiratory After the animal's condition is stabilized, medications are
effort) may be resumed during chronic, compensated dis adjusted over several days to weeks to determine optimal
ease. Strenuous exercise is not recommended. Antitussive long-term therapy. Furosemide is titrated to the lowest dose
therapy can be helpful i n dogs without p u l m o n a r y edema (and longest interval) that controls signs of C H F . Institution
but with persistent cough caused by mechanical mainstem of an A C E I is recommended for ongoing therapy if hydrala
bronchus compression (e.g., hydrocodone bitartrate, zine or nitroprusside was the initial vasodilator used. As
0.25 mg/kg by m o u t h q8-12h; or butorphanol, 0.5 mg/kg by the effects o f previously administered hydralazine wane,
m o u t h q6-12h). the first dose o f A C E I given should be half the usual dose
(i.e., 0.25 mg/kg by mouth). A n A C E I can be started at the nosed or decompensated C H F should be evaluated more
standard dose shortly after discontinuing a nitroprusside frequently (within several days to a week or so) until their
infusion. condition is stable. Those w i t h chronic heart failure that
appears well-controlled can be reevaluated less frequently,
Chronic Management of Advanced Disease usually several times per year. The medication supply, a d m i n
When C H F becomes refractory, therapy is intensified or istration compliance, drugs and doses being given, and diet
modified according to individual patient needs. The follow should be reviewed with the owner at each visit.
ing suggestions for modifying therapy are listed i n approxi A general physical exam w i t h particular attention to car
mate order of use. Recurrent pulmonary edema i n some diovascular parameters is important at each visit. A n E C G is
dogs responds to an increased dose o f furosemide and rest indicated i f an arrhythmia or unexpectedly low or high heart
for a few days. The dose can then be returned to previous or rate is found. W h e n an arrhythmia is suspected but not
a slightly higher level, i f possible. The A C E I dose should be documented o n routine E C G , ambulatory electrocardiogra
maximized i f this has not already been done (e.g., enalapril phy (e.g., 24-hour Holter monitoring) can be helpful. The
from once to twice daily). respiratory rate and pattern are also noted; thoracic radio
Pimobendan and/or digoxin can be added i f it is not graphs are warranted i f abnormal p u l m o n a r y sounds are
already being used. The dose o f digoxin is not titrated upward heard or i f the owner reports coughing, other respiratory
unless subtherapeutic serum concentrations are documented signs, or an increased resting respiratory rate. Other causes
(see Chapter 3). Spironolactone can be added, i f not already of cough should be considered i f neither p u l m o n a r y edema
being used (see Chapter 3). This aldosterone antagonist may nor venous congestion is seen radiographically and i f the
reduce the severity o f chronic refractory pulmonary edema resting respiratory rate has not increased. Left mainstem
or effusions as well as have beneficial effects o n cardiac bronchus compression by an enlarged L A can stimulate a dry
remodeling. Conversely, another diuretic with a different cough. C o u g h suppressants are helpful for this, but they
mechanism of action or the spironolactone/hydrochloro should be prescribed only after other causes o f cough are
thiazide combination product may be useful. ruled out.
Continued monitoring, especially o f renal function and Echocardiography may show evidence o f chordal rupture,
serum electrolyte concentrations, is important. Dietary progressive cardiomegaly, or worsened myocardial function.
sodium restriction can be intensified. If the A C E I and furo Frequent m o n i t o r i n g o f serum electrolyte concentrations
semide doses are already maximal, low-dose hydralazine (e. and renal function is important. Other routine b l o o d and
g., 0.25 to 0.5 mg/kg by m o u t h q l 2 h ) or amlodipine (e.g., urine tests are done periodically also. Dogs receiving digoxin
0.05 to 0.2 mg/kg by m o u t h q24h) can be added, although should have a serum concentration measured 7 to 10 days
blood pressure should be monitored. after treatment initiation or a dosage change. Additional
Intermittent tachyarrhythmias can promote decompen measurements are recommended i f signs consistent with
sated C H F as well as episodes o f transient weakness or toxicity appear or i f renal disease or electrolyte imbalance
syncope. Cough-induced syncope, atrial rupture, or other (hypokalemia) is suspected.
causes o f reduced cardiac output may also occur. Despite the The prognosis i n dogs that have shown clinical signs o f
periodic recurrence of signs o f C H F , many dogs w i t h chronic degenerative valve disease is quite variable. W i t h appropriate
A V valve regurgitation can enjoy a good quality o f life for therapy and attentive management o f complications, some
several years after the signs o f failure first appear. dogs live well for more than 4 years after the signs o f heart
failure first appear. Some dogs die during an initial episode
Patient Monitoring and Reevaluation of fulminant p u l m o n a r y edema. Survival for most symp
Client education regarding the disease process, the clinical tomatic dogs ranges from several months to a few years.
signs o f failure, and the drugs used to control them is essen
tial for long-term therapy to be successful. As the disease
progresses, medication readjustment (i.e., different dosages INFECTIVE ENDOCARDITIS
of currently used drugs and/or additional drugs) is expected.
Several c o m m o n potential complications o f chronic degen Etiology and Pathophysiology
erative A V valve disease can cause decompensation (see B o x Endocarditis is more c o m m o n i n dogs than i n cats. Bactere
6-1). At-home monitoring is important to detect early signs mia, either persistent or transient, is necessary for endocar
of decompensation. Respiratory (+/- heart) rate can be dial infection to occur. Recurrent bacteremia may occur with
monitored periodically when the dog is quietly resting or infections o f the skin, mouth, urinary tract, prostate, lungs,
sleeping (see p. 70; a persistent increase i n either can signal or other organs. Dentistry procedures are k n o w n to cause a
early decompensation. transient bacteremia. Other procedures are presumed to
Asymptomatic dogs should be reevaluated at least yearly cause transient bacteremia i n some cases (e.g., endoscopy,
in the context o f a routine preventive health program. The urethral catheterization, anal surgery, and other "dirty" pro
frequency of reevaluation i n dogs receiving medication for cedures). The likelihood o f a cardiac infection becoming
heart failure depends on the disease severity and whether any established is increased when organisms are highly virulent
complicating factors are present. Dogs w i t h recently diag or the bacterial load is heavy.
The endocardial surface of the valve is infected directly congestion and edema are usual. Clinical heart failure devel
from the b l o o d flowing past it. Previously normal valves may ops rapidly i n patients with severe valve destruction, rupture
be invaded by virulent bacteria, causing acute bacterial endo of chordae tendineae, and multiple valve involvement, or
carditis. Subacute bacterial endocarditis is thought to result when other predisposing factors are present. Cardiac func
from infection of previously damaged or diseased valves tion can be compromised by myocardial injury resulting
after a persistent bacteremia. Such damage may result from from coronary arterial embolization with myocardial infarc
mechanical trauma (e.g., jet lesions resulting from turbulent tion and abscess formation or from direct extension of the
blood flow or endocardial injury from a vascular catheter infection into the myocardium. Reduced contractility and
extending into the heart). Myxomatous degeneration of the atrial or ventricular tachyarrhythmias often result. Aortic
mitral valve has not been associated w i t h a higher risk for valve endocarditis lesions may extend into the A V node and
infective endocarditis. cause partial or complete A V block. Arrhythmias may cause
The lesions of endocarditis are typically located down weakness, syncope, and sudden death or contribute to the
stream from the disturbed b l o o d flow; c o m m o n sites include development of C H F .
the ventricular side of the aortic valve i n patients w i t h sub Fragments of vegetative lesions often break loose. Embo
aortic stenosis, the right ventricular side of a ventricular lization of other body sites causes infarction or metastatic
septal defect, and the atrial surface of a regurgitant mitral infection, which results i n diverse clinical signs. Larger and
valve. Bacterial clumping caused by the action of an agglu more mobile vegetations (based on echocardiographic
tinating antibody may facilitate attachment to the valves. appearance) are associated with higher incidence of embolic
Alternatively, chronic stress and mechanical trauma can pre events i n people; the same may occur in animals. Emboli can
dispose to the development of nonbacterial thrombotic be septic or bland (containing no infectious organisms).
endocarditis, a sterile accumulation of platelets and fibrin Septic arthritis, diskospondylitis, urinary tract infections,
o n the valve surface. Nonseptic emboli may break off from and renal and splenic infarctions are c o m m o n i n affected
such vegetations and cause infarctions elsewhere. Bacteremia animals. Local abscess formation resulting from septic
can also cause a secondary infective endocarditis at these thromboemboli contributes to recurrent bacteremia and
sites. fever. Hypertrophic osteopathy has also been associated with
The most c o m m o n organisms identified i n dogs and cats bacterial endocarditis. Circulating immune complexes as
with endocarditis have been Streptococcus sp., Staphylococcus well as cell-mediated responses contribute to the disease syn
sp., and Escherichia coli. Additional organisms isolated from drome. Sterile polyarthritis, glomerulonephritis, vasculitis,
infected valves have included Corynebacterium (Arcanobac and other forms of immune-mediated organ damage are
terium) sp., Pasteurella sp., Pseudomonas aeruginosa, Erysip c o m m o n . Rheumatoid factor and antinuclear antibody test
elothrix rhusiopathiae (E. tonsillaris), and others. Bartonella ( A N A ) results may be positive.
vinsonii subsp. berkhoffii and other Bartonella sp. have also
been found i n dogs w i t h endocarditis. Culture-negative Clinical Features
endocarditis may be caused by fastidious organisms or by The prevalence o f bacterial endocarditis is relatively low in
Bartonella spp.; i n a recent study of 71 dogs with infective dogs and even lower i n cats. Male dogs are affected more
endocarditis, Bartonella spp. was identified as the causative commonly than females. A n increased prevalence of endo
agent i n 45% of the patients w i t h a negative b l o o d culture carditis has been noted i n association with age. German
and i n 20% of the overall population. Shepherd Dogs and other large-breed dogs may be at greater
The mitral and aortic valves are most c o m m o n l y affected risk. Subaortic stenosis is a k n o w n risk factor for aortic
in dogs and cats. M i c r o b i a l colonization leads to ulceration valve endocarditis. Immunocompromised animals may also
of the valve endothelium. Subendothelial collagen exposure be at greater risk for endocarditis, but this has not been
in turn stimulates platelet aggregation and activation of the substantiated.
coagulation cascade, leading to the formation of vegetations. The clinical signs of endocarditis are quite variable. M a n y
Vegetations consist mainly of aggregated platelets, fibrin, affected animals have evidence of past or concurrent infec
blood cells, and bacteria. Newer vegetations are friable. W i t h tions, although often a clear history of predisposing factors
time, the lesions become fibrous and may calcify. As addi is absent. The presenting signs can result from left-sided
tional fibrin is deposited over bacterial colonies, they become C H F or arrhythmias, but cardiac signs may be overshadowed
protected from normal host defenses as well as many antibi by signs of systemic infarction, infection, immune-mediated
otics. Although vegetations usually involve the valve leaflets, damage, or a combination of these. Nonspecific signs of
lesions may extend to the chordae tendineae, sinuses of Val lethargy, weight loss, inappetence, recurrent fever, and weak
salva, mural endocardium, or adjacent myocardium. Vegeta ness may be the predominant abnormalities. Infective endo
tions cause valve deformity, including perforations or tearing carditis often mimics immune-mediated disease. Dogs with
o f the leaflet(s), and result i n valve insufficiency. Rarely, large endocarditis are c o m m o n l y evaluated for a "fever of unknown
vegetations may cause the valve to become stenotic. origin." Some of the consequences of infectious endocarditis
Valve insufficiency and subsequent volume overload are outlined i n Box 6-3. Endocarditis has been nicknamed
c o m m o n l y lead to C H E Because the mitral and/or aortic "the great imitator"; maintaining an index of suspicion for
valve is usually affected, left-sided C H F signs of pulmonary this disease is important.
BOX 6-3
Heart
Septic osteomyelitis
Valve insufficiency or stenosis Bone pain
Murmur Lameness
Congestive heart failure Myositis
Coronary embolization (aortic valve*) Muscle pain
Myocardial infarction
Brain and Meninges
Myocardial abscess
Myocarditis Abscesses
Decreased contractility (segmental or global) Associated neurologic signs
Arrhythmias Encephalitis and meningitis
Myocarditis (direct invasion by microorganisms) Associated neurologic signs
Arrhythmias
Vascular System in General
Atrioventricular conduction abnormalities (aortic valve*
Decreased contractility Vasculitis
Pericarditis (direct invasion by microorganisms) Thrombosis
Pericardial effusion Petechiae and small hemorrhages (e.g., eye, skin)
Cardiac tamponade (?) Obstruction
Infarction Lung
Reduced renal function Pulmonary emboli (tricuspid or pulmonic valves, rare*)
Abscess formation and pyelonephritis Pneumonia (tricuspid or pulmonic valves, rare*)
Reduced renal function
Nonspecific
Urinary tract infection
Renal pain Sepsis
Glomerulonephritis (immune mediated) Fever
Proteinuria Anorexia
Reduced renal function Malaise and depression
Shaking
Musculoskeletal
Vague pain
Septic arthritis Inflammatory leukogram
Joint swelling and pain Mild anemia
Lameness Positive antinuclear antibody test
Immune-mediated polyarthritis Positive blood cultures
Shifting-leg lameness
Joint swelling and pain
in an unexpected clinical setting or i n an animal w i t h a It may be difficult to obtain a definitive antemortem diag
murmur of recent onset, especially i f other suggestive nosis. Presumptive diagnosis of infective endocarditis is
signs are present. But a "new" m u r m u r can indicate nonin made on the basis of positive findings i n two or more b l o o d
fective acquired disease (e.g., degenerative valve disease, car cultures, i n addition to either echocardiographic evidence of
diomyopathy), previously undiagnosed congenital disease, vegetations or valve destruction or the documented recent
or physiologic alterations (e.g., fever, anemia). Conversely, appearance of a regurgitant murmur. Endocarditis is likely
endocarditis may develop i n an animal k n o w n to have a even when b l o o d culture results are negative or intermit
murmur resulting from another cardiac disease. A l t h o u g h tently positive i f there is echocardiographic evidence of veg
a change in m u r m u r quality or intensity over a short etations or valve destruction along w i t h a combination of
time frame may indicate active valve damage, physiologic other criteria (Box 6-4). A new diastolic murmur, hyperki
causes of m u r m u r variation are c o m m o n . The onset of a netic pulses, and fever are strongly suggestive of aortic valve
diastolic murmur at the left heartbase is suspicious for aortic endocarditis.
valve endocarditis, especially i f fever or other signs are Several samples of at least 10 m l of blood should be asep
present. tically collected over a 24-hour period for bacterial blood
BOX 6-4
* Adapted from Duke criteria for endocarditis. In Durack DT et al: N e w criteria for diagnosis of infective endocarditis: utilization of specific
echocardiographic findings, Am J Med 96:200, 1994.
culture, w i t h more than 1 hour elapsing between collections. the proficiency o f the echocardiographer. Because false-
Ideally, different venipuncture sites should be used for each negative and false-positive findings o f "lesions" may occur,
sample. Larger sample volumes (e.g., 20 to 30 ml) increase cautious interpretation o f images is important. M i l d valve
culture sensitivity. Both aerobic and anaerobic cultures have thickening and/or enhanced echogenicity may occur i n
been recommended, although the value of routine anaerobic patients w i t h early valve damage. Vegetative lesions appear
culture is questionable. Prolonged incubation (3 weeks) as irregular dense masses. As valve destruction progresses,
is recommended because some bacteria are slow-growing. ruptured chordae, flail leaflet tips, or other abnormal valve
Although blood culture results are positive i n many dogs motion can be seen. Differentiation o f mitral vegetations
with this disease, negative results do not necessarily rule out from degenerative thickening may be impossible, however,
infective endocarditis; i n a recent study, less than 50% of the especially i n the early stages. Nevertheless, vegetative endo
blood cultures i n dogs w i t h confirmed infective endocarditis carditis classically causes rough, ragged-looking valve thick
were positive. A s discussed above, Bartonella spp. is an ening; degenerative disease is associated with smooth
emerging pathogen that causes blood culture-negative endo valvular thickening. Poor or marginal-quality images or
carditis i n dogs; i n the same study, 4 5 % o f the dogs w i t h the use o f lower-frequency transducers can prevent iden
negative blood cultures were positive for Bartonella spp. o n tification o f some vegetations because of suboptimal
polymerase chain reaction ( P C R ) . Results may be negative resolution. Secondary effects o f valve dysfunction include
in the setting o f chronic endocarditis, recent antibiotic chamber enlargement from volume overload and flail or
therapy, intermittent bacteremia, and infection w i t h fastidi otherwise abnormal valve leaflet motion. Myocardial dys
ous or slow-growing organisms, as well as noninfective function and arrhythmias may also be evident. Aortic insuf
endocarditis. Serologic and P C R testing are also commer ficiency can cause fluttering o f the anterior mitral valve
cially available for Bartonella spp. leaflet during diastole as the regurgitant jet makes contact
Echocardiography is especially supportive i f oscillating with this leaflet. Doppler studies illustrate flow disturbances
vegetative lesions and abnormal valve m o t i o n can be identi (Fig. 6-5).
fied (Fig. 6-4). The visualization o f lesions depends o n The E C G may be normal or document premature beats,
their size and location, o n the image resolution, and tachycardias, conduction disturbances, or evidence of myo-
Clinicopathologic findings usually reflect an inflamma
tory process. Neutrophilia with a left shift is typical of acute
endocarditis, whereas mature neutrophilia with or without
monocytosis usually develops with chronic disease. Nonre
generative anemia has been associated with about half of
canine cases. Biochemical abnormalities are variable. Azote
mia, hyperglobulinemia, hematuria, pyuria, and proteinuria
are c o m m o n . The A N A results may be positive in dogs with
subacute or chronic bacterial endocarditis; i n a recent study,
75% of dogs with Bartonella vinsonii infection had positive
A N A test results.
Myocardial Diseases
of the Dog
low-output signs i n Doberman Pinschers. classic finding, although it may be obscured by an irregular
Dilation o f all cardiac chambers is typical i n dogs with heart rhythm. Systolic m u r m u r s o f mitral or tricuspid
D C M , although left atrial (LA) and LV enlargement usually regurgitation that are soft to moderate i n intensity are
predominate. The ventricular wall thickness may appear common.
decreased compared with the lumen size. Flattened, atrophic
papillary muscles and endocardial thickening are described. Diagnosis
Concurrent degenerative changes o f the A V valves are gener
ally only m i l d to moderate, i f present at all. Histopathologic RADIOGRAPHY
findings include scattered areas o f myocardial necrosis, The stage o f disease, chest conformation, and hydration
degeneration, and fibrosis, especially in the left ventricle. status influence the radiographic findings. Generalized
Narrowed (attenuated) myocardial cells with a wavy appear cardiomegaly is usually evident, although left heart enlarge
ance may be a c o m m o n finding. Inflammatory cell infil ment may predominate (Fig. 7-1). In D o b e r m a n Pinschers
trates, myocardial hypertrophy, and fatty infiltration (mainly the heart may appear minimally enlarged, except for the left
in Boxers and some Doberman Pinschers) are inconsistent atrium. In other dogs cardiomegaly may be severe and can
features. m i m i c the globoid cardiac silhouette typical o f large pericar
dial effusions. Distended pulmonary veins and pulmonary
Clinical Findings interstitial or alveolar opacities, especially i n the hilar and
The prevalence of D C M increases with age, although most dorsocaudal regions, accompany left heart failure with p u l
dogs presented with C H F are 4 to 10 years old. Males appear monary edema. The distribution o f pulmonary edema infil
to be affected more often than females. However, in Boxers trates may be asymmetric or widespread. Pleural effusion,
caudal vena cava distention, hepatomegaly, and ascites rhythm, although A F is often documented instead, especially
usually accompany right-sided C H F . in Great Danes and other giant breeds (see Fig. 2-11). Other
atrial tachyarrhythmias, paroxysmal or sustained ventricular
ELECTROCARDIOGRAPHY tachycardia, fusion complexes, and multiform V P C s are fre
The electrocardiogram ( E C G ) findings i n dogs with D C M quent findings. The Q R S complexes may be tall (consistent
are also variable. Sinus rhythm is usually the underlying with L V dilation), n o r m a l size, or small. Myocardial disease
FIG 7-1
R a d i o g r a p h i c e x a m p l e s of d i l a t e d c a r d i o m y o p a t h y in d o g s . Lateral (A) a n d dorsoventral
(B) v i e w s s h o w i n g g e n e r a l i z e d c a r d i o m e g a l y in a male L a b r a d o r Retriever. N o t e the
c r a n i a l p u l m o n a r y vein is slightly l a r g e r than the a c c o m p a n y i n g artery in (A). Lateral
(C) a n d d o r s o v e n t r a l (D) v i e w s of D o b e r m a n Pinscher d e p i c t i n g the prominent left atrial
a n d relatively m o d e r a t e ventricular e n l a r g e m e n t s c o m m o n l y found in affected d o g s of
this b r e e d . There is mild p e r i b r o n c h i a l p u l m o n a r y e d e m a a s w e l l .
often causes a widened Q R S complex with a slowed R-wave
descent and slurred ST segment. A bundle-branch block
pattern or other intraventricular conduction disturbance may
be observed. The P waves in dogs with sinus rhythm are fre
quently widened and notched, suggesting L A enlargement.
Twenty-four-hour Holter monitoring is useful for docu
menting frequent ventricular ectopy. This has been used as
a screening tool for cardiomyopathy in Doberman Pinschers
and Boxers (see p. 135). The presence of >50 V P C s / d a y or
any couplets or triplets is thought to predict future overt
D C M in Doberman Pinschers. Nevertheless, some dogs with FIG 7 - 2
M - m o d e e c h o c a r d i o g r a m from a d o g with d i l a t e d c a r d i o m y
<50 VPCs/day on initial evaluation may develop D C M after
o p a t h y at the c h o r d a l (left side of figure) a n d mitral v a l v e
several years. The frequency and complexity of ventricular
(right side of figure) levels. N o t e attenuated w a l l motion
tachyarrhythmias appear to be negatively correlated with (fractional s h o r t e n i n g = 18%) a n d the w i d e mitral v a l v e E
fractional shortening; sustained ventricular tachycardia has p o i n t - s e p t a l s e p a r a t i o n (28 mm).
been associated with increased risk of sudden death. Vari
ability in the number of V P C s between repeated Holter
recordings in the same dog can be high. If available, the
technique of signal averaged electrocardiography can reveal
the presence of ventricular late potentials, which may suggest
an increased risk for sudden death in Doberman Pinschers
with occult D C M .
ECHOCARDIOGRAPHY
Echocardiography is used to assess cardiac chamber dimen
sions and myocardial function and differentiate pericardial
effusion or chronic valvular insufficiency from D C M . Dilated
cardiac chambers and poor systolic ventricular wall and
septal motion are characteristic findings in dogs with D C M .
In severe cases only m i n i m a l wall motion is evident. A l l
chambers are usually affected, but right atrial (RA) and right
ventricular (RV) dimensions may appear normal, especially
in Doberman Pinschers and Boxers. L V systolic (as well as
diastolic) dimension is increased compared with normal
ranges for the breed, and the ventricle appears more
spherical. Fractional shortening and ejection fraction are
FIG 7-3
decreased (Fig. 7-2). Other c o m m o n features are a wide
M i l d mitral regurgitation is i n d i c a t e d b y a relatively small
mitral valve E point-septal separation and reduced aortic a r e a of d i s t u r b e d f l o w in this systolic f r a m e from a S t a n d a r d
root motion. LV free-wall and septal thicknesses are normal P o o d l e with d i l a t e d c a r d i o m y o p a t h y . N o t e the LA a n d LV
to decreased. The calculated end-systolic volume index (see d i l a t i o n . Right p a r a s t e r n a l l o n g a x i s v i e w , o p t i m i z e d for the
2
p. 41) is generally over 80 m l / m i n dogs with overt D C M left ventricular i n f l o w tract. LA, Left a t r i u m ; LV, left ventricle.
2
(<30 m l / m is considered normal). Evidence for abnormal
diastolic as well as systolic function can be found in dogs
with advanced disease. M i l d to moderate A V valve regur CLINICOPATHOLOGIC FINDINGS
gitation is usually seen with Doppler echocardiography Clinicopathologic findings are noncontributory in most
(Fig. 7-3). cases. In others, prerenal azotemia resulting from poor renal
Echocardiography is also used to screen for occult disease. perfusion or mildly increased liver enzyme activities result
There may be no clear abnormalities early in the disease. ing from passive hepatic congestion occur. Severe C H F may
Alternatively, apparently healthy Doberman Pinschers may be associated with hypoproteinemia, hyponatremia, and
have slightly reduced fractional shortening compared with hyperkalemia. Hypothyroidism with associated hypercholes
what is considered normal for other breeds. The following terolemia occurs i n some dogs with D C M . Others have a
echocardiographic criteria appear to indicate high risk for reduced serum thyroid hormone concentration without
overt D C M within 2 to 3 years in asymptomatic Doberman hypothyroidism (sick euthyroid); normal T S H and free T 4
Pinschers: L V I D d >46 m m (in dogs <42 kg) or >50 m m (in concentrations are c o m m o n . Increased circulating neuro
dogs >42 kg), LVIDs >38 m m , or V P C s during initial exam hormones (e.g., norepiniphrine, aldosterone, endothelin,
ination, FS < 25%, and/or mitral valve E point-septal separa natriuretic peptides) occur mainly in D C M dogs with overt
tion >8 m m (LVID, left ventricular internal diameter; d, C H F . Natriuretic peptide elevations i n dogs with occult
diastole; 5, systole). D C M are also reported i n some studies. Significant positive
correlations have been identified between L V dimensions (in
BOX 7-1
both diastole and systole) and atrial natriuretic peptide, as
well as endothelin (O'Sullivan et al., 2007). N e u r o h o r m o n a l Treatment Outline for Dogs w i t h Dilated
changes i n occult D C M were not associated w i t h time to Cardiomyopathy
C H F onset or sudden death i n this study; however, i n dogs
with overt C H F , increases i n N E and endothelin over a Mild to Moderate Signs of Congestive Heart Failure*
diltiazem may be added (see Table 4-2). Because these agents tional changes i n cardiac output; a venous P O >30 m m H g
2
can have negative inotropic effects, a low initial dose and is desirable.
A number o f other therapies may be useful in certain ARRHYTHMOGENIC RIGHT
dogs with D C M , although additional studies are needed VENTRICULAR CARDIOMYOPATHY
to define o p t i m a l recommendations. These i n c l u d e
omega-3 fatty acids, L-carnitine (in dogs w i t h low myocar CARDIOMYOPATHY IN BOXERS
dial carnitine concentrations), taurine (in dogs with low Myocardial disease i n Boxers has similar features to those of
plasma concentrations), l o n g - t e r m - b l o c k e r therapy people with A R V C . Histologic changes in the myocardium are
(e.g., carvedilol or metoprolol), and possibly others (see more extensive than those i n dogs of other breeds with car
Chapter 3, p. 69). Several palliative surgical therapies diomyopathy and include atrophy o f myofibers, fibrosis, and
for D C M have been described i n dogs but are not widely fatty infiltration. Focal areas o f myocytolysis, necrosis, hem
used. orrhage, and mononuclear cell infiltration are also common.
Although clinical features vary, the prevalence of ven
Monitoring tricular arrhythmias and syncope is high in Boxers with
M a n y dogs can be maintained fairly well for a variable time myocardial disease. A genetic basis is believed to exist given
w i t h chronic oral therapy. Owner education regarding the that the disease is more prevalent i n some bloodlines. Three
purpose, dosage, and adverse effects o f each drug used is also disease categories have been described. The first consists of
important. M o n i t o r i n g the dog's resting respiratory (and dogs with ventricular tachyarrhythmia but without clinical
heart) rate at home helps assess how well the patient's C H F signs. The second consists o f dogs that have syncope or
is controlled. Periodic reevaluation is important, but the weakness associated with paroxysmal or sustained ventricu
time frame depends on the animal's status. Visits once or lar tachycardia, despite n o r m a l heart size and L V function.
twice a week may be needed initially. Dogs with stable heart The third group comprises Boxers with poor myocardial
failure can be rechecked every 2 or 3 months. Serum electro function and C H F , as well as ventricular tachyarrhythmias.
lyte and creatinine (or B U N ) concentrations, an E C G , p u l Dogs with m i l d echocardiographic changes and those with
monary status, b l o o d pressure, serum digoxin concentration, syncope or weakness may later develop poor L V function
body weight, and other appropriate factors can be evaluated, and C H F . There appears to be geographical variation i n the
and therapy adjusted as needed. prevalence of these clinical presentations; for example,
tachyarrhythmias w i t h n o r m a l L V function are typical in
Prognosis affected U.S. Boxers, whereas L V dysfunction appears to be
The prognosis for dogs w i t h D C M is generally guarded to more c o m m o n i n parts o f Europe.
poor. Historically, most dogs do not survive longer than 3
months after the clinical manifestations o f C H F , although Clinical Findings
approximately 25% to 40% o f affected dogs live longer than Signs may appear at any age, but the mean age is reportedly
6 months i f initial response to therapy is good. The probabil 8.5 years (range <1-15 years). The most consistent clinical
ity o f survival for 2 years is estimated at 7.5% to 28%. finding is a cardiac arrhythmia. W h e n C H F occurs, left-sided
However, the advent o f newer therapies may change this signs are more c o m m o n than ascites or other signs of right-
bleak picture. Pleural effusion and possibly ascites and p u l sided heart failure. M a n y Boxers also develop a mitral insuf
monary edema have been identified as independent indica ficiency murmur.
tors o f poorer prognosis. The radiographic findings are variable; many Boxers have
Sudden death may occur even in the occult stage, before no visible abnormalities. Those with congestive signs gener
heart failure is apparent. Sudden death occurs in about 20% ally show evidence of cardiomegaly and pulmonary edema.
to 40% o f affected D o b e r m a n Pinschers. Although ventricu Echocardiographic findings also vary. M a n y Boxers have
lar tachyarrhythmias are thought to precipitate cardiac arrest normal cardiac size and function; others show chamber dila
most commonly, bradyarrhythmias may be involved i n some tion with reduced fractional shortening.
dogs. The characteristic E C G finding is ventricular ectopy.
Doberman Pinschers with occult D C M often experience V P C s occur singly, i n pairs, i n short runs, or as sustained
deterioration within 6 to 12 months. Dobermans i n overt ventricular tachycardia. Most ectopic ventricular complexes
C H F when initially presented generally do not live long, with appear upright i n leads II and aVF. Some Boxers have m u l
a reported median survival o f less than 7 weeks. The prog tiform V P C s . There usually is an underlying sinus rhythm.
nosis is worse if A F is present in dogs with C H F . Most symp A F is less c o m m o n . Supraventricular tachycardia, conduc
tomatic dogs are between 5 and 10 years o l d at the time tion abnormalities, and evidence o f chamber enlargement
of death. also are sometimes seen on E C G .
In each case, however, it is reasonable to assess the ani Twenty-four-hour Holter monitoring is often used as a
mal's response to initial treatment before pronouncing an screening tool for Boxer A R V C . It also is recommended to
unequivocally dismal prognosis. Early diagnosis may help evaluate the efficacy o f antiarrhythmic drug therapy. Fre
prolong life; further cardiac evaluation is indicated for dogs quent V P C s and/or complex ventricular arrhythmias are
with a history o f reduced exercise tolerance, weakness, or characteristic findings i n affected dogs. However, an absolute
syncope or in those i n which an arrhythmia, murmur, or number of V P C s / 2 4 - h o u r period that might separate normal
gallop sound is detected. from abnormal dogs is not (and may never be) clear. A n
arbitrary cut-off of >50 V P C s / 2 4 - h o u r period is often used tions (see p. 137), inflammation, trauma (see p. 139),
to designate an abnormal frequency. However, there can be ischemia, neoplastic infiltrations, and metabolic abnormali
enormous variability i n the number of V P C s between ties can impair normal contractile function. Hyperthermia,
repeated Holter recordings i n the same dog. Very frequent irradiation, electric shock, and other insults can also damage
V P C s or episodes of ventricular tachycardia are thought to the myocardium. Some substances are known cardiac toxins.
signal an increased risk for syncope and sudden death.
MYOCARDIAL TOXINS
Treatment Doxorubicin
Boxers with signs from tachyarrhythmias, but w i t h normal The antineoplastic drug doxorubicin induces both acute and
heart size and LV function, are treated with antiarrhythmic chronic cardiotoxicity. Histamine, secondary catecholamine
drugs. Some asymptomatic dogs found to have ventricular release, and free-radical production appear to be involved
tachycardia on Holter monitoring are also given an antiar in the pathogenesis of myocardial damage, which leads to
rhythmic drug. The best regimen(s) and when to institute decreased cardiac output, arrhythmias, and degeneration of
therapy are still not clear. Antiarrhythmic drug therapy that myocytes. Doxorubicin-induced cardiotoxicity is directly
is apparently successful in reducing V P C number based on related to the peak serum concentration of the drug; admin
Holter recording may still not prevent sudden death. Sotalol, istering the drug diluted (0.5 mg/ml) over 20 to 40 minutes
mexiletine with atenolol, amiodarone, or procainamide with minimizes the risk of developing cardiotoxicity. Progressive
atenolol have been advocated (see Chapter 4) because they myocardial damage and fibrosis have developed i n associa
2
might reduce the risk for sudden death from ventricular tion with cumulative doses of >160 m g / m and sometimes
2
fibrillation, but further study is needed. Some dogs require as low as 100 m g / m . In dogs that have normal pretreatment
treatment for persistent supraventricular tachyarrhythmias. cardiac function, clinical cardiotoxicity is u n c o m m o n until
2
Therapy for C H F is similar to that described for dogs with the cumulative dose exceeds 240 m g / m . It is difficult to
idiopathic D C M . Myocardial carnitine deficiency has been predict whether and when clinical cardiotoxicity w i l l occur.
documented in some Boxers with D C M and heart failure. Increases i n circulating cardiac troponin concentrations can
Some of these dogs have responded to oral L-carnitine sup be seen, but more work is needed to clarify the utility of this
plementation. Digoxin is used sparingly, i f at all, when ven i n monitoring dogs for doxorubicin-induced myocardial
tricular tachyarrhythmias are frequent. injury.
Cardiac conduction defects (infranodal A V block and
Prognosis bundle branch block) as well as ventricular and supraven
The prognosis for affected Boxers is guarded. Survival is tricular tachyarrhythmias can develop i n affected dogs. E C G
often <6 months i n those with C H F . Asymptomatic dogs changes do not necessarily precede clinical heart failure.
may have a more optimistic future, but the likelihood of Dogs with underlying cardiac abnormalities and those of
developing serious arrhythmias is high. Sudden death is breeds with a higher prevalence of idiopathic D C M are
common, presumably from V P C s leading to ventricular thought to be at greater risk for doxorubicin-induced car
fibrillation. The ventricular tachyarrhythmias may be refrac diotoxicity. Recently, carvedilol has been shown to minimize
tory to drug therapy. Furthermore, even i f most arrhythmias or prevent the development of doxorubicin-induced cardio
are suppressed, an increased survival is not assured. toxicity i n humans; we have had similar anecdotal experi
ences i n dogs. Clinical features of this cardiomyopathy are
ARRHYTHMOGENIC RIGHT similar to those of idiopathic D C M .
VENTRICULAR CARDIOMYOPATHY
IN NONBOXER DOGS Other Toxins
A form of cardiomyopathy that mainly affects the right ven Ethyl alcohol, especially i f given intravenously for the treat
tricle has been observed rarely i n dogs. It appears similar to ment of ethylene glycol intoxication, can cause severe myo
A R V C described i n people and cats (see p. 154). Pathologic cardial depression and death; slow administration of a
changes are characterized by widespread fibrous and fatty diluted (20% or less) solution is advised. Other cardiac
tissue replacement i n the R V myocardium. In certain geo toxins include plant toxins (e.g., Taxus, foxglove, black locust,
graphical areas, trypanosomiasis is a possible differential buttercups, lily-of-the-valley, gossypol), cocaine, anesthetic
diagnosis. Clinical manifestations are largely related to right- drugs, cobalt, catecholamines, and ionophores such as
sided C H F and severe ventricular tachyarrhythmias. M a r k e d monensin.
right heart dilation is typical. Sudden death is a c o m m o n
outcome i n people with A R V C . METABOLIC AND
NUTRITIONAL DEFICIENCY
L-carnitine
SECONDARY MYOCARDIAL DISEASE L-carnitine is an essential component of the mitochondrial
membrane transport system for fatty acids, which are the
Poor myocardial function may result from a variety o f iden hearts most important energy source. It also transports
tifiable insults and nutritional deficiencies. Myocardial infec potentially toxic metabolites out of the mitochondria i n the
form of carnitine esters. L-carnitine-linked defects i n myo ming from brain or spinal cord injury results in myocardial
cardial metabolism have been found i n some dogs with hemorrhage, necrosis, and arrhythmias (brain-heart syn
D C M . Rather than simple L-carnitine deficiency, one or drome). Muscular dystrophy of the fasciohumoral type
more underlying genetic or acquired metabolic defects are (reported i n English Springer Spaniels) may result in atrial
suspected. There may be an association between D C M and standstill and heart failure. Canine X-linked (Duchenne's)
carnitine deficiency in some families of Boxers, Doberman muscular dystrophy i n Golden Retrievers and other breeds
Pinschers, Great Danes, Irish Wolfhounds, Newfoundlands, also has been associated with myocardial fibrosis and miner
and Cocker Spaniels. L-carnitine is mainly present i n foods alization. Rarely, nonneoplastic (e.g., glycogen storage disease)
of animal origin. D C M has developed i n some dogs fed strict and neoplastic (metastatic and primary) infiltrates interfere
vegetarian diets. with normal myocardial function. Immunologic mechanisms
Plasma carnitine concentration is not a sensitive indicator may also play an important role in the pathogenesis of myo
of myocardial carnitine deficiency. M o s t dogs with myocar cardial dysfunction i n some dogs with myocarditis.
dial carnitine deficiency, diagnosed via endomyocardial
biopsy, have had normal or high plasma carnitine concentra ISCHEMIC MYOCARDIAL DISEASE
tions. Furthermore, the response to oral carnitine supple Acute myocardial infarction resulting from coronary embo
mentation is inconsistent. Subjective improvement may lization is u n c o m m o n . A n underlying disease associated with
occur, but few dogs have echocardiographic evidence of increased risk for thromboembolism, such as bacterial endo
improved function. Dogs that do respond show clinical carditis, neoplasia, severe renal disease, immune-mediated
improvement within the first m o n t h of supplementation; hemolytic anemia, acute pancreatitis, disseminated intravas
there may be some degree of improvement i n echo param cular coagulopathy, and/or corticosteroid use, underlies most
eters after 2 to 3 months. L-carnitine supplementation does cases. Sporadic reports o f myocardial infarction are associ
not suppress preexisting arrhythmias or prevent sudden ated with congenital ventricular outflow obstruction, patent
death. See p. 69 for supplementation guidelines. ductus arteriosus, hypertrophic cardiomyopathy, and mitral
insufficiency. Atherosclerosis of the major coronary arteries,
Taurine which can accompany severe hypothyroidism in dogs, rarely
Although most dogs with D C M are not taurine deficient, low leads to acute myocardial infarction. Clinical signs of acute
plasma taurine concentration is found i n some. L o w taurine, major coronary artery obstruction are likely to include
and sometimes carnitine, concentrations occur in Cocker arrhythmias, pulmonary edema, marked ST segment change
Spaniels with D C M . O r a l supplementation of these amino on E C G , and evidence o f regional or global myocardial con
acids can improve L V size and function as well as reduce the tractile dysfunction o n echocardiogram. H i g h circulating
need for heart failure medications i n this breed. L o w plasma cardiac troponin concentrations and possibly creatine kinase
taurine concentrations have also been found i n some Golden activity occur after myocardial injury and necrosis.
Retrievers, Labrador Retrievers, Saint Bernards, Dalmatians, Disease of small coronary vessels is recognized as well.
and other dogs with D C M . A normally adequate taurine Non-atherosclerotic narrowing of small coronary arteries
content is found in the diets of some such cases, although could be more clinically important than previously assumed.
others have been fed low-protein or vegetarian diets. The Hyalinization of small coronary vessels and intramural myo
role o f taurine supplementation is unclear. Although taurine- cardial infarctions have been described i n dogs with chronic
deficient dogs may show some echocardiographic improve degenerative A V valve disease, but they can occur in older
ment after supplementation, there is questionable effect o n dogs without valve disease as well. Fibromuscular arterio
survival time. Nevertheless, measurement of plasma taurine sclerosis of small coronary vessels is also described. These
or a trial of supplemental taurine for at least 4 months may changes in the walls of the small coronary arteries cause
be useful, especially in an atypical breed affected with D C M . luminal narrowing and can impair resting coronary blood
(See p. 69 for supplementation guidelines.) Plasma taurine flow as well as vasodilatory responses. Small myocardial
concentrations <25 (to 40) n m o l / m l and b l o o d taurine con infarctions and secondary fibrosis lead to reduced myocar
centrations <200 (or 150) n m o l / m l are generally considered dial function. Various arrhythmias can occur. Eventual C H F
deficient. Specific collection and submission guidelines is a cause of death in many cases with intramural coronary
should be obtained from the laboratory used. arteriosclerosis. Sudden death is a less c o m m o n sequela.
Larger breeds of dog may be predisposed, although Cocker
Other Factors Spaniels and Cavalier K i n g Charles Spaniels appear to be
Myocardial injury induced by free radicals may play a role i n commonly affected smaller breeds.
a number of diseases. Evidence for increased oxidative stress
has been found i n dogs with C H F and myocardial failure, but TACHYCARDIA-INDUCED
the clinical ramifications of this are unclear. Diseases such as CARDIOMYOPATHY
hypothyroidism, pheochromocytoma, and diabetes mellitus The term tachycardia induced cardiomyopathy (TICM) refers
have been associated with reduced myocardial function, but to the progressive myocardial dysfunction, activation of neu
clinical heart failure is unusual i n dogs secondary to these rohormonal compensatory mechanisms, and C H F that result
conditions alone. Excessive sympathetic stimulation stem from rapid, incessant tachycardias. The myocardial failure
may be reversible if the heart rate can be normalized in time. dynamic outflow obstruction causes. Partial systolic aortic
T I C M has been described i n several dogs with A V nodal valve closure may be seen as well. Other causes of LV hyper
reciprocating tachycardias associated with accessory conduc trophy include congenital subaortic stenosis, hypertensive
tion pathways that bypass the A V node (e.g., Wolff- renal disease, thyrotoxicosis, and pheochromocytoma. T h o
Parkinson-White; see p. 27). Rapid artificial pacing (e.g., racic radiographs may indicate L A and L V enlargement, with
>200 beats/min) is a c o m m o n model for inducing experi or without pulmonary congestion or edema. Some cases
mental myocardial failure that simulates D C M . appear radiographically normal. E C G findings may include
ventricular tachyarrhythmias and conduction abnormalities,
such as complete heart block, first-degree A V block, and
HYPERTROPHIC CARDIOMYOPATHY fascicular blocks. Criteria for L V enlargement are variably
present.
In contrast to cats, hypertrophic cardiomyopathy ( H C M )
is quite uncommon in dogs. A genetic basis is suspected, Treatment
although the cause is unknown. It is possible that several The general goals of H C M treatment are to enhance myo
disease processes lead to similar ventricular changes. The cardial relaxation and ventricular filling, control pulmonary
pathophysiology is similar to that of H C M i n cats (see Chapter edema, and suppress arrhythmias. A -blocker (see p. 89) or
8). Abnormal, excessive myocardial hypertrophy increases Ca++-channel blocker (see p. 91) may lower heart rate,
ventricular stiffness and leads to diastolic dysfunction. The I V prolong ventricular filling time, reduce ventricular contrac
hypertrophy is usually symmetric, but regional variation i n tility, and m i n i m i z e myocardial oxygen requirement, -
wall or septal thickness can occur. Compromised coronary blockers can also reduce dynamic L V outflow obstruction
perfusion is likely with severe ventricular hypertrophy. This and may suppress arrhythmias induced by heightened sym
leads to myocardial ischemia, which exacerbates arrhythmias, pathetic activity, whereas Ca++-blockers may facilitate myo
delays ventricular relaxation, and further impairs filling. H i g h cardial relaxation. Diltiazem has a lesser inotropic effect and
LV filling pressure predisposes to pulmonary venous conges w o u l d be less useful against dynamic outflow obstruction,
tion and edema. Besides diastolic dysfunction, systolic dynamic especially i n view of its vasodilating effect. Because - and
LV outflow obstruction occurs i n some dogs. Malposition of Ca++-channel blockers can worsen A V conduction abnor
the mitral apparatus may contribute to systolic anterior mitral malities, they may be relatively contraindicated i n certain
valve motion and LV outflow obstruction as well as to mitral animals. A diuretic and A C E I are indicated i f congestive signs
regurgitation. In some dogs asymmetric septal hypertrophy are present. Digoxin should not be used because it may
also contributes to outflow obstruction. L V outflow obstruc increase myocardial oxygen requirements, worsen outflow
tion increases ventricular wall stress and myocardial oxygen obstruction, and predispose to the development of ventricu
requirement while also impairing coronary blood flow. Heart lar arrhythmias. Exercise restriction is advised in dogs with
rate elevations magnify these abnormalities. HCM.
Clinical Features
H C M is most commonly diagnosed i n young to middle-age MYOCARDITIS
large-breed dogs, although there is a wide age distribution.
Various breeds are affected. There may be a higher preva A wide variety of agents can affect the myocardium, although
lence of H C M i n males. Clinical signs of C H F , episodic weak disease manifestations i n other organ systems may over
ness, and/or syncope occur in some dogs. Sudden death is shadow the cardiac involvement. The heart can be injured
the only sign in some cases. Ventricular arrhythmias second by direct invasion of the infective agent, by toxins it elabo
ary to myocardial ischemia are presumed to cause the low- rates, or by the host's i m m u n e response. Non-infective causes
output signs and sudden death. A systolic murmur, related of myocarditis include cardiotoxic drugs and drug hypersen
to either LV outflow obstruction or mitral insufficiency, may sitivity reactions. Myocarditis can cause persistent cardiac
be heard on auscultation. The systolic ejection m u r m u r of arrhythmias and progressively impair myocardial function.
ventricular outflow obstruction becomes louder when ven
tricular contractility is increased (e.g., with exercise or excite INFECTIVE MYOCARDITIS
ment) or when afterload is reduced (e.g., from vasodilator
use). A n S gallop sound is heard i n some affected dogs.
Etiology and Pathophysiology
4
Viral Myocarditis
Diagnosis Lymphocytic myocarditis has been associated with acute
Echocardiography is the best diagnostic tool for H C M . A n viral infections in experimental animals and in people.
abnormally thick left ventricle, with or without narrowing Cardiotropic viruses can play an important role in the patho
of the L V outflow tract area or asymmetrical septal hyper genesis of myocarditis and subsequent cardiomyopathy i n
trophy, and L A enlargement are characteristic findings. several species, but this is not recognized c o m m o n l y in dogs.
Mitral regurgitation may be evident on Doppler studies. Sys The host animal's i m m u n e responses to viral and nonviral
tolic anterior motion of the mitral valve may result from antigens contribute to myocardial inflammation and damage.
A syndrome of parvoviral myocarditis was well-known diagnosis. Treatment w i t h an appropriate antibiotic should
in the late 1970s and early 1980s. It is characterized by a be instituted pending diagnostic test results. Cardiac drugs
peracute necrotizing myocarditis and sudden death (with or are used as needed. Resolution of A V conduction block
without signs of acute respiratory distress) in apparently may not occur i n dogs despite appropriate antimicrobial
healthy puppies about 4 to 8 weeks old. Cardiac dilation therapy.
with pale streaks i n the myocardium, gross evidence of con
gestive failure, large basophilic or amorphophilic intranu Protozoal Myocarditis
clear inclusion bodies, myocyte degeneration, and focal Trypanosoma cruzi, Toxoplasma gondii, Neosporum caninum,
mononuclear cell infiltrates are typical necropsy findings. Babesia canis, and Hepatozoon canis are known to affect
This syndrome is u n c o m m o n now, probably as a result of the myocardium. Trypanosomiasis (Chagas' disease) has
maternal antibody production i n response to virus exposure occurred mainly i n young dogs i n Texas, Louisiana, Okla
and vaccination. Parvovirus may cause a form o f D C M i n homa, Virginia, and other southern states i n the United
young dogs that survive neonatal infection; viral genetic States. The possibility for human infection should be recog
material has been identified i n some canine ventricular myo nized; this is an important cause of human myocarditis and
cardial samples i n the absence of classic intranuclear inclu subsequent cardiomyopathy in Central and South America.
sion bodies. The organism is transmitted by bloodsucking insects of the
Canine distemper virus may cause myocarditis i n young family Reduviidae and is enzootic i n wild animals of the
puppies, but multisystemic signs usually predominate. H i s region. Amastigotes of T. cruzi cause myocarditis with a
tologic changes i n the myocardium are m i l d compared with mononuclear cell infiltrate and disruption and necrosis of
those i n the classic form of parvovirus myocarditis. Experi myocardial fibers. Acute, latent, and chronic phases of
mental herpesvirus infection of pups during gestation also Chagas' myocarditis have been described. Lethargy, depres
causes necrotizing myocarditis w i t h intranuclear inclusion sion, and other systemic signs, as well as various tachyar
bodies leading to fetal or perinatal death. rhythmias, A V conduction defects, and sudden death, are
seen i n dogs w i t h acute trypanosomiasis. Clinical signs are
Bacterial Myocarditis sometimes subtle. The disease is diagnosed in the acute stage
Bacteremia and bacterial endocarditis or pericarditis can by finding trypomastigotes in thick peripheral blood smears;
cause focal or multifocal suppurative myocardial inflamma the organism can be isolated i n cell culture or by inoculation
tion or abscess formation. Localized infections elsewhere i n into mice. Animals that survive the acute phase enter a latent
the body may be the source o f the organisms. Clinical signs phase of variable duration. D u r i n g this phase the parasit
include malaise; weight loss; and, inconsistently, fever. emia is resolved, and antibodies develop against the organ
Arrhythmias and cardiac conduction abnormalities are ism as well as cardiac antigens. Chronic Chagas' disease
c o m m o n , but murmurs are rare unless concurrent valvular is characterized by progressive right-sided or generalized
endocarditis or another underlying cardiac defect is present. cardiomegaly and various arrhythmias. Ventricular tach
Serial bacterial (or fungal) blood cultures, serology, or P C R yarrhythmias are most common, but supraventricular
may allow identification of the organism. Bartonella vinsonii tachyarrhythmias may occur. Right bundle branch block and
subspecies have been associated w i t h cardiac arrhythmias, A V conduction disturbances are also reported. Ventricular
myocarditis, endocarditis, and sudden death. dilation and reduced myocardial function are usually evident
echocardiographically. Clinical signs of biventricular failure
Lyme Carditis are c o m m o n . Antemortem diagnosis i n chronic cases may be
Lyme disease is more prevalent i n certain geographic areas, possible through serologic testing. Therapy in the acute stage
especially the northeastern, western coastal, and north is aimed at eliminating the organism and minimizing myo
central United States, as well as i n Japan and Europe, among cardial inflammation; several treatments have been tried
other areas. The spirochete Borrelia burgdorferi (or related with variable success. The therapy for chronic Chagas' disease
species) is transmitted to dogs by ticks (especially Ixodes is aimed at supporting myocardial function, controlling con
genus) and possibly other biting insects. Third-degree (com gestive signs, and suppressing arrhythmias.
plete) and high-grade second-degree A V block have been Toxoplasmosis and neosporiosis can cause clinical myo
identified i n dogs w i t h Lyme disease. Syncope, C H F , reduced carditis i n conjunction with generalized systemic infection,
myocardial contractility, and ventricular arrhythmias also especially i n the immunocompromised animal. The organ
are reported i n affected dogs. Pathologic findings of Lyme ism becomes encysted i n the heart and various other body
myocarditis include infiltrates of plasma cells, macrophages, tissues after the initial infection. W i t h rupture of these cysts,
neutrophils, and lymphocytes, with areas of myocardial expelled bradyzoites induce hypersensitivity reactions and
necrosis. These are similar to findings i n human Lyme car tissue necrosis. Other systemic signs often overshadow signs
ditis. A presumptive diagnosis is made on the basis of the of myocarditis. Immunosuppressed dogs with chronic toxo
finding of positive (or increasing) serum titers or a positive plasmosis (or neosporiosis) may be prone to active disease,
S N A P test and concurrent signs of myocarditis, with or including clinically relevant myocarditis, pneumonia, cho
without other systemic signs. The findings from endomyo rioretinitis, and encephalitis. Antiprotozoal therapy may be
cardial biopsy, i f available, may be helpful i n confirming the successful.
Babesiosis can be associated with cardiac lesions i n dogs, not proven to be clinically beneficial i n dogs with myocardi
including myocardial hemorrhage, inflammation, and necro tis, and considering the possible infective cause, they are not
sis. Pericardial effusion and variable E C G changes are also recommended as nonspecific therapy. Exceptions w o u l d
noted i n some cases. A correlation between plasma cardiac be confirmed immune-mediated disease, drug-related or
troponin I (cTnl) concentration and clinical severity, sur eosinophilic myocarditis, or confirmed nonresolving
vival, and cardiac histopathologic findings was shown i n myocarditis.
dogs with babesiosis.
H. canis may involve the myocardium during part of its NON-INFECTIVE MYOCARDITIS
life cycle; this was found i n dogs along the Texas coast. Infec Myocardial inflammation can result from the effects of
tion occurs as a result of ingesting the organism's definitive drugs, toxins, or i m m u n o l o g i c responses. A l t h o u g h there is
host, the brown dog tick (Rhipicephalus sanguineus). Clinical little clinical documentation for many of these i n dogs,
signs include stiffness, anorexia, fever, neutrophilia, and a large number of potential causes have been identified i n
periosteal new bone reaction. people. Besides the well-known toxic effects of doxorubicin
and catecholamines, other potential causes of non-infective
Other Causes myocarditis include heavy metals (e.g., arsenic, lead, mercury),
Rarely, fungi (Aspergillus, Cryptococcus, Coccidioides, Histo antineoplastic drugs (cyclophosphamide, 5-fluorouracil,
plasma, Paecilomyces), rickettsiae (Rickettsia rickettsii, interleukin-2, alpha-interferon), other drugs (e.g., thyroid
Ehrlichia canis, Bartonella elizabethae), algaelike organisms hormone, cocaine, amphetamines, lithium), and toxins (wasp
(Prototheca sp.), and nematode larval migration (Toxocara or scorpion stings, snake venom, spider bites). Immune-
sp.) cause myocarditis. Affected animals are usually immu mediated diseases and p h e o c h r o m o c y t o m a can cause
nosuppressed and have systemic signs of disease. Rocky myocarditis as well. Hypersensitivity reactions to many anti-
Mountain spotted fever (R. rickettsii) occasionally causes infective agents and other drugs have also been identified as
fatal ventricular arrhythmias, along with necrotizing vas causes of myocarditis i n people. Drug-related myocarditis is
culitis, myocardial thrombosis, and ischemia. Angiostrongy usually characterized by eosinophilic as well as lymphocytic
lus vasorum infection i n association with immune-mediated infiltrates.
thrombocytopenia has rarely caused myocarditis, thrombos
ing arteritis, and sudden death. TRAUMATIC MYOCARDITIS
Nonpenetrating or blunt trauma to the chest and heart is
Clinical Findings and Diagnosis more c o m m o n than penetrating wounds. Cardiac arrhyth
Unexplained onset of arrhythmias or heart failure after a mias are frequently observed after such trauma, especially i n
recent episode of infective disease or drug exposure is the dogs. Cardiac damage can result from impact against the
classic clinical presentation of acute myocarditis. However, chest wall, compression, or acceleration-deceleration forces.
definitive diagnosis is difficult because clinical and clinico Other possible mechanisms of myocardial injury and
pathologic findings are usually nonspecific and inconsistent. arrhythmogenesis include an autonomic imbalance, isch
A database including complete blood count, serum bio emia, reperfusion injury, and electrolyte and acid-base dis
chemical profile with creatine kinase activity, cardiac tropo turbances. Thoracic radiographs, serum biochemistries,
nin concentration, thoracic and abdominal radiographs, and circulating cardiac troponin concentrations, E C G , and echo
urinalysis are usually obtained. E C G changes could include cardiography are recommended i n the assessment of these
an ST segment shift, T-wave or Q R S voltage changes, A V cases. Echocardiography can define preexisting heart disease,
conduction abnormalities, and various arrhythmias. Echo global myocardial function, and unexpected cardiovascular
cardiographic signs of poor regional or global wall m o t i o n , findings, but it may not identify small areas of myocardial
altered myocardial echogenicity, or pericardial effusion may injury.
be evident. In dogs with persistent fever, serial bacterial (or Arrhythmias usually appear within 24 to 48 hours after
fungal) blood cultures may be useful. Serologic screening for trauma, although they can be missed on intermittent E C G
known infective causes may or may not be helpful. Histo recordings. V P C s , ventricular tachycardia, and accelerated
logic criteria for a diagnosis of myocarditis include inflam idioventricular rhythms (with rates of 60 to 100 beats/min
matory infiltrates with myocyte degeneration and necrosis. or slightly faster) are more c o m m o n than supraventricular
Endomyocardial biopsy specimens are currently the only tachyarrhythmias or bradyarrhythmias i n these patients.
means of obtaining a definitive antemortem diagnosis, but Accelerated idioventricular rhythms usually are manifested
if the lesions are focal, the findings may not be diagnostic. only when the sinus rate slows or pauses; they are benign i n
most dogs with normal underlying heart function and disap
Treatment pear with time (generally within a week or so). Antiarrhyth
Unless a specific etiology can be identified and treated, mic therapy for accelerated idioventricular rhythm i n this
therapy for suspected myocarditis is largely supportive. Strict setting is usually unnecessary. The patient as well as the E C G
rest, antiarrhythmic drugs (see Chapter 4), therapy to support should be monitored closely. M o r e serious arrhythmias
myocardial function and manage C H F signs (see Chapter 3), (e.g., faster rate) or hemodynamic deterioration may require
and other support are used as needed. Corticosteroids are antiarrhythmic therapy (see Chapter 4).
Traumatic avulsion of A V valve papillary muscles, septal Mauldin GE, Fox PR, Patnaik AK: Doxorubicin-induced cardiotoxi-
perforation, and rupture of the heart or pericardium have cosis: clinical features in 23 dogs, / Vet Intern Med 6:82, 1992.
also been reported. Traumatic papillary muscle avulsion Maxson TR et al: Polymerase chain reaction analysis for viruses in
causes acute volume overload w i t h acute onset of C H F . Signs paraffin-embedded myocardium from dogs with dilated cardio
myopathy or myocarditis, Am J Vet Res 62:130, 2001.
of low-output failure and shock, as well as arrhythmias, can
Meurs K M et al: Familial ventricular arrhythmias in Boxers, / Vet
develop rapidly after cardiac trauma.
Intern Med 13:437, 1999.
Meurs K M et al: Comparison of the effects of four antiarrhythmic
Suggested Readings treatments for familial ventricular arrhythmias in Boxers, / Am
NONINFECTIVE MYOCARDIAL DISEASE Vet Med Assoc 221:22, 2002.
Backus RC et al: Taurine deficiency in Newfoundlands fed com Meurs K M , Miller MW, Wright NA: Clinical features of dilated
mercially available complete and balanced diets, / Am Vet Med cardiomyopathy in Great Danes and results of a pedigree analy
Assoc 223:1130, 2003. sis: 17 cases (1990-2000), J Am Vet Med Assoc 218:729, 2001.
Baumwart RD et al: Clinical, echocardiographic, and electrocardio McEntee K et al: Usefulness of dobutamine stress tests for detection
graphic abnormalities in Boxers with cardiomyopathy and left of cardiac abnormalities in dogs with experimentally induced
ventricular systolic dysfunction: 48 cases (1985-2003), J Am Vet early left ventricular dysfunction, Am J Vet Res 62:448, 2001.
Med Assoc 226:1102, 2005. Minors SL, O'Grady MR: Resting and dobutamine stress echocar
Baumwart RD, Orvalho J, Meurs K M : Evaluation of serum cardiac diographic factors associated with the development of occult
troponin I concentration in boxers with arrhythmogenic right dilated cardiomyopathy in healthy Doberman Pinscher dogs,
ventricular cardiomyopathy, Am } Vet Res 68:524, 2007. / Vet Intern Med 12:369, 1998.
Borgarelli M et al: Prognostic indicators for dogs with dilated car O'Sullivan M L , O'Grady MR, Minors SL: Plasma big endothelin-1,
diomyopathy, / Vet Intern Med 20:104, 2006. atrial natriuretic peptide, aldosterone, and norepinephrine con
Calvert C A et al: Results of ambulatory electrocardiography in centrations in normal Doberman Pinschers and Doberman Pin
overtly healthy Doberman Pinschers with echocardiographic schers with dilated cardiomyopathy, / Vet Intern Med 21:92-99,
abnormalities, / Am Vet Med Assoc 217:1328, 2000. 2007.
Calvert CA, Jacobs GJ, Pickus CW: Bradycardia-associated episodic O'Sullivan M L , O'Grady MR, Minors SL: Assessment of diastolic
weakness, syncope, and aborted sudden death in cardiomyop- function by Doppler echocardiography in normal Doberman
athic Doberman Pinschers, / Vet Intern Med 10:88, 1996. Pinschers and Doberman Pinschers with dilated cardiomyopa
Calvert C A et al: Clinical and pathological findings in Doberman thy, J Vet Intern Med 21:81, 2007.
Pinschers with occult cardiomyopathy that died suddenly or Oyama M A , Sisson DD, Prosek R et al: Carvedilol in dogs
developed congestive heart failure: 54 cases (1984-1991), J Am with dilated cardiomyopathy, / Vet Intern Med 21:1272-1279,
Vet Med Assoc 210:505, 1997. 2007.
Calvert C A et al: Signalment, survival, and prognostic factors in Sisson DD, Thomas WP, Keene BW: Primary myocardial diseases
Doberman Pinschers with end-stage cardiomyopathy, / Vet Intern in the dog. In Ettinger SJ, Feldman EC, editors: Textbook of vet
Med 11:323, 1997. erinary internal medicine, ed 5, Philadelphia, 2000, WB Saunders,
Carroll M C , Cote E: Carnitine: a review, Compend Cont Educ 23:45, pp 874-895.
2001. Sleeper M M , Clifford CA, Laster LL: Cardiac troponin I in the
Dambach D M et al: Familial dilated cardiomyopathy of young Por normal dog and cat, / Vet Intern Med 15:501, 2001.
tuguese water dogs, / Vet Intern Med 13:65, 1999. Sleeper M M et al: Dilated cardiomyopathy in juvenile Portuguese
De Andrade JN et al: Reduction of diameter of the left ventricle of water dogs, / Vet Intern Med 16:52, 2002.
dogs by plication of the left ventricular free wall, Am J Vet Res Spier AW, Meurs K M : Evaluation of spontaneous variability in the
62:297, 2001. frequency of ventricular arrhythmias in Boxers with arrhythmio-
Dukes-McEwan J et al: Proposed guidelines for the diagnosis of genic right ventricular cardiomyopathy, / Am Vet Med Assoc
canine idiopathic dilated cardiomyopathy, / Vet Cardiol 5:7, 2003. 24:538, 2004.
Driehuys S, Van Winkle TJ, Sammarco C D et al: Myocardial infarc Tidholm A, Svensson H , Sylven C: Survival and prognostic factors
tion in dogs and cats: 37 cases (1985-1994), J Am Vet Med Assoc in 189 dogs with dilated cardiomyopathy, ] Am Anim Hosp Assoc
213:1444, 1998. 33:364, 1997.
Falk T, Jonsson L: Ischaemic heart disease in the dog: a review of Tidholm A, Haggstrom J, Jonsson L: Detection of attenuated wavy
65 cases, / Small Anim Pract 41:97, 2000. fibers in the myocardium of Newfoundlands without clinical or
Fascetti AJ et al: Taurine deficiency in dogs with dilated cardiomy echocardiographic evidence of heart disease, Am / Vet Res 61:238,
opathy: 12 cases (1997-2001), / Am Vet Med Assoc 223:1137, 2000.
2003. Tidholm A, Haggstrom J, Hansson K: Effects of dilated cardiomy
Freeman L M , Brown DJ, Rush JE: Assessment of degree of oxidative opathy on the renin-angiotensin-aldosterone system, atrial natri
stress and antioxidant concentration in dogs with idiopathic uretic peptide activity, and thyroid hormone concentrations in
dilated cardiomyopathy, J Am Vet Med Assoc 215:644, 1999. dogs, Am J Vet Res 62:961, 2001.
Freeman L M et al: Relationship between circulating and dietary Vollmar AC: The prevalence of cardiomyopathy in the Irish Wolf
taurine concentration in dogs with dilated cardiomyopathy, hound: a clinical study of 500 dogs, / Am Anim Hosp 36:126,
Vet Therapeutics 2:370, 2001. 2000.
Kittleson M D et al: Results of the multicenter spaniel trial (MUST): Vollmar AC et al: Dilated cardiomyopathy in juvenile Doberman
taurine- and carnitine-responsive dilated cardiomyopathy in Pinscher dogs, / Vet Cardiol 5:23, 2003.
American Cocker Spaniels with decreased plasma taurine con Wright K N et al: Radioffequency catheter ablation of atrioven
centration, / Vet Intern Med 11:204, 1997. tricular accessory pathways in 3 dogs with subsequent resolution
of tachycardia-induced cardiomyopathy, / Vet Intern Med 13:361, Fritz CL, Kjemtrup A M : Lyme borreliosis, / Am Vet Med Assoc
1999. 223:1261,2003.
Gould S M , Mclnnes EL: Immune-mediated thrombocytopenia
MYOCARDITIS associated with Angiostrongylus vasorum infection in a dog,
Barber JS, Trees AJ: Clinical aspects of 27 cases of neosporosis in / Small Anim Pract 40:227, 1999.
dogs, VetRec 139:439, 1996. Lobetti R, Dvir, E, Pearson J: Cardiac troponins in canine babesio
Bradley KK et al: Prevalence of American trypanosomiasis (Chagas sis, / Vet Intern Med 16:63, 2002.
disease) among dogs in Oklahoma, J Am Vet Med Assoc 217:1853, Meurs K M et al: Chronic Trypanosoma cruzi infection in
2000. dogs: 11 cases (1987-1996), / Am Vet Med Assoc 213:497,
Breitschwerdt EB et al: Bartonella vinsonii subsp. Berkhoffii and 1998.
related members of the alpha subdivision of the Proteobacteria Pisani B, Taylor DO, Mason JW: Inflammatory myocardial diseases
in dogs with cardiac arrhythmias, endocarditis, or myocarditis, and cardiomyopathies, Am J Med 102:459, 1997.
/ Clin Microbiol 37:3618, 1999. Snyder PS et al: Electrocardiographic findings in dogs with
Dvir E et al: Electrocardiographic changes and cardiac pathology motor vehicle-related trauma, / Am Anim Hosp Assoc 37:55,
in canine babesiosis, / Vet Cardiol 6:15, 2004. 2001.
C H A P T E R 8
Myocardial Diseases
of the Cat
HYPERTROPHIC C A R D I O M Y O P A T H Y
Etiology
Radiography The cause of primary or idiopathic hypertrophic cardiomy
Electrocardiography opathy ( H C M ) in cats is unknown, but a heritable abnor
Echocardiography mality is likely in many cases. Disease prevalence appears to
Subclinical Hypertrophic Cardiomyopathy be high i n several breeds, such as the Maine C o o n , Persian,
Clinically Evident Hypertrophic Cardiomyopathy Ragdoll, and American Shorthair. There are also reports of
Diuretic Therapy H C M in litter mates and other closely related domestic
Other Therapy for Acute Congestive Heart Failure shorthair cats. A n autosomal dominant inheritance pattern
Chronic Refractory Congestive Heart Failure has been found in some breeds. In human familial H C M ,
S E C O N D A R Y HYPERTROPHIC M Y O C A R D I A L many different gene mutations are known to exist. Although
DISEASE several c o m m o n human gene mutations have not yet simi
RESTRICTIVE C A R D I O M Y O P A T H Y larly been found in feline H C M , others may be i n the future.
DILATED C A R D I O M Y O P A T H Y Reduced myomesin (a sarcomeric protein) occurs in some
OTHER M Y O C A R D I A L DISEASES affected Maine C o o n cats. The same researchers (Meurs
Arrhythmogenic Right Ventricular Cardiomyopathy et al. 2005) also found a mutation in cardiac myosin-binding
Corticosteroid-Associated Heart Failure protein C in this breed. Another mutation has been
Myocarditis identified i n Ragdoll cats; testing for these mutations is cur
rently available (contact www.vetmed.wsu.edu/deptsVCGL/
felineTests.aspx).
In addition to mutations of genes that encode for myo
cardial contractile or regulatory proteins, possible causes of
the disease include an increased myocardial sensitivity to
or excessive production of catecholamines; an abnormal
hypertrophic response to myocardial ischemia, fibrosis, or
Myocardial disease i n cats encompasses a diverse collection trophic factors; a primary collagen abnormality; and abnor
of idiopathic and secondary processes affecting the myocar malities of the myocardial calcium-handling process. M y o
dium. The spectrum o f anatomic and pathophysiologic cardial hypertrophy with foci of mineralization occurs in
features is wide. Disease characterized by myocardial hyper cats with hypertrophic feline muscular dystrophy, an X -
trophy is most c o m m o n , although features of multiple linked recessive dystrophin deficiency similar to Duchenne
pathophysiologic categories co-exist i n some cats. Restrictive muscular dystrophy in people; however, congestive heart
pathophysiology develops often. Classic dilated cardiomy failure ( C H F ) is u n c o m m o n i n these cats. Some cats with
opathy is now u n c o m m o n i n cats; its features are similar to H C M have high serum growth hormone concentrations. It
those of dilated cardiomyopathy in dogs (see Chapter 7). is not clear whether viral myocarditis has a role in the patho
Myocardial disease i n some cats does not fit neatly into the genesis of feline cardiomyopathy. One study of myocardial
categories of hypertrophic, dilated, or restrictive cardiomy samples from cats with H C M evaluated by polymerase chain
opathy and therefore is considered indeterminate or unclas reaction ( P C R ) showed evidence of panleukopenia virus
sified cardiomyopathy. Arterial thromboembolism is a major D N A in approximately one third of the cats with myocardi
complication i n cats w i t h myocardial disease. tis but in none of the healthy control cats (Meurs, 2000).
Pathophysiology narrowing o f intramural coronary arteries, increased L V
Thickening of the left ventricular (LV) wall and/or interven filling pressure, decreased coronary artery perfusion pres
tricular septum is characteristic, but the extent and distribu sure, and insufficient myocardial capillary density for the
tion of hypertrophy i n cats with H C M are variable. M a n y degree of hypertrophy. Tachycardia contributes to ischemia
cats have symmetric hypertrophy, but some have asymmetric by increasing myocardial O requirements while reducing
2
septal thickening, and a few have hypertrophy limited to diastolic coronary perfusion time. Ischemia impairs early,
the free wall or papillary muscles. The L V lumen usually active ventricular relaxation, w h i c h further increases ven
appears small. Focal or diffuse areas of fibrosis occur w i t h i n tricular filling pressure, and over time leads to myocardial
the endocardium, conduction system, or myocardium; nar fibrosis. Ischemia can provoke arrhythmias and possibly
rowing of small intramural coronary arteries may also be thoracic pain.
noted. Areas of myocardial infarction as well as myocardial Atrial fibrillation (AF) and other tachyarrhythmias fur
fiber disarray may be present. ther impair diastolic filling and exacerbate venous conges
Myocardial hypertrophy and the accompanying changes tion; the loss of the atrial "kick" and the rapid heart rate
increase ventricular wall stiffness. Additionally, early active associated w i t h A F are especially detrimental. Ventricular
myocardial relaxation may be slow and incomplete, espe tachycardia or other arrhythmias may lead to syncope or
cially in the presence of myocardial ischemia. This further sudden death.
reduces ventricular distensibility and promotes diastolic dys Pulmonary venous congestion and edema result from
function. This ventricular stiffness impairs L V filling and increasing L A pressure. Increased pulmonary venous and
increases diastolic pressure. L V volume remains n o r m a l or capillary pressures are thought to cause pulmonary vasocon
decreased. Reduced ventricular volume results i n a lower striction; increased pulmonary arterial pressure and second
stroke volume, which may contribute to neurohormonal ary right-sided C H F signs may occur. Eventually, refractory
activation. Higher heart rates further interfere w i t h L V biventricular failure with profuse pleural effusion develops
filling, promote myocardial ischemia, and contribute to i n some cats with H C M . The effusion is usually a modified
pulmonary venous congestion and edema by shortening transudate, although it can be (or become) chylous.
the diastolic filling period. Contractility, or systolic function,
is usually normal i n affected cats. However, some cats Clinical Features
experience progression to ventricular systolic failure and H C M may be most c o m m o n i n middle-age male cats, but
dilation. clinical signs can occur at any age. Cats with milder disease
Progressively higher L V filling pressures lead to increased may be asymptomatic for years. Symptomatic cats are most
left atrial (LA) and pulmonary venous pressures. Progressive often presented for respiratory signs of variable severity or
L A dilation as well as pulmonary congestion and edema can acute signs o f thromboembolism (see p. 195). Respiratory
result. The degree of L A enlargement varies from m i l d to signs include tachypnea; panting associated w i t h activity;
massive. A thrombus is sometimes found w i t h i n the L V or dyspnea; and, only rarely, coughing (which can be misinter
attached to a ventricular wall, although it is more c o m m o n l y preted as vomiting). Disease onset may seem acute in seden
located i n the L A . Arterial thromboembolism is a major tary cats, even though pathologic changes have developed
complication of H C M as well as other forms of cardiomy gradually. Occasionally, lethargy or anorexia is the only evi
opathy i n cats (see Chapter 12). M i t r a l regurgitation devel dence of disease. Some cats have syncope or sudden death i n
ops i n some affected cats. Changes i n L V geometry, papillary the absence o f other signs. Stresses such as anesthesia, surgery,
muscle structure, or the systolic movement of the mitral fluid administration, systemic illnesses (e.g., fever or anemia),
valve (systolic anterior motion [SAM]) may prevent n o r m a l or boarding can precipitate C H F in an otherwise compen
valve closure. Valve insufficiency exacerbates the increased sated cat. Asymptomatic disease is discovered i n some cats
L A size and pressure. when a m u r m u r or gallop sound is heard during routine
Systolic dynamic L V outflow obstruction occurs i n some auscultation.
cats. This is also k n o w n as hypertrophic obstructive cardiomy Systolic murmurs compatible with mitral regurgitation
opathy or functional subaortic stenosis. Excessive asymmetric or L V outflow tract obstruction are c o m m o n . Some cats do
hypertrophy of the basilar interventricular septum may be not have an audible murmur, even those with marked
evident on echocardiograms or at necropsy. Systolic outflow ventricular hypertrophy. A diastolic gallop sound (usually
obstruction increases L V pressure, wall stress, and myocar S ) may be heard, especially i f heart failure is evident or
4
dial oxygen demand and promotes myocardial ischemia. imminent. Cardiac arrhythmias are relatively c o m m o n .
Mitral regurgitation is exacerbated by the tendency of Femoral pulses are usually strong, unless distal aortic throm
hemodynamic forces to pull the anterior mitral leaflet boembolism has occurred. The precordial impulse often
toward the interventricular septum during ejection ( S A M , feels vigorous. Prominent lung sounds, pulmonary crackles,
see Figure 8-3). Increased LV outflow turbulence c o m m o n l y and sometimes cyanosis accompany severe pulmonary
causes an ejection m u r m u r of variable intensity i n these edema. Pulmonary crackles are not always heard w i t h edema
cats. in cats. Pleural effusion usually attenuates ventral p u l m o
Several factors probably contribute to the development nary sounds. The physical examination may be normal in
of myocardial ischemia i n cats with H C M . These include subclinical cases.
Diagnosis (Fig. 8-2). Atrioventricular (AV) conduction delay, complete
A V block, or sinus bradycardia is occasionally found.
RADIOGRAPHY
Radiographic features of H C M include a prominent left ECHOCARDIOGRAPHY
atrium and variable L V enlargement (Fig. 8-1). The classic Echocardiography is the best means of diagnosis and dif
valentine-shaped appearance of the heart on dorsoventral or ferentiation of H C M from other disorders. The extent of
ventrodorsal views is not always present, although usually hypertrophy and its distribution within the ventricular wall,
the point of the left ventricular apex is maintained. The septum, and papillary muscles is shown by two-dimensional
cardiac silhouette appears normal in most cats with m i l d and M - m o d e echo studies. Doppler techniques can demon
H C M . Enlarged and tortuous pulmonary veins may be noted strate L V diastolic or systolic abnormalities.
i n cats with chronically high L A and pulmonary venous Widespread myocardial thickening is common, and the
pressure. Left-sided C H F produces variable degrees of patchy hypertrophy is often asymmetrically distributed among
interstitial or alveolar pulmonary edema infiltrates. The various LV wall, septal, and papillary muscle locations. Focal
radiographic distribution of pulmonary edema is variable; areas of hypertrophy also occur. Use of two-dimensional-
a diffuse or focal distribution throughout the lung fields is guided M - m o d e helps ensure proper beam position. Stan
c o m m o n , in contrast to the characteristic perihilar distribu dard M - m o d e views and measurements are obtained, but
tion of cardiogenic pulmonary edema seen i n dogs. Pleural thickened areas outside these standard positions should also
effusion is c o m m o n i n cats with advanced or biventricular be measured (Fig. 8-3). The diagnosis of early disease may
CHF. be questionable in cats with m i l d or only focal thickening.
Falsely increased thickness measurements (pseudohypertro
ELECTROCARDIOGRAPHY phy) can occur with dehydration and sometimes tachycar
M a n y (up to 70%) cats with H C M have electrocardiogram dia. Spurious diastolic thickness measurements also arise
( E C G ) abnormalities. These include criteria for L A or L V when the beam does not transect the wall/septum perpen
enlargement, ventricular and/or (less often) supraventricular dicularly and when the measurement is not taken at the end
tachyarrhythmias, and a left anterior fascicular block pattern of diastole, as can happen without simultaneous E C G record-
FIG 8-1
R a d i o g r a p h i c e x a m p l e s of feline h y p e r t r o p h i c c a r d i o m y o p a t h y . Lateral (A) a n d d o r s o v e n
tral (B) v i e w s s h o w i n g atrial a n d mild ventricular e n l a r g e m e n t in a m a l e Domestic
S h o r t h a i r cat. Lateral (C) v i e w of a c a t with h y p e r t r o p h i c c a r d i o m y o p a t h y a n d m a r k e d
pulmonary edema.
enlargement and pericardial or pleural effusion are occa
sionally detected.
Cats w i t h dynamic L V outflow tract obstruction also
often have S A M o f the mitral valve (Fig. 8-4) or premature
closure o f the aortic valve leaflets o n M - m o d e scans. Doppler
modalities can demonstrate mitral regurgitation and L V
outflow turbulence (Fig. 8-5), although optimal alignment
with the maximal-velocity outflow jet is often difficult and
it is easy to underestimate the systolic gradient.
L A enlargement may be m i l d to marked. Spontaneous
contrast (swirling, smoky echos) is visible w i t h i n the enlarged
L A of some cats. This is thought to result from b l o o d stasis
with cellular aggregations and to be a harbinger o f throm
boembolism. A thrombus is occasionally visualized w i t h i n
the left atrium, usually i n the auricle (Fig. 8-6).
Other causes o f myocardial hypertrophy (see p. 149)
should be excluded before a diagnosis o f idiopathic H C M is
made. Myocardial thickening can also result from infiltrative
disease. Variation in myocardial echogenicity or wall irregu
larities may be noted in such cases. Excess moderator bands
appear as bright, linear echos within the left ventricular
cavity.
Clinicopathologic Findings
Clinical pathology tests are often noncontributory. H i g h
concentrations o f circulating natriuretic peptides and cardiac
troponins occur in cats w i t h moderate to severe H C M . Vari
ably elevated plasma T N F concentrations have been found
a
i n cats with C H F .
Treatment
FIG 8 - 2 SUBCLINICAL HYPERTROPHIC
E l e c t r o c a r d i o g r a m from a c a t with h y p e r t r o p h i c c a r d i o m y CARDIOMYOPATHY
o p a t h y s h o w i n g o c c a s i o n a l ventricular premature c o m p l e x e s
a n d a left a x i s d e v i a t i o n . Leads I, II, III, at 2 5 m m / s e c .
Whether (and how) asymptomatic cats should be treated
1 c m = 1 mV. is controversial. It is unclear i f disease progression can be
slowed or survival prolonged by medical therapy before the
onset of clinical signs. According to anecdotal reports, some
ing or when using two-dimensional imaging o f insufficient cats show increased activity or improved "attitude" after
frame rate. A (properly obtained) diastolic L V wall or septal being treated with a [3-blocker or diltiazem on the basis o f
thickness >5.5 m m is considered abnormal. Cats with severe echocardiographic findings or an arrhythmia. W h e n moder
H C M have diastolic L V wall or septal thicknesses o f 8 m m ate to severe L A enlargement is found, especially with spon
or more, although the degree of hypertrophy is not neces taneous echocontrast, instituting antithrombotic prophylaxis
sarily correlated with the severity o f clinical signs. Doppler- is prudent (see Chapter 12).
derived estimates o f diastolic function, such as isovolumic Avoidance o f stressful situations likely to cause persistent
relaxation time, and mitral inflow and pulmonary venous tachycardia and reevaluation on a semiannual or annual
velocity patterns, as well as Doppler tissue imaging tech basis are usually advised. Secondary causes o f myocardial
niques are being employed more often to define disease char hypertrophy, such as systemic arterial hypertension and
acteristics. hyperthyroidism, should be ruled out (or treated, i f found).
Papillary muscle hypertrophy can be marked, and systolic
LV cavity obliteration is observed i n some cats. Increased CLINICALLY EVIDENT HYPERTROPHIC
echogenicity (brightness) o f papillary muscles and subendo CARDIOMYOPATHY
cardial areas is thought to be a marker for chronic myocar Goals o f therapy are to enhance ventricular filling, relieve
dial ischemia with resulting fibrosis. LV fractional shortening congestion, control arrhythmias, m i n i m i z e ischemia, and
(FS) is generally normal to increased. However, some cats prevent thromboembolism (Box 8-1). Furosemide is used
have mild to moderate LV dilation and reduced contractility only at the dosage needed to help control congestive signs.
(FS ~ 23%-29%; normal FS is 35%-65%). Right ventricular Moderate to severe pleural effusion is treated by thoraco-
FIG 8 - 3
E c h o c a r d i o g r a p h i c e x a m p l e s of feline h y p e r t r o p h i c c a r d i o m y o p a t h y . M - m o d e i m a g e
(A) at the left ventricular level from a 7-year-old m a l e Domestic S h o r t h a i r cat. The left
ventricular d i a s t o l i c free-wall a n d septal thicknesses a r e a b o u t 8 m m . T w o - d i m e n s i o n a l
right p a r a s t e r n a l short-axis v i e w s d u r i n g d i a s t o l e (B) a n d systole (C) in m a l e M a i n e C o o n
cat with h y p e r t r o p h i c obstructive c a r d i o m y o p a t h y . In (B) note the h y p e r t r o p h i e d a n d
bright p a p i l l a r y muscles. In (C) note the almost total systolic obliteration of the left
ventricular c h a m b e r . IVS, interventricular s e p t u m ; LV, left ventricle; LVW, left ventricular
free w a l l ; RV, right ventricle.
centesis, w i t h the cat restrained gently i n sternal position. therapies should be delayed until the cat's condition is more
Cats with severe C H F signs are given supplemental oxygen, stable.
parenteral furosemide, and sometimes other drugs to con Ventricular filling is improved by slowing the heart rate
trol edema (discussed i n more detail later). Once initial and enhancing relaxation. Stress and activity level should be
medications have been given, the cat should be allowed to minimized to the extent possible. Although the Ca++-channel
rest. The respiratory rate is noted initially and then every 30 blocker diltiazem, or a -blocker (see Chapter 4 and Table
minutes or so without disturbing the cat. Catheter place 4-2) have historically formed the foundation of long-term
ment, blood sampling, radiographs, and other tests and oral therapy, an angiotensin-converting enzyme inhibitor
FIG 8 - 4
A , T w o - d i m e n s i o n a l e c h o i m a g e in midsystole from the cat in Fig. 8-3, B a n d C . E c h o e s
from the anterior mitral leaflet a p p e a r within the LV outflow tract (arrow) b e c a u s e of
a b n o r m a l systolic anterior (toward the septum) motion ( S A M ) of the v a l v e . B , The M - m o d e
e c h o c a r d i o g r a m at the mitral v a l v e level a l s o s h o w s the mitral S A M (arrows). Ao, A o r t a ;
LA, left atrium; LV, left ventricle.
FIG 8 - 5
C o l o r flow D o p p l e r i m a g e taken in systole from a male
Domestic Longhair cat with h y p e r t r o p h i c obstructive c a r d i o
FIG 8 - 6
myopathy. N o t e the turbulent f l o w just a b o v e w h e r e the
E c h o c a r d i o g r a m o b t a i n e d from the right p a r a s t e r n a l short-
thickened interventricular septum protrudes into the left
a x i s position at the aortic-left atrial level in a n o l d m a l e
ventricular outflow tract a n d a small mitral insufficiency jet
Domestic S h o r t h a i r cat with restrictive c a r d i o m y o p a t h y . N o t e
into the LA, c o m m o n with S A M . Right p a r a s t e r n a l long a x i s
the massive left atrial e n l a r g e m e n t a n d thrombus (arrows)
view. A o , A o r t a ; LA, left atrium; LV, left ventricle.
within the a u r i c l e . A, A o r t a ; LA, left a t r i u m ; RVOT, right
ventricular outflow tract.
infarction, or concurrent hyperthyroidism. A n A C E I may
BOX 8-1
reduce neurohormonal activation and abnormal cardiac
Treatment Outline for Cats with Hypertrophic remodeling. It is sometimes used alone or combined with
Cardiomyopathy diltiazem or a -blocker. Long-term therapy generally also
includes therapy to reduce the likelihood of arterial throm
Severe, Acute Signs of CHF* boembolism (see Chapter 12). Dietary sodium restriction is
Supplemental O 2
recommended i f the cat w i l l accept such a diet, but it is more
Minimize patient handling important to forestall anorexia.
Furosemide (parenteral) Certain drugs are generally discouraged in cats with
Thoracocentesis, if pleural effusion present H C M . These include digoxin and other positive inotropic
Heart rate control and antiarrhythmic therapy, if indicated agents because they increase the myocardial oxygen demand
(can use IV diltiazem, esmolol, [+/-] or propranolol)
and can worsen dynamic L V outflow obstruction. A n y drug
+/- nitroglycerin (cutaneous)
that accelerates the heart rate is also potentially detrimental
+/- bronchodilator (e.g., aminophylline or theophylline)
because tachycardia shortens ventricular filling time and
+/- sedation
Monitor: respiratory rate, HR and rhythm, arterial blood
predisposes to myocardial ischemia. Arterial vasodilators can
pressure, renal function, serum electrolytes, etc. cause hypotension and reflex tachycardia, and cats with
H C M have little preload reserve. Hypotension can also exac
Mild To Moderate Signs of CHF* erbate dynamic outflow obstruction. Although ACEIs have
A C E inhibitor this potential, their vasodilating effects are usually mild.
-blocker (e.g., atenolol) or diltiazem
Furosemide Diuretic Therapy
Antithrombotic prophylaxis (aspirin, clopidogrel, heparin, Cats w i t h severe pulmonary edema are usually given intra
L M W H , or warfarin) muscular (IM) furosemide initially (2 mg/kg q1-4h; see Box
Exercise restriction 3-1 and p. 58), until an I V catheter can be placed without
Reduced-salt diet, if the cat will eat it
excessive stress to the cat. The respiratory rate and effort are
Chronic H C M Management* used to guide ongoing diuretic therapy. As respiratory dis
tress resolves, furosemide can be continued at a reduced dose
A C E inhibitor
-blocker (e.g., atenolol) or diltiazem
(-1 mg/kg q8-12h). Once pulmonary edema is controlled,
Furosemide (lowest effective dosage and frequency) furosemide is given orally and the dose gradually titrated
Antithrombotic prophylaxis (aspirin, clopidogrel, heparin, downward to the lowest effective level. A starting dose of
L M W H , or warfarin) 6.25 mg/cat q8-12h can be slowly reduced over days to weeks,
Thoracocentesis as needed depending o n the cat's response. Some cats do well with
+/- Spironolactone a n d / o r hydrochlorothiazide dosing a few times per week (or less), whereas others require
+/- Concurrent (3-blocker and diltiazem therapy it several times per day. Complications of excessive diuresis
+/- Additional antiarrhythmic drug therapy, if indicated include azotemia, anorexia, electrolyte disturbances, and
Home monitoring of resting respiratory rate (+HR if
poor L V filling. If the cat is unable to rehydrate itself by oral
possible)
water intake, cautious parenteral fluid administration may
Dietary salt restriction, if accepted
be needed (e.g., 15-20 ml/kg/day of 0.45% saline, 5% dex
Monitor renal function, electrolytes, etc.
trose i n water, or other low-sodium fluid).
M a n a g e other medical problems (rule out hyperthyroidism
and hypertension if not done previously)
+/- Positive inotropic drug (only for deteriorating systolic Other Therapy for Acute Congestive
function without LV outflow obstruction) Heart Failure
Nitroglycerin ointment may be used (q4-6h, see Box 3-1),
* See text and Chapters 3 and 4 for further details.
although no studies of its efficacy i n this situation have been
See Chapter 4 for additional ventricular antiarrhythmic drug
done. The bronchodilating and m i l d diuretic effects of ami
therapy.
See Chapter 12 for further details. nophylline (5 mg/kg q l 2 h , I M , I V ) may be helpful in cats
ACE, Angiotensin-converting enzyme; CHF, congestive heart failure; with severe pulmonary edema, as long as the drug does not
HR, heart rate; LMWH, low-molecular-weight heparin. increase the heart rate.
Butorphanol may be used to reduce anxiety (see Box 3-1).
(ACEI) may have greater benefit i n cats w i t h C H F . O p t i m a l Acepromazine may be used as an alternative and can promote
recommendations await further study. The decision to use peripheral redistribution of blood by its -blocking effects.
one particular drug over another is influenced by echocar Hypothermia may be exacerbated by peripheral vasodila
diographic or other findings i n the individual cat or the tion. M o r p h i n e should not be used i n cats. Airway suction
response to medication. Diltiazem is often used when severe, ing and mechanical ventilation with positive end-expiratory
symmetric L V hypertrophy is present. A -blocker is cur pressure can be considered i n extreme cases.
rently preferred for cats w i t h dynamic L V outflow obstruc Angiotensin-converting enzyme inhibitors. An
tion, tachyarrhythmias, syncope, suspected myocardial A C E I appears to have beneficial effects, especially i n cats with
refractory heart failure. Renin-angiotensin system inhibition into a flavored suspension for more accurate dosing. P i m o
may mitigate angiotensin II-mediated ventricular hypertro bendan or digoxin can also be used for treating refractory
phy. A C E inhibition might reduce L A size and ventricular/ right-sided C H F signs in cats without L V outflow obstruc
septal wall thickness, at least in some cats. Enalapril and tion and those w i t h progressive L V dilation and myocardial
benazepril are the agents used most often i n cats, although systolic failure i n end-stage disease. Frequent m o n i t o r i n g for
others are available (see Chapter 3 and Table 3-3). the development o f azotemia or electrolyte disturbances
Ca++-channel blockers. Ca++-channel blockers are is warranted.
thought to have beneficial effects in cats w i t h H C M by m o d
estly reducing heart rate and contractility (which reduces Prognosis
myocardial O demand). Diltiazem promotes coronary vaso
2 Several factors influence the prognosis for cats with H C M ,
dilation and may have a positive effect o n myocardial relax including the speed with which the disease progresses, the
ation. Verapamil is not recommended because of its variable occurrence of thromboembolic events and/or arrhythmias,
bioavailability and risk of toxicity in cats. A m l o d i p i n e has and the response to therapy. Asymptomatic cats with only
primarily vasodilatory effects and is not used for H C M m i l d to moderate L V hypertrophy and atrial enlargement
because it can provoke reflex tachycardia and worsen a sys often live well for several years. Cats with marked L A enlarge
tolic outflow gradient. ment and more severe hypertrophy appear to be at greater
Diltiazem is well-tolerated in many cases. Longer-acting risk for C H F , thromboembolism, and sudden death. L A size
diltiazem products are more convenient for chronic use, and age (i.e., older cats) appear to be negatively correlated
although the serum concentrations achieved can be variable. w i t h survival. M e d i a n survival time for cats w i t h C H F is
Dilacor (diltiazem) X R , dosed at half of an internal (60-mg) probably between 1 to 2 years. The prognosis is worse i n cats
tablet from the 240-mg capsule size q24(-12)h, or Cardizem with A F or refractory right-sided C H F . T h r o m b o e m b o l i s m
C D , compounded and dosed at 10 mg/kg q24h, are most and C H F confer a guarded prognosis (median survival of 2
often used. to 6 months), although some cats do well i f congestive signs
-adrenergic blockers. -blockers can reduce heart can be controlled and infarction of vital organs has not
rate and dynamic LV outflow obstruction to a greater extent occurred. Recurrence of thromboembolism is c o m m o n .
than diltiazem. They are also used to suppress tachyarrhyth
mias in cats. Sympathetic inhibition also leads to reduced
myocardial O demand, which can be important i n cats w i t h
2 SECONDARY HYPERTROPHIC
myocardial ischemia or infarction. By inhibiting catechol MYOCARDIAL DISEASE
amine-induced myocyte damage, -blockers may reduce
myocardial fibrosis. -blockers can slow active myocardial Myocardial hypertrophy is a compensatory response to
relaxation, although the benefits of heart rate reduction may certain identifiable stresses or diseases. M a r k e d L V wall and
outweigh this. septal thickening and clinical heart failure can occur i n some
Atenolol (see Chapter 4) is used most commonly. Pro of these cases, although they are generally not considered to
pranolol or another nonselective -blocker can also be used, be idiopathic H C M . Secondary causes should be ruled out
but these should be avoided until pulmonary edema is largely whenever L V hypertrophy is identified.
resolved. Antagonism of airway -receptors leading to bron
2 Evaluation for hyperthyroidism is indicated i n cats 6 years
choconstriction is a concern when using nonselective agents of age or older w i t h myocardial hypertrophy. Hyperthyroid
in C H F . Propranolol (a l i p i d soluble drug) causes lethargy ism alters cardiovascular function by its direct effects o n the
and depressed appetite in some cats. myocardium and through the interaction of heightened
Occasionally, a -blocker is added to diltiazem therapy sympathetic nervous system activity and excess thyroid
(or vice versa) i n cats with chronic refractory failure or to hormone on the heart and peripheral circulation. Cardiac
further reduce heart rate i n cats with AF. However, care must effects of thyroid hormone include myocardial hypertrophy
be taken to prevent bradycardia or hypotension i n animals and increased heart rate and contractility. The metabolic
receiving this combination. acceleration that accompanies hyperthyroidism causes a
hyperdynamic circulatory state characterized by increased
CHRONIC REFRACTORY CONGESTIVE cardiac output, oxygen demand, blood volume, and heart
HEART FAILURE rate. Systemic hypertension can further stimulate myocardial
Refractory pulmonary edema or pleural effusion is difficult hypertrophy. Manifestations of hyperthyroid heart disease
to manage. Moderate to large pleural effusions should be often include a systolic murmur, hyperdynamic arterial
treated by thoracocentesis. Various medical strategies may pulses, a strong precordial impulse, sinus tachycardia, and
help slow the rate of abnormal fluid accumulation, including various arrhythmias. Criteria for LV enlargement or hyper
maximizing the dosage of (or adding) an A C E I ; increasing trophy are often found on E C G , thoracic radiographs, or
the dosage of furosemide (up to 4 mg/kg q8h); increasing the echocardiogram. Signs of C H F develop i n approximately
dose of diltiazem or -blocker for greater heart rate control; 15% of hyperthyroid cats; most have n o r m a l to high FS, but
and adding spironolactone, with or without hydrochloro a few have poor contractile function. Cardiac therapy, i n
thiazide (see Table 3-3). Spironolactone can be compounded addition to treatment of the hyperthyroidism, may be neces-
sary for these cats. A (3-blocker can temporarily control many left heart filling pressures, combined with compensatory
of the adverse cardiac effects of excess thyroid hormone, neurohormonal activation, leads to left-sided or biventricu
especially tachyarrhythmias. Diltiazem is an alternative lar C H F . The duration of subclinical disease progression in
therapy. Treatment for C H F is the same as that described R C M is unknown.
for H C M . The rare hypodynamic (dilated) cardiac failure is
treated in the same way as dilated cardiomyopathy. Cardiac Clinical Features
therapy, including a (3-blocker, is not a substitute for anti Middle-aged and older cats are most often diagnosed with
thyroid treatment. R C M . Young cats are sometimes affected. Inactivity, poor
L V concentric hypertrophy is the expected response to appetite, vomiting, and weight loss of recent onset are
increased ventricular systolic pressure (afterload). Systemic c o m m o n i n the history. The clinical presentation varies but
arterial hypertension (see Chapter 11) increases afterload usually includes respiratory signs from pulmonary edema
because of high arterial pressure and resistance. Increased or pleural effusion. Clinical signs are often precipitated or
resistance to ventricular outflow also occurs w i t h a fixed acutely worsened by stress or concurrent disease that causes
(e.g., congenital) subaortic stenosis or dynamic L V outflow increased cardiovascular demand. Thromboembolic events
tract obstruction (hypertrophic obstructive cardiomyopa are also c o m m o n . Sometimes the condition is discovered by
thy). Cardiac hypertrophy also develops i n cats with hyper detecting abnormal heart sounds or arrhythmias on routine
somatotropism (acromegaly) as a result of growth hormone's exam or radiographic evidence of cardiomegaly.
trophic effects on the heart. C H F occurs i n some of these A systolic m u r m u r of mitral or tricuspid regurgitation, a
cats. Increased myocardial thickness occasionally results gallop sound, and arrhythmias are c o m m o n physical exam
from infiltrative myocardial disease, most notably from ination findings. Pulmonary sounds can be abnormal in cats
lymphoma. with pulmonary edema or pleural effusion. Femoral arterial
pulses are n o r m a l or slightly weak. Jugular vein distention
and pulsation are c o m m o n in cats with right-sided C H F
RESTRICTIVE CARDIOMYOPATHY signs. Acute signs of distal aortic (or other) thromboembo
lism may be the reason for presentation.
Etiology and Pathophysiology
Restrictive cardiomyopathy ( R C M ) is associated w i t h exten Diagnosis
sive endocardial, subendocardial, or myocardial fibrosis. The Diagnostic test results are frequently similar to those in
cause is not clear but probably is multifactorial. This condi cats w i t h H C M . Radiographs indicate L A or biatrial enlarge
tion may be a consequence of endomyocarditis or the end- ment (sometimes massive) and L V or generalized heart
stage o f myocardial failure and infarction caused by H C M . enlargement (Fig. 8-7). M i l d to moderate pericardial effu
Neoplastic (e.g., lymphoma) or other infiltrative or infec sion contributes to the cardiomegaly i n some cats. Proximal
tious diseases occasionally causes a secondary R C M . pulmonary veins may appear dilated and tortuous. Other
There are a variety of histologic findings i n cats with possible radiographic findings i n cats with C H F signs include
R C M , including marked perivascular and interstitial fibrosis, infiltrates of pulmonary edema, pleural effusion, and some
intramural coronary artery narrowing, and myocyte hyper times hepatomegaly.
trophy, as well as areas of degeneration and necrosis. Some C o m m o n E C G abnormalities include wide Q R S com
cats have extensive L V endomyocardial fibrosis w i t h chamber plexes, tall R waves, evidence of intraventricular conduction
deformity, or fibrous tissue bridging between the septum disturbances, wide P waves, and atrial tachyarrhythmias or
and L V wall. The mitral apparatus and papillary muscles may fibrillation. Echocardiography typically shows marked L A
be fused to surrounding tissue or distorted. (and sometimes right atrial [RA]) enlargement. There is
L A enlargement is prominent i n cats w i t h R C M , as a variable L V wall and interventricular septal thickening. Ven
consequence of chronically high L V filling pressure from tricular wall m o t i o n is often normal but may be somewhat
increased LV wall stiffness. The LV may be n o r m a l to reduced depressed (FS usually >25%). Hyperechoic areas of fibrosis
in size or mildly dilated. L V hypertrophy is variably present w i t h i n the L V wall and/or endocardial areas may be evident.
and may be regional. Intracardiac t h r o m b i and systemic Extraneous intraluminal echos representing excess modera
thromboembolism are c o m m o n . tor bands are occasionally seen. Sometimes, extensive L V
L V fibrosis impairs diastolic filling. Most affected cats endocardial fibrosis, with scar tissue bridging between the
have n o r m a l to only mildly reduced contractility, but this free-wall and septum, constricts part of the ventricular
may progress with time as more functional myocardium is chamber. Right ventricular (RV) dilation is often seen.
lost. Some cases develop regional L V dysfunction, possibly Sometimes an intracardiac thrombus is found, usually in the
from myocardial infarction, which decreases overall systolic left auricle or left atrium, but occasionally i n the left ven
function. These cases are perhaps better considered unclas tricle (see Fig. 8-6). M i l d mitral or tricuspid regurgitation
sified rather than restrictive. If mitral regurgitation is present, and a restrictive mitral inflow pattern can be seen with
it is usually m i l d . Arrhythmias, ventricular dilation, and Doppler studies. Some cats have marked regional wall dys
myocardial ischemia or infarction also contribute to the function, especially of the left ventricular free wall, which
development of diastolic dysfunction. Chronically elevated depresses FS, along with m i l d left ventricular dilation. These
FIG 8 - 7
Lateral (A) a n d d o r s o v e n t r a l (B) r a d i o g r a p h s from a n o l d e r D o m e s t i c S h o r t h a i r c a t with
restrictive c a r d i o m y o p a t h y s h o w m a r k e d left atrial e n l a r g e m e n t a n d p r o m i n e n t p r o x i m a l
p u l m o n a r y veins.
may represent cases of myocardial infarction or unclassified trolyte concentrations should be measured periodically.
cardiomyopathy rather than R C M . Furosemide and/or enalapril doses should be reduced if
The clinicopathologic findings are nonspecific. Pleural hypotension or azotemia occurs.
effusions are usually classified as modified transudate or Cats with refractory heart failure and pleural effusion are
chyle. Plasma taurine concentration is low i n some affected difficult to manage. In addition to thoracocentesis as needed,
cats and should be measured i f decreased contractility is the A C E I and furosemide dosages can be increased cau
identified. tiously. A d d i n g digoxin or pimobendan, i f not already being
used, may be helpful for cats with refractory failure. Other
Treatment and Prognosis strategies include adding spironolactone (with or without
Therapy for acute C H F is the same as for cats with H C M hydrochlorothiazide) or nitroglycerin ointment to the
(see p. 148). Cats that require inotropic support can be given regimen.
dobutamine by constant rate infusion (CRI). Management The prognosis is generally guarded to poor for cats with
of thromboembolism is described on p. 197. R C M and heart failure. Nevertheless, some cats survive more
Long-term therapy for heart failure includes furosemide than a year after diagnosis. Thromboembolism and refrac
at the lowest effective dosage; the resting respiratory rate, tory pleural effusion c o m m o n l y occur.
activity level, and radiographic findings are used to monitor
efficacy. A n A C E I is also used, starting with a very low dose
and increasing to the usual maintenance dose (see Table 3-3). DILATED CARDIOMYOPATHY
Ideally, blood pressure should be monitored when initiating
or adjusting this therapy. A -blocker is usually used for Etiology
tachyarrhythmias or i f myocardial infarction is suspected. In the late 1980s taurine deficiency was identified as a major
Alternatively, diltiazem can also be used, although its value cause of dilated cardiomyopathy ( D C M ) i n cats. This discov
in the face of significant fibrosis is controversial. Cats that ery prompted pet food manufacturers to increase the taurine
need chronic inotropic support can be given digoxin or content of commercial cat diets. Clinical D C M then became
pimobendan (see Table 3-3). Taurine supplementation may an u n c o m m o n disease in cats. Not all cats fed a taurine-
be helpful. Prophylaxis against thromboembolism is recom deficient diet develop D C M . Other factors besides a simple
mended (see p. 199), and a low-sodium diet should be fed, deficiency of this essential amino acid are likely to be involved
if accepted. Creatinine or the blood urea nitrogen and elec in the pathogenesis, including genetic factors and a possible
link with potassium depletion. Relatively few cases of D C M Pathophysiology
are identified now; many of these cats are not taurine deficient. D C M in cats has a similar pathophysiology to that in
D C M i n these cats may represent the end-stage of another dogs (see p. 129). Poor myocardial contractility is the char
myocardial metabolic abnormality, toxicity, or infection. acteristic feature (Fig. 8-8). Usually, all cardiac chambers
Doxorubicin causes characteristic myocardial histologic become dilated. A V valve insufficiency occurs secondary to
lesions in cats as it does i n dogs. Cats appear less likely to chamber enlargement and papillary muscle atrophy. As
develop clinical C H F from myocardial failure. Although i n cardiac output decreases, compensatory neurohormonal
very rare cases cats have echocardiographic changes consis mechanisms are activated, leading eventually to signs of
tent with D C M after receiving cumulative doses of 170 to C H F and low cardiac output. Besides pulmonary edema,
2
240 m g / m , clinically relevant doxorubicin-induced cardio pleural effusion and arrhythmias are c o m m o n in cats with
myopathy does not occur in the cat. DCM.
FIG 8 - 8
N o n s e l e c t i v e a n g i o g r a m from a 13-year-old f e m a l e S i a m e s e cat with d i l a t e d c a r d i o m y o p a
thy. A bolus of r a d i o g r a p h i c contrast material w a s injected into the jugular v e i n . A , Three
s e c o n d s after injection, s o m e contrast m e d i u m r emains in the right ventricle a n d pulmo
n a r y v a s c u l a t u r e . D i l a t e d p u l m o n a r y veins a r e seen entering the left atrium. N o t e the
d i l a t e d left atrium a n d ventricle. B , Thirteen s e c o n d s after the injection, the left heart a n d
p u l m o n a r y veins a r e still o p a c i f i e d , illustrating the p o o r c a r d i a c contractility a n d extremely
s l o w circulation time. The thin left ventricular c a u d a l w a l l a n d p a p i l l a r y muscles a r e better
seen in this f r a m e .
Clinical Features samples. N o r m a l whole b l o o d taurine concentrations exceed
D C M can occur at any age, although most affected cats are 200 n m o l / m l ; <140 n m o l / m l is considered deficient.
late-middle aged to geriatric. There is no breed or gender
predilection. Clinical signs often include anorexia, lethargy, Treatment and Prognosis
increased respiratory effort or dyspnea, dehydration, and The goals o f treatment are analogous to those for dogs with
hypothermia. Subtle evidence o f poor ventricular function D C M . Pleural fluid is removed by thoracocentesis. In cats
is usually found in conjunction with signs o f respiratory with acute C H F , furosemide is given to promote diuresis, as
compromise. Jugular venous distention, an attenuated pre described for H C M . Overly aggressive diuresis is discouraged
cordial impulse, weak femoral pulses, a gallop sound (usually because it can markedly reduce cardiac output i n these cases
S ), and a left or right apical systolic m u r m u r (of mitral or
3 w i t h poor systolic function. Supplemental O is recom
2
tricuspid regurgitation) are c o m m o n . Bradycardia and mended. The venodilator nitroglycerin may be helpful i n
arrhythmias are frequently heard, although many cats have cats with severe p u l m o n a r y edema. A C E I therapy is begun
a normal sinus rhythm. Increased lung sounds and p u l m o as soon as oral medication can be safely given. Other vaso
nary crackles can be auscultated in some cats, but pleural dilators (nitroprusside, hydralazine, or amlodipine) may
effusion may muffle ventral lung sounds. Some cats have help maximize cardiac output, although they increase the
signs of arterial thromboembolism (see p. 195). risk o f hypotension (see Box 3-1). B l o o d pressure, hydration,
renal function, electrolyte balance, and peripheral perfusion
Diagnosis should be monitored closely. Hypothermia is c o m m o n i n
Generalized cardiomegaly w i t h rounding o f the cardiac apex cats w i t h decompensated D C M ; external w a r m i n g is pro
is often seen on radiographs. Pleural effusion is c o m m o n and vided as needed.
may obscure the heart shadow and co-existing evidence o f Positive inotropic support is indicated. Dobutamine (or
pulmonary edema or venous congestion. Hepatomegaly dopamine) is administered by C R I for critical cases (see
may be detected; ascites is occasionally found. p. 60 and Box 3-1). Possible adverse effects include seizures
Typical E C G findings include a L V enlargement pattern, or tachycardia; i f they occur, the infusion rate is decreased
A V conduction disturbance, and tachyarrhythmias. Echocar by 50% or discontinued. O r a l inotropic therapy w i t h p i m o
diography is an important tool to differentiate D C M from bendan or digoxin (see p. 65 and Table 3-3) for maintenance
other myocardial pathophysiology. Findings are analogous therapy may be instituted. D i g o x i n tablets are usually used
to those in dogs with D C M (see p. 131). Some cats have areas because the elixir is distasteful to many cats. Toxicity can
of focal hypertrophy with hypokinesis o f only the LV wall or easily occur, especially i n cats receiving concurrent drug
septum. These may represent indeterminant myocardial therapy; serum digoxin concentration should be monitored
disease rather than typical D C M . A n intracardiac thrombus if this drug is used (see p. 66).
is identified in some cats, more often within the left atrium. Sometimes the diuretic and vasodilator therapy used for
Nonselective angiocardiography is a more risky alterna acute C H F leads to hypotension and can predispose to car
tive to echocardiography, as with other cardiomyopathies. diogenic shock i n cats with D C M . Half-strength saline solu
Characteristic angiographic findings include generalized tion w i t h 2.5% dextrose or other l o w - s o d i u m fluids can be
chamber enlargement, atrophied papillary muscles, small used intravenously with caution to help support blood pres
aortic diameter, and slow circulation time (see Fig. 8-8). sure (e.g., 20 to 35 ml/kg/day i n several divided doses or by
Complications o f angiography, especially i n cats w i t h poor CRI); potassium supplementation may be needed. Fluid can
myocardial function or C H F , include vomiting and aspira be administered subcutaneously i f necessary, although its
tion, arrhythmias, and cardiac arrest. The pleural effusion i n absorption from the extravascular space may be impaired i n
cats with D C M is usually a modified transudate, although these cases.
it can be chylous. Prerenal azotemia, mildly increased liver Chronic therapy for D C M i n cats that survive acute C H F
enzyme activity, and a stress leukogram are c o m m o n clini includes oral furosemide (tapered to the lowest effective
copathologic findings. Cats with arterial thromboembolism dosage), an A C E I , pimobendan or digoxin, antithrombotic
often have high serum muscle enzyme activities and may prophylaxis (p. 199), and (if the patient is taurine deficient)
have an abnormal hemostasis profile. Plasma or whole b l o o d supplemental taurine or a high-taurine diet. Taurine supple
taurine concentration measurement is recommended. Spe mentation is instituted as soon as practical, at 250 to 500 m g
cific instructions for sample collection and mailing should orally q l 2 h , when plasma taurine concentration is l o w or
be obtained from the specific laboratory. Plasma taurine cannot be measured. Clinical improvement, i f it occurs, is
concentrations are influenced by the amount o f taurine i n generally not apparent until after the first 1 to 2 weeks o f
the diet, the type o f diet, and the time o f sampling i n relation taurine supplementation, so supportive cardiac care is vital.
to eating; however, a plasma taurine concentration o f 20 to Improved systolic function is seen echocardiographically
30 nmol/ml or less i n a cat w i t h D C M is diagnostic for w i t h i n 6 weeks o f starting taurine supplementation i n most
taurine deficiency. Non-anorexic cats with a plasma taurine taurine-deficient cats. D r u g therapy may become unneces
concentration of <60 n m o l / m l probably should receive sary i n some cats after 6 to 12 weeks, but resolution of pleural
taurine supplementation or a different diet. W h o l e b l o o d effusion and p u l m o n a r y edema should be confirmed before
samples produce more consistent results than plasma weaning the cat from medications. If n o r m a l systolic func-
tion, based o n echocardiography, returns, the patient can be CORTICOSTEROID-ASSOCIATED
slowly weaned from supplemental taurine as long as a diet HEART FAILURE
k n o w n to support adequate plasma taurine concentrations Some cats develop C H F after receiving corticosteroid therapy.
(e.g., most name-brand commercial foods) is consumed. It is unclear whether this represents a previously unrecog
D r y diets with 1000 to 1200 m g o f taurine per kilogram o f nized form of feline heart failure, unrelated to preexisting
dry weight and canned diets w i t h 2000 to 2500 mg of taurine H C M , hypertension, or hyperthyroidism. A n acute onset
per kilogram of dry weight are thought to maintain normal of lethargy, anorexia, tachypnea, and respiratory distress is
plasma taurine concentrations i n adult cats. Reevaluation of described i n affected cats. Most cats have normal ausculta
the plasma taurine concentration 2 to 4 weeks after discon tory findings without tachycardia.
tinuing the supplement is advised. Moderate cardiomegaly, w i t h diffuse pulmonary infil
Taurine-deficient cats that survive a m o n t h after initial trates and m i l d or moderate pleural effusion, appears to be
diagnosis often can be weaned from all or most medications typical o n radiographic examination. Possible E C G findings
and appear to have approximately a 50% chance for 1-year include sinus bradycardia, intraventricular conduction
survival. The prognosis for cats that do not receive taurine abnormalities, atrial standstill, atrial fibrillation, and V P C s .
supplements or do not respond to taurine is guarded to poor. O n echocardiogram, most affected cats have some degree of
Thromboembolism i n cats with D C M is a grave sign. LV wall or septal hypertrophy and L A enlargement. Some
have A V valve insufficiency or abnormal systolic mitral
motion.
OTHER MYOCARDIAL DISEASES C H F is treated i n the same way as H C M ; corticosteroids
should be discontinued. Partial resolution of abnormal
ARRHYTHMOGENIC RIGHT cardiac findings and successful weaning from cardiac medi
VENTRICULAR CARDIOMYOPATHY cations are reported i n some cats.
Arrhythmogenic right ventricular cardiomyopathy ( A R V C )
is an idiopathic cardiomyopathy that is similar to the u n c o m MYOCARDITIS
m o n A R V C i n people. Characteristic features include m o d Inflammation of the myocardium and adjacent structures
erate to severe R V chamber dilation, w i t h either focal or may occur i n cats, as it does i n other species (see also p. 137).
diffuse R V wall thinning. R V wall aneurysm is also c o m m o n . In one study myocarditis was histologically identified in
Dilation of the right atrium and, less commonly, the left samples from more than half of cardiomyopathic cats but
atrium may occur. Myocardial atrophy w i t h fatty and/or none from cats i n the control group; viral D N A (panleuko
fibrous replacement tissue, focal myocarditis, and evidence penia) was found i n about one third of the cats with myo
of apoptosis are typical histologic findings. These are most carditis. However, the possible role of viral myocarditis in
prominent i n the R V wall. Fibrous tissue or fatty infiltration the pathogenesis of cardiomyopathy is not clear. Severe,
is sometimes found i n the L V and atrial walls. widespread myocarditis may cause C H F or fatal arrhyth
Signs of right-sided C H F are c o m m o n , with labored mias. Cats w i t h focal myocardial inflammation may be
respirations caused by pleural effusion, jugular venous dis asymptomatic. Acute and chronic viral myocarditis have
tention, ascites or hepatosplenomegaly, and occasionally been suspected. A viral cause is rarely documented, although
syncope. Lethargy and inappetence without overt heart feline coronavirus has been identified as a cause of
failure are sometimes the presenting signs. pericarditis-epicarditis.
Thoracic radiographs indicate right heart and sometimes Endomyocarditis has been documented mostly in
L A enlargement. Pleural effusion is c o m m o n . Ascites, caudal young cats. Acute death, w i t h or without preceding signs of
vena caval distention, and evidence o f pericardial effusion pulmonary edema for 1 to 2 days, is the most c o m m o n pre
may also occur. The E C G can document various arrhythmias sentation. Histopathologic characteristics of acute endo
in affected cats, including ventricular premature complexes myocarditis include focal or diffuse lymphocytic, plasmacytic,
( V P C s ) , ventricular tachycardia, A F , and supraventricular and histiocytic infiltrates w i t h few neutrophils. Myocardial
tachyarrhythmias. A right bundle branch block pattern degeneration and lysis are seen adjacent to the infiltrates.
appears to be c o m m o n ; some cats have first-degree A V block. Chronic endomyocarditis may have a m i n i m a l inflammatory
Echocardiography shows severe R A and R V enlargement. response but m u c h myocardial degeneration and fibrosis.
Other possible findings include abnormal muscular trabecu R C M could represent the end stage of nonfatal endomyocar
lation, aneurysmal dilation, areas o f dyskinesis, and para ditis. Therapy involves managing C H F signs and arrhyth
doxical septal motion. Tricuspid regurgitation appears to be mias, and other supportive care.
a consistent finding o n Doppler exam. Bacterial myocarditis may develop in association with
The prognosis is guarded once signs of heart failure sepsis or as a result of bacterial endocarditis or pericarditis.
appear. Recommended therapy includes diuretics as neces Experimental Bartonella sp. infection can cause subclinical
sary, an A C E I , and digoxin (or pimobendan). Additional lymphoplasmacytic myocarditis, but it is unclear whether
antiarrhythmic therapy may be needed (see Chapter 4). In natural infection plays a role i n the development of cardio
people w i t h A R V C , various tachyarrhythmias are a p r o m i myopathy i n cats. Toxoplasma gondii occasionally has been
nent feature and sudden death is c o m m o n . associated w i t h myocarditis, usually in immunosuppressed
cats as part of a generalized disease process. Traumatic myo MacDonald KA et al: Tissue Doppler imaging and gradient echo
carditis is recognized infrequently i n cats. cardiac magnetic resonance imaging in normal cats and cats with
hypertrophic cardiomyopathy, / Vet Intern Med 20:627, 2006.
Suggested Readings MacLean H N et al: N-terminal atrial natriuretic peptide immuno-
Baty CJ et al: Natural history of hypertrophic cardiomyopathy and reactivity in plasma of cats with hypertrophic cardiomyopathy,
aortic thromboembolism in a family of domestic shorthair cats, / Vet Intern Med 20:284, 2006.
/ Vet Intern Med 15:595, 2001. Meurs K M et al: Familial systolic anterior motion of the mitral
Bright JM, Herrtage M E , Schneider JF: Pulsed Doppler assessment valve and/or hypertrophic cardiomyopathy is apparently inher
of left ventricular diastolic function in normal and cardiomyop- ited as an autosomal dominant trait in a family of American
athic cats, J Am Anim Hosp Assoc 35:285, 1999. shorthair cats. Abstr, / Vet Intern Med 11:138, 1997.
Ferasin L et al: Feline idiopathic cardiomyopathy: a retrospective Meurs K M et al: Molecular screening by polymerase chain reaction
study of 106 cats (1994-2001), J Feline Med Surg 5:151, 2003. detects panleukopenia virus D N A in formalin-fixed hearts from
Fox PR: Hypertrophic cardiopathy: clinical and pathologic corre cats with idiopathic cardiomyopathy and myocarditis, Cardiovasc
lates, / Vet Cardiol 5:39, 2003. Pathol 9:119, 2000.
Fox PR: Endomyocardial fibrosis and restrictive cardiomyopathy: Meurs K M et al: Myomesin, a sarcomeric protein is reduced in
pathologic and clinical features, / Vet Cardiol 6:25-31, 2004. Maine Coon cats with familial hypertrophic cardiomyopathy,
Fox PR et al: Spontaneously occurring arrhythmogenic right ven / Vet Intern Med 15:281, 2001.
tricular cardiomyopathy in the domestic cat: a new animal model Meurs K M et al: A cardiac myosin binding protein C mutation in
similar to the human disease, Circulation 102:1863, 2000. the Maine Coon cat with familial hypertrophic cardiomyopathy,
Gaschen L et al: Cardiomyopathy in dystrophin-deficient hypertro Hum Mol Genet 14:3587, 2005.
phic feline muscular dystrophy, / Vet Intern Med 13:346, 1999. Pion PD, Kittleson M D , Thomas WP: Response of cats with dilated
Gavaghan BJ et al: Quantification of left ventricular diastolic wall cardiomyopathy to taurine supplementation, ] Am Vet Med Assoc
motion by Doppler tissue imaging in healthy cats and cats with 201:275, 1992.
cardiomyopathy, Am ] Vet Res 60:1478, 1999. Rush JE et al: The use of enalapril in the treatment of feline hyper
Harvey A M et al: Arrhythmogenic right ventricular cardiomyopa trophic cardiomyopathy, J Am Anim Hosp Assoc 34:38, 1998.
thy in two cats, / Small Anim Pract 46:151, 2005. Rush JE et al: Population and survival characteristics of cats with
Johnson L M et al: Pharmacokinetic and pharmacodynamic proper hypertrophic cardiomyopathy: 260 cases (1990-1999), J Am Vet
ties of conventional and CD-formulated diltiazem in cats, / Vet Med Assoc 220:202, 2002.
Intern Med 10:316, 1996. Sampedrano C C et al: Systolic and diastolic myocardial dysfunction
Kittleson M D et al: Familial hypertrophic cardiomyopathy in a in cats with hypertrophic cardiomyopathy or systemic hyperten
Maine Coon cat: an animal model of human disease, Circulation sion, J Vet Intern Med 20:1106, 2006.
99:3172, 1999. Schober KE, Bonagura JD: Doppler echocardiographic assessment
Koffas H et al: Pulsed tissue Doppler imaging in normal cats and of E: Ea and E: Vp as indicators of left ventricular filling pressure
cats with hypertrophic cardiomyopathy, / Vet Intern Med 20:65, in normal cats and cats with hypertrophic cardiomyopathy.
2006. Abstr, / Vet Intern Med 19:931, 2005.
Kraus MS, Calvert CA, Jacobs GJ: Hypertrophic cardiomyopathy in Schober KE, Maerz I: Assessment of left atrial appendage flow
a litter of five mixed-breed cats, / Am Anim Hosp Assoc 35:293, velocity and its relation to spontaneous echocardiographic con
1999. trast in 89 cats with myocardial disease, / Vet Intern Med 20:120,
Liu SK, Keene BW, Fox PR: Myocarditis in the dog and cat. 2006.
In Bonagura JD, editor: Kirk's current veterinary therapy XII, Smith SA et al: Corticosteroid-associated congestive heart failure in
Philadelphia, 1995, WB Saunders, pp 842-845. 12 cats, Intern } Appl Res Vet Med 2:159, 2004.
C H A P T E R 9
FIG 9-1
Lateral (A) a n d dorsoventral (B) r a d i o g r a p h s from a 5-year-old m a l e Persian c a t with a
c o n g e n i t a l p e r i t o n e o p e r i c a r d i a l d i a p h r a g m a t i c hernia (PPDH). N o t e the greatly e n l a r g e d
c a r d i a c silhouette c o n t a i n i n g fat, soft tissue, a n d g a s densities a s w e l l a s t r a c h e a l e l e v a
tion. There is o v e r l a p b e t w e e n the c a r d i a c a n d d i a p h r a g m a t i c b o r d e r s o n both v i e w s .
Presence of a portion of the stomach a n d d u o d e n u m w i t h i n the p e r i c a r d i u m is evident
after b a r i u m administration (C); o m e n t a l fat a n d liver a r e a l s o present w i t h i n the pericar
d i a l s a c . In C , the d o r s a l pleural fold b e t w e e n p e r i c a r d i u m a n d d i a p h r a g m is best
a p p r e c i a t e d (arrow).
FIG 9 - 2
Right p a r a s t e r n a l short-axis e c h o c a r d i o g r a m from a f e m a l e Persian c a t with peritoneoperi
cardial d i a p h r a g m a t i c h e r n i a (PPDH). The p e r i c a r d i u m (PERI), i n d i c a t e d b y arrows,
surrounds liver a n d o m e n t a l tissue a s w e l l a s the heart. LV, Left ventricle.
pathophysiologic signs and clinical presentation can m i m i c The fluid does not clot unless hemorrhage was very recent.
those seen with pericardial effusion. Radiographically, the Neoplastic hemorrhagic effusions are more likely in dogs
cardiac silhouette may appear enlarged and deformed. Echo older than 7 years. Middle-aged, large-breed dogs are most
cardiography or pneumopericardiography can reveal the likely to have idiopathic "benign" hemorrhagic effusion.
diagnosis. Surgical cyst removal, combined with partial peri Hemangiosarcoma ( H S A ) is by far the most common
cardiectomy, usually resolves the clinical signs. neoplasm causing hemorrhagic pericardial effusion in dogs;
Congenital defects of the pericardium itself are extremely it is u n c o m m o n i n cats. Hemorrhagic pericardial effusion
rare in dogs and cats; most are incidental postmortem find also occurs i n association with various heartbase tumors;
ings. Sporadic cases of partial (usually left-sided) or c o m pericardial mesotheliomas; malignant histiocytosis ( M H ) ;
plete absence of the pericardium are reported. A possible and, rarely, metastatic carcinoma. H S A s (see p. 167) usually
complication of partial absence of the pericardium is her arise within the right heart, especially in the right auricular
niation of a portion of the heart; this could cause syncope, appendage. Chemodectoma is the most c o m m o n heartbase
embolic disease, or sudden death. Echocardiography or tumor; it arises from chemoreceptor cells at the base of the
angiocardiography may allow antemortem diagnosis. aorta. Thyroid, parathyroid, lymphoid, and connective tissue
neoplasms also occur at the heartbase. Pericardial mesothe
lioma develops i n some dogs and cats and may m i m i c idio
PERICARDIAL EFFUSION pathic disease. L y m p h o m a involving various parts of the
heart is seen more often in cats than in dogs. Dogs with
M H and pericardial effusion usually have pleural effusion
Etiology and Types Of Fluid and ascites despite the fact that they do not have cardiac
In dogs most pericardial effusions are serosanguineous or tamponade.
sanguineous and are of neoplastic or idiopathic origin. Tran Idiopathic (benign) pericardial effusion is reported most
sudates, modified transudates, and exudates are found occa frequently in m e d i u m - to large-breed dogs. Golden Retriev
sionally in both dogs and cats. ers, Labrador Retrievers, and Saint Bernards may be predis
posed. A l t h o u g h dogs of any age can be affected, the median
HEMORRHAGE age is 6 to 7 years. M o r e cases have been reported in males
Hemorrhagic effusions are c o m m o n i n dogs. The fluid than females. M i l d pericardial inflammation, with diffuse or
usually appears dark red, with a packed cell volume ( P C V ) perivascular fibrosis and focal hemorrhage, is c o m m o n on
>7%, a specific gravity >1.015, and a protein concentration histologic exam. Layers of fibrosis suggest a recurrent process
>3 g/dl. Cytologic analysis shows mainly red blood cells, but in some cases. Constrictive pericardial disease is a potential
reactive mesothelial, neoplastic, or other cells may be seen. complication.
Other, less c o m m o n causes of intrapericardial hemor tamponade. Lung and/or tracheal compression can compro
rhage include left atrial rupture secondary to severe mitral mise ventilation and stimulate cough; esophageal compres
insufficiency (see p. 116), coagulopathy, penetrating trauma sion can cause dysphagia or regurgitation.
(including iatrogenic laceration of a coronary artery during
pericardiocentesis), and possibly uremic pericarditis. CARDIAC TAMPONADE
Cardiac tamponade develops when pericardial fluid accu
TRANSUDATES mulation raises intrapericardial pressure to or above the
Pure transudates are clear, with a low cell count (usually normal cardiac diastolic pressure. This external compression
<1000 cells/l), specific gravity (<1.012), and protein content of the heart progressively limits filling, initially of the right
(<2.5 g/dl). Modified transudates may appear slightly cloudy heart, then the left. Cardiac output subsequently falls while
or pink tinged. Their cellularity (~1000 to 8000 cells/l) is systemic venous pressure rises. Pressure i n all cardiac cham
still low, but total protein concentration (~2.5-5.0 g/dl) and bers and the great veins eventually becomes equilibrated
specific gravity (1.015-1.030) are higher than those of a pure during diastole. Neurohormonal compensatory mechanisms
transudate. In some dogs and cats, transudative effusions are activated as tamponade develops. Gradual pericardial
occur with congestive heart failure ( C H F ) , hypoalbumin fluid accumulation results i n signs of C H F because of com
emia, P P D H and pericardial cysts, and toxemias that increase pensatory volume retention and the direct effects o f impaired
vascular permeability (including uremia). These conditions cardiac filling. Manifestations of systemic venous congestion
usually are associated with relatively small-volume pericar and right-sided C H F (ascites and pleural effusion) usually
dial effusion; cardiac tamponade is rare. predominate because of the right heart's thinner wall and
low pressures. Pericardial effusion does not typically affect
EXUDATES cardiac contractility directly, but reduced coronary perfusion
Exudative effusions are cloudy to opaque or serofibrinous to during tamponade can impair both systolic and diastolic
serosanguineous. They typically have a high nucleated cell function. L o w cardiac output, arterial hypotension, and poor
count (usually much higher than 3000 cells/l), protein organ perfusion can ultimately lead to cardiogenic shock
content (often much above 3 g/dl), and specific gravity and death.
(>1.015). Cytologic findings are related to the etiology. The rate of pericardial fluid accumulation and the disten
Exudative pericardial effusions are found only rarely i n sibility of the pericardial sac determine whether and how
small animals, except i n cats with feline infectious peritoni quickly cardiac tamponade develops. Rapid accumulation of
tis (FIP). even a relatively small volume can raise intrapericardial pres
Infectious pericarditis is usually related to plant awn sure sharply. A gradual process is implied when the pericar
migration, bite wounds, or extension of a pleural or m e d i dial fluid volume is large. Cardiac tamponade is relatively
astinal infection. Various bacteria (aerobic and anaerobic), c o m m o n i n dogs but rare i n cats.
actinomycosis, coccidioidomycosis, disseminated tuberculo Pulsus paradoxus is the term used to describe the exagger
sis, and, rarely, systemic protozoal infections have been ated variation i n arterial b l o o d pressure that occurs during
identified. Sterile exudative effusions are reported with the respiratory cycle as a result of cardiac tamponade. D u r i n g
leptospirosis, canine distemper, and idiopathic pericardial inspiration intrapericardial and right atrial (RA) pressures
effusion i n dogs and with FIP and toxoplasmosis i n cats. FIP fall, which facilitates right heart filling and pulmonary
is the most important cause of symptomatic pericardial effu blood flow. A t the same time, left heart filling is reduced as
sion in cats. Chronic uremia occasionally causes a sterile, more blood is held i n the lungs and the interventricular
serofibrinous or hemorrhagic effusion. septum bulges leftward from the inspiratory increase i n
right ventricular ( R V ) filling; consequently, left heart output
Pathophysiology and systemic arterial pressure decrease during inspiration.
Fluid accumulation within the pericardial space causes clin The variation in systolic arterial pressure between inspira
ical signs when it raises intrapericardial pressure to or above tion and expiration is usually >10 m m H g i n patients w i t h
normal cardiac filling pressure. This accumulation impedes cardiac tamponade and pulsus paradoxus. Pulsus paradoxus
venous return and cardiac filling. As long as intrapericardial is not always discernible using palpation of the femoral
pressure remains low, cardiac filling and output remain pulse.
relatively normal. If fluid accumulates slowly, the pericar
dium may distend enough to accommodate the increased Clinical Features
effusate volume at relatively low pressure. However, peri Clinical findings in patients with cardiac tamponade usually
cardial tissue is relatively noncompliant. Rapid fluid accu reflect right-sided C H F as well as poor cardiac output. Before
mulation or a very large effusion causes a steep rise i n obvious ascites develops, possible nonspecific signs include
intrapericardial pressure, leading to cardiac tamponade. lethargy, weakness, poor exercise tolerance, and inappetence.
Pericardial fibrosis and thickening further limit the compli The history typically includes complaints of weakness, exer
ance of this tissue. cise intolerance, abdominal enlargement, tachypnea, syncope,
Pericardial effusion of very large volume may cause clin and cough. A history of collapse is more c o m m o n i n dogs
ical signs by virtue of its size, even without overt cardiac with neoplastic disease; dogs without a mass lesion are more
RADIOGRAPHY
Pericardial effusion enlarges the cardiac silhouette (Fig. 9-4).
A massive amount o f pericardial fluid causes the classic
globoid-shaped heart shadow on both radiographic views.
Smaller fluid volumes allow various cardiac contours to be
identified, especially dorsally. Other findings associated with
tamponade include pleural effusion, a distended caudal vena
cava, hepatomegaly, and ascites. Pulmonary infiltrates of
edema and distended pulmonary veins are seen ocasionally.
Some heartbase tumors cause tracheal deviation or a soft-
tissue mass effect. Metastatic lung lesions are c o m m o n in
dogs with hemangiosarcoma.
W h e n used, fluoroscopy demonstrates diminished to
absent motion of the cardiac shadow because of the fluid
FIG 9 - 3 surrounding the heart. Angiocardiography is used only
O l d e r m a l e B o x e r with c h r o n i c c a r d i a c t a m p o n a d e a n d rarely now to evaluate patients with pericardial effusion and
right-sided c o n g e s t i v e heart failure s e c o n d a r y to chemodec cardiac tumors; it typically reveals increased endocardial-
toma. The a b d o m e n is g r e a t l y d i s t e n d e d with ascites; to-pericardial distance. Cardiac neoplasms can cause dis
c h r o n i c loss of l e a n b o d y mass is e v i d e n t a l o n g the s p i n e , placement of normal structures, filling defects, and vascular
pelvis, a n d rib c a g e .
"blushing" (opacification of excessive, abnormal tumor-
associated vessels). Pneumopericardiography has also been
replaced by echocardiography. Pneumopericardiography
uses carbon dioxide or air injected into the drained pericar
likely to have obvious ascites. M a r k e d loss o f lean body mass dial sac to outline the heart, but it is rarely used these days.
occurs in some chronic cases (Fig. 9-3). Radiographs are taken from different orientations, but the
Jugular vein distention and/or positive hepatojugular left lateral and dorsoventral views are most helpful. These
reflux, hepatomegaly, ascites, labored respirations, and weak views allow the injected gas to outline the right atrial and
femoral pulses are c o m m o n physical examination findings. heartbase areas, respectively, where tumors are most common.
Pleural effusion and ascites are also c o m m o n in cats, as
well as dogs, with cardiac tamponade. A palpable decrease ELECTROCARDIOGRAPHY
i n arterial pulse strength during inspiration (pulsus para Although there are no pathognomonic electrocardiographic
doxus) might be discernible i n some dogs with tamponade. ( E C G ) findings, the following abnormalities are suggestive
Sinus tachycardia, pale mucous membranes, and prolonged of pericardial effusion: small amplitude Q R S complexes
capillary refill time are manifestations o f high sympathetic (<1 m V in dogs), electrical alternans, and ST segment eleva
tone. The precordial impulse is weak when the pericardial tion (epicardial injury current). Electrical alternans is a
fluid volume is large. Heart sounds are muffled i n patients recurring alteration i n the size of the Q R S complex (or
with moderate to large pericardial effusions. Lung sounds sometimes the T wave) with every other beat (Fig. 9-5). It
are muffled over the ventral thorax in those with pleural results from the back-and-forth swinging motion of the
effusion. Although pericardial effusion does not cause a heart within the pericardium. Electrical alternans is most
murmur, concurrent cardiac disease may do so. If fluid likely to be seen i n patients with large-volume pericardial
has rapidly accumulated, acute tamponade can lead to shock effusion; it may be most evident at heart rates between 90
and death without obvious signs of pleural effusion, ascites, and 140/min and/or in the standing position. Sinus tachy
or radiographic evidence o f cardiomegaly. In such cases,
cardia is c o m m o n with cardiac tamponade. Atrial or ven
jugular venous distention, hypotension, and pulmonary
tricular tachyarrhythmias may also occur.
edema may be evident. Infectious pericarditis may be accom
panied by fever; rarely, a pericardial friction rub might be ECHOCARDIOGRAPHY
heard.
Echocardiography is highly sensitive for detecting pericar
dial fluid, and it is the preferred diagnostic modality i f
Diagnosis radiographic changes are equivocal. Because fluid is sonolu
A central venous pressure ( C V P ) above 10 to 12 c m H O 2 cent, pericardial effusion appears as an echo-free space
is c o m m o n ; normally, C V P is <8 c m H O . C V P measure
2 between the bright parietal pericardium and the epicardium
ment is helpful when the jugular veins are difficult to (Fig. 9-6). A b n o r m a l cardiac wall motion and chamber
assess or it is unclear whether right heart filling pressure shape and intrapericardial or intracardiac mass lesions can
is elevated. Moderate- to large-volume pleural effusion also be imaged. W i t h large-volume pericardial effusion, the
should be drained before C V P measurement, not only to heart may appear to swing back and forth within the peri
stabilize the patient but also to minimize artifactual C V P cardial sac. Cardiac tamponade is manifested by diastolic
elevation. compression/collapse o f the right atrium and sometimes the
FIG 9 - 4
Lateral (A) a n d d o r s o v e n t r a l (B) r a d i o g r a p h s from a m i x e d - b r e e d d o g with l a r g e pericar
d i a l effusion. N o t e g l o b o i d s h a p e of c a r d i a c silhouette a n d distended c a u d a l v e n a c a v a (A).
FIG 9 - 5
Electrical alternans is evident o n this l e a d II e l e c t r o c a r d i o g r a m from a 10-year-old m a l e
B u l l d o g with a l a r g e p e r i c a r d i a l effusion. N o t e a l s o the small v o l t a g e Q R S c o m p l e x e s a n d
sinus t a c h y c a r d i a (heart rate a b o u t 1 7 0 b e a t s / m i n ) .
right ventricle (Fig. 9-7). It must be remembered that the Mesothelioma may not cause discrete mass lesions and
volume of effusion is not the main determinant of hemo therefore may be indistinguishable from idiopathic pericar
dynamic compromise but rather the intrapericardial pres dial effusion.
sure. The R V and R A walls are often well visualized and Sometimes pleural effusion, a markedly enlarged left
may appear hyperechoic because of the surrounding fluid. atrium, a dilated coronary sinus, or persistent left cranial
Better visualization of the heartbase and mass lesions is gen vena cava can be confused with pericardial effusion. Careful
erally obtained before pericardiocentesis is performed. scanning from several positions helps i n differentiating these
Careful evaluation of all portions of the right atrium and conditions. Identification of the parietal pericardium in rela
auricle, right ventricle, ascending aorta, and pericardium tion to the echo-free fluid helps differentiate pleural from
itself is important to screen for neoplasia. The left cranial pericardial effusion. Because the pericardium is a relatively
parasternal (and transesophageal) transducer positions are strong ultrasound reflector, by progressively dampening the
especially useful. Some mass lesions are difficult to visualize. returning echo signals, pericardial echos are seen to be the
FIG 9 - 6
E c h o c a r d i o g r a p h i c e x a m p l e s of p e r i c a r d i a l effusion. A , Short-axis M - m o d e v i e w at mitral
v a l v e a n d c h o r d a l levels. Large echo-free (fluid) s p a c e s a r e seen on either side of the
heart; the right ventricular w a l l is c l e a r l y v i s u a l i z e d . The small t w o - d i m e n s i o n a l i m a g e
a b o v e the M - m o d e s h o w s the heart (transected b y the M - m o d e cursor line) s u r r o u n d e d by
p e r i c a r d i a l fluid (which a p p e a r s b l a c k o n the i m a g e ) . B , Long-axis t w o - d i m e n s i o n a l v i e w
from left p a r a s t e r n a l position d e p i c t i n g a l a r g e h e a r t b a s e tumor a n d p e r i c a r d i a l effusion
in a S c h n a u z e r . PE, P e r i c a r d i a l effusion; T, tumor; IV, left ventricle; A, a o r t a .
FIG 9 - 7
Diastolic c o m p r e s s i o n of the right atrial w a l l (arrow) is evident in this left c a u d a l four-
c h a m b e r e c h o c a r d i o g r a m from a 3-year-old f e m a l e S a i n t B e r n a r d with c a r d i a c t a m p o n
a d e . LA, Left atrium; LV, left ventricle; PE, p e r i c a r d i a l effusion; RA, right atrium; RV, right
ventricle.
last to disappear. Most pericardial fluid accumulates near cause tamponade and often resolve with management of the
the cardiac apex because the pericardium adheres more underlying condition.
tightly to the heartbase; there is usually little fluid behind the Dogs w i t h idiopathic pericardial effusion are initially
left atrium. Furthermore, evidence o f collapsed lung lobes or treated conservatively by pericardiocentesis. After an infec
pleural folds can often be seen within pleural effusion. tious cause is ruled out by pericardial fluid culture or cyto
logic analysis, a glucocorticoid is often used (e.g., oral
CLINICOPATHOLOGIC FINDINGS prednisone, 1 mg/kg/day, tapered over 2-4 weeks); however,
Hematologic and biochemical test results are generally n o n its efficacy i n preventing recurrent idiopathic pericardial
specific. The complete b l o o d count ( C B C ) may suggest effusion is u n k n o w n . Sometimes a 1- to 2-week course of a
inflammation or infection. Cardiac H S A may be associated broad-spectrum antibiotic is used concurrently. Periodic
with a regenerative anemia, increased numbers of nucleated reevaluation o f these dogs by radiography or echocardiogra
red blood cells and schistocytes, and thrombocytopenia. phy is advised to detect recurrence. Apparent recovery occurs
M i l d hypoproteinemia is seen in some cases of pericardial after one or two pericardial taps i n about half of affected
effusion. Cardiac troponin concentration or enzyme activi dogs. Cardiac tamponade recurs after a variable time span
ties may be increased as a result of ischemia or myocardial (days to years) i n other cases. Some cases o f recurrent effu
invasion; m i l d increases i n liver enzyme activities and pre sion are caused by mesothelioma, M H , or other neoplasia,
renal azotemia may occur secondary to heart failure. Pleural which may become evident on repeated echocardiographic
and peritoneal fluids in dogs and cats with cardiac tampon exam.
ade are usually modified transudates. Recurrent effusion that does not respond to repeated
Pericardiocentesis (discussed in the next section) usually pericardiocenteses and antiinflammatory therapy is usually
yields a hemorrhagic effusion; occasionally the fluid is sup treated by subtotal pericardiectomy. Removal o f the pericar
purative. Samples are submitted for cytologic analysis and d i u m ventral to the phrenic nerves allows pericardial fluid
saved for possible bacterial (or fungal) culture. Nevertheless, drainage to the larger absorptive surface of the pleural space.
differentiation of neoplastic effusions from benign hemor The less invasive technique o f thoracoscopic partial pericar
rhagic pericarditis is usually impossible on the basis o f cytol diectomy has also been used successfully to treat idiopathic
ogy alone. Reactive mesothelial cells within the effusion may and some cases of neoplastic pericardial effusion; biopsy
closely resemble neoplastic cells; furthermore, chemodecto samples of the mass or masses (if identified) can be obtained
mas and HSAs may not shed cells into the effusion. There through thoracoscopy. Lateral and subxiphoid approaches
fore identifying a mass lesion with echocardiography is have been described. Percutaneous balloon pericardiotomy
helpful for diagnosis. The effusions i n patients w i t h l y m also appears to be an effective and even less invasive option
phoma or M H typically are consistent with a modified tran for some cases. This procedure is performed under general
sudate. Neoplastic cells usually are easily identified in dogs anesthesia w i t h fluoroscopic guidance. It involves placing a
and cats with lymphoma and in dogs with M H . M a n y neo percutaneous sheath introducer through the chest wall into
plastic (and other non-inflammatory) effusions have a p H the pericardial space, then inserting a large balloon dilation
of 7.0 or greater, whereas inflammatory effusions generally catheter. The sheath is adjusted so that the balloon can be
have lower p H . However, there appears to be too m u c h positioned across the pericardial membrane; as the balloon
overlap for pericardial p H to be used as a reliable discrimina is inflated, it stretches the hole i n the parietal pericardium.
tor. Pericardial fluid culture is performed i f cytology and p H There is some concern that adhesions developing around a
suggest an infectious or inflammatory cause. In some patients small pericardiotomy opening may result in fluid reaccumu
fungal titers (e.g., coccidioidomycosis) or other serologic lation or increased risk o f constrictive pericarditis.
tests are helpful. It is currently unclear whether analysis o f Neoplastic pericardial effusions are also initially drained
pericardial fluid for cardiac troponins or other substances to relieve cardiac tamponade. Therapy may involve attempted
will allow better differentiation o f the underlying etiology. surgical resection (depending on tumor size and location)
or surgical biopsy, a trial of chemotherapy (based on biopsy
Treatment and Prognosis or clinicopathologic findings), or conservative therapy until
It is important to differentiate cardiac tamponade from episodes o f cardiac tamponade become unmanageable. Sur
other causes of right-sided C H F because the treatment is gical resection o f H S A is often not possible because o f the
very different. Positive inotropic drugs do not ameliorate the size and extent o f the tumor. Small tumors involving only
signs of tamponade; diuretics and vasodilators can further the tip o f the right auricle have been successfully removed;
reduce cardiac output and exacerbate hypotension and use o f a pericardial patch graft may allow resection o f larger
shock. Pericardiocentesis (discussed i n the next section) is masses involving the lateral R A wall. However, auriculec
the immediate treatment of choice, and it also provides diag tomy alone rarely results i n prolonged long-term survival.
nostic information. Most signs o f C H F resolve after pericar Partial pericardiectomy may prevent the recurrence of tam
dial fluid is removed. A dose or two o f a diuretic may be ponade. The increased potential for tumor dissemination
useful after pericardiocentesis i n some animals. Pericardial throughout the thoracic cavity does not appear to affect
effusions secondary to other diseases that cause C H F , con survival time, compared with pericardiocentesis alone, in
genital malformations, or hypoalbuminemia do not usually dogs with H S A or mesothelioma. The prognosis in dogs with
R A H S A treated with surgery alone or i n those i n which entire pericardial sac can be fatal, and partial pericardiec
treatment is declined by the owners is poor (median survival tomy may enhance intrathoracic dissemination o f certain
of 2-3 weeks); most dogs w i t h atrial H S A have objective tumors such as mesothelioma and carcinoma.
responses to multiagent chemotherapy ( V A C protocol) and
survival times o f 4 to 8 months. Survival time i n dogs with PERICARDIOCENTESIS
mesothelioma may be slightly longer than i n those with Pericardiocentesis should be done immediately in animals
H S A , but the overall prognosis is poor. with cardiac tamponade. Administration of diuretics or
Heartbase tumors (e.g., chemodectoma) tend to be slow vasodilators without pericardiocentesis may cause further
growing and locally invasive and have a l o w metastatic hypotension and cardiogenic shock. Pericardiocentesis is
potential. Partial pericardiectomy may prolong survival for a relatively safe procedure when performed carefully.
years. Percutaneous balloon pericardiotomy may also be an Removal of even a small volume o f pericardial fluid can
effective palliative procedure. Because o f local invasion, markedly decrease intrapericardial pressure in animals with
complete surgical resection is rarely possible; attempts at tamponade.
aggressive resection often result i n severe bleeding and death. Pericardiocentesis is usually done from the right side to
However, small, well-defined masses may be completely minimize the risk o f trauma to the lung (via the cardiac
resectable. Surgical biopsy is indicated i f chemotherapy is notch) and major coronary vessels (located mostly on the
contemplated. Effusion secondary to myocardial l y m p h o m a , left). The need for sedation depends on the clinical status
usually easily diagnosed cytologically, often responds to peri and temperament o f the animal. The animal is usually placed
cardiocentesis and chemotherapy. i n left lateral or sternal recumbency for more secure restraint,
Infectious pericarditis should be treated aggressively with especially i f the animal is weak or excitable. Sometimes
appropriate antimicrobial drugs, as determined by microbial needle pericardiocentesis can be successfully performed on
culture and sensitivity testing. Surgical therapy is likely to be the standing animal, but the risk o f injury increases i f the
more effective than continuous drainage with an indwelling patient suddenly moves. A n elevated echocardiography table
pericardial catheter, and it also allows removal o f penetrating with a large cutout can also be used with good success; the
foreign bodies. The prognosis is guarded. Even w i t h success animal is placed i n right lateral recumbency, and the tap is
ful elimination o f infection, epicardial and pericardial fibrin performed from underneath. A n advantage to this method
deposition may lead to constrictive pericardial disease. is that fluid moves to the right side with gravity; however, i f
Pure hemorrhage into the pericardial space, whether the adequate space is not available for wide sterile skin prepara
result of trauma, rupture o f the left atrium, or a systemic tion or needle/catheter manipulation, this approach is not
coagulopathy, should be removed i f signs o f cardiac tampon advised. Echo guidance can be used but is not necessary
ade exist. O n l y enough b l o o d to control signs o f tamponade unless the effusion is of very small volume or appears com
should be removed because continued drainage may predis partmentalized.
pose to further bleeding. The remaining b l o o d is usually A variety o f equipment can be used for pericardiocentesis.
resorbed through the pericardium (autotransfusion). Surgery A butterfly needle/catheter (19- to 21-gauge) or appropri
may be needed to stop continued bleeding or remove large ately long hypodermic or spinal needle attached to extension
clots. Dogs that survive an initial episode o f intrapericardial tubing is adequate i n emergency situations. A n over-the-
bleeding from rupture o f the left atrium still have a guarded needle catheter system is a safer alternative because it reduces
to poor prognosis because o f recurrent tearing o f the left the risk o f cardiopulmonary laceration during fluid aspira
atrium. Animals w i t h intrapericardial hemorrhage o f unclear tion. The catheter is chosen according to patient size (e.g.,
cause should be evaluated for a coagulation disorder. W h e n 12- to 16-gauge, 4- to 6-inch long catheter for large dogs,
trauma-induced intrapericardial hemorrhage persists i n an down to 18- to 20-gauge, 1- to 2-inch long catheter for
animal with n o r m a l hemostasis, surgical exploration is small dogs or cats). A few extra small side holes may be
indicated. smoothly cut (with sterile scissors) near the tip of larger
catheters to increase fluid removal rate. D u r i n g initial cath
Complications eter placement the extension tubing is attached to the needle
Complications o f diseases causing pericardial effusion relate stylet. After the catheter is advanced into the pericardial
to (1) sequelae o f the fluid accumulation itself (e.g., cardiac space, the extension tubing is reattached directly to the cath
tamponade and compression o f surrounding structures eter. W i t h all methods, a three-way stopcock is placed
[lung, esophagus, trachea]), (2) immediate effects o f associ between the tubing and a collection syringe.
ated inflammatory processes (e.g., arrhythmias, local and A n E C G monitor should be i n place during pericardio
systemic effects o f infectious agents, further fluid forma centesis because needle/catheter contact with the heart com
tion), (3) pericardial fibrosis and subsequent constrictive m o n l y induces ventricular arrhythmias. The skin is shaved
pericarditis, (4) sequelae o f neoplastic processes (e.g., further over a wide area o f the right precordium (from about the
bleeding, metastases, local invasion and obstruction, seed third to seventh intercostal spaces and from sternum to cos
ing o f the pleura, loss o f function), and (5) complications o f tochondral junction) and surgically prepared. Sterile gloves
pericardiocentesis (discussed i n the next section). Overly and aseptic technique are used for the procedure. The punc
aggressive surgical attempts to remove cardiac tumors or the ture site is located by palpating to identify the point at which
the cardiac impulse feels strongest (usually between the CONSTRICTIVE PERICARDIAL DISEASE
fourth and sixth ribs just lateral to the sternum). Local anes
thesia is necessary when using large catheters and recom Etiology and Pathophysiology
mended for needle pericardiocentesis. Lidocaine (2%) is Constrictive pericardial disease is diagnosed occasionally
infiltrated with sterile technique at the skin puncture site, i n dogs but only rarely i n cats. This condition occurs when
into underlying intercostal muscles, and into the pleura. thickening and scarring o f the visceral and/or parietal
A small stab incision is made i n the skin to allow catheter pericardium restrict ventricular diastolic expansion and
entry. prevent n o r m a l cardiac filling. Both ventricles are affected.
Intercostal vessels are located just caudal to each rib and Usually the entire pericardium is involved symmetrically.
must be avoided when entering the chest. Once the needle Fusion o f parietal and visceral pericardial layers obliterates
has penetrated the skin, the operator's assistant should apply the pericardial space i n some cases. In others the visceral
gentle negative pressure to the attached syringe as the oper layer (epicardium) alone is involved. A small amount o f
ator slowly advances the needle toward the heart. It is some pericardial effusion (constrictive-effusive pericarditis) may
times helpful to aim the tip o f the needle toward the animal's be present.
opposite shoulder. The tubing is observed so that fluid w i l l Increased fibrous connective tissue and variable amounts
be seen as soon as it is aspirated. Pleural fluid (usually straw of inflammatory and reactive pericardial infiltrates are seen
colored) may enter the tubing first and is drained as m u c h on histopathologic exam. A l t h o u g h the etiology o f constric
as possible. The pericardium creates increased resistance to tive pericardial disease is often u n k n o w n , acute inflamma
needle advancement and may produce a subtle scratching tion with fibrin deposition and possibly varying degrees of
sensation. Gentle pressure is used to advance the needle pericardial effusion are thought to precede its development.
through the pericardium. A loss o f resistance may be noted Some cases i n dogs are attributable to recurrent idiopathic
with needle penetration, and fluid aspirated into the tubing hemorrhagic effusion, infectious pericarditis (resulting
usually appears dark red. If the needle comes into contact from actinomycosis, mycobacteriosis, coccidioidomycosis),
with the heart, a marked scratching or tapping sensation is a metallic foreign body i n the pericardium, tumors, and
usually felt, the needle may move w i t h the heartbeat, and idiopathic osseous metaplasia and/or fibrosis o f the
ventricular premature complexes are often provoked. The pericardium.
needle should be retracted slightly i f cardiac contact occurs. In advanced constrictive pericardial disease, ventricular
It is important to avoid excessive needle m o t i o n w i t h i n the filling is limited essentially to early diastole, before ventricu
chest. W h e n a catheter system is used, after the needle/stylet lar expansion is abruptly curtailed. A n y further ventricular
is well within the pericardial space, the catheter is advanced, filling is accomplished only at high venous pressures. C o m
the stylet removed, and the extension tubing attached to the promised filling reduces cardiac output, and compensatory
catheter. Initial fluid samples are saved for cytologic exam mechanisms o f heart failure cause fluid retention, tachycar
and possible culture, and then as m u c h fluid as possible is dia, and vasoconstriction.
aspirated.
Pericardial effusion usually appears quite hemorrhagic. Clinical Features
It can be distressing to see dark, bloody fluid being aspirated Middle-aged, large- to medium-breed dogs are most often
from near the heart, but pericardial fluid can be differenti affected. Males and G e r m a n Shepherd Dogs may be at higher
ated from intracardiac b l o o d i n several ways. Unless the fluid risk. Some dogs have a history o f pericardial effusion. C l i n i
is caused by very recent pericardial hemorrhage, it will not cal signs o f right-sided C H F predominate. A b d o m i n a l dis
clot. (A few drops can be placed on the table or into a serum tention (ascites), tachypnea or labored breathing, tiring,
tube to check.) The P C V o f pericardial fluid is usually m u c h syncope, weakness, and weight loss are c o m m o n complaints.
lower than that o f peripheral b l o o d (except i n some dogs These signs may develop over weeks to months. Ascites and
with H S A ) ; also, the supernatant is xanthochromic (yellow jugular venous distention are the most consistent clinical
tinged) when spun i n a hematocrit tube. As the pericardial findings, as i n dogs w i t h cardiac tamponade. Weakened
fluid is drained, the animal's E C G complexes increase i n femoral pulses and muffled heart sounds are also typical. A
amplitude, tachycardia diminishes, and the patient often diastolic pericardial knock sound, resulting from abrupt
takes a deep breath and appears more comfortable. deceleration o f ventricular filling i n early diastole, has been
described but is not often identified i n dogs. A systolic
Complications m u r m u r or click, probably caused by valvular disease rather
Complications o f pericardiocentesis include (1) cardiac than the pericardial pathology, or a diastolic gallop sound
injury or puncture causing arrhythmias (the most c o m m o n may be heard.
complication, although usually self-limiting when the needle
is withdrawn), (2) lung laceration causing pneumothorax Diagnosis
and/or hemorrhage, (3) coronary artery laceration with The diagnosis o f constrictive pericardial disease may be dif
myocardial infarction or further bleeding into the pericardial ficult. Typical radiographic findings include m i l d to moder
space, and (4) dissemination o f infection or neoplastic cells ate cardiomegaly, pleural effusion, and caudal vena cava
into the pleural space. distention. Reduced cardiac m o t i o n may be evident on fluo-
roscopy. Echocardiographic changes i n dogs w i t h constric threatening. Tachyarrhythmias are another complication of
tive pericardial disease may be subtle; suggestive findings surgery. In the postoperative period, a diuretic and possibly
include diastolic flattening of the left ventricular freewall and an angiotensin-converting enzyme inhibitor (ACEI) may be
abnormal septal motion. The pericardium may appear thick helpful. Positive inotropic and vasodilating drugs are not
ened and intensely echogenic, but differentiating this from usually indicated. Constrictive pericardial disease is progres
normal pericardial echogenicity may be impossible. Possible sive and, without successful surgical intervention, ultimately
E C G abnormalities include sinus tachycardia, P-wave pro fatal.
longation, and small Q R S complexes.
A C V P >15 m m H g is c o m m o n . Intracardiac hemody
namic measurements are most useful diagnostically. In addi CARDIAC TUMORS
tion to high mean atrial and diastolic ventricular pressures,
the atrial pressure waveform shows a prominent y descent Etiology and Pathophysiology
(during ventricular relaxation). This is i n contrast to cardiac Echocardiography has made the antemortem diagnosis of
tamponade, wherein the y descent is diminished. D u r i n g cardiac tumors more c o m m o n , although the overall preva
tamponade, ventricular diastolic expansion immediately lence of such neoplasms is low. Some cardiac tumors cause
raises intrapericardial pressure and impairs caval flow into severe clinical signs, whereas others are diagnosed fortu
the right atrium, thus preventing the n o r m a l early diastolic itously. Dogs with cardiac tumors tend to be middle-aged
decrease in C V P (y descent), although flow into the right and older. M o r e than 85% of affected dogs are between 7 and
atrium (and x descent on atrial waveform) continues during 15 years of age; however, very o l d dogs (>15 years) have a
ventricular contraction. W i t h constrictive pericardial disease, surprisingly low prevalence. Reproductive status influences
filling pressure is low only i n early diastole (during the time the relative risk for cardiac tumors i n dogs, despite a similar
of y descent). Another classic finding w i t h constrictive peri frequency of occurrence i n males and females overall. Neu
cardial disease is an early diastolic dip i n ventricular pres tered dogs have a greater relative risk, especially spayed
sure, followed by a mid-diastolic plateau, but this is not females, which have a risk that is four to five times greater
consistently seen in dogs. Results of angiocardiography may compared w i t h that of intact females. Intact and neutered
be normal, or they may show atrial and vena caval enlarge males also have greater risk than intact females. Certain
ment with increased endocardial-pericardial distance. breeds of dog have a higher prevalence of cardiac tumor
compared with the general population (Table 9-1). The age
Treatment and Prognosis distribution of cats with cardiac tumors is different from that
Therapy for constrictive pericardial disease consists of surgi of dogs; about 28% are 7 years old or younger. It is unknown
cal pericardiectomy. This is more successful when only the whether reproductive status affects relative risk for cardiac
parietal pericardium is involved. Constrictive pericardial tumors i n cats.
disease involving the visceral layer requires epicardial strip The most c o m m o n cardiac tumor i n dogs is H S A . Most
ping. This procedure increases the surgical difficulty and are located i n the right atrium and/or right auricle; some also
associated complications. Pulmonary thrombosis is report infiltrate the ventricular wall. H S A s usually are associated
edly a c o m m o n postoperative complication and can be life- w i t h hemorrhagic pericardial effusion and cardiac tampon-
TABLE 9-
Modified from W a r e W A , Hopper DL: Cardiac tumors in dogs: 1 9 8 2 - 1 9 9 5 , J Vet Intern Med 13:95, 1999.
CI, Confidence interval.
ade (see p. 158). Metastases are c o m m o n by the time o f Auscultation findings vary. Arrhythmias or muffled heart
diagnosis. Golden Retrievers, German Shepherd Dogs, Afghan sounds (if large pericardial effusion is present) are c o m m o n .
Hounds, Cocker Spaniels, English Setters, and Labrador Occasionally a m u r m u r is caused by neoplastic obstruction
Retrievers, among others, are at higher risk for this tumor. of intracardiac b l o o d flow, but murmurs associated w i t h
Masses at the heartbase are the second most frequently unrelated disease (e.g., degenerative mitral regurgitation) are
reported cardiac tumor i n dogs. They are usually neoplasms more c o m m o n . Auscultation findings may be normal.
of the chemoreceptor aortic bodies (chemodectoma, aortic
body tumors); ectopic thyroid or parathyroid, or mixed- Diagnosis
cell-type tumors also occur here. Heartbase tumors tend to Radiographic findings are also quite variable. The cardiac
be locally invasive around the root o f the aorta and sur silhouette may be n o r m a l or show an unusual bulge, a mass
rounding structures; metastases to other organs occur rarely. effect adjacent to the heart, or a globoid cardiac silhouette
Chemodectomas are reported more frequently i n brachyce compatible w i t h pericardial effusion. Intrapericardial masses
phalic dogs (specifically Boxers, Boston Terriers, and B u l l are obscured by pericardial effusion. Other radiographic
dogs) but affect individuals o f other breeds as well. Clinical findings that occur secondary to impaired cardiac filling
signs associated with heartbase tumors are usually related to include pleural effusion, evidence o f p u l m o n a r y edema, w i d
pericardial effusion and cardiac tamponade. ening o f the caudal vena cava (and/or p u l m o n a r y veins),
Mesothelioma occurs sporadically; there may be geo hepatomegaly, and ascites. Dorsal deviation o f the trachea
graphical variation i n its prevalence. Other primary tumors and increased perihilar opacity are seen i n some dogs w i t h
involving the heart are rare i n dogs but include myxoma, heartbase tumors. Evidence o f p u l m o n a r y metastases is
various types o f sarcoma, and other neoplasms. Most cases found w i t h some p r i m a r y or secondary (metastatic) cardiac
involve right-heart structures. Metastatic tumors, including neoplasms.
lymphoma, other sarcomas, and various carcinomas, may E C G findings sometimes show abnormalities suggesting
involve the heart as well. M H may involve the heart or peri the location and sequelae o f the underlying disease, such as
cardium; most affected dogs are either Golden Retrievers, chamber enlargement, pericardial effusion, and various
Labrador Retrievers, Rottweilers, or Greyhounds. M i l d peri arrhythmias. Echocardiography can depict cardiac masses
cardial effusion, without overt signs o f cardiac tamponade, and determine the presence or absence of pericardial effu
co-exists with pleural and abdominal effusion. sion as well as secondary changes i n cardiac chamber size,
Lymphoma is the most c o m m o n cardiac t u m o r i n cats. shape, and ventricular function. Doppler techniques allow
Various (mostly metastatic) carcinomas are the next most assessment o f associated b l o o d flow abnormalities. Heart-
c o m m o n cardiac neoplasms i n cats. H S A is u n c o m m o n ; base tumors that extend into the pericardial space are easier
other tumors (such as aortic body tumor, fibrosarcoma, to see when there is pericardial effusion, just as intracardiac
rhabdomyosarcoma) are reported only rarely i n cats. masses are accentuated by the echolucent intracardiac b l o o d
Cardiac tumors cause several pathophysiologic abnor surrounding them (Fig. 9-8). The left cranial parasternal
malities, depending on their location and size. Ultimately, transducer position may be especially useful i n evaluating
the patient's clinical signs can be referred to one or a c o m the ascending aorta, right auricle, and surrounding struc
bination of these. M a n y tumors impede cardiac filling by tures. Echocardiographic assessment of the tumor's location,
causing pericardial effusion and cardiac tamponade (dis size, attachment (pedunculated or broad based), and extent
cussed earlier). A n intrapericardial mass can itself externally (superficial or deeply invading adjacent myocardium) may
compress the heart as well as cause pericardial effusion. help in determining whether surgical resection or biopsy is
Alternatively, a tumor that grows i n an intracardiac location possible. Visualizing a suspected mass lesion in more than
can physically obstruct cardiac inflow or outflow. Myocardial one echocardiographic plane helps verify it and prevent the
tumor infiltration or secondary ischemia can disrupt the misinterpretation o f artifacts.
cardiac rhythm and impair contractility. If the tumor is small Pericardial fluid analysis is recommended, although
or has not yet markedly impaired cardiac function, clinical definitive diagnosis o f neoplasia cannot usually be made on
signs may be absent. the basis o f cytologic findings alone (see p. 163). Cardiac
l y m p h o m a or M H is more likely to be diagnosed o n pericar
Clinical Features dial fluid cytology. Nevertheless, visualization o f a cardiac
Signs of right-sided C H F result from b l o o d flow obstruction mass using echocardiography, computed tomography, pneu
within the right atrium or ventricle or from cardiac tampon mopericardiography, angiography, or another modality is
ade. Syncope, weakness associated w i t h exertion, and other usually necessary for diagnosis. Hematologic and serum bio
low output signs also result from cardiac tamponade, b l o o d chemical tests are generally nonspecific i n dogs and cats with
flow obstruction, arrhythmias, or impaired myocardial func cardiac tumors. Cardiac enzyme activities or circulation tro
tion secondary to cardiac tumors. Tachyarrhythmias o f any p o n i n concentrations may be high because o f ischemia or
type may also occur; intracardiac conduction disturbances myocardial invasion; m i l d increases i n serum alanine a m i
sometimes result from tumor infiltration. Lethargy or col notransferase activity and azotemia may occur with C H F .
lapse may relate to bleeding tumors (e.g., H S A ) present i n H S A is often associated w i t h a regenerative anemia, increased
extracardiac locations as well. number o f nucleated red b l o o d cells and schistocytes, leuko-
months. L y m p h o m a and M H should be treated using stan
dard protocols.
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C H A P T E R 10
Heartworm Disease
the new host when the mosquito takes another blood meal.
CHAPTER OUTLINE
L larvae migrate subcutaneously within the new host,
3
BOX 10-1
repeat adulticide therapy is guided by the patient's overall heartworms, although it is somewhat effective against male
health, performance expectations, and age. Complete w o r m worms and may sterilize adult female worms.
kill is probably not necessary; even i f some adult heartworms
survive, pulmonary arterial disease improves considerably Postadulticide Pulmonary Thromboembolic
after adulticide therapy. Complications
Thiacetarsamide is an older adulticide agent that may P u l m o n a r y arterial disease worsens from 5 to 30 days after
still be available. It has no advantages and several disadvan adulticide therapy and is especially severe i n previously
tages compared w i t h melarsomine. Likewise, the use o f other symptomatic dogs. It occurs because dead and dying worms
drugs, such as levamisole or stibophen, as adulticides is not lead to thrombosis and p u l m o n a r y artery obstruction, w i t h
recommended. Levamisole does not consistently k i l l adult exacerbation o f platelet adhesion, m y o i n t i m a l proliferation,
villous hypertrophy, granulomatous arteritis, perivascular dogs with occult H W D . Clinical manifestations of heart-
edema, and hemorrhage. P u l m o n a r y b l o o d flow obstruction w o r m pneumonitis include a progressively worsening cough,
and increased vascular resistance further strain the right crackles heard on auscultation, tachypnea or dyspnea, and
ventricle and increase oxygen demand. Poor cardiac output, sometimes cyanosis, weight loss, and anorexia. Eosinophilia,
hypotension, and myocardial ischemia may result. Severe basophilia, and hyperglobulinemia are inconsistent findings.
ventilation-perfusion mismatch may result from pulmonary Heartworm A g tests are usually positive. Diffuse interstitial
hypoperfusion, hypoxic vasoconstriction and bronchocon- and alveolar infiltrates, especially i n the caudal lobes, are
striction, pulmonary inflammation, and fluid accumulation. c o m m o n on radiographs; these can be similar to those in
Pulmonary thromboembolization is most likely to occur 7 dogs with pulmonary edema or blastomycosis. There is often
to 17 days after adulticide therapy. As expected, the caudal no clinically relevant cardiomegaly or pulmonary lobar
and accessory lung lobes are most c o m m o n l y and severely artery enlargement. Tracheal wash cytology usually reveals
affected. a sterile eosinophilic exudate with variable numbers of
Depression, fever, tachycardia, tachypnea or dyspnea, and well-preserved neutrophils and macrophages. Therapy with
cough are c o m m o n clinical signs. Hemoptysis, right-sided a glucocorticoid (prednisone, 1-2 mg/kg/day by mouth i n i
C H F , collapse, or death may also occur. Interstitial and alve tially) usually results i n rapid and marked improvement.
olar pulmonary inflammation and fluid accumulation cause Prednisone may be continued as needed, i n gradually tapered
p u l m o n a r y crackles on auscultation. Focal lung consolida doses (to 0.5 mg/kg every other day) and does not appear to
tion may cause areas of muffled lung sounds. Thoracic radio adversely affect the adulticide efficacy of melarsomine.
graphs show patchy alveolar infiltrates w i t h air bronchograms, Pulmonary eosinophilic granulomatosis is an u n c o m m o n
especially near the caudal lobar arteries. Thrombocytopenia syndrome that has been associated with H W D , although
or neutrophilia with a left shift may be seen on C B C . some affected dogs have negative heartworm tests. Its patho
Treatment of pulmonary thromboembolism includes genesis is thought to involve a hypersensitivity reaction to
strict rest (i.e., cage confinement) and glucocorticoid therapy heartworm A g or i m m u n e complexes, or both. Pulmonary
to reduce pulmonary inflammation (prednisone, 1 to 2 mg/ granulomas comprise a mixed mononuclear and neutro
kg/day by m o u t h initially, then tapering). Supplemental philic cell population, with many eosinophils and macro
oxygen therapy is recommended to reduce hypoxia phages. A proliferation of bronchial smooth muscle within
mediated pulmonary vasoconstriction. A bronchodilator granulomas and an abundance of alveolar cells i n the sur
(e.g., oral aminophylline, 10 mg/kg I M or I V q8h; or oral rounding area are c o m m o n findings. Lymphocytic and
theophylline, 9 mg/kg q6-8h), judicious fluid therapy (if eosinophilic perivascular infiltrates may also occur. Eosino
there is evidence of cardiovascular shock), and cough sup philic granulomas involving the l y m p h nodes, trachea,
pressants may be useful. Antibiotics have been given empir tonsils, spleen, G I tract, and the liver or kidneys may occur
ically, but they are of questionable benefit unless there is concurrently. The clinical signs of pulmonary eosinophilic
evidence of concurrent bacterial infection. Hydralazine has granulomatosis are similar to those of eosinophilic pneumo
reduced pulmonary vascular resistance experimentally, and nitis. Clinicopathologic findings variably include leukocyto
some dogs seem to respond clinically to diltiazem. Systemic sis, neutrophilia, eosinophilia, basophilia, monocytosis, and
hypotension and tachycardia must be avoided when using a hyperglobulinemia. In some cases an exudative, primarily
vasodilator. A s p i r i n is not recommended because there is no eosinophilic pleural effusion develops. Radiographic find
convincing evidence that it prevents thrombosis or reduces ings include multiple pulmonary nodules of varying size and
pulmonary arteritis. Heparin (200 to 400 U / k g sodium location with mixed alveolar and interstitial pulmonary
heparin administered subcutaneously q8h, or 50 to 100 U / k g infiltrates; hilar and mediastinal lymphadenopathy may also
calcium heparin administered subcutaneously q8-12h) may be present. Eosinophilic granulomatosis is treated initially
be considered for severe cases of thromboembolism. with prednisone (1 to 2 mg/kg q l 2 h ) ; however, additional
However, excessive bleeding is a possible serious adverse cytotoxic therapy may be needed as well. N o t all dogs respond
effect. Low-molecular-weight heparin might provide a safer completely, and relapses are c o m m o n , especially when
alternative to unfractionated heparin, but definitive recom therapy is reduced or discontinued. The response to i m m u
mendations are not yet available. nosuppressive drugs after relapse may be poor. Therapy
Endothelial changes i n survivors regress w i t h i n 4 to 6 for adult heartworms is given when pulmonary disease
weeks. Pulmonary hypertension and arterial disease, along improves.
with radiographic changes, d i m i n i s h over the next several Severe pulmonary arterial disease is more c o m m o n in
months. Eventually, pulmonary arterial pressure and the dogs with long-standing heartworm infection, in those with
contour of the proximal pulmonary arteries normalize, many adult worms, and i n active dogs. Severe cough, exercise
although some fibrosis may remain. intolerance, tachypnea or dyspnea, episodic weakness,
syncope, weight loss, and ascites are c o m m o n clinical signs;
Treatment of Dogs with Complicated HWD death sometimes occurs. Typical radiographic findings
include markedly enlarged, tortuous, and blunted pulmo
PULMONARY COMPLICATIONS nary arteries. P u l m o n a r y parenchymal infiltrates leading to
Immune-mediated pneumonitis occurs i n some dogs. Aller hypoxemia are seen i n some cases; these are treated with
gic or eosinophilic pneumonitis develops i n a m i n o r i t y of prednisone as described in the preceding paragraph. T h r o m -
bocytopenia and hemolysis may occur i n dogs w i t h severe with pulmonary hypertension, lead to the development of
pulmonary arterial disease and thromboembolism. M o n i right-sided congestive signs and poor cardiac output.
toring of platelet count and packed cell volume is recom Clinicopathologic findings may include microfilaremia,
mended. D I C develops i n some dogs. Conservative therapy Coombs-negative fragmentation hemolytic anemia (from
with oxygen, prednisone, and a bronchodilator (e.g., theoph red b l o o d cell trauma), azotemia, abnormal liver function,
ylline), as for postadulticide pulmonary thromboembolism, and increased liver enzyme activities; D I C is c o m m o n . Intra
should help improve oxygenation and reduce pulmonary vascular hemolysis results i n hemoglobinemia and hemo
artery pressures. Alternate-day, low-dose prednisone (e.g., globinuria. Thoracic radiographs indicate right heart and
0.5 mg/kg orally) is thought to have beneficial antiinflam pulmonary artery enlargement. The E C G usually suggests
matory effects, although long-term use of high corticoste R V enlargement. Ventricular or supraventricular premature
roid doses may reduce pulmonary b l o o d flow, increase risk complexes are c o m m o n . Echocardiography reveals a mass of
of thromboembolism, and inhibit vascular disease resolution. worms entangled at the tricuspid valve and i n the right
After the animal's condition is stabilized, the alternative atrium and venae cavae (Fig. 10-3). R V dilation and hyper
melarsomine protocol may be used. Use o f aspirin is dis trophy, paradoxical septal m o t i o n , and a small left ventricle
couraged, especially with hemoptysis. Prophylactic antibiot are also typical.
ics are sometimes recommended because o f the potential M o s t dogs die w i t h i n 24 and 72 hours as a result o f car
for secondary bacterial infections i n devitalized pulmonary diogenic shock complicated by metabolic acidosis, D I C , and
tissue. anemia unless they are aggressively treated. W o r m s must be
surgically removed from the vena cava and right atrium
RIGHT-SIDED CONGESTIVE as soon as possible. The dog is lightly sedated, i f necessary,
HEART FAILURE and local anesthesia is used. A right jugular venotomy w i t h
Severe pulmonary arterial disease and pulmonary hyperten the dog restrained i n left lateral recumbency is the usual
sion can cause C H F . Jugular venous distention or pulsation, approach. L o n g alligator forceps, an endoscopic basket
ascites, syncope, exercise intolerance, and arrhythmias are retrieval instrument, or horsehair brush device are used to
typical signs. Pleural or pericardial effusion as well as other grasp and withdraw the heartworms through the jugular
signs secondary to pulmonary arterial and parenchymal vein incision. The instrument is gently passed d o w n the vein
disease may also occur. Treatment is the same as for dogs into the right atrium; repositioning o f the animal's head and
with severe pulmonary arterial disease, with the addition of neck may be necessary to pass the instrument beyond the
furosemide (e.g., 1-2 mg/kg/day), an angiotensin-converting thoracic inlet. The goal is to retrieve as many worms as pos
enzyme inhibitor (ACEI; e.g., enalapril 0.5 mg/kg q12-24 h sible; generally, five to six unsuccessful attempts i n sequence
by mouth), and a sodium-restricted diet. Use of digoxin i n is the end point. Resistance to instrument withdrawal from
these cases is controversial; pimobendan has not been evalu the vein may occur i f too many worms are grasped at once
ated i n this setting but could be useful. or a cardiovascular structure is grabbed by forceps. Survival
rates o f 50% to 80% have been reported for dogs undergoing
CAVAL SYNDROME this procedure. Another technique that has been used i n very
The (vena) caval syndrome occurs i n heavily infected animals small dogs is right auricular cannulation performed via a
when venous inflow to the heart is obstructed by a mass o f thoracotomy to remove worms. (See Suggested Readings for
worms, leading to low-output cardiovascular shock. Other more information o n this technique.)
terms for this condition include postcaval syndrome, acute Cautious intravenous (IV) fluid administration with
hepatic syndrome, liver failure syndrome, dirofilarial hemoglo other supportive care is provided during and after surgical
binuria, and vena cava embolism. As the heartworm burden w o r m removal. Central venous pressure monitoring helps
increases, adult worms migrate to the right atrium and the clinician assess the effectiveness o f w o r m removal and
caudal vena cava from their preferred locations i n the p u l fluid therapy. Treatment w i t h a positive inotrope or sodium
monary artery and right ventricle. Factors other than w o r m bicarbonate is usually not necessary, but a broad spectrum
burden alone are probably also involved i n the development antibiotic is recommended. M o n i t o r i n g for anemia, t h r o m
of the caval syndrome, including degree of pulmonary bocytopenia, D I C , and organ dysfunction is important;
hypertension. Caval syndrome occurs more often i n geo treatment is given as indicated. Severe pulmonary thrombo
graphic areas where H W D is enzootic; up to 20% o f dogs embolism and renal or hepatic failure are associated w i t h
with H W D are estimated to be affected i n some areas. poor outcome. Dogs that survive acute caval syndrome can
Most dogs that develop caval syndrome have no history be treated w i t h adulticide w i t h i n a few weeks after stabiliza
of heartworm-related signs. Acute collapse is c o m m o n , often tion to eliminate remaining worms. The use o f a flexible
accompanied by anorexia, weakness, tachypnea or dyspnea, alligator forceps w i t h fluoroscopic or transesophageal echo
pallor, hemoglobinuria, and bilirubinuria. A tricuspid guidance has been advocated as a way to reduce the w o r m
insufficiency murmur, jugular distention and pulsations, burden i n the m a i n pulmonary artery and lobar branches
weak pulses, a l o u d and possibly split S , and a cardiac gallop
2 before adulticide therapy. This can reduce the risk for post
rhythm are often found. Sometimes coughing or hemoptysis adulticide thromboembolism i n heavily infected dogs,
and ascites occur. Tricuspid insufficiency and partial occlu although technical issues and the need for heavy sedation
sion of R V inflow caused by a mass of worms, i n conjunction or anesthesia may be limitations.
FIG 1 0 - 3
E c h o c a r d i o g r a m from a 9-year-old m a l e m i x e d - b r e e d d o g with c a v a l s y n d r o m e . The
transducer is in the right p a r a s t e r n a l short-axis position at a level just b e l o w the a o r t a . The
i m a g e s h o w s the e n l a r g e d a n d h y p e r t r o p h i e d right ventricle a n d its outflow tract. M a n y
s m a l l , bright p a r a l l e l e c h o e s a r e a p p a r e n t in the b o d y of the right ventricle (RV) in this
d i a s t o l i c f r a m e a n d a r e c a u s e d b y a c l u m p of h e a r t w o r m s e n t a n g l e d in the tricuspid v a l v e
a p p a r a t u s . N o t e a l s o the w i d e n e d m a i n p u l m o n a r y artery segment t y p i c a l of p u l m o n a r y
h y p e r t e n s i o n (small arrows). The interventricular septum is flattened a n d p u s h e d t o w a r d
the left ventricle (LV) b y h i g h right ventricular pressure (open arrow). The LV itself is small
b e c a u s e the h e a r t w o r m s obstruct b l o o d f l o w through the right heart. P A , M a i n p u l m o n a r y
artery.
cold winters and reinstituted 1 m o n t h before mosquito some cats recover, this phase is fatal i n others. Sudden death
season in the spring. Before beginning (or restarting) D E C can occur.
treatment, dogs must be negative for microfilariae (see In cats that survive, the acute inflammation subsides. Vas
p. 170). Puppies 6 months of age and older also should be cular injury leads to myointimal proliferations and muscular
tested for microfilariae. A n n u a l microfilaria tests are strongly hypertrophy i n affected pulmonary arteries. These lesions
recommended, even i n areas where the drug is given year- tend to be focal. This may be why clinically relevant p u l m o
round. To be effective, D E C must be given daily. If a lapse i n nary hypertension, secondary R V hypertrophy, and right-
D E C administration of <6 weeks has occurred, one dose o f sided C H F are u n c o m m o n i n cats. Dead and degenerating
a monthly preventive drug should restore protection. For worms cause recrudescence of pulmonary inflammation and
longer lapses, monthly chemoprophylaxis should be extended thromboembolism. Disease is most severe i n the caudal lung
for a year. Microfilaria-positive dogs should not be given lobes. Caudal lobar arterial obstruction can be caused by
D E C . Adverse reactions of variable severity may occur, espe villous proliferation, thrombi, or dead heartworms. Adult
cially in dogs with higher numbers of microfilariae. These worms are more likely to obstruct the p u l m o n a r y arteries of
may include lethargy progressing to vomiting, diarrhea, and cats (compared with dogs) by virtue of their relative size. The
bradycardia; some patients develop hypovolemic shock, bronchopulmonary circulation i n cats is thought to prevent
with tachypnea, tachycardia, recumbency, hypersalivation, pulmonary infarction.
and eventually death. I V dexamethasone (at least 2 mg/kg), Vomiting is c o m m o n i n cats with H W D . The mechanism
fluids, and other supportive measures have been used to treat for this may involve central stimulation (of the chemorecep
the hypovolemia and shock; atropine is used for severe bra tor trigger zone) by inflammatory mediators. Antiinflamma
dycardia. Dogs with this microfilaria-induced reaction that tory doses of a glucocorticoid often control this sign.
Infected cats generally have fewer adult worms than do graphs, and echocardiography is used. Microfilaria testing is
infected dogs. Heartworms mature more slowly, fewer only occasionally helpful.
numbers o f infective larvae mature to adults, and the adult
life span is shorter i n cats. However, live worms can persist TESTS FOR HEATWORM DISEASE
for 2 to 3 years. Heartworm-infected cats generally have IN CATS
fewer than eight adult worms i n the R V and pulmonary Serologic Tests
arteries, and most cats have only one or two worms. Never Feline heartworm A b tests are often used for screening;
theless, even one adult w o r m can cause death. Unisex infec however, although they are fairly sensitive, they are not spe
tion is c o m m o n . M o s t cats have no or only a brief period o f cific for adult heartworms. The ELISA-based A g tests are
microfilaremia. Aberrant w o r m migration is also more highly specific i n detecting adult heartworm infection, but
c o m m o n i n cats than dogs and complicates necropsy confir their sensitivity depends on the gender, age, and number of
mation o f infection. Aberrant sites have included the brain, worms. Serologic test results may be negative early in the
subcutaneous nodules, body cavities, and occasionally a infection, although the cat may have clinical signs. A g test
systemic artery. results are negative during the first 5 months after infection
and may be variably positive at 6 to 7 months; infections
Clinical Features w i t h mature female worms should be detected after 7 months.
Most reported cases have occurred i n cats 3 to 6 years o f age, False-negative heartworm A g test results are more likely in
although cats o f any age are susceptible. Domestic Shorthair cats because w o r m burden is typically low; also, a longer time
cats seem to be overrepresented. Male cats are overrepre is required for cats to become A g positive. Acute death and
sented i n some but not all studies. Cats living strictly indoors severe clinical signs may occur i n Ag-negative cats. Further
are not protected from infection. Infection is self-limiting i n more, postmortem diagnosis may be difficult i f the worms
some cats. Some researchers have noted an increase i n H W D are located i n distal pulmonary arteries or aberrant sites.
diagnosis during fall and winter, presumably after infection Occasionally, a positive A g test result occurs but no worms
i n the spring, but others have found fewer cases i n the latter are found on postmortem examination. Spontaneous w o r m
part of the year. death, worms overlooked during pulmonary evaluation, and
Clinical signs are variable and may be transient or n o n ectopic infection are likely reasons for this finding.
specific. Respiratory signs occur i n more than half o f symp
tomatic cats, especially dyspnea and/or paroxysmal cough, RADIOGRAPHY
w h i c h can m i m i c feline asthma. Other client complaints Radiographic findings that suggest H W D include pulmo
include lethargy, anorexia, vomiting, syncope, other neuro nary artery enlargement with or without visible tortuosity
logical signs, and sudden death. Vomiting, usually unrelated and pruning, R V or generalized cardiac enlargement, and
to eating, is c o m m o n and may be the only sign i n some diffuse or focal pulmonary bronchointerstitial infiltrates
infected cats. Severe clinical signs are usually associated with (Fig. 10-4). P u l m o n a r y hyperinflation is sometimes evident.
the arrival o f L worms i n the pulmonary arteries (and
5 The pulmonary artery and right heart changes are typically
H A R D surrounding the death o f some L ) and also w i t h
5 more subtle i n cats than dogs. Radiographic findings may
thromboembolism after the death o f one or more adult not correlate w i t h clinical signs or results o f serologic tests.
worms. The sudden onset o f neurologic signs, with or Pulmonary artery distention may be greatest within the first
without anorexia and lethargy, is c o m m o n during aberrant 7 months of infection; some regression may occur subse
w o r m migration. Such signs include seizures, dementia, quently, especially i n cranial arteries. The D V view is best for
apparent blindness, ataxia, circling, mydriasis, and hyper- evaluating caudal lobar arteries; these are more frequently
salivation. O n l y rarely do cardiopulmonary and neurologic abnormal o n radiographs. The right caudal lobar artery may
signs co-exist. A l t h o u g h heartworms can cause significant be more prominent; however, a left caudal pulmonary artery
pulmonary disease, some cats have no clinical signs. 1 . 6 multiplied by the w i d t h o f the ninth rib at the ninth
Auscultation may reveal pulmonary crackles, muffled intercostal space was reported as the most discriminating
lung sounds (either from pulmonary consolidation or pleural radiographic finding for separating heartworm-infected
effusion), tachycardia, and sometimes a cardiac gallop sound from non-infected cats (Schafer et al., 1995). The main p u l
or m u r m u r . Pleural effusion caused by right-sided C H F , as monary artery segment is not usually visible on D V or ven
well as syncope, is less c o m m o n i n cats than i n dogs w i t h trodorsal views i n cats because its location is more medial
H W D . However, chylothorax and ascites are occasionally than it is i n dogs. Marked right heart enlargement is more
associated w i t h H W D i n cats, and pneumothorax occurs likely when signs o f right-sided C H F (e.g., pleural effusion)
rarely. There are sporadic reports o f caval syndrome i n cats. exist. Thoracocentesis may be necessary to evaluate the heart,
Peracute respiratory distress, ataxia, collapse, seizures, pulmonary vasculature, and lung parenchyma when there
hemoptysis, or sudden death may occur. is pleural effusion. Ascites occurs i n some cats with H W D ,
but it is rare i n cats with heart failure resulting from
Diagnosis cardiomyopathy.
Definitive diagnosis is more difficult i n cats than dogs. A Both heartworm-associated pneumonitis as well as pul
combination o f serologic testing (see p. 170), thoracic radio monary thromboembolism produce pulmonary infiltrates;
FIG 1 0 - 4
Lateral (A) a n d d o r s o v e n t r a l (B) r a d i o g r a p h s from a c a t with h e a r t w o r m d i s e a s e . There
are interstitial infiltrates throughout the lung fields a n d e n l a r g e d p u l m o n a r y arteries seen
on both v i e w s .
focal perivascular and interstitial opacities are more c o m m o n generative anemia. Advanced pulmonary arterial disease and
than diffuse infiltrates. Radiographs are n o r m a l i n a small thromboembolism may be accompanied by neutrophilia
minority of heartworm-infected cats. (sometimes w i t h a left-shift), monocytosis, thrombocytope
Pulmonary arteriography may confirm a suspected diag nia, and D I C . Hyperglobulinemia, the most c o m m o n bio
nosis of H W D in a cat with a false-negative A g test result and chemical abnormality, occurs inconsistently. The prevalence
normal echocardiogram. The study may be performed using of glomerulopathies i n cats w i t h H W D is u n k n o w n , but it
a large-bore jugular catheter. M o r p h o l o g i c changes i n the does not appear to be high.
pulmonary arteries are outlined, and worms appear as linear Tracheal wash or bronchoalveolar lavage specimens may
filling defects. show an eosinophilic exudate that suggests allergic or para
sitic disease, similar to that found w i t h feline asthma or
ECHOCARDIOGRAPHY pulmonary parasites. This finding usually occurs between
Echocardiographic findings may be n o r m a l unless worms 4 and 8 months after infection. Later i n the disease, tracheal
are located in the heart, m a i n pulmonary artery segment, or wash findings may be unremarkable or indicate nonspecific
proximal left and right pulmonary arteries. However, heart- chronic inflammation. Pleural effusion resulting from heart-
worms may be visualized i n about one half to three fourths worm-induced C H F is generally a modified transudate,
of infected cats. Higher numbers o f worms increase the like although chylothorax occasionally develops.
lihood of identification with echocardiography. Because At around 6.5 to 7 months after infection, a transient
worms are seen more often i n the pulmonary arteries than (1 to 2 months i n duration), low-grade microfilaremia
in right heart chambers, an index o f suspicion and careful occurs i n about half o f infected cats. Therefore microfilaria
interrogation of these structures are important. concentration tests are usually negative. Nevertheless, a
concentration test may still prove valuable i n some i n d i
ELECTROCARDIOGRAPHY vidual cats. Between 3 and 5 m l , rather than 1 m l , o f b l o o d
E C G findings are often normal, but most cats w i t h heart- should be used to increase the probability o f detecting
worm-induced C H F have changes suggesting R V enlarge microfilariae.
ment. Arrhythmias appear to be u n c o m m o n . Advanced
pulmonary arterial disease and C H F are more likely to cause Treatment of Cats with Heartworm Disease
ventricular tachyarrhythmias.
MEDICAL THERAPY
OTHER TESTS AND COMPLICATIONS
Between one and two thirds of infected cats have peripheral Adulticide therapy is not recommended i n most cases
eosinophilia, usually from 4 to 7 months after infection. because the likelihood o f severe complications i n this species
M a n y times the eosinophil count is normal; basophilia is is high. Also, spontaneous cure is possible in cats because o f
uncommon. About one third of the cases have m i l d nonre- the shorter heartworm life span, and cats are not significant
reservoirs for H W D transmission to other animals. O n the tions. The risk is expected to be higher for heavily infected
basis o f a retrospective study (Atkins et al., 2000), cats treated cats. A n adulticide should never be given only on the basis
with thiacetarsamide had no survival advantage over those of a positive A g , Ab, or microfilaria test result. There is little
that were not treated with adulticide. clinical experience with melarsomine (Immiticide) in cats.
The recommended, and more conservative, approach for Doses of >3.5 mg/kg appear to be toxic in this species. IV
infected cats is to use prednisone as needed for respiratory thiacetarsamide (Caparsolate) has been used successfully at
signs and radiographically evident pulmonary interstitial the same doses used in dogs (2.2 mg/kg q l 2 h for 2 days) in
infiltrates. A m o n t h l y heartworm preventive drug is also combination with prednisone and extremely close monitor
advised but not a heartworm adulticide. Serologic tests (for ing for 2 weeks. Acute respiratory failure and death may
heartworm A b and Ag) are obtained every 6 to 12 months occur as a result o f dying worms or toxic effects of the
to monitor infection status. Ag-positive cats usually become arsenical drug. Profound depression and GI side effects also
negative w i t h i n 4 to 5 months o f w o r m death. It is unclear are c o m m o n after each dose. Pretreatment with an antihis
how long A b tests remain positive. Serial thoracic radio tamine and soluble glucocorticoid before thiacetarsamide
graphs and echocardiograms also can be useful for monitor administration is o f u n k n o w n efficacy. The effectiveness o f
ing cats that have had abnormal findings. Interstitial chronic ivermectin at the recommended prophylactic dose
pulmonary infiltrates usually respond to prednisone (e.g., against juvenile worms i n cats is not k n o w n . Results of adult
2 mg/kg/day by mouth, reduced gradually over 2 weeks to w o r m A g tests should be negative within 3 to 4 months of
0.5 mg/kg qod, then discontinued after 2 more weeks). Pred successful adulticide therapy, the time required for A b titers
nisone therapy may be repeated periodically i f respiratory to become negative is likely m u c h longer.
signs recur.
The possibility o f severe respiratory distress and death is SURGICAL THERAPY
always present, especially after spontaneous or adulticide Several approaches are described for removing adult heart-
induced w o r m death. P u l m o n a r y thromboembolism is more worms from cats, although they are technically challenging.
likely to produce a fatal outcome in cats than dogs. Clinical A right jugular venotomy may be used to reach worms i n the
findings with p u l m o n a r y thromboembolism include fever, right atrium and vena cava with small alligator forceps,
cough, dyspnea, hemoptysis, pallor, pulmonary crackles, endoscopic grasping or basket retrieval forceps, or another
tachycardia, and hypotension. Radiographic signs include device. W o r m removal via thoracotomy and right atriotomy
poorly defined, rounded or wedge-shaped interstitial opaci has also been done successfully. A left thoracotomy and pul
ties that obscure associated pulmonary vessels. Alveolar infil monary arteriotomy may permit w o r m extraction from
trates are seen i n some cases. Cats w i t h acute disease are within the p u l m o n a r y artery. A potentially fatal anaphylactic
given supportive care, which may include an I V glucocorti reaction associated with w o r m breakage could occur during
coid (e.g., 100 to 250 m g prednisone s o d i u m succinate), fluid such procedures. Presurgical treatment with a glucocorticoid
therapy, a bronchodilator, and supplemental oxygen. Diuret and antihistamine has been suggested. It is not known
ics are not indicated. A s p i r i n is currently not recommended whether pretreatment with heparin for several days can
for cats with H W D . A s p i r i n and other nonsteroidal antiin reduce thromboembolism associated with surgical w o r m
flammatory drugs have not been shown to produce benefit removal.
and may exacerbate p u l m o n a r y disease.
Right-sided C H F develops in some cats w i t h severe p u l MICROFILARICIDE THERAPY
monary arterial disease. C o u g h and other signs o f p u l m o Microfilaricide therapy is rarely necessary because microfila
nary interstitial disease or a thromboembolic event occur remia is brief. However, ivermectin and milbemycin should
inconsistently. Dyspnea (caused by pleural effusion) and be effective i n this setting.
jugular venous distention or pulsation are c o m m o n . Radio
graphic and E C G findings usually suggest R V enlargement. Heartworm Prevention in Cats
Therapy is directed at controlling the signs of heart failure. Heartworm prophylaxis is recommended for cats in endemic
This includes thoracocentesis as needed, cage rest, and cau areas. Selamectin (Revolution), ivermectin (Heartgard for
tious furosemide therapy (e.g., 1 mg/kg ql2-24h). A n A C E I cats), and milbemycin oxime (Interceptor Flavor Tabs for
Cats) are effective preventive drugs i n cats. Selamectin is
may be helpful. Digoxin is not usually recommended. P i m o used at the same dose as for dogs (6-12 mg/kg, topically).
bendan might be considered, but clinical experience is Selamectin also is useful for controlling fleas and earmites as
lacking. The cat's clinical progress and clinicopathologic well as h o o k w o r m and r o u n d w o r m infections in cats. Iver
abnormalities are used to guide supportive therapy. mectin is administered orally at 24 g/kg monthly (four
times the dose used i n dogs). The m i n i m u m recommended
Caval syndrome occurs rarely i n cats. Successful removal
dose for milbemycin is 2 mg/kg (about twice the dose used
of adult worms through a jugular venotomy is possible. i n dogs). A l l these agents are safe i n kittens 6 weeks or older.
Adulticide therapy may be considered for cats that con A heartworm A g test is recommended before beginning pro
tinue to manifest clinical signs despite prednisone treat phylaxis i f infection could have occurred 8 months or more
ment. Potentially fatal thromboembolism can occur, even in the past. These agents may be used i n seropositive cats.
with only one w o r m present. A b o u t a third o f adulticide
treated cats are expected to have thromboembolic complica
The efficacy of moxidectin or D E C for heartworm preven Kitoh K et al: Role of histamine in heartworm extract-induced
tion in cats is not known. shock in dogs, Am J Vet Res 62:770, 2001.
Kuntz C A et al: Use of a modified surgical approach to the right
atrium for retrieval of heartworms in a dog, J Am Vet Med Assoc
Suggested Readings 208:692, 1996.
GENERAL Lok JB et al: Activity of an injectable, sustained-release formulation
Bazzocchi C et al: Immunological role of the endosymbionts of moxidectin administered prophylactically to mixed breed
of Dirofilaria immitis: the Wolbachia surface protein activates dogs to prevent infection with Dirofilaria immitis, Am J Vet Res
canine neutrophils with production of IL-8, Vet Parasitol 117:73, 62:1721,2001.
2003. Rawlings CA et al: Surgical removal of heartworms, Semin Vet Med
Datz C: Update on canine and feline heartworm tests, Compend Surg 9:200, 1994.
Cont Educ Pract Vet 25:30, 2003.
Kellum HB, Stepien RL: Sildenafil citrate therapy in 22 dogs HEARTWORM DISEASE IN T H E C A T
with pulmonary hypertension, / Vet Intern Med 21:1258-1264, American Heartworm Society: 2007 Guidelines for the diagnosis,
2007. prevention, and management of heartworm (Dirofilaria immitis)
Litster A et al: Radiographic cardiac size in cats and dogs with infection in cats, retrieved on 1/27/08, American Heartworm
heartworm disease compared with reference values using the Society; www.heartwormsociety.org. Accessed 1/27/2008.
vertebral heart scale method: 53 cases, / Vet Cardiol 7:33, 2005. Atkins C et al: Prevalence of heartworm infection in cats with signs
McCall JW: The safety-net story about macrocyclic lactone heart- of cardiorespiratory abnormalities, J Am Vet Med Assoc 212:517,
worm preventives: a review, an update, and recommendations, 1998.
Vet Parasitol 133:197, 2005. Atkins C et al: Heartworm infection in cats: 50 cases (1985-1997),
f Am Vet Med Assoc 217:355, 2000.
HEARTWORM DISEASE IN T H E D O G Borgarelli M et al: Surgical removal of heartworms from the right
American Heartworm Society: 2005 Guidelines for the diagnosis, atrium of a cat, J Am Vet Med Assoc 211(1) 68, 1997.
prevention, and management of heartworm (Dirofilaria immitis) Browne LE et al: Pulmonary arterial disease in cats seropositive for
infection in dogs, retrieved on 1/27/08, American Heartworm Dirofilaria immitis but lacking adult heartworms in the heart and
Society; www.heartwormsociety.org. Accessed 1/27/2008. lungs, Am J Vet Res 66:1544, 2005.
Atkins CE, Miller MW: Is there a better way to administer heart- DeFrancesco TC et al: Use of echocardiography for the diagnosis
worm adulticidal therapy? Vet Med 98:310, 2003. of heartworm disease in cats: 43 cases (1985-1997), J Am Vet Med
Frank I et al: Systemic arterial dirofilariasis in five dogs, / Vet Intern Assoc 218:66, 2001.
Med 11:189, 1997. Dillon A R et al: Feline heartworm disease: correlations of clinical
Hettlich BF et al: Neurologic complications after melarsomine signs, serology, and other diagnosticsresults of a multi-center
dihydrochloride treatment for Dirofilaria immitis in three dogs, study, Vet Ther 1:176-, 2000.
J Am Vet Med Assoc 223:1456, 2003. Morchon R et al: Specific IgG antibody response against antigens
Hopper K, Aldrich J, Haskins SC: Ivermectin toxicity in 17 collies, of Dirofilaria immitis and its Wolbachia endosymbiont bacterium
/ Vet Intern Med 16:89, 2002. in cats with natural and experimental infections, Vet Parasitol
Kitagawa H et al: Comparison of laboratory test results before and 125:313, 2004.
after surgical removal of heartworms in dogs with vena caval Snyder PS et al: Performance of serologic tests used to detect heart-
syndrome,/Am Vet Med Assoc 213:1134, 1998. worm infection in cats,} Am Vet Med Assoc 216:693, 2000.
C H A P T E R 11
Systemic Arterial
Hypertension
Renal disease (tubular, glomerular, vascular) Retinopathy (edema, vascular tortuosity, hemorrhage, focal
Hyperadrenocorticism ischemia, atrophy)
Hyperthyroidism Choroidopathy (edema, vascular tortuosity, hemorrhage,
Pheochromocytoma focal ischemia)
Diabetes mellitus Retinal detachment (bullous or total)
Liver disease Hemorrhage (retinal, vitreal, hyphema)
Hyperaldosteronism Papilledema
Intracranial lesions (T intracranial pressure) Blindness
High-salt diet (?) Glaucoma
Obesity
Secondary corneal ulcers
Chronic anemia (cats)
Neurologic
Other Diseases Associated with Hypertension in People*
Edema, T intracranial pressure
Acromegaly Hypertensive encephalopathy (lethargy, behavioral changes)
Inappropriate antidiuretic hormone secretion Cerebrovascular accident (focal ischemia, hemorrhage)
Hyperviscosity/erythrocytosis Seizures or collapse episodes
Renin-secreting tumors
Renal
Hypercalcemia
Hypothyroidism with atherosclerosis Polyuria/polydipsia
Hyperestrogenism Glomerulosclerosis/proliferative glomerulitis
Coarctation of the aorta Renal tubular degenerative and fibrosis
Pregnancy Further deterioration in renal function
Central nervous system disease
Cardiac
* Essential hypertension is often associated with family history, high Left ventricular hypertrophy (overt heart failure rare)
salt intake, smoking, or obesity. Murmur or gallop sound
Aortic dilation
Aneurysm or dissection rare
that raise cardiac output (by increasing heart rate, stroke Other
volume, and/or blood volume) or by those that increase
Epistaxis
vascular resistance. Arterial B P normally is maintained
within narrow bounds by the actions o f the autonomic
nervous system (e.g., via arterial baroreceptors), various hor
monal systems (e.g., the renin-angiotensin system [ R A A S ] ,
aldosterone, vasopressin/antidiuretic hormone, and natri effects related to secondary hyperparathyroidism may be
uretic peptides), blood volume regulation by the kidney, and involved i n chronic renal failure.
other factors. H i g h perfusion pressure can damage capillary beds. In
Modulation of these systems by various disease condi most tissues capillary pressure is regulated by vasoconstric
tions can lead to chronic elevation of arterial BP. For example, tion of arterioles that feed the capillaries, although this
hypertension can result from increased sympathetic nervous control may be inadequate because of underlying organ
activity or responsiveness (e.g., hyperthyroidism, hyper disease. The continued arteriolar constriction secondary to
adrenocorticism), increased catecholamine production (e.g., chronic hypertension leads to hypertrophy and other vascu
pheochromocytoma), or volume expansion caused by lar remodeling changes that can further increase vascular
increased sodium retention (e.g., decreased glomerular fil resistance. These structural changes and vascular spasm can
tration and reduced sodium excretion in renal failure, hyper cause capillary hypoxia, tissue damage, hemorrhage, and
aldosteronism, hyperadrenocorticism, acromegaly). R A A S infarction, which can lead to organ dysfunction (Box 11-2).
activation, with subsequent salt and water retention and Organs that are particularly vulnerable to damage result
vasoconstriction, may result from intrarenal diseases (e.g., ing from chronic hypertension are the eye, kidney, heart, and
glomerulonephritis, chronic interstitial nephritis), enhanced brain. These structures are often referred to as target-organs
production of angiotensinogen (e.g., hyperadrenocorticism), or end-organs. In the eye hypertension often causes focal
and extrarenal diseases that increase sympathetic nervous perivascular edema, hemorrhage, and ischemia, especially i n
activity or interfere with renal perfusion (e.g., hyperthyroid the retina and choroid layers. Bullous or total retinal detach
ism, renal artery obstruction). Impaired production of ment is c o m m o n . Hyphema, vitreal hemorrhage, and optic
vasodilator substances (e.g., prostaglandins, kallikreins) and neuropathy can also occur. Renal glomerular hypertension
occurs when afferent arteriolar autoregulation is disrupted. protein : creatinine ratio [UPC]) is indicated in all hyperten
The resulting glomerular hyperfiltration can lead to glo sive patients. However, not all hypertensive patients with
merulosclerosis, renal tubular degeneration, and fibrosis. underlying chronic renal disease are azotemic. Other tests are
These changes contribute to renal function deterioration done as needed to rule out possible underlying diseases
and increasing vascular resistance; thus chronic hyperten or complications. These might include various endocrine
sion tends to perpetuate itself. Proteinuria is an important tests, thoracic and abdominal radiographs, ultrasonography
manifestation o f renal damage and has been associated (including echocardiography), electrocardiography, ocular
experimentally w i t h severity o f hypertension i n cats and examination, and serologic tests.
dogs. B l o o d pressure is not directly correlated w i t h serum Thoracic radiographs often reveal some degree of cardio
creatinine concentrations, and hypertension can develop megaly i n patients with chronic hypertension. Cats especially
prior to azotemia. Increased systemic arterial pressure and may have a prominent aortic arch and an undulating (wavy)
vascular resistance increase the afterload stress o n the heart appearance to the thoracic aorta, although these findings
and stimulate left ventricular hypertrophy. Increased cere may not be exclusive to hypertension. Electrocardiographic
bral vascular pressure can promote edema formation, raise ( E C G ) findings may suggest left atrial (LA) or left ven
intracranial pressure, and cause hemorrhage. tricular (LV) enlargement. Arrhythmias do not appear to be
common.
Clinical Features M i l d to moderate L V hypertrophy is seen on echocardiog
Clinically recognized arterial hypertension usually occurs i n raphy i n some cases, although often measurements are within
middle-aged to older dogs and cats, presumably because o f normal reference range. L V wall and septal hypertrophy may
the associated disease conditions. Cats w i t h severe end-organ be symmetric or asymmetric. Other echocardiographic find
disease secondary to hypertension tend to be geriatric. Signs ings may include m i l d L A enlargement and sometimes mitral
o f hypertension relate either to underlying disease or to end- or m i l d aortic regurgitation. Proximal aortic dilation is
organ damage caused by the hypertension itself. another echocardiographic finding i n some animals with
Ocular signs are the most c o m m o n presenting issue, systemic hypertension. Nelson et al. (2002) found that almost
especially sudden blindness, which usually results from acute all hypertensive cats, but not healthy older cats, had a ratio
retinal hemorrhage or detachment. A l t h o u g h the retina of proximal ascending aortic diameter : aortic valve annulus
may reattach, sight often does not return. Ocular fundic diameter o f 1.25.
changes associated w i t h hypertension include bullous to
complete effusive retinal detachment, intraretinal edema, BLOOD PRESSURE MEASUREMENT
and hemorrhage. Vascular tortuosity, hyperreflective scars, Several methods can be used to measure systemic arterial BP
retinal atrophy, papilledema, and perivasculitis are other signs. i n the clinic. Calculating the average of several measure
Hemorrhage i n the anterior or posterior chamber, closed- ments (generally between three and five) i n succession is
angle glaucoma, and cornal ulceration may also occur. recommended to increase accuracy. W h e n readings differ
Another c o m m o n complaint is polyuria and polydipsia, widely, the highest and lowest are discarded and an average
which can be associated with renal disease, hyperadrenocor value from at least three readings is used. H i g h pressures
ticism (in dogs), or hyperthyroidism (in cats). Furthermore, should be confirmed by repeated measurement sessions
hypertension itself causes a so-called pressure diuresis. E p i before a diagnosis o f hypertension is made. Anxiety related
staxis can result from vascular rupture i n the nasal mucosa. to the clinical setting may falsely increase b l o o d pressure i n
Hypertensive encephalopathy resulting from edema and vas some animals (i.e., the "white-coat effect"). Using the least
cular lesions can cause lethargy, seizures, abnormal menta restraint possible i n a quiet environment and allowing time
tion, collapse, or other neurologic or nonspecific signs. (e.g., 5 to 15 minutes) for acclimatization is best for awake
Paresis and other focal defects can occur as a result o f cere animals. Use o f a consistent technique and cuff size is
brovascular accident (stroke) caused by hypertensive arte important.
riolar spasm or hemorrhage.
A soft, systolic cardiac m u r m u r is c o m m o n l y heard on Direct Blood Pressure Measurement
auscultation i n animals w i t h hypertension. A gallop sound Arterial pressure is measured directly by a needle or catheter
may also be present, especially i n cats. Clinical heart failure placed into an artery and connected to a pressure transducer.
is u n c o m m o n . Direct arterial pressure measurement is considered the gold
standard, but it requires greater technical skill; moreover, in
Diagnosis awake animals the physical restraint and discomfort associ
B l o o d pressure measurements are indicated not only when ated with arterial puncture may falsely increase BP. Direct
signs compatible w i t h hypertension are found but also when arterial pressure measurement is more accurate than indirect
a disease associated w i t h hypertension is diagnosed. A diag methods i n hypotensive animals.
nosis o f arterial hypertension should be confirmed by mea For arterial pressure monitoring over a period of time, an
suring B P multiple times and o n different days. A routine indwelling arterial line is often the best approach. The dorsal
laboratory database (complete b l o o d count [ C B C ] ; serum metatarsal artery is c o m m o n l y used for this technique. A n
biochemical profile; and urinalysis, w i t h or without a urine electronic pressure monitor provides continuous measure-
merit of systolic and diastolic pressures and calculated mean ing cuff pressure oscillation signals. Veterinary models are
pressure. W i t h fluid-filled systems, the pressure transducer available (e.g., Cardell Veterinary B l o o d Pressure Monitor,
must be placed at the level of the patient's right atrium to Sharn, Inc; M e m o p r i n t , S&B m e d V E T ) . W i t h these systems
prevent a false increase or decrease of the measured pressure the flow occlusion cuff is inflated to a pressure above the
related to the effects of gravity on the fluid w i t h i n the con systolic pressure and then slowly deflated i n small pressure
necting tubing. The use of wireless, telemetric b l o o d pres decrements. The microprocessor measures and averages the
sure monitors for dogs is currently under investigation. resulting pressure oscillations that are characteristic of sys
When occasional BP measurement is needed, a small- tolic, diastolic, and/or mean pressures (depending o n the
gauge needle attached directly to a pressure transducer may system). Accurate results w i t h oscillometric methods depend
be used to puncture the dorsal metatarsal or femoral artery. on careful adherence to the directions for use and an i m m o
To prevent hematoma formation, direct pressure should be bile subject. Because muscle contraction can produce oscil
applied to the arterial puncture site for several minutes after lations, the l i m b used should not be bearing weight. A t least
removing the catheter or needle used for B P measurement. five readings should be obtained; the lowest and highest are
discarded, and the remaining measurements are averaged.
Indirect Blood Pressure Measurement The oscillometric method may be difficult to use effectively
Several noninvasive methods are available to indirectly in small dogs and cats; underestimation of systolic B P is
measure BP. These techniques involve the use of an inflatable common.
cuff that is placed around a limb, usually the radial artery D o p p l e r u l t r a s o n i c m e t h o d . This method employs
(most dogs) or brachial artery (small dogs and cats) or the the frequency change between emitted ultrasound and
median caudal artery of the tail to occlude blood flow. C o n returning echoes (from m o v i n g b l o o d cells or vessel wall) to
trolled release of cuff pressure is monitored to detect the detect b l o o d flow i n a superficial artery. This frequency
return of flow. Doppler ultrasonic flow detection and oscil change, the so-called Doppler shift, is converted to an audible
lometric methods are used most often. Both techniques signal. One system c o m m o n l y used i n animals is designed
produce measurements that correlate fairly well with direct to determine systolic pressure by detecting b l o o d cell
BP measurement but are not exactly predictive of it. Indirect flow (Ultrasonic Doppler Flow Detector, M o d e l 811, Parks
methods are most reliable i n normotensive and hypertensive Medical Electronics, Inc).
animals. The Doppler method has shown greater correlation Effective locations for pressure measurement include the
with direct BP measurement i n conscious cats compared dorsal metatarsal, palmar c o m m o n digital (forelimb), and
with the oscillometric method. Other methods, such as aus median caudal (tail) arteries. The probe is placed distal to
cultation and arterial palpation, are not recommended for the occluding cuff. A small area of hair is clipped over the
estimating BP. The auscultatory method (used to detect artery for probe placement. Ultrasonic coupling gel is applied
Korotkoff sounds i n people) is technically impractical to the flat Doppler flow probe to obtain air-free contact with
because of the limb conformation of dogs and cats. Direct the skin. The probe is positioned so that a clear flow signal
arterial palpation is not reliable for estimating B P because is heard; it must not be held so tightly that it occludes flow.
pulse strength depends on the pulse pressure (systolic minus The probe must remain still to m i n i m i z e noise; it can be
diastolic arterial pressure), not the absolute level of systolic taped i n place. A low volume setting on the Doppler unit or
or mean pressure. Pulse strength is also influenced by body a headset is used to m i n i m i z e patient anxiety caused by the
conformation and other factors. l o u d audio signals.
Cuff size and p l a c e m e n t . H u m a n pediatric- and The flow-occluding cuff is attached to a sphygmoma
infant-size cuffs can be used for indirect B P measurement i n nometer and inflated to about 20 to 30 m m H g above the
dogs and cats. The cuff must be the correct size for the point at which arterial flow ceases and no audible signals are
patient. The width of the inflatable balloon (bladder) w i t h i n heard. The cuff is slowly deflated (by a few m m H g per
the cuff should be about 30% (especially for cats) to 40% second). D u r i n g deflation, characteristic pulsatile flow
(especially for dogs) of the circumference of the extremity signals from b l o o d cell (or arterial wall) m o t i o n return
it surrounds. The length of the balloon should cover at least during systole. The systolic pressure is the pressure at w h i c h
60% of this circumference. Some of the cuff inflation pres b l o o d flow first recurs (indicated by brief swishing sounds).
sure goes toward tissue compression. Cuffs that are too Sometimes a change i n the flow sound from short and p u l
narrow are more affected by this phenomenon and produce satile to a longer, more continuous swishing can be detected
falsely increased pressure readings; cuffs that are too wide as cuff pressure diminishes; the pressure at w h i c h this change
may underestimate BP. The cuff bladder should be centered occurs is an approximation of diastolic pressure. Doppler
over the target artery. C o m m o n cuff locations are midway estimation of diastolic B P is less accurate because of its
between the elbow and carpus or i n the tibial region; skeletal subjective nature. The change i n flow sound is not always
prominences are avoided. The cuff should encircle the l i m b detectable, especially with small or stiff vessels. As with
snugly without being excessively tight. Tape (not just Velcro the oscillometric method, it may be difficult to obtain
on the cuff) is used to secure the cuff i n position. measurements in small or hypotensive animals w i t h the
O s c i l l o m e t r i c m e t h o d . The indirect oscillometric Doppler method. Patient movement also interferes with
method uses an automated system for detecting and process measurement.
Treatment and Prognosis for long-term antihypertensive therapy and monitoring
Antihypertensive therapy is indicated for animals w i t h severe as well as the potential for adverse medication effects are
hypertension and those w i t h clinical signs presumed to be considerations.
caused by hypertension. Measured B P i n such animals is Several drugs are used as antihypertensive agents i n dogs
generally over 180/120 m m H g . A l t h o u g h some cases con and cats (Table 11-1). Usually one drug is administered at a
stitute hypertensive emergencies that require immediate time, with initially l o w doses, and the animal is monitored
therapy and intensive monitoring (discussed i n more detail to assess efficacy. It may take 2 or more weeks for a significant
later), most hypertensive animals can be managed more con decrease i n B P to be observed. The drugs used most often
servatively (Box 11-3). Gradual reduction i n B P maybe safer are angiotensin-converting enzyme inhibitors (ACEIs), the
i n patients w i t h long-standing hypertension. Chronically Ca++-blocker amlodipine, and -adrenergic blockers. Therapy
high B P leads to vascular adaptations i n the cerebral auto- w i t h a single agent is effective i n some cases, whereas com
regulatory process; i f B P is suddenly reduced, cerebral perfu bination therapy may be needed for adequate B P control
sion may be adversely affected. It is unclear whether all dogs i n others. A n A C E I is recommended as the initial antihy
and cats w i t h moderate hypertension (e.g., repeatable sys pertensive drug i n dogs, and amlodipine i n cats, unless
tolic pressures of 160 to 180 m m Hg) benefit from specific hyperthyroidism is the underlying cause. For hyperthyroid-
antihypertensive treatment. Nevertheless, patients with high induced hypertension, atenolol or another -blocker is used
BP that persists after treatment for the primary disease, as first.
well as those with evidence o f end-organ damage, should be Ancillary strategies may be helpful i n patients with hyper
treated. The goal of therapy is to reduce the B P to below tension, although alone they are unlikely to markedly reduce
150/95 m m H g . The expense and time commitment required BP. Moderate dietary salt reduction (e.g., <0.22% to 0.25%
BOX 11-3
ACEI, Angiotensin-converting enzyme inhibitor; BP, arterial blood pressure; CBC, complete blood count; ECG, electrocardiogram.
TABLE 11-1
1-Adrenergic Blockers
ACEI, Angiotensin-converting enzyme inhibitor; PO, by mouth; IV, intravenous; CRI, constant rate infusion.
sodium on a dry matter basis) is advised for all cases. Diuretics are avoided or used only with caution i n animals
Although not expected to normalize B P by itself, it may with renal disease because they can lead to dehydration
enhance antihypertensive drug effectiveness. A high-salt diet and exacerbate azotemia. Serum potassium concentration
may contribute to development o f hypertension i n some should be monitored, especially i n cats with chronic renal
cats, although salt intake does not generally affect B P i n disease.
normal cats. Conversely, neurohormonal activation and The ability to m o n i t o r B P is important when antihyper
potassium excretion may be increased i n cats with renal tensive drugs are prescribed. Serial measurements are needed
dysfunction that are fed a low-sodium diet. Weight reduction to assess treatment efficacy and prevent hypotension. Adverse
is usually advised for obese animals. It is prudent to avoid effects o f antihypertensive therapy usually relate to hypoten
prescribing drugs that can potentiate vasoconstriction (e.g., sion, manifested by lethargy or ataxia, and reduced appetite.
phenylpropanolamine and other ( 1 - a d r e n e r g i c agonists). Attaining initial B P control may take several weeks. M o n i t o r
Glucocorticoids and progesterone derivatives should also ing may be done every 1 to 2 weeks to assess the efficacy o f
be avoided when possible because steroid hormones can antihypertensive treatment i n non-urgent cases. Once satis
increase BP. A diuretic (thiazide or furosemide; see Chapter factory regulation is achieved, B P should be measured at
3) may help by reducing b l o o d volume i n patients w i t h least every 2 or 3 months. Some animals become refractory
volume expansion, but a diuretic alone is rarely effective. to therapy that was initially effective. Increased antihyper-
tensive dosage, adjunctive therapy, or a change of antihyper -adrenergic blockers may reduce B P by decreasing heart
tensive drug can be tried. Continued attention to the rate, cardiac output, and renal renin release. Atenolol and
underlying disease process is important. Routine C B C , serum propranolol have been used most often (see p. 89). A
biochemistry profile, and urinalysis (with or without a U P C ) -blocker is recommended for cats with hyperthyroid-
are also recommended every 6 months. Decreasing the mag induced hypertension. However, -blockers are often inef
nitude of proteinuria associated with hypertension is a fective when used as the sole antihypertensive agent in cats
desired treatment outcome. w i t h renal disease.
The long-term prognosis for animals w i t h hypertension 1 -adrenergic antagonists oppose the vasoconstrictive
is usually guarded because underlying disease processes effects of these -receptors. Their main use is for hyperten
tend to be severe and progressive. Therapy for some primary sion caused by pheochromocytoma. Phenoxybenzamine is
diseases can exacerbate hypertension or complicate its a noncompetitive and -blocker used most often for
1 2
responsive to ACEIs. However, an A C E I may help protect terminated, the dosage should be gradually tapered down.
against hypertensive renal damage by preferentially reducing
efferent arteriolar constriction and reducing glomerular HYPERTENSIVE EMERGENCY
hypertension. Urgent antihypertensive therapy is indicated when new or
A m l o d i p i n e besylate is a long-acting dihydropyridine progressive signs of severe hypertension are identified.
Ca++-blocker that causes vasodilation without appreciable Examples include acute retinal detachment and hemorrhage,
cardiac effects. It can be effective as a primary antihyperten encephalopathy, or other evidence of intracranial hemor
sive agent in cats and has a duration of effect of at least 24 rhage, acute renal failure, aortic aneurysm, and acute heart
hours. A m l o d i p i n e generally does not alter serum creatinine failure.
concentration or body weight i n cats with chronic kidney Direct-acting vasodilator agents generally produce faster
disease. M i l d hypokalemia should respond to oral potassium reduction i n B P (e.g., nitroprusside, hydralazine). Nitroprus
supplementation. The drug is usually dosed once daily and side can be dosed to effect by constant intravenous (IV)
may be given with or without food. Administration q12h infusion, but arterial pressure should be closely monitored
may be used i n large cats or i n those that do not respond to prevent hypotension (see Table 11-1). Hydralazine given
sufficiently to the lower dose. Alternatively, a -blocker or intravenously or orally is an alternative, especially for dogs.
A C E I may be added for cats that do not respond adequately O r a l amlodipine can be effective i n quickly reducing blood
to amlodipine alone. A m l o d i p i n e tablets are difficult to pressure in cats and has less risk of inducing hypotension.
split evenly but they can be compounded using lactose as A n I V -blocker (propranolol, esmolol, or labetolol), ACEI
a diluent. (enalaprilat), or acepromazine (see Table 11-1) also can be
A m l o d i p i n e also is effective i n some dogs. A lower dose used. One of these agents can be added to oral hydralazine
is tried initially and titrated upward as necessary over a therapy i f that has not adequately reduced B P within 12
period of days. Amlodipine's half-life is about 30 hours in hours.
dogs; maximal effects occur 4 to 7 days after initiating W h e n hypertensive crisis is related to pheochromocy
therapy. Oral bioavailability is high, and peak plasma con toma or other cause of catecholamine excess, the -blocker
centrations are reached 3 to 8 hours after administration; phentolamine is used I V (see Table 11-1) and titrated to
plasma concentrations increase w i t h chronic therapy. The effect. A d d i t i o n of a -blocker can help mitigate pheochro
drug undergoes hepatic metabolism, but there is not exten mocytoma-induced tachyarrhythmias, but it should not be
sive first-pass elimination; caution is warranted when liver administered alone or before an -blocker is given. Use of a
function is poor. The drug is excreted through the urine and -blocker as the sole agent in this setting leaves 1-receptors
feces. A Ca++-channel blocker used as adjunctive therapy unopposed and is likely to exacerbate hypertension. Antihy
with an A C E I i n dogs may control B P while yielding a bal pertensive treatment is recommended for 2 to 3 weeks before
anced effect o n glomerular pressure and glomerular filtra surgery for pheochromocytoma excision, i f possible. For
tion rate ( G F R ) through equal dilation of afferent and inoperable pheochromocytoma, therapy is continued orally
efferent arterioles. to prevent hypertensive emergencies.
Suggested Readings Jensen JL et al: Plasma renin activity and angiotensin I and aldo
Acierno MJ, Labato M A : Hypertension in dogs and cats, Compend sterone concentrations in cats with hypertension associated with
Cont Educ Pract Vet 26:336, 2004. chronic renal disease, Am J Vet Res 58:535, 1997.
Arnold R M : Pharm profile: amlodipine, Compend Contin Educ lepson RE et al: Effect of control of systolic blood pressure on
23:558, 2001. survival in cats with systemic hypertension, / Vet Intern Med
Belew A M , Barlett T, Brown SA: Evaluation of the white coat effect 21:402, 2007.
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C H A P T E R 12
Thromboembolic Disease
vitamin K-dependent glycoprotein, also is involved i n coun Anatomic abnormality (e.g., aneurysm, A-V fistula)
tering thrombosis.
Increased Coagulability
Malfunction of one or more of these systems promotes
Glomerular disease/protein-losing nephropathy
thrombosis.
Hyperadrenocorticism
Immune-mediated hemolytic anemia (+/- thrombocytopenia)
Pathophysiology
Pancreatitis
T E disease is more likely when changes in n o r m a l hemostatic Protein-losing enteropathy
processes create conditions that favor clot formation or Sepsis/infection
impair thrombolysis. Three general situations (so-called Neoplasia
Virchow's triad) promote pathologic thrombosis: abnormal Disseminated intravascular coagulation
endothelial structure or function, slowed or static b l o o d Heart disease
flow, and a hypercoagulable state (either from increased pro-
coagulant substances or decreased anticoagulant or fibrino
lytic substances). A number o f c o m m o n diseases produce
such conditions (Box 12-1). coagulant mechanisms. This occurs with sepsis and likely
Diseases that induce severe or widespread endothelial other systemic inflammatory conditions as well. Neoplastic
injury also cause loss o f n o r m a l endothelial antiplatelet, anti invasion, vascular disruption resulting from other disease,
coagulant, and fibrinolytic functions. Increased coagulability and postischemic injury also induce endothelial damage.
and platelet activation favor pathologic thrombosis. Injured Mechanical trauma to the vascular endothelium (as w i t h
endothelium also releases tissue factor as well as antifibrino catheterization) can also precipitate T E disease, especially
lytic factors. Subendothelial tissue, exposed because o f when other predisposing conditions exist. P u l m o n a r y artery
endothelial cell damage, promotes thrombosis by acting as endothelial injury resulting from heartworm disease ( H W D )
a substrate for clot formation and stimulating platelet adher is well k n o w n (see Chapter 10). The inflammatory reaction
ence and aggregation. to dead or dying worms and w o r m fragments exacerbates
Systemic release o f inflammatory cytokines (e.g., tumor the endothelial damage and prothrombotic conditions.
necrosis factor [ T N F ] , various interleukins, platelet activat Stagnant b l o o d flow promotes thrombosis by impeding
ing factor, nitric oxide) can cause widespread endothelial the dilution and clearance o f coagulation factors. Poor flow
injury, induce tissue factor expression, and also inhibit anti- can promote local tissue hypoxia and endothelial injury as
well. A b n o r m a l turbulence has also been associated w i t h with decreased fibrinolysis (resulting from increased plas
thrombus formation. Turbulence can mechanically injure minogen activator inhibitor [PAI] activity) and high levels
the endothelial surface. of several coagulation factors. Diabetes mellitus is occa
Hypercoagulability may develop secondary to various sionally associated w i t h T E disease in dogs. Platelet hyper
systemic diseases i n dogs and cats; multiple mechanisms are aggregability and possibly hypofibrinolysis are thought to
thought to be involved. Nevertheless, thrombus formation be involved. Occasionally, a patient with clinically relevant
i n such cases may also depend o n altered endothelial integ T E disease does not have any detectable abnormality that
rity or b l o o d flow. A T deficiency is a c o m m o n cause o f can result in hypercoagulability (e.g., Greyhounds with
hypercoagulability. Excessive loss, increased consumption, or aortic T E disease not associated with detectable hemostatic
possibly inadequate hepatic synthesis leads to A T deficiency. or cardiovascular abnormalities). Cats with myocardial
Decreased protein C activity and other mechanisms may disease (see Chapter 8) are at risk for intracardiac thrombus
also contribute to hypercoagulability. formation and subsequent arterial embolization. The mech
Increased platelet aggregability has been associated w i t h anisms involved probably relate to poor intracardiac
neoplasia, some heart diseases, diabetes mellitus, and blood flow (especially within the left atrium), altered
nephrotic syndrome i n some animals. Thrombocytosis blood coagulability, local tissue or blood vessel injury, or a
alone, without an increase i n platelet aggregability, is not combination o f these. Increased platelet reactivity occurs
thought to increase the risk for thrombosis. i n some o f these cats. A b n o r m a l turbulence may be a
Defective fibrinolysis can promote pathologic thrombosis factor when mitral regurgitation occurs. D I C may accom
by preventing efficient breakdown o f physiologic clots. This pany thromboembolism. Some cats with T E disease have
can result from either reduced levels o f fibrinolytic sub decreased plasma arginine and vitamin B and B concen
6 12
stances (e.g., t-PA, plasminogen, urokinase) or increased trations; hyperhomocysteinemia may be a factor in some
production o f plasminogen activator inhibitors; the latter cases. Hyperhomocysteinemia and low plasma vitamin B
is a major mechanism of T E disease in" humans with concentrations are risk factors for thromboembolism in
hypertension. people. It is not k n o w n i f hypercoagulability induced by
Pancreatitis, shock, trauma, sepsis, neoplasia, severe hep a genetic abnormality exists i n some cats, as it does in
atopathy, heatstroke, immune-mediated disease, and other people.
conditions can lead to gross thrombosis as well as dissemi
nated intravascular coagulopathy ( D I C ) . D I C involves
massive activation o f t h r o m b i n and plasmin, w i t h general PULMONARY THROMBOEMBOLISM
ized consumption o f coagulation factors and platelets. D I C
produces extensive thrombosis as well as hemorrhage i n the Pulmonary thromboemboli i n dogs are associated with
microcirculation, resulting i n widespread tissue ischemia H W D , other heart diseases, immune-mediated hemolytic
and multiorgan failure. anemia ( I M H A ) , neoplasia, D I C , sepsis, hyperadrenocorti
Protein-losing nephropathy (resulting from glomerulo cism, nephrotic syndrome, pancreatitis, trauma, hypothy
nephritis, renal amyloid deposition, or hypertensive injury) roidism, and right atrial thrombus related to infection.
can lead to marked A T deficiency. Because o f its small size, Pulmonary T E disease appears to be rare i n cats com
A T is lost through damaged glomeruli more easily than most pared with dogs, except i n those with H W D . Nevertheless,
procoagulant proteins, which predisposes to thrombosis. pulmonary T E disease has been associated with a variety o f
Protein-losing enteropathies also cause A T deficiency, but systemic and inflammatory disorders i n cats, including neo
concurrent loss of larger proteins tends to maintain a balance plasia, H W D , anemia (probably immune mediated), pancre
between procoagulant and anticoagulant factors. Other atitis, glomerulonephritis, encephalitis, pneumonia, heart
factors also may contribute to T E disease i n animals w i t h disease, sepsis, glucocorticoid administration, protein-losing
protein-losing nephropathies, such as increased platelet enteropathy, and hepatic lipidosis.
aggregation secondary to hypoalbuminemia. Pulmonary T E disease that causes pulmonary hyper
Thrombosis associated with immune-mediated hemo tension variably produces right ventricular enlargement
lytic anemia ( I M H A ) is also thought to be multifactorial, and hypertrophy, interventricular septal flattening, and
with the systemic inflammatory (immune-mediated) high tricuspid regurgitation jet velocities. Sometimes a
response playing a large role. Thrombocytopenia, hyperbili clot is identified w i t h i n the pulmonary artery or right
rubinemia, and hypoalbuminemia have been identified as atrium.
risk factors for T E disease. The role o f high-dose corticoste
roid therapy i n pathologic thrombosis is unclear. However,
T E disease is relatively c o m m o n i n animals receiving exog SYSTEMIC ARTERIAL
enous corticosteroids and i n those w i t h hyperadrenocorti THROMBOEMBOLISM IN CATS
cism (see next paragraph). Other predisposing factors are
usually concurrent i n these cases as well. The most c o m m o n cause for arterial T E disease in cats is
T E disease occurs i n some dogs with spontaneous hyper cardiomyopathy (see Chapter 8). T h r o m b i initially form in
adrenocorticism. This endocrinopathy has been associated the left heart and can become quite large. Although some
remain in the heart (usually the left atrial [LA] appendage; Signs o f pain and poor systemic perfusion are usually
see Figure 8-6), others embolize to the distal aorta or, less present. Hypothermia and azotemia are c o m m o n . A cardiac
often, other sites. Marked L A enlargement may magnify the murmur, gallop sound, or arrhythmia is often identified, but
risk for thromboembolus formation, but this is controver these signs are not always evident even with underlying heart
sial. Neoplastic and systemic inflammatory disease are some disease. Clinical signs o f heart disease before the T E event
times associated with systemic thromboemboli i n cats. are often absent. Tachypnea and open-mouth breathing are
Hyperthyroidism may be a risk factor for T E disease in cats c o m m o n i n cats with acute arterial embolization, despite the
independent o f its cardiac effects. In some cases, no predis absence o f overt congestive heart failure ( C H F ) . These signs
posing condition is identified. may represent a pain response, although increased p u l m o
Systemic arterial emboli usually lodge at the aortic trifur nary venous pressure could be involved. Thoracic radio
cation (so-called saddle thrombus; Figure 12-1), but iliac, graphs should be obtained as soon as possible because it is
femoral, renal, brachial, and other arteries can be affected important to determine whether pulmonary edema under
depending on embolus size and flow path. Besides obstruct lies the respiratory signs.
ing flow in the affected artery, thromboemboli release vaso Acute h i n d l i m b paresis without palpable femoral pulses
active substances that induce vasoconstriction and is typical. C o m m o n clinical findings are summarized in Box
compromise collateral blood flow development around the 12-2. M o t o r function i n the rear limbs is m i n i m a l to absent
obstructed vessel. Tissue ischemia results and causes further in most cases, although the cat is usually able to flex and
damage and inflammation. A n ischemic neuromyopathy extend the hips. Sensation to the lower limbs is poor. One
occurs in the affected limb(s), with peripheral nerve dys side may show greater deficits than the other. E m b o l i are
function and degeneration as well as pathologic changes in occasionally small enough to lodge more distally i n only one
associated muscle tissue. limb, which causes paresis o f the lower limb alone. E m b o l i
Coronary thromboembolism with myocardial necrosis zation o f a brachial artery produces (usually right) forelimb
has occurred in cats with cardiac disease, especially severe monoparesis. Intermittent claudication (see p. 201) occurs
hypertrophic cardiomyopathy or infective endocarditis, as rarely. T h r o m b o e m b o l i w i t h i n the renal, mesenteric, or pul
well as from carcinoma emboli. monary arterial circulation may result in failure o f these
organs and death. E m b o l i to the brain could induce seizures
Clinical Features or various neurological deficits.
Arterial T E disease i n cats usually causes acute and dramatic
clinical signs secondary to tissue ischemia (Fig. 12-2). Male Diagnosis
cats are at higher risk for thromboembolism, but this gender Thoracic radiography is used to screen for cardiopulmonary
bias appears to be related to the prevalence o f hypertrophic abnormalities such as evidence for heart failure or other
cardiomyopathy. Distal aortic embolization occurs i n most disease associated with thromboemboli (e.g., glomerulone
cases. However, the clinical findings depend on the area phritis, neoplasia, H W D ) . Most cats with arterial T E disease
embolized as well as the extent and duration o f arterial have some degree o f cardiomegaly (especially L A enlarge
blockage. ment) when cardiomyopathy is the underlying cause. Signs
of heart failure include dilated pulmonary veins, pulmonary
edema, or pleural effusion. A few affected cats have no radio
graphic evidence o f cardiomegaly.
Echocardiography delineates the type o f myocardial
disease and may reveal the presence o f an intracardiac throm
bus (see Figure 8-6). The most c o m m o n site for intracardiac
t h r o m b i is the left auricular appendage. Most cats with arte
rial T E disease associated with cardiomyopathy have some
degree o f L A enlargement. A n L A dimension o f >20 m m
(measured from the two-dimensional long-axis four-
chamber view) may increase the risk for T E disease, although
more than half o f aortic T E disease cases i n one study had a
smaller left atrium (Smith, 2003). If echocardiography is
unavailable, nonselective angiocardiography can help define
the nature o f underlying cardiac disease and determine the
location and extent o f the thromboembolism.
Cats w i t h arterial thromboembolism often have azotemia.
This can be prerenal, resulting from poor systemic perfusion
FIG 1 2 - 1
or dehydration; primary renal, resulting from embolization
Postmortem i m a g e with o p e n e d distal a o r t a , from a c a t with
c a r d i o m y o p a t h y . A t h r o m b o e m b o l u s (just left of the forceps of the renal arteries or preexisting kidney disease; or a c o m
tip) is l o d g e d at the aortic trifurcation. The rear limbs a r e to bination o f both. Metabolic acidosis, D I C , electrolyte abnor
the left in the i m a g e ; c r a n i a l is to the right. malities (especially low serum sodium, calcium, potassium,
FIG 1 2 - 2
A , C a t with t h r o m b o e m b o l i s m to the distal a o r t a . The left rear limb w a s d r a g g e d b e h i n d
as the c a t tried to w a l k ; there w a s slightly better function in the right rear. B , The p a d s of
the left rear p a w (right s i d e of image) in this c a t w e r e p a l e r a s w e l l a s c o o l e r c o m p a r e d
with the left f o r e p a w (left side of i m a g e ) .
BOX 12-2
A c u t e limb p a r e s i s Lethargy/weakness
Posterior p a r e s i s S i g n s of heart d i s e a s e (inconsistent)
Monoparesis Systolic murmur
Intermittent c l a u d i c a t i o n G a l l o p sounds
C h a r a c t e r i s t i c s of affected limb(s) Arrhythmias
Painful Cardiomegaly
C o o l distal limbs S i g n s of c o n g e s t i v e heart failure
Pale f o o t p a d s Pulmonary e d e m a
Cyanotic nailbeds Effusions
A b s e n t arterial pulse Hematologic a n d biochemical abnormalities
C o n t r a c t u r e of affected muscles (especially g a s t r o c n e m i u s Azotemia
a n d c r a n i a l tibial) Increased a l a n i n e a m i n o t r a n s f e r a s e activity
Tachypnea/dyspnea Increased a s p a r t a t e a m i n o t r a n s f e r a s e activity
Rule out c o n g e s t i v e heart failure versus p a i n o r other Increased lactate d e h y d r o g e n a s e activity
pulmonary disease Increased c r e a t i n e k i n a s e activity
V o c a l i z a t i o n (pain a n d distress) H y p e r g l y c e m i a (stress)
Hypothermia L y m p h o p e n i a (stress)
Anorexia D i s s e m i n a t e d intravascular c o a g u l a t i o n
and elevated phosphorus), and stress hyperglycemia are Other causes of acute posterior paresis to be considered
c o m m o n . Hyperkalemia may develop secondary to ischemic include intervertebral disk disease, spinal neoplasia (e.g.,
muscle damage and reperfusion. Skeletal muscle damage and lymphoma), trauma, fibrocartilaginous infarction, diabetic
necrosis are accompanied by elevations o f alanine amino neuropathy, and possibly myasthenia gravis.
transferase and aspartate aminotransferase activities, begin
ning w i t h i n 12 hours o f the T E event and peaking by 36 Treatment and Prognosis
hours. Widespread muscle injury causes lactate dehydroge The goals o f treatment are to manage concurrent C H F and
nase and creatine kinase activities to be increased soon after arrhythmias (if present), prevent extension o f the embolus
the event; elevations i n these enzyme activities may persist and formation of additional thrombi, promote collateral cir
for weeks. Metabolic acidosis, D I C , and hyperkalemia may culation, and provide supportive care (Box 12-3). The treat
also be present secondary to ischemic muscle damage and ment of heart failure is outlined i n Chapter 8 and Box 8-1.
reperfusion. Cats with arterial T E disease usually have a Propranolol is discouraged i n cats with cardiomyopathy
normal coagulation profile. and arterial thromboembolism because its nonselective
BOX 1 2-3
-blocking effect may contribute to peripheral vasoconstric be used to help alleviate pain for up to 3 days, but because
tion from unopposed -receptors, and the drug has no it takes about 12 hours to become effective, another analge
antithrombotic effects at clinical doses. sic is used simultaneously d u r i n g this initial p e r i o d . Respira
A n analgesic is recommended, especially for the first 24 tory depression and reduced gastrointestinal (GI) motility
to 36 hours, because this is a painful condition. B u t o r p h a n o l are potential side effects.
(0.15 to 0.5 mg/kg, administered intramuscularly into the Acepromazine is not recommended for animals w i t h arte
cranial lumbar area or subcutaneously q l - 3 h ) has been rec rial T E disease, despite its -adrenergic receptor-blocking
ommended, especially for the first 24 to 36 hours after the effects. Improved collateral flow has not been documented,
embolic event. Low-dose morphine (0.1 to 0.3 mg/kg q3-6h, and hypotension and exacerbation o f dynamic ventricular
administered intramuscularly or subcutaneously) could be outflow obstruction (in cats w i t h hypertrophic obstructive
considered, but some cats experience dysphoria. A fentanyl cardiomyopathy) are potential adverse effects. Other sup
patch (25 g/h size) applied to a shaved area of skin could portive care is given to improve and maintain adequate
tissue perfusion, minimize further endothelial damage and q6-8h for 2 to 4 days is one protocol. M o n i t o r i n g the patient's
blood stasis, and optimize organ function as well as to allow activated partial thromboplastin time (aPTT) is recom
time for collateral circulation development. mended, although results may not accurately predict serum
Antiplatelet and anticoagulant therapies are used to heparin concentrations. Pretreatment coagulation testing is
reduce platelet aggregation and growth of existing thrombi. done for comparison, and the goal is to prolong the a P T T to
A l t h o u g h fibrinolytic therapy is used i n some cases, dosage 1.5 to 2.5 times baseline. Activated clotting time is not rec
uncertainties, the need for intensive care, and the potential ommended to monitor heparin therapy. Hemorrhage is the
for serious complications stemming from reperfusion injury major complication. Protamine sulfate can be used to coun
limit its use. teract heparin-induced bleeding. However, an overdose of
A s p i r i n (acetylsalicylic acid) is used c o m m o n l y to block protamine can paradoxically cause irreversible hemorrhage.
platelet activation and aggregation i n patients with, or at risk Dosage guidelines for protamine sulfate are as follows:
for, T E disease. A s p i r i n irreversibly inhibits cyclooxygenase, 1 mg/100 U of heparin is given i f the heparin was given
which reduces prostaglandin and thromboxane A synthesis 2 within the previous 60 minutes; 0.5 mg/100 U of heparin is
and therefore subsequent platelet aggregation, serotonin given i f the heparin was given more than 1 but less than 2
release, and vasoconstriction. Because platelets cannot syn hours earlier; and 0.25 mg/100 U of heparin is given i f more
thesize additional cyclooxygenase, this reduction o f proco than 2 hours have elapsed since heparin was administered.
agulant prostaglandins and thromboxane persists for the Fresh frozen plasma may be needed to replenish AT. Heparin
platelets life span (7 to 10 days). Endothelial production of treatment is continued until the patient is stable and has
prostacyclin (also via the cyclooxygenase pathway) is reduced been o n antiplatelet therapy for a few days.
by aspirin but only transiently as endothelial cells synthesize L M W H is a safer alternative to unfractionated heparin.
additional cyclooxygenase. Aspirin's benefit may relate more L M W H products are a diverse group of depolymerized
to in situ thrombus formation; efficacy i n acute arterial heparin that vary i n size, structure, and pharmacokinetics.
thromboembolism is u n k n o w n . Adverse effects of aspirin Their smaller size prevents simultaneous binding to throm
tend to be m i l d and u n c o m m o n , but the optimal dose is bin and AT. L M W H products have more effect against factor
unclear. Cats lack an enzyme (glucuronyl transferase) that X a through their inactivation of AT. Because they have
is needed to metabolize aspirin, so less frequent dosing is m i n i m a l ability to inhibit thrombin, they are less likely to
required compared with dogs. In cats with experimental cause bleeding. L M W H products have greater bioavailability
aortic thrombosis, 10 to 25 mg/kg (1.25 grains/cat) given by and a longer half-life than unfractionated heparin when
m o u t h once every (2 to) 3 days inhibited platelet aggregation given subcutaneously because of lesser binding to plasma
and improved collateral circulation. However, low-dose proteins as well as endothelial cells and macrophages.
aspirin (5 mg/cat q72h) has also been used with fewer G I However, L M W H products do not markedly affect coagula
adverse effects, although its efficacy i n preventing T E events tion times, so m o n i t o r i n g a P T T is generally not necessary.
is u n k n o w n . Aspirin therapy is started when the patient is L M W H effect can be monitored indirectly by anti-Xa activ
able to take food and oral medications. ity. O p t i m a l anti-Xa activity level i n cats is not known;
Other antiplatelet drugs are being studied. The thieno the target range i n people is reported as 0.5 to 1.0 U / m l ,
pyridines inhibit adenosine diphosphate ( A D P ) - b i n d i n g at although 0.3 to 0.6 U / m l has also been used. The L M W H
platelet receptors and subsequent ADP-mediated platelet products have differences in biological and clinical effects
aggregation. Clopidogrel (Plavix; 18.75 mg/cat P O q24h) and are not interchangeable. The most effective dosage for
appears to have significant antiplatelet effects; daily dosing the various L M W H products is not clearly established in
may be possible. dogs and cats. C o m m o n l y used dosages of dalteparin sodium
Heparin is indicated to limit extension of existing t h r o m b i (Fragmin; 100-150 U / k g administereed subcutaneously q8-
and prevent further T E episodes; it does not promote throm 24h) and enoxaparin (Lovenox; 1 mg/kg administered sub
bolysis. Unfractionated heparin and a number of low-molec cutaneously ql2-24h) were extrapolated from human use.
ular-weight heparin ( L M W H ) products are available. However, according to a recent study (Alwood et al., 2007),
Heparin's main anticoagulant effect is produced through A T these doses do not produce a (human) target level of anti-Xa
activation, which i n turn inhibits factors I X , X , X I , and X I I activity i n cats. Although enoxaparin produced anti-Xa
and thrombin. Unfractionated heparin binds thrombin as activity close to this level at 4 hours postdose, activity was
well as AT. Heparin also stimulates release of tissue factor undetectable 8 hours later. O n the basis of this study, the
inhibitors from vascular sites, which helps reduce (extrinsic) predicted optimal dose and dosing interval to maintain anti-
coagulation cascade activation. O p t i m a l dosing protocols for X a activity within the (human) therapeutic range in normal
animals are not k n o w n . Unfractionated heparin is usually cats are as follows: dalteparin, 150 U / k g administered sub
given as an initial intravenous (IV) bolus followed by sub cutaneously q4h; and enoxaparin, 1.5 mg/kg administered
cutaneous (SC) injections (see B o x 12-3). Heparin is not subcutaneously q6h. The optimal therapeutic range in cats
given I M because of the risk for hemorrhage at the injection as well as the most effective dosage i n sick cats are not yet
site. Heparin doses (from 75 to 500 U / k g ) have been used known.
with uncertain efficacy. A n initial I V dose of 200 IU/kg, Drugs used to promote clot lysis include streptokinase
followed by 150 to 200 I U / k g administered subcutaneously and h u m a n recombinant tissue plasminogen activator
(rt-PA). These agents increase conversion o f plasminogen to Surgical clot removal is generally not advised i n cats.
plasmin to facilitate fibrinolysis. Veterinary experience with The surgical risk is high, and significant neuromuscular
these agents is quite limited. Although they effectively break ischemic injury is likely to have already occurred by the time
down clots, complications related to reperfusion injury and of surgery. Clot removal using an embolectomy catheter
hemorrhage, the high mortality rate, the cost o f therapy, the has not been very effective i n cats.
intensive care required, and the lack o f clearly established In general, the prognosis is poor i n cats with arterial T E
dosing protocols have prevented their widespread use. Fur disease. Historically, only a third o f cats survive the initial
thermore, a clear survival advantage has not been shown. If episode. However, survival statistics improve when cats eu
used, this therapy is best instituted within 3 to 4 hours o f thanized without therapy are excluded or when only cases
vascular occlusion. A n intensive care setting, including con from recent years are analyzed. Survival is better i f only one
tinuous serum potassium concentration (or electrocardio l i m b is involved and/or i f some motor function is preserved
graphic [ECG]) monitoring to detect reperfusion-induced at presentation. H y p o t h e r m i a and C H F at presentation are
hyperkalemia, is recommended. both associated with poor survival i n cats. Other negative
Streptokinase is a nonspecific plasminogen activator that factors may include hyperphosphatemia, progressive hyper
promotes the breakdown o f fibrin as well as fibrinogen. This kalemia or azotemia, progressive l i m b injury (continued
action leads to the degradation o f fibrin w i t h i n t h r o m b i and muscle contracture after 2 to 3 days, necrosis), severe L A
clot lysis but also potentially leads to systemic fibrinolysis, enlargement, presence o f intracardiac t h r o m b i or spontane
coagulopathy, and bleeding. Streptokinase also degrades ous contrast ("swirling smoke") o n echocardiogram, D I C ,
factors V, VIII, and prothrombin. Although its half-life is and history o f thromboembolism.
about 30 minutes, fibrinogen depletion continues for m u c h Barring complications, l i m b function should begin to
longer. Streptokinase has been used with variable success i n return w i t h i n 1 to 2 weeks. Some cats become clinically
a small number of dogs w i t h arterial T E disease. The reported n o r m a l w i t h i n 1 to 2 months, although residual deficits may
protocol is 90,000 I U of I V streptokinase infused over 20 to persist for a variable time. Tissue necrosis may require w o u n d
30 minutes, then at a rate o f 45,000 I U / h o u r for 3 (to 8) management and skin grafting. Permanent limb deformity
hours. D i l u t i o n o f 250,000 I U into 5 m l saline, then into develops i n some cats, and amputation is occasionally neces
50 m l to yield 5000 U / m l for infusion w i t h a syringe p u m p sary. Repeated events are c o m m o n . Significant embolization
has been suggested for cats. Adverse effects are m i n o r i n of the kidneys, intestines, or other organs carries a grave
some cases, and bleeding may respond to discontinuing prognosis.
streptokinase. However, there is a risk for serious hemor
rhage, and the mortality rate i n clinical cases is high. Acute PROPHYLAXIS AGAINST ARTERIAL
hyperkalemia (secondary to thrombolysis and reperfusion THROMBOEMBOLISM
injury), metabolic acidosis, bleeding, and other complica Prophylactic therapy w i t h an antiplatelet or anticoagulant
tions are thought to be responsible for causing death. Strep drug is c o m m o n l y used i n animals thought to be at increased
tokinase can increase platelet aggregability and induce risk for T E disease. These include cats with cardiomyopathy
platelet dysfunction. It is unclear i f lower doses w o u l d be (especially those w i t h marked L A enlargement, echocardio
effective with fewer complications. Streptokinase combined graphic evidence for intracardiac spontaneous contrast or
with heparin therapy can increase the risk o f hemorrhage, thrombus, or a previous T E event) and animals with sepsis,
especially when coagulation times are increased. Streptoki I M H A , severe pancreatitis, or other procoagulant condi
nase is potentially antigenic because it is produced by (- tions. However, the efficacy o f T E prophylaxis is unknown,
hemolytic streptococci. N o survival benefit has been shown and a strategy that consistently prevents thromboembolism
for streptokinase therapy compared with conventional (i.e., is not yet identified.
aspirin and heparin) treatment i n cats. Drugs used for arterial T E prophylaxis include aspirin,
rt-PA is a single-chain polypeptide serine protease w i t h a clopidogrel, warfarin (Coumadin), and L M W H . A s p i r i n
higher specificity for fibrin within thrombi and a low affinity and clopidogrel present a low risk for serious hemor
for circulating plasminogen. Although the risk o f hemor rhage and require less monitoring compared with warfarin.
rhage is less than with streptokinase, there is the potential Adverse G I effects (e.g., vomiting, inappetence, ulceration,
for serious bleeding as well as other side effects. rt-PA is also hematemesis) occur i n some animals. Buffered aspirin
potentially antigenic i n animals because it is a h u m a n protein. formulation or an aspirin-Maalox combination product
Like streptokinase, rt-PA induces platelet dysfunction but may be helpful. Low-dose aspirin (5 mg/cat every t h i r d day)
not hyperaggregability. Experience with rt-PA is very limited, has been advocated i n cats. Although adverse effects are
and the optimal dosage is not k n o w n . A n I V dose o f 0.25 to unlikely w i t h this dose, it is not k n o w n whether antipla
1 mg/kg/h up to a total o f 1 to 10 mg/kg was used i n a small telet effectiveness is compromised. Warfarin (discussed i n
number of cats; although signs o f reperfusion occurred, the more detail later) is associated w i t h greater expense and
mortality rate was high. The cause o f death i n most cats was a higher rate o f fatal hemorrhage. N o survival benefit has
attributed to reperfusion (hyperkalemia, metabolic acidosis) been shown for warfarin compared w i t h aspirin i n cats.
and hemorrhage, although C H F and arrhythmias were also In some reports, recurrent t h r o m b o e m b o l i s m occurred i n
involved. almost half of cats treated w i t h warfarin. Clopidogrel or
L M W H prophylaxis may be more efficacious, with less sion with fresh frozen plasma, packed red blood cells, or
risk o f hemorrhage, but more experience with this therapy whole fresh b l o o d is sometimes necessary.
is needed. Recurrent T E events occurred i n 20% o f cats
in one study (Smith, 2004). L M W H is expensive and must
be given by daily S C injection, but some owners are SYSTEMIC ARTERIAL
motivated to do this. In cats without thrombocytopenia, THROMBOEMBOLISM IN DOGS
aspirin may be used concurrently. Diltiazem, at clinical doses,
does not appear to have significant platelet-inhibiting Arterial T E disease i n dogs is relatively u n c o m m o n com
effects. pared with cats. Nevertheless, it has been associated with
Warfarin inhibits the enzyme (vitamin K epoxide reduc many conditions, including protein-losing nephropathies,
tase) responsible for activating the v i t a m i n K-dependent hyperadrenocorticism, neoplasia, chronic interstitial nephri
factors (II, VII, IX, and X ) , as well as proteins C and S. Initial tis, H W D , hypothyroidism, gastric dilatation-volvulus, pan
warfarin treatment causes transient hypercoagulability creatitis, and several cardiovascular diseases. Kidney disease
because anticoagulant proteins have a shorter half-life than was present i n about half of the dogs with T E disease in
most procoagulant factors. Therefore heparin (e.g., 100 I U / one report (Van Winkle, 1993). Vegetative endocarditis is
kg administered subcutaneously q8h) is given for 2 to 4 days the most c o m m o n cardiac disease associated with systemic
after warfarin is initiated. There is wide variability i n dose thromboembolism. Other cardiovascular conditions that
response and potential for serious bleeding, even i n cats that have been associated with canine T E disease include patent
are monitored closely. Warfarin is highly protein-bound; ductus arteriosus (surgical ligation site), dilated cardiomy
concurrent use o f other protein-bound drugs or change i n opathy, myocardial infarction, arteritis, aortic intimal fibro
serum protein concentration can markedly alter the antico sis, atherosclerosis, aortic dissection, granulomatous
agulant effect. Bleeding may be manifested as weakness, leth inflammatory erosion into the left atrium, and other thrombi
argy, or pallor rather than overt hemorrhage. A baseline in the left heart. T E disease is a rare complication of arterio
coagulation profile and platelet count are obtained, and venous ( A - V ) fistulae; it may relate to venous stasis from
aspirin discontinued, before beginning treatment. The usual distal venous hypertension. Aortic T E has occurred i n Grey
initial warfarin dose is 0.25 to 0.5 m g (total dose) adminis hounds without overt underlying abnormalities as well as in
tered orally q24-48h i n cats. Uneven distribution o f drug those w i t h protein-losing nephropathy or intramuscular
w i t h i n the tablets is reported, so compounding rather than hemangiosarcoma i n the thigh muscles. Affected dogs
administering tablet fragments is recommended. D r u g typically present for intermittent rear limb lameness (clau
administration and b l o o d sampling times should be dication) and have weak femoral pulses on the affected
consistent. side, and the thrombi are obvious during abdominal
The dose is adjusted either on the basis o f prothrombin ultrasonography.
time (PT) or the international normalization ratio (INR). Atherosclerosis is u n c o m m o n i n dogs, but it has been
The I N R is a more precise method that has been recom associated with T E disease i n this species, as it has i n people.
mended to prevent problems related to variation i n c o m Endothelial disruption i n areas o f atherosclerotic plaque,
mercial P T assays. The I N R is calculated by dividing the hypercholesterolemia, increased PAI-1, and possibly other
animal's P T by the control P T and raising the quotient to mechanisms may be involved i n thrombus formation. A t h
the power o f the international sensitivity index (ISI) o f the erosclerosis may develop with profound hypothyroidism,
thromboplastin used i n the assay, or I N R = (animal P T / hypercholesterolemia, or hyperlipidemia. The aorta as well
ISI
control P T ) . The ISI is provided with each batch o f t h r o m as coronary and other m e d i u m to large arteries are affected.
boplastin made. Extrapolation from h u m a n data suggests Myocardial and cerebral infarctions occur i n some cases, and
that an I N R o f 2 to 3 is as effective as higher values, with there is a high rate o f interstitial myocardial fibrosis in
less chance for bleeding. Using a warfarin dose o f 0.05 affected dogs.
to 0.1 mg/kg/day i n the dog achieves this I N R i n about 5 Vasculitis related to infectious, inflammatory, immune-
to 7 days. Heparin overlap until the I N R is >2 is recom mediated, or toxic disease occasionally underlies T E events.
mended. W h e n P T is used to m o n i t o r warfarin therapy, a Arteritis of immune-mediated pathogenesis is described in
goal of 1.25 to 1.5 (to 2) times pretreatment P T at 8 to 10 some young Beagles and other dogs. Inflammation and
hours after dosing is advised; the animal is weaned off necrosis that affect small to medium-sized arteries may be
heparin when the I N R is >1.25. The P T is evaluated (several associated w i t h thrombosis.
hours after dosing) daily initially, then at progressively Coronary artery thromboembolism causes myocardial
increasing time intervals (e.g., twice a week, then once a ischemia and infarction. Infective endocarditis, neoplasia
week, then every m o n t h to 2 months) as long as the cat's that involves the heart directly or by neoplastic emboli, cor
condition appears stable. onary atherosclerosis, dilated cardiomyopathy, degenerative
If the P T or I N R increases excessively, warfarin is discon mitral valve disease with C H F , and coronary vasculitis are
tinued and vitamin K1 administered (1 to 2 mg/kg/day reported causes. In other dogs coronary T E events have
administered orally or subcutaneously) until the P T is occurred with severe renal disease, I M H A , exogenous corti
normal and the packed cell volume ( P C V ) is stable. Transfu costeroids or hyperadrenocorticism, and acute pancreatic
necrosis. These cases may have T E lesions i n other locations disease and for p u l m o n a r y changes i n animals suspected to
as well. have p u l m o n a r y thromboemboli. Evidence for C H F or other
pulmonary disease associated w i t h T E disease (e.g., neopla
Clinical Features sia, H W D , other infections) may also be found.
There appear to be no age, breed, or sex predilections for A complete echocardiographic exam is important to
arterial T E disease i n dogs. As in cats, the distal aorta is the define whether (and what type of) heart disease might be
most c o m m o n location for clinically recognized thrombo present. T h r o m b i w i t h i n the left or right heart chambers
emboli. In contrast to cats, most dogs have some clinical and proximal great vessels can be readily seen w i t h two-
signs from 1 to 8 weeks before presentation. Less than a dimensional echocardiography. In dogs with coronary T E
quarter of cases have peracute paralysis without prior signs disease, the echocardiographic examination may indicate
of lameness, as usually occurs in cats. Signs related to the T E reduced myocardial contractility w i t h or without regional
event include pain, hindlimb paresis, lameness or weakness dysfunction. Areas o f myocardial fibrosis secondary to
(which may be progressive or intermittent), and chewing or chronic ischemia or infarction appear hyperechoic c o m
hypersensitivity o f the affected limb(s) or lumbar area. pared with the surrounding myocardium. T h r o m b o e m
Although about half o f affected dogs present with sudden b o l i i n the distal aorta (or other vessel) may be visible by
paralysis, this is often preceded by a variable period o f lame ultrasonography as well. Doppler studies can demonstrate
ness. Intermittent claudication, c o m m o n i n people with partial or complete obstruction to b l o o d flow i n some
peripheral occlusive vascular disease, may be a manifestation cases.
of distal aortic T E disease. This involves pain, weakness, and Angiography may be used to document vascular occlu
lameness that develop during exercise. These signs intensify sion when ultrasonography is inconclusive or unavailable. It
until walking becomes impossible, then disappear with rest. also can show the extent o f collateral circulation. The choice
Inadequate perfusion during exercise leads to lactic acid of selective or nonselective technique depends o n patient size
accumulation and cramping. and the suspected location o f the clot.
Physical examination findings i n dogs with aortic t h r o m Routine laboratory test results depend largely on the
boembolism are similar to those i n cats, including absent or disease process underlying the T E event(s). Systemic arterial
weak femoral pulses, cool extremities, h i n d l i m b pain, loss o f T E disease also produces elevated muscle enzyme concentra
sensation in the digits, hyperesthesia, cyanotic nailbeds, and tions from skeletal muscle ischemia and necrosis. Aspartate
neuromuscular dysfunction. Occasionally, a brachial or other aminotransferase (AST) and alanine aminotransferase (ALT)
artery is embolized. T E disease involving an abdominal activities rise soon after the T E event. Widespread muscle
organ causes abdominal pain, with clinical and laboratory injury causes increased lactate dehydrogenase and creatine
evidence of damage to the affected organ. kinase ( C K ) activities as well.
Coronary artery thromboembolism is likely to be associ Coagulation test results i n patients with T E disease are
ated with arrhythmias, as well as ST segment and T wave variable. The concentration o f FDPs or D-dimer may be
changes on E C G . Ventricular (or other) tachyarrhythmias increased, but this can occur i n patients with inflammatory
are common, but i f the atrioventricular (AV) nodal area is disease and is not specific for a T E event or D I C . Modestly
injured, conduction block may result. Clinical signs o f acute increased D - d i m e r concentrations occur i n diseases such as
myocardial infarction/necrosis may m i m i c those o f p u l m o neoplasia, liver disease, and I M H A . This could reflect sub
nary T E disease; these include weakness, dyspnea, and col clinical T E disease or another clot activation mechanism
lapse. Respiratory difficulty may develop as a result o f because these conditions are associated with a procoagulant
pulmonary abnormalities or left heart failure (pulmonary state. Body cavity hemorrhage also causes a rise in D-dimer
edema) depending on the underlying disease and degree o f concentrations. Because this condition is associated with
myocardial dysfunction. Some animals with respiratory dis increased fibrin formation, elevated D-dimer levels may not
tress have no radiographically evident pulmonary infiltrates. indicate T E disease i n such cases. The specificity o f D-dimer
Increased pulmonary venous pressure preceding overt edema testing for pathologic thromboembolism is lower at lower
(from acute myocardial dysfunction) or concurrent p u l m o D-dimer concentrations, but the high sensitivity at lower
nary emboli are potential causes. Other findings i n animals concentrations provides an important screening tool. D-
with myocardial necrosis include sudden death, tachycardia, dimer testing appears to be as specific for D I C as F D P mea
weak pulses, increased lung sounds or crackles, cough, surement. A number o f assays have been developed to
cardiac murmur, hyperthermia or sometimes hypothermia, measure D-dimer concentrations i n dogs; some are qualita
and (less commonly) G I signs. Signs o f other systemic disease tive or semiquantitative (i.e., latex agglutination, immuno
may be concurrent. Acute ischemic myocardial injury that chromatographic, and immunofiltration tests), others are
causes sudden death may not be detectable o n routine more quantitative (i.e., immunoturbidity, enzymatic i m m u
histopathology noassays). It is important to interpret D - d i m e r results i n the
context o f other clinical and test findings. Assays for circulat
Diagnosis ing A T and proteins C and S are also available for dogs and
Thoracic radiography is used to screen for cardiac abnor cats. Deficiencies of these proteins are associated with
malities, especially i n animals with systemic arterial T E increased risk o f thrombosis.
Thromboelastography ( T E G ) provides an easy point-of- serum electrolyte concentrations are monitored daily or
care method o f assessing global hemostasis and is quite valu more frequently i f fibrinolytic therapy is used. Continuous
able when evaluating patients with T E disease. E C G monitoring during the first several days can help the
clinician detect acute hyperkalemia associated with reperfu
Treatment and Prognosis sion (see Chapter 2, p. 31). In general, the prognosis is
The goals o f therapy are the same as for cats w i t h T E disease: poor.
Stabilize the patient by supportive treatment as indicated,
prevent extension o f the existing thrombus and additional PROPHYLAXIS AGAINST ARTERIAL
T E events, and reduce the size o f the thromboembolus THROMBOEMBOLISM
and restore perfusion. Supportive care is given to improve Prophylactic strategies are the same as for cats. Aspirin,
and maintain adequate tissue perfusion, m i n i m i z e further L M W H , warfarin, or possibly clopidogrel are agents to con
endothelial damage and b l o o d stasis, and optimize organ sider. If warfarin is used, the usual initial warfarin dose is 0.25
function as well as to allow time for collateral circulation to 0.5 m g (total dose) administered orally q24(to 48)h in cats;
development. Correcting or managing underlying disease(s), 0.1 to 0.2 mg/kg administered orally q24h i n dogs. A loading
to the extent possible, is also important. Antiplatelet dose of ~0.2 mg/kg for 2 days appears to be safe in dogs.
and anticoagulant therapies are used to reduce platelet
aggregation and growth o f existing t h r o m b i as i n cats (see p.
199). The results of the T E G , i f available, should be used to VENOUS THROMBOSIS
monitor response to anticoagulants i n patients with T E
disease. Thrombosis i n large veins is more likely to be clinically
Management strategies used for T E disease are outlined evident than thrombosis i n small vessels. Cranial vena caval
in Box 12-3. Although fibrinolytic therapy is used i n some thrombosis has been associated w i t h I M H A and/or immune-
cases, dosage uncertainties, the need for intensive care, and mediated thrombocytopenia, sepsis, neoplasia, protein-
the potential for serious complications limit its use. The losing nephropathies, mycotic disease, heart disease, and
reported streptokinase protocol for dogs is 90,000 I U infused glucocorticoid therapy (especially in patients with systemic
intravenously over 20 to 30 minutes, then continued at a rate inflammatory disease) i n dogs. Most cases have more than
of 45,000 I U / h o u r for 3 (to 12) hours. In dogs, rt-PA has one predisposing factor. A n indwelling jugular catheter
been used as 1 mg/kg boluses administered intravenously increases the risk for cranial caval thrombosis, probably by
q1h for 10 doses, w i t h I V fluid, other supportive therapy, and causing vascular endothelial damage or laminar flow disrup
close monitoring. The half-life o f t-PA is about 2 to 3 minutes tion or by acting as a nidus for clot formation.
i n dogs, but effects persist longer because o f b i n d i n g to Portal vein thrombosis, along with D I C , has occurred in
fibrin. The consequences o f reperfusion injury present dogs with pancreatitis and pancreatic necrosis. Peritonitis,
serious complications to thrombolytic therapy. The i r o n che neoplasia, hepatitis, protein-losing nephropathy, I M H A , and
lator deferoxamine mesylate has been used i n an attempt to vasculitis have also been diagnosed occasionally in dogs
reduce oxidative damage caused by free radicals involving with portal thrombosis. A high proportion of dogs with
iron. A l l o p u r i n o l also has been used but with uncertain incidental portal or splenic vein thrombosis are receiving
results. Clot removal using an embolectomy catheter has not corticosteroids.
been very effective i n cats but might be more successful i n Systemic venous thrombosis produces signs related to
dogs o f larger size. increased venous pressure upstream from the obstruction.
Fluid therapy is used to expand vascular volume, support Thrombosis o f the cranial vena cava can lead to the cranial
blood pressure, and correct electrolyte and acid/base abnor caval syndrome. The cranial caval syndrome is characterized
malities depending o n individual patient needs. However, by bilaterally symmetric subcutaneous edema o f the head,
for animals with heart disease and especially C H F , fluid neck, and forelimbs; another cause o f this syndrome is exter
therapy is given only w i t h great caution (if at all). Hypother nal compression o f the cranial cava, usually by a neoplastic
mia that persists after circulating volume is restored can be mass. Pleural effusion occurs commonly. This effusion is
addressed with external warming. Specific treatment for often chylous because l y m p h flow from the thoracic duct
heart disease, C H F , and arrhythmias is provided as indicated into the cranial vena cava is also impaired. Palpable throm
(see Chapters 3 and 4 and other relevant chapters). Acute bosis extends into the jugular veins i n some cases. Because
respiratory signs may signal C H F , pain, or p u l m o n a r y throm vena caval obstruction reduces pulmonary blood flow and
boembolism. Differentiation is important because diuretic left heart filling, signs of poor cardiac output are common.
or vasodilator therapy could worsen perfusion i n animals Vena caval thrombosis may be visible on ultrasound
without C H F . exam, especially when the clot extends into the right atrium.
Because acute arterial embolization is particularly painful, Portal vein thrombosis and thromboemboli i n the aorta or
analgesic therapy is important i n such cases, especially for other large peripheral vessels can also be documented on
the first 24 to 36 hours (see Box 12-3). Loosely bandaging ultrasound examination.
the affected limb(s) to prevent self-mutilation may be needed Clinicopathic findings generally reflect underlying disease
in some animals w i t h aortic T E disease. Renal function and as well as tissue damage resulting from vascular obstruction.
Cranial caval thrombosis has been associated with thrombo cardial necrosis: 28 cases, / Am Anim Hosp Assoc 36:199,
cytopenia. 2000.
Laste NJ, Harpster NK: A retrospective study of 100 cases of feline
distal aortic thromboembolism: 1977-1993, / Am Anim Hosp
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Alwood AJ et al: Anticoagulant effects of low-molecular-weight McMichael M A et al: Plasma homocysteine, B vitamins, and amino
heparins in healthy cats, / Vet Intern Med 21:378, 2007. acid concentrations in cats with cardiomyopathy and arterial
Boswood A, Lamb CR, White RN: Aortic and iliac thrombosis in thromboembolism, / Vet Intern Med 14:507, 2000.
six dogs, / Small Anim Pract 41:109, 2000. Moore K E et al: Retrospective study of streptokinase administra
Bright JM, Dowers K, Powers BE: Effects of the glycoprotein Ilb/IIIa tion in 46 cats with arterial thromboembolism, / Vet Emerg Crit
antagonist abciximab on thrombus formation and platelet func Care 10:245, 2000.
tion in cats with arterial injury, Vet Ther 4:35, 2003. Nelson OL, Andreasen C: The utility of plasma D-dimer to
Buchanan JW, Beardow AW, Sammarco CD: Femoral artery occlu identify thromboembolic disease in dogs, /Vet Intern Med 17:830,
sion in Cavalier King Charles Spaniels, / Am Vet Med Assoc 2003.
211:872, 1997. Olsen L H et al: Increased platelet aggregation response in Cavalier
Carr AP, Panciera DL, Kidd L: Prognostic factors for mortality and King Charles Spaniels with mitral valve prolapse, / Vet Intern Med
thromboembolism in canine immune-mediated hemolytic 15:209, 2001.
anemia: a retrospective study of 72 dogs, / Vet Intern Med 16:504, Palmer KG, King LG, Van Winkle TJ: Clinical manifestations and
2002. associated disease syndromes in dogs with cranial vena cava
Cook AK, Cowgill LD: Clinical and pathological features of protein- thrombosis: 17 cases (1989-1996), f Am Vet Med Assoc 213:220,
losing glomerular disease in the dog: a review of 137 cases (1985- 1998.
1992), J Am Anim Hosp Assoc 32:313, 1999. Schermerhorn TS, Pembleton-Corbett JR, Kornreich B: Pulmonary
De Laforcade A M et al: Hemostatic changes in dogs with naturally thromboembolism in cats, / Vet Intern Med 18:533, 2004.
occurring sepsis, / Vet Intern Med 17:674, 2003. Schoeman JP: Feline distal aortic thromboembolism: a review of 44
Driehuys S et al: Myocardial infarction in dogs and cats: 37 cases cases (1990-1998), / Feline Med Surg 1:221, 1999.
(1985-1994), J Am Vet Med Assoc 213:1444, 1998. Smith CE et al: Use of low molecular weight heparin in cats: 57
Fox PR, Petrie JP, Hohenhaus AE: Peripheral vascular disease. In cases (1999-2003), J Am Vet Med Assoc 225:1237, 2004.
Ettinger SJ, Feldman EC, editors: Textbook of veterinary internal Smith SA et al: Arterial thromboembolism in cats: acute crisis in
medicine, ed 6, Philadelphia, 2005, WB Saunders, pp 1145- 127 cases (1992-2001) and long-term management with low-
1165. dose aspirin in 24 cases, / Vet Intern Med 17:73, 2003.
Good LI, Manning A M : Thromboembolic disease: physiology Smith SA, Tobias A H : Feline arterial thromboembolism: an
of hemostasis and pathophysiology of thrombosis, Compend update, Vet Clin North Am: Small Anim Pract 34:1245,
Contin Educ Pract Vet 25:650, 2003. 2004.
Good LI, Manning A M : Thromboembolic disease: predispositions Stokol T et al: D-dimer concentrations in healthy dogs and dogs
and clinical management, Compend Contin Educ Pract Vet 25:660, with disseminated intravascular coagulation, Am ] Vet Res 61:393,
2003. 2000.
Hogan DF et al: Antiplatelet effects and pharmacodynamics of Thompson MF, Scott-Moncrieff JC, Hogan DF: Thrombolytic
clopidogrel in cats,/Am Vet Med Assoc 225:1406, 2004. therapy in dogs and cats, J Vet Emerg Crit Care 11:111,
Hogan DF et al: Evaluation of antiplatelet effects of ticlopidine in 2001.
cats, Am J Vet Res 65:327, 2004. Van Winkle TJ, Hackner SG, Liu SM: Clinical and pathological
Kidd L, Stepien RL, Amrheiw DP: Clinical findings and coronary features of aortic thromboembolism in 36 dogs, / Vet Emerg Crit
artery disease in dogs and cats with acute and subacute myo Care 3:13, 1993.
Diuretics
Continued
Drugs Used in Cardiovascular Disorderscont'd
GENERIC N A M E TRADE N A M E DOG CAT
Other Vasodilators
Antiarrhythmic Drugs
Class I
Class II
Class III
Class IV
Continued
Drugs Used i n Cardiovascular Disorderscont'd
Antiarrhythmic Drugs
Sympathomimetics
Heartworm Prevention
Antithrombotic Agents
PO, By mouth; IV, intravenous; IM, intramuscular; SC, subcutaneous; CHF, congestive heart failure; CRI, constant rate infusion; RR, respiratory
rate.
PART TWO RESPIRATORY SYSTEM DISORDERS
Eleanor C . Hawkins
C H A P T E R 13
Clinical Manifestations of
Nasal Disease
General Diagnostic Approach to Dogs and Cats with Chronic Nasal Discharge
History Aspergillus titer Nasal swab cytologic evalua Complete blood count
Physical examination tion (cryptococcosis) Platelet count
Funduscopic examination Cryptococcal antigen titer Coagulation times
Thoracic radiographs Viral testing Buccal mucosal bleeding time
Feline leukemia virus Tests for tick-borne diseases (dogs)
Feline immunodeficiency virus Arterial blood pressure
+ / - Herpesvirus von Willebrand's factor assay (dogs)
+ / - Calicivirus
Phase IIAll Patients (General Anesthesia Required)
Nasal radiography or computed tomography
Oral examination
Rhinoscopy: external nares and nasopharynx
Nasal biopsy/histologic examination
Deep nasal culture
Fungal
Bacterial
to severe inflammation, and bacteria. Tests to identify her w h i c h acute viral infection is not suspected. These diagnos
pesvirus and calicivirus infections may be performed i n cats tic tests are performed w i t h the dog or cat under general
w i t h acute and chronic rhinitis. These tests are most useful anesthesia. Nasal radiographs or C T scans are obtained first,
i n evaluating cattery problems rather than the condition o f followed by oral examination and rhinoscopy and then spec
an individual cat (see Chapter 15). i m e n collection. This order is recommended because the
Fungal titer determinations are available for aspergillosis results of radiography or C T and rhinoscopy are often useful
i n dogs and cryptococcosis i n dogs and cats. The test for i n the selection of biopsy sites. In addition, hemorrhage from
aspergillosis detects antibodies i n the b l o o d . A single positive biopsy sites could obscure or alter radiographic and rhino
test result strongly suggests active infection by the organism; scopic detail i f the specimen were collected first. In dogs and
however, a negative titer does not rule out the disease. In cats suspected o f having acute foreign body inhalation, rhi
either case, the result o f the test must be interpreted i n con noscopy is performed first i n the hopes o f identifying and
junction w i t h results o f nasal imaging, rhinoscopy, and nasal removing the foreign material. (See Chapter 14 for more
histology and culture. detail o n nasal radiography, C T , and rhinoscopy.)
The b l o o d test o f choice for cryptococcosis is the latex The combination o f radiography, rhinoscopy, and nasal
agglutination capsular antigen test ( L C A T ) . Because organ biopsy has a diagnostic success rate o f approximately 80% in
ism identification is usually possible i n specimens from dogs. Dogs w i t h persistent signs i n which a diagnosis cannot
infected organs, organism identification is the m e t h o d o f be obtained following the assessment described earlier
choice for a definitive diagnosis. The L C A T is performed i f require further evaluation. It is more difficult to evaluate the
cryptococcosis is suspected but an extensive search for the success rate for cats. H i g h proportions o f cats with chronic
organism has failed. The L C A T is also performed i n animals nasal discharge suffer from feline chronic rhinosinusitis
w i t h a confirmed diagnosis as a means o f m o n i t o r i n g thera (idiopathic rhinitis) and are diagnosed only through exclu
peutic response (see Chapter 98). sion. Cats are evaluated further only i f signs suggestive of
In general, nasal radiography or computerized tomogra another disease are found during any part of their evaluation
phy ( C T ) , rhinoscopy, and biopsy are required to establish a or i f the clinical signs are progressive or intolerable to the
diagnosis o f intranasal disease i n most dogs and i n cats i n owners.
Nasal C T is considered i f not performed previously and conjunctivitis and fever, may be present as well as a history
if a diagnosis has not been made. C T provides excellent of exposure to other cats or kittens.
visualization of all o f the nasal turbinates and may allow the Dogs i n which acute, paroxysmal sneezing develops should
identification o f small masses that are not visible on nasal undergo prompt rhinoscopic examination (see Chapter 14).
radiography or rhinoscopy. C T is also more accurate than W i t h time, foreign material may become covered w i t h mucus
nasal radiography i n determining the extent o f nasal tumors. or migrate deeper into the nasal passages, and any delay i n
Magnetic resonance imaging ( M R I ) may be more accurate performing rhinoscopy may interfere with the identification
than C T i n the assessment o f soft tissues, such as nasal neo and removal o f the foreign bodies. Nasal mites are also iden
plasia. In the absence o f a diagnosis, nasal imaging (prefer tified rhinoscopically. In contrast, cats sneeze more often as
ably C T or M R I ) , rhinoscopy, and biopsy can be repeated a result o f acute viral infection rather than a foreign body.
after a 1- to 2-month delay. Immediate rhinoscopic examination is not indicated unless
Exploratory rhinotomy with turbinectomy is the final there has been k n o w n exposure to a foreign body or the
diagnostic test. Surgical exploration o f the nose allows direct history and physical examination findings do not support a
visualization of the nasal cavity for the presence o f foreign diagnosis o f viral upper respiratory infection.
bodies, mass lesions, or fungal mats and for obtaining b i o p
sies and culture specimens. The potential benefits o f surgery, REVERSE SNEEZING
however, should be weighed against the potential complica Reverse sneezing is a paroxysm o f noisy, labored inspiration
tions associated with rhinotomy and turbinectomy. The Sug initiated by nasopharyngeal irritation. Such irritation can be
gested Readings section offers surgical references. the result o f a foreign body located dorsal to the soft palate
or nasopharyngeal inflammation. Foreign bodies usually
originate from grass or plant material that is prehended into
SNEEZING the oral cavity and which, presumably, is coughed up or
migrates into the nasopharyx. Epiglottic entrapment o f the
soft palate has also been proposed as a cause. The majority
Etiology and Diagnostic Approach of cases are idiopathic. Small-breed dogs are usually affected,
A sneeze is an explosive release o f air from the lungs through and signs may be associated with excitement or drinking.
the nasal cavity and mouth. It is a protective reflex to expel The paroxysms last only a few seconds and do not signifi
irritants from the nasal cavity. Intermittent, occasional sneez cantly interfere w i t h respiration. A l t h o u g h these animals
ing is considered normal. Persistent, paroxysmal sneezing usually display this sign throughout their life, the problem
should be considered abnormal. Disorders c o m m o n l y asso rarely progresses.
ciated with acute-onset, persistent sneezing include nasal The diagnosis is generally made by a thorough history
foreign body and feline upper respiratory infection. The and physical examination. Generally, no treatment is needed
canine nasal mite, Pneumonyssoides caninum, and exposure because the episodes are self-limiting. Some owners report
to irritating aerosols are less c o m m o n causes o f sneezing. A l l that massaging the neck shortens an ongoing episode or that
the nasal diseases considered as differential diagnoses for administration o f antihistamines decreases the frequency
nasal discharge are also potential causes for sneezing; and severity o f episodes, but controlled studies are lacking.
however, animals with these diseases generally present with Further evaluation for potential nasal or pharyngeal disor
nasal discharge as the primary complaint. ders is indicated i f syncope, exercise intolerance, or other
The owners should be questioned carefully concerning signs o f respiratory disease are reported or i f the reverse
the possible recent exposure of the pet to foreign bodies sneezing is severe or progressive.
(e.g., rooting i n the ground, running through grassy fields),
powders, and aerosols or, i n cats, exposure to new cats or
kittens. Sneezing is an acute phenomenon that often subsides STERTOR
with time. A foreign body should not be excluded from the
differential diagnoses just because the sneezing subsides. In Stertor refers to coarse, audible snoring or snorting sounds
the dog a history of acute sneezing followed by the develop associated w i t h breathing. It indicates upper airway obstruc
ment of a nasal discharge is suggestive o f a foreign body. tion. Stertor is most often the result o f pharyngeal disease
Other findings may help narrow the list of differential (see Chapter 16). Intranasal causes o f stertor include obstruc
diagnoses. Dogs with foreign bodies may paw at their nose. tion caused by congenital deformities, masses, exudate, or
Foreign bodies are typically associated with unilateral, muco b l o o d clots. Evaluation for nasal disease proceeds as described
purulent nasal discharge, although serous or serosanguine for nasal discharge.
ous discharge may be present initially. Foreign bodies i n the
caudal nasopharynx may cause gagging, retching, or reverse
sneezing. The nasal discharge associated w i t h reactions to FACIAL DEFORMITY
aerosols, powders, or other inhaled irritants is usually bilat
eral and serous i n nature. In cats other clinical signs sup Carnaissal tooth root abscess i n dogs can result i n swelling,
portive of a diagnosis of upper respiratory infection, such as often with drainage, adjacent to the nasal cavity and beneath
FIG 1 3 - 4
F a c i a l deformity c h a r a c t e r i z e d b y firm swelling over the maxilla in t w o cats. A , Deformity
in this c a t w a s the result of c a r c i n o m a . N o t i c e the ipsilateral b l e p h a r o s p a s m . B , Deformity
in this c a t w a s the result of c r y p t o c o c c o s i s . A p h o t o m i c r o g r a p h of the fine-needle aspirate
of this swelling is p r o v i d e d in F i g . 1 3 - 2 .
the eye. Excluding dental disease, the most c o m m o n causes Henderson SM: Investigation of nasal disease in the cat: a retrospec
of facial deformity adjacent to the nasal cavity are neoplasia tive study of 77 cases, / Fel Med Surg 6:245, 2004.
and, i n cats, cryptococcosis (Fig. 13-4). Visible swellings can Lent SE et al: Evaluation of rhinoscopy and rhinoscopy-assisted
mucosal biopsy in diagnosis of nasal disease in dogs: 119 cases
often be evaluated directly through fine-needle aspiration or
(1985-1989), J Am VetMedAssoc 201:1425, 1992.
punch biopsy (see Fig. 13-2). Further evaluation proceeds as
Pomrantz JS et al: Comparison of serologic evaluation via agar gel
for nasal discharge i f such an approach is not possible or is
immunodiffusion and fungal culture of tissue for diagnosis of
unsuccessful. nasal aspergillosis in dogs, f Am Vet Med Assoc 203:1319, 2007.
Slatter D: Textbook of small animal surgery, ed 3, St Louis, 2003, WB
Suggested Readings Saunders.
Demko JL et al: Chronic nasal discharge in cats, J Am Vet Med Assoc Strasser JL et al: Clinical features of epistaxis in dogs: a retrospective
230:1032, 2007. study of 35 cases (1999-2002), J Am Anim Hosp Assoc 41:179,
Fossum TW: Small animal surgery, ed 3, St Louis, 2007, Mosby. 2005.
C H A P T E R 14
FIG 1 4 - 3
Positioning of a d o g for frontal sinus r a d i o g r a p h s . The
e n d o t r a c h e a l a n d anesthetic tubes a r e d i s p l a c e d laterally i
this instance b y t a p i n g them to a n upright metal cylinder.
FIG 1 4 - 2
Intraoral r a d i o g r a p h of a c a t with c a r c i n o m a . N o r m a l fine
turbinate pattern is visible o n the left s i d e (L) of n a s a l c a v i t y
a n d p r o v i d e s b a s i s for c o m p a r i s o n with the right side (R).
Turbinate pattern is less a p p a r e n t o n right s i d e , a n d a n a r e a
of turbinate lysis c a n b e seen a d j a c e n t to the first premolar.
* Note that these descriptions represent typical cases and are not specific findings.
accurate localization o f mass lesions for subsequent biopsy provides good visualization through the external nares i n
than nasal radiography, and it is instrumental for radio most patients. Endoscopes without biopsy or suction chan
therapy treatment planning. Determination o f the integrity nels are preferable because o f their small outside diameter.
of the cribriform plate is important i n treatment planning Some o f these systems are relatively inexpensive, including
for nasal aspergillosis. C T may also identify the presence o f one model that can be attached to a standard otoscope
lesions i n animals w i t h undiagnosed nasal disease when handle for the light source (Fig. 14-9). Scopes designed for
other techniques have failed. Typical lesions are as described arthroscopy, cystoscopy, and sexing o f birds also work well.
i n B o x 14-1. M R I may be more accurate than C T i n the In m e d i u m to large dogs, a flexible pediatric bronchoscope
assessment o f soft tissues, such as nasal neoplasia. (e.g., 4 - m m outer diameter) can be used. Flexible endo
scopes are now available i n smaller sizes, similar to small
rigid scopes, although they are relatively more expensive and
RHINOSCOPY fragile. If an endoscope is not available, the rostral region of
the nasal cavity can be examined w i t h an otoscope. H u m a n
Rhinoscopy allows visual assessment o f the nasal cavity pediatric otoscopic cones ( 2 - to 3 - m m diameter) can be
through the use o f a rigid or flexible endoscope or an oto purchased for examining cats and small dogs.
scopic cone. Rhinoscopy is used to visualize and remove General anesthesia is required for rhinoscopy. Rhinos
foreign bodies; to grossly assess the nasal mucosa for the copy is usually performed immediately after nasal imaging
presence o f inflammation, turbinate erosion, mass lesions, unless a foreign body is strongly suspected. The oral cavity
fungal plaques, and parasites; and to aid i n the collection o f and caudal nasopharynx should be assessed first. D u r i n g the
nasal specimens for histopathologic examination and culture. oral examination the hard and soft palates are visually exam
Complete rhinoscopy always includes a thorough examina ined and palpated for deformation, erosions, or defects, and
tion o f the oral cavity and caudal nasopharynx, i n addition the gingival sulci are probed for fistulae.
to visualization of the nasal cavity through the external nares. The caudal nasopharynx is evaluated for the presence of
The extent o f visualization depends o n the quality o f the nasopharyngeal polyps, neoplasia, and foreign bodies.
equipment and the outside diameter o f the rhinoscope. A Foreign bodies, particularly grass or plant material, are c o m
narrow ( 2 - to 3 - m m diameter), rigid fiberoptic endoscope m o n l y found i n this location i n cats and occasionally i n dogs.
FIG 1 4 - 8
C T scans of n a s a l cavity of t w o different d o g s at the level of the e y e s . A , N o r m a l n a s a l
turbinates a n d intact n a s a l septum a r e present. B , N e o p l a s t i c mass is present within the
right cavity; it is e r o d i n g through the h a r d p a l a t e (white arrow), the frontal b o n e into the
retrobulbar s p a c e (small black arrows), a n d the n a s a l septum. The tumor a l s o extends into
the right frontal sinus. F, Frontal sinus; E, e n d o t r a c h e a l tube; T, t o n g u e .
FIG 1 4 - 1 0
The c a u d a l n a s o p h a r y n x is best e x a m i n e d with a flexible
e n d o s c o p e that is p a s s e d into the o r a l cavity a n d retro-
flexed 1 8 0 d e g r e e s a r o u n d the e d g e of the soft p a l a t e , a s
s h o w n in this r a d i o g r a p h .
FIG 1 4 - 1 2
V i e w of the internal nares (thin arrows) o b t a i n e d b y p a s s i n g
a flexible b r o n c h o s c o p e a r o u n d the e d g e of the soft palate in
NASAL BIOPSY: INDICATIONS
a d o g with nasal d i s c h a r g e . A soft tissue mass (broad arrow) AND TECHNIQUES
is blocking the normally thin septum a n d is partially obstructing
the a i r w a y lumens. C o m p a r e this v i e w with the a p p e a r a n c e Visualization o f a foreign body or nasal parasites during
of the n o r m a l septum a n d right internal naris in F i g . 14-11 rhinoscopy establishes a diagnosis. For many dogs and cats,
BOX 14-2
Mass
Neoplasia
Nasopharyngeal polyp
Cryptococcosis
M a t of f u n g a l h y p h a e or f u n g a l g r a n u l o m a (aspergillosis,
penicilliosis, rhinosporidiosis)
Turbinate Erosion
Mild
Feline herpesvirus
Chronic inflammatory process
Marked
Aspergillosis
Neoplasia
Cryptococcosis
Penicilliosis
Fungal Plaques
Aspergillosis
Penicilliosis
Parasites
M i t e s : Pneumonyssoides caninum
FIG 14-13 W o r m s : Capillaria (Eucoleus) boehmi
A , R h i n o s c o p i c v i e w through the external naris of a d o g
with aspergillosis s h o w i n g e r o s i o n of turbinates a n d a Foreign Bodies
green-brown g r a n u l o m a t o u s mass. B , A closer v i e w of the
fungal mat shows white, filamentous structures (hyphae).
FIG 14-14
R h i n o s c o p i c v i e w through the external naris. A , A single n a s a l mite is seen in this d o g
with Pneumonyssoides caninum. B , A thin white w o r m is seen in this d o g with Capillaria
(Eucoleus) boehmi.
however, the diagnosis must be based o n cytologic, histo oral cavity and internal nares, with the tip o f the catheter
logic, and microbiologic evaluation o f nasal biopsy speci pointing rostrally. W i t h the animal i n sternal recumbency
mens. Nasal biopsy specimens should be obtained immediately and the nose pointed toward the floor, approximately 100 m l
after nasal imaging and rhinoscopy while the animal is still of sterile saline solution is forcibly injected i n pulses by
anesthetized. These earlier procedures can help localize the syringe. The fluid exiting the external nares is collected i n a
lesion, m a x i m i z i n g the likelihood o f obtaining material rep bowl and can be examined cytologically. Occasionally nasal
resentative o f the p r i m a r y disease process. mites can be identified i n nasal flushings. Magnification or
Nasal biopsy techniques include nasal swab, nasal flush, placement o f dark paper behind the specimen for contrast
pinch biopsy, and turbinectomy. Fine-needle aspirates can may be needed to visualize the mites. A portion o f fluid can
be obtained from mass lesions as described i n Chapter 75. also be filtered through a gauze sponge. Large particles
P i n c h biopsy is the preferred nonsurgical method o f speci trapped i n the sponge can be retrieved and submitted for
men collection. It is more likely to provide pieces o f nasal histopathologic analysis. These specimens are often insuffi
tissue that extend beneath the superficial inflammation, cient for providing a definitive diagnosis.
which is c o m m o n to many nasal disorders, than nasal swabs
or flushes. In addition, the pieces o f tissue obtained w i t h this PINCH BIOPSY
more aggressive method can be evaluated histologically, Pinch biopsy is the author's preferred method of nasal biopsy.
whereas the material obtained w i t h the less traumatic tech In the p i n c h biopsy technique, alligator cup biopsy forceps
niques may be suitable only for cytologic analysis. H i s ( m i n i m u m size, 2 x 3 m m ) are used to obtain pieces o f nasal
topathologic examination is preferred over cytologic mucosa for histologic evaluation (Fig. 14-15). Full-thickness
examination i n most cases because the marked inflamma tissue specimens can be obtained, and guided specimen col
tion that accompanies many nasal diseases makes it difficult lection is more easily performed with this technique than
to cytologically differentiate p r i m a r y from secondary inflam w i t h previously described methods. The biopsy forceps are
mation and reactive from neoplastic epithelial cells. Carci passed adjacent to a rigid endoscope and directed to any
nomas can also appear cytologically as l y m p h o m a and vice gross lesions. If a flexible scope is used, biopsy instruments
versa. can be passed through the biopsy channel of the endoscope.
Regardless o f the technique used (except for nasal swab), The resulting specimens are extremely small and may not be
the cuff o f the endotracheal tube should be inflated (avoid of sufficient quality for diagnostic purposes. Larger alligator
ing overinflation) and the caudal pharynx packed with gauze forceps are preferred. If lesions are not present grossly but
sponges to prevent the aspiration o f fluid. Intravenous crys are present radiographically or by CT, the biopsy instrument
talloid fluids (10 to 20 m l / k g / h plus replacement o f esti can be guided using the relationship of the lesion to the
mated b l o o d loss) are recommended during the procedure upper teeth.
to counter the hypotensive effects o f prolonged anesthesia After the first piece is taken, bleeding w i l l prevent further
and b l o o d loss from hemorrhage after biopsy. Blood-clotting visual guidance; therefore the forceps are passed blindly to
capabilities should be assessed before the more aggressive the position identified during rhinoscopic examination (e.g.,
biopsy techniques are performed i f there is any history o f meatus involved and depth from external naris). If a mass is
hemorrhagic exudate or epistaxis or any other indication o f present, the forceps are passed i n a closed position until just
coagulopathy. before the mass is reached. The forceps are then opened and
passed a short distance farther until resistance is felt. Larger
NASAL SWAB forceps, such as a mare uterine biopsy instrument, are useful
The least traumatic techniques are the nasal swab and nasal for collecting large volumes o f tissue from m e d i u m to large
flush. Unlike the other collection techniques, nasal swabs can size dogs w i t h nasal masses. No forceps should ever be passed
be collected from an awake animal. Nasal swabs are useful into the nasal cavity deeper than the level of the medial canthus
for identifying cryptococcal organisms cytologically and of the eye without visual guidance to keep from penetrating the
should be collected early i n the evaluation o f cats with cribriform plate.
chronic rhinitis. Other findings are generally nonspecific. A m i n i m u m o f six tissue specimens (using a 2 X 3 m m
Exudate immediately w i t h i n the external nares or draining forcep or larger) should be obtained from any lesion. If no
from the nares is collected using a cotton-tipped swab. Rela localizable lesion is identified radiographically or rhinoscop
tively small swabs are available (e.g., D a c r o n swabs; Puritan ically, multiple biopsies (usually 6 to 10) are obtained ran
M e d i c a l Products C o . L L C ) that can facilitate specimen col d o m l y from both sides o f the nasal cavity.
lection from cats w i t h m i n i m a l discharge. The swab is then
rolled o n a microscope slide. Routine cytologic stains are TURBINECTOMY
generally used, although India i n k can be applied to demon Turbinectomy provides the best tissue specimens for histo
strate cryptococcal organisms (see Chapter 98). logic examination and allows the clinician to remove
abnormal or poorly vascularized tissues, debulk fungal
NASAL FLUSH granulomas, and place drains for subsequent topical nasal
Nasal flush is a m i n i m a l l y invasive technique. A soft catheter therapy. Turbinectomy is performed through a rhinotomy
is positioned i n the caudal region o f the nasal cavity v i a the incision and is a more invasive technique than those previ-
FIG 1 4 - 1 5
C u p b i o p s y f o r c e p s a r e a v a i l a b l e in different s i z e s . To o b t a i n sufficient tissue, a m i n i m u m
size of 2 x 3 mm is r e c o m m e n d e d . The l a r g e r forceps a r e p a r t i c u l a r l y useful for o b t a i n i n g
b i o p s i e s from n a s a l masses in d o g s .
ously described. Turbinectomy is a reasonably difficult carotid artery o n the involved side can be ligated without
surgical procedure that should be considered only when subsequent adverse effects. R h i n o t o m y should not be
other less invasive techniques have failed to establish the attempted. In the vast majority of animals, only time or cold
diagnosis. Potential operative and postoperative complica saline infusions are required to control hemorrhage. The fear
tions include pain, excessive hemorrhage, inadvertent entry of severe hemorrhage should not prevent the collection of
into the cranial vault, and recurrent nasal infections. Cats good-quality tissue specimens.
may be anorectic postoperatively. Placement o f an esopha Trauma to the brain is prevented by never passing any
gostomy or gastrostomy tube (see Chapter 30) should be object into the nasal cavity beyond the level o f the medial
considered i f necessary to provide a means for meeting canthus o f the eye without visual guidance. The distance
nutritional requirements during the recovery period. (See from the external nares to the medial canthus is noted by
Suggested Readings i n Chapter 13 for information o n the holding the instrument or catheter against the face, with the
surgical procedure.) tip at the medial canthus. The level o f the nares is marked
o n the instrument or catheter w i t h a piece o f tape or marking
Complications pen. The object should never be inserted beyond that
The major complication associated w i t h nasal biopsy is h e m mark.
orrhage. The severity o f hemorrhage depends o n the method Aspiration o f b l o o d , saline solution, or exudate into the
used to obtain the biopsy, but even w i t h aggressive tech lungs must be avoided. A cuffed endotracheal tube should
niques the hemorrhage is rarely life threatening. W h e n any be i n place d u r i n g the procedure, and the caudal pharynx
technique is used, the floor o f the nasal cavity is avoided to should be packed w i t h gauze after visual assessment o f the
prevent damage to major b l o o d vessels. For m i n o r hemor oral cavity and nasopharynx. The cuff should be sufficiently
rhage, the rate of administration o f intravenous fluids should inflated to prevent audible leakage o f air during gentle c o m
be increased and manipulations w i t h i n the nasal cavity pression o f the reservoir bag o f the anesthesia machine.
should be stopped until the bleeding subsides. C o l d saline Overinflation o f the cuff may lead to tracheal trauma or tear.
solution with or without diluted epinephrine (1:100,000) The nose is pointed toward the floor over the end o f the
can be gently infused into the nasal cavity. Persistent severe examination table, allowing b l o o d and fluid to drip out from
hemorrhage can be controlled by packing the nasal cavity the external nares after rhinoscopy and biopsy. Finally, the
with umbilical tape. The tape must be packed through the caudal pharynx is examined d u r i n g gauze removal and
nasopharynx as well as through the external nares or the before extubation for visualization o f continued accumula
blood will only be redirected. Similarly, placing swabs or tion o f fluid. Gauze sponges are counted d u r i n g placement
gauze i n the external nares serves only to redirect b l o o d and then recounted during removal so that none is inadver
caudally. In the rare event of uncontrolled hemorrhage, the tently left behind.
NASAL CULTURES: SAMPLE COLLECTION biotic therapy. Sensitivity data from bacterial cultures con
AND INTERPRETATION sidered to represent significant infection may help i n
antibiotic selection. (See Chapter 15 for further therapeutic
Microbiologic cultures o f nasal specimens are recommended recommendations.)
but can be difficult to interpret. Aerobic and anaerobic bac The role of Mycoplasma spp. i n respiratory tract infec
terial cultures, mycoplasmal cultures, and fungal cultures can tions of dogs and cats is still being elucidated. Cultures for
be performed on material obtained by swab, nasal flush, or Mycoplasma spp. and treatment with appropriate antibiotics
tissue biopsy. According to Harvey (1984), the n o r m a l nasal are a consideration for cats with chronic rhinosinusitis.
flora can include Escherichia coli, Staphylococcus, Streptococ A diagnosis o f nasal aspergillosis or penicilliosis requires
cus, Pseudomonas, Pasteurella, and Aspergillus organisms and the presence of several supportive signs, and fungal cultures
a variety of other aerobic and anaerobic bacteria and fungi. are indicated whenever fungal disease is one of the differen
Thus bacterial or fungal growth from nasal specimens does tial diagnoses. The growth o f Aspergillus or Penicillium
not necessarily confirm the presence o f infection. organisms is considered along with other clinical data, such
Cultures should be performed on specimens collected as radiographic and rhinoscopic findings, and serologic
within the caudal nasal cavity o f anesthetized patients. titers. Fungal growth supports a diagnosis o f mycotic rhini
Bacterial growth from superficial specimens, such as nasal tis only when other data also support the diagnosis. The fact
discharge or swabs inserted into the external nares o f unanes that fungal infection occasionally occurs secondary to nasal
thetized patients, is unlikely to be clinically significant. It tumors should not be overlooked during initial evaluation
is difficult for a culture swab to be passed into the caudal and m o n i t o r i n g o f therapeutic response. The sensitivity of
nasal cavity without its being contaminated w i t h superficial fungal culture can be greatly enhanced by collecting a swab
(insignificant) organisms. Guarded specimen swabs can or biopsy for culture directly from a fungal plaque or granu
prevent contamination but are relatively expensive. Alter l o m a with rhinoscopic guidance.
natively, mucosal biopsies from the caudal nasal cavity can
be obtained for culture using sterilized biopsy forceps; the Suggested Readings
results may be more indicative o f true infection than those Codner EC et al: Comparison of computed tomography with radi
from swabs because, i n theory, the organisms have invaded ography as a noninvasive diagnostic technique for chronic nasal
disease in dogs,} Am Vet Med Assoc 202:1106, 1993.
the tissues. Superficial contamination may still occur.
Detweiler DA et al: Computed tomographic evidence of bulla effu
Regardless o f the method used, the growth o f many colo
sion in cats with sinonasal disease: 2001-2004, / Vet Intern Med
nies o f one or two types o f bacteria more likely reflects
20:1080, 2006.
infection than the growth o f many different organisms. Harvey CE: Therapeutic strategies involving antimicrobial treat
The microbiology laboratory should be asked to report all ment of the upper respiratory tract in small animals, / Am Vet
growth. Otherwise, the laboratory may report only one or Med Assoc 185:1159, 1984.
two organisms that are more often pathogenic and provide Lefebvre J: Computed tomography as an aid in the diagnosis of
misleading information about the relative purity o f the chronic nasal disease in dogs, / Small Anim Pract 46:280, 2005.
culture. The presence o f septic inflammation based o n his McCarthy TC: Rhinoscopy: the diagnostic approach to chronic
tologic examination of nasal specimens and a positive nasal disease. In McCarthy TR, editor: Veterinary endoscopy for
response to antibiotic therapy support a diagnosis o f the small animal practitioner, St Louis, 2005, Saunders, p 137.
Padrid PA et al: Endoscopy of the upper respiratory tract of the dog
bacterial infection contributing to clinical signs. A l t h o u g h
and cat. In Tarns TR, editor: Small animal endoscopy, ed 2, St
bacterial rhinitis is rarely a primary disease entity, improve
Louis, 1999, Mosby, p 357.
ment i n nasal discharge may be seen i f the bacterial compo
Schoenborn W C et al: Retrospective assessment of computed tomo
nent o f the problem is treated; however, the improvement is graphic imaging of feline sinonasal disease in 62 cats, Vet Rad
generally transient unless the underlying disease process can Ultrasound 44:198, 2003.
be corrected. Some animals i n which a p r i m a r y disease Willard M D et al: Endoscopic examination of the choane in dogs
process is never identified or cannot be corrected (e.g., cats and cats: 118 cases (1988-1998), J Am Vet Med Assoc 215:1301,
with chronic rhinosinusitis) respond well to long-term anti 1999.
C H A P T E R 15
Disorders of the
Nasal Cavity
Clinical Features
CHAPTER OUTLINE
Clinical manifestations o f feline U R I can be acute, chronic
FELINE UPPER RESPIRATORY I N F E C T I O N and intermittent, or chronic and persistent. Acute disease is
BACTERIAL RHINITIS the most c o m m o n . The clinical signs o f acute U R I include
NASAL M Y C O S E S fever, sneezing, serous or mucopurulent nasal discharge,
Cryptococcosis conjunctivitis and ocular discharge, hypersalivation, anorexia,
Aspergillosis and dehydration. F H V can also cause corneal ulceration,
N A S A L PARASITES abortion, and neonatal death, whereas F C V can cause oral
Nasal mites ulcerations, m i l d interstitial pneumonia, or polyarthritis.
Nasal capillariasis Rare, short-lived outbreaks of highly virulent strains o f cali
N A S O P H A R Y N G E A L POLYPS civirus have been associated w i t h severe upper respiratory
NASAL TUMORS disease, signs o f systemic vasculitis (facial and l i m b edema
ALLERGIC RHINITIS progressing to focal necrosis) and high rates o f mortality.
IDIOPATHIC RHINITIS Bordetella can cause cough and, i n young kittens, pneumo
Feline C h r o n i c Rhinosinusitis nia. Signs o f Chlamydophila infection are usually limited to
Canine Chronic/Lymphoplasmacytic Rhinitis conjunctivitis.
Some cats that recover from the acute disease have peri
odic recurrence of acute signs, usually i n association w i t h
stressful or immunosuppressive events. Other cats may have
chronic, persistent signs, most notably a serous to m u c o p u
rulent nasal discharge w i t h or without sneezing. C h r o n i c
FELINE UPPER RESPIRATORY INFECTIONnasal discharge can presumably result from persistence o f an
active viral infection or from irreversible damage to t u r b i
Etiology nates and mucosa by F H V ; the latter predisposes the cat to
Upper respiratory infections (URIs) are c o m m o n i n cats. an exaggerated response to irritants and secondary bacterial
Feline herpesvirus ( F H V ) , also k n o w n as feline rhinotrache rhinitis. Unfortunately, correlation between tests to confirm
itis virus, and feline calicivirus (FCV), cause nearly 90% o f exposure to or the presence o f viruses and clinical signs is
these infections. Bordetella bronchiseptica and Chlamydophila poor (Johnson et al., 2005). Because the role o f viral infec
felis (previously k n o w n as Chlamydia psittaci) are less c o m tion i n cats w i t h chronic rhinosinusitis is not well under
monly involved. Other viruses and Mycoplasmas may play a stood, cats w i t h chronic signs o f nasal disease are discussed
primary or secondary role, whereas other bacteria are con i n the section o n feline chronic rhinosinusitis (p. 232).
sidered secondary pathogens.
Cats become infected through contact w i t h actively Diagnosis
infected cats, carrier cats, and fomites. Cats that are young, Acute U R I is usually diagnosed o n the basis o f history and
stressed, or immunosuppressed are most likely to develop physical examination findings. Specific tests that are avail
clinical signs. Infected cats often become carriers o f F H V or able to identify F H V , F C V , Bordetella, and Chlamydophila
F C V after resolution of the clinical signs. The duration o f organisms include fluorescent antibody testing, virus isola
the carrier state is not k n o w n but may last from weeks to tion procedures or bacterial cultures, polymerase chain reac
years. Bordetella can be isolated from asymptomatic cats, tion ( P C R ) , and serum antibody titers. Fluorescent antibody
although the effectiveness o f transmission o f disease from tests for F H V and F C V are performed o n smears prepared
such cats is not known. from conjunctival scrapings, pharyngeal swabs, or tonsillar
swabs or o n impression smears from tonsillar biopsy speci days, then q72h) can be prescribed for cats that are difficult
mens. Virus isolation tests and P C R can be performed on to medicate.
pharyngeal, conjunctival, or nasal swabs (using sterile swabs Cats with F H V infection may benefit from treatment with
made o f cotton) or on tissue specimens such as tonsillar lysine. It has been postulated that excessive concentrations
biopsy specimens or mucosal scraping. Tissue specimens are of lysine may antagonize arginine, a promoter o f herpesvirus
preferred for virus isolation and P C R . Specimens are placed replication. Lysine (500 mg/cat q l 2 h ) , obtained from health
i n appropriate transport media. Routine cytologic prepara food stores, is added to food. Administration o f feline re
tions o f conjunctival smears can be examined for intracy combinant omega interferon or human recombinant -2b
toplasmic inclusion bodies suggestive o f Chlamydophila interferon may also be of some benefit i n FHV-infected cats
infections, but these findings are nonspecific. A l t h o u g h (Siebeck et al., 2006).
routine bacterial cultures o f the oropharynx can be used to Chlamydophila infection should be suspected i n cats with
identify Bordetella, the organism can be found i n healthy and conjunctivitis as the primary problem and i n cats from cat
infected cats. Demonstration o f rising antibody titers against teries i n which the disease is endemic. O r a l antibiotics are
a specific agent over 2 to 3 weeks suggests active infection. administered for 3 weeks. In addition, chloramphenicol or
Regardless o f the method used, close coordination with the tetracycline ophthalmic ointment should be applied at least
pathology laboratory o n specimen collection and handling three times daily and continued for a m i n i m u m o f 14 days
is recommended for optimal results. after the resolution of signs.
Tests to identify specific agents are particularly useful i n Corneal ulcers resulting from F H V are treated with topical
cattery outbreaks i n which the clinician is asked to recom antiviral drugs, such as trifluridine, idoxuridine, or adenine
m e n d specific preventive measures. Multiple cats, both with arabinoside. One drop should be applied to each affected eye
and without clinical signs, should be tested when performing five to six times daily for no longer than 2 to 3 weeks. Routine
cattery surveys. Specific diagnostic tests are less useful for ulcer management is also indicated. Tetracycline or chloram
testing individual cats because their results do not alter phenicol ophthalmic ointment is administered two to four
therapy; false-negative results may occur i f signs are the times daily. Topical atropine is used for mydriasis as needed
result o f permanent nasal damage or i f the specimen does to control pain. Treatment is continued for 1 to 2 weeks after
not contain the agent, and, positive results may merely reflect epithelialization has occurred.
a carrier cat that has a concurrent disease process causing Topical and systemic corticosteroids are contraindicated
the clinical signs. The exception to this generalization is i n d i i n cats with acute U R I or ocular manifestations of F H V
vidual cats with suspected Chlamydophila infection, i n which infection. They can prolong clinical signs and increase viral
case specific effective therapy can be recommended. shedding.
Treatment o f cats with chronic signs is discussed on
Treatment p. 233.
In most cats U R I is a self-limiting disease, and treatment o f
cats with acute signs includes appropriate supportive care. Prevention in the Individual Pet Cat
Hydration and nutritional needs should be provided when Prevention of U R I i n all cats is based on avoiding exposure
necessary. D r i e d mucus and exudate should be cleaned from to the infectious agents (e.g., F H V , F C V , Bordetella and Chla
the face and nares. The cat can be placed i n a steamy bath mydophila organisms) and strengthening i m m u n i t y against
r o o m or a small r o o m with a vaporizer for 15 to 20 minutes infection. Most household cats are relatively resistant to pro
two or three times daily to help clear excess secretions. Severe longed problems associated with URIs, and routine health
nasal congestion is treated w i t h pediatric topical deconges care with regular vaccination using a subcutaneous product
tants such as 0.25% phenylephrine or 0.025% oxymetazo is adequate. Vaccination decreases severity o f clinical signs
line. A drop is gently placed i n each nostril daily for a resulting from URIs but does not prevent infection. Owners
m a x i m u m o f 3 days. If longer therapy is necessary, the decon should be discouraged from allowing their cats to roam
gestant is withheld for 3 days before beginning another 3-day freely outdoors.
course to prevent possible rebound congestion after w i t h Subcutaneous modified-live virus vaccines for F H V and
drawal o f the drug (based on problems with rebound conges F C V are used for most cats and are available i n combination
tion that occurs i n people). Another option for prolonged with panleukopenia vaccine. These vaccines are convenient
decongestant therapy is to alternate daily the naris treated. to administer, do not result in clinical signs when used cor
Antibiotic therapy to treat secondary infection is i n d i rectly, and provide adequate protection for cats that are not
cated i n cats with severe clinical signs. The initial antibiotic heavily exposed to these viruses. These vaccines are not effec
of choice is ampicillin (22 mg/kg q8h) or amoxicillin (22 mg/ tive i n kittens while maternal i m m u n i t y persists. Kittens are
kg q8h to q12h), because they are often effective, are associ usually vaccinated beginning at 6 to 10 weeks o f age and
ated with few adverse reactions, and can be administered to again i n 3 to 4 weeks. A t least two vaccines must be given
kittens. If Bordetella, Chlamydophila, or Mycoplasma spp. is initially, with the final vaccine administered after the kitten
suspected, doxycycline (5 to 10 mg/kg q12h, followed by a is 16 weeks old. A booster vaccination is recommended 1
bolus o f water) or chloramphenicol (10 to 15 mg/kg q l 2 h ) year after the final vaccine i n the initial series. Subsequent
should be used. A z i t h r o m y c i n (5 to 10 mg/kg q24h for 3 booster vaccinations are recommended every 3 years, unless
the cat has increased risk of exposure to infection. A study bacterial rhinitis, and it is difficult to make a definitive diag
by Lappin et al. (2002) indicates that detection of F H V and nosis because o f the diverse flora i n the n o r m a l nasal cavity
F C V antibodies i n the serum of cats is predictive o f suscep (see Chapter 14). M i c r o s c o p i c evidence of neutrophilic
tibility to disease and therefore may be useful i n determining inflammation and bacteria is a nonspecific finding i n the
need for revaccination. Queens should be vaccinated before majority o f animals w i t h nasal signs (Fig. 15-1). Bacterial
breeding. cultures o f swabs or nasal mucosal biopsies collected deep
Subcutaneous modified-live vaccines for F H V and F C V w i t h i n the nasal cavity can be performed. The growth o f
are safe but can cause disease i f introduced into the cat by many colonies o f only one or two organisms may represent
the normal oronasal route of infection. The vaccine should significant infection. G r o w t h of many different organisms or
not be aerosolized i n front o f the cat. Vaccine inadvertently small numbers of colonies probably represents n o r m a l flora.
left on the skin after injection should be washed off i m m e The microbiology laboratory should be requested to report
diately before the cat licks the area. all growth. Specimens for Mycoplasmal cultures should be
Modified-live vaccines should not be used i n pregnant placed in appropriate transport media for culture using spe
queens. Killed products are available for F H V and F C V cific isolation methods. Beneficial response to antibiotic
that can be used in pregnant queens. Killed vaccines have therapy is often used to support a diagnosis o f bacterial
also been recommended for cats with feline leukemia virus involvement.
(FeLV) or feline immunodeficiency virus (FIV) infection.
Modified-live vaccines for F H V and F C V are also avail Treatment
able for intranasal administration. Signs of acute U R I occa The bacterial component o f nasal disease is treated w i t h
sionally occur after vaccination. Attention should be paid to antibiotic therapy. If growth obtained by bacterial culture
ensure that panleukopenia is included i n the intranasal is believed to be significant, sensitivity information can be
product or that a panleukopenia vaccine is administered used i n selecting antibiotics. Anaerobic organisms may be
subcutaneously. involved. Broad-spectrum antibiotics that may be effective
Vaccines against Bordetella or Chlamydophila are recom include amoxicillin (22 mg/kg q8-12h), trimethoprim-
mended for use only i n catteries or shelters where these sulfadiazine (15 mg/kg q l 2 h ) , chloramphenicol (50 mg/kg
infections are endemic. Infections with Bordetella or Chla q8h for dogs; 10 to 15 mg/kg q l 2 h for cats), or clindamycin
mydophila are less c o m m o n than F H V and F C V infection, (5.5 to 11 mg/kg q l 2 h ) . Doxycycline (5 to 10 mg/kg q l 2 h ,
and disease resulting from Bordetella infections occurs p r i followed by a bolus o f water) or chloramphenicol is often
marily i n cats housed i n crowded conditions. Furthermore, effective against Bordetella and Mycoplasma organisms.
these diseases can be effectively treated w i t h antibiotics.
Prognosis
The prognosis for cats with acute U R I is good. C h r o n i c
disease does not develop i n most pet cats.
BACTERIAL RHINITIS
Acute bacterial rhinitis caused by Bordetella bronchiseptica
occurs occasionally i n cats (see the section on feline upper
respiratory infection) and rarely i n dogs (see the section o n
canine infectious tracheobronchitis i n Chapter 21). It is pos
sible that Mycoplasma can act as primary nasal pathogens.
In the vast majority o f cases, bacterial rhinitis is a secondary
complication and not a primary disease process. Bacterial
rhinitis occurs secondarily to almost all diseases o f the nasal
cavity. The bacteria that inhabit the nasal cavity i n health are
quick to overgrow when disease disrupts n o r m a l mucosal
defenses. Antibiotic therapy often leads to clinical improve
ment, but the response is usually temporary. Therefore m a n
agement of dogs and cats with suspected bacterial rhinitis
should include a thorough diagnostic evaluation for an under
FIG 1 5 - 1
lying disease process, particularly when signs are chronic.
A p h o t o m i c r o g r a p h of a slide p r e p a r e d from a n a s a l s w a b
of a patient with c h r o n i c mucopurulent d i s c h a r g e s h o w s the
Diagnosis
t y p i c a l findings of mucus, neutrophilic i n f l a m m a t i o n , a n d
Most dogs and cats with bacterial rhinitis have m u c o p u r u intracellular a n d extracellular b a c t e r i a . These f i n d i n g s a r e
lent nasal discharge. N o clinical signs are pathognomonic for not specific a n d g e n e r a l l y reflect s e c o n d a r y p r o c e s s e s .
For acute infection or i n cases i n w h i c h the p r i m a r y infection is rare i n cats. The discharge can be m u c o i d , muco
etiology (e.g., foreign body, diseased tooth root) has been purulent w i t h or without hemorrhage, or purely hemor
eliminated, antibiotics are administered for 7 to 10 days. rhagic. The discharge can be unilateral or bilateral. Sneezing
C h r o n i c infections require prolonged treatment. Antibiotics may be reported. Features that are highly suggestive of asper
are administered initially for 1 week. If a beneficial response gillosis are sensitivity to palpation o f the face or depigmenta
is seen, the drug is continued for a m i n i m u m o f 4 to 6 weeks. tion and ulceration of the external nares (see Fig. 13-1). Lung
If signs recur after discontinuation of drug after 4 to 6 weeks, involvement is not expected.
the same antibiotic is reinstituted for even longer periods. Systemic aspergillosis i n dogs is generally caused by
If no response is seen after the initial week o f treatment, Aspergillus terreus and other Aspergillus spp. rather than A.
the drug should be discontinued. Another antibiotic can be fumigatus. It is an unusual, generally fatal disease that occurs
tried, although further evaluation for another, as yet uniden primarily i n G e r m a n Shepherd Dogs. Nasal signs are not
tified, p r i m a r y disorder should be pursued. Further diagnos reported.
tic evaluation is particularly warranted i n dogs because,
compared w i t h cats, they less frequently have idiopathic Diagnosis
disease. Frequent stopping and starting of different antibiot N o single test result is diagnostic for infection with aspergil
ics every 7 to 14 days is not recommended and may predis losis. The diagnosis is based on the cumulative findings o f a
pose the animal to the growth o f resistant gram-negative comprehensive evaluation of a dog w i t h appropriate clinical
infections. signs. In addition, aspergillosis can be an opportunistic
infection, and underlying nasal disease must always be con
Prognosis sidered.
Bacterial rhinitis is usually responsive to antibiotic therapy. Radiographic signs of aspergillosis include well-defined
However, long-term resolution o f signs depends o n the iden lucent areas w i t h i n the nasal cavity and increased radiolu
tification and correction o f any underlying disease process. cency rostrally (see F i g . 14-7). Typically no destruction of
the vomer or facial bones occurs, although the bones may
appear roughened. However, destruction of these bones or
NASAL MYCOSES the cribriform plate may occur i n dogs w i t h advanced disease.
Increased fluid opacity may be present. Fluid opacity within
CRYPTOCOCCOSIS the frontal sinus can represent a site o f infection or mucus
Cryptococcus neoformans is a fungal agent that infects cats accumulation from obstructed drainage. In some patients
and, less commonly, dogs. It most likely enters the body the frontal sinus is the only site o f infection.
through the respiratory tract and, i n some animals, may dis Rhinoscopic abnormalities include erosion of nasal tur
seminate to other organs. In cats clinical signs usually reflect binates and fungal plaques, which appear as white-to-green
infection o f the nasal cavity, central nervous system ( C N S ) , plaques of m o l d o n the nasal mucosa (see Fig. 14-13). Failure
eyes, or skin and subcutaneous tissues. In dogs signs o f C N S to visualize these lesions does not rule out aspergillosis. C o n
involvement are most c o m m o n . The lungs are c o m m o n l y firmation that presumed plaques are indeed fungal hyphae
infected i n both species, but clinical signs of lung involve can be achieved by cytology (Fig. 15-2) and culture of mate
ment (e.g., cough, dyspnea) are rare. Clinical features, diag rial collected by biopsy or swab under visual guidance.
nosis, and treatment o f cryptococcosis are discussed i n D u r i n g rhinoscopy, plaques are mechanically debulked by
Chapter 98.
ASPERGILLOSIS
Aspergillus fumigatus is a n o r m a l inhabitant o f the nasal
cavity i n many animals. In some dogs and, rarely, cats, it
becomes a pathogen. The m o l d form o f the organism can
develop into visible fungal plaques that invade the nasal
mucosa ("fungal mats") and fungal granulomas. A n animal
that develops aspergillosis may have another nasal condition,
such as neoplasia, foreign body, p r i o r trauma, or i m m u n e
deficiency that predisposes the animal to secondary fungal
infection. Excessive exposure to Aspergillus organisms may
explain the frequent occurrence o f disease i n otherwise
healthy animals. Another type o f fungus, Penicillium, can
cause signs similar to those o f aspergillosis.
Clinical Features
FIG 15-2
Aspergillosis can cause chronic nasal disease i n dogs of any B r a n c h i n g h y p h a e of Aspergillus fumigatus from a s w a b of
age or breed but is most c o m m o n i n young male dogs. Nasal a visualized fungal plaque.
scraping or vigorous flushing to increase the efficacy o f The animal is anesthetized and oxygenated through a
topical treatment. cuffed endotracheal tube. The dog is positioned i n dorsal
Aspergillus organisms can generally be seen histologically recumbency w i t h the nose pulled d o w n parallel with the
in biopsy specimens o f affected nasal mucosa after routine table (Figs. 15-3 and 15-4). For a large-breed dog, a 24 Fr
staining techniques, although special staining can be per Foley catheter w i t h a 5-ml balloon is passed through the
formed to identify subtle involvement. Neutrophilic, lym oral cavity, around the soft palate, and into the caudal naso
phoplasmacytic, or mixed inflammation is usually also pharynx such that the bulb is at the junction of the hard and
present. Multiple biopsy specimens should be obtained soft palates. The bulb is inflated w i t h approximately 10 m l
because the mucosa is affected multifocally rather than dif of air to ensure a snug fit. A laparotomy sponge is inserted
fusely. Invasion of fungal organisms into the nasal mucosa within the oropharynx, caudal to the balloon and ventral to
is indicative o f infection. the soft palate to help h o l d the balloon i n position and
Results of fungal cultures are difficult to interpret, unless further obstruct the nasal pharynx. Additional laparotomy
the specimen is obtained from a visualized plaque. The sponges are packed carefully into the back o f the m o u t h
organism can be found i n the nasal cavity o f n o r m a l animals, around the tracheal tube to prevent any drug that might leak
and false-negative culture results can also occur. A positive past the nasopharyngeal packing from reaching the lower
culture, in conjunction with other appropriate clinical and airways.
diagnostic findings, supports the diagnosis. A 10 Fr polypropylene urinary catheter is passed into the
Positive serum antibody titers also support a diagnosis o f dorsal meatus o f each nasal cavity to a distance approxi
infection. Although titers are indirect evidence o f infection, mately midway between the external naris and the medial
animals with Aspergillus organisms as a n o r m a l nasal inhab canthus o f the eye. The correct distance is marked on the
itant do not usually develop measurable antibodies against catheters with tape to prevent accidentally inserting the cath
the organism. Pomerantz et al. (2007) found that serum eters too far during the procedure. A 12 Fr Foley catheter
antibodies had a sensitivity o f 67%, a specificity o f 98%, a with a 5-ml balloon is passed adjacent to the polypropylene
positive predictive value o f 98%, and a negative predictive catheter into each nasal cavity. The cuff is inflated and pulled
value of 84% for the diagnosis of nasal aspergillosis. Their snugly against the inside o f the naris. A small suture is placed
study included 21 dogs with aspergillosis, 25 dogs with n o n - across each naris lateral to the catheter to prevent balloon
fungal rhinitis, and 12 dogs with nasal neoplasia. migration. A gauze sponge is placed between the endotra
cheal tube and the incisive ducts behind the upper incisors
Treatment to m i n i m i z e leakage.
The current treatments o f choice for nasal aspergillosis A solution o f 1% clotrimazole is administered through
are topical clotrimazole, with a success rate of 80% to 90% the polypropylene catheters. Approximately 30 m l is used for
with one or more treatments, and oral itraconazole, with a each side i n a typical retriever-size dog. Each Foley catheter
success rate o f 60% to 70%. O r a l therapy is simpler to is checked for filling during the initial infusion and is then
administer than topical therapy but is somewhat less suc clamped when clotrimazole begins to drip from the catheter.
cessful, requires prolonged treatment, and is relatively expen The solution is viscous, but excessive pressure is not required
sive. Itraconazole is administered orally at a dose o f 5 mg/kg for infusion. A d d i t i o n a l clotrimazole is administered during
every 12 hours and must be continued for 60 to 90 days or the next hour at a rate that results i n approximately 1 drop
longer. (See Chapter 98 for a complete discussion o f this every few seconds from each external naris. In dogs of the
drug.) size described, a total o f approximately 100 to 120 m l w i l l be
Successful topical treatment o f aspergillosis was originally used.
documented with enilconazole administered through tubes After the initial 15 minutes, the head is tilted slightly to
placed surgically into both frontal sinuses and both sides o f one side and then the other for 15 minutes each and then
the nasal cavity. The drug was administered through the back into dorsal recumbency for 15 minutes. After this hour
tubes twice daily for 7 to 10 days. Subsequently, it was dis of contact time, the dog is rolled into sternal recumbency
covered that the over-the-counter drug clotrimazole was w i t h the head hanging over the end of the table and the nose
equally efficacious when infused through surgically placed pointing toward the floor. The catheters are removed from
tubes over a 1-hour period. D u r i n g the 1-hour infusion, the the external nares, and the clotrimazole and resulting mucus
dogs were kept under anesthesia and the caudal nasopharynx are allowed to drain. Drainage w i l l usually subside i n 10 to
and external nares were packed to allow filling o f the nasal 15 minutes. A flexible suction tip may be used to expedite
cavity. It has since been demonstrated that good distribution this process. The laparotomy pads are then carefully removed
of the drug can be achieved using a noninvasive technique from the nasopharynx and oral cavity and counted to ensure
(discussed i n the next paragraphs). Success with clotrima that all are retrieved. The catheter i n the nasopharynx is
zole using this technique has been similar to that docu removed. A n y drug w i t h i n the oral cavity is swabbed or
mented with infusion through surgically placed tubes. suctioned.
Debridement of visible fungal plaques during rhinoscopy Two potential complications o f clotrimazole treatment
and before topical therapy appears to increase the rate o f are aspiration pneumonia and meningoencephalitis. M e n i n
success. goencephalitis is generally fatal and results when clotrima-
FIG 15-3
D o g with n a s a l mycotic infection p r e p a r e d for 1-hour s o a k with c l o t r i m a z o l e . A cuffed
e n d o t r a c h e a l tube is in p l a c e (E). A 2 4 Fr Foley catheter (broad arrow) is in the c a u d a l
n a s o p h a r y n x . A 12 Fr Foley catheter (narrow arrows) is obstructing e a c h nostril. A 1 0 Fr
p o l y p r o p y l e n e catheter (red arrowheads) is p l a c e d m i d w a y into e a c h d o r s a l meatus for
infusion of the d r u g . L a p a r o t o m y s p o n g e s a r e used to further p a c k the c a u d a l n a s o p h a r
y n x , a r o u n d the t r a c h e a l tube a n d the c a u d a l o r a l cavity.
FIG 15-4
S c h e m a t i c d i a g r a m of a cross section of the h e a d of a d o g p r e p a r e d for 1-hour s o a k with
c l o t r i m a z o l e , et, E n d o t r a c h e a l tube; npf, Foley catheter p l a c e d in c a u d a l n a s o p h a r y n x ; s,
p h a r y n g e a l s p o n g e s ; ic, p o l y p r o p y l e n e infusion catheter; nf, rostral Foley catheter obstruct
ing nostril; hp, h a r d p a l a t e ; s p , soft p a l a t e ; cp, cribriform plate; rfs, rostral frontal sinus;
mfs, m e d i a l frontal sinus; Ifs, lateral frontal sinus. (Reprinted with p e r m i s s i o n from M a t h e w s
K G et a l : C o m p u t e d t o m o g r a p h i c assessment of n o n i n v a s i v e intranasal infusions in d o g s
with f u n g a l rhinitis, Vet Surg 2 5 : 3 0 9 , 1 9 9 6 . )
zole and its carrier, polyethylene glycol (PEG), make contact often located i n the frontal sinuses and caudal nasal cavity.
with the brain through a compromised cribriform plate. It Marks et al. (1994) report the greatest success i n identifying
is difficult to determine the integrity o f the cribriform plate mites by flushing the nasal cavities w i t h halothane i n oxygen.
before treatment without the aid o f computed tomography The anesthetic mixture causes the mites to migrate to the
(CT) or magnetic resonance imaging ( M R I ) , although caudal nasopharynx, where the mites are visualized using an
marked radiographic changes i n the caudal nasal cavity endoscope.
should increase concern. Fortunately, complications are not
common. Treatment
Clinical signs generally resolve i n 1 to 2 weeks. A second M i l b e m y c i n oxime (0.5 to 1 mg/kg, orally, every 7 to 10 days
1-hour soak is performed if signs persist after 2 weeks. O n e for three treatments) has been used successfully for treating
cause of treatment failure is the inability o f clotrimazole to nasal mites. Ivermectin has also been used for treatment
reach all sites of infection. As previously mentioned, removal (0.2 mg/kg, administered subcutaneously and repeated i n
of fungal plaques with rhinoscopic guidance is thought to 3 weeks), but it is not safe for certain breeds. A n y dogs
improve response to therapy. One or both frontal sinuses are i n direct contact w i t h the affected animal should also be
often infected, and it may be necessary to trephine the treated.
affected sinus, debulk any fungal granulomas, and directly
administer clotrimazole into the sinus. In rare cases, infec Prognosis
tion extends beyond the nasal cavity (e.g., into the retrobul
The prognosis for dogs w i t h nasal mites is excellent.
bar space). Itraconazole treatment is indicated i n these
patients. NASAL CAPILLARIASIS
Some clinicians have had success using the combination
Nasal capillariasis is caused by a nematode, Capillaria (Euco
of itraconazole and another oral antifungal agent, terbin
leus) boehmi, originally identified as a w o r m o f the frontal
afine, for the treatment o f aspergillosis. Published studies are
sinuses i n foxes. The adult w o r m is small, thin, and white and
not available (see Chapter 98).
lives o n the mucosa o f the nasal cavity and frontal sinuses of
Some dogs have a persistant nasal discharge after treat
dogs (see Fig. 14-14, B). The adults shed eggs that are swal
ment for aspergillosis i n the absence o f identifiable active
lowed and pass i n the feces. C l i n i c a l signs include sneezing
fungal infection. These dogs may have secondary bacterial
and mucopurulent nasal discharge, w i t h or without hemor
rhinitis or sensitivity to inhaled irritants because o f the
rhage. The diagnosis is made by identifying double opercu
damaged nasal anatomy and mucosa and are managed as
lated Capillaria (Eucoleus) eggs on routine fecal flotation
described i n the section on canine chronic/lymphoplasma
(similar to the eggs o f Capillaria (Eucoleus) aerophila; see Fig.
cytic rhinitis in this chapter.
20-12, C) or visualizing adult worms during rhinoscopy.
Treatments include ivermectin (0.2 mg/kg, orally, once) or
Prognosis
fenbendazole (25 to 50 mg/kg q12h for 10 to 14 days). Success
The prognosis for dogs with nasal aspergillosis has improved
of treatment should be confirmed w i t h repeated fecal exami
with the availability of new antifungal agents. For most
nations, i n addition to resolution o f clinical signs. Repeated
animals a fair-to-good prognosis is warranted.
treatments may be necessary, and reinfection is possible i f
exposure to contaminated soil continues.
NASAL PARASITES
NASOPHARYNGEAL POLYPS
NASAL MITES
Pneumonyssoides caninum is a small white mite approxi Nasopharyngeal polyps are benign growths that occur most
mately 1 m m i n size (see Fig. 14-14, A ) . Most infestations are often i n kittens and young adult cats, although they are
clinically silent, but some dogs may have moderate-to-severe occasionally found i n older animals. Their origin is u n k n o w n ,
clinical signs. but they are often attached to the base o f the eustachian tube.
They can extend into the external ear canal, middle ear,
Clinical Features and Diagnosis pharynx, and nasal cavity. Grossly, they are pink, p o l y p o i d
A common clinical feature o f nasal mites is sneezing, which growths, often arising from a stalk (Fig. 15-5). Because o f
is often violent. Head shaking, pawing at the nose, reverse their gross appearance, they are sometimes mistaken for
sneezing, chronic nasal discharge, and epistaxis can also neoplasia.
occur. These signs are similar to those caused by nasal foreign
bodies. The diagnosis is made by visualizing the mites during Clinical Features
rhinoscopy or by retrograde nasal flushing, as described i n Respiratory signs caused by nasopharyngeal polyps include
Chapter 14. The mites can be easily overlooked i n the stertorous breathing, upper airway obstruction, and serous
retrieved saline solution; they should be specifically searched to-mucopurulent nasal discharge. Signs o f otitis externa
for with slight magnification or by placing dark material or otitis media/interna, such as head tilt, nystagmus, or
behind the specimen for contrast. Further, the mites are Horner's syndrome, can also occur.
a course o f prednisolone i n some cats. Prednisolone was
administered at 1 to 2 mg/kg every 24 hours for 2 weeks,
then at half the original dose for 1 week, then every other
day for 7 to 10 more days. A course of antibiotics (e.g.,
amoxicillin) was also administered.
Prognosis
The prognosis is excellent, but treatment of recurrent dis
ease may be necessary. Regrowth of a polyp can occur at the
original site i f abnormal tissue remains, with signs o f recur
rence typically appearing w i t h i n 1 year. Bulla osteotomies
should be considered i n cats w i t h recurrence and signs of
otitis media i f not performed w i t h initial treatment.
NASAL TUMORS
The majority of nasal tumors i n the dog and cat are malig
nant. Adenocarcinoma, squamous cell carcinoma, and undif
ferentiated carcinoma are c o m m o n nasal tumors i n dogs.
L y m p h o m a and adenocarcinoma are c o m m o n i n cats. Fibro
FIG 15-5
sarcomas and other sarcomas also occur i n both species.
A nasopharyngeal polyp w a s visualized during rhinoscopy
through the exterior naris of a c a t with c h r o n i c n a s a l Benign tumors include adenomas, fibromas, papillomas, and
d i s c h a r g e . The p o l y p w a s e x c i s e d b y traction a n d has a n transmissible venereal tumors (the latter only i n dogs).
o b v i o u s stalk.
Clinical Features
Nasal tumors usually occur i n older animals but cannot be
Diagnosis excluded from the differential diagnosis of young dogs and
Identification of a soft tissue opacity above the soft palate cats. N o breed predisposition has been consistently identi
radiographically and gross visualization o f a mass i n the fied. Collies and Irish Setters were overrepresented i n a report
nasopharynx, nasal cavity, or external ear canal support a of malignant nasal tumors i n dogs by Evans et al. (1989).
tentative diagnosis o f nasopharyngeal polyp. Complete eval The clinical features o f nasal tumors (usually chronic)
uation of cats w i t h polyps also includes a deep otoscopic reflect the locally invasive nature of these tumors. Nasal
examination and radiographs or C T scans o f the osseous discharge is the most c o m m o n complaint. The discharge can
bullae to determine the extent o f involvement. The majority be serous, m u c o i d , mucopurulent, or hemorrhagic. One
of cats with polyps have otitis media, detectable radiograph or both nostrils can be involved. W i t h bilateral involvement,
ically as thickened bone or increased soft tissue opacity o f the discharge is often worse from one nostril compared with
the bulla (see Fig. 14-6). The definitive diagnosis is made by the other. For many animals the discharge is initially unilat
histopathologic analysis o f tissue biopsy; the specimen is eral and progresses to bilateral. Sneezing may be reported.
usually obtained d u r i n g surgical excision. Nasopharyngeal Obstruction o f the nasal cavity by the tumor may cause
polyps are composed o f inflammatory tissue, fibrous con decreased or absent air flow through one o f the nares.
nective tissue, and epithelium. Deformation o f the facial bones, hard palate, or maxillary
dental arcade may be visible (see Fig. 13-4). Tumor growth
Treatment extending into the cranial vault can result i n neurologic
Treatment o f nasopharyngeal polyps consists o f surgical signs. G r o w t h into the orbit may cause exophthalmos or
excision. Surgery is usually performed through the oral inability to retropulse the eye. Animals only rarely experi
cavity by traction. In addition, bullae osteotomy should ence neurologic signs (e.g., seizures, behavior changes,
be considered i n cats w i t h radiographic or C T evidence o f abnormal mental status) or ocular abnormalities as the
involvement o f the osseous bullae. Rarely, r h i n o t o m y is primary complaints (i.e., no signs o f nasal discharge). Weight
required for complete removal. loss and anorexia may accompany the respiratory signs but
A n early study by Kapatkin et al. (1990) reported that 5 are often absent.
of 31 cats had regrowth o f an excised polyp. O f the five cats
w i t h regrowth, four had not had bulla osteotomies. These Diagnosis
findings support the importance o f addressing involvement A diagnosis o f neoplasia is based on clinical features and
of the osseous bulla i n cats w i t h polyps. However, a subse supported by typical abnormalities detected by imaging of
quent study by Anderson et al. (2000) reported successful the nasal cavity and frontal sinuses or rhinoscopy. A defini
treatment with traction alone, particularly when followed by tive diagnosis requires histopathologic examination of a
biopsy specimen, although fine needle aspirates o f nasal performed after megavoltage radiotherapy (Adams et al.,
masses may provide conclusive results. Imaging (radiogra 2005).
phy, CT, or M R I ) and rhinoscopic abnormalities can reflect Treatment o f malignant nasal tumors with surgery alone
soft tissue mass lesions; turbinate, vomer bone, or facial does not result i n prolonged survival times; it may indeed
bone destruction (see Figs. 14-2,14-4, and 14-8, B); or diffuse shorten survival times. It is doubtful that all abnormal tissue
infiltration of the mucosa with neoplastic and inflammatory can be excised i n the majority o f cases.
cells. Chemotherapy may be attempted when radiation therapy
Biopsy specimens, including tissue from deep within has failed or is not a viable option. Carcinomas may be
the lesion, should be obtained i n all patients for histologic responsive to cisplatin, carboplatin, or multiagent chemo
confirmation. Nasal neoplasms frequently cause a marked therapy. (See Chapter 77 for a discussion o f general princi
inflammatory response of the nasal mucosa and, i n some ples for the selection o f chemotherapy.)
patients, secondary bacterial or fungal infection. A cytologic Treatment with piroxicam, a nonsteroidal antiinflamma
diagnosis of neoplasia must be accepted cautiously, taking tory drug, can be considered for dogs w i t h carcinoma for
into consideration concurrent inflammation and potentially which radiation therapy is not elected. Partial remissions or
marked hyperplastic and metaplastic change. Furthermore, improvement i n clinical signs have been reported for some
in some cases the cytologic characteristics o f l y m p h o m a and dogs with transitional cell carcinoma o f the urinary bladder,
carcinoma w i l l m i m i c each other, which may lead to an oral squamous cell carcinoma, and several other carcinomas.
erroneous classification. Potential side effects include gastrointestinal ulceration
Not all cases o f neoplasia w i l l be diagnosed on initial (which can be severe) and kidney damage. For dogs with
evaluation of the dog or cat. Imaging, rhinoscopy, and biopsy other types o f tumors and cats, improvement o f clinical signs
may need to be repeated i n 1 to 3 months i n animals with may be seen with antiinflammatory doses o f glucocorticoids.
persistent signs in which a definitive diagnosis has not been Prednisolone is prescribed for cats, and either prednisone or
made. C T and M R I are more sensitive techniques for imaging prednisolone for dogs (0.5 to 1 mg/kg/day; tapered to lowest
nasal tumors than routine radiography, and one o f these effective dose). Neither drug should be given i n conjunction
should be performed when available (see Fig. 14-8, B). Surgi with piroxicam.
cal exploration is occasionally necessary to obtain a defini
tive diagnosis. Prognosis
Once a definitive diagnosis is made, determining the The prognosis for dogs and cats with untreated malignant
extent of disease can help i n assessing the feasibility o f surgi nasal tumors is poor. Survival after diagnosis is usually only
cal or radiation therapy versus chemotherapy. Some infor a few months. Euthanasia is often requested because o f per
mation can be obtained from high-quality nasal radiographs, sistent epistaxis or discharge, labored respirations, anorexia
but C T and M R I are more sensitive methods for evaluating and weight loss, or neurologic signs. Epistaxis is a poor prog
the extent of abnormal tissue. Aspirates of mandibular nostic indicator. In a study o f 132 dogs w i t h untreated nasal
lymph nodes should be examined cytologically for evidence carcinoma by Rassnick et al. (2006), the median survival
of local spread. Thoracic radiographs are evaluated, although time of dogs with epistaxis was 88 days (95% confidence
pulmonary metastases are u n c o m m o n at the time o f initial interval (CI), 65-106 days) and o f dogs without epistaxis was
diagnosis. Cytologic evaluation of bone marrow aspirates 224 days (95% C I , 54-467 days). The overall median survival
and abdominal radiographs or ultrasound are indicated for time was 95 days (range 7-1114 days).
patients with lymphoma. Cats with l y m p h o m a are also tested Radiation therapy can prolong survival and improve
for FeLV and FIV. quality o f life i n some animals. The therapy is well tolerated
by most animals, and i n those that achieve remission the
Treatment quality o f life is usually excellent. Studies o f dogs treated with
Treatment of benign tumors should include surgical exci megavoltage radiation, with or without prior surgical treat
sion. Malignant nasal tumors can be treated with radiation ment, by Theon et al. (1993) and H e n r y et al. (1998) found
therapy (with or without surgery) and/or chemotherapy. median survival times o f approximately 13 months. Survival
Palliative treatment can also be tried. The treatments of rates for 1 and 2 years were 55% to 60% and 25% to 45%,
choice for cats with nasal l y m p h o m a are chemotherapy using respectively. For dogs receiving megavoltage radiation fol
standard lymphoma protocols (see Chapter 80), radiation lowed by surgical debulking, median survival time was 47.7
therapy, or both. Radiation therapy avoids the systemic months, w i t h survival rates for 2 and 3 years o f 69% and
adverse effects of chemotherapeutic drugs but may be insuf 58%, respectively (Adams et al., 2005). The dogs i n the study
ficient if the tumor involves other organs. by Adams et al. (2005) that d i d not receive postradiotherapy
Radiation therapy is the treatment o f choice for most surgery had a median survival o f 19.7 months and lower
other malignant nasal tumors. Surgical debulking before 2- and 3-year survival rates (44% and 24%, respectively).
radiation is recommended i f orthovoltage radiation w i l l be A study by Evans et al. (1989) o f dogs receiving orthovolt
used. Surgery is not beneficial before megavoltage radiation age radiation therapy after surgical debulking reported a
(cobalt or linear accelerator), but improved success o f treat median survival time of 16.5 months, a 1-year survival rate o f
ment has been recently reported with surgical debulking 54% and a 2-year survival rate o f 43%. N o r t h r u p et al. (2001)
report a median survival time o f approximately 7 months, a biopsy reveals eosinophilic inflammation. It is possible that
1-year survival rate of 37%, and a 2-year survival rate o f only w i t h chronic disease, a mixed inflammatory response occurs,
17% i n dogs treated with surgery and orthovoltage radiation. obscuring the diagnosis. There should be no indication i n
Less information is available concerning prognosis i n any o f the diagnostic tests o f an aggressive disease process,
cats. According to Straw et al. (1986), six cats w i t h malignant parasites or other active infection, or neoplasia.
neoplasms (three with lymphoma) that received radiation
therapy had a mean survival time o f 19 months. A study by Treatment
Theon et al. (1994) o f 16 cats with n o n l y m p h o i d neoplasia Removing the offending allergen from the animal's environ
receiving radiation therapy showed a 1 -year survival rate o f ment or diet is the ideal treatment o f allergic rhinitis. W h e n
44% and a 2-year survival rate o f 17%. O f eight cats with this is not possible, a beneficial response may be achieved
nasal l y m p h o m a treated with cyclophosphamide, vincris w i t h antihistamines. Chlorpheniramine can be administered
tine, and prednisolone ( C O P ) , six (75%) achieved complete orally at a dose o f 4 to 8 mg/dog every 8 to 12 hours or
remission (Teske et al., 2002). M e d i a n survival time was 358 2 mg/cat every 8 to 12 hours. The second-generation anti
days, and the estimated 1 -year survival rate was 75%. Accord histamine cetirizine (Zyrtec, Pfizer) may be more successful
ing to preliminary data from Arteaga et al. (2007), cats w i t h in cats. A pharmacokinetic study o f this drug i n healthy cats
nasal l y m p h o m a treated with radiation and chemotherapy found a dosage o f 1 mg/kg, administered orally every 24
had a median survival time o f 511 days. hours, to maintain plasma concentrations similar to those
reported i n people (Papich et al., 2006). Glucocorticoids may
be used i f antihistamines are unsuccessful. Prednisone is
ALLERGIC RHINITIS initiated at a dose o f 0.25 mg/kg every 12 hours until signs
resolve. The dose is then tapered to the lowest effective
Etiology amount. If treatment is effective, signs w i l l generally resolve
Allergic rhinitis has not been well characterized i n dogs or w i t h i n a few days. Drugs are continued only as long as needed
cats. However, dermatologists provide anecdotal reports o f to control signs.
atopic dogs rubbing the face (possibly indicating nasal p r u
ritus) a n d experiencing serous nasal discharge, i n addition Prognosis
to dermatologic signs. Allergic rhinitis is generally consid The prognosis for dogs and cats with allergic rhinitis is excel
ered to be a hypersensitivity response w i t h i n the nasal cavity lent i f the allergen can be eliminated. Otherwise, the prog
and sinuses to airborne antigens. It is possible that food nosis for control is good, but a cure is unlikely.
allergens play a role i n some patients. Other antigens are
capable o f inducing a hypersensitivity response as well, and
thus the differential diagnoses must include parasites, other IDIOPATHIC RHINITIS
infectious diseases, and neoplasia.
Idiopathic rhinitis is a more c o m m o n diagnosis i n cats com
Clinical Features pared w i t h dogs. The diagnosis cannot be made without a
Dogs or cats w i t h allergic rhinitis experience sneezing and/or thorough diagnostic evaluation to rule out specific diseases
serous or mucopurulent nasal discharge. Signs may be acute (see Chapters 13 a n d 14).
or chronic. Careful questioning o f the owner may reveal
a relationship between signs a n d potential allergens. For FELINE CHRONIC RHINOSINUSITIS
instance, signs may be worse during certain seasons; i n the
presence o f cigarette smoke; or after the introduction o f a Etiology
new brand o f kitty litter, new perfumes, cleaning agents, Feline chronic rhinosinusitis has long been presumed to be
furniture, or fabric i n the house. Note that worsening o f a result o f viral infection with F H V or F C V (see the section
signs may simply be a result o f exposure to irritants rather o n feline upper respiratory infection, p. 223). Persistent viral
than an actual allergic response. Debilitation o f the animal infection has been implicated, but studies have failed to show
is not expected. an association between tests indicating exposure to or infec
tion w i t h these viruses and clinical signs. It is possible that
Diagnosis infection w i t h these viruses results i n damaged mucosa that
Identifying a historical relationship between signs and a par is more susceptible to bacterial infection or that mounts an
ticular allergen a n d then achieving resolution o f signs after excessive inflammatory response to irritants or normal nasal
removal o f the suspected agent from the animal's environ flora. Preliminary studies have failed to show an association
ment support the diagnosis o f allergic rhinitis. W h e n this with feline chronic rhinosinusitis and Bartonella infection,
approach is not possible or successful, a thorough diagnostic based o n serum antibody titers or P C R o f nasal tissue
evaluation o f the nasal cavity is indicated (see Chapters 13 (Berryessa et al., 2007). In the absence o f a k n o w n etiology,
and 14). Nasal radiographs reveal increased soft tissue opacity this disease w i l l be denoted by the term idiopathic feline
with m i n i m a l or no turbinate destruction. Classically, nasal chronic rhinosinusitis.
Clinical Features and Diagnosis
BOX 15-1
Chronic m u c o i d or mucopurulent nasal discharge is the
most c o m m o n clinical sign of idiopathic feline chronic r h i Management Considerations for Cats with Idiopathic
nosinusitis. The discharge is typically bilateral. Fresh b l o o d Chronic Rhinosinusitis
may be seen i n the discharge o f some cats but is not usually
Facilitate Drainage of Discharge
a primary complaint. Sneezing may occur. Given that this is
an idiopathic disease, the lack of specific findings is i m p o r Vaporizer treatments
tant. Cats should have no funduscopic lesions, no lymphade Topical saline administration
nopathy, no facial or palate deformities, and healthy teeth Nasal cavity flushes under anesthesia
Topical decongestants
and gums. Anorexia and weight loss are rarely reported.
Thorough diagnostic testing is indicated, as described i n Decrease Irritants in the Environment
Chapters 13 and 14. Results of such testing do not support
Improvement of indoor air quality
the diagnosis of a specific disease. Usual nonspecific findings
include turbinate erosion, mucosal inflammation, and Control Secondary Bacterial Infections
increased mucus accumulation as assessed by nasal imaging Long-term antibiotic treatment
and rhinoscopy; neutrophilic or mixed inflammation w i t h
Treat Possible Mycoplasma Infection
bacteria o n cytology of nasal discharge; and neutrophilic
and/or lymphoplasmacytic inflammation o n nasal biopsy. Antibiotic treatment
Nonspecific abnormalities attributable to chronic inflamma
Treat Possible Herpesvirus Infection
tion, such as epithelial hyperplasia and fibrosis, may also be
Lysine treatment
seen. Secondary bacterial rhinitis or Mycoplasma infection
may be identified. Reduce Inflammation
Second-generation antihistamine treatment
Treatment
Oral prednisolone treatment
Cats with idiopathic chronic rhinosinusitis often require
management for years. Fortunately, most o f these cats are Surgical Intervention
healthy i n all other respects. Treatment strategies include Turbinectomy
facilitating drainage o f discharge; decreasing irritants i n the Frontal sinus ablation
environment; controlling secondary bacterial infections;
treating possible Mycoplasmal or F H V infection; reducing
inflammation; and, as a last resort, performing a turbinec
tomy and frontal sinus ablation (Box 15-1). C h r o n i c antibiotic therapy may be required to manage
Keeping secretions moist, performing intermittent nasal secondary bacterial infections. Broad-spectrum antibiotics
flushes, and judiciously using topical decongestants facilitate such as amoxicillin (22 mg/kg q8-12h) or t r i m e t h o p r i m -
drainage. Keeping the cat i n a r o o m w i t h a vaporizer, for sulfadiazine (15 mg/kg q l 2 h ) are often successful. C h l o r a m
instance, during the night, can provide symptomatic relief phenicol (10 to 15 m g / k g q l 2 h ) and doxycycline (5 to
by keeping secretions moist. Alternatively, drops of sterile 10 mg/kg q l 2 h , followed by a bolus o f water) have activity
saline can be placed into the nares. Some cats experience a against some bacteria and Chlamydophila and Mycoplasma
marked improvement i n clinical signs for weeks after flush organisms and can be effective i n some cats when other
ing of the nasal cavity w i t h copious amounts o f saline or drugs have failed. This author reserves fluoroquinolones for
dilute betadine solution. General anesthesia is required, and cats w i t h documented resistant gram-negative infections. If
the lower airways must be protected w i t h an endotracheal a beneficial response to antibiotic therapy is seen w i t h i n 1
tube, gauze sponges, and positioning o f the head to facilitate week of its initiation, the antibiotic should be continued for
drainage from the external nares. Topical decongestants, as at least 4 to 6 weeks. If a beneficial response is not seen, the
described for feline upper respiratory infection (see page antibiotic is discontinued. Note that the frequent stopping
224), may provide symptomatic relief d u r i n g episodes o f and starting o f different antibiotics every 7 to 14 days is not
severe congestion. recommended and may predispose the cat to resistant gram-
Irritants i n the environment can further exacerbate negative infections. Cats that respond well d u r i n g the pro
mucosal inflammation. Irritants such as smoke (from tobacco longed course o f antibiotics but that relapse shortly after
or fireplace) and perfumed products should be avoided. discontinuation o f the drug despite 4 to 6 weeks o f relief are
Motivated clients can take steps to improve the air quality i n candidates for continuous long-term antibiotic therapy.
their homes, such as by cleaning the carpet, furniture, Treatment w i t h the previously used antibiotic often can be
drapery, and furnace; regularly replacing air filters; and using successfully reinstituted. A m o x i c i l l i n administered twice
an air cleaner. The A m e r i c a n L u n g Association has a useful daily is often sufficient.
Web site with nonproprietary recommendations for i m p r o v Treatment w i t h lysine may be effective i n cats w i t h
ing indoor air quality (www.lungusa.org ). active herpesvirus infections. It has been postulated that
excessive concentrations o f lysine may antagonize arginine, M a n y specific causes o f nasal disease result i n a concur
a promoter o f herpesvirus replication. Because the specific rent inflammatory response because o f the disease itself or
organism(s) involved is rarely k n o w n , trial therapy is i n i t i as a response to the secondary effects of infection or enhanced
ated. Lysine (500 mg/cat q12h), which can obtained from response to irritants; this makes a thorough diagnostic eval
health food stores, is added to food. A m i n i m u m o f 4 weeks uation of these cases imperative. Windsor et al. (2006) per
is necessary to assess success o f treatment. formed multiple P C R assays on paraffin-embedded nasal
Anecdotal success i n occasional cats has been reported tissue from dogs w i t h idiopathic chronic rhinitis and failed
with treatment w i t h the second-generation antihistamine to find evidence for a role o f bacteria (based on D N A load),
cetirizine (Zyrtec, Pfizer) as described for allergic rhinitis canine adenovirus-2, parainfluenza virus, Chlamydophila
(see p. 232). N o efficacy studies are available. spp. or Bartonella spp. i n affected dogs. H i g h amounts of
Cats w i t h severe signs that persist despite the previously fungal D N A were found i n affected dogs, suggesting a pos
described methods o f supportive care may benefit from glu sible contribution to clinical signs. Alternatively, the result
cocorticoids to reduce inflammation. However, certain risks may simply reflect decreased clearance o f fungal organisms
are involved. Glucocorticoids may further predispose the cat from the diseased nasal cavity.
to secondary infections, increase viral shedding, and mask Although not supported i n the previously quoted study,
signs o f a more serious disease. Glucocorticoids should be a potential role for Bartonella infection has been suggested
prescribed only after a complete diagnostic evaluation has on the basis o f a study that found an association between
been performed to rule out other diseases. Prednisolone is seropositivity for Bartonella spp. and nasal discharge or epi
administered at a dose o f 0.5 mg/kg every 12 hours. If a staxis ( H e n n et a l , 2005) and a report o f three dogs with
beneficial response is seen w i t h i n 1 week, the dose is gradu epistaxis and evidence of infection w i t h Bartonella spp.
ally decreased to the lowest effective dose. A dose as l o w as (Breitschwerdt et al., 2005). A study i n our laboratory
0.25 mg/kg every 2 to 3 days may be sufficient to control (Hawkins et al., 2008) failed to find an obvious association
clinical signs. If a clinical response is not seen w i t h i n 1 week, between bartonellosis and idiopathic rhinitis, i n agreement
the drug should be discontinued. w i t h findings by W i n d s o r et al. (2006).
Cats with severe or deteriorating signs that persist despite
conscientious care are candidates for turbinectomy and Clinical Features and Diagnosis
frontal sinus ablation, assuming a complete diagnostic The clinical features and diagnosis of idiopathic canine
evaluation to eliminate other causes o f chronic nasal dis chronic rhinitis are similar to those described for idiopathic
charge has been performed (Chapters 13 and 14). Turbinec feline chronic rhinosinusitis. C h r o n i c m u c o i d or muco
tomy and frontal sinus ablation are difficult surgical purulent nasal discharge is the most c o m m o n clinical sign
procedures. Major b l o o d vessels and the cranial vault must and is typically bilateral. Fresh b l o o d may be seen i n the
be avoided, and tissue remnants must not be left behind. discharge o f some dogs, but it is not usually a primary com
Anorexia can be a postoperative problem; placement o f an plaint. Given that it is an idiopathic disease, the lack of
esophagostomy or gastrostomy tube (see p. 30) provides an specific findings is important. Dogs should have no fundu
excellent means for meeting nutritional requirements i f nec scopic lesions, no lymphadenopathy, no facial or palate
essary after surgery. Complete elimination o f respiratory deformities, and healthy teeth and gums. Anorexia and
signs is unlikely, but signs may be more easily managed. The weight loss are rarely reported. Thorough diagnostic testing
reader is referred to surgical texts by Fossum or Slatter for is indicated, as described i n Chapters 13 and 14. Results
a description o f the surgical techniques (see Suggested of such testing do not support the diagnosis of a specific
Readings). disease. Usual nonspecific findings include turbinate erosion,
mucosal inflammation, and increased mucus accumula
CANINE CHRONIC/ tion as assessed by nasal imaging and rhinoscopy; neutro
LYMPHOPLASMACYTIC RHINITIS philic or mixed inflammation w i t h bacteria on cytology
of nasal discharge; and lymphoplasmacytic and/or neutro
Etiology philic inflammation on nasal biopsy. Nonspecific abnor
Idiopathic chronic rhinitis i n dogs is sometimes character malities attributable to chronic inflammation, such as
ized by the inflammatory infiltrates seen i n nasal mucosal epithelial hyperplasia and fibrosis, can also be seen. Sec
biopsies; thus the disease lymphoplasmacytic rhinitis has ondary bacterial rhinitis or Mycoplasma infection may be
been described. It was originally reported to be a steroid- identified.
responsive disorder (Burgener et al., 1987), but a subsequent
report by W i n d s o r et al. (2004) and clinical experience Treatment
suggest that corticosteroids are not always effective i n the Treatment o f idiopathic canine chronic rhinitis is also similar
treatment o f lymphoplasmacytic rhinitis. It is not u n c o m to that described for idiopathic feline rhinosinusitis. Dogs
m o n for neutrophilic inflammation to be found, predomi are treated for secondary bacterial rhinitis (as described on
nantly or along w i t h lymphoplasmacytic infiltrates. For these p. 233), and efforts are made to decrease irritants i n the
reasons, the less specific term idiopathic canine chronic rhi environment (see p. 233). As w i t h cats, some dogs w i l l benefit
nitis w i l l be used. from efforts to facilitate the draining o f nasal discharge by
humidification of air or instillation o f sterile saline into the Evans S M et al: Prognostic factors and survival after radiotherapy
nasal cavity. for intranasal neoplasms in dogs: 70 cases (1974-1985), J Am Vet
Burgener et al. (1987) reported successful treatment o f Med Assoc 194:1460, 1989.
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pressive doses of prednisone (1 mg/kg q l 2 h ) . A positive
Fossum TW: Small animal surgery, ed 3, St Louis, 2007, Mosby.
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Gunnarsson LK et al: Clinical efficacy of milbemycin oxime in the
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to the treatment regimen (see Chapter 103). Unfortunately, logic or molecular evidence of Bartonella spp infection and idio
immunosuppressive treatment is not always effective. If clin pathic rhinitis in dogs (Accepted), J Am Vet Med Assoc, 2008.
ical signs worsen during treatment with corticosteroids, the Henn JB et al: Seroprevalence of antibodies against Bartonella
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lohnson LR et al: Assessment of infectious organisms associated
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et al. (2006). azole therapy for the treatment of chronic idiopathic (lympho
Dogs with severe or nonresponsive signs are candidates plasmacytic) rhinitis in dogs. Abstr, British Small Animal
for rhinotomy and turbinectomy, as described for cats o n Veterinary Association Annual Congress, Prague, Czech Repub
lic, 2006.
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Maggs D) et al: Effects of L-lysine and L-arginine on in vitro rep
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C H A P T E R 16
Clinical Manifestations
of Laryngeal and
Pharyngeal Disease
Laryngeal paralysis
Laryngeal neoplasia
Obstructive laryngitis
Laryngeal collapse
W e b formation
Trauma
FIG 1 6 - 1 Foreign body
Patients with extrathoracic (upper) airway obstruction often Extraluminal mass
present in respiratory distress as a result of a progressive Acute laryngitis
worsening of airway obstruction after an exacerbating
event.
Clinical Features
CHAPTER OUTLINE
Laryngeal paralysis can occur at any age and i n any breed,
LARYNGEAL PARALYSIS although the idiopathic form is most c o m m o n l y seen i n
BRACHYCEPHALIC AIRWAY SYNDROME older large-breed dogs. Clinical signs of respiratory distress
OBSTRUCTIVE LARYNGITIS and stridor are a direct result of narrowing of the airway at
LARYNGEAL NEOPLASIA the arytenoid cartilages and vocal folds. The owner may also
note a change i n voice (i.e., bark or meow). Most patients
are presented for acute respiratory distress, i n spite of the
chronic, progressive nature of this disease. Decompensation
LARYNGEAL PARALYSIS is frequently a result of exercise, excitement, or high environ
mental temperatures, resulting i n a cycle o f increased respi-
Laryngeal paralysis refers to a failure o f the arytenoid carti
lages to abduct d u r i n g inspiration, creating extrathoracic
(upper) airway obstruction. The abductor muscles are inner BOX 1 8-
vated by the left and right recurrent laryngeal nerves. If
Potential Causes o f Laryngeal Paralysis
clinical signs develop, both arytenoid cartilages are usually
affected. Idiopathic
Ventral Cervical Lesion
Etiology
Trauma to nerves
Potential causes o f laryngeal paralysis are listed i n Box 18-1.
Direct trauma
Laryngeal paralysis is most often idiopathic. Trauma or neo
Inflammation
plasia involving the ventral neck can damage the recurrent Fibrosis
laryngeal nerves directly or through inflammation and scar Neoplasia
ring. Masses or trauma involving the anterior thoracic cavity O t h e r inflammatory o r mass lesion
can also cause damage to the recurrent laryngeal nerves as
Anterior Thoracic Lesion
they course around the subclavian artery (right side) or
ligamentum arteriosum (left side). Dogs w i t h polyneuropa Neoplasia
thy-polymyopathy can be presented w i t h laryngeal paralysis Trauma
as the predominant clinical sign. Polyneuropathies i n turn Postoperative
Other
have been associated w i t h immune-mediated diseases, endo
O t h e r inflammatory o r mass lesion
crinopathies, or other systemic disorders (see Chapter 71).
Congenital laryngeal paralysis has been documented i n the Polyneuropathy and Polymyopathy
Bouvier des Flandres and is suspected i n Siberian Huskies Idiopathic
and Bull Terriers. A laryngeal paralysis-polyneuropathy Immune m e d i a t e d
complex has been described i n young Dalmations, Rott Endocrinopathy
weilers, and Great Pyrenees. Anecdotally, there may be an Hypothyroidism
increasing incidence o f idiopathic laryngeal paralysis i n O t h e r systemic d i s o r d e r
older G o l d e n and Labrador Retrievers, and i n one study 47 Toxicity
of 140 dogs (34%) w i t h laryngeal paralysis were Labrador Congenital disease
Retrievers ( M a c P h a i l et al., 2001). Laryngeal paralysis is Myasthenia gravis
u n c o m m o n i n cats.
ratory efforts; increased negative airway pressures, w h i c h
BOX 1 8-2
suck the soft tissue into the airway; and pharyngeal edema
and inflammation, which lead to further increased respira Diagnostic Evaluation of Dogs and Cats with Confirmed
tory efforts. Cyanosis, syncope, and death can occur. Dogs Laryngeal Paralysis
with respiratory distress require immediate emergency
Underlying Cause
therapy.
Some dogs w i t h laryngeal paralysis exhibit gagging or Thoracic radiographs
coughing w i t h eating or have overt aspiration pneumonia, Cervical radiographs
presumably resulting from concurrent pharyngeal dysfunc Serum biochemical panel
Thyroid hormone evaluation
tion or a more generalized polyneuropathy-polymyopathy.
Ancillary tests in select cases
Diagnosis Evaluation for polyneuropathy-polymyopathy
Electromyography
A definitive diagnosis o f laryngeal paralysis is made through
Nerve conduction measurements
laryngoscopy (see p. 239). Movement o f the arytenoid carti Antinuclear antibody test
lages is observed during a light plane o f anesthesia while the Antiacetylcholine receptor antibody test
patient is taking deep breaths. In laryngeal paralysis the ary
tenoid cartilages and vocal folds remain closed d u r i n g inspi Concurrent Pulmonary Disease
ration and open slightly during expiration. The larynx does Thoracic radiographs
not exhibit the n o r m a l coordinated movement associated
Concurrent Pharyngeal Dysfunction
with breathing, opening o n inspiration and closing o n expi
Evaluation of gag reflex
ration. Additional laryngoscopic findings may include pha
Observation of patient swallowing food and water
ryngeal edema and inflammation. The larynx and pharynx
Fluoroscopic observation of barium swallow
are also examined for neoplasia, foreign bodies, or other
diseases that might interfere w i t h n o r m a l function and for Concurrent Esophageal Dysfunction
laryngeal collapse (see p. 241). Thoracic radiographs
Once a diagnosis o f laryngeal paralysis is established, Contrast-enhanced esophagram
additional diagnostic tests should be considered to identify Fluoroscopic observation of barium swallow
underlying or associated diseases, to rule out concurrent
pulmonary problems (e.g., aspiration pneumonia) that may
be contributing to the clinical signs, and to rule out concur
rent pharyngeal and esophageal motility problems (Box
18-2). The latter is especially important i f surgical correction coids (e.g., prednisone, 0.5 mg/kg given orally q l 2 h initially)
for the treatment o f laryngeal paralysis is being considered. and cage rest may reduce secondary inflammation and
If the diagnostic tests fail to identify a cause, idiopathic edema o f the pharynx and larynx and enhance airflow.
laryngeal paralysis is diagnosed.
Prognosis
Treatment The overall prognosis for dogs w i t h laryngeal paralysis
In animals with respiratory distress, emergency medical treated surgically is fair to good. A s many as 90% o f owners
therapy to relieve upper airway obstruction is indicated (see of dogs w i t h laryngeal paralysis that underwent unilateral
Chapter 26). Following stabilization and a thorough diag arytenoid lateralization consider the procedure successful 1
nostic evaluation, surgery is usually the treatment o f choice. year or longer after surgery (White, 1989; H a m m e l et al.,
Even when specific therapy can be directed at an associated 2006). M a c P h a i l et al. (2001) reported a median survival
disease (e.g., hypothyroidism), complete resolution o f c l i n i time o f 1800 days (nearly 5 years) for 140 dogs that under
cal signs of laryngeal paralysis is rarely seen. Also, most cases went various surgical procedures, although the mortality
are idiopathic, and signs are generally progressive. rate from postoperative complications was high at 14%. The
Various laryngoplasty techniques have been described, most c o m m o n complication is aspiration pneumonia. A
including arytenoid lateralization (tie-back) procedures, guarded prognosis is warranted for patients w i t h signs o f
partial laryngectomy, and castellated laryngoplasty. The goal aspiration, dysphagia, megaesophagus, or systemic polyneu
of surgery is to provide an adequate opening for the flow o f ropathy or polymyopathy. Dogs w i t h laryngeal paralysis as
air but not one so large that the animal is predisposed to an early manifestation o f generalized polyneuropathy or
aspiration and the development o f pneumonia. Several oper polymyopathy may have progression o f signs.
ations to gradually enlarge the glottis may be necessary to
minimize the chance o f subsequent aspiration. The recom
mended initial procedure for most dogs and cats is unilateral BRACHYCEPHAUC AIRWAY SYNDROME
arytenoid lateralization.
If surgery is not an option, medical management consist The term brachycephalic airway syndrome, or upper airway
ing o f antiinflammatory doses o f short-acting glucocorti- obstruction syndrome, refers to the multiple anatomic abnor-
obstruction, including l o u d breathing sounds, stertor,
increased inspiratory efforts, cyanosis, and syncope. Clinical
signs are exacerbated by exercise, excitement, and high envi
ronmental temperatures. The increased inspiratory effort
c o m m o n l y associated w i t h this syndrome may cause second
ary edema and inflammation o f the laryngeal and pharyn
geal mucosae and enhance eversion o f the laryngeal saccules
or laryngeal collapse, further narrowing the glottis, exacer
bating the clinical signs, and creating a vicious cycle. As a
result, some dogs may be presented w i t h life-threatening
upper airway obstruction that requires immediate emer
gency therapy. Concurrent gastrointestinal signs are c o m
m o n l y reported.
Diagnosis
A tentative diagnosis is made o n the basis o f the breed,
clinical signs, and the appearance of the external nares (Fig.
18-2). Stenotic nares are generally bilaterally symmetric, and
the alar folds may be sucked inward during inspiration,
thereby worsening the obstruction to airflow. Laryngoscopy
(see Chapter 17) and radiographic evaluation o f the trachea
(see Chapter 20) are necessary to fully assess the extent and
severity of abnormalities. Most other causes o f upper airway
obstruction (see Chapter 26, and Boxes 16-1 and 16-2) can
also be ruled i n or out o n the basis of the results of these
diagnostic tests.
Treatment
Therapy should be designed to enhance the passage of air
FIG 18-1
through the upper airways and to m i n i m i z e the factors
T w o B u l l d o g p u p p i e s (A) a n d a Boston Terrier (B) with
that exacerbate the clinical signs (e.g., excessive exercise and
b r a c h y c e p h a l i c a i r w a y s y n d r o m e . A b n o r m a l i t i e s c a n include
stenotic n a r e s , e l o n g a t e d soft p a l a t e , e v e r t e d l a r y n g e a l excitement, overheating). Surgical correction of the ana
saccules, laryngeal collapse, a n d hypoplastic trachea. tomic defects is the treatment o f choice. The specific surgical
procedure selected depends o n the nature of the existing
problems and can include widening o f the external nares
malities c o m m o n l y found i n brachycephalic dogs and, to a and removal o f excessive soft palate and everted laryngeal
lesser extent, i n short-faced cats such as Himalayans. The saccules.
predominant anatomic abnormalities include stenotic nares, Correction o f stenotic nares is a simple procedure and
elongated soft palate, and, i n Bulldogs, hypoplastic trachea. can lead to a surprising alleviation of the signs i n affected
Prolonged upper airway obstruction resulting i n increased patients. Stenotic nares can be safely corrected at 3 to 4
inspiratory efforts may lead to eversion o f the laryngeal sac months of age, ideally before clinical signs develop. The soft
cules and, ultimately, laryngeal collapse. The severity o f these palate should be evaluated at the same time and also cor
abnormalities varies, and one or any combination o f these rected i f elongated. Such early relief o f obstruction should
abnormalities may be present i n any given brachycephalic decrease the amount o f negative pressure placed on the pha
dog or short-faced cat (Fig. 18-1). ryngeal and laryngeal structures during inspiration and
Concurrent gastrointestinal signs such as ptyalism, regur decrease progression o f disease.
gitation, and v o m i t i n g are c o m m o n i n dogs w i t h brachyce Medical management consisting of the administration of
phalic airway syndrome (Poncet et al., 2005) U n d e r l y i n g short-acting glucocorticoids (e.g., prednisone, 0.5 mg/kg
gastrointestinal disease may be a concurrent problem i n given orally q l 2 h initially) and cage rest may reduce the
these breeds o f dogs or may result from or be exacerbated secondary inflammation and edema of the pharynx and
by the increased intrathoracic pressures generated i n response larynx and enhance airflow, but it w i l l not eliminate the
to the upper airway obstruction. problem. Emergency therapy may be required to alleviate the
upper airway obstruction i n animals presenting i n respira
Clinical Features tory distress (see Chapter 26).
The abnormalities associated w i t h the brachycephalic airway Weight management and concurrent treatment for gas
syndrome impair the flow o f air through the extrathoracic trointestinal disease should not be neglected i n patients with
(upper) airways and cause clinical signs o f upper airway brachycephalic airway syndrome.
but is differentiated from neoplasia o n the basis o f the
histopathologic evaluation o f biopsy specimens. Inflamma
tory infiltrates can be granulomatous, pyogranulomatous,
or lymphocytic-plasmacytic. Etiologic agents have not been
identified.
This syndrome is poorly characterized and probably
includes several different diseases. Some animals respond to
glucocorticoid therapy. Prednisone or prednisolone (1.0 m g /
kg given orally q l 2 h ) is used initially. Once the clinical signs
have resolved, the dose o f prednisone can be tapered to the
lowest amount that effectively maintains remission o f clini
cal signs. Conservative excision o f the tissue obstructing the
airway may be necessary i n animals w i t h severe signs o f
upper airway obstruction or large granulomatous masses.
The prognosis varies, depending o n the size o f the lesion,
the severity o f laryngeal damage, and the responsiveness o f
the lesion to glucocorticoid therapy.
LARYNGEAL NEOPLASIA
Neoplasms originating from the larynx are u n c o m m o n i n
dogs and cats. M o r e commonly, tumors originating i n tissues
adjacent to the larynx, such as thyroid carcinoma and l y m
phoma, compress or invade the larynx and distort n o r m a l
laryngeal structures. C l i n i c a l signs o f extrathoracic (upper)
FIG 1 8 - 2
C a t with severely stenotic nares (A), a s c o m p a r e d with the airway obstruction result. Laryngeal tumors include carci
nares of a normal c a t (B). Early c o r r e c t i o n of stenotic nares n o m a (squamous cell, undifferentiated, and adenocarci
a n d other a m e n a b l e u p p e r a i r w a y obstructions, such a s a n noma), l y m p h o m a , melanoma, mast cell tumors and other
e l o n g a t e d soft p a l a t e , is highly r e c o m m e n d e d . sarcomas, and benign neoplasia. L y m p h o m a is the most
c o m m o n tumor i n cats.
Clinical Features
Prognosis The clinical signs o f laryngeal neoplasia are similar to those
The prognosis depends o n the severity o f the abnormalities of other laryngeal diseases and include noisy respiration,
at the time of diagnosis and the ability to surgically correct stridor, increased inspiratory efforts, cyanosis, syncope, and
them. The clinical signs w i l l progressively worsen i f the a change i n bark or meow. Mass lesions can also cause con
underlying problems go uncorrected. The prognosis after current dysphagia, aspiration pneumonia, or visible or pal
early surgical correction of the abnormalities is good for pable masses i n the ventral neck.
many animals. Laryngeal collapse (see p. 241) is generally
considered a poor prognostic indicator, although a recent Diagnosis
study demonstrated that even dogs w i t h severe laryngeal Extralaryngeal mass lesions are often identified by palpation
collapse can respond well to surgical intervention (Torrez et of the neck. P r i m a r y laryngeal tumors are rarely palpable
al., 2006). Permanent tracheostomy can be considered as a and are best identified by laryngoscopy. Laryngeal radio
salvage procedure i n animals w i t h severe collapse that are graphs, ultrasonography, or computed tomography can be
not responsive. A hypoplastic trachea is not surgically cor useful i n assessing the extent o f disease. Differential diagno
rectable, but there is no clear relationship between the degree ses include obstructive laryngitis, nasopharyngeal polyp,
of hypoplasia and morbidity or mortality. foreign body, traumatic granuloma, and abscess. For a defin
itive diagnosis o f neoplasia to be made, histologic examina
tion o f a biopsy specimen o f the mass must be done. A
OBSTRUCTIVE LARYNGITIS diagnosis o f malignant neoplasia should not be made o n the
basis o f the gross appearance alone.
Nonneoplastic infiltration of the larynx w i t h inflam
matory cells can occur i n dogs and cats, causing irregular Treatment
proliferation, hyperemia, and swelling of the larynx. The therapy used depends o n the type o f t u m o r identified
Clinical signs of an upper airway obstruction result. The histologically. Benign tumors should be excised surgically, i f
larynx may appear grossly neoplastic during laryngoscopy possible. Complete surgical excision o f malignant tumors is
rarely possible, although ventilation may be improved and Hendricks JC: Brachycephalic airway syndrome, Vet Clin North Am
time may be gained to allow other treatments such as radia Small Anim Pract 22:1145, 1992.
tion or chemotherapy to become effective. Complete laryn lakubiak MJ et al: Laryngeal, laryngotracheal, and tracheal masses
gectomy and permanent tracheostomy may be considered i n in cats: 27 cases (1998-2003), J Am Anim Hosp Assoc 41:310,
2005.
select animals.
MacPhail C M et al: Outcome of and postoperative complica
tions in dogs undergoing surgical treatment of laryngeal par
Prognosis
alysis: 140 cases (1985-1998), / Am Vet Med Assoc 218:1949,
The prognosis i n animals with benign tumors is excellent i f 2001.
the tumors can be totally resected. Malignant neoplasms are Mahony O M et al: Laryngeal paralysis-polyneuropathy complex in
associated with a poor prognosis. young Rottweilers, / Vet Intern Med 12:330, 1998.
Poncet C M et al: Prevalence of gastrointestinal tract lesions in 73
Suggested Readings brachycephalic dogs with upper respiratory syndrome, / Small
Braund K G et al: Laryngeal paralysis-polyneuropathy complex in Anim Pract 46:273, 2005.
young Dalmatians, Am J Vet Res 55:534, 1994. Riecks T W et al: Surgical correction of brachycephalic airway
Burbridge H M : A review of laryngeal paralysis in dogs, Br Vet J syndrome in dogs: 62 cases (1991-2004), J Am Vet Med Assoc
151:71, 1995. 230:1324, 2007.
Costello M F et al: Acute upper airway obstruction due to laryngeal Schachter S et al: Laryngeal paralysis in cats: 16 cases (1990-1999),
disease in 5 cats, Vet Emerg Crit Care 11:205, 2001. J Am Vet Med Assoc 216:1100, 2000.
Gabriel A et al: Laryngeal paralysis-polyneuropathy complex Torrez C V et al: Results of surgical correction of abnormalities
in young related Pyrenean mountain dogs, / Small Anim Pract associated with brachycephalic airway syndrome in dogs in
47:144, 2006. Australia, / Small Anim Pract 47:150, 2006.
Hammel SP et al: Postoperative results of unilateral arytenoid lat White RAS: Unilateral arytenoid lateralisation: an assessment
eralization for treatment of idiopathic laryngeal paralysis in of technique and long term results in 62 dogs with laryngeal
dogs: 39 cases (1996-2002),} Am Vet Med Assoc 228:1215, 2006. paralysis, / Small Anim Pract 30:543, 1989.
C H A P T E R 19
Clinical Manifestations
of Lower Respiratory
Tract Disorders
monly seen for evaluation o f cough. Lower respiratory tract Hemoptysis is the coughing up o f b l o o d . Blood-tinged
diseases that interfere with the oxygenation o f b l o o d can saliva may be observed w i t h i n the oral cavity or dripping
result i n respiratory distress, exercise intolerance, weakness, from the commissures o f the m o u t h after a cough. H e m o p
cyanosis, or syncope. Nonlocalizing signs such as fever, tysis is an unusual clinical sign that most c o m m o n l y occurs
anorexia, weight loss, and depression also occur and are the in animals w i t h heartworm disease or pulmonary neoplasia.
only presenting sign i n some animals. In rare instances, Less c o m m o n causes o f hemoptysis are mycotic infections,
potentially misleading signs, such as vomiting, can occur i n foreign bodies, severe congestive heart failure, thromboem
animals with lower respiratory tract disease. Auscultation bolic disease, l u n g lobe torsion, and some systemic bleeding
and thoracic radiography help localize the disease to the disorders such as disseminated intravascular coagulation
lower respiratory tract i n these animals. The two major pre (see B o x 19-2).
senting signs i n animals with lower respiratory tract disease, Intensity o f cough is useful i n prioritizing the differential
cough and respiratory distress, can be further characterized diagnoses. C o u g h associated with airway inflammation (i.e.,
by a careful history and physical examination. bronchitis) or large airway collapse is often l o u d , harsh, and
paroxysmal. The cough associated with tracheal collapse is
COUGH often described as a "goose-honk." C o u g h resulting from
A cough is an explosive release of air from the lungs through tracheal disease can usually be induced by palpation o f the
the mouth. It is generally a protective reflex to expel material trachea, although the concurrent involvement o f deeper
from the airways, although inflammation or compression of airways is possible. C o u g h associated w i t h pneumonias and
the airways can also stimulate cough. C o u g h is sometimes p u l m o n a r y edema is usually soft.
caused by disease outside of the lower respiratory tract. Chy The association o f coughing with temporal events can be
lothorax can cause cough. A l t h o u g h not well documented i n helpful. C o u g h resulting from tracheal disease is exacerbated
dogs or cats, gastroesophageal reflux and postnasal drip are by pressure o n the neck, such as pulling o n the animal's
common causes of cough i n people. collar. C o u g h caused by heart failure tends to occur more
BOX 19-1
Differential Diagnoses for Lower Respiratory Tract Disease in Dogs and Cats
frequently at night, whereas cough caused by airway inflam cats have m i n i m a l l y visible respiratory efforts. Cats that
m a t i o n (bronchitis) tends to occur more frequently u p o n show noticeable chest excursions or open-mouth breathing
rising from sleep or d u r i n g and after exercise or exposure to are severely compromised. Patients i n overt distress require
cold air. The client's perception o f frequency may be biased rapid physical assessment and immediate stabilization before
by the times o f day d u r i n g w h i c h they have the most contact further diagnostic testing, as discussed i n Chapter 26.
w i t h their pets, often i n the evenings and during exercise.
Surprisingly, cats w i t h many o f the disorders listed i n B o x Resting Respiratory Rate
19-2 do not cough. In cats that cough, the index o f suspicion Resting respiratory rate can be used as an indicator of p u l
for bronchitis, l u n g parasites, and heartworm disease is monary function i n patients that are not yet i n respiratory
high. distress. The measurement is ideally made at home by the
owner, w h i c h spares the patient the stress of the veterinary
EXERCISE INTOLERANCE AND hospital. The n o r m a l respiratory rate o f a dog or cat without
RESPIRATORY DISTRESS stress, at rest, is less than 20 respirations per minute. A rate
Diseases o f the lower respiratory tract can compromise the of up to 30 respirations per minute is generally considered
lung's function o f oxygenating the b l o o d through a variety n o r m a l during a routine physical examination.
of mechanisms (see the section o n b l o o d gas analysis i n
Chapter 20). C l i n i c a l signs o f such compromise begin as Mucous Membrane Color
m i l d l y increased respirations and subtly decreased activity Cyanosis, i n w h i c h n o r m a l l y p i n k mucous membranes are
and progress through exercise intolerance (manifested as bluish, is a sign o f severe hypoxemia and indicates that the
reluctance to exercise or respiratory distress w i t h exertion) increased respiratory effort is not sufficiently compensating
to overt respiratory distress at rest. Because o f compensatory for the degree o f respiratory dysfunction. Pallor of mucous
mechanisms, the ability of most pets to self-regulate their membranes is a more c o m m o n sign o f acute hypoxemia
activity, and the inability o f pets to communicate, many resulting from respiratory disease.
veterinary patients w i t h c o m p r o m i s e d l u n g function arrive
i n overt respiratory distress. Dogs i n overt distress w i l l often Breathing Pattern
stand w i t h their neck extended and elbows abducted. M o v e Patients i n respiratory distress resulting from diseases of the
ments of the abdominal muscles may be exaggerated. Healthy lower respiratory tract, excluding the large airways, typically
Physical Examination
BOX 19-2 Measurement o f respiratory rate, assessment o f mucous
membrane color, and observation o f the breathing pattern
Differential Diagnoses for Productive C o u g h * i n Dogs
were described i n the previous sections. A complete physical
and Cats
examination, i n c l u d i n g a fundic examination, is warranted
Edema to identify signs o f disease that may be concurrently or sec
Heart failure ondarily affecting the lungs (e.g., systemic mycoses, meta
Noncardiogenic pulmonary edema static neoplasia, megaesophagus). The cardiovascular system
should be carefully evaluated. M i t r a l insufficiency m u r m u r s
Mucus or Exudate are frequently auscultated i n older small-breed dogs brought
Canine infectious tracheobronchitis to the clinician w i t h the primary complaint o f cough. M i t r a l
Canine chronic bronchitis insufficiency is often an incidental finding, but the clinician
Feline bronchitis (idiopathic) must consider both cardiac and respiratory tract diseases as
Allergic bronchitis
differential diagnoses i n these animals. M i t r a l insufficiency
Bacterial infection (bronchitis or pneumonia)
can lead to left atrial enlargement w i t h compression o f
Parasitic disease
the mainstem b r o n c h i , causing cough, or to congestive heart
Aspiration pneumonia
Fungal pneumonia (severe) failure. Dogs i n congestive heart failure are nearly always
tachycardic, and any cough is usually soft. Other signs o f
Blood (Hemoptysis) heart disease include prolonged capillary refill time, weak or
Heartworm disease irregular pulses, abnormal jugular pulses, ascites or subcuta
Neoplasia neous edema, gallop rhythms, and pulse deficits. Thoracic
Fungal pneumonia radiographs and occasionally echocardiography may be
Thromboembolism needed before cardiac problems can be comfortably ruled
Severe heart failure out as a cause o f lower respiratory tract signs.
Foreign body
Thoracic auscultation. Careful auscultation o f the
Lung lobe torsion
upper airways and lungs is a critical component o f the phys
Systemic bleeding disorder
ical examination i n dogs and cats w i t h respiratory tract
Radiography
Thoracic radiographs are indicated i n dogs and cats with
lower respiratory tract signs. Neck radiographs should also
be obtained i n animals with suspected tracheal disease. Radi
FIG 1 9 - 1
ography is perhaps the single most helpful diagnostic tool i n
Auscultation of the respiratory tract b e g i n s with the stetho
s c o p e positioned over the t r a c h e a (stethoscope position (1)). the evaluation o f dogs and cats with intrathoracic disease.
After assessing u p p e r a i r w a y s o u n d s , the stethoscope is It helps i n localizing the problem to an organ system (i.e.,
positioned to e v a l u a t e the c r a n i o v e n t r a l , central, a n d d o r s a l cardiac, pulmonary, mediastinal, pleural), identifying the
lung fields o n both sides of the chest (stethoscope positions area of involvement within the lower respiratory tract (i.e.,
(2), (3), a n d (4)). N o t e that the lung fields extend from the vascular, bronchial, alveolar, interstitial), and narrowing the
thoracic inlet to a p p r o x i m a t e l y the seventh rib a l o n g the
list of potential differential diagnoses. It also helps i n the
sternum a n d to a p p r o x i m a t e l y the ninth intercostal s p a c e
a l o n g the s p i n e (thin red line). C o m m o n mistakes a r e to formulation o f a diagnostic plan (see Chapter 20). A d d i
neglect the cranioventral lung fields, r e a c h e d b y p l a c i n g the tional diagnostic tests are necessary i n most animals to estab
stethoscope b e t w e e n the forelimb a n d the chest, a n d to lish a definitive diagnosis.
position the stethoscope t o o f a r c a u d a l l y , b e y o n d the lung
fields a n d o v e r the liver. (Thick black line indicates position Complete Blood Count
of the thirteenth rib.)
The C B C of patients with lower respiratory tract disease may
show the anemia o f inflammatory disease, polycythemia sec
ondary to chronic hypoxia, or a white b l o o d cell response
A n y asymmetry i n the sounds between the left and right characteristic o f an inflammatory process of the lungs. The
sides is abnormal. hematologic changes are insensitive, however, and an absence
N o r m a l l u n g sounds have been described historically as a of abnormalities cannot be used as the basis for ruling out
mixture o f "bronchial" and "vesicular" sounds, although all inflammatory lung diseases. For instance, only half of dogs
sounds originate from the large airways. The bronchial with bacterial pneumonia have a neutrophilic leukocytosis
sounds are most prominent i n the central regions o f the and left shift. Abnormalities are also not specific. For instance,
lungs. They are tubular sounds similar i n character to those eosinophilia is c o m m o n l y encountered as a result of hyper
heard over the trachea, but they are quieter. Vesicular sounds sensitivity or parasitic disease involving organs other than
are most prominent i n the peripheral lung fields. They are the lung.
soft and have been likened to a breeze b l o w i n g through
leaves. These n o r m a l sounds are best described as "normal PULMONARY SPECIMENS AND SPECIFIC
breath sounds." DISEASE TESTING
Decreased lung sounds over one or both sides o f the Based o n results o f the history, physical examination, tho
thorax occur i n dogs and cats w i t h pleural effusion, pneu racic radiographs, and C B C , a prioritized list of differential
mothorax, diaphragmatic hernia, or mass lesions. Surpris diagnoses is developed. A d d i t i o n a l diagnostic tests (Fig.
ingly, consolidated lung lobes and mass lesions can result i n 19-2) are nearly always required to achieve a definitive diag
enhanced lung sounds because of the improved transmission nosis, which is necessary for optimal therapy and outcome.
of airway sounds from adjacent lobes. A b n o r m a l lungs Selection o f appropriate tests is based o n the most likely dif
sounds are described as increased breath sounds (alterna ferential diagnoses, the localization of disease within the
tively, harsh lung sounds), crackles, or wheezes. Increased lower respiratory tract (e.g., diffuse bronchial disease, single
breath sounds are a nonspecific finding but are c o m m o n i n mass lesion), the degree of respiratory compromise of the
patients w i t h pulmonary edema or pneumonia. Crackles are patient, and the client's motivation for optimal care.
nonmusical, discontinuous noises that sound like paper Invasive and noninvasive tests are available. Noninvasive
being crumpled or bubbles popping. Diseases resulting i n tests have the obvious advantage of being nearly risk free but
the formation o f edema or an exudate w i t h i n the airways are usually aimed at confirming a specific diagnosis. Most
(e.g., p u l m o n a r y edema, infectious or aspiration pneumo patients w i t h lower respiratory tract disease require collec-
FIG 19-2
D i a g n o s t i c a p p r o a c h for d o g s a n d cats with l o w e r r e s p i r a t o r y tract d i s e a s e .
tion o f a pulmonary specimen for microscopic and m i c r o do not provide a diagnosis i n a patient with progressive
biologic analysis to further narrow the list of differential disease, thoracoscopy or thoracotomy with lung biopsy is
diagnoses or make a definitive diagnosis. A l t h o u g h the pro indicated.
cedures for specimen collection from the lung are considered Valuable information about patients with lower respira
invasive, they carry varying degrees o f risk, depending o n the tory tract disease can also be obtained by assessing lung
procedure used and the degree o f respiratory compromise function through arterial b l o o d gas analysis. Results are
of the patient. The risk is m i n i m a l i n many instances. rarely helpful i n making a final diagnosis, but they are useful
Noninvasive tests include serology for pulmonary patho in determining degree o f compromise and i n monitoring
gens, fecal examinations for parasites, and specialized response to therapy. Pulse oximetry, a noninvasive technique
imaging techniques such as fluoroscopy, angiography, to measure oxygen saturation o f the b l o o d , is particularly
computed tomography ( C T ) , ultrasonography, magnetic valuable i n m o n i t o r i n g patients w i t h respiratory compro
resonance imaging ( M R I ) , and nuclear imaging. Techniques mise during anesthetic procedures or respiratory crises.
for collection of pulmonary specimens that can be per
formed without specialized equipment include tracheal Suggested Readings
wash, bronchoalveolar lavage, and transthoracic lung aspira Hamlin RL: Physical examination of the pulmonary system, Vet
tion. Visually guided specimens can be collected during Clin N Am Small Anim Pract 30:1175, 2000.
bronchoscopy. Bronchoscopy has the additional benefit of Kotlikoff M I et al: Lung sounds in veterinary medicine. Part II:
allowing visual assessment of the airways. If analysis o f Deriving clinical information from lung sounds, Compend Cont
lung specimens and results of reasonable noninvasive tests Ed Pract Vet 6:462, 1984.
C H A P T E R 20
THORACIC RADIOGRAPHY
GENERAL PRINCIPLES
General Principles Thoracic radiographs play an integral role i n the diagnostic
Trachea evaluation o f dogs and cats with clinical signs related to the
Lungs lower respiratory tract. They are also indicated for the eval
ANGIOGRAPHY uation o f animals w i t h vague, nonspecific signs of disease to
ULTRASONOGRAPHY detect occult pulmonary disease. Thoracic radiographs can
COMPUTED TOMOGRAPHY A N D MAGNETIC be helpful i n localizing disease processes, narrowing and pri
RESONANCE IMAGING oritizing the differential diagnoses, determining the extent
NUCLEAR IMAGING of disease involvement, and m o n i t o r i n g the progression of
PARASITOLOGY disease and response to treatment.
SEROLOGY A m i n i m u m o f two views o f the thorax should be taken
TRACHEAL W A S H in all dogs and cats. Right lateral and ventrodorsal ( V D )
Techniques views usually are preferred. The sensitivity o f radiographs in
Specimen H a n d l i n g the detection o f lesions is improved i f both right and left
Interpretation o f Results lateral views are obtained. These are indicated i f disease of
NONBRONCHOSCOPIC BRONCHOALVEOLAR the right middle lung lobe, metastatic disease, or other subtle
LAVAGE changes are suspected. The side of the lung away from the
Technique for N B - B A L i n Cats table is more aerated, thereby providing more contrast for
Technique for N B - B A L i n Dogs soft-tissue opacities, and is slightly magnified compared with
Recovery o f Patients Following B A L the side against the table. Dorsoventral ( D V ) views are taken
Specimen H a n d l i n g to evaluate the dorsal pulmonary arteries i n animals with
Interpretation o f Results suspected heartworm disease, pulmonary thromboembo
Diagnostic Y i e l d lism, or pulmonary hypertension. The combination o f D V
TRANSTHORACIC L U N G ASPIRATION A N D and V D views has the same advantages as the combination
BIOPSY of right and left lateral views i n detecting subtle changes in
Common Lower Respiratory Tract Differential Diagnoses Differential Diagnoses for Dogs and Cats with Abnormal
for Dogs and Cats with Respiratory Signs and Normal Pulmonary Vascular Patterns on Thoracic Radiographs
Thoracic Radiographs
Enlarged Arteries
Respiratory Distress Heartworm disease
Pulmonary thromboembolism Pulmonary thromboembolism
Acute aspiration Pulmonary hypertension
Acute pulmonary hemorrhage
Enlarged Veins
Acute foreign body inhalation
Left-sided heart failure
Cough
Enlarged Arteries and Veins (Pulmonary Overcirculation)
Canine infectious tracheobronchitis
Canine chronic bronchitis Left-to-right shunts
Collapsing trachea Patent ductus arteriosus
Feline bronchitis (idiopathic) Ventricular septal defect
Acute foreign body inhalation Atrial septal defect
Gastroesophageal reflux*
Small Arteries and Veins
* Gastroesophageal reflux is a common cause of cough in people. Pulmonary undercirculation
Documentation in dogs a n d cats is limited, but the possibility should Cardiovascular shock
also be considered. Hypovolemia
Severe dehydration
vessels to the caudal lung lobes o n the V D or D V view. N o r Blood loss
mally, the b l o o d vessels should taper gradually from the Hypoadrenocorticism
Pulmonic valve stenosis
left atrium (pulmonary vein) or right ventricle (pulmonary
Hyperinflation of the lungs
arteries) toward the periphery o f the lungs. C o m p a n i o n
Feline bronchitis (idiopathic)
arteries and veins should be similar i n size. Arteries and veins
Allergic bronchitis
have a consistent relationship w i t h each other and the asso
ciated bronchus. O n lateral radiographs the pulmonary
artery is dorsal and the p u l m o n a r y vein is ventral to the
bronchus. O n V D or D V radiographs the p u l m o n a r y artery The finding o f smaller-than-normal arteries and veins
is lateral and the pulmonary vein is medial to the bronchus. may indicate the presence of pulmonary undercirculation
Vessels that are pointed directly toward or away from the or hyperinflation. Undercirculation most often occurs in
X - r a y beam are "end-on" and appear as circular nodules. combination w i t h microcardia resulting from hypoadreno
They are distinguished from lesions by their association with corticism or other causes o f severe hypovolemia. P u l m o n i c
a linear vessel and adjacent bronchus. stenosis may also cause radiographically visible undercir
A b n o r m a l vascular patterns generally involve an increase culation i n some dogs. Hyperinflation is associated with
or decrease i n the size o f arteries or veins (Box 20-2). The obstructive airway disease, such as allergic or idiopathic
finding o f arteries larger than their c o m p a n i o n veins i n d i feline bronchitis.
cates the presence o f p u l m o n a r y hypertension or t h r o m b o
embolism, most c o m m o n l y caused by heartworm disease, a Bronchial Pattern
finding seen i n both dogs and cats (Fig. 20-2). The p u l m o Bronchial walls are normally most easily discernible radio-
nary arteries often appear tortuous and truncated i n such graphically at the hilus. They should taper and grow thinner
animals. Concurrent enlargement o f the m a i n pulmonary as they extend toward the periphery o f each lung lobe. Bron
artery and right side o f the heart may be seen i n affected chial structures are not normally visible radiographically
dogs. There may also be interstitial, bronchial, or alveolar i n the peripheral regions o f the lungs. The cartilage may be
infiltrates i n cats and dogs w i t h heartworm disease as a result calcified i n older dogs and chondrodystrophic breeds, making
of concurrent inflammation, edema, or hemorrhage. the walls more prominent but still sharply defined.
Veins larger than their c o m p a n i o n arteries indicate the A bronchial pattern is caused by thickening of the bron
presence of congestion resulting from left-sided heart failure. chial walls or bronchial dilation. Thickened bronchial walls
P u l m o n a r y edema may also be present. are visible as "tram lines" and "doughnuts" i n the peripheral
D i l a t i o n o f both arteries and veins is an unusual finding, regions o f the lung (Fig. 20-3). T r a m lines are produced by
except i n young animals. The finding o f p u l m o n a r y over- airways that r u n transverse to the X - r a y beam, causing the
circulation is suggestive of left-to-right cardiac or vascular appearance of parallel thick lines with an air stripe i n
shunts, such as patent ductus arteriosus and ventricular between. Doughnuts are produced by airways that are point
septal defects. ing directly toward or away from the beam, causing a thick
BOX 20-3
C a n i n e c h r o n i c bronchitis
Feline bronchitis (idiopathic)
A l l e r g i c bronchitis
C a n i n e infectious tracheobronchitis
Bacterial infection
M y c o p l a s m a l infection
P u l m o n a r y parasites
Alveolar Pattern
Alveoli are not normally visible radiographically. Alveolar
patterns occur when the alveoli are filled with fluid-dense
material (Box 20-4). The fluid opacity may be caused by
edema, inflammation, hemorrhage, or neoplastic infiltrates,
which generally originate from the interstitial tissues. The
fluid-filled alveoli are silhouetted against the walls of the
airways they surround. The result is a visible stripe o f air
from the airway l u m e n i n the absence o f definable airway
walls. This stripe is an air bronchogram (Fig. 20-5). If the
fluid continues to accumulate, the airway lumen will eventu
ally also become filled w i t h fluid, resulting i n the formation
of solid areas o f fluid opacity, or consolidation.
Edema most often results from left-sided heart failure
(see Chapter 22). In dogs the fluid initially accumulates i n
FIG 2 0 - 3
A bronchointerstitial pattern is present in this lateral radio the perihilar region, and eventually the entire l u n g is affected.
graph from a cat with i d i o p a t h i c bronchitis. The b r o n c h i a l In cats patchy areas of edema can be present initially through
component results from thickening of the b r o n c h i a l w a l l s out the l u n g fields. The finding of enlarged p u l m o n a r y veins
and is characterized b y " d o u g h n u t s " a n d "tram lines." In supports the cardiac origin o f the infiltrates. Noncardiogenic
this radiograph the bronchial c h a n g e s a r e most a p p a r e n t in edema is typically most severe i n the caudal l u n g lobes.
the c a u d a l lung lobes.
Inflammatory infiltrates can be caused by infectious
agents, noninfectious inflammatory disease, or neoplasia.
circle to be seen radiographically, with the airway l u m e n The location of the infiltrative process can often help estab
creating the "hole." The walls of the bronchi tend to be indis lish a tentative diagnosis. F o r example, diseases o f airway
tinct. The finding of thickened walls indicates the presence origin, such as most bacterial and aspiration pneumonias,
of bronchitis and results from an accumulation of mucus or primarily affect the dependent lung lobes (i.e., the right
exudate along the walls within the lumens, an infiltration of middle and cranial lobes and the left cranial lobe). In con-
FIG 2 0 - 4
Lateral r a d i o g r a p h of a d o g with c h r o n i c bronchitis a n d b r o n c h i e c t a s i s . The a i r w a y
lumens a r e greatly e n l a r g e d , a n d n o r m a l t a p e r i n g of the a i r w a y w a l l s is not s e e n .
BOX 20-4
Pulmonary Edema
Bacterial p n e u m o n i a
Aspiration pneumonia
Hemorrhage
P u l m o n a r y contusion
Pulmonary thromboembolism
Neoplasia
Fungal pneumonia
FIG 2 0 - 5
Systemic c o a g u l o p a t h y
Lateral v i e w of the thorax of a d o g with a s p i r a t i o n pneumo
n i a . A n a l v e o l a r pattern is evident b y the i n c r e a s e d soft-
* A n y of the differential diagnoses for interstitial patterns (Boxes
tissue o p a c i t y with a i r b r o n c h o g r a m s . A i r b r o n c h o g r a m s a r e
20-5 and 20-6) can cause an alveolar pattern if associated with
b r o n c h i a l a i r stripes without visible b r o n c h i a l w a l l s . In this
severe inflammation, edema, or hemorrhage.
r a d i o g r a p h the pattern is most severe in the ventral (depen
dent) r e g i o n s of the l u n g , consistent with bacterial or
aspiration pneumonia.
trast, diseases o f vascular origin, such as dirofilariasis and
t h r o m b o e m b o l i , p r i m a r i l y affect the caudal lung lobes.
Localized processes involving only one lung lobe suggest the Interstitial Pattern
presence o f a foreign body, neoplasia, abscess, granuloma, or The p u l m o n a r y interstitial tissues confer a fine, lacy pattern
lung lobe torsion. to the p u l m o n a r y parenchyma of many dogs and cats as they
Hemorrhage usually results from trauma. T h r o m b o e m age, i n the absence of clinically apparent respiratory disease.
bolism, neoplasia, coagulopathies, and fungal infections can They are not normally visible o n inspiratory radiographs i n
also cause hemorrhage into the alveoli. young adult animals.
A b n o r m a l interstitial patterns are reticular (unstruc and some eosinophilic l u n g diseases or idiopathic interstitial
tured), nodular, or reticulonodular i n appearance. A nodular pneumonias may be indistinguishable from neoplastic
interstitial pattern is characterized by the finding o f roughly lesions. In the absence o f strong clinical evidence, malignant
circular, fluid-dense lesions i n one or more lung lobes. neoplasia must be confirmed cytologically or histologically.
However, the nodules must be nearly 1 c m i n diameter to be If this is not possible, radiographs can be obtained again 4
routinely detected. Interstitial nodules may represent active weeks later to evaluate for progression o f disease.
or inactive inflammatory lesions or neoplasia (Box 20-5). Neoplastic involvement o f the p u l m o n a r y parenchyma
Active inflammatory nodules often have poorly defined cannot be totally excluded o n the basis o f thoracic radio
borders. Mycotic infections typically result i n the formation graph findings because malignant cells are present for a
of multiple, diffuse nodules. The nodules may be small while before lesions reach a radiographically detectable size.
(miliary; Fig. 20-6) or large and coalescing. Parasitic granu The sensitivity o f radiography i n identifying neoplastic
lomas are often multiple, although paragonimiasis can result nodules can be improved by obtaining left and right lateral
in the formation of a single pulmonary nodule. Abscesses views of the thorax.
can form as a result of foreign bodies or as a sequela to bac The reticular interstitial pattern is characterized by a
terial pneumonia. N o d u l a r patterns may also be seen o n the diffuse, unstructured, lacy increase i n the opacity o f the
radiographs obtained i n animals w i t h some eosinophilic pulmonary interstitium, w h i c h partially obscures n o r m a l
lung diseases and idiopathic interstitial pneumonias.
Inflammatory nodules can persist as inactive lesions after
the disease resolves. In contrast to active inflammatory
nodules, however, the borders of inactive nodules are often
well demarcated. Nodules may also become mineralized i n
some conditions, such as histoplasmosis. Well-defined, small,
inactive nodules are sometimes seen i n healthy older dogs
without a history of disease. Radiographs taken several
months later i n these animals typically show no change i n
the size of these inactive lesions.
Neoplastic nodules may be singular or multiple (Fig.
20-7). They are often well defined, although secondary
inflammation, edema, or hemorrhage can obscure the
margins. There is no radiographic pattern that is diagnostic
for neoplasia. Lesions caused by parasites, fungal infections,
FIG 2 0 - 6
Lateral v i e w of the thorax in a d o g with b l a s t o m y c o s i s . A
miliary, n o d u l a r interstitial pattern is present. Increased soft-
BOX 20-5 tissue o p a c i t y a b o v e the b a s e of heart m a y b e the result of
hilar l y m p h a d e n o p a t h y .
Differential Diagnoses for Dogs and Cats w i t h N o d u l a r
Interstitial Patterns
Neoplasia
Mycotic Infection
Blastomycosis
Histoplasmosis
Coccidioidomycosis
Pulmonary Parasites
Aelurostrongylus infection
Paragonimus infection
Abscess
Bacterial p n e u m o n i a
Foreign b o d y
ULTRASONOGRAPHY
Ultrasonography is used to evaluate pulmonary mass lesions
adjacent to the body wall, diaphragm, or heart and also
consolidated lung lobes (Fig. 20-11). Because air interferes
with the sound waves, aerated lungs and structures sur
rounded by aerated lungs cannot be examined. However,
some patients w i t h a reticular interstitial pattern o n thoracic
radiographs have sufficient infiltrates to be visualized where
they abut the body wall. The consistency of lesions often can
be determined to be solid, cystic, or fluid filled. Some solid
masses are hypolucent and appear to be cystic on ultrasono
grams. Vascular structures may be visible, particularly with
Doppler ultrasound, and this can be helpful i n identifying
lung lobe torsion. Ultrasonography can also be used to guide
needles or biopsy instruments into solid masses for speci
m e n collection. It is used for evaluating the heart i n animals
with clinical signs that cannot be readily localized to either
FIG 30-10 the cardiac or the respiratory systems. Ultrasonographic
V e n t r o d o r s a l v i e w of the t h o r a x in a c a t s h o w i n g a cystic evaluation of patients w i t h pleural disorders is discussed i n
lesion (arrowheads) in the left c a u d a l lung l o b e . Differential Chapter 24.
d i a g n o s e s i n c l u d e d n e o p l a s i a a n d Paragonimus infection.
nation for eggs or larvae is a simple, noninvasive tool for the Toxoplasma gondii occasionally causes pneumonia i n dogs
diagnosis o f such infestations. However, because shedding is and cats. Dogs do not shed Toxoplasma organisms i n the
intermittent, parasitic disease cannot be included solely o n feces, but cats may. However, the shedding of eggs is part of
the basis o f negative fecal examination findings. M u l t i p l e (at the direct life cycle o f the organisms and does not correlate
least three) examinations should be performed i n animals with the presence o f systemic disease resulting from the indi
that are highly suspected o f having parasitic disease. If pos rect cycle. Infection is therefore diagnosed by finding
sible, several days should be allowed to elapse between each tachyzoites i n pulmonary specimens or indirectly on the
collection of feces. basis of serologic findings.
Routine fecal flotation can be used to concentrate eggs M i g r a t i n g intestinal parasites can cause transient pulmo
from C. aerophila. High-density fecal flotation (specific nary signs i n y o u n g animals. M i g r a t i o n most often occurs
gravity [s.g.], 1.30 to 1.35) can be used to concentrate P. before the mature adults develop i n the intestine, and thus
kellicotti eggs. Sedimentation techniques are preferred for eggs may not be found i n feces.
concentrating and identifying P. kellicotti eggs, particularly
i f few eggs are present. Larvae are identified through the
use o f the Baermann technique. However, O. osleri larvae SEROLOGY
are insufficiently motile for reliable identification with this
technique, and zinc sulfate (s.g., 1.18) flotation is recom Serologic tests can detect a variety of pulmonary pathogens.
mended. Even so, false-negative results are c o m m o n in cases A n t i b o d y tests provide only indirect evidence o f infection,
with O. osleri. A l l of these techniques can be readily per however. In general, they should be used only to confirm a
formed at m i n i m a l expense. Methods for sedimentation suspected diagnosis, not to screen for disease. Whenever
and the Baermann technique are described i n Boxes 20-7 possible, identification o f the infectious organisms is the
and 20-8. preferred method o f diagnosis. Tests available for c o m m o n
TABLE 20-
Capillaria aerophila Dog and cat Eggs Routine flotation of Barrel shaped, yellow, with prominent,
feces, airway transparent, asymmetric bipolar
specimens plugs; slightly smaller than Trichuris
eggs; 60-80 m x 30-40 m
Paragonimus Dog and cat Eggs High-density flotation or O v a l , golden-brown, single,
kellicotti sedimentation of operculated; operculum flat with
feces, airway prominent shoulders; 75-118 m x
specimens 42-67 m
Aelurostrongylus Cat Larvae Baermann technique of Larvae with S-shaped tail; dorsal spine
abstrusus feces, airway present; 350-400 m x 17 m;
specimens eggs or larvated eggs may be seen
in airway specimens
Oslerus osleri Dog Larvae, eggs Tracheal wash, Larvae have S-shaped tail without
bronchial brushing of dorsal spine; rarely found eggs are
nodules, zinc sulfate thin-walled, colorless, and larvated;
flotation of feces 8 0 x 5 0 m
Crenosoma vulpis Dog Larvae Baermann technique of Larvae have tapered tail without
feces, airway severe kinks or spines; 250-300 m;
specimens larvated eggs may be seen in
airway specimens
Sedimentation of Feces for Concentration of Eggs Baermann Technique for Concentration of Larvae
Data from Urquhart G M et al: Veterinary parasitology, ed 2, Data from Urquhart G M et al: Veterinary parasitology, ed 2,
Oxford, 1996, Blackwell Science. O x f o r d , 1996, Blackwell Science.
Comparisons of Techniques for Collecting Specimens from the Lower Respiratory Tract
SITE O F SPECIMEN
TECHNIQUE COLLECTION SIZE ADVANTAGES DISADVANTAGES INDICATIONS
Tracheal wash Large airways Moderate Simple technique Airway must be involved Bronchial and
Minimal expense for specimen to alveolar disease
N o special equipment represent disease Because of safety
Complications rare M a y induce and ease,
Volume adequate for bronchospasm in consider for any
cytology and culture patients with lung disease
hyperreactive airways, Less likely to be
particularly cats representative of
interstitial or
small focal
processes
Bronchoalveolar Small airways, Large Simple technique General anesthesia Small airway,
lavage alveoli, Nonbronchoscopic required alveolar, or
sometimes technique requires no Special equipment and interstitial disease
interstitium special equipment expertise required for Routine during
and minimal expense bronchoscopic bronchoscopy
Bronchoscopic technique collection
allows airway Generally not
evaluation and recommended for
directed sampling animals with increased
Resultant hypoxemia is respiratory efforts or
transient and respiratory distress
responsive to oxygen Capability to provide
supplementation oxygen supplementation
Safe for animals in is required
stable condition M a y induce
Large volume of lung bronchospasm in
sampled patients with
High cytologic quality hyperreactive airways,
Large volume for analysis particularly cats
Lung aspirate Interstitium, Small Simple technique Potential for complications: Solid masses
alveoli Minimal expense pneumothorax, adjacent to chest
when N o special equipment hemothorax, wall (for solitary/
flooded Solid masses adjacent to pulmonary hemorrhage localized
body wall: excellent Relatively small area of disease, see also
representation with lung sampled Thoracotomy or
minimal risk Specimen adequate only Thoracoscopy
for cytology with Lung Biopsy)
Specimen blood Diffuse interstitial
contaminated disease
syringe is injected into the catheter. Immediately after this, Endotracheal Technique
many aspiration attempts are made. After each aspiration, The endotracheal technique is performed by passing a 3.5-5F
the syringe must be disconnected from the catheter and the male dog urinary catheter through a sterilized endotracheal
air evacuated without losing any o f the retrieved fluid. A s p i tube. The animal is anesthetized with a short-acting intrave
rations should be forceful and repeated at least five or six nous agent to a sufficient depth to allow intubation. A short-
times so that small volumes o f airway secretions that have acting barbiturate, propofol, or, i n cats, a combination of
been aspirated into the catheter are pulled the entire length ketamine and acepromazine or diazepam is effective.
of the catheter into the syringe. Premedication with atropine, particularly i n cats, is recom
The procedure is repeated using additional boluses of mended to m i n i m i z e contamination of the trachea with saliva.
saline u n t i l a sufficient amount o f fluid is retrieved for anal Cats with lower respiratory tract disease may have airway
ysis. A total o f 1.5 to 3 m l o f turbid fluid is adequate i n most hyperreactivity and generally should be administered a bron
instances. The clinician does not need to be concerned about chodilator before the tracheal wash. Terbutaline (0.01 mg/kg)
" d r o w n i n g " the animal w i t h the infusion o f the modest can be given subcutaneously to cats not already receiving oral
volumes o f fluid described because the fluid is rapidly bronchodilators. It is also prudent to keep a metered dose
absorbed into the circulation. Failure to retrieve adequate inhaler of albuterol at hand to administer through the endo
volumes o f visibly turbid fluid can be the result o f several tracheal tube or by mask i f breathing becomes labored.
technical difficulties, as outlined i n Figure 20-14. A sterilized endotracheal tube should be passed without
The catheter is removed after sufficient fluid is collected. dragging the tip through the oral cavity. The animal's mouth
A sterile gauze sponge w i t h antiseptic ointment is then is opened wide w i t h the tongue pulled out, a laryngoscope
immediately placed over the catheter site, and a light bandage is used, and, i n cats, sterile topical lidocaine is applied to the
is wrapped around the neck. This bandage is left i n place for laryngeal cartilages to ease passage of the tube with m i n i m a l
several hours while the animal rests quietly i n a cage. These contamination.
precautions m i n i m i z e the likelihood that subcutaneous The urinary catheter is passed through the endotracheal
emphysema or pneumomediastinum will develop. tube to the level of the carina (approximately the fourth
FIG 20-14
O v e r c o m i n g p r o b l e m s with t r a c h e a l w a s h fluid c o l l e c t i o n . G r e e n b o x e s i n d i c a t e p r o b l e m s ,
blue b o x e s indicate p o s s i b l e c a u s e s , a n d o r a n g e b o x e s i n d i c a t e r e m e d i e s .
intercostal space), maintaining sterile technique. The wash
procedure is performed as described for the transtracheal
technique. Slightly larger boluses o f saline may be required,
however, because o f the larger volume o f the catheter. Use o f
a catheter larger than 5F seems to reduce the yield o f the
wash except when secretions are extremely viscous.
SPECIMEN HANDLING
The cells collected i n the wash fluid are fragile. The fluid
is ideally processed w i t h i n 30 minutes o f collection, with
m i n i m a l manipulation. Bacterial culture is performed o n at
least 0.5 to 1 m l o f fluid. Fungal cultures are performed i f
mycotic disease is a differential diagnosis, and Mycoplasma
cultures are considered for cats and dogs with signs o f b r o n
chitis. Cytologic preparations are made both from the fluid FIG 20-15
and from any mucus w i t h i n the fluid. Both fluid and mucus Photomicrograph of a Blastomyces organism from the lungs
are examined because infectious agents and inflammatory of a dog with blastomycosis. The organisms stain deeply
cells can be concentrated i n the mucus, but the protein basophilic, are 5 to 15 m in diameter, and have a thick
aceous material causes cells to c l u m p and interferes with refractile cell wall. Often, as in this figure, broad-based
budding forms are seen. The cells present are alveolar
evaluation o f the cell morphology. M u c u s is retrieved w i t h a
macrophages and neutrophils. (Bronchoalveolar lavage
needle, and squash preparations are made. Direct smears o f
fluid, Wright stain.)
the fluid itself can be made, but such specimens are often
hypocellular. Sediment or cytocentrifuge preparations are
generally necessary to make adequate interpretation pos
sible. Straining the fluid through gauze to remove the mucus
is discouraged because infectious agents may be lost i n the
process. Routine cytologic stains are used.
Microscopic examination of slides includes the identifica
tion of cell types, qualitative evaluation o f the cells, and an
examination for infectious agents. Cells are evaluated quali
tatively for evidence o f macrophage activation, neutrophil
degeneration, lymphocyte reactivity, and characteristics o f
malignancy. Epithelial hyperplasia secondary to inflamma
tion should not be overinterpreted as neoplasia, however.
Infectious agents such as bacteria, protozoa (Toxoplasma
gondii), fungi (Histoplasma, Blastomyces, and Cryptococcus
organisms), and parasitic larvae or eggs may be present (see
Fig. 20-12, and Figs. 20-15 through 20-17). Because only one FIG 2 0 - 1 6
or two organisms may be present o n an entire slide, a thor P h o t o m i c r o g r a p h of Histoplasma o r g a n i s m s from the lungs
ough evaluation is indicated. of a d o g with histoplasmosis. The o r g a n i s m s a r e small (2 to
4 m) a n d r o u n d , with a d e e p l y staining center a n d a
INTERPRETATION OF RESULTS lighter-staining h a l o . They a r e often f o u n d within p h a g o c y t i c
cells: in this figure, a n a l v e o l a r m a c r o p h a g e . (Bronchoalveo
N o r m a l tracheal wash fluid contains primarily respiratory
lar l a v a g e fluid, W r i g h t stain.)
epithelial cells. Few other inflammatory cells are present (Fig.
20-18). Occasionally, macrophages are retrieved from the
small airways and alveoli because the catheter was extended from drainage of saliva into the trachea, which usually occurs
into the lungs beyond the carina or because relatively large in cats that hypersalivate or dogs that are heavily sedated,
volumes o f saline were used. M o s t macrophages are not acti particularly i f the head and neck are extended more than
vated. In these instances the presence of macrophages does briefly for the passage o f the endotracheal tube or transtra
not indicate disease but rather reflects the acquisition o f cheal catheter. O r a l contamination is indicated by the finding
material from the deep lung (see the section o n nonbron of numerous squamous epithelial cells, often coated with
choscopic bronchoalveolar lavage). bacteria, and Simonsiella organisms (Fig. 20-19). Simonsiella
Slides are examined for evidence o f overt oral contamina organisms are large basophilic rods that are frequently found
tion, w h i c h can occur during transtracheal washing i f the stacked uniformly o n one another along their broad side.
catheter needle was inadvertently inserted p r o x i m a l to the Specimens with overt oral contamination generally do not
cricothyroid ligament. Rarely, dogs can cough the catheter provide accurate information about the airways, particularly
up into the oropharynx. O r a l contamination can also result with regard to bacterial infection.
Cytologic results of tracheal wash fluid are most useful cant, whereas the growth of bacteria i n culture may or may
when pathogenic organisms or malignant cells are identified. not be significant because low numbers o f bacteria can be
The presence of pathogens such as Toxoplasma gondii, sys present i n the large airways o f healthy animals. In general,
temic fungal organisms, and parasites provide a definitive the cytologic identification o f bacteria and their growth i n
diagnosis. The finding o f bacterial organisms i n cytologic culture without multiplication i n enrichment broth are sig
preparations without evidence o f oral contamination i n d i nificant findings. Bacteria that are not seen cytologically and
cates the presence o f infection. The growth o f any of the that grow only after incubation i n enrichment media can
systemic mycotic agents i n culture is also clinically signifi- result from several situations. For example, the bacteria may
be causing infection without being present i n high numbers
because of the prior administration o f antibiotics or because
of the collection o f a nonrepresentative specimen. The bac
teria may also be clinically insignificant and represent n o r m a l
tracheal inhabitants or result from contamination during
collection. Other clinical data must therefore be considered
when interpreting such findings. The role o f Mycoplasma sp.
in respiratory disease o f the dog and cat is not well under
stood. These organisms cannot be seen o n cytologic prepara
tions and are difficult to grow i n culture. Specific transport
media is necessary. G r o w t h o f Mycoplasma organisms from
tracheal wash fluid may indicate primary or secondary infec
tion or be an insignificant finding. Treatment is generally
recommended.
Criteria o f malignancy for m a k i n g a diagnosis o f neo
plasia must be interpreted w i t h extreme caution. Overt char
acteristics o f malignancy must be present i n many cells i n
FIG 2 0 - 1 7
the absence o f concurrent inflammation for a definitive
Photomicrograph of Toxoplasma gondii tachyzoites from the
diagnosis to be made.
lungs of a c a t with acute t o x o p l a s m o s i s . The extracellular
tachyzoites a r e crescent s h a p e d with a centrally p l a c e d The type o f inflammatory cells present i n tracheal wash
nucleus. They a r e a p p r o x i m a t e l y 6 m in length. (Bronchoal fluid can assist i n narrowing the differential diagnoses,
veolar l a v a g e fluid, W r i g h t stain.) although a mixed inflammatory response is c o m m o n .
FIG 2 0 - 1 8
Tracheal w a s h fluid from a healthy d o g s h o w i n g ciliated epithelium a n d f e w inflammatory
cells.
response is also usually present. Hemorrhage can be caused
by neoplasia, mycotic infection, heartworm disease, throm
boembolism, foreign body, lung lobe torsion, or coagulopa
thies. Evidence of hemorrhage is seen occasionally i n animals
with congestive heart failure or severe bacterial pneumonia.
NONBRONCHOSCOPIC
BRONCHOALVEOLAR LAVAGE
Indications and Complications
Bronchoalvelolar lavage ( B A L ) is considered for the diagnos
tic evaluation o f patients with lung disease involving the
small airways, alveoli, or interstitium that are not i n respira
tory distress (see Table 20-2). A large volume o f lung is
FIG 20-19
T r a c h e a l w a s h fluid s h o w i n g e v i d e n c e of o r o p h a r y n g e a l sampled by B A L (Figs. 20-20 and 20-21). The collected spec
c o n t a m i n a t i o n . The numerous, uniformly s t a c k e d b a s o p h i l i c imens are o f large volume, providing more than adequate
rods a r e Simonsiella o r g a n i s m s , n o r m a l inhabitants of the material for routine cytology, cytology involving special
o r a l cavity. These o r g a n i s m s , a s w e l l a s m a n y other stains (e.g., G r a m stains, acid-fast stains), multiple types of
b a c t e r i a , a r e a d h e r i n g to a s q u a m o u s epithelial c e l l .
cultures (e.g., bacterial, fungal, mycoplasmal), or other spe
S q u a m o u s epithelium is a n o t h e r i n d i c a t i o n of c o n t a m i n a t i o n
cific tests that might be helpful i n particular patients (e.g.,
from the o r a l cavity.
flow cytometry, polymerase chain reaction [PCR]). Cyto
logic preparations from B A L fluid are o f excellent quality
Neutrophilic (suppurative) inflammation is c o m m o n i n bac and consistently provide large numbers of well-stained cells
terial infections. Before antibiotic therapy is initiated, the for examination.
neutrophils may be (but are not always) degenerative, and Although general anesthesia is required, the procedure is
organisms can often be seen. N e u t r o p h i l i c inflammation associated w i t h few complications and can be performed
may be a response to a variety o f other diseases. For instance, repeatedly i n the same animal to follow the progression of
it can be caused by other infectious agents or seen i n patients disease or observe the response to therapy. The primary
with canine chronic bronchitis, idiopathic pulmonary fibro complication o f B A L is transient hypoxemia. The hypoxemia
sis or other idiopathic interstitial pneumonias, or even neo generally can be corrected with oxygen supplementation, but
plasia. Some cats w i t h idiopathic bronchitis have neutrophilic animals exhibiting increased respiratory efforts or respira
inflammation rather than the expected eosinophilic response tory distress i n r o o m air are not good candidates for this
(see Chapter 21). The neutrophils i n these instances are gen procedure. Patients with hyperreactive airways, particularly
erally nondegenerative. cats, are treated with bronchodilators, as described previ
Eosinophilic inflammation reflects a hypersensitivity ously, for endotracheal washing. For patients with bacterial
response, and c o m m o n diseases resulting i n eosinophilic or aspiration pneumonia, tracheal washing routinely results
inflammation include allergic bronchitis, parasitic disease, i n an adequate specimen for cytologic and microbiologic
and eosinophilic lung disease. Parasites that affect the lung analysis and avoids the need for general anesthesia i n these
include primary lungworms or flukes, migrating intestinal patients.
parasites, and heartworms. Over time, m i x e d inflammation B A L is a routine part o f diagnostic bronchoscopy, during
can occur i n patients w i t h hypersensitivity. It is occasionally w h i c h visually guided B A L specimens can be collected from
possible for nonparasitic infections or neoplasia to cause specific diseased lung lobes. However, nonbronchoscopic
eosinophilia, usually as part of a mixed inflammatory response. techniques ( N B - B A L ) have been developed that allow B A L
Macrophagic (granulomatous) inflammation is charac to be performed with m i n i m a l expense i n routine practice
terized by the finding o f increased numbers o f activated settings. Because visual guidance is not possible using these
macrophages, generally present as a component of mixed methods, they are used primarily for patients with diffuse
inflammation along w i t h increased numbers of other inflam disease. However, the technique described for cats probably
matory cells. Activated macrophages are vacuolated and have samples the cranial and middle regions of the lung on the
increased amounts o f cytoplasm. This response is nonspe side of the cat placed against the table, whereas the technique
cific unless an etiologic agent can be identified. described for dogs consistently samples one o f the caudal
Lymphocytic inflammation alone is u n c o m m o n . V i r a l or lung lobes.
rickettsial infection, idiopathic interstitial pneumonias, and
l y m p h o m a are considerations. TECHNIQUE FOR NB-BAL IN CATS
True hemorrhage can be differentiated from a traumatic A sterile endotracheal tube and syringe adapter are used i n
specimen collection by the presence o f erythrophagocytosis cats to collect lavage fluid (Fig. 20-22; see also Fig. 20-21).
and hemosiderin-laden macrophages. An inflammatory Cats, particularly those with signs of bronchitis, should be
FIG 2 0 - 2 0
The r e g i o n of the l o w e r respiratory tract that is s a m p l e d b y b r o n c h o a l v e o l a r l a v a g e (BAL)
in c o m p a r i s o n with the r e g i o n s a m p l e d b y t r a c h e a l w a s h (TW). The solid red line (b)
within the a i r w a y s represents a b r o n c h o s c o p e or m o d i f i e d f e e d i n g tube. The o p e n lines (c)
represent the t r a c h e a l w a s h catheter. B r o n c h o a l v e o l a r l a v a g e y i e l d s fluid representative of
the d e e p l u n g , w h e r e a s t r a c h e a l w a s h y i e l d s fluid representative of p r o c e s s e s involving
major a i r w a y s .
FIG 20-21
The r e g i o n of the l o w e r respiratory tract p r e s u m e d to b e s a m p l e d b y n o n b r o n c h o s c o p i c
b r o n c h o a l v e o l a r l a v a g e in cats using a n e n d o t r a c h e a l tube.
FIG 20-22
B r o n c h o a l v e o l a r l a v a g e using a n e n d o t r a c h e a l tube in a cat. The fluid retrieved is grossly
f o a m y b e c a u s e of the surfactant present. The p r o c e d u r e is p e r f o r m e d q u i c k l y b e c a u s e the
a i r w a y is c o m p l e t e l y o c c l u d e d d u r i n g the infusion a n d a s p i r a t i o n of fluid.
treated with bronchodilators before the procedure, as des TECHNIQUE FOR NB-BAL IN DOGS
cribed previously for tracheal wash (endotracheal technique), A n inexpensive 122-cm 16F Levin-type polyvinyl chloride
to decrease the risk of bronchospasm. The cat is premedi stomach tube (Argyle stomach tube, Tyco Healthcare Group
cated with atropine (0.05 mg/kg subcutaneously) and anes L P ) can be used i n dogs to collect lavage fluid. The tube must
thetized with ketamine and acepromazine or diazepam, given be modified for successful N B - B A L . Sterile technique is
intravenously. The endotracheal tube is passed as cleanly as maintained throughout. The distal end o f the tube is cut off
possible through the larynx to m i n i m i z e oral contamination. to remove the side openings. The proximal end is cut off to
T o achieve sufficient cleanliness, the tip of the tongue is pulled remove the flange and shorten the tube to a length slightly
out, a laryngoscope is used, and sterile lidocaine is applied greater than the distance from the open end o f the dog's
topically to the laryngeal mucosa. The cuff is then inflated endotracheal tube to the last rib. A syringe adapter is placed
sufficiently to create a seal, but overinflation is avoided to within the p r o x i m a l end o f the tube (Fig. 20-23).
prevent tracheal rupture (i.e., use a 3 - m l syringe and inflate Recovery of B A L fluid can be improved by tapering the
cuff i n 0.5-ml increments only until no leak is audible when distal end of the tube. Tapering is readily achieved using a
gentle pressure is placed o n the oxygen reservoir bag). metal, single-blade, handheld pencil sharpener that has been
The cat is placed i n lateral recumbency with the most autoclaved and is used only for this purpose (see Fig. 20-23,
diseased side, as determined by physical and radiographic A and B).
findings, against the table. Oxygen (100%) is administered The dog is premedicated with atropine (0.05 mg/kg
for several minutes through the endotracheal tube. The anes subcutaneously) or glycopyrrolate (0.005 mg/kg subcutane
thetic adapter is then removed from the endotracheal tube ously) and anesthetized using a short-acting protocol that
and replaced with a sterile syringe adapter, using caution to will allow intubation, such as with propofol, a short-acting
avoid contamination o f the end of the tube or adapter. barbiturate, or the combination of medetomidine and butor
Immediately, a bolus o f warmed, sterile 0.9% saline solution phanol. If the dog is o f sufficient size to accept a size 6 or
(5 m l / k g body weight) is infused through the tube over larger endotracheal tube, the dog is intubated with a sterile
approximately 3 seconds. Immediately after infusion, suction endotracheal tube placed as cleanly as possible to minimize
is applied by syringe. A i r is eliminated from the syringe, and oral contamination o f the specimen. The modified stomach
several aspiration attempts are made until fluid is no longer tube w i l l not fit through a smaller endotracheal tube, so the
recovered. The procedure is repeated using a total o f two or technique must be performed without an endotracheal tube
three boluses of saline solution. The cat is allowed to expand or a smaller stomach tube must be used. If no endotracheal
its lungs between the infusions o f saline solution. After the tube is used, extreme care must be taken to m i n i m i z e oral
last infusion, the syringe adapter is removed (because it contamination i n passing the modified stomach tube, and
greatly interferes with ventilation) and excess fluid is drained an appropriate-sized endotracheal tube should be available
from the large airways and endotracheal tube by elevating to gain control o f the airway i n case o f complications and
the caudal half of the cat a few inches off o f the table. A t this for recovery.
point, the cat is cared for as described i n the section o n Oxygen (100%) is provided through the endotracheal
recovery o f patients after B A L . tube or by face mask for several minutes. The modified
FIG 2 0 - 2 4
Bronchoalveolar lavage using a modified stomach tube in a
FIG 2 0 - 2 3
dog. The tube is passed through a sterile endotracheal tube
The catheter used for nonbronchoscopic bronchoalveolar
and lodged in a bronchus. A syringe preloaded with saline
lavage in dogs is a modified 16F Levin-type stomach tube.
and air is held upright during infusion so that the saline is
The tube is shortened by cutting off both ends. A simple
infused first, followed by the air.
pencil sharpener (inset A) is used to taper the distal end of
the tube (inset B). A syringe adapter is added to the
proximal end. Sterility is maintained throughout.
possible, patients are monitored w i t h pulse oximetry (p. 283)
before and throughout the procedure and d u r i n g recovery.
stomach tube is passed through the endotracheal tube using After the procedure, 100% oxygen is provided through an
sterile technique until resistance is felt. The goal is to wedge endotracheal tube for as long as the dog or cat w i l l allow
the tube snugly into an airway rather than have it abut an intubation. Several gentle "sighs" are performed with the
airway division. Therefore the tube is withdrawn slightly, anesthesia bag to help expand any collapsed portions of lung.
then passed again, until resistance is consistently felt at the Bronchospasms are a reported complication o f B A L i n
same depth. Rotating the tube slightly during passage may people, and increased airway resistance has been documented
help achieve a snug fit. Remember that i f the endotracheal i n cats after bronchoscopy and B A L (Kirschvink et al., 2005).
tube is not m u c h larger than the stomach tube, ventilation Albuterol i n a metered dose inhaler should be o n hand to
is restricted at this point and the procedure should be c o m administer through the endotracheal tube or by spacer and
pleted expediently. mask i f needed.
For medium-size dogs and larger, two 3 5 - m l syringes are After extubation the mucous membrane color, pulses, and
prepared i n advance, each with 25 m l of saline and 5 m l o f character o f respirations are monitored closely. Crackles can
air. While the modified stomach tube is held i n place, a 2 5 - m l be heard for several hours after B A L and are not cause for
bolus of saline is infused through the tube, followed by the concern. Treatment w i t h oxygen supplementation is contin
5 m l of air, by holding the syringe upright during infusion ued by mask, oxygen cage, or nasal catheter i f there are any
(Fig. 20-24). Gentle suction is applied immediately after indications o f hypoxemia. Oxygen supplementation is rarely
infusion, using the same syringe. It may be necessary to necessary for more than 10 to 15 minutes after B A L , even i n
withdraw the tube slightly i f negative pressure is felt. The animals w i t h diseased lungs; however, the ability to provide
tube should not be withdrawn more than a few millimeters. supplementation for longer periods is a prerequisite for the
If it is withdrawn too far, air w i l l be recovered instead o f performance o f this procedure.
fluid. The second bolus o f saline is infused and recovered i n
the same manner, with the tube i n the same position. The SPECIMEN HANDLING
dog is cared for as described i n the next section. Successful B A L yields fluid that is grossly foamy, a result
In very small dogs, it is prudent to reduce the volume of of the surfactant from the alveoli. A p p r o x i m a t e l y 50% to
saline used i n each bolus, particularly i f a smaller diameter 80% o f the total volume o f saline instilled is expected to be
stomach tube is used. Overinflation o f the lungs with exces recovered. Less w i l l be obtained from dogs w i t h tracheo
sive fluid volumes should be avoided. bronchomalacia (collapsing airways). The fluid is placed o n
ice immediately after collection and is processed as soon as
RECOVERY OF PATIENTS possible, with m i n i m u m manipulation to decrease cell lysis.
FOLLOWING BAL For convenience, retrieved boluses can be combined for analy
Regardless of the method used, B A L causes a transient sis; however, fluid from the first bolus usually contains more
decrease i n the arterial oxygen concentration, but this hypox cells from the larger airways, and fluid from later boluses is
emia responds readily to oxygen supplementation. Where more representative o f the alveoli and interstitium.
The B A L fluid is analyzed cytologically and microbio are made through the identification of organisms or abnor
logically. Nucleated cell counts are performed o n undiluted mal cell populations. Fungal, protozoal, or parasitic organ
fluid using a hemocytometer. Cells are concentrated onto isms may be present i n extremely low numbers i n B A L
slides for differential cell counts and qualitative analysis specimens; therefore the entire concentrated slide prepara
using cytocentrifugation or sedimentation techniques. Excel tion must be carefully scanned. Profound epithelial hyper
lent-quality slides result that are stained using routine cyto plasia can occur i n the presence of an inflammatory response
logic procedures. Differential cell counts are performed by and should not be confused w i t h neoplasia.
counting at least 200 nucleated cells. Slides are scrutinized If quantitative bacterial culture is available, growth of
3
for evidence o f macrophage activation, lymphocyte reactiv organisms at greater than 1.7 X 10 colony-forming units
ity, neutrophil degeneration, and criteria o f malignancy. A l l ( C F U ) / m l has been reported to indicate infection (Peeters
slides are examined thoroughly for possible etiologic agents, et a l , 2000). In the absence o f quantitative numbers, growth
such as fungi, protozoa, parasites, and bacteria (see Figs.
20-12 and 20-15 to 20-17). As described for tracheal wash,
visible strands of mucus can be examined for etiologic agents
by squash preparation.
Approximately 5 m l of fluid is used for bacterial culture.
A d d i t i o n a l fluid is submitted for fungal culture i f mycotic
disease is among the differential diagnoses. Mycoplasma
cultures are considered i n cats and dogs w i t h signs o f
bronchitis.
INTERPRETATION OF RESULTS
N o r m a l cytologic values for B A L fluid are inexact because of
inconsistency i n the techniques used and variability among
individual animals o f the same species. In general, total
nucleated cell counts i n n o r m a l animals are less than 400 to
500/l. Differential cell counts from healthy dogs and cats
are listed i n Table 20-3.
Interpretation o f B A L fluid cytology and cultures is essen
tially the same as that described for tracheal wash fluid,
although the specimens are more representative o f the deep
lung than the airways. In addition, the n o r m a l cell popula
tion o f macrophages must not be misinterpreted as being FIG 2 0 - 2 5
indicative o f macrophagic or chronic inflammation (Fig. B r o n c h o a l v e o l a r l a v a g e fluid from a normal d o g . N o t e that
20-25). A s for all cytologic specimens, definitive diagnoses alveolar macrophages predominate.
TABLE 20-3
Differential C e l l Counts from Bronchoalveolar Lavage F l u i d from N o r m a l A n i m a l s
Macrophages 70 11 71 10 81 11 78 15
Lymphocytes 7 + 5 5 + 3 2 5 0.4 0.6
Neutrophils 5 5 7 4 15 12 5 5
Eosinophils 6 6 16 7 2 3 16 14
Epithelial cells 1 1
M a s t cells 1 1
* M e a n SD, 6 clinically and histologically normal dogs. (From Kuehn N F : Canine bronchoalveolar lavage profile. Thesis for masters of
science degree, West Lafayette, Ind, 1 9 8 7 , Purdue University.)
M e a n SE, 1 1 clinically normal cats. (From King RR et al: Bronchoalveolar lavage cell populations in dogs and cats with eosinophilic
pneumonitis. In Proceedings of the Seventh Veterinary Respiratory Symposium, Chicago, 1988, Comparative Respiratory Society.)
M e a n SD, 9 clinically normal dogs. (From Hawkins EC et al: Use of a modified stomach tube for bronchoalveolar lavage in dogs, J Am
VetMedAssoc 2 1 5 : 1 6 3 5 , 1999.)
M e a n SD, 3 4 specific pathogen-free cats. (From Hawkins EC et al: Cytologic characterization of bronchoalveolar lavage fluid collected
through an endotracheal tube in cats, Am J Vet Res 55:795, 1994.)
of organisms on a plate directly inoculated with B A L fluid is vessels, or nerves. If a solitary localized mass lesion is present,
considered significant, whereas growth from fluid that occurs thoracotomy and biopsy should be considered rather than
only after multiplication i n enrichment broth may also be a transthoracic sampling because this permits both the diag
result of normal inhabitants or contamination. Patients that nosis o f the problem and the potentially therapeutic benefits
are already receiving antibiotics at the time o f specimen col of complete excision.
lection may have significant infection with few or no bacte Transthoracic l u n g aspirates can be obtained i n animals
ria by culture. with a diffuse interstitial radiographic pattern. In some o f
these patients, solid areas o f infiltrate i n lung tissue i m m e
DIAGNOSTIC YIELD diately adjacent to the body wall can be identified ultraso
A retrospective study o f B A L fluid cytologic analysis i n dogs nographically even though they are not apparent on thoracic
at referral institutions showed that B A L findings provided radiographs (see Fig. 20-11). Ultrasound guidance o f the
the basis for a definitive diagnosis i n 25% o f cases and were aspiration needle into the areas o f infiltrate should improve
supportive of the diagnosis i n an additional 50%. O n l y dogs diagnostic yield and safety. If areas o f infiltrate cannot be
in which a definitive diagnosis was obtained by any means identified ultrasonographically, B A L should be considered
were included. Definitive diagnoses were possible on the before lung aspiration i n animals that can tolerate the pro
basis of B A L only i n those animals i n which infectious organ cedure because it yields a larger specimen for analysis and,
isms were identified or i n those cases i n which overtly malig i n this author's o p i n i o n , carries less risk than transthoracic
nant cells were present i n specimens i n the absence of marked aspiration i n patients that are not experiencing increased
inflammation. B A L has been shown to be more sensitive respiratory efforts or distress. Tracheal wash (if B A L is not
than radiographs i n identifying pulmonary involvement possible) and appropriate ancillary tests are also generally
with lymphosarcoma. Carcinoma was definitively identified indicated before lung aspiration i n these patients because
in 57% of cases, and other sarcomas were not found i n B A L they carry little risk.
fluid. Fungal pneumonia was confirmed i n only 2 5 % o f
cases, although organisms were found i n 67% o f cases i n a TECHNIQUES
previous study o f dogs with overt fungal pneumonia. The site o f collection i n animals with localized disease adja
cent to the body wall is best identified with ultrasonography.
If ultrasonography is not available or the lesion is surrounded
TRANSTHORACIC LUNG ASPIRATION by aerated lung, the site is determined o n the basis o f
AND BIOPSY two radiographic views. The location o f the lesion during
inspiration i n all three dimensions is identified by its rela
Indications and Complications tionship to external landmarks: the nearest intercostal space
Pulmonary parenchymal specimens can be obtained by or rib, the distance from the costochondral junctions, and
transthoracic needle aspiration or biopsy. A l t h o u g h only a the depth into the lungs from the body wall. If available,
small region of lung is sampled by these methods, collection fluoroscopy or C T also can be used to guide the needle or
can be guided by radiographic findings or ultrasonography biopsy instrument.
to improve the likelihood of obtaining representative speci The site o f collection i n animals with diffuse disease is a
mens. As with tracheal wash and B A L , a definitive diagnosis caudal l u n g lobe. The needle is inserted between the seventh
will be possible i n patients with infectious or neoplastic to ninth intercostal spaces, approximately two thirds o f the
disease. Patients with non-infectious inflammatory diseases distance from the costochondral junctions to the spine.
require thoracoscopy or thoracotomy with lung biopsy for a The animal must be restrained for the procedure, and
definitive diagnosis. sedation or anesthesia is necessary i n some. Anesthesia is
Potential complications o f transthoracic needle aspira avoided, i f possible, because the hemorrhage created by
tion or biopsy include pneumothorax, hemothorax, and p u l the procedure is not cleared as readily from the lungs i n an
monary hemorrhage. The procedures are not recommended anesthetized dog or cat. The skin at the site o f collection is
in animals with suspected cysts, abscesses, pulmonary hyper shaved and surgically prepared. Lidocaine is injected into the
tension, or coagulopathies. Severe complications are u n c o m subcutaneous tissues and intercostal muscles to provide local
mon, but these procedures should not be performed unless anesthesia.
the clinician is prepared to place a chest tube and otherwise L u n g aspiration can be performed w i t h an injection
support the animal i f necessary. needle, spinal needle, or a variety o f thin-walled needles
Lung aspirates and biopsy specimens are indicated for the designed specifically for lung aspiration i n people. Spinal
nonsurgical diagnosis o f intrathoracic mass lesions that are needles are readily available i n most practices, are sufficiently
in contact with the thoracic wall. The risk o f complications long to penetrate through the thoracic wall, and have a stylet.
in these animals is relatively low because the specimens can A 22-gauge, 1.5- to 3.5-inch (3.75- to 8.75-cm) spinal needle
be collected without disrupting aerated lung. Obtaining is usually adequate.
aspirates or biopsy specimens from masses that are far from The clinician wears sterile gloves. The needle with stylet
the body wall and near the mediastinum carries the addi is advanced through the skin several rib spaces from the
tional risk of lacerating important mediastinal organs, desired biopsy site. The needle and skin are then moved to
the biopsy site. This is done because air is less likely to enter needle, and the contents o f the needle are then forced onto
the thorax through the needle tract following the procedure one or more slides. Grossly, the material is bloody i n most
i f the openings i n the skin and chest wall are not aligned. cases. Squash preparations are made. Slides are stained
The needle is then advanced through the body wall to the using routine procedures and then evaluated cytologically.
pleura. The stylet is removed, and the needle hub is i m m e Increased numbers o f inflammatory cells, infectious agents,
diately covered by a finger to prevent pneumothorax u n t i l a or neoplastic cell populations are potential abnormalities.
12-ml syringe can be placed o n the hub. D u r i n g inspiration Alveolar macrophages are n o r m a l findings i n parenchymal
the needle is thrust into the chest to a depth predetermined specimens and should not be interpreted as representing
from the radiographs, usually about 1 i n c h (2.5 c m ) , while chronic inflammation. They should be carefully examined
suction is applied to the syringe (Fig. 20-26). T o keep from for evidence o f phagocytosis o f bacteria, fungi, or red b l o o d
inserting the needle too deeply, the clinician may p i n c h the cells and for signs o f activation. Epithelial hyperplasia can
needle shaft w i t h the t h u m b and forefinger o f the nondom occur i n the presence o f inflammation and should not be
inant h a n d at the desired m a x i m u m depth o f insertion. confused w i t h neoplasia. Sometimes the liver is aspirated
D u r i n g insertion the needle can be twisted along its l o n g axis inadvertently, particularly i n deep-chested dogs, yielding a
i n an attempt to obtain a core o f tissue. The needle is then population o f cells that may resemble those from adenocar
immediately withdrawn to the level o f the pleura. Several cinoma. However, hepatocytes typically contain bile pigment.
quick stabs into the l u n g can be made along different lines Bacterial culture is indicated i n some animals, although the
to increase the yield. volume o f material obtained is quite small.
Each stab should take only a second. Prolonging the time Transthoracic l u n g core biopsies can be performed i n
that the needle is w i t h i n the l u n g tissue increases the likeli animals w i t h mass lesions. They are collected after an aspi
h o o d o f complications. The l u n g tissue w i l l be m o v i n g w i t h rate has proved to be nondiagnostic. Needle biopsy instru
respirations, resulting i n laceration o f tissue, even i f the ments can be used to biopsy lesions adjacent to the chest wall
needle is held steady. (e.g., E Z C o r e biopsy needles, Products G r o u p International).
The needle is withdrawn from the body wall w i t h a Smaller-bore, thin-walled lung biopsy instruments can be
m i n i m a l amount o f negative pressure maintained by the obtained from medical suppliers for h u m a n patients. These
syringe. It is unusual for the specimen to be large enough to instruments collect smaller pieces o f tissue but are less dis
have entered the syringe. The needle is removed from the ruptive to n o r m a l lung. Ideally, sufficient material is col
syringe, the syringe is filled with air and reattached to the lected for histologic evaluation. If not, squash preparations
are made for cytologic studies.
BRONCHOSCOPY
Indications
Bronchoscopy is indicated for the evaluation o f the major
airways i n animals w i t h suspected structural abnormalities,
for visual assessment o f airway inflammation or pulmonary
hemorrhage, and as a means o f collecting specimens i n
animals with undiagnosed lower respiratory tract disease.
Bronchoscopy can be used to identify structural abnormali
ties o f the major airways, such as tracheal collapse, mass
lesions, tears, strictures, lung lobe torsions, bronchiectasis,
bronchial collapse, and external airway compression. Foreign
bodies or parasites may be identified. Hemorrhage or inflam
mation involving or extending to the large airways may also
be seen and localized.
Specimen collection techniques performed i n conjunc
tion w i t h bronchoscopy are valuable diagnostic tools because
they can be used to obtain specimens from deeper regions
of the l u n g than is possible w i t h the tracheal wash technique,
FIG 20-26 and visually directed sampling o f specific lesions or lung
Transthoracic lung aspiration performed with a spinal lobes is also possible. Animals undergoing bronchoscopy
needle. Note that sterile technique is used. The needle shaft
must receive general anesthesia, and the presence o f the
can be pinched with a finger and thumb at the maximum
scope w i t h i n the airways compromises ventilation. Therefore
depth to which the needle should be passed. The finger and
thumb thus act as a guard to prevent overinsertion of the bronchoscopy is contraindicated i n animals with severe
needle. Although this patient is under general anesthesia, respiratory tract compromise unless the procedure is likely
this is not usually indicated. to be therapeutic (e.g., foreign body removal).
Technique relatively small incision can be performed. If disease is obvi
Bronchoscopy is technically more demanding than most ously disseminated throughout the lungs such that surgical
other endoscopic techniques. The patient is often experienc intervention w i l l not be therapeutic, biopsies o f abnormal
ing some degree of respiratory compromise, w h i c h poses tissue can be obtained w i t h these methods v i a small i n c i
increased anesthetic and procedural risk. Airway hyperreac sions. F o r patients with questionable findings or apparently
tivity may be exacerbated by the procedure, particularly i n localized disease, thoracoscopy or " m i n i " thoracotomy
cats.(Kirschvink et al., 2005) A small-diameter, flexible endo can be transitioned to a full thoracotomy during the same
scope is needed and should be sterilized before use. The anesthesia.
bronchoscopist should be thoroughly familiar with n o r m a l
airway anatomy to ensure that every lobe is examined. B A L
is routinely performed as part o f diagnostic bronchoscopy BLOOD GAS ANALYSIS
after thorough visual examination of the airways. The reader
is referred to chapters i n other textbooks for details about Indications
performing bronchoscopy and bronchoscopic B A L (Kuehn, The measurement o f partial pressures o f oxygen (PaO ) and 2
2004; M c K i e r n a n , 2005; Hawkins, 2004). Bronchoscopic carbon dioxide (PaCO ) i n arterial b l o o d specimens provides
2
images o f normal airways are shown i n Fig. 20-27. Reported information about p u l m o n a r y function. Venous b l o o d anal
cell counts from bronchoscopically collected B A L fluid are ysis is less useful because venous b l o o d oxygen pressures are
provided i n Table 20-3. greatly affected by cardiac function and peripheral circula
Abnormalities that may be observed during bronchos tion. Arterial b l o o d gas measurements are indicated to doc
copy and their c o m m o n clinical correlations are listed i n ument pulmonary failure, to differentiate hypoventilation
Table 20-4. A definitive diagnosis may not be possible o n the from other causes o f hypoxemia, to help determine the
basis o f the findings yielded by gross examination alone. need for supportive therapy, and to m o n i t o r the response to
Specimens are collected through the biopsy channel for cyto therapy. Respiratory compromise must be severe for abnor
logic, histopathologic, and microbiologic analysis. Bronchial malities to be measurable because the body has tremendous
specimens are obtained by bronchial washing, bronchial compensatory mechanisms.
brushing, or pinch biopsy. Material for bacterial culture can
be collected with guarded culture swabs. The deeper l u n g is TECHNIQUES
sampled by B A L or transbronchial biopsy. Foreign bodies are Arterial b l o o d is collected i n a heparinized syringe. D i l u t i o n
removed with retrieval forceps. of specimens w i t h l i q u i d heparin can alter b l o o d gas results.
Therefore commercially available syringes preloaded with
lyophilized heparin are recommended (e.g., M i c r o ABG,
THORACOTOMY OR THORACOSCOPY 1-ml luer slip syringe with 25-g needle and 50 U heparin,
WITH LUNG BIOPSY V i t a l Signs, Inc). Alternatively, the procedure for hepariniz
ing syringes as described by H o p p e r et al. (2005) should be
Thoracotomy and surgical biopsy are performed i n animals followed: 0.5 m l o f l i q u i d sodium heparin is drawn into a
with progressive clinical signs o f lower respiratory tract 3-ml syringe w i t h a 25 g needle. The plunger is drawn back
disease that has not been diagnosed using less invasive means. to the 3 m l mark. A l l air is then expelled from the syringe.
Although thoracotomy carries a greater risk than the previ This procedure for expelling air and excess heparin is repeated
ously mentioned diagnostic techniques, the m o d e r n anes three times.
thetic agents, surgical techniques, and m o n i t o r i n g capabilities The femoral artery is c o m m o n l y used (Fig. 20-28). The
now available have made this procedure routine i n many animal is placed i n lateral recumbency. The upper rear l i m b
veterinary practices. Analgesic drugs are used to manage the is abducted, and the rear l i m b resting on the table is restrained
postoperative pain, and complication-free animals are dis i n a partially extended position. The femoral artery is pal
charged as soon as 2 to 3 days after surgery. Surgical biopsy pated i n the inguinal region, close to the abdominal wall,
provides excellent-quality specimens for histopathologic using two fingers. The needle is advanced into the artery
analysis and culture. A b n o r m a l lung tissue and accessible between these fingers. The artery is thick walled and loosely
lymph nodes are biopsied. attached to adjacent tissues; thus the needle must be sharp
Excisional biopsy o f abnormal tissue can be therapeutic and positioned exactly o n top o f the artery. A short, jabbing
in animals with localized disease. Removal o f localized neo m o t i o n facilitates entry.
plasms, abscesses, cysts, and foreign bodies can be curative. The dorsal pedal artery is useful for arterial collection i n
The removal of large localized lesions can improve the medium-sized and large dogs. The position o f the artery is
matching of ventilation and perfusion, even i n animals with illustrated i n Fig. 20-29.
evidence o f diffuse lung involvement, thereby i m p r o v i n g the Once the needle has penetrated the skin, suction is
oxygenation o f b l o o d and reducing clinical signs. applied. O n entry o f the needle into the artery, b l o o d should
In practices where thoracoscopy is available, this less inva enter the syringe quickly, sometimes i n pulses. Unless the
sive technique can be used for initial assessment o f intra animal is severely compromised, the b l o o d w i l l be bright red
thoracic disease. Similarly, a " m i n i " thoracotomy through a compared with the dark red of venous blood. D a r k red b l o o d
FIG 2 0 - 2 7
B r o n c h o s c o p i c i m a g e s of n o r m a l a i r w a y s . The labels for the l o b a r b r o n c h i a r e from a
useful nomenclature system for the major a i r w a y s a n d their b r a n c h e s b y A m i s et a l .
( 1 9 8 6 ) . A , C a r i n a , the d i v i s i o n b e t w e e n the right (R) a n d left (L) mainstem b r o n c h i .
B , Right mainstem b r o n c h u s . The c a r i n a is off the right s i d e of the i m a g e . The o p e n i n g s to
the right c r a n i a l (RB1), right m i d d l e (RB2), a c c e s s o r y (RB3), a n d right c a u d a l (RB4)
b r o n c h i a r e visible. C , Left mainstem b r o n c h u s . The c a r i n a is off the left side of the i m a g e .
The o p e n i n g s to the left c r a n i a l (LB1) a n d left c a u d a l (LB2) b r o n c h i a r e visible. The left
c r a n i a l l o b e (LB1) d i v i d e s i m m e d i a t e l y into c r a n i a l (narrow arrow) a n d c a u d a l (broad
arrow) b r a n c h e s . (Amis T C et a l : Systematic identification of e n d o b r o n c h i a l a n a t o m y
d u r i n g b r o n c h o s c o p y in the d o g , Am J Vet Res 4 7 : 2 6 4 9 , 1 9 8 6 . )
or b l o o d that is difficult to draw into the syringe may be from Pressure is applied even after unsuccessful attempts i f there
a vein. M i x e d samples from both the artery and vein can also is any possibility that the artery was entered.
be collected accidentally, particularly from the femoral site. A l l air bubbles are eliminated from the syringe. The
After removal o f the needle, pressure is applied to the needle is covered by a cork or rubber stopper, and the entire
puncture site for 5 minutes to prevent hematoma formation. syringe is placed i n crushed ice unless the b l o o d specimen is
TABLE 20-4
Bronchoscopic Abnormalities and T h e i r C l i n i c a l Correlations
Trachea
H y p e r e m i a , loss of n o r m a l v a s c u l a r pattern, e x c e s s Inflammation
mucus, e x u d a t e
Redundant tracheal m e m b r a n e Tracheal collapse
Flattened c a r t i l a g e rings Tracheal collapse
Uniform n a r r o w i n g Hypoplastic trachea
Strictures Prior trauma
M a s s lesions Fractured rings, foreign b o d y g r a n u l o m a , n e o p l a s i a
Tears Usually c a u s e d b y e x c e s s i v e e n d o t r a c h e a l tube cuff pressure
Carina
Bronchi
INTERPRETATION OF RESULTS
Approximate arterial b l o o d gas values for n o r m a l dogs and
cats are provided i n Table 20-5. M o r e exact values should be
obtained for n o r m a l dogs and cats using the actual ana
lyzer.
Position for o b t a i n i n g a n arterial b l o o d s p e c i m e n from the A b n o r m a l PaO and PaCO values can result from technical
2 2
range. The oxyhemoglobin dissociation curve describing the in dogs and cats with lung regions w i t h l o w V / Q by provid
relationship between the saturated hemoglobin level and ing supplemental oxygen therapy administered by face mask,
FIG 2 0 - 3 0
Oxygen-hemoglobin dissociation curve (approximation).
Central nervous system disease previously. Both hypoxemia and hypercapnia are seen i n the
Polyneuropathy setting o f extremely severe embolization.
Polymyopathy Diffusion abnormalities alone do not result i n clinically
Neuromuscular junction disorders (myasthenia significant hypoxemia but can occur i n conjunction with
gravis) V / Q mismatching i n diseases such as idiopathic pulmonary
Extreme fatigue (prolonged distress) fibrosis and noncardiogenic pulmonary edema. Gas is normally
Restriction of lung expansion exchanged between the alveoli and the blood by diffusing
Thoracic wall abnormality
across the respiratory membrane. This membrane consists
Excessive thoracic bandage
of the fluid lining the alveolus, alveolar epithelium, alveolar
Pneumothorax
basement membrane, interstitium, capillary basement m e m
Pleural effusion
brane, and capillary endothelium. Gases must also diffuse
Increased dead space (low alveolar ventilation)
Severe chronic obstructive pulmonary disease/ through plasma and red b l o o d cell membranes. Functional
emphysema and structural adaptations that facilitate diffusion between
End-stage severe pulmonary parenchymal disease the alveoli and red b l o o d cells provide an efficient system for
Severe pulmonary thromboembolism this process, which is rarely affected significantly by disease.
oxygen gradient ( A - a gradient), which factors out the effects can occur i n spite of a n o r m a l PaO . The formula for calculat
2
of ventilation and the inspired oxygen concentration o n PaO 2 ing the total oxygen content o f arterial b l o o d (CaO ) is pro 2
The premise o f the A-a gradient is that PaO (a) is nearly 2 health is oxygenated hemoglobin. In a normal dog (PaO , 2
equal (within 10 m m H g i n r o o m air) to the partial pressure 100 m m H g ; hemoglobin, 15 g/dl), oxygenated hemoglobin
of oxygen i n the alveoli, P A O (A), i n the absence o f a dif2 accounts for 20 m l o f O / d l , whereas dissolved oxygen
2
fusion abnormality or V / Q mismatch. In the presence of accounts for only about 0.3 m l of O / d l . 2
a diffusion abnormality or V / Q mismatch, the difference The quantity o f hemoglobin is routinely appraised by the
widens (greater than 15 m m H g i n r o o m air). Examination complete b l o o d count. It can also be estimated on the basis
of the equation reveals that hyperventilation, resulting i n a of the packed cell volume (by dividing the packed cell volume
lower PaCO , results i n a higher P A O . Conversely, hypoven
2 2 by 3). The oxygen saturation of hemoglobin (SaO ) is depen 2
tilation, resulting i n a higher PaCO , results i n a lower P A O . 2 2 dent o n the PaO , as depicted by the sigmoid shape of
2
error may be i n one o f the measured values or i n the assumed can shift the oxygen-hemoglobin dissociation curve to the
R value (see Table 20-6). left or right (e.g., p H , temperature, or 2,3-diphosphoglycer-
Clinical examples o f the calculation and interpretation o f ate concentrations) or interfere with oxygen binding with
the A-a gradient are provided i n B o x 20-10. hemoglobin (e.g., carbon monoxide toxicity or methemo
globinemia). Some laboratories measure SaO . 2
Oxygen Content, Delivery, and Utilization Oxygen must also be successfully delivered to the tissues,
The c o m m o n l y reported b l o o d gas value PaO reflects the 2 and this depends on cardiac output and local circulation.
pressure o f oxygen dissolved i n arterial blood. This value is Ultimately, the tissues must be able to effectively utilize the
TABLE 20-6
PaO SaO
2 2 Relationship is defined by sigmoid oxygen-hemoglobin dissociation curve. Curve
plateaus at greater than 9 0 % SaO with PaO values greater than 80 mm H g .
2 2
(0.003 x PaO ) 2 concentration. In health, more than 6 0 times more oxygen is delivered by
hemoglobin than is dissolved in plasma (PaO ). 2
Paco = PAco 2 2 These values are increased with hypoventilation at alveolar level and decreased
with hypoventilation.
PAo = Flo (P - PH O) - P a c o / R
2 2 B 2 2 Partial pressure of oxygen in alveolar air available for exchange with blood
on room air at sea level: PAo = 2 changes directly with inspired oxygen concentration and inversely with Paco . 2
150 mm Hg - P a c o / 0 . 8 2 R is assumed to be 0.8 for fasting animals. With normally functioning lungs
(minimal V / Q mismatch), alveolar hyperventilation results in increased PAo and 2
hypoventilation alone. Low Pao with a wide A-a gradient (>15 mm Hg in room
2
A - a , Alveolar-arterial oxygen gradient (mm Hg); C o o , oxygen content of arterial blood (ml of O / d l ) ; Flo , fraction of oxygen in inspired
2 2 2
air (%); Hgb, hemoglobin concentration (g/dl); P a c o , partial pressure of C O 2 2 in arterial blood (mm Hg); PAco , partial pressure of O in
2 2
alveolar air (mm Hg); P a o , partial pressure of O in arterial blood (mm Hg); PAo , partial pressure of O in alveolar air (mm Hg); P ,
2 2 2 2 B
barometric (atmospheric) pressure (mm Hg); P H O , partial pressure of water in alveolar air (100%
2 humidified) (mm Hg); pH, negative
+ +
logarithm of H concentration (decreases with increased H ); R, respiratory exchange quotient (ratio of O uptake per C O 2 2 produced); S a o 2
amount of hemoglobin saturated with oxygen (%); V/Q, ratio of ventilation to perfusion of alveoli.
If both the PaCO and the bicarbonate concentration are
BOX 20-10 2
is 80 mm Hg. The A-a gradient is 8 mm Hg. His hypox dissociation curve (see Fig. 20-30). Pulse oximetry is n o n
emia can be explained by hypoventilation. invasive, can be used to continuously m o n i t o r a dog or cat,
Later the same day, the dog develops crackles bilaterally. provides immediate results, and is affordable for most prac
Repeat blood gas analysis shows a PaO of 6 0 mm Hg
2
tices. It is a particularly useful device for m o n i t o r i n g animals
and a PaCO of 48 mm Hg. His calculated PAo is
2 2
with respiratory disease that must undergo procedures
90 mm Hg. The A-a gradient is 3 0 mm Hg. Hypoventila
requiring anesthesia. It can also be used i n some cases to
tion continues to contribute to the hypoxemia, but
hypoventilation has improved. The widened A-a gradi m o n i t o r the progression of disease or the response to therapy.
ent indicates V / Q mismatch. This dog has aspirated M o r e and more clinicians are using these devices for the
gastric contents into his lungs. routine m o n i t o r i n g o f animals under general anesthesia,
particularly i f the number o f personnel is limited, because
alarms can be set to warn o f marked changes i n values.
tions have acute cough and often nasal discharge. This form
CHAPTER OUTLINE
of the disease is similar to canine infectious tracheobronchi
tis and is self-limiting. The severe form o f the disease is
GENERAL CONSIDERATIONS
characterized by pneumonia. Canine influenza is discussed
C A N I N E INFECTIOUS T R A C H E O B R O N C H I T I S
i n Chapter 22.
C A N I N E C H R O N I C BRONCHITIS
General Management
D r u g Therapies
Management of Complications
CANINE INFECTIOUS
FELINE B R O N C H I T I S (IDIOPATHIC)
TRACHEOBRONCHITIS
Emergency Stabilization Etiology
Environment
Canine infectious tracheobronchitis, or "kennel cough," is a
Glucocorticoids
highly contagious, acute disease that is localized i n the
Bronchodilators
airways. One or more infectious agents cause it, including
Other Potential Treatments
canine adenovirus 2 ( C A V 2 ) , parainfluenza virus (PIV),
Failure to Respond
canine respiratory coronavirus and Bordetella bronchiseptica.
COLLAPSING TRACHEA A N D
Bordetella organisms infect ciliated respiratory epithelium
TRACHEOBRONCHOMALACIA
(Fig. 21-1) and can decrease mucociliary clearance. Other
ALLERGIC B R O N C H I T I S
organisms may become involved as secondary pathogens.
O S L E R U S OSLERI
In most dogs the disease is self-limiting, w i t h resolution of
clinical signs i n approximately 2 weeks.
Clinical Features
GENERAL CONSIDERATIONS Affected dogs are first seen because o f the sudden onset o f a
severe productive or nonproductive cough, w h i c h is often
C o m m o n diseases of the trachea and b r o n c h i include exacerbated by exercise, excitement, or the pressure o f the
canine infectious tracheobronchitis, canine chronic b r o n c h i collar o n the neck. Palpating the trachea easily induces
tis, feline bronchitis, collapsing trachea, and allergic b r o n c h i the cough. Gagging, retching, or nasal discharge can also
tis. Oslerus osleri infection is an important consideration i n occur. A recent history (i.e., w i t h i n 2 weeks) o f boarding,
young dogs. hospitalization, or exposure to a puppy or dog that has
Other diseases may involve the airways, either p r i m a r i l y similar signs is c o m m o n . Puppies recently obtained from pet
or concurrently with pulmonary parenchymal disease. stores, kennels, or shelters have often been exposed to the
These diseases, such as viral, mycoplasmal, and bacterial pathogens.
infection; other parasitic infections; and neoplasia are dis The majority o f dogs w i t h infectious tracheobronchitis
cussed i n Chapter 22. Feline bordetellosis can cause signs o f are considered to have "uncomplicated," self-limiting disease
bronchitis (e.g., cough) but is more often associated w i t h and do not show signs of systemic illness. Therefore dogs
signs of upper respiratory disease (see the section o n feline showing respiratory distress, weight loss, persistent anorexia,
upper respiratory infection, i n Chapter 15) or bacterial or signs o f involvement o f other organ systems, such as
pneumonia (see the section o n bacterial pneumonia, i n diarrhea, chorioretinitis, or seizures, may have some other,
Chapter 22). Dogs with m i l d canine influenza virus infec more serious disease, such as canine distemper, severe canine
TABLE 21-1
AGENT DOSAGE
Dextromethorphan 1 to 2 m g / k g , q 6 - 8 h orally
Butorphanol 0 . 5 m g / k g , q 6 - 1 2 h orally
H y d r o c o d o n e bitartrate 0 . 2 5 m g / k g , q 6 - 1 2 h orally
FIG 2 1 - 1
P h o t o m i c r o g r a p h of a tracheal b i o p s y from a d o g infected or thoracic radiograph findings. A s discussed i n Chapter 19
with Bordetella bronchiseptica. The o r g a n i s m s a r e small it is not always possible to recognize a productive cough in
b a s o p h i l i c rods that a r e visible a l o n g the ciliated b o r d e r of dogs. Therefore cough suppressants should be used judi
the epithelial cells. ( G i e m s a stain courtesy D. M a l a r k e y . ) ciously to treat frequent or severe cough, allow for restful
sleep, and prevent exhaustion.
A variety o f cough suppressants can be used in dogs
influenza, or a mycotic infection. A l t h o u g h u n c o m m o n , (Table 21-1). Dextromethorphan is available i n over-the-
serious respiratory complications can result from infectious counter preparations; however, it has questionable efficacy
tracheobronchitis. Secondary bacterial pneumonia can in dogs. C o l d remedies with additional ingredients such as
develop, particularly i n puppies, immunocompromised antihistamines and decongestants should be avoided. Pedi
dogs, and dogs that have preexisting lung abnormalities such atric l i q u i d preparations are palatable for most dogs, and the
as chronic bronchitis. Dogs w i t h chronic airway disease or alcohol contained i n them may also have a m i l d tranquilizing
tracheal collapse can experience an acute, severe exacerba effect. Narcotic cough suppressants are more likely to be
tion o f their chronic problems, and extended management effective. Butorphanol is available as a veterinary labeled
may be necessary to resolve the signs associated w i t h infec product (Torbutrol, Fort Dodge A n i m a l Health). Hydroco
tion i n these animals. Bordetella infection has been associ done bitartrate is a potent alternative for dogs with refrac
ated w i t h canine chronic bronchitis. tory cough.
In theory, antibiotics are not indicated for most dogs with
Diagnosis infectious tracheobronchitis for two reasons: (1) The disease
Uncomplicated cases o f kennel cough are diagnosed on the is usually self-limiting and tends to resolve spontaneously,
basis of the presenting signs. However, differential diagnoses regardless o f any specific treatment that is implemented, and
should also include the early presentation o f a more serious (2) no antibiotic protocol has been proven to eliminate Bor
disease and the m i l d form o f canine influenza. Diagnostic detella organisms from the airways. In practice, however,
testing is indicated for dogs w i t h systemic, progressive, or antibiotics are often prescribed, and their use is justified
unresolving signs. Tests to be considered include thoracic because o f the potential role o f Bordetella i n the disease.
radiographs, a complete b l o o d count ( C B C ) , tracheal wash Fluoroquinolones have the advantage o f reaching high con
fluid analysis, and polymerase chain reaction ( P C R ) testing, centrations i n the airway secretions, but their use is ideally
paired serology, or other tests for canine influenza (see reserved for more serious infections. Other antibiotics that
p. 302) and other respiratory pathogens. Tracheal wash fluid are effective against many Bordetella isolates include amoxi
cytology shows acute inflammation, and bacterial culture o f cillin w i t h clavulanate (20 to 25 mg/kg q8h), doxycycline (5
the fluid can be useful for identifying any bacteria involved to 10 mg/kg q l 2 h , followed by a bolus o f water), and chlor
in the disease. Concurrent antibiotic sensitivity information amphenicol (50 mg/kg q8h). Beta-lactam antibiotics do
is helpful i n selecting antibiotics. not generally reach therapeutic concentrations in airway
secretions o f healthy (not inflamed) subjects. If such an anti
Treatment biotic is used for bronchial infections, the high end of the
Uncomplicated infectious tracheobronchitis is a self-limiting dosage range should be used and the drug administered
disease. Rest for at least 7 days, specifically avoiding exercise every 8 hours. The ability of doxycycline to reach therapeu
and excitement, is indicated to m i n i m i z e the continual irrita tic concentration w i t h i n the airways is questionable because
tion o f the airways caused by excessive coughing. C o u g h in the dog it is highly protein bound, although the presence
suppressants are valuable for the same reason but should not of inflammatory cells may increase locally available concen
be given i f the cough is productive or i f exudate is suspected trations o f the drug. Bacterial susceptibility data from tra
to be accumulating i n the lungs o n the basis o f auscultation cheal wash fluid can be used to guide the selection of an
appropriate antibiotic. Antibiotics are administered for 5 tial for the housing o f dogs with clinical signs o f infectious
days beyond the time the clinical signs resolve or for at least tracheobronchitis.
14 days. Injectable and intranasal vaccines are available for the
Administration of gentamicin by nebulization can be three major pathogens involved i n canine infectious tracheo
considered for refractory cases or i n outbreaks of infection bronchitis (i.e., C A V 2 , PIV, B. bronchiseptica). Injectable
involving dogs housed together, although no controlled modified-live virus vaccines against C A V 2 and P I V are ade
studies have been published. A n early study by Bemis et al. quate for most pet dogs. They are conveniently included i n
(1997) showed that bacterial populations o f Bordetella i n the most combination distemper vaccines. Because maternal
trachea and bronchi were reduced for up to 3 days after antibodies interfere w i t h the response to the vaccines,
treatment with nebulized gentamicin but not orally a d m i n puppies must be vaccinated every 2 to 4 weeks, beginning
istered antibiotics, and clinical signs were reduced. Note that at 6 to 8 weeks of age and through 14 to 16 weeks of age.
the numbers of organisms returned to pretreatment values At least two vaccines must be given initially. For most
within 7 days. Some clinicians have since reported success i n healthy dogs, a booster is recommended after 1 year,
managing difficult cases and outbreaks with this treatment followed by subsequent vaccinations every 3 years (see
(Miller et al., 2003). The protocol used by Bemis et al. (1997) Chapter 94).
is 50 mg of gentamicin sulfate i n 3 m l of sterile water, deliv Dogs at high risk for disease, such as those i n kennels
ered by nebulizer and face mask (see Fig. 22-1) for 10 minutes where the disease is endemic or those that are frequently
every 12 hours for 3 days. Sterile technique must be m a i n boarded, may benefit from vaccines incorporating B. bron
tained to keep from delivering additional bacteria to the chiseptica. These vaccines do not prevent infection but
airways. Nebulization of drugs has the potential to induce aim to decrease clinical signs i f infection occurs. They may
bronchospasms, so dogs should be carefully observed during also reduce the duration o f shedding o f organisms after
the procedure. Pretreatment with bronchodilators should infection. A study by Ellis et al. (2001) indicated that
be considered, and additional bronchodilators (metered both intranasal and parenteral Bordetella vaccines afford
dose inhaler and/or injectable) should be at hand for use as similar protection based o n antibody titers, clinical signs,
needed. upper airway cultures, and histopathologic examination
Glucocorticoids should not be used. A field trial con of tissues after exposure to organisms. The greatest benefit
ducted by Thrusfield et al. (1991) failed to demonstrate any was achieved by administering both forms o f vaccine
benefit of steroid therapy, either alone or i n combination sequentially at a 2-week interval. Unfortunately, the paren
with antibiotics. teral vaccine used i n the study was a killed bacterin that is
If clinical signs have not resolved within 2 weeks, further no longer available. The dogs i n this study were vaccinated
diagnostic evaluation is indicated. See Chapter 22 for the between 14 to 18 weeks o f age. Also i n experimental settings,
management of complicated cases of infectious tracheo protection against challenge following intranasal vaccination
bronchitis with bacterial pneumonia. against B. bronchiseptica and P I V began by 72 hours after
vaccination and persisted for at least 13 months (Gore et al.,
Prognosis 2005; Jacobs et al., 2005). Intranasal Bordetella vaccines
The prognosis for recovery from uncomplicated infectious occasionally cause clinical signs, predominantly cough. The
tracheobronchitis is excellent. signs are generally self-limiting but are disturbing to most
owners.
Prevention
Canine infectious tracheobronchitis can be prevented by
minimizing an animal's exposure to organisms and through CANINE CHRONIC BRONCHITIS
vaccination programs. Excellent nutrition, routine deworm
ing, and avoidance o f stress improve the dog's ability Etiology
to respond appropriately to infection without showing Canine chronic bronchitis is a disease syndrome defined as
serious signs. cough occurring on most days o f 2 or more consecutive
Bordetella may persist i n the airways of dogs for up to 3 months i n the past year i n the absence o f other active disease.
months after infection. To m i n i m i z e exposure to Bordetella Histologic changes of the airways are those o f long-term
or respiratory viruses, dogs are kept isolated from puppies inflammation and include fibrosis, epithelial hyperplasia,
or dogs that have been recently boarded. Careful sanitation glandular hypertrophy, and inflammatory infiltrates. Some
should be practiced i n kenneling facilities. Caretakers should of these changes are irreversible. Excessive mucus is present
be instructed i n the disinfection of cages, bowls, and runs, within the airways, and small airway obstruction occurs.
and anyone working with the dogs must wash their hands In people chronic bronchitis is strongly associated with
after handling each animal. Dogs should not be allowed to smoking. It is presumed that canine chronic bronchitis is a
have face-to-face contact. Adequate air exchange and h u m i d consequence o f a long-standing inflammatory process initi
ity control are necessary i n rooms housing several dogs. ated by infection, allergy, or inhaled irritants or toxins. A
Recommended goals are at least 10 to 15 air exchanges per continuing cycle o f inflammation likely occurs as mucosal
hour and less than 50% humidity. A n isolation area is essen damage, mucus hypersecretion, and airway obstruction
impairs n o r m a l mucociliary clearance, and inflammatory Dogs w i t h chronic bronchitis are often brought to a veter
mediators amplify the response to irritants and organisms. inarian because o f sudden exacerbation of signs. The change
in signs may result from transient worsening o f the chronic
Clinical Features bronchitis, perhaps after a period o f unusual excitement,
C h r o n i c bronchitis occurs most often i n middle-aged or stress, or exposure to irritants or allergens; from a secondary
older, small-breed dogs. Breeds c o m m o n l y affected include complication, such as bacterial infection; or from the devel
Terriers, Poodles, and Cocker Spaniels. Small-breed dogs are opment of a concurrent disease, such as left atrial enlarge
also predisposed to the development o f collapsing trachea ment and bronchial compression or heart failure (Box 21-1).
and mitral insufficiency w i t h left atrial enlargement causing In addition to obtaining a routine complete history, the client
compression o f the mainstem bronchi. These causes for should be carefully questioned about the character of the
cough must be differentiated, and their contribution to the cough and the progression of signs. Detailed information
development o f the current clinical features determined, for should be obtained regarding the following: environmental
appropriate management to be implemented. conditions, particularly exposure to smoke, other potential
Dogs w i t h chronic bronchitis are evaluated because o f irritants and toxins, or allergens; exposure to infectious
l o u d , harsh cough. M u c u s hypersecretion is a component o f agents, such as boarding or exposure to puppies; and all pre
the disease, but the cough may sound productive or nonpro vious and current medications and the response to treatment.
ductive. The cough has usually progressed slowly over O n physical examination, increased breath sounds, crack
months to years, although clients usually report the initial les, or occasionally wheezes are auscultated in animals with
onset as acute. There should be no systemic signs o f illness chronic bronchitis. End-expiratory clicks caused by main-
such as anorexia or weight loss. A s the disease progresses, stem bronchial or intrathoracic tracheal collapse may be
exercise intolerance becomes evident; then incessant cough heard i n animals w i t h advanced disease. A prominent or split
ing or overt respiratory distress is seen. second heart sound occurs i n animals with secondary p u l
Potential complications o f chronic bronchitis include monary hypertension. Dogs with respiratory distress (end-
bacterial or mycoplasmal infection, tracheobronchomalacia stage disease) characteristically show marked expiratory efforts
(see p. 297), p u l m o n a r y hypertension (Chapter 22), and because o f the narrowing and collapse of the intrathoracic
bronchiectasis. Bronchiectasis is the term for permanent dila
tion o f the airways (Fig. 21-2; see also Fig. 20-4). Bronchiec
tasis can be present secondary to other causes of chronic
airway inflammation, airway obstruction, and i n association BOX 21-1
w i t h certain congenital disorders such as ciliary dyskinesia
Diagnostic Considerations for Dogs w i t h Signs Consistent
(i.e., i m m o t i l e cilia syndrome). Bronchiectasis caused by
w i t h Canine C h r o n i c Bronchitis
traction o n the airways, rather than bronchial disease, can be
seen with idiopathic p u l m o n a r y fibrosis. Generally, all the Other Active Disease (Rather than Canine
major airways are dilated i n dogs w i t h bronchiectasis, but Chronic Bronchitis)
occasionally it is localized. Recurrent bacterial infections and Bacterial infection
overt bacterial pneumonia are c o m m o n complications i n M y c o p l a s m a l infection
dogs with bronchiectasis. Bronchial c o m p r e s s i o n (e.g., left atrial enlargement)
Pulmonary parasites
Heartworm disease
A l l e r g i c bronchitis
Neoplasia
Foreign b o d y
Chronic aspiration
G a s t r o e s o p h a g e a l reflux*
Diagnosis
Canine chronic bronchitis is defined as a cough occurring
on most days of 2 or more consecutive months i n the past
year in the absence of other active disease. Therefore chronic
bronchitis is diagnosed on the basis of not only clinical signs
but also the elimination of other diseases from the list of
differential diagnoses (see Box 21-1). The possibility of sec
ondary disease complicates this simple definition.
A bronchial pattern with increased interstitial markings FIG 21-3
B r o n c h o s c o p i c v i e w of the right c a u d a l b r o n c h u s of a d o g
is typically seen on thoracic radiographs, but changes are
with c h r o n i c bronchitis a n d severe b r o n c h o m a l a c i a . The
often m i l d and difficult to distinguish from clinically insig
a i r w a y s a p p e a r n o r m a l d u r i n g inspiration (A) but c o m
nificant changes associated w i t h aging. In a study by Mantis pletely c o l l a p s e d u r i n g e x p i r a t i o n , obliterating the lumen
et al. (1998), thoracic radiographs had a sensitivity o f 50% of the a i r w a y (B).
to 65% for the diagnosis of chronic bronchitis. Thoracic
radiographs are most useful for ruling out other active
disease and identifying concurrent or secondary disease. transposition o f the abdominal and thoracic organs, such
Tracheal wash or bronchoalveolar lavage ( B A L ) fluid that left-sided structures are found o n the right and vice
should be collected at the time o f the initial presentation and versa) is seen in 50% of such dogs. Dextrocardia occurring
after a persistent exacerbation o f signs. Neutrophilic or mixed in association with chronic bronchitis is extremely suggestive
inflammation and increased amounts of mucus are usually of this disease. Sperm motility can be evaluated i n intact
present. The finding o f degenerative neutrophils indicates male dogs. The finding o f n o r m a l sperm motility rules out
the possibility o f a bacterial infection. A l t h o u g h not a spe a diagnosis of ciliary dyskinesia. The disease is diagnosed on
cific finding, airway eosinophilia is suggestive of a hypersen the basis o f the rate at which radioisotopes deposited at the
sitivity reaction, as can occur with allergy, parasitism, or carina are cleared and the findings from electron micro
heartworm disease. Slides should be carefully examined for scopic examination o f bronchial biopsy, nasal biopsy, or
organisms. Bacterial cultures are performed and the results sperm specimens.
interpreted as discussed in Chapter 20. A l t h o u g h the role o f
Mycoplasma infections i n these cases is not well understood, Treatment
Mycoplasma cultures are also considered. C h r o n i c bronchitis is managed symptomatically, with spe
Bronchoscopy, with specimen collection, is performed i n cific treatment possible only for concurrent or complicating
selected cases, primarily to help rule out other diseases. The diseases that are identified. Each dog with chronic bronchitis
maximal benefit o f bronchoscopy is obtained early i n the is presented at a different stage o f the disease, with or without
course of disease, before severe permanent damage has concurrent or secondary cardiopulmonary disease (see Box
occurred and while the risk o f the procedure is m i n i m a l . 21-1). Hence each dog must be managed individually. Ideally,
Gross abnormalities visualized by bronchoscopy include an medications are initiated one at a time to assess the most
increased amount o f mucus, roughened mucosa, and hyper effective combination. It w i l l likely be necessary to modify
emia. Major airways may collapse during expiration as a treatment over time.
result of weakened walls (Fig. 21-3), and polypoid mucosal
proliferation may be present. Bronchial dilatation is seen i n GENERAL MANAGEMENT
animals with bronchiectasis. Exacerbating factors, either possible or proven, are avoided.
Further diagnostic procedures are indicated to rule out Potential allergens are considered i n dogs with eosinophilic
other potential causes of chronic cough, and the selection o f inflammation and trial elimination pursued (see the section
these depends on the presenting signs and the results of the on allergic bronchitis, p. 299). Exposure to irritants such as
previously discussed diagnostic tests. Diagnostic tests to be smoke (from tobacco or fireplace) and perfumed products
considered include heartworm tests, fecal examinations for should be avoided i n all dogs. Motivated clients can take
pulmonary parasites, echocardiography, and systemic evalu steps to improve the air quality in their home, such as carpet,
ation (i.e., C B C , serum biochemical panel, urinalysis). Echo furniture, and drapery cleaning; cleaning o f the furnace and
cardiography may reveal evidence of secondary pulmonary the frequent replacement of air filters; and the use of an air
hypertension, including right heart enlargement (i.e., cor cleaner. The American Lung Association has a useful Web
pulmonale). site with nonproprietary recommendations for i m p r o v i n g
Ciliary dyskinesia, in which ciliary m o t i o n is abnormal, is indoor air quality (www.lungusa.org ). Excitement or stress
uncommon but should be considered i n young dogs w i t h can cause an acute worsening o f signs i n some animals, and
bronchiectasis or recurrent bacterial infection. A b n o r m a l i short-term tranquilization w i t h acepromazine or sedation
ties exist in all ciliated tissues, and situs inversus (i.e., lateral w i t h phenobarbital can be helpful i n relieving the signs.
It is n o r m a l for flora from the oropharynx to be aspirated dosage is not reduced by one third to one half. Potential
into the airways. Routine dental prophylaxis and teeth brush adverse effects include gastrointestinal signs, cardiac arrhyth
ing w i l l help maintain a healthy oral flora and may decrease mias, nervousness, and seizures. Serious adverse effects are
any contributions o f n o r m a l aspiration to ongoing airway extremely rare at therapeutic concentrations.
inflammation i n these patients w i t h reduced mucociliary Variability in sustained plasma concentrations has
clearance. been found for different long-acting theophylline products.
A i r w a y hydration should be maintained to facilitate Dosage recommendations are currently available for a
mucociliary clearance. Adequate airway hydration is best generic product from a specific manufacturer (Box 21-2). If
achieved by maintaining systemic hydration. Therefore beneficial effects are not seen, the patient is predisposed to
diuretic therapy is not recommended i n these patients. For adverse effects, or adverse effects occur, plasma theophylline
severely affected dogs, placing the animal i n a steamy bath concentrations should be measured. Therapeutic peak con
r o o m or i n a r o o m with a vaporizer daily may provide symp centrations for bronchodilation, based on data from people,
tomatic relief, although the moisture does not penetrate very are 5 to 20 g/ml. Plasma is collected during peak concentra
deeply into the airways. Nebulization o f saline w i l l allow tions, generally 4 to 5 hours after administration o f a long-
moisture to go more deeply i n the lungs. This technique is acting product or 1.5 to 2 hours after administration of
discussed further i n the section o n bacterial pneumonia i n immediate release products. Measurement of concentrations
Chapter 22. immediately before the next scheduled dose might provide
Patients that are overweight and/or unfit may benefit useful information concerning duration of therapeutic
from weight loss (Chapter 54) and exercise. Exercise should concentrations.
be tailored to the dog's current fitness level and degree o f Theophylline and related drugs that are not long acting
pulmonary dysfunction to keep from causing excessive respi are useful i n specific circumstances but must be adminis
ratory efforts or even death. Observing the dog during tered three times daily (see Box 21-2). Palatable elixirs of
specific exercise, such as a short walk, while i n the client's
presence may be necessary to make initial recommendations.
Instructing clients i n the measurement o f respiratory rate,
observation o f mucous membrane color, and signs of BOX 21-2
increased respiratory effort w i l l improve their ability to
Common Bronchodilators for Use in Dogs and Cats
assess their dog's status d u r i n g exercise.
Methylxanthines
DRUG THERAPIES Aminophylline
Medications to control clinical signs include bronchodila Cat: 5 m g / k g orally q12h
tors, glucocorticoids, and cough suppressants. Dog: 11 m g / k g orally q8h
Theophylline, a methylxanthine bronchodilator, has been Oxtriphylline elixir (Choledyl, Parke-Davis)
used for years for the treatment o f chronic bronchitis i n Cat: None
people and dogs. This drug became unpopular w i t h physi Dog: 14 m g / k g orally q8h
cians when newer bronchodilators w i t h fewer side effects Theophylline base (immediate release)
Cat: 4 m g / k g orally q12h
became available. However, recent research i n people sug
Dog: 9 m g / k g orally q8h
gests that theophylline is effective i n treating the underlying
Long-acting theophylline (Theochron or TheoCap, Inwood
inflammation of chronic bronchitis, even at concentrations
Laboratories, Inwood, N Y ) *
below those resulting i n bronchodilation (hence, reducing Cat: 15 m g / k g q24h, in evening
side effects), and that the antiinflammatory effects may Dog: 10 m g / k g q12h
be synergistic w i t h those o f glucocorticoids. Theophylline
may also improve mucociliary clearance, decrease fatigue Sympathomimetics
TABLE 21-2
Clinical Features
Tracheal collapse is c o m m o n in middle-aged toy and m i n i a
ture dogs, although it also can occur early i n life and i n
large-breed dogs. Signs may occur acutely but then slowly
progress over months to years. The p r i m a r y clinical feature
in most dogs is a nonproductive cough, described as a "goose
honk." The cough is worse during excitement or exercise
or when the collar exerts pressure o n the neck. Eventually
(usually after years o f chronic cough), respiratory distress
caused by obstruction to airflow may be brought o n by
excitement, exercise, or overheating. Systemic signs such as
weight loss, anorexia, and depression are not expected. Occa
sionally, dogs are presented p r i m a r i l y for signs o f upper
airway obstruction without cough, also exacerbated d u r i n g
excitement, exercise, or hot weather. Stertorous sounds may
be heard during periods o f increased respiratory efforts.
FIG 21-6
Such signs are usually the result of extrathoracic tracheal
Lateral r a d i o g r a p h of the t h o r a x a n d neck of a d o g with
collapse. Tracheal collapse is rare i n cats, and most often it c o l l a p s i n g t r a c h e a taken d u r i n g i n s p i r a t i o n . The extratho
occurs secondary to a tracheal obstruction such as a tumor r a c i c a i r w a y stripe is severely n a r r o w e d c r a n i a l to the
or traumatic injury. t h o r a c i c inlet.
FIG 2 1 - 8
B r o n c h o s c o p i c i m a g e s from a d o g with tracheal c o l l a p s e
(A). The dorsal tracheal membrane is much w i d e r than that of
a normal d o g (B). The a i r w a y lumen is greatly c o m p r o m i s e d .
Treatment
M e d i c a l therapy is adequate treatment for most animals. In
a study o f 100 dogs by White et al. (1994), medical therapy
resulted i n resolution o f signs for at least 1 year i n 7 1 % of
cases. Dogs that are overweight are placed o n a weight-
reducing diet. Harnesses should be used instead of collars,
FIG 2 1 - 7 and owners should be counseled to keep their dogs from
Lateral r a d i o g r a p h s of a d o g with t r a c h e o b r o n c h o m a l a c i a . becoming overheated (e.g., they should not be left i n a car).
During inspiration (A) the t r a c h e a a n d mainstem b r o n c h i
Excessive excitement should also be avoided. Sedatives such
a r e nearly n o r m a l . During e x p i r a t i o n (B) the intrathoracic
as phenobarbital are prescribed for some animals, and these
t r a c h e a a n d mainstem b r o n c h i a r e m a r k e d l y n a r r o w e d .
Evaluation of the p u l m o n a r y p a r e n c h y m a should not b e can be administered before k n o w n stressful events.
attempted using films e x p o s e d during e x p i r a t i o n . C o u g h suppressants are used to control signs and disrupt
the potential cycle o f perpetuating cough (see Table 21-1).
The dose and frequency of administration of cough suppres
eter easier to identify than by routine radiography. The sen sants are adjusted as needed. Initially, high, frequent dosing
sitivity o f fluoroscopy i n detecting airway collapse is may be needed to break the cycle o f coughing. Subsequently,
enhanced if the patient can be induced to cough during the it is often possible to decrease frequency of administration
evaluation by applying pressure to the trachea. Some degree and dose. Bronchodilators may be beneficial i n dogs with
of collapse is probably n o r m a l d u r i n g cough, and i n people signs o f chronic bronchitis (see p. 290). Antiinflammatory
a diagnosis o f tracheobronchomalacia is generally made if doses o f glucocorticoids can be given for a short period
the l u m i n a l diameter decreases by greater than 50% d u r i n g d u r i n g exacerbation of signs (prednisone, 0.5 to 1 mg/kg
forced exhalation. q l 2 h for 3 to 5 days, then tapered and discontinued over 3
Bronchoscopy is also useful i n the diagnosis o f airway to 4 weeks). Long-term use is not recommended because of
collapse (Fig. 21-8; see also Fig. 21-3). The b r o n c h i o f smaller potential detrimental side effects such as obesity, but this is
dogs may be difficult to evaluate by radiography or fluoro often necessary to control signs i n patients with chronic
scopy but are easily examined bronchoscopically. Broncho bronchitis. Dogs w i t h signs referable to mitral insufficiency
scopy and the collection o f airway specimens (such as by are managed for this disease (see Chapter 8). Dogs with
B A L ) is useful for identifying exacerbating or concurrent abnormalities causing upper airway obstruction are treated
conditions. w i t h corrective surgical procedures.
evaluations performed during episodes o f persistent exacer
bations o f signs. A n i m a l s i n which severe signs develop
despite appropriate medical care have a guarded prognosis,
and motivated clients should be referred for possible stent
placement.
ALLERGIC BRONCHITIS
Allergic bronchitis is a hypersensitivity response o f the
airways to an allergen or allergens. The offending allergens
are presumably inhaled, although food allergens could also
be involved. A definitive diagnosis requires identification of
allergen(s) and resolution of signs after elimination o f the
allergen(s). Large controlled studies describing allergic bron
FIG 21-9
Lateral r a d i o g r a p h of the d o g with t r a c h e a l c o l l a p s e s h o w n
chitis i n dogs or cats are lacking. A study by Prost (2004)
in Fig. 2 1 - 6 after p l a c e m e n t of a n intraluminal stent. The presented as an abstract found that 15 o f 20 cats had positive
stent is has a meshlike structure a n d extends nearly the intradermal skin tests to aeroallergens. For cats that reacted
entire length of the t r a c h e a . to storage mites or cockroach antigen, discontinuation o f
any dry food was recommended (i.e., only canned food was
Antibiotics are not indicated for the routine management provided). Remission o f signs occurred i n 3 cats with only
of a collapsing trachea. Dogs i n which tracheal wash or B A L this treatment. Immunotherapy (desensitization) appeared
fluid analysis has revealed evidence of infection should be to reduce or eliminate signs i n some o f the other cats. A s a
treated with appropriate antibiotics (selected o n the basis of preliminary study, other treatments were also given to the
the results of sensitivity testing). Because most antibiotics do study cats, and a control population was not described.
not reach high concentrations i n the airways, relatively high It is likely that some patients with allergic bronchitis
doses of antibiotics should be administered for several weeks, are misdiagnosed because of difficulty i n identifying spe
as described for canine chronic bronchitis (p. 291). A n y cific allergens. In dogs long-standing allergic bronchitis may
other potential related problems identified during the diag result i n the permanent changes recognized as canine chronic
nostic evaluation are addressed. bronchitis. In cats failure to identify specific allergen(s)
Management of dogs i n acute distress w i t h signs o f either results i n a diagnosis of idiopathic feline bronchitis.
extrathoracic airway obstruction or intrathoracic large Allergic bronchitis i n dogs may result i n acute or chronic
airway obstruction is discussed i n Chapter 26. cough. Rarely, respiratory distress and wheezing occur. The
Surgical treatment of a collapsing trachea should be con physical examination and radiographic findings reflect the
sidered for animals that are no longer responsive to medical presence o f bronchial disease, as described i n the section o n
management, usually because of respiratory difficulty. The canine chronic bronchitis. Eosinophilic inflammation is
introduction of intraluminal stents has greatly reduced the expected i n tracheal wash or B A L fluid. Heartworm tests and
morbidity and improved the success of surgical intervention. fecal examinations for p u l m o n a r y parasites are performed
The most c o m m o n l y used stents are self-expanding and to eliminate parasitism as the cause o f the eosinophilic
made of nickel-titanium alloys (Fig. 21-9). In experienced inflammation. In dogs younger than than 2 years o f age,
hands, these stents are simple to place during a short period bronchoscopic evaluation for Oslerus osleri also should be
of anesthesia using fluoroscopic or bronchoscopic guidance. considered (see the following section). Allergic bronchitis i n
There is m i n i m a l morbidity associated w i t h stent placement, cats has the same presentation and results o f diagnostic
and response is immediate and often dramatic. However, testing as described for idiopathic feline bronchitis, w i t h
clinical signs (particularly cough) may not completely resolve, eosinophilia expected i n airway specimens.
collapse of airways beyond the trachea and concurrent c o n d i Management o f allergic bronchitis is initially focused o n
tions are not directly addressed (often resulting i n the contin identifying and eliminating potential allergens from the
ued need for medical management), and complications such environment (see the section o n feline bronchitis). Diet trials
as granuloma formation and stent fracture can occur. Results w i t h novel protein and carbohydrate sources also can be
from stent placement are sufficiently encouraging that m o t i considered. According to the preliminary study previously
vated clients with a dog that is failing medical management described, a change i n diet to canned food may be beneficial
of tracheal collapse should be referred to someone experi in some cases. Such experimentation w i t h environment and
enced in stent placement for further consideration of this option. diet is possible only i n patients w i t h clinical signs that are
sufficiently m i l d to delay the administration of glucocorti
Prognosis coids and bronchodilators, as described i n the sections o n
In most dogs clinical signs can be controlled w i t h conscien canine chronic bronchitis and feline bronchitis (idiopathic).
tiously performed medical management, w i t h diagnostic Elimination trials can still be pursued once clinical signs are
controlled w i t h medications, but confirmation o f a benefi
cial effect w i l l require discontinuation o f the medication
and, for a definitive diagnosis to be made, reintroduction o f
the allergen. The latter may not be necessary or practical i n
all cases.
OSLERUS OSLERI
Etiology
Oslerus osleri is an u n c o m m o n parasite o f young dogs,
usually those younger than 2 years o f age. The adult worms FIG 21-10
B r o n c h o s c o p i c v i e w of multiple nodules at the c a r i n a of a
live at the carina and mainstem b r o n c h i and cause a local,
d o g infected with Oslerus osleri.
nodular inflammatory reaction w i t h fibrosis. First-stage
larvae are coughed up and swallowed. The m a i n cause of
infection i n dogs appears to be through intimate contact
Suggested Readings
with their dam as puppies.
Bach JF et al: Evaluation of the bioavailability and pharmacokinet
Clinical Features ics of two extended-release theophylline formulations in dogs,
7 Am Vet Med Assoc 224:1113, 2004.
Young affected dogs have an acute, l o u d , nonproductive Bemis DA et al: Aerosol, parenteral, and oral antibiotic treatment
cough and occasionally wheezing. The dogs appear other of Bordetella bronchiseptica infections in dogs, / Am Vet Med
wise healthy, making the initial presentation indistinguish Assoc 170:1082, 1977.
able from that o f canine infectious tracheobronchitis. Bidgood T et al: Comparison of plasma and interstitial fluid con
However, the cough persists, and eventually airway obstruc centrations of doxycycline and meropenem following constant
tion occurs as a result o f the formation o f reactive nodules. rate intravenous infusion in dogs, Am J Vet Res 64:1040, 2003.
Buonavoglia et al: Canine respiratory viruses, Vet Res 38:455,
Diagnosis 2007.
Dye JA et al: Chronopharmacokinetics of theophylline in the cat,
Nodules at the carina occasionally can be recognized radio-
/ Vet Pharmacol Ther 13:278, 1990.
graphically. Cytologic examination o f tracheal wash fluid i n
Ellis JA et al: Effect of vaccination on experimental infection with
some dogs shows the characteristic ova or larvae, providing
Bordetella bronchiseptica in dogs, / Am Vet Med Assoc 218:367,
the basis for a definitive diagnosis (see Table 20-1). Rarely, 2001.
larvae are found i n fecal specimens using zinc sulfate Gore T: Intranasal kennel cough vaccine protecting dogs from
(s.g. 1.18) flotation (preferred) or the Baermann technique experimental Bordetella bronchiseptica challenge within 72 hours,
(see Box 20-8). Vet Record 156:482, 2005.
The most sensitive diagnostic method is bronchoscopy, Graham-Mize C A et al: Bioavailability and activity of prednisone
w h i c h enables the nodules to be readily seen (Fig. 21-10). and prednisolone in the feline patient. Abstr., Vet Dermatol
Brushings o f the nodules are obtained and immediately 15(Suppl 1):9, 2004.
evaluated cytologically to detect the larvae. Material can be Guenther-Yenke C L et al: Pharmacokinetics of an extended-release
theophylline product in cats,} Am Vet Med Assoc 231:900, 2007.
examined directly i n saline solution or stained with new
Jacobs AAC et al: Protection of dogs for 13 months against Borde
methylene blue. If a definitive diagnosis is not obtained from
tella bronchiseptica and canine parainfluenza virus with a modi
analysis o f the brushings, biopsy specimens are obtained.
fied live vaccine, Vet Record 157:19, 2005.
Johnson LR: Tracheal collapse: diagnosis and medical and surgical
Treatment
treatment, Vet Clin North Am Small Anim Pract 30:1253, 2000.
Treatment w i t h ivermectin (400 g / k g orally or subcutane Johnson LR et al: Clinical and microbiologic findings in dogs with
ously) is recommended. The same dose is administered again bronchoscopically diagnosed tracheal collapse: 37 cases (1990-
every 3 weeks for four treatments. This treatment has not 1995), J Am Vet Med Assoc 219:1247, 2001.
been extensively investigated, however, and is not an approved Mantis P et al: Assessment of the accuracy of thoracic radiography
use o f this drug. It cannot be administered to Collies or in the diagnosis of canine chronic bronchitis, / Small Anim Pract
related breeds. A n alternative treatment is fenbendazole 39:518, 1998.
McKiernan BC: Current uses and hazards of bronchodilator therapy.
(50 mg/kg q24h for 7 to 14 days).
In Kirk RW et al, editors: Current veterinary therapy XI, Phila
Prognosis delphia, 1992, WB Saunders.
McKiernan BC: Diagnosis and treatment of chronic bronchitis:
The prognosis for dogs treated w i t h ivermectin is good; the twenty years of experience, Vet Clin North Am Small Anim Pract
drug appears to be successful i n eliminating infection i n 30:1267, 2001.
the limited number o f dogs that have been treated. Follow- Miller D J M et al: Gentamicin aerosolization for the treatment of
up o f individual patients is indicated to ensure successful infectious tracheobronchitis. Abstr., Proceed Am Coll Vet Intern
elimination. Med, 2003.
Moise NS et al: Bronchopulmonary disease. In Sherding RG, editor: Randolf IF et al: Prevalence of mycoplasmal and ureaplasmal recov
The cat: diseases and clinical management, New York, 1989, ery from tracheobronchial lavages and of mycoplasmal recovery
Churchill Livingstone. from pharyngeal swab specimens in cats with or without pulmo
Moritz A et al: Management of advanced tracheal collapse in dogs nary disease, Am J Vet Res 54:897, 1993.
using intraluminal self-expanding biliary wall stents, / Vet Intern Ridyard A: Heartworm and lungworm in dogs and cats in the UK,
Med 18:31, 2004. In Practice 27:147, 2005.
Outerbridge C A et al: Oslerus osleri tracheobronchitis: treatment Speakman A l et al: Antibiotic susceptibility of canine Bordetella
with ivermectin in 4 dogs, Can J Vet 39:238, 1998. bronchiseptica isolates, Vet Microbiol 71:193, 2000.
Padrid PA et al: Cyproheptadine-induced attenuation of type-I Thrusfield M V et al: A field investigation of kennel cough:
immediate hypersensitivity reactions of airway smooth muscle efficacy of different treatments, / Small Anim Pract 32:455,
from immune-sensitized cats, Am ] Vet Res 56:109, 1995. 1991.
Padrid P: Feline asthma: diagnosis and treatment, Vet Clin North Wheeldon EB et al: Chronic respiratory disease in the dog, / Small
Am Small Anim Pract 30:1279, 2000. Anim Pract 18:229, 1977.
Prost C: Treatment of allergic feline asthma with allergen avoidance White RAS et al: Tracheal collapse in the dog: is there really a role
and specific immunotherapy. Abstr., Vet Dermatol 13(Suppl 1): for surgery? A survey of 100 cases, / Small Anim Pract 35:191,
55, 2004. 1994.
C H A P T E R 22
Disorders of the
Pulmonary Parenchyma
and Vasculature
Diagnosis
A diagnosis o f canine influenza should be considered i n all
dogs with acute cough until proven otherwise because it is
VIRAL PNEUMONIAS highly transmissible to susceptible dogs. The diagnosis of
pneumonia is made by the radiographic detection of a bron
CANINE INFLUENZA chointerstitial or bronchoalveolar pattern or both in dogs
showing appropriate clinical signs. A tracheal wash is recom
Etiology mended to determine the types of bacteria involved and their
The canine influenza virus appears to be a recent adaptation antibiotic sensitivity.
from an equine influenza virus (Crawford et al., 2005). Sero Confirmation of the diagnosis of influenza is possible
logic evidence has been found to support its existence among through several methods: serology, ELISA for antigen detec
racing greyhounds since 1999 (Anderson et a l , 2007). There tion, virus isolation, and polymerase chain reaction ( P C R )
fore most dogs are susceptible to infection regardless o f age, for viral R N A . Serology has several advantages compared
and spread among dogs i n contact w i t h one another, espe with the other methods because blood is simple to collect,
cially those housed together, is rapid. The virus is transmit the resultant serum is stable, and infection can be detected
ted through respiratory secretions that are aerosolized or even after viral shedding has ceased. However, rapid confir
contaminate objects, including hands, clothing, bowls, and mation o f the diagnosis is not possible through serology
because rising antibody titers are required to confirm the Veterinary Medical Association (www.avma.org/public_
diagnosis. M o r e timely results are possible with antigen health/influenza/canine_guidelines.asp).
detection (Directigen F l u A , Becton, D i c k i n s o n and
Company) and P C R . Preliminary data by Spindel et al. OTHER VIRAL PNEUMONIAS
(2007) using nasal swabs for specimens indicate that P C R is Several other viruses can infect the lower respiratory tract,
much more sensitive i n detecting virus than antigen detec but rarely do signs o f viral pneumonia predominate. The
tion by ELISA or virus isolation. Other specimens that can role of canine adenovirus 1 and parainfluenza virus i n canine
be submitted for virus isolation or P C R are pharyngeal infectious tracheobronchitis has already been discussed (see
swabs, tracheal wash fluid, or lung tissue. Results from any Chapter 21). In dogs canine distemper virus can also infect
test for viral detection can be falsely negative because o f the the respiratory epithelium. Clinical signs o f pneumonia
relatively short period o f shedding after the development o f usually result from a secondary bacterial pneumonia. Infec
signs i n many patients. For best results, samples are collected tion o f the gastrointestinal tract or central nervous system
from febrile dogs very early i n the course o f disease. can also occur i n dogs with distemper (see Chapter 97). In
cats, calicivirus can cause pneumonia, but this manifestation
Treatment of infection is rare. The dry form o f feline infectious perito
In dogs with the m i l d form of disease, cough w i l l generally nitis can affect the lungs, but cats are generally seen because
persist for several weeks even when treated with antibiotics of signs o f involvement o f other organs. Feline infectious
and cough suppressants. M u c o p u r u l e n t nasal discharge can peritonitis is discussed i n Chapter 97.
be a result of secondary bacterial infection and may respond
to antibiotics.
Dogs with pneumonia require aggressive supportive care, BACTERIAL PNEUMONIA
including intravenous fluid therapy i f needed to maintain
systemic (and therefore airway) hydration. A variety o f Etiology
bacteria have been isolated from infected dogs, including A wide variety o f bacteria can infect the lungs. C o m m o n
Streptococcus equi subsp. zooepidemicus and gram-negative bacterial isolates from dogs and cats with pulmonary infec
organisms that are resistant to c o m m o n l y prescribed antibi tions include Bordetella bronchiseptica, Streptococcus spp.,
otics. Broad spectrum antibiotics should be prescribed i n i Staphylococcus spp., Escherichia coli, Pasteurella spp., Klebsi
tially and can be modified later on the basis o f culture and ella spp., Proteus spp., and Pseudomonas spp. Anaerobic
sensitivity results and response to therapy. Initial choices organisms can be part o f m i x e d infections, particularly i n
include the combination o f ampicillin with sulbactam and animals with aspiration pneumonia or with l u n g lobe con
either a fluoroquinolone or an aminoglycoside or mero solidation. Mycoplasma organisms have been isolated from
penem. (For additional information on treating bacterial dogs and cats with pneumonia, but their exact role is not
pneumonia, see p. 304) known.
Bacteria can colonize the airways, alveoli, or interstitium.
Prognosis The term pneumonia means inflammation o f the lung, but
Most dogs that are exposed to the influenza virus w i l l become the term is not specific for bacterial disease. Infection that
infected. Dogs with the m i l d form of the disease fully recover, clinically appears to be limited to the airways and peribron
although cough may persist for as long as a m o n t h . The chial tissues is called bacterial bronchitis. If all three regions
prognosis is more guarded for dogs that develop the severe are involved, the disease is called either bacterial broncho
form of the disease. Overall mortality has been reported to pneumonia or bacterial pneumonia. M o s t cases o f bacterial
be <5% (Yoon et a l , 2005). pneumonia result from bacteria of the oral cavity and
pharynx entering the lungs via the airways, which causes
Prevention a bronchopneumonia involving primarily the gravity-
Vaccination is the most promising approach for prevention, dependent cranial and ventral lung lobes (see Fig. 20-5).
but no vaccines are currently available. In veterinary hospi Bacteria that enter the lung through the hematogenous route
tals, animal shelters, and other kenneling facilities, i m m e d i usually cause pneumonia that assumes a caudal or diffuse
ate isolation of dogs with signs of influenza is indicated pattern and marked interstitial involvement.
and strict isolation protocols must be followed. The virus is Bacterial pneumonia is a c o m m o n lung disease, particu
readily killed by routine disinfectants. Successful prevention larly i n dogs. C o m m u n i t y - a c q u i r e d infectious pneumonia
of spread of organisms depends on careful cleaning and has been described i n puppies (Radhakrishnan et a l , 2007),
disinfection of tables, cages, bowls, and any other objects i n most often caused by Bordetella bronchiseptica (49% of
contact with infected dogs. In addition, strict attention to cases). However, consideration should also be given for pre
detail is necessary regarding hand cleaning after contact with disposing abnormalities. In adult dogs, a predisposing abnor
any animal and using disposable barrier protection (e.g., mality usually exists. Abnormalities to consider i n all patients
gloves, booties, outerwear) when working with infected dogs include the aspiration o f ingested material or gastric c o n
or contaminated areas. Recommendations for managers and tents because o f cleft palate, megaesophagus, or other causes
workers of kennel facilities are provided by the American of aspiration pneumonia (p. 309); decreased clearance from
the lungs o f normally inhaled debris, particularly i n animals yield, specimens should be collected before antibiotic therapy
with chronic bronchitis, ciliary dyskinesia, or bronchiectasis; is initiated. A tracheal wash specimen is generally sufficient.
immunosuppression resulting from drugs, malnutrition, Septic neutrophilic inflammation is typically found in
stress, or endocrinopathies; other infections, including animals with bacterial pneumonia, and growth o f organisms
canine influenza, canine distemper, feline leukemia virus o n bacterial culture is expected. Examination o f a gram-
infection, or feline immunodeficiency virus infection; the stained preparation w i l l provide early guidance i n antibiotic
inhalation or migration o f foreign bodies; and, rarely, neo selection pending results o f culture and will also assist in
plasia or fungal or parasitic infections. the identification of anaerobes or unusual organisms (e.g.,
Mycobacteria and filamentous organisms).
Clinical Features A conscientious effort is also made to identify any under
Dogs and cats with bacterial p n e u m o n i a are evaluated lying problems. In some animals, such as those with mega-
because o f respiratory signs, systemic signs, or both. Respira esophagus, the initiating cause is obvious. Further diagnostic
tory signs can include cough (which is usually productive tests are indicated i n other animals, depending on the results
and soft), a bilateral mucopurulent nasal discharge, exercise of the clinicopathologic evaluation. These may include
intolerance, and respiratory distress. C o u g h is less c o m m o n bronchoscopy to search for airway abnormalities or foreign
i n cats w i t h pneumonia. Systemic signs include lethargy, bodies, conjunctival scrapings to look for distemper virus,
anorexia, fever, and weight loss. The animal may have a serologic tests to determine whether the animal has a fungal
history of chronic airway disease or regurgitation. Cats, par infection, tests for influenza virus, and hormonal assays to
ticularly kittens, from stressful housing situations (e.g., over determine whether the animal has hyperadrenocorticism.
crowding) appear predisposed to develop pneumonia as a Ciliary dyskinesia is discussed briefly i n Chapter 21. The
result o f Bordetella infections. Dogs with complicated infec diagnostic evaluation for aspiration pneumonia is discussed
tious tracheobronchitis may have a recent history o f harsh on p. 309.
cough and a history consistent w i t h exposure, as described
i n Chapter 21. Other potential predisposing factors, as listed Treatment
i n the preceding paragraph, are pursued through careful
history taking. Antibiotics
Fever may be present o n physical examination but is The treatment o f bacterial pneumonia consists of antibiotics
identified i n only about half o f patients. Crackles and and supportive care, with follow-up evaluation (Box 22-1).
occasionally expiratory wheezes may be auscultated, with the The antibiotic sensitivity of the involved organisms is diffi-
abnormal lung sounds often prominent over the cranioven
tral l u n g fields.
AELUROSTRONGYLUS ABSTRUSUS goal, and glucocorticoid therapy may interfere with the
Aelurostrongylus abstrusus is a small w o r m that infects the effectiveness o f the antiparasitic drugs. Bronchodilators may
small airways and pulmonary parenchyma o f cats. Snails or provide symptomatic relief and presumably do so without
slugs serve as intermediate hosts. M o s t cats w i t h infection interference with antiparasitic drug action. The prognosis i n
have no clinical signs. Those cats that do are usually young. animals with the infection is excellent.
The clinical signs are those o f bronchitis. The abnormalities
seen o n radiographs may also reflect bronchitis, although a CRENOSOMA VULPIS
diffuse miliary or nodular interstitial pattern is present i n Crenosoma vulpis is a l u n g w o r m o f foxes that can also infect
some cats. Eosinophilic inflammation may be apparent i n dogs. Dogs living i n Atlantic Canada and parts of Europe are
peripheral b l o o d and airway specimens. most c o m m o n l y diagnosed with this disease, while the diag
A definitive diagnosis is made through the identification nosis remains rare i n the U n i t e d States. However, it is pos
of larvae, w h i c h may be present i n fecal specimens prepared sible that with increased residential development into fox
using the Baermann technique (see Fig. 20-12, A) or i n habitats, the frequency of cases i n this country will increase.
airway specimens obtained by tracheal washing or b r o n The w o r m resides i n the airways (i.e., trachea, bronchi, bron
choalveolar lavage. M u l t i p l e fecal specimens should be chioles). Snails or slugs serve as intermediate hosts. The
examined i n suspected cases because the larvae are not clinical signs are those o f allergic or chronic bronchitis. T h o
always present. racic radiographs may have a bronchointerstitial or patchy
Cats should be treated with fenbendazole at the same alveolar pattern or occasionally a nodular pattern. Infection
dosage as that used for the treatment o f capillariasis. In one is diagnosed definitively through the identification o f the
study, the dosage o f 50 mg/kg orally q24h for 15 days was larvae i n fecal specimens using the Baermann technique
effective i n eliminating infection i n all four cats treated described i n B o x 20-8, tracheal wash fluid, or bronchoalveo
(Grandi et al., 2005). In contrast with a previous report, lar lavage fluid (see Fig. 20-12, B). M u l t i p l e fecal specimens
ivermectin (0.4 mg/kg, administered subcutaneously) was should be examined i n suspected cases because the larvae are
not effective i n one cat treated. The response to treatment not always present. A single oral dose of milbemycin oxime
is monitored by thoracic radiographs and periodic fecal (0.5 mg/kg) was effective i n resolving clinical signs and elim
examinations. Treatment may have to be repeated i n some ination o f larvae from feces collected 4 to 6 weeks after
cases. treatment i n 32 dogs (Conboy, 2004). This treatment may
Antiinflammatory therapy with glucocorticoids alone not be effective against immature larvae. A s with other pul
often causes the clinical signs to resolve. However, eliminat monary parasites, the response to treatment is monitored
ing the underlying parasitic disease is a preferable treatment with thoracic radiographs and periodic fecal examinations.
ASPIRATION PNEUMONIA
BOX 22-2
Etiology
Underlying Causes of Aspiration Pneumonia in Dogs
A small amount of fluid and bacteria is aspirated from the
and Cats*
oropharynx into the airways o f healthy animals, but n o r m a l
airway clearance mechanisms prevent infection. Organisms Esophageal Disorders
from the oropharynx are thought to be the source o f bacte Megaesophagus, Chapter 31
ria in many animals with bacterial pneumonia, specifically Reflux esophagitis, Chapter 31
bacterial bronchopneumonia (see p. 303). In people such Esophageal obstruction, Chapter 31
infection is termed aspiration pneumonia. In veterinary med Myasthenia gravis (localized), Chapter 71
icine the term aspiration pneumonia is generally used to refer Bronchoesophageal fistulae
to the inflammatory lung disease that occurs as a result o f
Localized Oropharyngeal Abnormalities
the inhalation o f overt amounts o f solid or l i q u i d material
Cleft palate
into the lungs. The materials that are usually aspirated are
Cricopharyngeal motor dysfunction, Chapter 31
stomach contents or food. N o r m a l laryngeal and pharyngeal
Laryngoplasty, Chapter 17
function prevents aspiration i n healthy animals, although
Brachycephalic airway syndrome, Chapter 17
occasionally an excited puppy or a dog running through tall
grass aspirates a foreign body. Otherwise, the presence o f Systemic Neuromuscular Disorders
aspiration pneumonia i n an animal o f any age indicates an Myasthenia gravis, Chapter 71
underlying predisposing abnormality (Box 22-2). Polyneuropathy, Chapter 71
Aspiration pneumonia is a c o m m o n complication of Polymyopathy, Chapter 72
animals with regurgitation. Megaesophagus is the most
Decreased Mentation
common cause of regurgitation (see Chapter 31). Other
causes of regurgitation (e.g., reflux esophagitis, esophageal General anesthesia
Sedation
obstruction) are less c o m m o n . Another cause o f aspiration
i Post ictus, Chapter 6 7
pneumonia is localized or systemic neurologic or muscular
| Head trauma
disease affecting the normal swallowing reflexes of the larynx
| Severe metabolic disease
or pharynx. These reflexes can also be depressed i n dogs or
cats with abnormal levels of consciousness or i n those that Iatrogenic**
are anesthetized. Laryngeal paralysis does not always lead to Force-feeding
the development of aspiration pneumonia, but aspiration is Stomach tubes, Chapter 30
a potential complication of therapeutic laryngoplasty. It can
Vomiting (in Combination with Other Predisposing
also occur i n animals with abnormal pharyngeal anatomy
Factors), Chapter 28
resulting from mass lesions, brachycephalic airway syn
drome, or cleft palate. Bronchoesophageal fistulae are a rare
* Discussions of these abnormalities can be found on the given
cause of aspiration pneumonia.
chapter numbers.
Aggressive force-feeding, especially i n mentally depressed * * O v e r z e a l o u s feeding, incorrect tube placement, or loss of lower
animals, and improper placement o f stomach tubes into esophageal sphincter competence because of presence of tube.
the trachea are iatrogenic causes o f aspiration pneumonia.
Mineral o i l administered to prevent hairballs can be a cause
of aspiration pneumonia i n cats because the tasteless and This response can become organized, resulting i n the forma
odorless o i l is poorly handled by the pharynx. tion o f granulomas.
The damage to the lung resulting from aspiration may Bacterial infection may result from the aspiration o f
stem from chemical damage, obstruction o f the airways, contaminated material, such as ingesta that remained i n
infection, and the resulting inflammatory response to each the esophagus. A c i d i c gastric contents are probably sterile,
of these factors. Gastric acid causes severe chemical injury to although i n people the contents are considered contami
the lower airways. Tissue necrosis, hemorrhage, edema, and nated i f antacids have been taken, i f an intestinal obstruction
bronchoconstriction ensue, and a marked acute inflam is present, or with periodontal disease. Note that many vet
matory response is initiated. H y p o x e m i a resulting from erinary patients have periodontal disease. Regardless of the
decreased alveolar ventilation and compliance can be fatal. sterility o f the aspirated material, the resultant damage to
Severe respiratory distress can occur from physical the lungs by gastric acid greatly predisposes the animal to
obstruction o f the airways by the aspirated material. In most the development o f a secondary infection.
cases only small airways are obstructed, but rarely a large The inhalation o f mineral o i l elicits a chronic inflam
piece of food will obstruct a major airway. Obstruction is matory response. The clinical signs i n this setting are often
subsequently exacerbated by reflex bronchoconstriction and m i l d , but i n rare instances they may be severe. Radiographic
inflammation. Inhaled solid material initiates an inflamma abnormalities persist and can be erroneously interpreted as
tory reaction that includes an abundance o f macrophages. representing neoplastic lesions.
Clinical Features B l o o d gas analysis can be helpful i n differentiating
Dogs and cats with aspiration pneumonia are frequently hypoventilation from ventilation-perfusion abnormalities
presented for acute, severe respiratory signs. Systemic signs (see Chapter 20), although a combination of abnormalities
such as anorexia and depression are c o m m o n , and these exists i n most animals with aspiration pneumonia. Animals
patients may even present i n shock. V o m i t i n g , regurgitation, with evidence o f profound hypoventilation may have either
or eating may have preceded the onset o f distress. Other a large airway obstruction or muscle weakness secondary to
patients are seen because o f chronic intermittent or pro an underlying neuromuscular disorder such as myasthenia
gressive signs o f coughing or increased respiratory efforts. gravis. B l o o d gas analysis also assists i n the therapeutic man
Occasionally, patients show only signs o f depression or the agement of these animals and can be used effectively to
predisposing disease. A thorough history is obtained, with monitor the response to therapy.
all organ systems carefully reviewed. The owners are spe Diagnostic evaluation is indicated to identify potential
cifically questioned about force-feeding and medication underlying diseases (see B o x 22-2). This may include a thor
administration. ough oral and pharyngeal examination, contrast-enhanced
Fever may be present, but it is an inconsistent finding. radiographic studies to evaluate the esophagus, or specific
Crackles are often auscultated, particularly over the depen neuromuscular tests.
dent lung lobes. Wheezes are heard i n some cases. Once a
patient is i n stable condition, a thorough neuromuscular Treatment
examination is performed. The ability o f the patient to Suctioning o f the airways is helpful only for animals that
prehend and swallow food and water should also be aspirate i n the hospital while already anesthetized or un
observed. conscious, when it can be performed immediately after
aspiration. If a bronchoscope is immediately available, suc
Diagnosis tioning can be performed through the biopsy channel, which
Aspiration pneumonia is usually diagnosed on the basis o f affords visualized guidance. Alternatively, a sterile soft rubber
the suggestive radiographic findings i n conjunction with tube attached to a suction p u m p can be passed blindly into
evidence o f a predisposing condition. Thoracic radiographs the airways through an endotracheal tube. Excessive suction
typically show diffuse, increased interstitial opacities with may result i n lung lobe collapse. Therefore low-pressure,
alveolar flooding (air bronchograms) and consolidation intermittent suction is used, followed by expansion of the
of the dependent lung lobes (see Fig. 20-5). Radiographic lungs with several positive-pressure ventilations using an
abnormalities may not be apparent until 12 to 24 hours after anesthetic or A m b u bag. Airway lavage is contraindicated.
aspiration, however. Occasionally, nodular interstitial pat Animals i n severe respiratory distress should be treated
terns are seen i n chronic cases. Large nodules can form with fluid therapy, oxygen supplementation, bronchodila
around solids; miliary nodules often form i n animals that tors, and glucocorticoids. Fluids are administered intrave
have aspirated mineral o i l . Large airway obstruction is sus nously at high rates to treat shock (see Chapter 30) and
pected i f radiographs show a soft-tissue mass w i t h i n a large should be continued after initial stabilization of the animal's
airway, but this is an unusual finding. A marked, diffuse condition to maintain systemic hydration, which is necessary
alveolar pattern can be seen i n dogs that have severe second to maximize the effectiveness o f airway clearance mecha
ary edema (see the section on p u l m o n a r y edema, p. 319). nisms. However, overhydration must be avoided because o f
The peripheral b l o o d count can reflect the pulmonary a tendency for pulmonary edema.
inflammatory process, but it is often normal. Neutrophils are Oxygen supplementation (see Chapter 27) is initiated
examined for the presence of toxic changes suggestive o f immediately i n compromised animals. Positive-pressure
sepsis. ventilation is required for animals i n severe respiratory dis
Tracheal wash is indicated for all animals that can tolerate tress that is unresponsive to oxygen therapy.
the procedure to identify complicating bacterial infection Bronchodilators can be administered to decrease bron
and obtain antibiotic sensitivity data. A marked inflamma chospasms and ventilatory muscle fatigue. They are most
tory response characterized by a predominance o f neutro likely to be effective i n cats. Bronchodilators can worsen
phils is seen i n cytologic specimens. B l o o d resulting from ventilatiomperfusion ( V / Q ) mismatching, exacerbating
hemorrhage may be seen i n specimens from animals i n the hypoxemia. They are discontinued i f no improvement
acute period after aspiration. Bacteria may also be seen. is seen or clinical signs appear to worsen after their
Bacterial cultures should always be performed. administration.
Bronchoscopy can be used to grossly examine the airways Rapid-acting glucocorticoids are administered for the
and detect and remove large solids. However, the likelihood treatment o f shock. Their use i n the absence o f shock is
of a large airway obstruction is very small, so bronchoscopy controversial. The antiinflammatory effects of glucocorti
is performed only i f there are clear signs o f large airway coids can be beneficial, but glucocorticoids can interfere with
obstruction (see Chapter 26) or i f the animal is not c o n n o r m a l host defense mechanisms i n tissues that have already
scious and therefore does not require general anesthesia for been severely compromised. This author reserves the use of
the procedure. glucocorticoids for patients that have severe respiratory
compromise and a deteriorating clinical picture despite and idiopathic bronchitis are by far the most c o m m o n eosin
appropriate antibiotic therapy and supportive care. L o w ophilic lung diseases seen i n cats and are discussed i n Chapter
(antiinflammatory) doses o f short-acting preparations are 21. Interstitial infiltration, with or without concurrent b r o n
administered for up to 48 hours. chitis, is sometimes referred to as pulmonary infiltrates with
Animals with a large airway obstruction can benefit from eosinophils (PIE) and is typically seen i n dogs. Eosinophilic
bronchoscopy and foreign body removal. However, routine pulmonary granulomatosis is a severe type of PIE seen i n dogs
bronchoscopy is not indicated because of the risk o f the and is characterized by the development o f nodules and
general anesthesia needed during the procedure and the often hilar lymphadenopathy. It must be differentiated from
infrequency of large airway obstructions. a mycotic infection and neoplasia. The term eosinophilic
Antibiotics are administered immediately i n animals that bronchopneumopathy is also used to describe eosinophilic
are presented i n severe distress or with overt systemic signs lung disease. These names are descriptive only and likely
of sepsis. Selected antibiotics should have a broad spectrum encompass a variety of hypersensitivity disorders o f the
of activity and be administered intravenously. Such drugs lung.
include meropenem or combinations o f either ampicillin Because eosinophilic inflammation is a hypersensitivity
with sulbactam and a fluoroquinolone or ampicillin with response, an underlying antigen source is actively pursued i n
sulbactam and an aminoglycoside (see the section o n bacte- affected animals. Considerations include heartworms, p u l
rial pneumonia, p. 303). monary parasites, drugs, and inhaled allergens. F o o d allergy
A tracheal wash is performed i n stable patients before could play a role i n these disorders, but this association has
initiation o f antibiotics to document the presence o f infec not been explored. Potential allergens are discussed further
tion and obtain antibiotic sensitivity data. This information i n the section o n allergic bronchitis, Chapter 21. Bacteria,
is particularly valuable because prolonged treatment is often fungi, and neoplasia can also induce a hypersensitivity
needed and also because research i n h u m a n medicine has response, but this response often is not the predominant
amply demonstrated that resistant secondary infections finding. In many cases no underlying disease can be found.
can develop after aspiration i n patients given antibiotics i n i Eosinophilic pulmonary granulomatosis is strongly associ
tially or on an empirical basis. A s discussed for bacterial ated with heartworm disease.
pneumonia, the high incidence o f gram-negative and
mixed infections make assumptions regarding antibiotic Clinical Features
sensitivity prone to error. Pending results o f culture, it is Eosinophilic lung diseases are seen i n young and older
reasonable to initiate treatment with a penicillin with a dogs. Affected dogs are evaluated because o f progressive
beta-lactamase inhibitor (e.g., amoxicillin-clavulanate or respiratory signs, such as cough, increased respiratory efforts,
ampicillin with sulbactam). Because infection can occur as and exercise intolerance. Systemic signs such as anorexia
a later complication i n these patients, frequent m o n i t o r i n g and weight loss are usually m i l d . L u n g sounds are often
with physical examination, C B C , and thoracic radiographs normal, although crackles or expiratory wheezes are
is necessary to detect any deterioration consistent with sec possible.
ondary infection. Tracheal wash is repeated i f infection is
suspected. Diagnosis
Further therapeutic and m o n i t o r i n g considerations are The finding o f peripheral eosinophilia is included i n some
discussed i n the section o n bacterial pneumonia (p. 303). definitions o f PIE, but it is not present i n all animals with
Underlying diseases are treated to prevent recurrence. the disease, n o r is it a specific finding. A diffuse interstitial
pattern is seen o n thoracic radiographs. Eosinophilic p u l m o
Prognosis nary granulomatosis results i n the formation o f nodules,
Animals with m i l d signs o f disease and a correctable under usually with indistinct borders. These nodules can be quite
lying problem have an excellent prognosis. The prognosis is large, and hilar lymphadenopathy m a y also be present. A
worse for animals with more severe disease or uncorrectable patchy alveolar opacity and consolidation o f the l u n g lobes
underlying problems. can occur as well.
P u l m o n a r y specimens must be examined to establish a
diagnosis o f PIE. I n some cases o f PIE, evidence o f eosino
EOSINOPHILIC LUNG DISEASE philic inflammation m a y be found i n tracheal wash fluid.
(PULMONARY INFILTRATES WITH M o r e aggressive techniques for collecting pulmonary speci
EOSINOPHILS AND EOSINOPHILIC mens, such as bronchoalveolar lavage, lung aspiration, or
PULMONARY GRANULOMATOSIS) lung biopsy, are required to identify the eosinophilic response
i n other cases. Other inflammatory cell populations are fre
Eosinophilic lung disease is a broad term describing inflam quently present i n lesser numbers i n such specimens.
matory lung disease i n which the predominant infiltrating Potential antigen sources should be considered, and p u l
cell is the eosinophil. Eosinophilic inflammation can involve monary specimens should be carefully examined for the
primarily the airways or the interstitium. Allergic bronchitis presence o f infectious agents and features o f malignancy.
Heartworm tests and fecal examinations for pulmonary septa include alveolar epithelium, epithelial basal lamina,
parasites are indicated i n all cases. capillary endothelial basal lamina, and capillary endothe
l i u m . Other cells include fibroblasts and alveolar macro
Treatment phages. T o make a diagnosis of idiopathic disease, the k n o w n
A n y primary disease identified during the diagnostic evalu etiologies o f interstitial lung disease must be ruled out as
ation o f these animals is treated directly. Eliminating the completely as possible. Etiologies o f interstitial lung disease
source o f the antigen that may be triggering the excessive are numerous and include many infectious agents and some
i m m u n e response may result i n a cure. toxins and neoplasia.
Antiinflammatory therapy with glucocorticoids is Idiopathic pulmonary fibrosis is the most well-described
indicated for dogs i n w h i c h an antigen source cannot be idiopathic interstitial pneumonia i n dogs and cats. Some of
identified and for dogs with heartworm disease i f the eosin the eosinophilic lung diseases (not including allergic or idio
ophilic inflammation is causing respiratory compromise (see pathic feline bronchitis) may also be part of this group of
Chapter 10). Dogs with eosinophilic granulomatosis often diseases (see p. 311). Other inflammatory lung diseases of
require more aggressive immunosuppressive therapy. the interstitium i n which a cause cannot be identified are
Dogs are typically treated with glucocorticoids, such as occasionally seen i n dogs and cats. The lesions may represent
prednisone, at an initial dosage of 1 to 2 mg/kg orally every a form o f vasculitis, a component o f systemic lupus erythe
12 hours. Clinical signs and thoracic radiographs are used to matosus, i m m u n e complex disease, or some other hypersen
m o n i t o r the animal's response to therapy, and initially these sitivity response. These diseases are rare, however, and not
should be assessed every week. Once the clinical signs have well documented. A l u n g biopsy must be performed for a
resolved, the dosage o f glucocorticoids is decreased to the definitive diagnosis to be made. A clinical diagnosis is made
lowest effective one. If signs have remained i n remission for only after extensive testing has been done to rule out more
3 months, discontinuation o f therapy can be attempted. If c o m m o n causes of lung disease, particularly infectious agents
signs are exacerbated by glucocorticoid therapy, immediate and neoplasia, and after a prolonged positive response to
reevaluation to search for underlying infectious agents is immunosuppressive therapy. L y m p h o m a t o i d granulomato
indicated. sis is a nodular interstitial disease that exhibits clinical signs
Dogs with large nodular lesions (eosinophilic granuloma similar to those seen i n animals with eosinophilic p u l m o
tosis) should be treated with a combination o f glucocorti nary granulomatosis. It was initially considered to be an
coids and a cytotoxic agent. Prednisone is administered to inflammatory l u n g disease but is currently considered to be
these animals at a dosage o f 1 mg/kg orally every 12 hours, lymphoproliferative neoplasia o f the lung (see p. 314).
i n combination with cyclophosphamide at a dosage o f
2
50 m g / m orally every 48 hours. Clinical signs and thoracic IDIOPATHIC PULMONARY FIBROSIS
radiographs are evaluated every 1 to 2 weeks until remission In people idiopathic pulmonary fibrosis is the clinical diag
is achieved. C B C s are also done every 1 to 2 weeks to detect nosis that is defined by the histopathologic diagnosis o f usual
excessive bone marrow suppression resulting from the cyclo interstitial pneumonia. However, the histopathologic pattern
phosphamide. Attempts to discontinue therapy can be made of usual interstitial pneumonia can be seen as a result of
after several months of remission. It may be necessary to other diseases, and according to the American Thoracic
discontinue the cyclophosphamide earlier than this because Society/European Respiratory Society consensus statement
long-term treatment is associated with sterile hemorrhagic (2002), the diagnosis o f idiopathic pulmonary fibrosis also
cystitis. (See Chapter 78 for further discussion o f the adverse requires (1) the exclusion o f other k n o w n causes of intersti
effects o f cyclophosphamide therapy.) The effectiveness o f tial lung diseases including drug toxicities, environmental
other immunosuppressive drugs, such as cyclosporine, have exposures, and collagen vascular diseases; (2) characteristic
not been reported. radiographic or computed tomographic abnormalities; and
(3) characteristic pulmonary function abnormalities. In vet
Prognosis erinary medicine the latter criterion may be difficult to apply,
A wide spectrum o f disease is seen i n terms o f both but attention should be paid to the other criteria.
the severity o f the signs and the underlying causes. The The characteristic lesions that result i n the histopatho
prognosis is generally fair to good. However, the prognosis logic pattern o f usual interstitial pneumonia are as follows:
is guarded i n dogs with severe eosinophilic pulmonary fibrosis, areas o f fibroblast proliferation, metaplasia of the
granulomatosis. alveolar epithelium, and m i l d to moderate inflammation.
Honeycomb change may occur as a result o f enlarged air
spaces lined by abnormal alveolar epithelium. The lungs are
IDIOPATHIC INTERSTITIAL PNEUMONIASheterogeneously affected, with areas o f normal lung inter
mixed with abnormal regions. The abnormal regions are
The term idiopathic interstitial pneumonia generally denotes often subpleural. A defect i n w o u n d healing has been hypoth
inflammatory and/or fibrotic infiltration of the lungs involv esized as the cause.
ing primarily the alveolar septa. Small airways, alveoli, and Idiopathic pulmonary fibrosis has been recently described
the pulmonary vasculature may also be affected. The alveolar i n cats o n the basis of histologic lesions which are quite
Clinical Features
A breed predisposition is seen i n dogs w i t h p u l m o n a r y fibro
sis. West H i g h l a n d W h i t e Terriers are most frequently
reported, w i t h fewer cases documented among Staffordshire
Bull Terriers, Jack Russell Terriers, C a i r n Terriers, and Schip
perkes. Both dogs and cats tend to be middle-aged or older
at the time o f presentation, although characteristic signs
have been found i n patients as young as 2 years o f age.
Signs are most often slowly progressive over months. In
cats the duration o f signs may be shorter, w i t h 6 o f 23 cats
having shown signs for only 2 days to 2 weeks ( C o h n et al.,
2004). Respiratory compromise is the most prominent clin
ical sign o f pulmonary fibrosis, manifested as exercise intol
erance and/or rapid, labored breathing. C o u g h often occurs,
but i f it is the predominant sign, higher consideration for a
diagnosis o f bronchitis should be given. Syncope may occur
in dogs.
Crackles are the hallmark auscultatory finding i n dogs
and are noted i n some cats. Wheezes are heard i n approxi
mately half o f dogs and some cats. The abnormal breathing
pattern is typically tachypnea with relatively effortless
expiration.
Diagnosis
Thoracic radiographs o f dogs w i t h pulmonary fibrosis
typically show a diffuse interstitial pattern. The abnormal
densities generally must be moderate to severe to be distin
guished from age-related change. A bronchial pattern is
often noted concurrently, contributing to the overlap i n
signs between pulmonary fibrosis and chronic bronchitis.
Evidence o f pulmonary hypertension may be seen (see
FIG 2 2 - 3 p. 316). Radiographs o f cats w i t h this disease may show
Photomicrographs of a lung b i o p s y from a c a t with idio diffuse or patchy infiltrate (Fig. 22-4). Patterns may be inter
pathic p u l m o n a r y fibrosis. A t lower p o w e r (A) there is stitial, bronchial, alveolar, or m i x e d but are often quite severe.
distortion a n d obliteration of the normal p u l m o n a r y architec
Bronchiectasis, caused by traction o n the airways, may be
ture b e c a u s e of replacement of the p a r e n c h y m a with
noted i n either species w i t h advanced disease.
d i s o r g a n i z e d b a n d s of fibrous tissue a n d scattered mono
nuclear inflammatory cells. There a r e f e w r e c o g n i z a b l e Results of the C B C , serum biochemistry panel, and u r i
alveoli in this section. The a l v e o l a r septae a r e t h i c k e n e d , nalysis are generally unremarkable. Polycythemia may be
a n d metaplasia of the a l v e o l a r epithelium is present. A t present secondary to chronic hypoxemia. Screening tests to
higher p o w e r (B) subpleural alveoli s h o w m a r k e d distortion identify other etiologies o f interstitial lung disease include
with marked septal fibrosis a n d type 2 epithelial h y p e r p l a
fecal examinations for parasites, heartworm tests, and appro
s i a . Although normal a r e a s of the lung a r e not s h o w n , the
priate infectious disease serology.
disease is c h a r a c t e r i z e d b y heterogeneity of lesions within
the lung. (Photomicrographs courtesy Stuart Hunter.) A i r w a y specimens should be collected i n sufficiently
stable patients, primarily to assist i n the identification o f
other causes of lung disease. M i l d to moderate inflammation
may be seen i n patients with pulmonary fibrosis, but this is
similar to those i n people ( C o h n et al., 2004; W i l l i a m s et al., a nonspecific finding. Bronchoscopy may also be useful i n
2006; Fig. 22-3). Unlike the disease that affects people and some patients for identifying other causes o f lung disease,
cats, the disease i n dogs has been associated with the primary such as chronic bronchitis.
lesion of collagen deposition i n the alveolar septa with no Typical lesions identified by computed tomography are
fibroblastic foci (Norris et al., 2005). often used i n making a presumptive diagnosis o f idiopathic
Neoplasia can occur concurrently with idiopathic p u l m o pulmonary fibrosis i n people. Similar lesions may be seen i n
nary fibrosis i n people and was reported i n 6 of 23 cats some dogs w i t h the disease (Johnson et al., 2005). Results o f
(Cohn et al., 2004). The lesions of pulmonary fibrosis can computed tomography i n cats have not been reported.
also be misinterpreted as carcinoma, and 4 o f 23 cats con A definitive diagnosis o f p u l m o n a r y fibrosis requires a
sidered to have pulmonary fibrosis were initially given a lung biopsy obtained by thoracotomy or thoracoscopy. The
pathologic diagnosis o f carcinoma. expense and invasiveness o f biopsy preclude its use i n some
Nevertheless, individual patients, particularly dogs, can
survive for longer than a year. The mean survival time in
dogs i n one study was 18 months from the onset of signs,
with survival up to 3 years (Corcoran et al., 1999). The prog
nosis i n cats is poorer. O f 23 cats, 14 died or were euthanized
within weeks of the onset o f signs and only 7 of 23 survived
longer than 1 year ( C o h n et al., 2004).
PULMONARY NEOPLASIA
Primary pulmonary tumors, metastatic neoplasia, and m u l
ticentric neoplasia can all involve the lungs. Most primary
pulmonary tumors are malignant. Carcinomas predominate
and include adenocarcinoma, bronchoalveolar carcinoma,
and squamous cell carcinoma. Sarcomas and benign tumors
FIG 22-4
Lateral thoracic radiograph from a cat with idiopathic pulmo are m u c h less c o m m o n . Small cell carcinoma, or oat cell
nary fibrosis showing a diffuse interstitial pattern with patchy tumor, which occurs frequently in people, is rare in dogs
areas of alveolar disease in the caudal lung lobes. Pericar and cats.
dial and mediastinal fat are also seen. Radiographic abnor The lungs are a c o m m o n site for the metastasis of
malities in cats with fibrosis are quite variable, including the malignant neoplasia from other sites i n the body and
range of interstitial, bronchial, alveolar, or mixed patterns.
even from primary pulmonary tumors. Neoplastic cells can
be carried i n the bloodstream and trapped i n the lungs,
patients. Furthermore, the lack o f specific treatment recom where there is low blood flow and an extensive capillary
mendations for pulmonary fibrosis is a deterrent. However, network. Lymphatic spread or local invasion can also
biopsy should be considered i n patients that are stable and occur.
whose owners have sufficient resources. The less invasive Multicentric tumors can involve the lungs. Such tumors
tests cannot completely rule out the existence o f a different, include lymphoma, malignant histiocytosis, and masto
directly treatable disease (e.g., atypical bacterial infection, cytoma. A n unusual lymphoproliferative tumor limited to
fungal disease, parasitism), and more aggressive treatment involvement o f the lung is lymphomatoid granulomatosis.
for pulmonary fibrosis could be recommended with histo This neoplasm is characterized by the infiltration of pleo
logic confirmation o f the diagnosis. morphic lymphoreticular and plasmacytoid cells around and
into blood vessels, with accompanying eosinophils, neutro
Treatment phils, lymphocytes, and plasma cells.
Even i n people, large, well-controlled studies have not been Multiple tumors of different origins can occur in the same
performed to determine the ideal treatment strategy for animal. In other words, the presence o f a neoplasm in one
idiopathic pulmonary fibrosis (Hoyles et al., 2006). Most site o f the body does not necessarily imply that the same
individuals are treated with prednisone at l o w dosages and tumor is also present i n the lungs.
azathioprine. Cyclophosphamide is used routinely by some
physicians and only during exacerbations by others. C o r t i Clinical Features
costeroids alone are not considered to be effective. M a n y Neoplasms are most c o m m o n i n older animals but also
other drugs, including colchicine and penicillamine, have occur in young adult animals. Tumors involving the lungs
been tried or investigated, but thus far none have been can produce a wide spectrum o f clinical signs. These signs
proved convincingly effective. Survival rates 5 years after the are usually chronic and slowly progressive, but peracute
diagnosis remain only 20% to 30% with treatment. manifestations such as pneumothorax or hemorrhage can
Most dogs and cats have been treated with corticosteroids also occur.
and bronchodilators. Theophylline derivatives have the the Most signs reflect respiratory tract involvement. Infiltra
oretical potential to provide some benefit through potentia tion o f the lung by the tumor can cause interference with
tion o f steroid activity. O n the basis o f clinical experience oxygenation, leading to increased respiratory efforts and
with people, the addition o f azathioprine or cyclophospha exercise intolerance. Mass lesions can compress airways, pro
mide may be of benefit. Animals with severe pulmonary voking cough and obstructing ventilation. Erosion through
hypertension may benefit from treatment o f this complica vessels can result i n pulmonary hemorrhage. The blood loss
tion (p. 316). can be sudden, resulting i n acute hypovolemia and anemia
in addition to respiratory compromise. Edema, nonseptic
Prognosis inflammation, or bacterial infection can occur secondary to
The prognosis for idiopathic pulmonary fibrosis i n dogs and the tumor. Erosion through the airways can result in pneu
cats is poor, with relentless progression of disease expected. mothorax. Pleural effusion of nearly any character can form.
In rare cases, the caudal or cranial venae cavae are obstructed,
resulting i n the development o f ascites or head and neck
edema, respectively.
Nonspecific signs i n dogs and cats with pulmonary neo
plasms include weight loss, anorexia, depression, and fever.
Gastrointestinal signs may be the primary complaint. V o m i t
ing and regurgitation may be the presenting signs i n cats i n
particular. Lameness may be the presenting sign i n patients
with hypertrophic osteopathy secondary to thoracic mass
lesions and i n cats with metastasis of carcinoma to their
digits.
Some animals with lung neoplasia have no clinical signs
at all, and the tumor is discovered as an incidental finding
on thoracic radiographs or at postmortem examination.
Animals with metastatic or multicentric lung neoplasia can
be seen because of signs o f tumor involvement i n another FIG 22-5
organ. Bronchoalveolar lavage fluid from the dog whose lateral
Lung sounds may be normal, decreased, or increased. thoracic radiograph showing a severe, unstructured intersti
tial pattern is depicted in Fig. 20-8. M a n y clumps of deeply
They are decreased over all lung fields i n animals with
staining epithelial cells showing marked criteria of malig
pneumothorax or pleural effusion. Localized decreased or nancy were seen. O n e such clump is shown here. A
increased lung sounds can be heard over regions that are diagnosis of carcinoma was made. Note that a cytologic
consolidated. In a few patients, crackles and wheezes can be diagnosis of carcinoma should not be made if there is
auscultated. There may be evidence o f other organ involve concurrent inflammation. The surrounding lighter-staining
ment or hypertrophic osteopathy. cells are alveolar macrophages, the normal predominant
cell type in bronchoalveolar lavage fluid.
Diagnosis
Neoplasia is definitively diagnosed through the histologic or
cytologic identification of criteria o f malignancy i n popula
tions of cells i n pulmonary specimens (Fig. 22-5). Thoracic establish a diagnosis. Tracheal wash fluid cytology rarely
radiographs are c o m m o n l y evaluated initially, and findings results i n a definitive diagnosis. It is generally necessary to
can support a tentative diagnosis of neoplasia. Radiographs evaluate lung aspirates, bronchoalveolar lavage fluid, or lung
can also be used to identify the location of disease, and this biopsy specimens.
information helps the clinician select the most appropriate It may be appropriate to delay the collection o f p u l m o
technique for specimen collection. nary specimens i n asymptomatic animals with multifocal
Good-quality radiographs, including both left and right disease or animals with significant unrelated problems.
lateral projections, should be evaluated. Primary pulmonary Rather, radiographs are obtained again i n 4 to 6 weeks to
tumors can cause localized mass lesions (see Figs. 20-7 and document the progression o f lesions. Such delay is never
20-10) or the consolidation of an entire lobe (see Fig. 20-9, recommended i n dogs or cats with potentially resectable
A ) . T u m o r margins are often distinct but can be ill-defined disease.
as a result of associated inflammation and edema. Cavitation The confirmation o f malignant neoplasia i n other
may be evident. Metastatic or multicentric disease results i n organs i n conjunction with typical thoracic radiographic
a diffuse reticular, nodular, or reticulonodular interstitial abnormalities is often adequate for making a presumptive
pattern (see Fig. 20-8). In cats primary lung tumors often diagnosis o f pulmonary metastases. Overinterpretation o f
have a diffuse distribution by the time o f presentation, and subtle radiographic lesions should be avoided. Conversely,
the radiographic pattern may be suggestive of bronchitis, the absence o f radiographic changes does not eliminate the
edema, or pneumonia. possibility o f metastatic disease.
Pulmonary neoplasia is occasionally associated with hem Evaluation of the thorax by computed tomography
orrhage, edema, inflammation, infection, or airway occlu should be considered i n patients with k n o w n or suspected
sion that can contribute to the formation of alveolar patterns neoplasia. C o m p u t e d tomography is m u c h more sensitive
and consolidation. Lymphadenopathy, pleural effusion, or than thoracic radiography i n the detection o f metastatic
pneumothorax can also be identified by radiography i n some disease (see Chapter 20). In patients with localized disease
patients with neoplasia. for w h o m surgical excision is being planned, computed
Nonneoplastic disease, including fungal infection, lung tomography provides more detailed anatomic information
parasites, the aspiration of mineral o i l , eosinophilic granu regarding the involvement o f adjacent structures and is also
lomatosis, atypical bacterial infections, and inactive lesions more accurate i n identifying involvement of tracheobron
from previous disease, can produce similar radiographic chial l y m p h nodes, compared with radiography (Paoloni
abnormalities. Pulmonary specimens must be evaluated to et al., 2006).
Treatment PULMONARY HYPERTENSION
Solitary pulmonary tumors are treated by surgical resection.
To obtain clear margins, usually the entire l u n g lobe that is Etiology
involved must be excised. L y m p h node biopsy specimens, as Increased pulmonary arterial pressure (i.e., pulmonary sys
well as biopsy specimens from any grossly abnormal lung, tolic pressure >30 m m H g ) is called pulmonary hypertension.
are obtained for histologic analysis. The diagnosis is most accurately made by direct pressure
In animals with a large mass lesion, respiratory signs may measurements via cardiac catheterization, a procedure
abate after excision, even i f metastatic lesions are present rarely performed i n dogs or cats. A n estimation of pulmo
throughout the lungs. If the lesions cannot be removed sur nary artery pressure can be made by Doppler echocardiog
gically, chemotherapy can be attempted (see Chapter 77). N o raphy i n patients with pulmonary or tricuspid valvular
protocol is uniformly effective for the treatment o f primary insufficiency (see Chapter 6). The increasing availability of
lung tumors. this technology has increased awareness o f the existence
Metastatic neoplasms o f the lungs are treated with che of pulmonary hypertension i n veterinary medicine. Causes
motherapy. In most animals the initial protocol is deter of pulmonary hypertension include obstruction to venous
m i n e d by the expected sensitivity o f the primary tumor. drainage as can occur with heart disease (see Chapter 6),
Unfortunately, metastatic neoplasms do not always have the increased pulmonary b l o o d flow caused by congenital heart
same response to specific agents as the primary tumor. lesions (see Chapter 5), and increased pulmonary vascular
Multicentric tumors are treated with standard chemo resistance. Genetic factors may influence the occurrence of
therapeutic protocols, regardless o f whether the lungs are pulmonary hypertension i n some individuals but not i n
involved. Multicentric tumors are discussed i n Chapter 79. others with the same disease. W h e n no underlying disease
L y m p h o m a t o i d granulomatosis is treated with chemother can be identified to explain the hypertension, a clinical diag
apy designed to treat l y m p h o m a (see Chapter 80). nosis o f primary (idiopathic) pulmonary hypertension is
made.
Prognosis Pulmonary vascular resistance can be increased as a
The prognosis for animals with benign neoplasms is excel result of pulmonary thromboembolism (seep. 317) or heart-
lent, but these tumors are u n c o m m o n . The prognosis for w o r m disease (see Chapter 10). Vascular resistance can
animals with malignant neoplasia is potentially related to also be increased as a complication of chronic pulmonary
several variables, w h i c h include t u m o r histology, presence o f parenchymal disease, such as canine chronic bronchitis
regional l y m p h node involvement, and presence o f clinical (see p. 287) and idiopathic pulmonary fibrosis (see p. 312).
signs. Survival times o f several years are possible after surgi A simplistic explanation for increased vascular resistance
cal excision. Ogilvie et al. (1989) reported that o f 76 dogs as a complication o f pulmonary disease is the adaptive
with primary pulmonary adenocarcinoma, surgical excision response o f the lung to improve the matching of venti
resulted i n remission (i.e., elimination o f all macroscopic lation and perfusion ( V / Q ) through hypoxic vasoconstric
evidence o f tumor) i n 55 dogs. The median survival time o f tion. However, i n people other factors are thought to
dogs that went into remission was 330 days, whereas the contribute significantly to the development of hypertension
survival time i n dogs that d i d not achieve remission was 28 associated with pulmonary disease, including endothelial
days. A t the completion of the study, 10 dogs remained alive. dysfunction, vascular remodeling, and possibly thrombosis
M c N i e l et al. (1997) found that the histologic score o f the in situ.
tumor, presence o f clinical signs, and regional l y m p h node
metastases were significantly associated with the prognosis Clinical Features and Diagnosis
i n 67 dogs with primary l u n g tumors. M e d i a n survival times Pulmonary hypertension is diagnosed more commonly i n
for dogs with and without clinical signs were 240 and 545 dogs than cats. Clinical signs include those o f progressive
days, respectively. M e d i a n survival times for dogs with and hypoxemia and can be difficult to distinguish from any
without l y m p h node involvement were 26 and 452 days, underlying cardiac or pulmonary disease. Signs of pulmo
respectively. M e d i a n survival times for dogs with papillary nary hypertension include exercise intolerance, weakness,
carcinoma were 495 days, compared with 44 days for dogs syncope, and respiratory distress. Physical examination may
with other histologic t u m o r types. Survival times ranged reveal a l o u d split S heart sound (see Chapter 6). Radio
2
from 0 to 1437 days. A report o f 21 cats with primary lung graphic evidence of pulmonary hypertension may be present
tumors found a median survival time of 115 days after i n severely affected patients and includes pulmonary artery
surgery ( H a h n et al., 1998). Cats with moderately differenti enlargement and right-sided cardiomegaly. Radiographs are
ated tumors had a median survival time o f 698 days (range evaluated closely for underlying cardiopulmonary disease.
of 13 to 1526 days), whereas cats with poorly differentiated The diagnosis o f pulmonary hypertension is most often
tumors had a median survival time o f 75 days (range o f 13 made through Doppler echocardiography. Use of this modal
to 634 days). The prognosis for animals with multicentric ity to estimate pulmonary artery pressure requires the pres
neoplasms is not k n o w n to depend o n the presence or ence o f pulmonary or tricuspid regurgitation and a highly
absence o f pulmonary involvement. skilled echocardiographer.
Treatment
BOX 22-3
Pulmonary hypertension is best treated by identifying and
aggressively managing the underlying disease process. In Abnormalities Potentially Associated with Pulmonary
people pulmonary hypertension associated with chronic Thromboembolism*
bronchitis is usually m i l d and not directly treated. L o n g -
Surgery
term oxygen therapy is often provided, but this treatment is
Severe trauma
rarely practical for veterinary patients. Direct treatment can
Hyperadrenocorticism, Chapter 53
be attempted i n patients showing clinical signs o f pulmonary
Immune-mediated hemolytic anemia
hypertension i f no underlying disease is identified or Hyperlipidemia, Chapter 5 4
management fails to improve pulmonary arterial pressures. Glomerulopathies, Chapter 4 3
Unfortunately, little is k n o w n about the treatment of p u l m o Dirofilariasis and adulticide therapy, Chapter 10
nary hypertension i n animals, and adverse consequences can Cardiomyopathy, Chapters 7 and 8
occur through worsening of V / Q matching or other drug- Endocarditis, Chapter 6
related side effects. Therefore careful m o n i t o r i n g o f clinical Pancreatitis, Chapter 4 0
signs and pulmonary artery pressures is indicated. The drug Disseminated intravascular coagulation, Chapter 8 7
Clinical Manifestations of
the Pleural Cavity and
Mediastinal Disease
GENERAL CONSIDERATIONS
PLEURAL E F F U S I O N : FLUID C L A S S I F I C A T I O N A N D
DIAGNOSTIC APPROACH
PLEURAL EFFUSION: FLUID
Transudates and M o d i f i e d Transudates
CLASSIFICATION AND
Septic and Nonseptic Exudates
DIAGNOSTIC APPROACH
Chylous Effusions
The presence of pleural effusion i n a dog or cat is usually
Hemorrhagic Effusions
confirmed by thoracic radiography or thoracocentesis (see
Effusions Caused by Neoplasia
Chapter 24). In animals presented i n respiratory distress
PNEUMOTHORAX
with suspected pleural effusion, thoracocentesis is performed
MEDIASTINAL M A S S E S
immediately to stabilize the animal's condition before radio
PNEUMOMEDIASTINUM
graphs are taken. A l t h o u g h thoracocentesis is more invasive
than radiography, the potential therapeutic benefit of the
procedure far outweighs the small risk o f complications.
Animals i n stable c o n d i t i o n at presentation can be evaluated
GENERAL CONSIDERATIONS initially w i t h thoracic radiographs to confirm the presence
and location o f fluid before thoracocentesis is performed.
C o m m o n abnormalities of the pleural cavity i n the dog and Ultrasonography is a valuable tool for the evaluation of
cat include the accumulation of fluid (pleural effusion) or patients w i t h pleural effusion. If equipment is available o n
air (pneumothorax) i n the pleural space. Mediastinal masses site, animals i n critical condition can be examined ultraso
and pneumomediastinum are also discussed i n this chapter. nographically w i t h m i n i m a l stress to confirm both the pres
Respiratory signs caused by pleural disease result from inter ence of fluid and direct needle placement for thoracocentesis.
ference with normal expansion of the lungs. Exercise intoler Ultrasonography is also useful i n evaluating the thorax for
ance is an early sign; overt respiratory distress ultimately the presence o f mass lesions, hernias, and primary cardiac or
occurs. Physical examination findings that assist i n localizing pericardial disease. Because sound waves cannot pass through
the cause of respiratory compromise to the pleural space aerated lungs, any masses must be adjacent to the chest wall,
include increased respiratory rate and decreased lung sounds heart, or diaphragm to be detected by ultrasound. The pres
on auscultation (see Chapter 26). W i t h increasing c o m p r o ence of pleural fluid facilitates the ultrasonographic evalua
mise, increased abdominal excursions during breathing may tion of the chest. If the patient is stable, it is preferable to
be seen. Breathing effort may be increased during inspiration evaluate the thorax ultrasonographically before removing
relative to expiration, but this finding is not always obvious. the pleural fluid.
In cats with mediastinal masses, decreased compressibility o f Thoracic radiographs should be taken again after as m u c h
the anterior thorax may be palpable. Thoracic radiography, fluid or air as possible has been removed from the pleural
thoracocentesis, or both are performed to confirm the pres space and the lungs have had time to reexpand. Full expan
ence of pleural space disease. sion o f the lungs is required for accurate evaluation o f the
Pulmonary thromboembolism (PTE) can cause a pleural pulmonary parenchyma. The presence o f fluid also obscures
effusion. The effusion is generally m i l d and may be an visibility o f heart size and shape and mass lesions.
exudate or a modified transudate. P T E should be considered Cytologic analysis o f pleural fluid obtained by thoraco
as a diagnosis particularly i n patients whose respiratory centesis is indicated for the diagnostic evaluation o f all
TABLE 23-1
Diagnostic Approach in Dogs and Cats with Pleural Effusion Based on Fluid Type
FLUID TYPE C O M M O N DISEASE DIAGNOSTIC TESTS
Pure and modified Right-sided heart failure Evaluate pulses, auscultation, E C G , thor rad, echo
transudates Pericardial disease See right-sided heart failure
Hypoalbuminemia (pure transudate) Serum albumin concentrations
Neoplasia Thor rad and US, CT, thoracoscopy, thoracotomy
Diaphragmatic hernia Thor rad and US
Nonseptic exudates Feline infectious peritonitis (FIP) Pleural fluid cytology is generally sufficient. In questionable
cases available tests are many, but none has shown
good specificity for diagnosing FIP. Consider systemic
evaluation, ophthalmoscopic examination, serum or fluid
electrophoresis, coronavirus antibody titer, PCR of tissues
or effusion (see Chapter 97)
Neoplasia See Neoplasia above
Diaphragmatic hernia See Diaphragmatic hernia above
Lung lobe torsion Thor rad and US, bronchoscopy, thoracotomy
Septic exudates Pyothorax Gram staining, aerobic and anaerobic cultures, serial thor
rad
Chylous effusion Chylothorax See Box 25-1
Hemorrhagic effusion Trauma History
Bleeding disorder Systemic examination, coagulation tests (ACT, PT, PTT),
platelet count
Neoplasia See Neoplasia above
Lung lobe torsion See Lung lobe torsion above
ACT, Activated, clotting time; CT, computed tomography; ECG, electrocardiography; echo, echocardiography; PCR, polymerase chain
reaction; PT, prothrombin time; PTT, partial thromboplastin time; thor rad, thoracic radiography; US, ultrasonography.
animals with pleural effusion. Measurement o f the protein concentration of up to 3.5 g/dl and nucleated cell counts of
concentration and total nucleated cell count, as well as the up to 5000/l. The primary cell types include neutrophils as
qualitative assessment of individual cells, is essential for well as mononuclear cells.
accurately classifying the fluid, formulating a diagnostic Transudates and modified transudates form as a result of
plan, and initiating appropriate therapy (Table 23-1). increased hydrostatic pressure, decreased plasma oncotic
Pleural fluid is classified as a transudate, modified tran pressure, or a lymphatic obstruction. Increased hydrostatic
sudate, or exudate o n the basis o f protein concentration and pressure occurs i n association with right-sided congestive
nucleated cell count. Further classification o f fluid may be heart failure or pericardial disease. Physical examination
possible on the basis o f other cytologic or biochemical fea findings such as abnormal jugular pulses, gallop rhythms,
tures. Clinically useful fluid categories include septic exudate, arrhythmias, or m u r m u r s support a diagnosis of heart
chylous effusion, hemorrhagic effusion, and effusion caused disease. Heart sounds may be muffled i n animals with peri
by neoplasia. A l t h o u g h various types o f fluid have typical cardial effusions. Thoracic radiography (after fluid removal),
gross appearances (Fig. 23-1), reliance o n gross appearance electrocardiography, and echocardiography are indicated for
alone w i l l lead to the misclassification o f fluid and missed cardiac evaluation (see Chapter 2).
diagnoses (through the failure to identify organisms or Decreased plasma oncotic pressure is a result of hypoal
abnormal cell populations) i n some cases. In addition to the b u m i n e m i a . Effusions secondary to hypoalbuminemia alone
inflammatory cell types i n each cytologic category described are pure transudates, having very low protein concentra
in the subsequent sections, mesothelial cells are generally tions. Subcutaneous edema may be detected i n dependent
present and are often reactive. areas of the body. A decreased production of albumin causes
hypoalbuminemia i n patients with liver disease, and an
TRANSUDATES AND MODIFIED increased loss o f albumin causes it i n patients with glo
TRANSUDATES merulopathies or protein-losing enteropathies. The total
Pure transudates are fluids with l o w protein concentrations plasma protein concentration shown by refractometry
of less than 2.5 to 3 g/dl and l o w nucleated cell counts of less during the initial evaluation of the dog or cat can provide an
than 500 to 1000/l. The p r i m a r y cell types are mononuclear early indication o f hypoalbuminemia. Serum biochemical
cells, composed o f macrophages, lymphocytes, and mesothe analysis provides an exact measurement of the albumin
lial cells. Modified transudates have a slightly higher protein concentration. In general, albumin concentrations must be
FIG 2 3 - 1
Characteristic gross a p p e a r a n c e of the various types of pleural effusion. N o t e that
cytologic analysis should a l w a y s b e p e r f o r m e d to ensure a c c u r a t e classification of fluid
a n d to a v o i d missing d i a g n o s t i c o r g a n i s m s or neoplastic cells. A , Transudate. Fluid is
nearly clear. B , M o d i f i e d transudate. Fluid is slightly o p a q u e a n d , in this e x a m p l e , red-
tinged. C , N o n s e p t i c exudate. Fluid is more o p a q u e . The fluid s h o w n is from a c a t with
feline infectious peritonitis (FIP). FIP fluid is characteristically straw c o l o r e d with grossly
visible fibrin clots. D , Septic e x u d a t e . Fluid has a purulent a p p e a r a n c e , with cellular
debris gravitating t o w a r d the bottom of the tube. E, C h y l o u s effusion. Fluid is milky white.
F, H e m o r r h a g i c effusion. H e m o r r h a g i c effusions a r e bright to d a r k r e d . In this c a s e ,
cytologic e x a m i n a t i o n r e v e a l e d filamentous o r g a n i s m s demonstrating the i m p o r t a n c e of
cytologic a n a l y s i s .
lower than 1 g/dl before transudation occurs caused only findings do not entirely rule out the existence o f a tear i n the
because of hypoalbuminemia. diaphragm, however.
Lymphatic obstruction can be caused by neoplasia and Neoplasia must be considered as a differential diagnosis
diaphragmatic hernias. Diaphragmatic hernias should be for patients with any type of effusion, although it is rare for
suspected in any animal with a history of trauma. The trauma a pure transudate to develop. (See the section o n effusions
may have been recent or may have occurred years ago. caused by neoplasia for further discussion.)
Although a modified transudate usually forms as a result of
chronic diaphragmatic hernia, an exudative fluid can also be SEPTIC AND NONSEPTIC EXUDATES
found. Diaphragmatic hernias are identified by radiography Exudates have a high protein concentration (greater than
or ultrasonography. Occasionally, it is necessary to adminis 3 g/dl) compared with that i n transudates. Nucleated cell
ter barium orally and perform an upper gastrointestinal counts are also high (greater than 5000/l). Cell types i n
series or to intraperitoneally administer water-soluble iodin nonseptic exudates include neutrophils, macrophages, eosin
ated contrast media and perform peritoneography to confirm ophils, and lymphocytes. The macrophages and lymphocytes
the presence of a diaphragmatic hernia. N o r m a l imaging may be activated, and typically the neutrophils are nonde-
generative. There is no evidence o f organisms. Differential CHYLOUS EFFUSIONS
diagnoses i n animals with nonseptic exudates include feline Chylous effusion (chylothroax) results from the leakage of
infectious peritonitis (FIP), neoplasia, chronic diaphrag fluid from the thoracic duct, which carries lipid-rich lymph
matic hernia, lung lobe torsion, and resolving septic exu from the body. Such leakage can be idiopathic, congenital,
dates. Prior treatment with antibiotics i n animals with a or secondary to trauma, neoplasia, cardiac disease, pericar
septic effusion can alter the characteristics o f the neutrophil dial disease, dirofilariasis, lung lobe torsion, or diaphrag
population i n the fluid, making them appear nondegenera matic hernia. Chyle is usually milky white and turbid (see
tive, and decrease the number o f organisms present i n the Fig 23-1, E), largely as a result o f chylomicrons that carry fats
fluid to an undetectable level. Therefore pleural fluid analy from the intestines. The fluid is occasionally blood tinged,
sis should be performed before treatment is initiated so that although this finding may also be an artifact from prior
bacterial infection is not overlooked. thoracocentesis. It is also possible to obtain clear and color
Cats with FIP can present with fever or chorioretinitis i n less fluids, particularly i n anorectic animals, but this is
addition to respiratory signs (see Chapter 97). The pleural uncommon.
fluid protein concentration is often very high i n such animals, Chyle has the cytologic characteristics o f a modified tran
approaching serum concentrations. It is c o m m o n to see sudate or nonseptic exudate with moderate concentrations
fibrin strands or clots i n the fluid. Careful cytologic evalua of protein, usually greater than 2.5 g/dl. The nucleated cell
tion of the fluid is essential to differentiate FIP fluid from count is low to moderate, ranging from 400 to 10,000/l.
exudates caused by pyothorax or malignant l y m p h o m a . The Early i n the disease the predominant cell type is the small
evaluation of animals for diaphragmatic hernia was described lymphocyte. A few neutrophils may also be present. W i t h
i n the previous section and is described for neoplasia i n a time, nondegenerative neutrophils become more predomi
following section (i.e., Effusion Caused by Neoplasia). nant and there are fewer lymphocytes. Macrophages also
Spontaneous l u n g lobe torsions are most c o m m o n i n increase i n number with time, and plasma cells may be
dogs with deep, narrow thoracic cavities. In addition to present.
causing an effusion, torsions can be seen i n dogs and cats A diagnosis o f chylothorax is confirmed by measuring the
secondary to pleural effusion. Underlying pulmonary disease concentrations of triglycerides i n the pleural fluid and serum.
resulting i n lobe atelectasis can also contribute to the devel Each specimen should be well mixed by the laboratory before
opment o f torsion. T o r s i o n should be considered i n animals a portion is analyzed because o f the tendency for the lipid
with a preexisting effusion or pulmonary disease i f their portion to rise to the surface. The triglyceride content i n
condition suddenly deteriorates. The effusion is often a n o n - chyle is high compared with that i n serum. Rarely, the test
septic exudate, but it may be chylous or hemorrhagic. Signs w i l l need to be repeated after a meal i n anorectic animals.
of lung lobe torsion may be identified through thoracic radi M o s t cases o f chylothorax are idiopathic, but this diag
ography or ultrasonography (see Chapter 20). Bronchoscopy nosis can be made only after the other disorders have been
or thoracotomy is required to verify the condition i n some ruled out. Treatment is most likely to be successful i f an
animals. underlying problem is identified and treated directly. (See
Septic exudates often have extremely high nucleated cell Chapter 25 for a complete discussion of chylothorax.)
counts (e.g., 50,000 to more than 100,000/l), and degener
ate neutrophils are the predominant cells. Bacteria can often HEMORRHAGIC EFFUSIONS
be observed w i t h i n neutrophils and macrophages as well as Hemorrhagic effusions are grossly red as a result o f the large
extracellularly (see Fig. 25-1). The fluid may have a foul odor. red b l o o d cell content. Hemorrhagic effusions have greater
Septic exudates are diagnostic for pyothorax. Pyothorax can than 3 g/dl of protein and more than 1000 nucleated cells/l,
occur spontaneously, secondary to wounds that penetrate with a distribution similar to that o f peripheral blood. Over
into the thoracic cavity through the chest wall or esophagus, time the numbers o f neutrophils and macrophages increase.
secondary to migrating grass awns or other foreign bodies, Hemorrhagic effusions (except those obtained immediately
or as an extension of bacterial pneumonia. Sterile technique after bleeding into the thorax) are readily distinguished from
should be used during thoracocentesis and chest tube place the recovery o f peripheral blood through traumatic thora
ment i n all animals with pleural effusion or pneumothorax cocentesis by several features: hemorrhagic effusions have
to prevent iatrogenic infection. erythrophagocytosis and an inflammatory response on cyto
G r a m staining and both aerobic and anaerobic bacterial logic evaluation, hemorrhagic effusions do not clot, and the
cultures with antibiotic sensitivity testing should be per packed cell volume ( P C V ) o f hemorrhagic effusions is lower
formed on the fluid. Culture and sensitivity testing provide than that of peripheral blood.
valuable information that can be used for selecting appropri Hypovolemia and anemia may contribute to the clinical
ate antibiotics and m o n i t o r i n g therapy. M i x e d bacterial signs o f patients with hemothorax (see Chapter 26). H e m o
infections are c o m m o n . However, bacteria do not grow from thorax can result from trauma, systemic bleeding disorders,
cultures o f all septic exudates, and results are not available neoplasia, and lung lobe torsion. Rarely, septic exudates are
for several days. G r a m staining provides immediate informa grossly hemorrhagic (see Fig 23-1, F) and are distinguished
tion that can be used to help select antibiotics and is helpful cytologically. Respiratory distress caused by hemothorax
i n cases i n which bacteria cannot be grown from the fluid. may be the only clinical sign i n animals with some bleeding
disorders, including rodenticide intoxication. A n activated Leaks through the thoracic wall can occur after a trau
clotting time and platelet count should be performed early matic injury or as a result o f a faulty pleural drainage
in the evaluation o f these animals, followed by more specific system. A i r can also enter the thorax during abdominal
clotting tests (i.e., prothrombin time and partial thrombo surgery through a previously undetected diaphragmatic
plastin time). Hemangiosarcoma o f the heart or lungs is a hernia. These causes are readily identified.
common neoplastic cause o f a hemorrhagic effusion, but Pneumothorax resulting from pulmonary air can occur
malignant cells are rarely identified cytologically. Neoplastic after blunt trauma to the chest (i.e., traumatic pneumotho
effusions are discussed further i n the next section. rax) or as a result o f existing p u l m o n a r y lesions (i.e., spon
taneous pneumothorax). Traumatic pneumothorax occurs
EFFUSIONS CAUSED BY NEOPLASIA frequently, and the history and physical examination find
Neoplasia within the thoracic cavity can result i n most types ings allow this to be diagnosed. P u l m o n a r y contusions are
of effusion (modified transudates, exudates, chylous effu often present i n these animals.
sion, or hemorrhagic effusion). Neoplasms may involve any Spontaneous pneumothorax occurs when preexisting
of the intrathoracic structures, including the lungs, medias pulmonary lesions rupture. Cavitary l u n g diseases include
tinal tissues, pleura, heart, and l y m p h nodes. In some cases, blebs, bullae, and cysts, which can be congenital or idiopathic
neoplastic cells exfoliate from the tumor into the effusion, or result from prior trauma, chronic airway disease, or
and an early diagnosis can be made through fluid cytology. Paragonimus infection. Necrotic centers can develop i n
This is often possible i n patients with mediastinal l y m p h o m a . neoplasms, thromboembolized regions, abscesses, and gran
Unfortunately, other than i n cases o f lymphoma, it can be ulomas involving the airways, and these can rupture, allowing
difficult or impossible to establish a definitive diagnosis o f air to escape into the pleural space. (See Chapter 20 for
neoplasia on the basis o f cytologic findings i n the pleural further discussion o f cavitary lesions, and Chapter 25 for
fluid alone. Inflammation can result i n considerable hyper further discussion o f spontaneous pneumothorax.)
plastic changes of mesothelial cells that are easily confused Dogs and cats with pneumothorax and a recent history
with neoplastic cells. A cytologic diagnosis of neoplasia other of trauma are managed conservatively. Cage rest, the removal
than lymphoma should he made with extreme caution. of accumulating air by periodic thoracocentesis or by chest
In the majority of cases, neoplastic cells are not present tube, and radiographic m o n i t o r i n g are indicated. If abnor
in the fluid or a cytologic diagnosis cannot be made. T h o mal radiographic opacities persist without improvement for
racic radiography and ultrasonography should be performed more than several days i n trauma patients, further diagnos
to evaluate the thorax for evidence o f neoplasia (see Chapter tic tests should be performed, as described i n the section o n
24). Ultrasonography can be used to differentiate localized spontaneous pneumothorax (see Chapter 25).
accumulations of fluid from soft tissue masses. If soft
tissue masses are detected, aspirates or biopsy specimens
are obtained for cytologic or histopathologic evaluation. MEDIASTINAL MASSES
A definitive diagnosis cannot be made on the basis o f the
radiograph findings or ultrasound images alone. Mediastinal masses can cause inspiratory distress as a result
Diffuse neoplastic infiltration of the pleura and some of displacement o f lung tissue by the mass itself or by the
masses cannot be seen with these imaging techniques. secondary pleural effusion that may develop. A d d i t i o n a l
Repeated thoracic radiography, computed tomography, tho clinical signs such as coughing, regurgitation, and facial
racoscopy, or surgical exploration may be necessary i n such edema may also be present. Neoplasia is the primary dif
cases. ferential diagnosis. L y m p h o m a involving the mediastinum is
c o m m o n , particularly i n cats. Other types o f neoplasms
include t h y m o m a and rarely thyroid carcinoma, parathyroid
PNEUMOTHORAX carcinoma, and chemodectoma. Nonneoplastic mass lesions
such as abscesses, granulomas, hematomas, and cysts are
Pneumothorax is the accumulation of air i n the pleural other possibilities.
space. The diagnosis is confirmed by means o f thoracic radi Mediastinal masses i n cats can often be palpated during
ography. The pleural cavity is normally under negative pres gentle compression o f the anterior thorax. Radiographically,
sure, which keeps the lungs expanded i n health. However, mediastinal masses appear as soft tissue opacities i n the ante
if an opening forms between the pleural cavity and the rior mediastinum (Fig. 23-2). However, it can be difficult
atmosphere or the airways o f the lungs, air is transferred to accurately identify a mediastinal mass i f pleural fluid is
into the pleural space because of this negative pressure. present. Pleural fluid can both m i m i c the appearance of a
A tension pneumothorax occurs if a one-way valve is created mass and obscure its borders. Ultrasonography done before
by tissue at the site of leakage, such that air can enter into removal o f the pleural fluid is helpful i n identifying a mass
the pleural space during inspiration but cannot return to the and determining the extent to w h i c h surrounding structures
airways or atmosphere during expiration. Increased intra are involved.
pleural pressure and resultant respiratory distress occur Thoracocentesis and fluid analysis should be performed
quickly. i n animals with pleural effusion. L y m p h o m a can frequently
guide biopsy. Alternatively, sites for sampling can be deter
mined from two radiographic views of the thorax. The dorsal
mediastinal area and heart should be avoided when obtain
ing biopsy samples. A study by Lana et al. (2006) demon
strated the usefulness o f flow cytometry of mediastinal mass
aspirates i n differentiating l y m p h o m a from thymoma i n
dogs.
Surgical exploration or thoracoscopy may be necessary to
biopsy small lesions, cavitary lesions, and lesions adjacent to
the heart or main b l o o d vessels. Complete excision of the
mass should be attempted at that time, unless lymphoma is
diagnosed. (Specific recommendations for the management
of dogs and cats with mediastinal neoplasia are given in
Chapter 79)
PNEUMOMEDIASTINUM
Pneumomediastinum is identified radiographically. Subcu
taneous emphysema or pneumothorax can occur concur
rently or secondarily. Respiratory compromise most often
results from pneumothorax. Mediastinal air c o m m o n l y orig
inates from rupture or tears i n the trachea, bronchi, or
alveoli. These leaks can occur as a result of bite wounds of
the neck or sudden changes i n intrathoracic pressure result
ing from coughing, blunt trauma, or excessive respiratory
efforts against obstructed airways. Potential iatrogenic
causes include tracheal washing, tracheostomy, and endotra
cheal tube placement (usually caused by excessive endotra
cheal tube cuff pressure). A i r can also enter the mediastinum
FIG 2 3 - 2 through esophageal tears, generally resulting from foreign
V e n t r o d o r s a l v i e w of the t h o r a x of a c a t with a n anterior bodies.
m e d i a s t i n a l mass. Soft tissue o p a c i t y fills the a n t e r i o r Strict cage rest is indicated for animals with pneumo
m e d i a s t i n u m a n d o b s c u r e s the b o r d e r of the heart.
mediastinum to facilitate natural sealing of the tear. If air
continues to accumulate, causing respiratory compromise,
bronchoscopy should be performed to identify tracheal or
be diagnosed through the identification o f malignant cells in
bronchial lacerations that may require surgical repair.
the effusion. Transthoracic fine-needle aspiration or biopsy
can be performed to obtain specimens for microscopic eval Suggested Readings
uation o f the mass itself. Aspiration cytology is generally
Hardie E M et al: Tracheal rupture in cats: 16 cases (1983-1998),
performed initially, followed by biopsy i f a cytologic diagno
J Am Vet Med Assoc 214:508, 1999.
sis is not obtained. Transthoracic biopsy specimens can be Lana S et al: Diagnosis of mediastinal masses in dogs by flow
obtained relatively safely, particularly i f the lesion is solid cytometry, / Vet Intern Med 20:1161, 2006.
rather than cystic. Ultrasonography can be helpful i n deter Scott JA et al: Canine pyothorax: pleural anatomy and pathophysi
m i n i n g the consistency of the mass and can also be used to ology, Compend Contin Educ Pract Vet 25:172, 2003.
C H A P T E R 24
COMPUTED TOMOGRAPHY
As discussed i n Chapter 20, computed tomography is more
sensitive than radiographs for evaluating the thorax. It is
useful to determine the extent o f mass lesions prior to tho
racotomy and to increase the likelihood o f localizing cavitary
FIG 24-3 lesions i n patients with spontaneous pneumothorax.
Lateral thoracic r a d i o g r a p h o b t a i n e d in a d o g with pulmo
nary n e o p l a s i a a n d sternal a n d hilar l y m p h a d e n o p a t h y . The
sternal n o d e is the soft tissue o p a c i t y resting o n the c a u d a l
half of the s e c o n d sternebra. The hilar n o d e s a r e identified
THORACOCENTESIS
by the i n c r e a s e d soft tissue o p a c i t y a r o u n d the c a r i n a .
Several discrete p u l m o n a r y nodules a r e a l s o present. Thoracocentesis is indicated for the collection o f diagnostic
specimens i n dogs and cats with pleural effusion, for removal
of pleural fluid or air to stabilize the c o n d i t i o n o f dogs and
cats with impaired ventilation, and before radiographic
toward the abnormality. Space-occupying lesions can cause evaluation o f intrathoracic structures i n dogs and cats with
the mediastinum to shift i n the opposite direction. pleural fluid or air. Possible complications of thoracocentesis
The lymph nodes and heart are mediastinal structures but are pneumothorax caused by lung laceration, hemothorax,
are considered separately to ensure a careful evaluation. The and iatrogenic pyothorax. Complications are extremely rare
sternal nodes are located immediately dorsal to the sternum if careful technique is used.
near the thoracic inlet at the level of the first to third sterne- Thoracocentesis is performed with the animal in lateral
brae (Fig. 24-3). Enlargement is seen on lateral views and has or sternal recumbency, depending o n w h i c h position is
the appearance of a discrete mass lesion. The hilar nodes are less stressful. F l u i d or air is usually present bilaterally
located at the heartbase around the carina. Enlargement is throughout the pleural space and can be retrieved from the
seen as a generalized increased soft tissue opacity i n the seventh intercostal space (ICS) by placing the needle approx
perihilar region and is most easily seen o n the lateral view. imately two thirds of the distance from the costochondral
C o m m o n differential diagnoses for hilar lymphadenopathy junction toward the spine. If initial attempts are unsuccess
are lymphoma and fungal infections (especially histoplas ful, other sites are tried or the animal's position is changed.
mosis). Other differential diagnoses include metastatic F l u i d may be more successfully retrieved from gravity-
neoplasia, eosinophilic pulmonary granulomatosis, and dependent sites (i.e., closer to the costochondral junctions)
mycobacterial infections. A n y inflammatory disease can and air from nondependent sites. Thoracic radiographs are
potentially cause lymphadenopathy. Other considerations i n useful i n choosing sides for thoracocentesis i n the event o f
animals with an increased perihilar opacity o n radiographs unilateral effusions. Ultrasonography is useful for guiding
include atrial enlargement and heartbase tumors. needle placement i n patients i n w h i c h fluid collection proves
Evaluation of the heart is described i n Chapters 1 and 2. difficult.
Right-sided heart failure and pericardial effusion can cause A local anesthetic can be administered at the site o f tho
pleural fluid accumulation. racocentesis. Sedation is rarely required but may be useful
for decreasing patient stress. The site is shaved and surgically
prepared, and the procedure is performed using sterile tech
ULTRASONOGRAPHY nique. M o s t often, a butterfly catheter, three-way stopcock,
and syringe are used. The removal o f fluid or air by syringe
Ultrasonography is indicated i n the diagnostic evaluation o f is associated with movement o f the syringe, and the tubing
dogs and cats with pleural effusion to search for masses, of the butterfly catheter prevents this movement from affect
diaphragmatic hernia, lung lobe torsion, and cardiac disease. ing the position o f the needle within the thoracic cavity. A i r
Mediastinal masses, masses involving the pulmonary paren and most fluids can be retrieved through a 21-gauge but
chyma adjacent to the body wall, and masses extending into terfly catheter. A larger needle may be required to collect
the thorax from the body wall may be identified and their extremely viscous fluids, such as fluid from feline infectious
echogenicity evaluated. Ultrasonography can also be used to peritonitis or pyothorax. The three-way stopcock is attached
to the catheter to keep air from entering the thorax d u r i n g centesis and therapy for shock are performed to stabilize
emptying or changing o f the syringe. dogs and cats i n critical condition before chest tubes are
W i t h the syringe snugly attached and the stopcock open placed.
between the catheter and syringe (closed to r o o m air), the The major complication o f chest tubes is pneumothorax
needle is advanced through the skin only. The needle and caused by a leak i n the apparatus. Animals with chest tubes
skin are then moved about two rib spaces to the actual col- must be carefully monitored at all times to make sure that
lection site. This technique prevents air from entering the they do not disrupt the tubing connections, pull the tube
chest through the needle tract after the procedure (an part of the way out of the chest so that there are fenestrations
unlikely scenario). The needle is then advanced into the outside the body wall, or bite through the tubing. A n y leaks
thorax immediately i n front o f the rib to avoid the intercos- in the system can result i n a life-threatening pneumothorax
tal vessels and nerves. The needle is held with a hand resting within minutes. If an animal with a chest tube must be left
on the chest wall so that it will not move relative to the res- unattended, the tube should be clamped off close to the body
pirations or movement o f the animal. Slight negative pres- wall and should be well protected by bandage material.
sure is applied to the catheter by the syringe so that entry Hemothorax, iatrogenic pyothorax, and pneumothorax
into the pleural space is immediately identified by the recov- caused by lung laceration can also occur, but these problems
ery o f fluid or air. Once the needle has entered the pleural are generally prevented through the use of careful aseptic
space, the tip is aimed away from the l u n g by lowering the technique.
wings o f the catheter toward the body wall. Ideally, the bevel Pediatric chest tubes can be obtained from hospital supply
of the needle should face toward the lungs. companies. These tubes have multiple fenestrations, are
A n alternative to a butterfly catheter is an intravenous calibrated along their length, and are radiopaque. For treat-
over-the-needle catheter. In large dogs a 3 - or 5 - i n c h ing pyothorax, the tube should be as large as w i l l fit between
(8- or 13-cm) 14- to 16-gauge catheter can be used. These the ribs. The size of the tube is less critical for control o f
catheters are soft and produce less trauma than butterfly pneumothorax. Before placement the end of the tube is
catheters while i n the pleural space and permit the animal occluded with a syringe adapter, a three-way valve, and a
to be repositioned or rolled to improve fluid or air removal. hose clamp (Fig. 24-4, A ) .
The longer length, compared with a butterfly needle, may Sterile technique is used during placement of the chest
be needed to reach the pleural space i n large-breed or obese tube. In an animal with unilateral disease, the tube is placed
dogs. A few side holes can be added to the distal end o f the in the involved side o f the thorax. Either side can be used i n
catheter using a surgical blade and sterile technique to an animal with bilateral disease. The lateral side of the animal
increase the sites where fluid can enter. The holes should be over the caudal rib cage is shaved and surgically prepared.
spaced far apart, should not take up more than one fifth o f The animal is anesthetized or heavily sedated. If the animal
the circumference o f the catheter, and should have no rough is sedated, a local anesthetic is placed subcutaneously at the
edges because the catheter might then break off in the animal tenth ICS and within the subcutaneous tissues, intercostal
during removal. Extension tubing and a three-way stopcock muscles, and pleura at the seventh ICS. The dorsoventral
are attached to the catheter immediately after placement. A orientation is one half to two thirds the distance from the
small skin incision, just slightly larger than the catheter, w i l l costochondral junction to the thoracolumbar musculature.
facilitate placement. A s with the butterfly catheter, slight This distance should correspond to the level where the ribs
negative pressure is maintained by syringe so that entry into are maximally bowed.
the pleural space is immediately identified. The catheter tip The length o f tube to be advanced into the chest must be
is then directed cranially to allow positioning of the catheter determined from thoracic radiographs or by external land-
between the lungs and chest wall, preventing trauma to the marks o n the animal. The tube should extend from the tenth
lung tissue. ICS to the first rib. The fenestrations i n the tube must not
After fluid specimens are saved for cytologic and m i c r o - extend outside the point o f exit from the pleural cavity.
biologic analysis, as m u c h fluid or air as possible is removed, A stab incision is made through the skin at the tenth ICS.
except i n patients with acute hemothorax (see Chapter 26). A purse-string suture is then placed around the opening but
is not tied. Some chest tubes made for humans contain a
stylet. Smaller chest tubes are inserted with the aid of curved
CHEST TUBES: INDICATIONS AND hemostats. The tip o f the tube is grasped with the tip o f the
PLACEMENT hemostats with the tube parallel to the body of the clamps
(see Fig. 24-4, B).
Chest tube placement is indicated for the treatment o f dogs The tube, with the stylet or hemostats, is then tunneled
and cats with pyothorax (see Chapter 25). Chest tubes are subcutaneously from the tenth to the seventh ICS. If hemo-
also indicated for the management o f pneumothorax i f air stats are used, the tips are directed away from the animal's
continues to accumulate despite multiple thoracocenteses. body (see Fig. 24-4, C). Once the tip reaches the seventh
Chest tubes provide a means to prevent fluid and air from ICS, the stylet or hemostats are raised perpendicular to the
accumulating i n the pleural space until the underlying cause chest wall. The p a l m o f the hand is placed over the end of
of the pleural disorder resolves. If possible, needle thoraco- the stylet or the hemostat handles, and the tube is thrust
tube from being withdrawn i f tension is accidentally applied
to the tubing. The opening in the skin is covered with a
sterile sponge with antiseptic ointment. A light wrap is
placed around the tube to hold it against the chest wall. The
wrap must not be too tight. A wrap that is too tight can greatly
decrease chest wall compliance and increase the work of
breathing i n these compromised animals. The hose clamp is
placed o n the tube between the animal and the three-way
valve to further protect against pneumothorax whenever
suction is not being applied to the tube. A n Elizabethan
collar is always placed o n the animal because a single bite
through the tube can be fatal.
Thoracic radiographs are taken to evaluate the tube posi
tion and the effectiveness of drainage. T w o views must be
evaluated. Ideally, the tube should extend along the ventral
FIG 2 4 - 5 aspect o f the pleural space to the thoracic inlet. The most
After a n assistant pulls the skin f o r w a r d , a n i n c i s i o n c a n b e important sign o f adequate tube placement is the absence of
m a d e through the skin at the seventh intercostal s p a c e a n d areas o f persistent fluid or air accumulation. If areas of fluid
blunt dissection is used to r e a c h the p l e u r a . A chest tube or air persist, it may be necessary to replace the tube or place
c a n b e p o p p e d into the p l e u r a l s p a c e with m i n i m a l t r a u m a
a second tube i n the opposite side.
to the u n d e r l y i n g l u n g . W h e n the skin is r e l e a s e d , the tube
Once a chest tube is i n place and is determined to be i n
will c o u r s e through a s u b c u t a n e o u s tunnel to prevent a i r
leaks a r o u n d the tube. a satisfactory position, its effectiveness must be monitored
regularly by thoracic radiography, generally every 24 to 48
hours. The animal must also be monitored for the develop
through the body wall with one rapid m o t i o n (see Fig. ment of secondary complications. These include infection
24-4, D). Once the tube has entered the pleural space, it is and the leakage o f air. The bandage should be removed at
quickly advanced forward until the predetermined length least daily. The site where the tube enters the skin should
has entered the chest while the stylet or hemostats are w i t h be evaluated for signs o f inflammation or subcutaneous
drawn (see Fig. 24-4, E). emphysema. The tube and skin sutures should be examined
A n alternative technique can be used to m i n i m i z e trauma for signs o f m o t i o n . The skin around the tube is kept clean,
to the lungs caused when thrusting the tube through the and a sterile sponge is replaced over the entry site of the tube
body wall. In this technique, after the skin incision has been before rebandaging. Stopcock ports should be protected with
made and a purse-string suture placed, an assistant standing sterile caps when not i n use. Gloves should be w o r n and the
at the head of the animal draws the skin o f the thorax crani stopcock ports wiped with hydrogen peroxide before use.
ally to p u l l the skin opening forward from the tenth to the
seventh ICS (Fig. 24-5). W i t h the skin held i n this position,
hemostats are used to bluntly dissect through the thoracic THORACOSCOPY AND THORACOTOMY
and intercostal musculature to the pleura. A t this point the
chest tube with the stylet or hemostats is easily popped A definitive diagnosis for the cause o f pleural effusion is
through the pleura into the chest with m i n i m a l force. The sometimes elusive. In such cases, thoracoscopy or thoracot
tube is then advanced and the skin released. o m y may be necessary to allow visual assessment of the
A i r will be sucked into the pleural cavity d u r i n g tube thoracic cavity and the collection o f specimens for histologic
placement regardless o f the method used. This air must be and bacteriologic analysis. Mesotheliomas and pleural carci
immediately removed through the tube using a 35-ml nomatosis are often diagnosed through these methods.
syringe. The purse-string suture is then tied around the tube.
Immediately external to the skin entrance, the tube is attached Suggested Readings
to the body wall by suturing the tape that is formed as a DeRycke L M et al: Thoracoscopic anatomy of dogs positioned in
butterfly around the tube to the skin o n either side o f it (see lateral recumbency, J Am Anim Hosp Assoc 37:543, 2001.
Fig. 24-4, F) or by using a Chinese finger trap suture around Suter PF: Thoracic radiography, Wettswil, Switzerland, 1994, Peter F
the tube and attached to the skin. This prevents the chest Suter.
C H A P T E R 25
Disorders of the
Pleural Cavity
treatment of pyothorax. A l t h o u g h treatment with antibiotics be necessary depending o n the viscosity o f the pleural fluid
alone often causes dramatic improvement i n the animal's and the collapsibility o f the tubes. The collection systems
clinical c o n d i t i o n initially, the signs generally recur, and must be carefully monitored for the occurrence of leaks or
complications o f the prolonged infection, such as fibrosis or malfunctions that could cause a fatal pneumothorax.
abscesses, are more likely (Fig. 25-2). Indwelling chest tubes Intermittent suction by syringe is ideally performed every
provide the best drainage and can be used to keep the exudate 2 hours for the first days of treatment, with arrangements
from accumulating d u r i n g the initial days o f antibiotic made for drainage to continue during the night. W i t h i n a
therapy. Dogs and cats i n critical condition at presentation few days the volume o f fluid produced will decrease, and the
are stabilized through the use o f needle thoracocentesis and interval can then be lengthened. If such intensive care is not
shock therapy before chest tube placement. Intermittent possible, an effort should still be made to empty the chest of
needle thoracocentesis is m i n i m a l l y effective for draining fluid at least once late i n the evening to m i n i m i z e the accu
the pleural cavity and is not recommended for treatment mulation o f exudate overnight.
unless the owner cannot afford the expense o f chest tube Lavage o f the chest cavity is performed twice daily and
management. consists of the removal of any fluid within the chest, followed
Chest tube placement and assessment o f positioning by the slow infusion o f warmed sterile saline solution into
are discussed i n Chapter 24. A n i m a l s probably respond most the chest. A volume of approximately 10 ml/kg of body
rapidly to constant suctioning o f the exudate from the chest, weight is infused, but the infusion should be discontinued
although intermittent suction is certainly adequate and often if any distress is noted. After this the animal is gently rolled
FIG 25-3
Cytologic preparation of a specimen of a pleural effusion from a cat being treated
successfully for pyothorax with chest tube drainage and antibiotics. Compared with the
fluid shown in Fig. 25-1, the nucleated cell count is low, the neutrophils are nondegenera
tive, organisms are not present, and mononuclear cells are appearing (Cytocentrifuge prep).
from side to side, and the fluid is removed. Sterile technique phils w i l l persist but should no longer appear degenerative
is used throughout the procedure. The volume recovered (Fig. 25-3). W h e n these criteria have been met and no pockets
should be about 75% o f the volume infused. If less fluid is of fluid are seen o n thoracic radiographs, the chest tube
retrieved, this may indicate that the chest tube is no longer is removed and the animal is m o n i t o r e d clinically for at
providing adequate drainage and should be assessed by least 24 hours for the development o f pneumothorax or
radiograph or ultrasonography. There is no obvious benefit the recurrence o f effusion. Thoracic radiographs can be
from the addition o f antibiotics, antiseptics, or enzymes to taken to more sensitively evaluate the animal for these
the lavage solution. The addition of heparin (1500 U / 1 0 0 m l ) potential problems.
to the lavage fluid may decrease fibrin formation. Thoracic radiographs are evaluated 1 week after removal
A l l adapter ports connected to the chest tube should be of the chest tube and 1 week and 1 m o n t h after discontinu
covered with sterile caps when not i n use. W h e n accessing ation of the antibiotic therapy. These radiographs are
the ports, the clinician should wear gloves and remember to obtained so that a localized nidus o f disease such as a foreign
wipe the ports with hydrogen peroxide before use. body or an abscess can be identified and also so that recur
Thoracic radiographs are taken every 24 to 48 hours to rence o f a pyothorax can be detected before large volumes
ensure that the chest is being completely drained o f fluid. of pleural fluid accumulate. Such niduses are often invisible
Failure to monitor the effectiveness o f drainage radiograph when large volumes o f pleural fluid are present or while
ically can lead to costly prolongation o f the intensive care aggressive therapy is i n progress.
required for maintenance o f the chest tube. Exploratory thoracotomy is indicated for the removal of
Serum electrolyte concentrations are also monitored. a suspected nidus o f infection and i n those animals that do
M a n y dogs and cats with pyothorax are dehydrated and ano not respond to medical therapy. In the latter instance surgery
rectic at presentation and require intravenous fluid therapy. may be necessary to remove fibrotic and diseased tissue or a
Supplementation of the intravenous fluid with potassium foreign body. Failure to respond is suggested by the contin
may be necessary. ued need for a chest tube for longer than 1 week after the
The decision to discontinue drainage and remove the start o f appropriate antibiotic treatment and drainage,
chest tube is based o n the fluid volume and cytologic char although reported cases that have undergone complete
acteristics. The volume o f fluid recovered should have recovery after medical management have required drainage
decreased to less than 2 ml/kg/day. Slides o f the fluid are by chest tubes for longer periods. Furthermore, persistence
prepared daily and evaluated cytologically. Bacteria should of large pockets o f fluid i n spite of appropriate chest tube
no longer be visible intracellularly or extracellularly. N e u t r o placement may necessitate the decision to perform a thora-
cotomy earlier. C o m p u t e d tomography o f the chest may be be identified i n most animals, i n which case idiopathic chy
a more sensitive method for detecting persistent pulmonary lothorax is diagnosed.
lesions than thoracic radiography. Rooney et al. (2002) rec Fibrosing pleuritis and pericarditis can be associated with
ommended consideration for thoracotomy particularly i n chylothorax. Cats, i n particular, may develop fibrosing pleu
dogs that have radiographic evidence o f mediastinal or p u l ritis, w h i c h can interfere with normal expansion of the lungs
monary lesions or i f Actinomyces spp. are identified i n the even after thoracocentesis. Inflammation and thickening of
pleural fluid. the pericardium could contribute to the further formation
of chylous effusion.
Prognosis
M o s t cases o f pyothorax are idiopathic. The prognosis for Clinical Features
animals w i t h pyothorax is fair to good i f it is recognized early Chylothorax can occur i n dogs or cats o f any age. Afghan
and treated aggressively. W a d d e l l et al. (2002) reported a H o u n d s and Shiba Inus appear to be predisposed to the
survival rate for cats o f 66%, excluding those that were disorder. The primary clinical sign is respiratory distress
euthanatized before treatment. In their report, 5 o f 80 cats typical o f pleural effusion. Although the distress is often
required thoracotomy. Treatment success i n dogs has been acute i n onset, more subtle signs have generally been present
reported to be as high as 100% w i t h medical therapy alone for more than a month. Lethargy, anorexia, weight loss, and
(Piek et al., 2000). However, i n a study by Rooney et al. exercise intolerance are c o m m o n . In some cases cough is the
(2002) o f 26 dogs, only 25% of dogs were successfully treated only presenting sign.
medically whereas 78% responded favorably to thoracotomy.
One possible explanation for the poor success o f medical Diagnosis
management i n the latter study is the geographic location Chylothorax is diagnosed by thoracic radiographs and the
in a region o f the country where grass awn migration is identification o f chyle through cytologic and biochemical
common. evaluation o f pleural fluid obtained by thoracocentesis (see
Exploratory surgery is necessary to ensure complete reso Chapter 23). Lymphopenia and panhypoproteinemia may be
lution o f the problem i n dogs or cats w i t h foreign bodies i n present i n peripheral blood.
the thoracic cavity. Radiolucent foreign bodies can be diffi Once chylothorax has been diagnosed, further diagnostic
cult to find, however, and the prognosis for pyothorax sec tests are performed to identify potential underlying disease
ondary to them is more guarded. Long-term complications (Box 25-1). These tests include thoracic ultrasonography;
of pyothorax such as pleural fibrosis and restrictive lung echocardiography; microfilarial examination and adult
disease are u n c o m m o n . antigen testing for heartworm disease; and, i n cats, the mea
surement o f thyroid hormone concentrations. Lymphangi
ography can be used to identify lymphangiectasia, sites of
CHYLOTHORAX obstruction, and, rarely, sites of leakage from the thoracic
duct. Lymphangiography is performed before the surgical
Etiology ligation o f lymphatics is attempted.
Chylothorax is the accumulation of chyle w i t h i n the thoracic
cavity. The chyle originates from the thoracic duct, w h i c h Treatment
carries triglyceride-rich fluid from the intestinal lymphatics Thoracocentesis and appropriate fluid therapy are used to
and empties into the venous system i n the anterior thorax. stabilize dogs and cats w i t h chylothorax, as needed, at pre
The fluid also contains lymphocytes, protein, and fat-soluble sentation. Electrolyte abnormalities may be present. A con
vitamins. Thoracic duct rupture after thoracic trauma can certed effort is made to identify any underlying cause of
result i n transient chylothorax. However, most cases are not the chylothorax so that it can be directly treated. Elimination
the result o f a ruptured duct. Possible causes o f nontrau of the underlying problem may result i n resolution of the
matic chylothorax include generalized lymphangiectasia, chylothorax, although medical management (as described
inflammation, and obstruction o f lymphatic flow. Flow can later for idiopathic chylothorax) is generally required for
be obstructed for physical reasons, such as neoplasia, or as a several weeks or even months. The exception is chylothorax
result o f increased venous pressures. of traumatic origin, w h i c h generally resolves within 1 to 2
Chylothorax can be categorized as congenital, traumatic, weeks.
or nontraumatic. A congenital predisposition may exist i n A routinely successful treatment for idiopathic chylotho
animals i n w h i c h chylothorax develops later i n life. T r a u rax has not been established. Medical management is ini
matic events that induce chylothorax can be surgical (e.g., tially attempted because spontaneous remission occurs i n
thoracotomy) or nonsurgical (e.g., being hit by a car). N o n some cases. In the absence of resolution with medical therapy,
traumatic causes o f chylothorax include neoplasia, par thoracic duct ligation and pericardectomy are recommended.
ticularly mediastinal l y m p h o m a i n cats; cardiomyopathy, M e d i c a l management consists primarily o f intermittent
dirofilariasis, pericardial disease, and other causes o f right- thoracocentesis and a low-fat diet. Thoracocentesis is per
sided heart failure; lung lobe torsion; diaphragmatic hernia; formed as needed on the basis o f the owner's observation of
and systemic lymphangiectasia. N o underlying disease can increased respiratory rate or effort or decreased activity or
macrophage function. The resorption o f effusion may
BOX 25-
thereby be enhanced and fibrosis o f the pleura m i n i m i z e d .
Diagnostic Tests to Identify Underlying Diseases in Dogs The drug is available over the counter at health food stores.
and Cats with Chylothorax A dosage o f 50 to 100 m g / k g given orally every 8 hours is
recommended.
Complete Blood Count, Serum Biochemical
Surgical management is considered i f clinical signs have
Panel, Urinalysis
not i m p r o v e d w i t h i n 2 to 3 months o f medical therapy or
Evaluation of systemic status if signs are intolerable. The recommended surgical manage
Cytologic Examination of Fluid ment o f chylothorax includes thoracic duct ligation and
pericardectomy. Thoracic duct ligation is technically difficult
Infectious agents
and is ideally performed by an experienced surgeon. M u l t i
Neoplastic cells (especially lymphoma)
ple ligations o f the thoracic duct and its collaterals are per
Thoracic Radiographs (After Fluid Removal) formed. The ducts are identified by lymphangiography
Anterior mediastinal masses before surgery, and lymphangiography is repeated after liga
Other neoplasia tion to assess the success o f ligation. Pericardectomy is rec
Cardiac disease ommended at the time o f thoracic duct ligation and is
Heartworm disease associated with an improved outcome (Fossum et al., 2004).
Pericardial disease Placement o f pleuroperitoneal or pleurovenous shunts or
Ultrasonography (Ideally, in the Presence of Fluid) mesh w i t h i n the diaphragm to allow fluid to drain away from
the pleural space has also been recommended for the m a n
Anterior mediastinum
agement o f chylothorax and should be considered i f medical
Mass
and surgical treatment are unsuccessful. These drainage p r o
Heart (echocardiography)
Cardiomyopathy cedures provide a route for the leaking chyle to reenter the
Heartworm disease circulation without producing the respiratory compromise
Pericardial disease associated w i t h pleural effusion. Unfortunately, drains often
Congenital heart disease become nonfunctional w i t h i n months o f placement.
Other fluid densities adjacent to body wall
Neoplasia Prognosis
Lung lobe torsion The prognosis for chylothorax has generally been regarded
as guarded unless the chylothorax was traumatically induced
Heartworm Antibody and Antigen Tests
or the result o f a reversible c o n d i t i o n . However, a study by
Heartworm disease
Fossum et al. (2004) indicated an overall success rate for
Lymphangiography thoracic duct ligation and pericardectomy o f 100% i n dogs
and 90% i n cats. It is not possible to predict the contribution
Preoperative and postoperative assessment of thoracic
duct of fibrosing pleuritis to clinical signs i n cats w i t h this c o m
plication. In cats w i t h continued respiratory difficulties fol
lowing resolution o f effusion, decortication o f the l u n g is
considered.
appetite. Initially, thoracocentesis may need to be performed
every 1 to 2 weeks. The interval between thoracocenteses w i l l
gradually lengthen if the chylothorax is responsive to medical SPONTANEOUS PNEUMOTHORAX
management. Ultrasound guidance o f the needle during
thoracocentesis is especially helpful i n removing pockets o f Spontaneous pneumothorax occurs when preexisting p u l
chyle from the pleural cavity, and by increasing the effective monary cavitary lesions rupture. It is m u c h less c o m m o n
ness of drainage, it can prolong the interval between thora than traumatic pneumothorax and occurs more often i n
cocenteses. dogs than cats. Rapid, profound respiratory distress occurs
A low-fat, nutritionally complete diet is fed (see Chapter i n the subset o f animals i n w h i c h a tension pneumothorax
54). In humans medium-chain triglyceride o i l is absorbed develops. Cavitary lesions can be congenital or idiopathic
directly into the bloodstream, bypassing the lymphatics, and or result from p r i o r trauma, chronic airway disease (e.g.,
can be used as a fat supplement. Unfortunately, i n dogs these idiopathic feline bronchitis), or Paragonimus infection.
triglycerides have been shown to enter the thoracic duct. Necrotic centers can develop i n neoplasms, thromboembo
Nevertheless, they can be added to the diet i f additional lized regions (e.g., from dirofilariasis), abscesses, and granu
calories are desired. lomas involving the airways, and these can rupture, allowing
Medical management may be facilitated by the adminis air to escape into the pleural space. (See Chapter 20 for
tration of rutin, a benzopyrone drug. R u t i n has been used i n further discussion o f cavitary lesions.)
humans for the treatment of lymphedema. It is thought to Thoracocentesis is useful for initial stabilization o f the
decrease the protein content o f the effusion by affecting animal's condition. If frequent thoracocentesis is needed to
thorax). In large dogs a one-way H e i m l i c h valve can be used
rather than suction.
Regardless of the treatment used, recurrence is a possibil
ity. Accurate diagnosis o f the underlying lung disease and
determination o f the extent o f involvement through a tho
racotomy assist i n determining the prognosis.
NEOPLASTIC EFFUSION
Neoplastic effusions resulting from mediastinal l y m p h o m a
are treated with radiation or chemotherapy (see Chapter 80).
Effusions caused by mesothelioma or carcinoma of the
pleural surfaces may respond to palliative therapy with intra
cavitary infusions o f cisplatin or carboplatin (see M o o r e ,
1992). Placement of pleuroperitoneal shunts or intermittent
FIG 25-4 thoracocentesis to alleviate the degree o f respiratory c o m
Blebs c a n b e seen in this intra-operative i m a g e of the lung promise can also be considered to prolong the life of patients
of a d o g that p r e s e n t e d with s p o n t a n e o u s p n e u m o t h o r a x . that have no clinical signs beyond those resulting from the
The s i z e of these b l e b s p r e c l u d e d their identification b y
accumulation o f pleural effusion.
either t h o r a c i c r a d i o g r a p h y o r c o m p u t e d t o m o g r a p h y .
(Courtesy Dr. G u i l l a u m e Pierre C h a n o i t . )
Suggested Readings
A u J) et al: Use of computed tomography for evaluation of lung
control the pneumothorax, a chest tube is placed (see Chapter lesions associated with spontaneous pneumothorax in dogs: 12
24). Dogs and cats are evaluated for underlying disease with cases (1999-2002), } Am Vet Med Assoc 228:733, 2006.
thoracic radiographs (repeated after full lung expansion), Fossum T W et al: Chylothorax in cats: 37 cases (1969-1989), ] Am
computed tomography o f the thorax, multiple fecal exami Vet Med Assoc 198:672, 1991.
Fossum T W et al: Chylothorax associated with right-sided heart
nations for Paragonimus ova (see Chapter 20), heartworm
failure in 5 cats, / Am Vet Med Assoc 204:84, 1994.
tests, and possibly tracheal wash fluid analysis or bronchos
Fossum TW: Small animal surgery, ed 3, St Louis, 2007, Mosby.
copy. C o m p u t e d tomography is m u c h more sensitive for the
Holtsinger R H et al: Spontaneous pneumothorax in the dog: a
identification o f bullae or blebs and should be performed retrospective analysis of 21 cases, ] Am Anim Hosp Assoc 29:195,
before thoracotomy. In a study by A u et al. (2006), thoracic 1993.
radiography identified bullae or blebs i n only 2 o f 12 dogs Lipscomb VJ et al: Spontaneous pneumothorax caused by pulmo
with spontaneous pneumothorax whereas computed tomog nary blebs and bullae in 12 dogs, J Am Anim Hosp Assoc 39:435,
raphy was successful i n identifying lesions i n 9 o f these 2003.
dogs. Moore AS: Chemotherapy for intrathoracic cancer in dogs and cats,
Patients w i t h Paragonimus infections generally respond to Problems in Vet Med 4:351, 1992.
medical treatment (See Chapter 22). Otherwise, surgical Piek CJ et al: Pyothorax in 9 dogs, Vet Q 22:107, 2000.
Puerto D A et al: Surgical and nonsurgical management of and
therapy is indicated for most animals. In a review of 21 cases,
selected risk factors for spontaneous pneumothorax in dogs: 64
Holtsinger et al. (1993) found that most dogs w i t h spontane
cases (1986-1999), J Am Vet Med Assoc 220:1670, 2002.
ous pneumothorax managed medically w i t h chest tubes and
Rooney M B et al: Medical and surgical treatment of pyothorax
suction ultimately required surgery during the initial hospi
in dogs: 26 cases (1991-2001), / Am Vet Med Assoc 221:86,
talization or u p o n subsequent recurrence o f pneumothorax 2002.
to resolve the problem. Because unobserved recurrence of Scott JA et al: Canine pyothorax: clinical presentation, diagnosis,
spontaneous pneumothorax can be fatal, conservative treat and treatment, Compend Contin Educ Pract Vet 25:180, 2003.
ment is believed to carry more risk than surgery. Further Smeak D D et al: Treatment of chronic pleural effusion with pleu
more, a report o f 64 cases by Puerto et al. (2002) showed that roperitoneal shunts in dogs: 14 cases (1985-1999), ] Am Vet Med
recurrence and mortality rates for dogs w i t h spontaneous Assoc 219:1590, 2001.
pneumothorax were lower i n dogs that had surgery c o m Thompson MS et al: Use of rutin for the medical management of
idiopathic chylothorax in four cats, J Am Vet Med Assoc 215:245,
pared w i t h dogs that were treated conservatively. A median
1999.
sternotomy is generally recommended to allow exposure o f
Waddell LS et al: Risk factors, prognostic indicators, and outcome
all lung lobes because it is often not possible to localize all
of pyothorax in cats: 80 cases (1986-1999), J Am Vet Med Assoc
cavitary lesions preoperatively (Fig. 25-4). A b n o r m a l tissue 221:819, 2002.
is evaluated histologically and microbiologically for a defin Walker A L et al: Bacteria associated with pyothorax of dogs and
itive diagnosis. cats: 98 cases (1989-1998), J Am Vet Med Assoc 216:359, 2000.
Conservative therapy consists o f cage rest and chest tube White H L et al: Spontaneous pneumothorax in two cats with small
placement w i t h continuous suction (see the section o n pyo airway disease, J Am Vet Med Assoc 222:1573, 2003.
C H A P T E R 26
Emergency Management
of Respiratory Distress
Upper A i r w a y Obstruction: Decreases Anxiety a n d Lessens Respiratory Efforts, Decreasing Negative Pressure
within Upper Airways
Hydromorphone Dogs 0.05 m g / k g IV, IM; can repeat IV q3mim to effect; duration, 2-4 hr
Cats 0.025-0.05 m g / k g IV, IM; can repeat IV q3min to effect but stop if mydriasis
occurs; duration, 2-4 hr
Butorphanol Cats 0.1 m g / k g IV, IM, SQ; can repeat IV q3min to effect; duration, 1-6 hr
Buprenorphine Dogs and cats 0.005 m g / k g IV, IM; repeat to effect; duration, 4-8 hr
TABLE 26-1
Localization of Respiratory Tract Disease by Physical Examination Findings in Dogs and Cats with Severe
Respiratory Distress
PLEURAL
SPACE
LARGE AIRWAY DISEASE P U L M O N A R Y P A R E N C H Y M A L DISEASE DISEASE
EXTRATHORACIC OBSTRUCTIVE
(UPPER) INTRATHORACIC OBSTRUCTIVE RESTRICTIVE A N D RESTRICTIVE
T, Slightly increased; , increased; , markedly increased; i , decreased; N1, normal. Normal respiratory rates for dogs and cats at rest
are 20/min. In the hospital setting, rates of 30/min are generally accepted as normal.
(see Table 26-1). Excursions o f the chest may be increased or stertor is usually heard, generally during inspiration.
(i.e., deep breaths are taken). Breath sounds are often A history o f voice change may be present with laryngeal
increased. disease.
Laryngeal paralysis and brachycephalic airway syndrome
EXTRATHORACIC (UPPER) are the most c o m m o n causes o f upper airway obstruction
AIRWAY OBSTRUCTION (see Chapter 18). Other laryngeal and pharyngeal diseases
Patients w i t h extrathoracic (upper) airway obstruction typ are listed i n Boxes 16-1 and 16-2. Severe tracheal collapse can
ically have the greatest breathing effort d u r i n g inspiration, result i n extrathoracic or intrathoracic large airway obstruc
w h i c h is generally prolonged relative to expiration. Stridor t i o n or both. Rarely, other diseases o f the extrathoracic
obstruction typically have the greatest breathing effort
during expiration, which is generally prolonged relative to
inspiration. The most c o m m o n cause o f intrathoracic large
airway obstruction is collapse o f the mainstem b r o n c h i
and/or intrathoracic trachea (tracheobronchomalacia; see
Chapter 21). A high-pitched, wheezing, coughlike sound is
often heard during expiration i n these patients, and crackles
or wheezes may be auscultated. Other differential diagnoses
include foreign body, advanced Oslerus infection, tracheal
neoplasia, tracheal stricture, and bronchial compression by
extreme hilar lymphadenopathy.
Sedation, oxygen supplementation, and m i n i m i z i n g stress
as described for the management o f upper airway obstruc
FIG 26-1 tion are often effective i n stabilizing these patients as well.
Patients with extrathoracic (upper) a i r w a y obstruction often H i g h doses o f hydrocodone or butorphenol w i l l provide
present in acute respiratory distress b e c a u s e of a progres cough suppression and sedation (see Chapter 21). Dogs w i t h
sive w o r s e n i n g of a i r w a y obstruction after a n e x a c e r b a t i n g
chronic bronchitis may benefit from bronchodilators and
event. M e d i c a l intervention is n e a r l y a l w a y s successful in
corticosteroids.
b r e a k i n g this c y c l e a n d s t a b i l i z i n g the patient's respiratory
status.
Ancillary Therapy:
Oxygen Supplementation
and Ventilation
From Court M H et al: Inhalation therapy: oxygen administration, humidification, and aerosol therapy, Vet Clin North Am Small Anim Pract
15:1041, 1985.
* After cage is filled, flow is adjusted based on oxygen concentration as measured by oxygen sensor.
FIG 2 7 - 2
D o g with intranasal catheter in p l a c e for delivery of o x y g e n .
The catheter is sutured to the m u z z l e less than 1 c m from its
exit from the naris a n d is further a n c h o r e d with sutures to
FIG 2 7 - 1 the face s o that it exits b e h i n d the a n i m a l ' s h e a d . A n
A n o x y g e n h o o d c a n b e used for recumbent a n i m a l s a s a E l i z a b e t h a n c o l l a r is routinely used to prevent the a n i m a l
substitute for a n o x y g e n mask. In this patient o x y g e n is from r e m o v i n g the catheter.
b e i n g d e l i v e r e d through a n o p e n i n g in the top of the h o o d ,
a n d the light blue o p e n i n g that will a c c o m m o d a t e s t a n d a r d
anesthesia tubing is left o p e n for circulation of air. R e g a r d with nasal secretions, however. Soft red rubber or infant
less of the method used to i n c r e a s e the o x y g e n in inspired feeding tubes or polyurethane catheters can be used. Tube
air, a m e a n s for e s c a p e of e x p i r e d C O is essential.
2
size is based o n patient size. In general, a 3.5 to 5 French tube
( D i s p o s a - H o o d , Utah M e d i c a l Products, Inc., M i d v a l e , Utah.)
is used for cats, and a 5 to 8 French tube is used for dogs.
The method o f placement has been described by
Fitzpatrick et al. (1986). First, the length o f tubing to be
oxygen mask. A means for escape o f exhaled air must always inserted into the nasal cavity is measured against the head
be provided to prevent the buildup o f C O 2 within the hood. of the animal. The tubing should reach the level of the car
nassial tooth. Sedation is rarely necessary. A water-soluble
NASAL CATHETERS lubricant or 0.2% lidocaine jelly is applied to the length of
Nasal catheters can be used for long-term oxygen supple the catheter that will be within the nasal cavity. Next, 0.2%
mentation (Fig. 27-2). The animal is relatively free to move lidocaine is dripped gently into the nasal cavity through the
and is accessible for evaluation and treatment. M o s t animals naris with the animal's nose pointed upward. The catheter is
tolerate the catheter well. Catheters can become obstructed then passed through the naris, initially aimed dorsomedially
through the naris, then immediately ventromedially. Once TRACHEAL TUBES
the correct length o f catheter has been inserted, it is gently Tracheal tubes are placed through the tracheal rings and
bent beneath the lateral cartilage and sutured to the muzzle are readily tolerated by conscious animals. It is rare that an
no farther than 1 c m caudal to the exit from the naris. The animal requires an emergency tracheostomy. Nearly all such
catheter can be further anchored to the face with sutures, animals can be stabilized using other techniques. Thus tra
traveling between the eyes to behind the animal's head. A n cheal tubes can be placed using a careful, sterile surgical
Elizabethan collar is placed on the patient to prevent the technique. Tracheal tubes are generally used for the manage
animal from removing the catheter. ment o f animals with an upper airway obstruction. R o o m
A sterile intravenous set can be connected to the catheter. air often contains adequate oxygen for use i n animals with
The intravenous line can be attached to a half-filled bottle an upper airway obstruction once the obstruction has been
of sterile saline solution and positioned above the fluid level. bypassed.
Oxygen is then delivered through the bottle, below the fluid The tube itself should have a diameter nearly as wide as
level, providing some moisture as the oxygen bubbles through the tracheal lumen and a length o f 5 to 10 rings. It is neces
the saline. sary to use high-volume, low-pressure cuffs to prevent tra
cheal damage and subsequent stricture. D o u b l e - l u m e n tubes
TRANSTRACHEAL CATHETERS are ideal for this method. The inner tube can be removed for
Oxygen can be administered through a jugular catheter cleaning and replaced easily. Single-lumen tubes also work
placed with a sterile technique through the trachea. This and may be necessary i n small animals.
approach is particularly useful for the emergency stabi Tracheal tubes are usually placed with the animal anes
lization o f animals with an upper airway obstruction. thetized with a short-acting agent. The trachea is exposed
Branditz et al. (1989) have described a method for cardio through a ventral midline incision made just beneath the
pulmonary resuscitation that can be performed by one larynx. The trachea is entered through an incision made a
person by administering oxygen at a high flow rate o f few rings below the cricoid cartilage, parallel to the trachea
15 L / m i n through a tracheal catheter. In this method a large and perpendicular to the rings, and through just enough
jugular catheter is placed as described for transtracheal rings to allow passage o f the tube. Either end o f the incision
washing (see Chapter 20). can be widened with a small transverse incision. Stay sutures
are placed on each side o f the incision to facilitate initial
ENDOTRACHEAL TUBES placement o f the tube as well as later replacement i f the
Endotracheal tubes are used to administer oxygen during tube is accidentally or intentionally removed. The tube is
surgical procedures and cardiopulmonary resuscitation. then inserted into the opening. W i t h m i n i m a l pressure o n
They can be used to bypass most upper airway obstructions the airway, it is tied with gauze around the neck o f the
for emergency stabilization. Pure oxygen can be adminis animal. Few or no sutures are used to close the incision to
tered for short periods. Longer supplementation requires prevent the collection o f air subcutaneously. A gauze sponge
the mixing of 100% oxygen with r o o m air. Ventilation can with a slit cut i n it and coated with antiseptic ointment can
be provided with a cuffed endotracheal tube. T r a u m a to the be placed over the incision and around the tube.
trachea is decreased through the use o f high-volume, low- The tube must be monitored for obstruction and
pressure cuffs and by inflating the cuff with the least amount cleaned. The inner tube o f double-lumen tubes can be easily
of pressure necessary to create a seal. If positive-pressure removed for this purpose. The tube is cleaned every 30 to
ventilation is not being used, the cuff can remain deflated. 60 minutes initially, with the interval increased as less
Because endotracheal tubes are not tolerated by alert secretions accumulate. Sterile technique is used when han
animals, tracheal tubes are preferred for long-term manage dling the tubes, and they must be replaced i f they become
ment. Conscious animals i n which endotracheal tubes are contaminated.
used must be given sedatives, analgesics, paralyzing agents, Single-lumen tubes are difficult to remove and replace
or a combination of these drugs. The combination o f hydro safely for the first few days unless stay sutures are left i n place.
morphone and diazepam is adequate i n some animals. Pen Periodic cleaning can be performed with the tube i n place.
tobarbital, administered intravenously to effect, can be added Sterile saline solution is instilled into the tube for this
if necessary. The combination o f ketamine and Valium may purpose. T o perform suctioning, a sterile urinary catheter
be safer for the initial intubation o f patients that are hypox with several openings at the end is attached to a suction unit
emic. Following intubation and improvement i n hypoxemia, and passed through the tube. The trachea and tracheal tube
morphine and pancuronium can be given. are then suctioned to remove secretions. Suctioning is per
The cuff should be deflated when possible to m i n i m i z e formed for short intervals to allow the lungs to reinflate.
tracheal damage. The tube must be cleaned periodically to Cleaning is performed every few hours initially, then less
remove secretions (see the recommendations for tracheal frequently i f secretions are not accumulating.
tube cleaning), and frequent flushing o f the oral cavity is A smaller tube can be used once the animal is able to
performed. Moisture must be added to the inspired gases, as oxygenate adequately with r o o m air. The tube can be removed
previously discussed. when the animal can oxygenate by breathing around a small
tube with the lumen obstructed. The incision is allowed to Animals with severe lung disease may be unable to main
heal without suturing. The tip o f the tube is cultured for tain adequate oxygenation without ventilatory support.
bacteria. Positive-pressure ventilation is routinely necessary for the
Antibiotics are not administered prophylactically. A n y management of patients with acute respiratory distress syn
existing infection or infections that occur during therapy are drome ( A R D S ; see Chapter 22, p. 319). As previously noted,
treated on the basis o f culture and sensitivity information. the long-term administration o f air with an oxygen concen
tration greater than 50% results i n serious lung damage. If
OXYGEN CAGES the PaO cannot be maintained at greater than 60 m m H g
2
Oxygen cages provide an oxygen-enriched environment without excessive oxygen supplementation, ventilatory
with m i n i m a l stress to animals. However, the animal is support is indicated.
isolated from direct contact, which can be a disadvantage. The delivery o f air by positive pressure is different from
Other environmental factors, such as humidity, temperature, the normal inhalation of air by negative pressure. W i t h pos
and carbon dioxide concentration, must be monitored and itive pressure, the distribution of ventilation within the lungs
controlled or extreme stress and even death can occur. The is altered. The intrathoracic pressure increases each time the
animal is totally dependent on proper cage function. The lungs are filled with air, which results i n decreased venous
ability o f the cage to maintain the correct environment varies return to the heart. A l o n g with other effects, systemic hypo
with the specific cage as well as with each animal. C o m m e r tension results and can be severe enough to cause acute renal
cial cages are available for veterinary use. Incubators from failure. Compliance o f the lungs also decreases over time i n
h u m a n hospitals can be modified for small animals. animals receiving positive-pressure ventilation. As the lungs
become stiffer, greater pressures are necessary to expand
them. Careful m o n i t o r i n g o f animals is essential during ven
VENTILATORY SUPPORT tilation. Important variables to monitor include blood gas
values, compliance, mucous membrane color, capillary refill
The purposes o f ventilatory support are to decrease the time, pulse quality, arterial blood pressure, central venous
retention o f carbon dioxide and to improve oxygenation. pressure, lung sounds, and urine output. The extensive
Ventilatory support is labor intensive and associated with nursing care and monitoring required for these patients
complications, however. It is used when other means o f usually limit the use o f long-term ventilatory support to
respiratory support are not adequate. large referral hospitals.
The retention o f carbon dioxide, or hypercapnia, occurs
i n animals that are unable to ventilate adequately. Spontane Suggested Readings
ous ventilation can be impaired by neurologic dysfunction, Branditz FK et al: Continuous transtracheal oxygen delivery during
such as that w h i c h occurs with severe head trauma, polyneu cardiopulmonary resuscitation: an alternative method of ventila
ropathies, and some toxicities. Ventilatory support is recom tion in a canine model, Chest 95:441, 1989.
mended i n such animals i f the PaCO level increases to more
2
Court M H et al: Inhalation therapy: oxygen administration, humid
than 60 m m H g . Hypoventilation caused by a pleural effu ification, and aerosol therapy, Vet Clin North Am Small Anim
sion or pneumothorax is treated by removing the fluid or Pract 15:1041, 1985.
air, not by positive-pressure ventilation. Hypoventilation Fitzpatrick RK et al: Nasal oxygen administration in dogs and cats:
experimental and clinical investigations, ] Am Anim Hosp Assoc
caused by an upper airway obstruction is treated by estab
22:293, 1986.
lishing a patent airway.
McKiernan BC: Principles of respiratory therapy. In Kirk RW,
A n i m a l s with cerebral edema, usually caused by trauma, editor: Current veterinary therapy VIII, Philadelphia, 1983, WB
may benefit from ventilatory support to maintain the PaCO 2
Saunders, p 216.
within 20 to 30 m m H g . The resultant decrease i n b l o o d flow Moon PF et al: Mechanical ventilation. In Kirk RW et al, editors:
to the brain may decrease the total intracranial volume, Current veterinary therapy XI, Philadelphia, 1992, WB Saunders,
thereby decreasing pressure on the brain. p 98.
Drugs Used i n Respiratory Disorders
Acepromazine 0.05 IV, IM, S C (maximum, 4 mg) 0.05 IV, IM, S C (maximum, 1 mg)
Amikacin Amiglyde 5-10 IV, S C q8h Same
Aminophylline 11 P O , IV, IM q8h 5 P O , IV, IM q12h
Amoxicillin Amoxi-tab 22 P O q8-12h Same
Amoxi-drop
Amoxicillin-clavulanate Clavamox 20-25 P O q8h Same
Ampicillin 22 P O , IV, S C q8h Same
Ampicillin-sulbactam Unasyn 22 m g / k g (ampicillin) IV q8h Same
Atropine 0.05 S C Same
Azithromycin Zithromax 5-10 m g / k g P O q24h for 3 days, 5-10 m g / k g P O q24h for 3 days,
then q 4 8 - 7 2 h then q72h
Butorphanol Torbutrol 0.5 P O q6-l 2h (antitussive) Not recommended
Cefazolin 20-25 IM, IV q8h Same
Cephalexin Keflex 20-40 P O q8h Same
Cetirizine Zyrtec 1 P O q24h
Chloramphenicol 5 0 P O , IV, S C q8h 10-15 P O , IV, S C q12h
Chlorpheniramine Chlor-Trimeton 4-8 m g / d o g q8-12h 2 mg/cat q8-l 2h
Clindamycin Antirobe 5.5-11 P O , IV, S C q12h Same
Cyclophosphamide Cytoxan 2
5 0 m g / m P O q48h Same
Cyproheptadine Periactin 2 mg/cat P O q12h
Dexamethasone Azium 0.1-0.2 IV q l 2 h Same
Dextromethorphan 1-2 P O q6-8h Not recommended
Diazepam Valium 0.2-0.5 IV
Diphenhydramine Benadryl 1 IM; 2-4 P O Same
Doxycycline 5-10 P O , IV q12h Same
Enrofloxacin Baytril 10-20 P O , IV, S C q24h
Fenbendazole (for Panacur 25-50 m g / k g P O q12h for 14 Same
lungworms) days
Furosemide Lasix 2 P O , IV, IM q8-12h Same
Glycopyrrolate 0.005 IV, S C Same
Heparin 200-300 U / k g S C q8h Same
Hydrocodone bitartrate Hycodan 0.25 P O q6-12h Not recommended
Hydromorphone 0.05 IV, IM; can repeat IV q3min 0.025-0.05 IV, IM; can repeat IV
to effect; duration 2-4h q3min to effect; stop if
mydriasis occurs
Itraconazole (for Sporanox 5 PO q l 2 h with food
aspergillosis)
Ivermectin See text for specific parasites See text for specific parasites
Ketamine Ketaset Vetalar 2-5 IV
Lysine 5 0 0 mg/cat P O q l 2 h
Marbofloxacin Zeniquin 3-5.5 P O q24h Same
Meropenem Merrem IV 8 IV, S C q8h Same
Methylprednisolone acetate Depo-Medrol 10 mg/cat IM q2-4 weeks
Metronidazole Flagyl 10 PO q8h 10 PO q l 2 h
0.5-1 P O q7-10d for 3 treatments
Milbemycin (for nasal mites) Interceptor -
Morphine 0.1 IV; repeat q3min to effect;
duration l-4h
Oxtriphylline Choledyl 14 P O q8h
Oxymetazoline 0.025% Afrin (0.025%) 1 drop/nostril q24h for 3 days,
then withhold for 3 days
Phenylephrine 0.25% Neo-Synephrine 1 drop/nostril q24h for 3 days,
(0.25%) then withhold for 3 days
Praziquantel (for Droncit 23 P O q8h for 3 days Same
Paragonimus)
Continued
Drugs Used in Respiratory Disorderscont'd
GENERIC N A M E TRADE N A M E DOGS (mg/kg*) CATS ( m g / k g * )
A
PART THREE DIGESTIVE S Y S T E M DISORDERS
M i c h a e l D. W i l l a r d
C H A P T E R 28
Clinical Manifestations of
Gastrointestinal Disorders
Causes of Dysphagia
O r a l Pain O r a l Mass
exclude disease. Subtle masses or those dorsal to the larynx caused by n o r m a l oral flora. Biopsies o f these lesions are
may sometimes be aspirated more accurately w i t h ultraso often not done aggressively because they bleed profusely and
nographic guidance. M u l t i p l e aspirations are usually done are hard to suture. The clinician should avoid major vessels
before a wedge or p u n c h biopsy is performed. (e.g., the palatine artery) and use silver nitrate to stop hem
Incisional biopsy specimens must include generous orrhage. It is better to have difficulty stopping hemorrhage
amounts o f submucosal tissues. M a n y oral tumors cannot be after obtaining an adequate biopsy specimen than less
diagnosed o n the basis o f findings from superficial biopsy difficulty stopping hemorrhage after obtaining a nondiag
specimens because o f superficial necrosis and i n f l a m m a t i o n nostic specimen. If diffuse oral mucosal lesions are noted,
search carefully for vesicles (e.g., pemphigus), and i f these graphic studies (e.g., cinefluoroscopy or fluoroscopy) are
are found, remove them intact for histopathologic and best for detecting and defining neuromuscular dysphagia. If
immunofluorescent studies. If vesicles are not found, then at neuromuscular problems are seemingly ruled out by these
least two or three tissue samples representing a spectrum o f radiographic studies, then anatomic lesions and occult causes
new and old lesions should be submitted for analysis. of pain (e.g., soft tissue inflammation or infection) must be
If oral examination findings are not helpful, plain oral reconsidered.
and laryngeal radiographs are usually the best next steps.
Oral cultures are rarely cost-effective because the n o r m a l
oral flora makes interpretation of the results difficult. Even DISTINGUISHING REGURGITATION
animals with severe halitosis or stomatitis secondary to bac FROM VOMITING
terial infection rarely benefit from bacterial culture, unless FROM EXPECTORATION
there is a draining tract or abscess.
Halitosis often accompanies dysphagia, i n w h i c h case it is Regurgitation is the expulsion o f material (i.e., food, water,
usually more productive to determine the cause o f the dys saliva) from the mouth, pharynx, or esophagus. It must be
phagia. If halitosis occurs without dysphagia, the clinician differentiated from v o m i t i n g (the expulsion of material from
should first be sure that the odor is abnormal and then check the stomach and/or intestines) and expectoration (the expul
for the ingestion o f odoriferous substances (e.g., feces). A sion o f material from the respiratory tract). Historical and
thorough oral examination is still the most important test. physical examination findings sometimes allow differentia
Halitosis not attributable to an oropharyngeal lesion may be tion o f these three (Table 28-1). Expectoration is generally
originating from the esophagus. Contrast-enhanced radio associated with coughing at the time o f the event. However,
graphs or esophagoscopy may reveal the presence o f tumors because dogs that cough and gag excessively may stimulate
or retained food secondary to stricture or weakness. If the themselves to v o m i t as well, careful history taking is i m p o r
history and oral examination are unrevealing except for the tant. Animals that regurgitate and occasionally those that
finding of mild-to-moderate tartar accumulation, the teeth vomit may cough as a result o f aspiration, but oral expulsion
should be cleaned to try to alleviate the problem. is not consistently correlated with coughing in these patients.
Drooling is usually caused by nausea, oral pain, or dys The criteria i n Table 28-1 are only guidelines. Some
phagia. The approach to the diagnosis of oral pain and dys animals that appear to be regurgitating are v o m i t i n g and vice
phagia is described under the appropriate headings. Nausea
is considered in the section on vomiting.
Dysphagic animals without demonstrable lesions or pain
may have neuromuscular disease. Dysphagia of muscular TABLE 2 8 -
origin usually results from atrophic myositis (see Chapter
Aids to Differentiate Regurgitation from Vomiting*
31). The finding of swollen, painful temporal muscles sug
gests acute myositis. The combination o f severe temporal- SIGN REGURGITATION VOMITING
masseter muscle atrophy and difficulty opening the m o u t h
Prodromal n a u s e a t No Usually
(even when the animal is anesthetized) is suggestive o f
Retching No Usually
chronic temporal-masseter myositis. Biopsy o f affected
Material produced
muscles is indicated, but the clinician must ensure that
Food
muscle tissue is retrieved; it is easy to obtain only fibrous scar No
Bile
tissue. It may help to have serum analyzed for antibodies to Blood (undigested) (digested or
type 2 M muscle fibers, a finding consistent with masticatory undigested)
muscle myositis but not polymyopathy. A m o u n t of material A n y amount A n y amount
Neurogenic dysphagia is caused by disorders i n the oral Time relative to Anytime Anytime
(i.e., also called prehensile), pharyngeal, or cricopharyngeal eating
phases of swallowing (disorders o f the latter two phases are Distention o f c e r v i c a l No
discussed in the section on regurgitation). Rabies should esophagus
Dipstick analysis of
always be considered, despite its relative rarity. After rabies
material
is presumptively ruled out, cranial nerve deficits (especially
pH >7 <5 or >8
deficits of cranial nerves V , V I I , I X , XII) should be consid
Bile No
ered. Because the clinical signs vary depending o n the nerve
(or nerves) affected, a careful neurologic examination must T h e s e a r e guidelines that often help distinguish v o m i t i n g from
be done. regurgitation. However, occasional animals will require plain a n d /
FIG 28-1
G e n e r a l d i a g n o s t i c a p p r o a c h to r e g u r g i t a t i o n in the d o g a n d cat.
BOX 28-5
Box 28-4
Causes of Esophageal Obstruction Causes of Esophageal Weakness
C o n g e n i t a l Causes
Congenital Causes
Causes o f V o m i t i n g
M o t i o n Sickness (Acute)
Cicatrix
Diet
Torsion/volvulus
Dietary indiscretion
Gastrointestinal/Abdominal Inflammation
Dietary intolerance
(Acute o r Chronic)
Emetogenic Substances (Acute)
I n f l a m m a t o r y b o w e l disease
Drugs: almost a n y d r u g c a n cause v o m i t i n g (especially d r u g s Gastritis
a d m i n i s t e r e d o r a l l y [PO]), but the f o l l o w i n g d r u g s seem espe without ulcers/erosions
cially likely to cause v o m i t i n g : with ulcers/erosions
Digoxin non-obstructing f o r e i g n b o d y
Cyclophosphamide Enteritis (acute)
Cisplatin Parvovirus
Dacarbazine H e m o r r h a g i c gastroenteritis
Doxorubicin Parasites (acute o r c h r o n i c ) , especially Physaloptera
Erythromycin Pancreatitis
Penicillamine Peritonitis (acute o r chronic)
TetracycIine/doxycycline Colitis (acute o r chronic)
A m o x i c i l l i n clavulanic a c i d
Nonsteroidal antiinflammatory drugs E x t r a a l i m e n t a r y Tract Diseases (Acute o r Chronic)
Xylazine Uremia
Toxic chemicals A d r e n a l insufficiency
Strychnine Hypercalcemia
H e a v y metals H e p a t i c insufficiency o r disease
Cholecystitis
G a s t r o i n t e s t i n a l Tract O b s t r u c t i o n (Acute o r Chronic)
Diabetic ketoacidosis
Gastric o u t f l o w obstruction Pyometra
Benign p y l o r i c stenosis Endotoxemia/septicemia
Foreign o b j e c t
M i s c e l l a n e o u s Causes (Acute o r Chronic)
G a s t r i c a n t r a l mucosal h y p e r t r o p h y
Neoplasia Dysautonomia
N o n n e o p l a s t i c infiltrative disease ( e . g . , pythiosis) Feline h y p e r t h y r o i d i s m
Gastric m a l p o s i t i o n i n g Postoperative nausea
Gastric dilation o r volvulus (see nonproductive retching) Overeating
Partial gastric d i l a t i o n / v o l v u l u s (does not a l w a y s cause Idiopathic hypomotility
clinical signs) Central nervous system disease
Intestinal "Limbic" e p i l e p s y
Foreign o b j e c t Tumor
N o n l i n e a r objects Meningitis
Linear objects Increased i n t r a c r a n i a l pressure
Neoplasia Sialoadenitis/sialoadenosis*
Intussusception Behavior
tinal (GI) tract obstruction, (4) abdominal (especially (i.e., red) or partially digested (i.e., "coffee grounds" or
alimentary tract) i n f l a m m a t i o n or irritation, and (5) extra- "dregs").
gastrointestinal tract diseases that may stimulate the m e d u l In animals w i t h acute v o m i t i n g without hematemesis, the
lary v o m i t i n g center or the chemoreceptor trigger zone (Box clinician should first search for obvious causes (e.g., inges
28-6). Occasionally, central nervous system ( C N S ) disease, tion o f a foreign body, intoxication, organ failure, parvovi
behavior, and learned reactions to specific stimuli may rus) as well as for secondary fluid, electrolyte, or acid-base
cause v o m i t i n g . If the cause o f the v o m i t i n g is not apparent abnormalities or sepsis that require prompt, specific therapy.
o n the basis o f the history and physical examination findings, If the animal's c o n d i t i o n seems stable and there is no obvious
the next step depends o n whether the v o m i t i n g is acute cause, symptomatic treatment is often used for 1 to 3 days.
or chronic and whether there is hematemesis (Figs. 28-2 If the a n i m a l is too sick for the clinician to take a chance on
and 28-3). Remember that b l o o d i n vomitus m a y be fresh guessing wrong, i f the v o m i t i n g persists for 2 to 4 days after
FIG 2 8 - 2
G e n e r a l d i a g n o s t i c a p p r o a c h to v o m i t i n g in the d o g a n d c a t . C B C , C o m p l e t e b l o o d
count; FeLV, feline leukemia virus; FIV, feline i m m u n o d e f i c i e n c y virus; CSF, c e r e b r o s p i n a l
f l u i d ; EEG, e l e c t r o e n c e p h a l o g r a m ; MRI, m a g n e t i c resonance i m a g i n g .
the start of symptomatic therapy, or if the condition worsens objects, masses, pancreatitis, peritonitis, poor serosal con
during this initial time, then more aggressive diagnostic trast i n the region o f the pancreas, free abdominal fluid, or
testing is usually indicated. free abdominal gas. A b d o m i n a l ultrasonography can be
The clinician should search for historical evidence o f the more revealing than plain radiographs; however, radiographs
ingestion of foreign objects, toxins, inappropriate food, or may be more sensitive i n revealing some foreign bodies. A
drugs. Physical examination is used to look for abdominal C B C , serum biochemistry profile, and urinalysis are also
abnormalities (e.g., masses), linear foreign objects caught indicated. Cats should be tested for feline leukemia virus,
under the tongue, and evidence of extraabdominal disease feline immunodeficiency virus, and hyperthyroidism. It may
(e.g., uremia, hyperthyroidism). The clinician should always be necessary to measure serum bile acid concentrations (or
consider the possibility o f linear foreign bodies i n v o m i t i n g b l o o d a m m o n i a concentrations) or perform an A C T H -
cats and carefully examine the base o f the tongue. Chemical stimulation test (or at least resting serum Cortisol concentra
restraint (e.g., ketamine H C l , 2.2 mg/kg of body weight given tions) to identify hepatic or adrenal insufficiency that is not
intravenously) may be necessary to examine this area prop indicated by results o f routine serum biochemistry profiles.
erly. The abdomen is palpated to search for masses or pain, If results o f the C B C , chemistry profile, urinalysis, and
but even careful palpation may miss short ileocolic intus routine abdominal imaging are not diagnostic, the next step
susceptions i n the craniodorsal area o f the abdomen. It is is usually either contrast-enhanced abdominal radiography
reasonable to perform fecal examination for parasites because or endoscopy plus biopsy. Endoscopy is usually more cost-
they can be the cause of vomiting. If a cause cannot be found effective than contrast-enhanced radiography i n v o m i t i n g
and the animal is not unduly ill, the clinician may prescribe patients. D u r i n g endoscopy the clinician should biopsy the
a therapeutic trial (e.g., pyrantel and a dietary trial; see Table stomach and duodenum, regardless o f the gross mucosal
30-7 and Chapter 30). Therapeutic trials should be designed appearance. In cats endoscopic biopsy o f the ileum and
so that the failure of a treatment allows the clinician to ascending colon may be required to reveal the cause of v o m
exclude at least one disease and then look for others. iting. If laparotomy is chosen over endoscopy, the entire
If acute vomiting does not respond to symptomatic abdomen should be examined and biopsy o f the stomach,
therapy or i f the animal is so sick that the clinician cannot duodenum, jejunum, ileum, mesenteric l y m p h node, liver,
take a chance on symptomatic therapy being ineffective, and, i n cats, the pancreas should be performed.
aggressive diagnostic testing is indicated. Animals with acute If the cause o f v o m i t i n g is undiagnosed after biopsy, the
or chronic vomiting without hematemesis should undergo basis for previously excluding the different diseases should
abdominal imaging (i.e., radiography, ultrasonography) to be reviewed. Diseases may be inappropriately ruled out (or
look for problems such as an intestinal obstruction, foreign diagnosed) because the clinician does not understand the
FIG 2 8 - 3
G e n e r a l d i a g n o s t i c a p p r o a c h to hematemesis in the d o g a n d c a t . PCV, Packed cell
v o l u m e ; CBC, c o m p l e t e b l o o d count.
limitations of certain tests. For example, dogs with hypoad never diagnosed on the basis o f fecal examination results.
renocorticism may have n o r m a l electrolyte concentrations; Finally, the clinician may have to consider less c o m m o n dis
inflammatory gastric and bowel disease may be localized eases that are more difficult to diagnose (e.g., idiopathic
to one area o f the stomach or intestine and rarely causes gastric hypomotility, occult C N S disease, "limbic epilepsy").
significant changes i n the white b l o o d cell count; hyperthy
roid cats may have n o r m a l serum thyroxine concentrations;
dogs and cats with hepatic failure may have n o r m a l serum HEMATEMESIS
alanine aminotransferase and alkaline phosphatase activi
ties; dogs and cats with pancreatitis may have n o r m a l serum The clinician must often use history and physical examina
amylase and lipase activities and n o r m a l abdominal ultra tion to help identify hematemesis as well as distinguish it
sound examinations; and Physaloptera infections are almost from other problems. Hematemesis may involve expulsion
of digested blood (i.e., "coffee grounds") or fresh blood. respiratory tract), or G U E (Box 28-7). Historical and physical
Animals with oral lesions that have blood dripping from examination findings may help i n ruling out a coagulopathy
their lips do not have hematemesis. Likewise, hemoptysis or respiratory tract disease as the cause. However, platelet
(i.e., coughing up blood) is not hematemesis. counts and the clotting capability (e.g., one-stage p r o t h r o m
The clinician should further distinguish v o m i t i n g that b i n time, partial thromboplastin time, buccal mucosal bleed
produces specks o f blood from v o m i t i n g i n which there is ing time) are preferred. The clinician should then l o o k for
substantial blood present. The former may be caused by obvious causes o f G U E (e.g., acute gastritis, hemorrhagic
gastric mucosal trauma secondary to vigorous v o m i t i n g from gastroenteritis [ H G E ] , ulcerogenic drugs [e.g., nonsteroidal
any cause, and animals with such "hematemesis" should gen antiinflammatory drugs, dexamethasone], recent severe
erally be treated as described i n the previous section on hypovolemic shock, systemic inflammatory response syn
vomiting. Patients that produce more substantial amounts o f drome, abdominal masses that may involve the gastric
blood generally should be approached differently. Although mucosa, cutaneous mast cell tumors). It is important to
hematemesis is usually caused by gastroduodenal ulceration remember that a mast cell tumor can grossly m i m i c almost
and erosion ( G U E ) , the clinician should not automatically any other benign or malignant neoplasm, especially lipomas.
start treating affected patients with antacids, cytoprotective If acute gastritis, H G E , nonsteroidal antiinflammatory
agents, or sucralfate. Shock (e.g., hypovolemic, septic) and drug-induced G U E , or G U E resulting from shock is strongly
acute abdominal conditions should be eliminated first. The suspected, the clinician may elect a limited diagnostic workup
clinician should check the hematocrit and plasma total (e.g., C B C , serum biochemistry panel) to define the degree
protein concentration to determine whether a blood transfu of blood loss and look for evidence o f renal or hepatic or
sion is necessary (see Fig. 28-3). The clinician should next try adrenal failure. Then the animal can be treated symptom
to identify the cause, whether it is a coagulopathy (uncom atically for 3 to 5 days (see pp. 407-409) to see what effect
mon), the ingestion of b l o o d from another site (e.g., the this has i n controlling clinical signs. Endoscopy is not neces-
BOX 2 8 - 7
Causes o f Hematemesis
BOX 28-8
Diet
Bacterial causes
Intolerance/allergy Salmonella spp.
Poor-quality f o o d Clostridium perfringens
Rapid d i e t a r y c h a n g e (especially in p u p p i e s a n d kittens) V e r o t o x i n - p r o d u c i n g Escherichia coli
Bacterial f o o d p o i s o n i n g Campylobacter jejuni
Yersinia enterocolitica (questionable)
Parasites
Various other b a c t e r i a
Helminths Rickettsial infection
Protozoa Salmon p o i s o n i n g
Giardia
O t h e r Causes
Tritrichomonas (feline)
Coccidia Hemorrhagic gastroenteritis
Intussusception
Infectious Causes
"Irritable b o w e l s y n d r o m e "
Viral causes Ingestion of " t o x i n s "
Parvovirus (canine, feline) " G a r b a g e c a n " intoxication (spoiled foods)
C o r o n a v i r u s (canine, feline) Chemicals
Feline leukemia virus ( i n c l u d i n g infections s e c o n d a r y to H e a v y metals
it) Various drugs (antibiotics, antineoplastics, anthelmintics,
a n t i i n f l a m m a t o r i e s , d i g i t a l i s , lactulose)
Feline i m m u n o d e f i c i e n c y virus (specifically infections sec
A c u t e pancreatitis ( d i a r r h e a usually modest c o m p o n e n t of
o n d a r y to it)
Various other viruses (e.g., rotavirus, c a n i n e distemper clinical signs but c a n b e major)
virus) Hypoadrenocorticism
TABLE 28-2
* F a i l u r e to lose w e i g h t o r c o n d i t i o n is t h e m o s t r e l i a b l e i n d i c a t i o n t h a t a n a n i m a l h a s l a r g e b o w e l d i s e a s e . H o w e v e r , a n i m a l s w i t h c o l o n i c
histoplasmosis, p y t h i o s i s , l y m p h o m a , o r s i m i l a r infiltrative d i s e a s e s m a y h a v e w e i g h t loss d e s p i t e l a r g e b o w e l i n v o l v e m e n t .
H e m a t o c h e z i a b e c o m e s m u c h m o r e i m p o r t a n t as a d i f f e r e n t i a t i n g f e a t u r e in a n i m a l s t h a t a r e l o s i n g w e i g h t . Its p r e s e n c e in such a n i m a l s
confirms the p r e s e n c e o f l a r g e b o w e l i n v o l v e m e n t (either b y itself o r in c o m b i n a t i o n w i t h small b o w e l d i s e a s e ) d e s p i t e w e i g h t loss.
originates from the small or large intestine. History is the when enzymes are added to their diet. If EPI is incorrectly
best tool (Table 28-2). Failure to lose weight or body condi ruled out i n such a case, then unnecessary endoscopies or
tion despite chronic diarrhea almost always indicates large operations often result. Antibiotic-responsive enteropathy
bowel disease. Weight loss usually indicates the presence o f (ARE) may be responsible for causing such a failure to
small bowel disease, although severe large bowel diseases respond to proper enzyme supplements and dietary changes.
(e.g., pythiosis, histoplasmosis, malignancy) may cause Therefore the clinician should definitively diagnose or rule
weight loss. Animals with weight loss resulting from severe out E P I before proceeding with other diagnostic tests or
large bowel disease usually have obvious signs o f colonic treatments.
involvement (i.e., fecal mucus, marked tenesmus, hemato Malabsorptive intestinal disease may be protein-losing
chezia). If there is tenesmus, the clinician must ascertain (PLE) or nonprotein-losing (Fig. 28-4). The serum albumin
whether it was present when the disease began; i f tenesmus concentration will usually be markedly decreased (i.e., 2.0 g/
did not begin until late i n the course, it may be due simply dl or less; normal, 2.5 to 4.4 g/dl) i n the former but not i n
to perineal scalding or anal soreness resulting from chronic the latter; hypoglobulinemia may develop in patients with
irritation. P L E . Diarrhea occurs only i f the absorptive capacity o f the
Chronic small intestinal diarrhea can be categorized as colon is exceeded. Therefore a dog or cat can be losing weight
maldigestion, nonprotein-losing malabsorptive disease, and because of small intestinal malabsorption and not have diar
protein-losing malabsorptive disease. Maldigestion is princi rhea (see the section o n weight loss). If an animal has marked
pally caused by exocrine pancreatic insufficiency (EPI) and hypoproteinemia not resulting from protein-losing nephrop
rarely causes significant hypoalbuminemia (i.e., serum athy, hepatic insufficiency, or skin lesions, then P L E must be
albumin concentration o f 2.0 g/dl or less i f the normal range the m a i n consideration.
is 2.5 to 4.4 g/dl). F i l m digestion tests for fecal trypsin activ In patients with nonprotein-losing malabsorptive disease,
ity, Sudan staining of feces for undigested fats, and fat the clinician may perform additional diagnostic tests (e.g.,
absorption tests yield many false-negative and false-positive intestinal biopsy) or design therapeutic trials depending on
results. The most sensitive and specific test for EPI is measur how i l l the patient is. Therapeutic trials are the best way to
ing the serum trypsin-like immunoreactivity (TLI; see diagnose antibiotic responsive enteropathy (ARE) or dietary
p. 388), which is indicated i n dogs with chronic small intes responsive disease. A R E cannot reliably be diagnosed on the
tinal diarrhea. The cPLI test may have use i n diagnosing EPI, basis o f quantitated duodenal culture, and decreased serum
but this is not yet certain. EPI is rare i n cats, but i f suspected, cobalamin plus increased serum folate concentrations are o f
an fTLI (feline TLI) is recommended. dubious sensitivity. However, i f a therapeutic trial is per
Diagnosing EPI by treating the animal and evaluating its formed, the clinician must be sure that it is done properly
response to therapy is not recommended. If the animal has (e.g., long enough, correct dose) so that it w i l l almost cer
apparently responded to pancreatic enzyme supplementa tainly succeed i f the animal has the suspected disease. If the
tion, the enzymes should be repeatedly withheld and then patient seems particularly i l l (e.g., substantial weight loss) or
readministered to ensure that the enzymes are responsible if P L E is suspected, ultrasonography and intestinal biopsy
for resolution of the diarrhea. A false-positive diagnosis o f are often the preferred next steps because spending 2 to 3
EPI results in the unnecessary supplementation of expensive weeks waiting to see i f a therapeutic trial will work can be
enzymes. Second, up to 15% of dogs with EPI do not respond disasterous i f the therapy is incorrect and the disease pro-
FIG 2 8 - 4
G e n e r a l d i a g n o s t i c a p p r o a c h to small intestinal d i a r r h e a in the d o g a n d cat. C S C ,
C o m p l e t e b l o o d count; FeLV, feline leukemia virus; FIV, feline i m m u n o d e f i c i e n c y virus, TLI,
trypsin-like immunoreactivity.
gresses. If diagnostic tests are chosen, abdominal imaging raphy reveals a localized lesion that cannot be reached with
(especially ultrasonography) followed by gastroduodenos an endoscope, then laparotomy is necessary as opposed to
copy or colonoscopy are typical next steps because the endoscopy. Otherwise, endoscopy is quicker and safer than
findings can help determine the cause o f P L E and nonpro laparotomy and may allow the clinician to biopsy lesions not
tein-losing enteropathies i n patients that do not have A R E seen from the serosal surface. Endoscopic biopsy specimens
or dietary responsive disease (Boxes 28-9 and 28-10). Absorp can be nondiagnostic i f the endoscopist has not been care
tive tests and b a r i u m contrast-enhanced radiographs are fully trained i n taking biopsy specimens. If laparotomy is
rarely helpful. A b d o m i n a l ultrasonography may be diagnos performed i n hypoalbuminemic animals, it may be prudent
tic i f it shows lymphadenopathy or intestinal infiltrates that to use nonabsorbable suture material and/or perform intes
can be aspirated percutaneously. Laparotomy or endoscopy tinal serosal patch grafting. The presence o f distended
can be performed to obtain biopsy specimens. If ultrasonog intestinal lymphatics or lipogranulomas is suggestive of
l y m p h a n g i e c t a s i a . I f a cause is n o t s h o w n b y i n t e s t i n a l b i o p s y f o r m u c o s a l t h i c k e n i n g o r p r o l i f e r a t i o n . T h e r e c t u m is t h e
specimens, t h e m a i n possible reasons f o r t h i s are t h a t t h e m o s t c o m m o n site o f c a n i n e c o l o n i c n e o p l a s i a , a n d finding
specimens w e r e i n a d e q u a t e (e.g., n o t deep e n o u g h , f r o m t h e o b v i o u s m u c o s a l lesions i n d i c a t e s t h e n e e d f o r b i o p s y . I f t h e
w r o n g place, t o o m u c h a r t i f a c t ) , t h e a n i m a l has o c c u l t g i a r rectal m u c o s a seems n o r m a l a n d t h e a n i m a l has n o t lost
diasis, t h e a n i m a l has A R E , t h e a n i m a l has a d i e t a r y i n t o l e r w e i g h t o r b e c o m e h y p o a l b u m i n e m i c (i.e., a l b u m i n < 2 . 0 g /
ance, o r there is l o c a l i z e d l y m p h a n g i e c t a s i a o r i n f l a m m a t i o n d l ) , i t is o f t e n m o s t a p p r o p r i a t e t o first t r y t h e r a p e u t i c t r i a l s .
at a site o t h e r t h a n t h e o n e b i o p s i e d .
D o g s w i t h c h r o n i c large i n t e s t i n a l d i a r r h e a ( B o x 2 8 - 1 1 )
s h o u l d first u n d e r g o a d i g i t a l r e c t a l e x a m i n a t i o n t o search
BOX 2 8 - 1 0
Cat Cat
BOX 28-1 1
Dog I n f l a m m a t o r y b o w e l disease
Dietary responsive (intolerance o r a l l e r g y ; i m p o r t a n t a n d Neoplasia
common) Lymphoma
Fiber-responsive (important a n d c o m m o n ) Adenocarcinoma
Functional disorder (so-called "irritable b o w e l syndrome")
Cat
Parasitism
W h i p w o r m s (regionally i m p o r t a n t a n d c o m m o n ) D i e t a r y responsive (intolerance o r a l l e r g y ; i m p o r t a n t a n d
Giardia (regionally i m p o r t a n t a n d c o m m o n s m a l l b o w e l common)
disease that sometimes mimics large b o w e l disease) Fiber-responsive ( i m p o r t a n t a n d c o m m o n )
Heterobilharzia (regionally important) Functional d i s o r d e r (so-called irritable b o w e l syndrome)
Bacterial diseases I n f l a m m a t o r y b o w e l disease
"Clostridial" colitis (important a n d c o m m o n ) Tritrichomonas
Histiocytic ulcerative colitis ( p r i n c i p a l l y Boxers a n d French Feline leukemia virus infection (including infections second
Bulldogs) a r y to it)
Fungal infections (regionally i m p o r t a n t a n d c o m m o n ) Feline i m m u n o d e f i c i e n c y virus infection (specifically infec
Histoplasmosis tions s e c o n d a r y to it)
Pythiosis
However, multiple fecal examinations to detect whipworms, HEMATOCHEZIA
Giardia (a small bowel problem that can m i m i c large bowel
disease), and Tritrichomonas are appropriate. Therapeutic If the patient has hematochezia (fresh blood i n the feces) and
trials usually consist of high-fiber diets, hypoallergenic diets, diarrhea, the problem should usually be approached in the
antibiotics to control "clostridial" colitis, or treatment for same way as that for animals with large bowel diarrhea (see
whipworms. p. 362). The patient with normal stools plus hematochezia is
Additional diagnostic tests that may be done instead o f approached slightly differently. Streaks of blood on the
therapeutic trials principally include obtaining biopsy spec outside o f otherwise normal feces usually indicates the pres
imens of the colonic mucosa by colonoscopy, fecal cultures, ence of a distal colonic or rectal lesion, whereas b l o o d that
assays for clostridial toxin, and antigen tests for specific is mixed into the feces suggests that bleeding is occurring
organisms (e.g., Campylobacter). Fecal cultures for specific higher i n the colon. Coagulopathies are rarely a cause o f
pathogens (e.g., Salmonella spp.) should be done i f the rectal bleeding only. Focal bleeding lesions i n the distal colon,
history indicates the possiblity o f a contagious disorder or i f rectum, or perineal region (Box 28-12) are especially impor
the animal is not responding to seemingly appropriate tant. Acute hematochezia may also result from trauma.
therapy. Fecal cultures should be done before the animal A thorough digital rectal examination is the best initial
receives enemas or intestinal lavagae solutions. Unless there step (even i f anesthesia is necessary). The clinician should
is some epidemiologic reason to suspect an infectious bac express each anal sac repeatedly and examine the contents.
teria, fecal cultures tend to be low-yield procedures that are If the problem is chronic and results of these tests are unin
difficult to interpret. formly negative, then colonoscopy and biopsy are usually
If the results o f these tests are not diagnostic, the clinician indicated. A n excellent barium enema is usually inferior to
must consider three m a i n possibilities. First, the biopsy a good endoscopic examination. Biopsy specimens should
specimens may not be representative o f the entire colonic include the submucosa, or some neoplastic lesions will be
mucosa. For example, i f the disease is localized to the region missed. Hematochezia is rarely severe enough to cause
of the ileocolic valve, it will be necessary to use a flexible anemia; however, a C B C can be performed to look for and
endoscope to reach the area. Second, the pathologist may evaluate the cause o f anemias.
not have recognized the lesions. This occasionally happens,
especially if animals have colonic histoplasmosis or neopla
sia. T h i r d , there may be no mucosal lesions. This typically MELENA
occurs i n animals with a dietary intolerance or allergy,
"clostridial" colitis, chronic giardiasis, or irritable bowel syn Melena is caused by digested b l o o d and is seen as coal tar
drome (i.e., fiber-responsive diarrhea), all c o m m o n prob black (not dark) feces. The clinician must be extremely
lems in dogs. careful to distinguish melena from stools that are intensely
BOX 2 8 - 1 2
Dog
D i e t a r y responsive (intolerance o r a l l e r g y ; common)
A n a l - R e c t a l Disease
" C l o s t r i d i a l " colitis (common)
A n a l sacculitis ( i m p o r t a n t a n d c o m m o n ) H e m o r r h a g i c gastroenteritis (important)
Neoplasia Parvoviral enteritis (important a n d common)
Rectal a d e n o c a r c i n o m a (important) Histoplasmosis (regionally i m p o r t a n t a n d c o m m o n )
Rectal p o l y p (important) Pythiosis
Colorectal leiomyoma or leiomyosarcoma Intussusception
Perianal fistulas (important) Ileocolic
Anal foreign body Cecocolic
Rectal p r o l a p s e I n f l a m m a t o r y b o w e l disease
Anal-rectal t r a u m a ( e . g . , f o r e i g n b o d y , thermometer, e n e m a Colonic trauma
tube, fecal l o o p , pelvic fractures) Coagulopathy
C o l o n i c / l n t e s t i n a l Disease Cat
Dog Dog
BOX 2 8 - 1 5
Causes o f C o n s t i p a t i o n
Iatrogenic Causes
Intraluminal a n d intramural disorders
Drugs Tumor
Opiates Granuloma
Anticholinergics Cicatrix
Carafate (sucralfate) Rectal f o r e i g n b o d y
Barium C o n g e n i t a l stricture
Extraluminal disorders
Behavioral/Environmental Causes Tumor
C h a n g e in h o u s e h o l d / r o u t i n e Granuloma
Soiled litter b o x / n o litter b o x Abscess
House t r a i n i n g H e a l e d pelvic fracture
Inactivity Prostatomegaly
Prostatic o r p a r a p r o s t a t i c cyst
Refusal t o Defecate
Sublumbar lymphadenopathy
Behavioral
Colonic W e a k n e s s
Pain in r e c t a l / p e r i n e a l a r e a (see Box 2 8 - 1 4 )
Inability to assume position to d e f e c a t e Systemic disease
Orthopedic problem Hypercalcemia
Neurologic problem Hypokalemia
Hypothyroidism
D i e t a r y Causes
Localized neuromuscular disease
Excessive fiber in d e h y d r a t e d animal Spinal c o r d t r a u m a
A b n o r m a l diet Pelvic nerve damage
Hair Dysautonomia
Bones C h r o n i c , massive d i l a t i o n of the colon causing irreversible
Indigestible material ( e . g . , plants, plastic) stretching of the c o l o n i c musculature
Pseudocoprostasis Severe d e h y d r a t i o n
D e v i a t i o n of rectal c a n a l : perineal h e r n i a I d i o p a t h i c m e g a c o l o n (especially cats)
Ultrasound-guided fine-needle aspiration o f infiltrative
colonic lesions sometimes yields diagnostic findings, but
BOX 2 8 - 1 6
colonoscopy (especially rigid) allows a more reliable biopsy
Causes o f Weight Loss
specimen to be obtained. If a thorough diagnostic workup
fails to identify a cause in a patient with a grossly dilated Food
colon, idiopathic megacolon may be present. N o t e n o u g h (especially if there a r e multiple animals)
Poor q u a l i t y o r l o w c a l o r i c density
Inedible
FECAL INCONTINENCE
A n o r e x i a (see Box 2 8 - 1 7 )
D y s p h a g i a (see Box 2 8 - 1 )
Fecal incontinence is caused by neuromuscular disease (e.g.,
cauda equine syndrome, lumbosacral stenosis) or a partial R e g u r g i t a t i o n / V o m i t i n g (i.e., losing e n o u g h calories to
rectal obstruction. Severe irritative proctitis may cause a c c o u n t f o r w e i g h t loss; see Boxes 2 8 - 4 to 2 8 - 6 )
urge incontinence. Animals with rectal obstructions con M a l d i g e s t i v e Disease
tinually try to defecate because the anal canal is filled
Exocrine p a n c r e a t i c insufficiency (usually but not a l w a y s
with feces. Proctitis is suspected on the basis o f rectal exam associated w i t h d i a r r h e a )
ination findings and confirmed by proctoscopy and biopsy
findings. Neuromuscular disease is suspected i f an abnormal M a l a b s o r p t i v e Disease (see Box 2 8 - 9 )
anal reflex is found, usually in conjunction with other neu Small intestinal disease ( m a y b e associated w i t h n o r m a l
rologic defects in the anal, perineal, h i n d l i m b , or coccygeal stools)
region. Defects i n the coccygeal region are discussed i n
Malassimilation
Chapter 70.
O r g a n failure
C a r d i a c failure
H e p a t i c failure
WEIGHT LOSS
Renal failure
A d r e n a l failure
Weight loss is usually caused by one of several categories o f
problems (Box 28-16). If other problems with more defined Cancer C a c h e x i a
lists of differentials (e.g., ascites, vomiting, diarrhea, poly Excessive U t i l i z a t i o n o f Calories
uria/polydipsia) are also present, they should usually be Lactation
investigated first because it may be easier to find the cause. Increased w o r k
If there are no such concurrent problems that allow relatively Extremely c o l d e n v i r o n m e n t
prompt localization of the disease, the clinician should then Pregnancy
determine what the animal's appetite was when the weight Increased c a t a b o l i s m resulting f r o m f e v e r / i n f l a m m a t i o n
loss began (Fig. 28-5). Almost any disease can cause anorexia. Hyperthyroidism
Weight loss despite a good appetite usually indicates
Increased Loss of N u t r i e n t s
maldigestion, malabsorption, or excessive utilization (e.g.,
Diabetes mellitus
hyperthyroidism, lactation) or inappropriate loss (e.g., dia
Protein-losing n e p h r o p a t h y
betes mellitus) of calories.
Protein-losing e n t e r o p a t h y
The animal's history should be reviewed for evidence
of dietary problems, dysphagia, regurgitation, vomiting, or N e u r o m u s c u l a r Disease
increased use of calories (e.g., lactation, work, extremely cold Lower motor neuron disease
temperature). Signalments suggestive o f particular diseases
(e.g., hyperthyroidism i n older cats, hepatic failure i n younger
dogs with signs of portosystemic shunts) should be recog
nized. It is important to remember that diarrhea may be failure, or a paraneoplastic syndrome. Cats should be tested
absent in animals with severe small intestinal disease. for circulating feline leukemia virus antigen and antibodies
Physical examination is performed to identify abnormal to feline immunodeficiency virus. Serum T (and sometimes 4
ities that might help localize the problem to a particular fT ) concentrations should be determined in middle-aged to
4
body system (e.g., nasal disease preventing n o r m a l olfaction, older cats. If clinical pathology data are not helpful, imaging
dysphagia, arrhythmia suggestive of cardiac failure, weakness is usually the next step. Thoracic radiographs (ventrodorsal
suggestive of neuromuscular disease, abnormally sized or and both lateral views) are important because significant
shaped organs, abnormal fluid accumulations). Retinal thoracic disease cannot be ruled out on the basis o f physical
examination may identify inflammatory or infiltrative dis examination findings alone. M o s t cats and some dogs can be
eases, especially i n cats. palpated well enough that abdominal radiographs are not
A C B C , serum biochemistry profile, and urinalysis should cost-effective early i n the workup. However, abdominal
be done next to search for evidence o f inflammation, organ ultrasonography may reveal focal or infiltrative lesions that
FIG 2 8 - 5
G e n e r a l d i a g n o s t i c a p p r o a c h to w e i g h t loss in the d o g a n d c a t . CBC, C o m p l e t e b l o o d
count; FeLV, feline leukemia virus; FIV, feline i m m u n o d e f i c i e n c y virus; ACTH, a d r e n o c o r t i
c o t r o p i c h o r m o n e ; EEG, e l e c t r o e n c e p h a l o g r a p h y ; EMG, e l e c t r o m y o g r a p h y ; CT, c o m p u t e d
t o m o g r a p h y ; CSF, c e r e b r o s p i n a l f l u i d ; MRI, m a g n e t i c resonance i m a g i n g .
cannot be palpated (plain radiographs reveal such lesions Other possible diagnostic tools include tests to evaluate
less frequently). the C N S (i.e., cerebrospinal fluid analysis, electroencepha
If the cause o f weight loss remains u n k n o w n after these lography, computed tomography, magnetic resonance
steps have been taken, additional tests are necessary. Daily imaging; animals that are anorectic as a result o f severe C N S
physical examinations can be an important means o f local disease do not always have obvious cranial nerve deficits or
izing the problem. Fever o f u n k n o w n origin may be noted seizures) and peripheral nerves and muscles (i.e., electromy
(see Chapter 90). Organ function testing (e.g., serum bile ography, muscle or nerve biopsies; sometimes the weakness
acid concentrations, A C T H - s t i m u l a t i o n testing, serum T L I , associated with neuropathies and myopathies is mistaken for
serum cobalamin) is reasonable. Likewise, if serum T concen 4 lethargy). (See Chapter 64.) If the cause of the weight loss
trations are n o r m a l i n a cat with suspected hyperthyroidism, still remains undiagnosed and the history and physical
the serum fT concentration should be determined or other
4 examination findings are still noncontributory, occult cancer
tests (e.g., nuclear scintigraphy) performed (see Chapter 51). becomes a major differential diagnosis. In such cases, the
If the cause o f weight loss still remains undiagnosed, the clinician may have to wait and retest later with the hope that
clinician should consider performing gastric and intestinal the disease will progress enough to be detected.
biopsy (preferably endoscopically). If a laparotomy is per Causes o f weight loss that can be particularly difficult to
formed instead, the entire abdomen should be examined, diagnose include gastric disease that does not cause vomit
multiple biopsy samples o f the alimentary tract obtained, ing, intestinal disease that does not cause vomiting or
and biopsy o f the liver and mesenteric lymph nodes done. diarrhea, hepatic disease with normal serum alanine
Biopsy o f the pancreas should also be done i n cats. aminotransferase or alkaline phosphatase activities, occult
inflammatory disease, hypoadrenocorticism with n o r m a l ABDOMINAL EFFUSION
serum electrolyte concentrations, occult cancer, "dry" feline
infectious peritonitis, and C N S disease without cranial nerve A b d o m i n a l effusion is usually caused by hypoalbuminemia,
deficits or seizures. portal hypertension, or peritoneal inflammation. Effusions
resulting from alimentary tract disorders are primarily
caused by P L E or alimentary tract rupture (i.e., septic peri
ANOREXIA tonitis). Some animals with P L E have n o r m a l stools, with
ascites being the presenting complaint. Malignant tumors
The approach to the diagnostic evaluation of animals with may obstruct lymphatic flow or increase vascular permeabil
anorexia of uncertain cause is similar to that for animals with ity, causing modified transudates to form or nonseptic peri
weight loss (see Fig. 28-5), and the differential diagnoses tonitis to develop. Modified transudates usually result from
are also similar (Box 28-17). Inflammatory disease is often hepatic or cardiac disease or from malignant conditions. For
detected by the C B C or the finding of fever (see Chapter 90). further information on abdominal effusions, see Chapters 35
GI disease may produce anorexia without vomiting or diar and 36.
rhea. Cancer cachexia (with anorexia as the predominant
sign) may stem from relatively small tumors that are not
grossly detectable, although this is rare. Finally, C N S disease ACUTE ABDOMEN
must be considered whenever there is altered mentation.
However, altered mentation may resemble the depression Acute abdomen refers to various abdominal disorders pro
and lethargy commonly seen in animals with other diseases. ducing shock (hypovolemic or septic), sepsis, or severe pain
(Box 28-18). Causes may include alimentary tract obstruc
tion or leakage, vascular compromise (e.g., congestion,
torsion, volvulus, ischemia), inflammation, neoplasia, or
BOX 2 8 - 1 7 sepsis. The diagnostic evaluation of this problem is deter
mined by the severity of the clinical signs (Fig. 28-6).
Major Causes of Anorexia
Shock and gastric dilation or volvulus ( G D V ) must be
I n f l a m m a t o r y Disease identified and treated immediately. Once these conditions
Bacterial infections are eliminated, the next major decision is whether to perform
| Viral infections exploratory surgery or initiate medical therapy. A n i m a l s
Fungal infections with abdominal masses, foreign objects, bunched-up loops
Rickettsial infections of painful small intestine (e.g., linear foreign body), or spon
Protozoal infections taneous septic peritonitis should typically undergo surgery
Sterile inflammation as soon as supportive therapy has made the risk of anesthe
Immune-mediated disease
sia acceptable. If the cause of the acute abdomen is uncertain,
N e o p l a s t i c disease
it can be difficult to determine whether surgery is indicated.
Necrosis
Surgery is not necessarily beneficial and may even be detri
Pancreatitis
Fever of u n k n o w n o r i g i n
mental to animals with conditions such as pancreatitis, par
voviral enteritis, pyelonephritis, or prostatitis. Typically,
A l i m e n t a r y Tract Disease abdominal imaging (i.e., plain abdominal radiography or
Gastric or intestinal disease ultrasonongraphy) and clinical pathologic studies (i.e., C B C ,
D y s p h a g i a (especially resulting from pain) chemistry panel) should be performed before a laparotomy
is performed. Ultrasound can reveal changes (e.g., infiltration)
N a u s e a (stimulation of the m e d u l l a r y v o m i t i n g center f o r
that radiographs cannot detect, sometimes allowing diagno
a n y reason, even if it is not sufficient to cause v o m i t i n g ,
sis via aspiration (and potentially eliminating the need for
especially gastric o r intestinal disease; see Box 2 8 - 6 )
surgery). However, radiographs occasionally detect lesions
Metabolic Disease (e.g., small foreign bodies) that were missed ultrasonograph
ically. Imaging may reveal spontaneous pneumoperitoneum,
O r g a n failure ( e . g . , kidney, a d r e n a l , liver, heart)
abdominal masses, foreign objects, alimentary tract obstruc
Hypercalcemia
Diabetic ketoacidosis tion, gastric or mesenteric torsion (these require surgical
H y p e r t h y r o i d i s m (usually causes p o l y p h a g i a , but some cats treatment), or free peritoneal fluid (this requires abdomino
have apathetic hyperthyroidism) centesis and fluid analysis for management). A b a r i u m series
is seldom needed and may complicate later therapy/surgery.
Central N e r v o u s S y s t e m Disease
If optimal medical therapy is being given and the animal's
Cancer Cachexia condition is clearly deteriorating or does not improve after
Anosmia 2 to 5 days of therapy, or i f the animal continues to have
excruciating pain, it is often appropriate to recommend
Psychologic Causes
exploratory surgery. Inform the client that y o u may discover
BOX 2 8 - 1 8
Septic I n f l a m m a t i o n O r g a n Distention o r O b s t r u c t i o n
Septic peritonitis Gastric d i l a t i o n o r volvulus (important a n d c o m m o n )
Perforated gastric ulcer ( N S A I D s , tumor) (important) Intestinal obstruction resulting from m a n y causes (important
Perforated intestines (tumor, post-op d e h i s c e n c e , linear and common)
foreign body, severe inflammation) (important a n d Intussusception (important)
common) Dystocia
Devitalized intestines (intussusception, t h r o m b o s i s / i n f a r c t ) Mesenteric volvulus (rare)
Ruptured gallbladder d u e to septic cholecystitis o r Incarcerated obstruction (rare)
mucocoele
Abscess/Infection Ischemia
Splenic Torsion o f spleen, liver l o b e , testicle, o r other o r g a n
Hepatic T h r o m b o e m b o l i s m o f a b d o m i n a l organ(s)
Cholecystitis
Prostatic O t h e r Causes o f A b d o m i n a l Pain (see Box 2 8 - 1 9 )
Renal Abdominal Hemorrhage
Pyometra (ruptured)
Abdominal neoplasia (hemangiosarcoma, hepatocellular
Nonseptic I n f l a m m a t i o n carcinoma; important a n d common)
Pancreatitis ( i m p o r t a n t a n d c o m m o n ) Trauma
Uroabdomen (important) C o a g u l o p a t h y (important)
Pansteatitis
Abdominal Neoplasia
BOX 2 8 - 1 9
Poor P a l p a t i o n Technique
Neoplasm
M u s c u l o s k e l e t a l S y s t e m (Mimics A b d o m i n a l Pain)
Infection (rare)
Fractures
Urogenital System
Intervertebral disk disease (important a n d c o m m o n )
Diskospondylitis (important) Pyelonephritis (important)
Abscesses Lower u r i n a r y tract infection
Prostatitis (common)
Peritoneum
N o n s e p t i c cystitis ( c o m m o n in cats)
Peritonitis Cystic o r ureteral obstruction o r rupture ( c o m m o n , especially
Septic ( i m p o r t a n t a n d c o m m o n ) after trauma)
N o n s e p t i c ( e . g . , u r o a b d o m e n ; important) Urethritis or obstruction (common)
A d h e s i o n s (rare) Metritis
Uterine torsion (rare)
G a s t r o i n t e s t i n a l Tract
Neoplasm
Gastrointestinal ulcer Testicular torsion (rare)
Foreign o b j e c t (especially linear) Mastitis (does n o t cause true a b d o m i n a l p a i n but mimics
Neoplasm a b d o m i n a l pain)
A d h e s i o n s (rare)
Miscellaneous Causes
Intestinal ischemia (rare)
Intestinal spasm (rare) Postoperative p a i n (especially if a n i m a l has a tight suture
See also Box 2 8 - 1 8 , under O r g a n Distention o r Obstruction line)
Iatrogenic causes
H e p a t o b i l i a r y Tract
Misoprostol
Hepatitis Bethanechol
A d r e n a l i t i s (associated w i t h h y p o a d r e n o c o r t i c i s m ; rare)
Cholelithiasis o r cholecystitis
H e a v y metal i n t o x i c a t i o n (rare)
Pancreas V a s c u l o p a t h y (rare)
Pancreatitis ( i m p o r t a n t a n d c o m m o n ) Rocky M o u n t a i n spotted fever vasculitis
Infarct
Spleen
Torsion (rare)
Rupture
FIG 2 8 - 6
G e n e r a l d i a g n o s t i c a p p r o a c h to acute a b d o m e n in the d o g a n d c a t . CBC, C o m p l e t e
b l o o d count.
the animal has a disorder not surgically correctable (espe A n animal with true abdominal pain may show obvious
cially pancreatitis) or that nothing abnormal may be found. discomfort (e.g., it paces or repeatedly assumes different
In the latter case, the clinician should biopsy various abdom positions, repeatedly looks at or licks its abdomen) and may
inal organs and then treat the animal's symptoms while whine, growl, or snap i f the abdomen is touched. Some dogs
awaiting biopsy results. stretch out and assume a "praying" position (i.e., the "posi
tion o f r e l i e f ) . Other animals have inconspicuous signs
(e.g., the animal grunts or tries to walk away when palpated,
ABDOMINAL PAIN the abdomen is tensed) that are easily missed. O n the other
hand, a poor or rough abdominal palpation technique i n
"Abdominal" pain must first be determined to be abdominal normal animals may elicit a guarding response that can
and not extraabdominal in origin (e.g., thoracolumbar pain m i m i c abdominal pain. The m a i n causes of abdominal pain
is often erroneously assessed as being abdominal i n origin). are listed i n B o x 28-19.
BOX 2 8 - 2 0
| Tissue
Pyometra
Pregnancy Free in a b d o m e n
H e p a t o m e g a l y (infiltrative o r i n f l a m m a t o r y disease, lipidosis, Transudate, m o d i f i e d transudate, e x u d a t e , b l o o d , chyle
neoplasia)
Gas
S p l e n o m e g a l y (infiltrative o r i n f l a m m a t o r y disease, neopla
sia, hematoma) C o n t a i n e d in organ(s)
R e n o m e g a l y ( n e o p l a s i a , infiltrative disease, compensatory Stomach (gastric d i l a t i o n o r volvulus)
hypertrophy) Intestines (resulting f r o m obstruction)
Miscellaneous neoplasia In p a r e n c h y m a t o u s organs (e.g., liver) resulting from
G r a n u l o m a ( e . g . , pythiosis) infection w i t h g a s - p r o d u c i n g b a c t e r i a
Free in a b d o m e n
Fluid
Iatrogenic (after l a p a r o s c o p y o r l a p a r o t o m y )
C o n t a i n e d in organ(s) A l i m e n t a r y tract or female r e p r o d u c t i v e tract rupture
C o n g e s t i o n resulting from torsion, volvulus, or right-sided Bacterial m e t a b o l i s m (peritonitis)
heart failure
Fat
Spleen
Liver Obesity
Cysts Lipoma
Paraprostatic cyst
W e a k A b d o m i n a l Muscles
Perinephric cyst
H e p a t i c cyst Hyperadrenocorticism
Hydronephrosis
Intestines o r stomach (resulting f r o m obstruction o r ileus) Feces
If the patient has abdominal pain, the goal is to determine on abdominal masses and enlarged organs, unless there is a
the source. If the pain is originating from w i t h i n the abdom reason not to (e.g., hepatomegaly caused by severe right-
inal cavity, the diagnostic approach depends o n its severity, sided heart failure). Fine-needle aspiration is usually safe,
the progression o f disease, and whether there are any although the leakage of septic contents or implantation
obvious causes. The steps taken i n diagnosing the cause of neoplastic cells may occur. Ultrasonography helps deter
of abdominal pain are similar to those taken i n an animal mine the potential for hemorrhage or leakage (e.g., cyst,
with acute abdomen. Some causes of abdominal pain can mass with ultrasonographic characteristics of hemangiosar
be difficult to diagnose (e.g., acute pancreatitis, localized coma). The finding of a spontaneous pneumoperitoneum
peritonitis). suggests alimentary tract rupture or septic peritonitis and is
an indication for immediate surgical exploration. A hollow
viscus dilated with gas may indicate obstruction (i.e., gastric
ABDOMINAL DISTENTION dilation, intestinal obstruction) or physiologic ileus (see pp.
OR ENLARGEMENT 384 and 436; Figs. 29-5 and 32-4). Surgery is indicated i f an
obstruction seems likely. If abdominal musculature weak
A b d o m i n a l distention or enlargement may be associated ness is suspected, the clinician should test for hyperadreno
with an acute abdomen, but these conditions are typically corticism. Results of a C B C , serum biochemistry panel, and
separate problems. It is best to believe clients who claim urinalysis are used to look for specific organ involvement
there is abdominal enlargement until good cause is found to (e.g., hyperadrenocorticism). Contrast-enhanced alimentary
do otherwise. There are six main causes o f abdominal disten or urinary tract radiographs may be useful i n selected cases,
tion (Box 28-20). although ultrasonography often makes such techniques
The first concern is whether an acute abdomen is present unnecessary.
(e.g., G D V , septic peritonitis, hemoabdomen plus shock).
After an acute abdomen is ruled out, it should be possible Suggested Readings
to classify the enlargement o n the basis o f the physical
Harkin KR: Constipation, tenesmus, dyschezia, and fecal inconti
examination and abdominal imaging (i.e., radiography or nence. In Ettinger SJ et al, editors: Textbook of veterinary internal
ultrasonography) findings, according to the criteria i n medicine, ed 6, Philadelphia, 2005, WB Saunders.
B o x 28-20. Obesity and pregnancy should be obvious. Spec Hoover JP et al: Anorexia. In Ettinger SJ et al, editors: Textbook
imens of free abdominal fluid should be obtained and ana of veterinary internal medicine, ed 6, Philadelphia, 2005, WB
lyzed as described i n Chapter 36. Biopsy should be performed Saunders.
A
Kelly K M : Melena and hematochezia. In Ettinger SJ et al, editors: Twedt D C : Vomiting. In Ettinger SJ et al, editors: Textbook of
Textbook of veterinary internal medicine, ed 6, Philadelphia, 2005, veterinary internal medicine, ed 6, Philadelphia, 2005, W B
WB Saunders. Saunders.
Marretta SM: Ptyalism. In Ettinger SJ et al, editors: Textbook of vet Willard M D et al: Gastrointestinal, pancreatic, and hepatic dis
erinary internal medicine, ed 6, Philadelphia, 2005, WB Saunders. orders. In Willard M D et al, editors: Small animal clinical
Steiner JM: Diarrhea. In Ettinger SJ et al, editors: Textbook of vet diagnosis by laboratory methods, ed 4, Philadelphia, 2004, W B
erinary internal medicine, ed 6, Philadelphia, 2005, WB Saunders. Saunders.
C H A P T E R 29
CHAPTER OUTLINE
PHYSICAL EXAMINATION
PHYSICAL E X A M I N A T I O N
Routine physical examination is the first step in evaluating
ROUTINE LABORATORY EVALUATION
animals with alimentary tract disease, although oral exami
Complete Blood C o u n t
nation is sometimes skipped in uncooperative animals.
Coagulation
If oral, abdominal, or rectal disease is a major concern and
Serum Biochemistry Profile
the patient refuses to allow examination o f the area, it
Urinalysis
is reasonable and appropriate to sedate or anesthetize
FECAL PARASITIC E V A L U A T I O N
the patient to examine and palpate this area. A c o m m o n
F E C A L D I G E S T I O N TESTS
example of this is a vomiting cat with a possible linear
M I S C E L L A N E O U S FECAL ANALYSES
foreign body lodged under the tongue; the clinician must
BACTERIAL FECAL CULTURE
thoroughly examine the mouth, even i f it requires chemical
C Y T O L O G I C E V A L U A T I O N O F FECES
restraint.
R A D I O G R A P H Y O F THE ALIMENTARY TRACT
The clinician should methodically identify individual
U L T R A S O N O G R A P H Y O F THE A L I M E N T A R Y TRACT
organs during abdominal palpation. In dogs the small intes
I M A G I N G O F THE O R A L CAVITY, P H A R Y N X , A N D
tine, large intestine, and urinary bladder can usually be
ESOPHAGUS
found (unless there is an abdominal effusion, abdominal
Indications
pain, or obesity). In cats both kidneys are usually palpable.
Indications for Imaging o f the Esophagus
In both species the clinician can usually detect substan
I M A G I N G O F THE S T O M A C H A N D SMALL
tial splenomegaly, hepatomegaly, intestinal or mesenteric
INTESTINE
masses, and intestinal foreign objects. A b d o m i n a l pain may
Indications for Radiographic Imaging of the A b d o m e n
be subtle; some animals will cry out during gentle palpation,
without Contrast M e d i a
whereas many just tense their abdomen (i.e., guarding) or
Indications for Ultrasonography o f the Stomach and
try to move away. A rough palpation technique can cause a
Small Intestines
normal animal to tense up or vocalize during palpation,
Indications for Contrast-Enhanced Gastrograms
m i m i c k i n g the reaction o f an animal with abdominal pain.
Indications for Contrast-Enhanced Studies o f the Small
Light, careful palpation permits the definition of as much of
Intestine
the internal abdominal contents as possible. If sufficient
Indications for B a r i u m Contrast Enemas
abdominal fluid is present to prevent meaningful abdominal
P E R I T O N E A L FLUID A N A L Y S I S
palpation, ballottement of the abdomen should produce a
D I G E S T I O N A N D A B S O R P T I O N TESTS
fluid wave.
SERUM C O N C E N T R A T I O N S OF VITAMINS
D u r i n g a rectal examination, the examiner should be
O T H E R S P E C I A L TESTS F O R A L I M E N T A R Y T R A C T
able to identify and evaluate the colonic mucosa, anal sph
DISEASE
incter, anal sacs, pelvic canal bones, muscular support
ENDOSCOPY
for the rectum, urogenital tract, and luminal contents.
BIOPSY T E C H N I Q U E S A N D S U B M I S S I O N
However, it is particularly easy to misinterpret mucosal
Fine-Needle Aspiration Biopsy
polyps as mucosal folds and to miss partial strictures that
Endoscopic Biopsy
are large enough to allow a single digit to pass through
Full-Thickness Biopsy
easily.
ROUTINE LABORATORY EVALUATION measuring h u m a n a l b u m i n result i n falsely low measure
ments of canine albumin.
COMPLETE B L O O D COUNT Ill animals (especially those receiving multiple drugs) are
Complete blood counts (CBCs) are especially important i n at risk for secondary renal or hepatic failure. Very young and
animals at risk for neutropenia (e.g., parvoviral enteritis, very small animals easily become hypoglycemic i f they
severe sepsis), infection (e.g., aspiration pneumonia), or cannot eat or absorb ingested nutrients. Finally, finding
anemia (e.g., pale mucous membranes, melena, hemateme hypercalcemia or hypoalbuminemia may provide a clue to
sis) and also i n those that have fever, weight loss, or anorexia the underlying problem (i.e., make some disorders more
resulting from an occult cause. The clinician should always likely) i n animals with weight loss or anorexia.
evaluate absolute numbers of the different types o f white
blood cells ( W B C s ) , not the percentages, because an animal URINALYSIS
may have an abnormal percentage o f a particular W B C and Urinalysis is required to accurately evaluate renal function
yet have a normal absolute number of cells (and vice versa). and, i n conjunction with the urine protein:creatinine ratio,
If the animal is anemic, the clinician should evaluate the to help identify the cause of hypoalbuminemia. U r i n e should
C B C for evidence o f iron deficiency (e.g., hypochromasia, always be obtained before fluid therapy is begun.
microcytosis, thrombocytosis, increased red b l o o d cell dis
tribution width).
FECAL PARASITIC EVALUATION
COAGULATION
A platelet count is important. Platelet numbers can be esti Fecal flotation is indicated i n almost every animal with ali
mated on the basis o f correctly made b l o o d smears (i.e., a mentary tract disease or weight loss, especially i n puppies
dog should have an average of 8 to 30 platelets per oil immer and kittens. Even i f it is not the primary problem, parasitism
sion field; finding 1 platelet per field suggests a platelet count may cause additional debilitation. Concentrated salt or
of approximately 15,000 to 20,000/l). Coagulation panels sugar solutions are typically used for fecal flotation. The
may detect unsuspected coagulopathies (e.g., disseminated former are usually superior, although incorrectly made
intravascular coagulation). Activated clotting times are crude solutions may not force heavier ova (e.g., whipworms) to
estimates of the intrinsic clotting pathway; partial thrombo float. Moreover, concentrated salt solutions can distort
plastin times are more sensitive. Mucosal bleeding time is an Giardia cysts, making identification difficult. A zinc sulfate
excellent screening test for coagulopathies severe enough to flotation solution is preferred for detecting nematode ova
cause clinical bleeding. and Giardia cysts. Centrifugation is strongly recommended;
it promotes separation o f cysts from the fecal matter
SERUM BIOCHEMISTRY PROFILE and results i n a more sensitive fecal examination. Some
Serum biochemistry profiles that include alanine transami parasites intermittently shed small numbers o f ova or cysts,
nase and alkaline phosphatase activities, as well as the b l o o d necessitating repeated fecal analyses for diagnosis. W h i p
urea nitrogen, creatinine, total protein, albumin, sodium, w o r m and Giardia infections can be especially difficult to
potassium, chloride, total C O , cholesterol, calcium, phos
2 diagnose.
phorus, magnesium, bilirubin, and glucose concentrations, The ova o f the most c o m m o n tapeworm species are con
are important i n animals with severe vomiting, diarrhea, tained i n segments and are not found by flotation tech
ascites, unexplained weight loss, or anorexia. These values niques. Nanophyetus salmincola (the fluke that transmits
are crucial to correctly diagnosing the animal's problem and salmon poisoning) is detected by many flotation solutions,
appropriately treating it. The clinician cannot predict the although sedimentation examinations are required to detect
changes that w i l l occur or the magnitude o f the changes i n most other fluke ova. Cryptosporidiosis can be detected
a particular animal, even when the cause o f the disease is by flotation techniques, but higher magnification (X1000)
known. The total carbon dioxide concentration is not as must be used. The clinician should send the feces to a
definitive as b l o o d gas analysis but helps define the acid-base laboratory that is familiar w i t h this coccidium and is able
status, which also cannot be accurately predicted. to perform special procedures to detect it. E L I S A methodol
The albumin concentration is more useful than the total ogy is more sensitive than fecal examination for finding
protein concentration. Hyperglobulinemia, which has many Cryptosporidia.
causes (e.g., heartworms, chronic dermatitis, ehrlichiosis) i n Direct fecal examination, although convenient, is not sen
a hypoalbuminemic dog can cause the serum total protein sitive for nematodes and should not replace flotation tech
concentration to be normal. Severe hypoalbuminemia (i.e., niques. However, occasionally amebiasis, strongyloidiasis,
less than 2.0 g/dl) is important diagnostically; it is more and w h i p w o r m infections missed by flotation procedures
commonly found in animals with infiltrative alimentary can be detected i n this way. M o t i l e Giardia and Tritricho
tract disease, parvoviral diarrhea, intestinal lymphangiecta monas trophozoites may be found i f the feces are very fresh
sia, gastrointestinal blood loss, or ascites. It is important to and the smear is adequately diluted w i t h saline solution.
have the serum albumin measured by technology designed Direct examination seems about half as sensitive as zinc
for canine and feline albumin; some techniques used for sulfate flotation techniques i n detecting giardiasis.
Fecal sedimentation is time-consuming and offers no MISCELLANEOUS FECAL ANALYSES
advantage i n detecting c o m m o n gastrointestinal tract para
sites. However, it does detect fluke ova missed by other tech Enzyme-linked immunosorbent assays (ELISAs) can be used
niques, especially the ova o f Eurytrema spp., Platynosomum to detect various antibodies or antigens. The test for canine
spp., and Amphimerus spp. plus Heterobilharzia. parvovirus seems to be very specific. However, virus may not
Feces may be preserved by m i x i n g equal volumes o f feces be found i n the feces for the first 24 to 48 hours, and it may
and 10% neutral buffered formalin or by using commercially be necessary to repeat the test i n 2 to 3 days i f initial results
available kits. Polyvinyl alcohol is used i n the latter, and feces are negative i n a dog strongly suspected o f having parvoviral
preserved i n this manner can be examined weeks to months infection. In addition, although dogs with parvoviral diar
later. These techniques are especially useful if one cannot rhea initially shed large amounts of virus, fecal shedding
immediately examine feces for protozoal cysts. decreases substantially during the ensuing 7 to 14 days. A
repeatedly negative test result therefore does not rule out
parvoviral infection, but it does necessitate a consideration
FECAL DIGESTION TESTS of other acute, febrile gastroenteritides (e.g., salmonellosis).
This test is particularly valuable i f there are epidemiologic
Examining feces for undigested food particles by staining considerations (e.g., breeding kennel).
thin fecal smears with the Sudan stain (for fat) or iodine (for ELISAs for detecting a Giardia-specific antigen i n human
starch and muscle fibers) is of dubious value. Although the (ProSpecT/Microplate ELISA assay for Giardia, Alexon, Inc.)
finding of excessive amounts o f undigested fecal fat is sug and canine/feline feces ( S N A P Giardia Test, Idexx Laborato
gestive o f exocrine pancreatic insufficiency (EPI), this test ries) are available. The S N A P Giardia test appears to be sen
has many false-positive and false-negative results. If EPI is a sitive and specific but has not been carefully compared with
differential diagnosis, serum trypsin-like immunoreactivity multiple zinc sulfate flotation examinations i n clinical
(TLI) is a better way to confirm the diagnosis (see the section patients. It has the advantage of being able to be performed
on digestion and absorption tests). in the practice. A n IFA test ( M E R I F L U O R Cryptosporidium/
Fecal analysis for proteolytic activity (i.e., the fecal trypsin Giardia direct immunofluorescent kit, Meridian Bioscience,
content) also tests for E P I . Qualitative estimates (e.g., fecal Inc.) appears to be specific but has the disadvantage of
film digestion, fecal gelatin digestion) are unreliable. Q u a n requiring that feces be sent to a commercial laboratory.
titative analysis is seldom needed because the T L I test is ELISAs for detecting cryptosporidial antigens i n feces
easier and more pleasant to perform. It is rarely necessary to (ProSpecT C r y p t o s p o r i d i u m Microplate Assay, Meridian
quantitate fecal proteolytic activity to diagnose EPI caused Diagnostics, Inc. and ProSpecT Cryptosporidium micro-
by pancreatic duct obstruction, something T L I does not plate assay, Remel Inc.) appear to be more sensitive than
detect. In this test feces are collected for 3 consecutive days routine fecal examinations. Special staining of fecal smears
and stored frozen until sent to the laboratory. However, this with a modified Ziehl-Neelsen acid-fast technique is also
is an exceedingly rare situation. sensitive, albeit more labor intensive. A n I F A test ( M E R I
Quantitated fecal fat analysis is seldom indicated. F L U O R Cryptosporidium/Giardia direct immunofluorescent
Although sensitive for detecting fat malabsorption and mal kit, M e r i d i a n Bioscience, Inc.) was not as sensitive as the
digestion, it is expensive and unpleasant to perform and does ELISAs when looking for Cryptosporidia.
not differentiate malabsorption from E P I . Electron microscopy can be used to identify various viral
Fecal occult b l o o d analyses are seldom useful because particles (e.g., coronavirus, astrovirus) i n feces. Because the
most pets eat meat by-products that cause a positive reac E L I S A is usually adequate for detecting parvovirus, electron
tion. False-positive reactions may also be produced by microscopy is rarely necessary. However, it is reasonable to
cimetidine, oral iron preparations, and some vegetables. Fur choose this technique i f other test results are not diagnostic
thermore, the sensitivity o f different techniques varies, and there are epidemiologic considerations. Fecal samples
making it difficult to accurately compare results. Finally, blood for electron microscopy analysis should be obtained early
is often not distributed homogeneously throughout the i n the disease because fecal viral concentrations may de
feces, and a negative result could stem from a sampling error crease dramatically within 7 to 14 days after the onset of
(especially i n animals with lower intestinal tract problems). signs. Furthermore, some delicate viruses (e.g., coronavirus)
If analysis for fecal occult b l o o d is desired, the optimal degenerate quickly, and the feces from animals suspected of
approach is to feed the animal a meat-free diet for 3 to 4 days having such an infection must be handled appropriately if
before performing the test. Tests using the reagents benzi meaningful results are to be obtained. It is important that
dine or orthotoluidine to detect hemoglobin tend to be very clinicians contact their laboratory for instructions on sample
sensitive (and hence less specific), whereas those using guaiac handling.
are less sensitive (and thus more specific). A sensitive and Assays for bacterial toxins i n feces sometimes help i m p l i
specific fluorometric method has been validated i n dogs. cate specific bacteria as causing diarrhea. There are numer
Repeated testing may be necessary to demonstrate intermit ous ELISA tests available for detecting Clostridum difficile
tent bleeding. toxin i n h u m a n feces; however, the sensitivity o f these tests
for canine feces appears to be poor. The tissue culture assay CYTOLOGIC EVALUATION OF FECES
for Clostridum difficile toxin in feces is sensitive but only
performed in research laboratories. ELISA tests (Clostridium Fecal cytologic evaluations may identify etiologic agents or
perfringens Enterotoxin Test, TechLab) and reverse passive inflammatory cells. In this method a thin, air-dried smear is
latex agglutination tests (Oxoid PET-RPLA, Unipath Co.) stained with Gram's or a Romanowsky-type stain (e.g., Diff-
tests for Clostridium perfringens enterotoxin are available. Quik). The latter identifies cells better than Gram's stain
However, the results of these tests do not clearly correlate does.
with presence or absence of disease. Their value in clinical Finding excessive numbers of spore-forming bacteria (e.g.,
cases is still being defined. more than 3 to 4 per1000xfield)was once thought to strongly
There are both culture techniques (InPouch TF, BioMed suggest clostridial colitis (see Fig. 33-1). However, the pres
Dianonstics) and polymerase chan reaction (PCR) tests for ence of spores is neither specific nor sensitive for clostridial
Tritrichomonas fetus in feline feces. The culture technique colitis. Finding that the bacterial population is relatively
can be done in the practice and appears to be sensitive and uniform morphologically is of uncertain value, other than to
specific; it is more sensitive than direct fecal examination. show that the normal bacterial flora is disrupted. However,
no comments can be made relative to cause or effect.
Short, curved, gram-negative rods (i.e., "commas" or
BACTERIAL FECAL CULTURE "seagull wings") are suggestive of campylobacteriosis. The
larger spirochetes, which are often plentiful in diarrheic
Fecal culture is seldom indicated in small animals unless a feces, are not C. jejuni and are of uncertain pathogenicity.
contagious disease is strongly suspected or other test findings Although cytologic preparations are not critically analyzed
(e.g., endoscopy and biopsy) are nondiagnostic. Specific in diarrheic small animals, fecal cytologic analysis for Cam
culture techniques for the detection of each pathogen are pylobacter spp. is a specific, albeit insensitive, method in
recommended. Therefore the clinician should contact the people. Fungal organisms (e.g., Histoplasma capsulatum,
laboratory before submitting feces, informing them specifi Cyniclomyces guttulatus Candida spp.) are rarely found by
cally what bacteria to attempt to grow and following their fecal examination; cytologic examination of mucosal scrap
instructions regarding the handling of specimens. It is impor ings or histologic examination of biopsy specimens is usually
tant to remember that fecal culture cannot be used to diag necessary to diagnose histoplasmosis.
nose small intestinal antibiotic-responsive enteropathy (ARE). The finding of leukocytes in feces indicates the presence
The pathogens most likely to be cultured from feces from of a transmural colonic inflammation instead of just a
small animals are C. perfringens, C. difficile, Salmonella spp., superficial mucosal inflammation. However, a definitive
Campylobacter jejuni, Yersinia enterocolitica, and verotoxin- diagnosis of a particular cause is not possible.
producing strains of Escherichia coli. Confirmation of toxin
production of isolates can be performed using PCR tech
niques or bioassay. Aeromonas spp. and Plesiomonas spp. may RADIOGRAPHY OF THE
also cause diarrhea. Salmonella spp. are best cultured by ALIMENTARY TRACT
inoculating at least 1 g of fresh feces into an enrichment
medium and subsequendy a selective medium specific for Imaging (i.e., radiography) allows structures to be evaluated
Salmonella spp. It is sometimes possible to culture Salmo that cannot be adequately assessed during physical examina
nella from the colonic mucosa. A PCR technique has been tion (e.g., esophagus, stomach) and may detect abnormali
used recently in the evaluation of equine feces and may be ties missed by abdominal palpation (e.g., gastric mass,
useful for the evaluation of canine and feline feces. To culture foreign object, splenic parenchymal mass). Plain radiographs
C. jejuni, very fresh feces must be inoculated onto selective should always be obtained before contrast-enhanced radio
media and incubated at approximately 40 C instead of 37 graphs because (1) the former may yield diagnostic findings,
C. If inoculation is to be delayed, special transport media (2) contrast-enhanced radiographs may be contraindicated,
should be used, not routine commercial transport devices and (3) plain radiographs are needed to ensure a correct
(e.g., culturette swabs). PCR testing is available for Campy radiographic technique during the contrast procedure. Con
lobacter spp. in canine and feline feces (GI Lab, Texas A & M trast-enhanced radiographs may be able to detect abnor
University). The clinical value is still being defined. malities (e.g., a gastric outflow tract obstruction) that plain
It is important to note that the mere presence of any of radiographs cannot.
these bacteria in an animal's feces does not confirm that they Radiographs are generally useful in the diagnostic workup
are causing disease. Culture results must be correlated with of animals with dysphagia, regurgitation, vomiting, abdom
clinical signs and the results of other laboratory tests. inal mass or distention, abdominal pain, or acute abdomen.
Candida spp. are occasionally cultured from feces. The They are occasionally helpful in animals with constipation,
finding is often of uncertain significance, but the organisms weight loss, or anorexia of unknown cause, but other tests
may cause problems in some animals (e.g., those receiving are usually indicated first in such animals and often render
chemotherapy). imaging unnecessary. Radiographic findings are rarely diag-
nostic i n dogs or cats with diarrhea or copious abdominal dynamic studies (i.e., fluoroscopy, cinefluoroscopy) are nec
effusion. essary i f one is looking for dysphagia of neuromuscular
origin. These studies are performed by feeding conscious
animals various forms of barium (i.e., liquid, paste, and
ULTRASONOGRAPHY OF THE mixed with food).
ALIMENTARY TRACT
Findings
Ultrasonography may be done i n combination w i t h or Foreign objects, fractures, bone lysis, soft tissue masses or
instead o f radiography; however, it is extremely operator densities, and emphysema are c o m m o n l y found. The bone
dependent. It is often useful i n animals w i t h an acute surrounding the tooth roots should be examined for evi
abdomen, abdominal effusion, vomiting, diarrhea, weight dence o f lysis and the temporomandibular joints for signs of
loss, or anorexia o f u n k n o w n cause and also i n those with arthritis. It is important to remember to consider the bilat
an abdominal mass, distention, or pain. Ultrasonography eral symmetry o f the skull; one side should be compared
can be used to identify pancreatitis, infiltrations i n various with the other when evaluating the V D projection. W h e n
organs, and intussusceptions that radiography misses. Fur performing contrast-enhanced or dynamic studies, the clini
thermore, effusions, which render radiographs useless, cian should watch for the aspiration of barium, the strength
enhance ultrasonographic contrast. Ultrasonography can with which the bolus is propelled into the esophagus, and
be more informative than radiography when determining the synchronization o f the opening o f the cricopharyngeal
whether an animal with an acute abdomen requires surgery. muscle with the pharyngeal phase of swallowing.
Finally, ultrasonography can be used to guide the percutane
ous aspiration and biopsy o f intraabdominal lesions that INDICATIONS FOR I M A G I N G OF
would otherwise necessitate surgery or laparoscopy. THE E S O P H A G U S
Indications for evaluating the esophagus include regurgita
Techniques tion (including pharyngeal dysphagia), pain when swallow
A 5 M H z probe is probably the most utilitarian. H a i r is often ing, unexplained recurrent pneumonia or cough, and
clipped so that there is no trapped air that could compromise thoracic "masses" (seen radiographically) o f undetermined
the quality o f the image. F l u i d can be infused into the origin. A b a r i u m contrast-enhanced esophagram is neces
abdomen or stomach to improve the evaluation, but this is sary unless plain films reveal the presence o f an esophageal
infrequently needed. foreign object, evidence o f esophageal perforation (e.g., a
pleural effusion or pneumothorax), or an obvious hiatal
Findings hernia. Finding obvious megaesophagus on plain radio
The thickness, echodensity, and homogeneity of organs (e.g., graphs is usually considered sufficient, but some dogs with
liver, spleen, intestine, stomach, mesenteric l y m p h nodes, megaesophagus on plain radiographs demonstrate normal
masses) may be assessed. Intraparenchymal infiltrates that function when barium is administered. Ultrasonography is
cannot be detected radiographically may also be found. The seldom useful for dogs and cats with esophageal disease,
particular ultrasonographic findings seen i n specific disor unless there is a thoracic mass.
ders o f the alimentary tract are discussed i n subsequent
chapters dealing with the disorders. Techniques
L i q u i d b a r i u m is the best contrast agent for esophageal
studies; it provides excellent detail and, if aspirated, is not as
IMAGING OF THE ORAL CAVITY, noxious as paste or food. The clinician must be careful not
PHARYNX, AND ESOPHAGUS to administer drugs that affect esophageal motility (e.g.,
xylazine, ketamine, anesthesia). The animal should take
INDICATIONS several swallows o f dilute barium from a syringe, after which
Animals with dysphagia, oral pain, halitosis o f u n k n o w n right lateral and V D views are quickly obtained. If possible,
cause, or a swelling or mass should generally undergo the clinician should perform fluoroscopy as the animal swal
imaging. If dysphagia o f neuromuscular origin is suspected, lows the b a r i u m to assess esophageal motility and look for
dynamic studies (i.e., fluoroscopy) are recommended. U l t r a partial esophageal obstruction, segmental esophageal weak
sonography can be particularly informative i n the evaluation ness, gastroesophageal reflux, and esophageal-pharyngeal
of any infiltrates or masses. reflux (i.e., cricopharyngeal incompetence). Radiographs
may be taken i f a lesion is found fluoroscopically. If
Techniques fluoroscopy is not available, multiple radiographs (usually
Anesthesia is necessary so that animals can be properly lateral projections) are taken i n rapid succession, beginning
positioned for radiographs o f the skull. Lateral, dorsoventral very shortly (i.e., 5 to 10 seconds) after swallowing.
( D V ) , and oblique views are used to detect foreign objects B a r i u m paste is acceptable i f liquid is not available.
or fractures. O p e n - m o u t h ventrodorsal ( V D ) views and Hypertonic, iodine-contrast agents do not achieve as good a
end-on views o f the nose may also be helpful. However, contrast as barium and cause severe problems i f aspirated;
isotonic water-soluble iodine contrast agents are better. If
radiographic studies performed with liquid or paste contrast
agents do not detect an abnormality i n an animal i n w h i c h
esophageal disease is strongly suspected, the study should be
repeated using a mixture o f b a r i u m and food (both canned
food and dry kibble). Such studies may detect partial stric
tures or muscular weakness not found i n previous studies.
If barium is retained i n the esophagus but little or none
enters the stomach, the animal should be held i n a vertical
position so that gravity facilitates the migration of b a r i u m
into the stomach. If barium readily enters the stomach, this
indicates that there is no lower esophageal sphincter obstruc
tion. If a hiatal hernia is suspected but not seen, a lateral
radiograph of the caudal thorax may be taken while the
abdomen is manually compressed. This is done i n an attempt
to force the stomach to herniate into the thorax so that the
hernia can be demonstrated. FIG 29-1
If esophageal disease seems likely but is not found by Lateral thoracic r a d i o g r a p h from a d o g that w a s seen
static radiographs, fluoroscopic studies are required. It may because of c o u g h i n g . N o t e the d i l a t e d , air-filled e s o p h a g u s
(arrows). C o n t r a s t - e n h a n c e d e s o p h a g r a m (with fluoroscopy)
be necessary to observe the esophagus for several minutes
o b t a i n e d 2 d a y s later d o c u m e n t e d n o r m a l e s o p h a g e a l size
(or longer) before some abnormalities (e.g., gastroesopha a n d function.
geal or esophageal-pharyngeal reflux) occur. In animals with
marginal esophageal disease, fluoroscopy may be necessary
to document that primary or secondary esophageal waves
are present but are either weak or not readily stimulated. times causes pneumothorax, emphysematous mediastinitis,
If an esophageal perforation is suspected (e.g., septic or a pleural or mediastinal effusion.
pleuritis or mediastinitis, pneumomediastinum or pneumo Contrast-enhanced esophagrams should be considered
thorax), an isotonic, iodine contrast m e d i u m may be used. i n animals with suspected esophageal disease and i n those
However, the only purpose o f such a study is to localize the with unidentified thoracic masses because many esophageal
perforation. If the clinician already knows where the leakage tumors radiographically resemble pulmonary parenchymal
is likely to be (e.g., there is a bone foreign body i n the esoph masses (see Fig. 31-5). Contrast-enhanced esophagrams may
agus), radiographs are of dubious value; exploratory surgery also show that structures that seemingly involve the esopha
is usually a better option. gus actually do not. A n obstruction is suggested on contrast-
enhanced esophagrams i f the b a r i u m c o l u m n terminates
Findings abruptly as it travels caudally; weakness usually causes con
Esophageal dilation, foreign objects, soft tissue densities, trast to be retained throughout the esophagus (Fig. 29-3)
spondylosis suggestive o f spirocercosis, and hiatal hernia unless it is segmental. A partial obstruction is suggested by
may often be identified on plain films. A n air-filled esopha the retention of barium-impregnated food but not o f l i q u i d
gus is not always diagnostic of pathologic esophageal weak or paste (see Fig. 31-4).
ness. Although it is tempting to use plain radiograph findings A b a r i u m contrast study may reveal malpositioning (e.g.,
as the basis for the diagnosis of esophageal disease when hiatal hernia; see Fig. 31-2). However, the finding o f a prop
there is an "obvious" abnormality, it is easy to misinterpret erly positioned structure on one study does not ensure that
plain films or miss abnormalities that a b a r i u m contrastl- it will stay properly positioned (e.g., some hiatal hernias slide
enhanced study reveals. Even the finding of a dilated, gas- i n and out o f the diaphragm and may be normally posi
filled esophagus on plain thoracic films does not definitively tioned when the radiograph is taken). Gastroesophageal
diagnose "megaesophagus." Rarely, animals with a dilated, reflux and esophagitis also may be difficult to diagnose
air-filled esophagus on plain films are found to have n o r m a l radiographically. B a r i u m may adhere to a severely diseased
esophageal function when evaluated with b a r i u m contrast- mucosa, but less severe esophagitis may not be detected. In
enhanced radiographs (Fig. 29-1). Likewise, the appearance addition, normal dogs may have an episode o f gastroesoph
of an accumulation of foodlike material i n the classic loca ageal reflux during a contrast study, whereas dogs with
tion for a vascular ring anomaly may be caused by a localized pathologic gastroesophageal reflux may not have reflux
esophageal weakness or a thymic cyst. during a short examination.
M a n y foreign objects i n the esophagus (e.g., bones) can If the animal is believed to be regurgitating but the b a r i u m
be seen on plain radiographs. However, excellent radio contrast-enhanced radiographs are unrevealing, either the
graphic technique is necessary because some bones (espe assessment o f regurgitation is wrong or there is occult
cially poultry bones) as well as rawhide treats are relatively disease, i n which case reexamination of the esophagus with
radiolucent (Fig. 29-2). A n esophageal perforation some- fluoroscopy or endoscopy or both must be done.
FIG 2 9 - 2
A , Lateral thoracic r a d i o g r a p h from a d o g w i t h a foreign o b j e c t in the esophagus (arrows).
N o t e the c o n c o m i t a n t pleural effusion. A chicken b o n e h a d p e r f o r a t e d the e s o p h a g u s , a n d
septic pleuritis w a s present. ( A from A l l e n D, editor: Small animal medicine, Philadelphia,
1 9 9 1 , JB Lippincott.) B , Lateral t h o r a c i c r a d i o g r a p h f r o m a d o g w i t h a r a w h i d e treat in
the e s o p h a g u s . The density representing the b o n e (arrows) is more diffuse than w a s seen
in A a n d looks m o r e like a p u l m o n a r y p a r e n c h y m a l density than a b o n e .
IMAGING OF THE STOMACH AND foreign objects and alimentary tract dilation resulting from
SMALL INTESTINE obstruction, foreign objects, or masses.
neum, abdominal effusions, and displaced organs suggestive intestinal distention is found but is very localized and seems
of a mass or adhesion. out of place (e.g., has herniated), a strangulated or incarcerated
Gastric outflow tract obstruction is easy to diagnose when intestinal obstruction (see Fig. 33-9) should be considered.
there is marked gastric distention (Fig. 29-4). However, if the Linear foreign bodies rarely produce gas-distended bowel
patient has recently vomited, the stomach may be empty and loops. Instead, they tend to cause the intestines to bunch
contracted. Gastric dilation, especially with volvulus, is easily together, and sometimes small gas bubbles are present (see
recognized (see Fig. 32-4). Radiodense foreign objects are Fig. 33-10). This occurs because the intestines "gather" around
easily seen, but radiolucent foreign objects are seen only if the linear foreign object as they try to propel it aborad. This
they are outlined by swallowed air. "gathering" or "bunching" plus the fact that linear foreign
Intestinal obstructions are usually easier to diagnose on bodies tend primarily to affect the upper small intestines (i.e.,
the basis of plain radiograph findings than are gastric duodenum) mean that it is rare that they cause gas-distended
obstructions; obstructed intestines distended with air, fluid, loops o f bowel. Sometimes pleated (i.e., "accordian-like")
or ingesta are not readily emptied when the patient vomits intestines can be seen on plain radiographs (see Fig. 33-10).
(unless it is a high, duodenal obstruction). However, intesti It is difficult to determine the thickness o f intestines on
nal distention (i.e., ileus) may be caused by inflammation plain radiographs. Animals with diarrhea and an increased
(i.e., adynamic or physiologic ileus) as well as obstruction amount of intestinal fluid are often misdiagnosed as having
(i.e., mechanical, occlusive, or anatomic ileus). A n a t o m i c thickened intestinal walls.
ileus (i.e., obstruction) typically produces a nonuniform Decreased serosal contrast is due to either lack of fat or
intestinal distention with a greater degree o f distention than excessive abdominal fluid (see Chapter 36). Displacement of
is seen with physiologic ileus (Fig. 29-5). If "stacking" o f the an organ (Fig. 29-7) often means that there is a mass present.
distended intestines or sharp bends and turns in the dilated Pneumoperitoneum is diagnosed i f both the thoracic and
intestines are seen, this also suggests anatomic ileus. Lateral abdominal surfaces o f the diaphragm or the serosal surfaces
radiographs obtained with the animal standing rarely aid in of the liver, stomach, or kidneys are easily seen (see Fig.
differentiating anatomic from physiologic ileus. Even expe 34-1, A). Pneumoperitoneum may also be documented by
rienced radiologists occasionally misdiagnose physiologic the finding o f only a few gas bubbles in the peritoneal cavity
ileus as representing an obstruction. Thus diseases producing (see Fig. 34-1, B).
severe inflammation (e.g., parvoviral enteritis) may clinically
and radiographically m i m i c an intestinal obstruction. INDICATIONS FOR U L T R A S O N O G R A P H Y
Special types o f intestinal obstruction are associated with O F THE S T O M A C H A N D
unique radiographic findings. If the entire intestinal tract is S M A L L INTESTINES
uniformly distended with gas (Fig. 29-6) and the clinical Ultrasonography usually reveals almost any soft tissue change
signs fit, mesenteric volvulus may be diagnosed. If marked that plain radiographs detect in addition to infiltrations that
FIG 29-4
Plain lateral r a d i o g r a p h f r o m a d o g w i t h gastric o u t f l o w obstructi on. N o t e the d i l a t e d
stomach p r o t r u d i n g past the costal a r c h (arrows).
FIG 29-5
A , Plain lateral a b d o m i n a l r a d i o g r a p h f r o m a d o g w i t h a n intestinal obstruction causing
intestinal d i s t e n t i o n . N o t e the m a r k e d l y i n c r e a s e d d i a m e t e r of the small intestinal lumen
(arrows). B , Plain lateral a b d o m i n a l r a d i o g r a p h from a d o g w i t h peritonitis c a u s i n g
p h y s i o l o g i c ileus. N o t e the lesser d e g r e e of small intestinal distention c o m p a r e d w i t h that
in A . The l a r g e gas-filled structure is the gastric pylorus (arrows). (Courtesy Dr. Kenita
Rogers, Texas A & M University, C o l l e g e Station, Tex.)
radiographs cannot detect. Ultrasonography is particularly and it is easy to miss small foreign objects (especially in the
useful for detecting intussusceptions, pancreatitis, abdomi stomach i f there is food and gas present). Ultrasonography
nal infiltrative disease, and small amounts of effusion not will not detect bony changes and modest microhepatica that
seen radiographically; for evaluating the hepatic paren are easily detected by radiographs. The skill of the ultraso
chyma; and for identifying abdominal neoplasia i n animals nographer determines the usefulness of the technique.
with a substantial effusion. Ultrasonography is m u c h more
revealing than radiography i n animals with m i n i m a l body Technique
fat that have little or no radiographic contrast in the abdomen. Before ultrasonography is performed, the abdominal hair
However, very dehydrated animals may be difficult to image, usually should be clipped to improve the quality of the
infiltrates (Fig. 29-8, A ) , intussusceptions (Fig. 29-8, B ) ,
enlarged l y m p h nodes (Fig. 29-8, C ) , masses (Fig. 29-8, D),
some radiolucent foreign objects, and small amounts o f free
peritoneal fluid that radiographs cannot detect. If tissue
infiltrates are found, they can sometimes be aspirated by the
fine-needle technique.
Technique
FIG 2 9 - 6 The animal should not be allowed to eat for at least 12
Lateral a b d o m i n a l r a d i o g r a p h from a d o g that h a d a n acute hours (preferably 24 hours) before the procedure, and feces
onset of v o m i t i n g , a b d o m i n a l p a i n , a n d shock. There is a
should be removed with enemas. Plain radiographs should
uniform intestinal distention that is not as g r e a t as that in
Fig. 2 9 - 5 , A. H o w e v e r , distention is m o r e than that seen in
be obtained immediately before the contrast-enhanced films
Fig. 2 9 - 5 , 8. Some intestinal loops h a v e assumed a vertical to verify that the abdomen has been properly prepared and
orientation (arrows), w h i c h suggests the existence of a n the radiographic technique is correct and to determine
obstruction. This d o g h a d a mesenteric volvulus. (Courtesy whether the diagnosis cannot be made on the basis o f the
Dr. Susan Yanoff, U.S. Military.) plain radiographic findings. L i q u i d b a r i u m sulfate is then
administered orally (8 to 10 m l / k g i n small dogs and cats and
5 to 8 m l / k g i n large dogs). Iohexol can be administered
orally (i.e., 700 to 875 m g I/kg, w h i c h is about 11/4 to 11/2 m l /
kg). The agent should be administered via a stomach tube to
ensure adequate gastric filling and optimal evaluation o f the
stomach. The animal should not receive motility-altering
drugs (e.g., xylazine, parasympatholytics), which delay outflow.
Immediately after b a r i u m administration, radiographs
are taken i n the left and right lateral plus D V and V D projec
tions. Radiographs i n the lateral and D V projections should
be obtained again at 15 and 30 minutes and perhaps also at
1 to 3 hours. The right lateral view causes b a r i u m to pool i n
the pylorus, the left lateral view causes it to p o o l i n the gastric
body, the D V view causes it to p o o l along the greater curva
ture, and the V D view allows better evaluation o f the pylorus
and antrum. Double-contrast gastrograms provide more
FIG 2 9 - 7 detail than single-contrast gastrograms. They are performed
Lateral a b d o m i n a l r a d i o g r a p h from a d o g w i t h a l a r g e by administering b a r i u m via a stomach tube, then removing
g r a n u l o m a caused b y pythiosis. Small intestinal loops a r e most o f the b a r i u m through the same tube and insufflating
d i s p l a c e d dorsally a n d c a u d a l l y (small arrows). The b o r d e r
the stomach with gas until it is mildly distended.
of the mass is not d i s c e r n i b l e except w h e r e it displaces
If available, fluoroscopy is best performed immediately
small intestinal loops. The f i n d i n g of a d i l a t e d intestinal l o o p
(long arrows) is consistent w i t h obstruction. after administration o f the barium. It can be used to evaluate
gastric motility, gastric outflow, and the maximal opening
size o f the pylorus. If the animal is fed b a r i u m mixed with
examination. This is not necessary i n animals with m i n i m a l food (only recommended if gastric outflow tract obstruction
hair. Because air in the stomach or intestines limits the use is suspected despite n o r m a l l i q u i d b a r i u m study findings),
fulness of ultrasonography, exercise, drugs (e.g., some nar gastric emptying will be markedly delayed compared with
cotics) that cause hyperventilation, and enemas should be that seen when the animal is fed liquid barium.
avoided before the examination.
Findings
Findings Gastric emptying is considered delayed if liquid b a r i u m does
Ultrasonography should detect almost any soft tissue change not enter the d u o d e n u m 15 to 30 minutes after administra
that plain radiographs detect, plus gastric and intestinal tion or i f the stomach fails to almost completely empty a
FIG 29-8
A , U l t r a s o n o g r a p h i c i m a g e of t w o sections of small intestine f r o m a cat w i t h a n a l i m e n t a r y
tract l y m p h o m a . The n o r m a l intestine o n the right is 2 . 8 mm thick (see the t w o " + ' s " noted
as D 2 ) , w h e r e a s the a b n o r m a l intestine o n the left is 4.5 mm thick (D1) because of
neoplastic infiltrates. B , U l t r a s o n o g r a p h i c i m a g e o f a n ileocolic intussusception that w a s
not o b v i o u s o n p l a i n a b d o m i n a l r a d i o g r a p h s . There a r e t w o intestinal w a l l s (small arrows)
seen o n e a c h side of the lumen (large arrow). C , A n e n l a r g e d mesenteric l y m p h n o d e in a
d o g c a u s e d b y l y m p h o m a , seen b y u l t r a s o n o g r a p h y . The l y m p h n o d e w a s not detected on
r a d i o g r a p h s o r b y a b d o m i n a l p a l p a t i o n . D , Ultrasound i m a g e of the gastric antrum from
a d o g w i t h b e n i g n gastric p o l y p s . O n e p o l y p c a n be seen (arrows) p r o t r u d i n g into the
gastric lumen. (Courtesy Dr. Linda H o m c o , C o r n e l l University, I t h a c a , N.Y.)
liquid barium meal in 3 hours (see Fig. 32-2). L u m i n a l filling persistent spot of barium is identified in the stomach long
defects (e.g., growths and radiolucent foreign objects), ulcers, after the organ has emptied itself of the contrast agent (see
pyloric lesions preventing gastric emptying, and infiltrative Fig. 32-6). The duodenum should be scrutinized in a search
lesions may be seen using this method (see Fig. 32-2, C ) . for constrictions and infiltrative lesions because many vom
However, normal peristalsis, ingesta, or gas bubbles may iting animals have disease there (e.g., inflammatory bowel
resemble an abnormality; therefore a change must be seen disease, tumors) rather than in the stomach (see Chapter 33).
on at least two separate films before the clinician can diag
nose disease. INDICATIONS FOR CONTRAST-
Contrast-enhanced gastrograms are not as sensitive as ENHANCED STUDIES OF THE
endoscopy for detecting gastric ulceration, and they cannot S M A L L INTESTINE
detect erosions. Ulcers are documented radiographically i f V o m i t i n g is the principal reason for performing contrast
barium is seen to enter the gastric or duodenal wall or i f a studies of the upper small intestine. Contrast-enhanced
radiographs are particularly useful for distinguishing ana
tomic from physiologic ileus. O r a d obstructions are easier to
demonstrate than aborad ones i f the contrast m e d i u m is
administered orally. If a very aborad obstruction is suspected
(e.g., ileocolic intussusception), a barium enema (or prefer
ably ultrasonography) is often better than an upper gastro
intestinal contrast series. Although linear foreign objects
usually produce subtle findings on plain radiographs, they
often cause a classic "pleating" or "bunching" o f the intes
tines to be seen on contrast films (see Fig. 33-10, C ) .
Animals with diarrhea seldom benefit from contrast
studies of the intestines because normal radiographic
findings do not exclude the presence o f severe intestinal
disease, and even i f radiographic findings indicate the pres
ence of infiltrative disease, it is still necessary to obtain a
biopsy specimen to determine the cause. Contrast series are
sometimes useful i f the clinician is trying to decide whether
to perform endoscopy or surgery. However, it is usually more
cost-effective to perform endoscopy or surgery and skip the FIG 2 9 - 9
contrast-enhanced radiographs. Lateral c o n t r a s t - e n h a n c e d r a d i o g r a p h f r o m a d o g w i t h
Use o f iodinated contrast agents (preferably iohexol) is d u o d e n a l l y m p h o m a . N o t e the s c a l l o p e d a p p e a r a n c e to the
reasonable if an alimentary tract perforation is suspected. m a r g i n of the small intestine (arrows).
However, i f spontaneous septic peritonitis is strongly sus
pected, it can usually be definitively diagnosed by ultra
sound-guided abdominocentesis and fluid analysis. If "Enteritis" is often incorrectly diagnosed i f a fine "brush
ultrasound is unavailable and b l i n d abdominocentesis is border" i n the lumen is found. However, this finding actually
unrevealing in such a patient, it is usually better to perform results from the b a r i u m normally distributing itself among
a thorough exploratory laparotomy than contrast-enhanced villi, not from enteritis. Infiltration is denoted by scalloped
radiography. margins (sometimes called thumb-printing); such a pattern
(Fig. 29-9) may be seen i n the setting of neoplasia (e.g.,
Technique lymphoma), inflammatory bowel disease, fungal infection
Liquid barium sulfate is administered as described for con (e.g., histoplasmosis), or parvoviral enteritis. However, its
trast-enhanced gastrography. Lateral and V D radiographs absence does not rule out the presence o f infiltrative disease.
should be obtained immediately and then 30, 60, and 120 Focal dilations not caused by obstruction (i.e., diverticula)
minutes after barium administration. Additional films are are rare and usually represent a localized neoplastic infiltrate.
obtained as necessary. The study is completed once contrast In rare instances, unsuspected intestinal b l i n d loops or short-
has reached the colon. If chemical restraint is absolutely bowel syndromes may be detected. M o t i l i t y problems may
necessary, acetylpromazine may be used. Fluoroscopy is cause slowed passage o f the contrast through the alimentary
rarely needed for these studies. tract.
Hypertonic iodinated contrast agents are inferior to
barium for small intestinal studies because they decrease the INDICATIONS FOR B A R I U M
intestinal transit time and can cause considerable fluid shifts CONTRAST E N E M A S
by osmotically drawing fluid into the gastrointestinal tract. If ultrasound and flexible colonoscopy are available, there is
Their potential advantages rarely outweigh the disadvan seldom any need for barium enemas. If only rigid colonos
tages. Iohexol is safer and produces better detail than the copy is available, barium enemas are needed to evaluate the
hypertonic iodinated compounds. ascending and transverse colon, areas inaccessible to rigid
scopes. If colonoscopy is unavailable, a barium enema may
Findings be useful for looking for infiltrative lesions (e.g., rectal-colonic
In a complete intestinal obstruction, the barium c o l u m n neoplasia causing hematochezia), a partial or complete
cannot advance beyond a certain point, and the intestines obstruction, or ileocolic or cecocolic intussusception. It can
orad to this point are typically dilated. A partial obstruction also evaluate the colon orad to a near-complete rectal obstruc
may be denoted by delayed passage past a certain point tion to determine whether there are more infiltrative lesions
(there may or may not be dilation o f the intestines orad to or obstructions besides the one palpated near the rectum.
this point) or constriction o f the lumen. Because it is easy to
overinterpret contrast-enhanced radiographs o f the intes Technique
tines, changes must be seen o n at least two different films The patient should be fasted for at least 24 hours, and then
taken at different times before a disease is diagnosed. the colon must be emptied and cleaned by enemas or ali-
mentary tract lavage solutions, or both. The animal should catheter (e.g., a dialysis catheter, a sterile teat cannula, or an
be anesthetized and a balloon-tipped catheter placed in the 18-gauge cephalic catheter with additional holes cut with a
colon. The balloon is then inflated so that b a r i u m cannot scalpel) may be successful. It is sometimes best to allow fluid
leak out the rectum. Approximately 7 to 10 m l o f liquid to drain out o f the catheter without applying negative pres
barium/kg at body temperature is infused into the colon sure.
until it is uniformly distended, and lateral and V D radio If peritoneal inflammation is suspected but abdominal
graphs are obtained. The colon may then be emptied of fluid cannot be retrieved, a diagnostic peritoneal lavage may
barium and insufflated with air to achieve a double-contrast be performed. In this method a sterile catheter (preferably
barium enema, which provides greater detail. If too m u c h with multiple fenestrations) is inserted into the abdomen
barium is administered, the ileum may fill with the contrast and warm, sterile physiologic saline solution (20 ml/kg) is
agent, obscuring colonic detail and making the study less administered rapidly. The abdomen is massaged vigorously
useful. for 1 to 2 minutes, and then some of the fluid is aspirated.
The aspirate is evaluated cytologically.
Findings
B a r i u m enemas unreliably detect mucosal disease (i.e., ulcers,
inflammation). If the animal has been properly prepared, DIGESTION AND ABSORPTION TESTS
these enemas can reveal intraluminal filling defects re
presenting ileocolic or cecocolic intussusception (see Fig. Exocrine pancreatic function may be tested by measuring
33-11), proliferative colonic neoplasia (e.g., polyps, adeno fecal proteolytic activity (not recommended), fat absorption
carcinoma), extraluminal compression denoted by smooth- with and without pancreatic enzymes (not recommended),
surfaced displacement of the b a r i u m from the colonic lumen, or serum T L I (recommended).
and infiltrative disease (i.e., a roughened, partial obstruction Fat absorption testing is simple but o f questionable sen
or an "apple core" lesion) (Fig. 29-10). However, it is imper sitivity and specificity. It is no longer recommended. The
ative that a change be found on at least two films to ensure reader is referred to prior editions o f this text for a descrip
that it is not an artifact. tion o f the test and interpretation.
Serum T L I is the most sensitive and specific test for EPI
and is convenient (i.e., submit 1 m l of refrigerated serum
PERITONEAL FLUID ANALYSIS obtained after an overnight fast) and readily available. The
T L I assay detects circulating proteins produced by a nor
Fluid analysis is discussed in detail in Chapter 36. The mally functioning exocrine pancreas and is even valid in
fluid is obtained by performing abdominocentesis with a animals receiving pancreatic enzyme supplements orally.
syringe and needle. If this technique fails, a multifenestrated Pancreatitis, renal failure, and severe malnutrition may
increase the serum T L I concentrations, but this rarely causes
results to be misinterpreted. However, i f EPI is caused by
obstruction o f the pancreatic ducts (apparently rare) as
opposed to acinar cell atrophy or destruction (common), the
serum T L I test may not detect maldigestion. In such cases, a
quantitative fecal proteolytic assay is required.
N o r m a l dogs have serum T L I activities of 5.2 to 35 g/L.
Values of less than 2.5 g/L confirm a diagnosis of EPI. Normal
cats have higher values (28 to 115 g/L). The serum TLI assay
is primarily indicated in dogs with chronic small intestinal
diarrhea or chronic weight loss o f u n k n o w n origin. Because
feline EPI is rare, the test is seldom necessary i n cats. Although
principally used to detect EPI, serum T L I values substantially
greater than normal are suggestive of pancreatitis.
SERUM CONCENTRATIONS
OF VITAMINS
possibly because o f the high incidence o f A R E in such proton p u m p inhibitors). Resting serum gastrin concentra
animals. Severe mucosal disease, especially i n the region of tions may vary, with occasional values i n the normal range
the ileum, may also cause serum cobalamin concentrations in animals w i t h gastrinoma. Provocative testing should be
to be decreased, ostensibly because o f malabsorption o f the considered i n dogs strongly suspected o f having gastrinoma
vitamin. Perhaps the major indications for measuring serum but with n o r m a l baseline serum gastrin concentrations (see
cobalamin are to look for evidence o f intestinal disease i n Chapter 52).
patients with weight loss of uncertain cause and to better Testing for urease activity i n gastric mucosa is sometimes
define cats with k n o w n small intestinal disease (cobalamin- done i f the clinician is looking for Helicobacter sp. i n the
deficient cats can experience metabolic complications). If stomach. This bacteria has strong urease activity. To perform
the serum cobalamin is low i n a patient with weight loss o f this, one or preferably two fresh pieces o f gastric mucosa are
unknown cause, it is likely that small intestinal disease is placed into urease agar and observed for up to 24 hours. If
responsible. B-complex vitamin supplementation may cause these urease-producing bacteria are present, their enzyme
an increased serum cobalamin concentration. will split the urea i n the agar into a m m o n i a and the p H
Dietary folate is absorbed i n the small intestine. If indicator i n the agar will change from amber to p i n k (some
there are many bacteria in the upper small intestine, these times this occurs within 15 minutes). Tubes o f urease agar
sometimes synthesize and release folate, causing the serum may be obtained from microbiologic supply houses. There
concentrations to be increased. Likewise, severe intestinal are also special kits designed to detect Helicobacter spp. In
mucosal disease may decrease absorption, causing lower dogs and cats there is no good evidence that this test is more
serum concentrations. B-complex vitamin supplementation advantageous than special staining (e.g., Warthin-Starry) o f
may increase serum folate concentrations. multiple gastric biopsy specimens.
Because bright light degrades cobalamin, samples should Intestinal permeability testing can be performed, and
be frozen and kept in the dark during storage and transport. finding increased permeability seems to be a reliable marker
The specificity o f decreased serum cobalamin and increased of small intestinal disease. However, at this time it is impos
folate concentrations for A R E is questionable. sible to diagnose a patient with increased small intestinal
permeability as having a particular disease. Currently, the
major value to such testing seems to be (1) determining that
OTHER SPECIAL TESTS FOR ALIMENTARY a patient with clinical signs o f uncertain cause has small
TRACT DISEASE intestinal disease and (2) evaluating response to therapy i n
difficult-to-manage patients. This test is seldom done i n
Antibodies to acetylcholine receptors should be measured i f clinical cases.
the clinician is looking for a cause of dysphagia or esophageal Fecal alpha-1 protease inhibitor can be measured i n feces
weakness that could be of neuromuscular origin (see p. 422). and is a marker for gastrointestinal protein loss. Clinically,
Serum is obtained and sent to a laboratory that can perform this test is rarely indicated but could be helpful when trying
a validated assay for the species being evaluated. Increased to distinguish whether hypoalbuminemia is at least partly
titers to such antibodies are strongly suggestive o f myasthe due to a protein-losing enteropathy i n a patient with k n o w n
nia gravis, even i f there are no systemic signs. False-positive renal protein loss or hepatic insufficiency.
results are rare. Testing can be done by D r . Diane Shelton Tests for Pythium insidiosum are available. E L I S A tests for
(Comparative Neuromuscular Laboratory, Basic Science antibodies and P C R testing for antigen can be done at Lou
Building, University of California at San Diego, L a Jolla, C A isana State University (Dr. A m y Grooters, College o f Veteri
92093-0612). nary Medicine, Lousiana State University, Baton Rouge, L A
Measurement of antibodies to 2 M muscle fibers can be 70803).
helpful in dogs with suspected masticatory muscle myositis
(see p. 420). These antibodies are typically not found i n dogs
with polymyositis, whereas most dogs with masticatory ENDOSCOPY
myositis have them. Serum is required for the test and can
be sent to D r . Diane Shelton for testing. Endoscopy is often cost-effective i f radiographic and ultra
Serum gastrin concentrations are measured i n animals sonographic findings have been nondiagnostic i n animals
with signs suggestive o f gastrinoma (i.e., chronic vomiting, with chronic vomiting, diarrhea, or weight loss. It permits
weight loss, and diarrhea i n older animals, especially i f there rapid exploration o f selected sections o f the alimentary tract
is concurrent esophagitis or duodenal ulceration). Gastrin and mucosal biopsy without the need for a thoracotomy or
stimulates gastric acid secretion and is trophic for the gastric laparotomy. Although excellent for detecting morphologic
mucosa. Serum for assay o f gastrin is harvested from an changes (e.g., masses, ulcers, obstruction), it is insensitive for
animal after an overnight fast and rapidly frozen. The serum revealing abnormal function (e.g., esophageal weakness).
gastrin concentration may be increased i n animals with gas Rigid endoscopy is easier to perform and less expensive
trinoma, a gastric outflow tract obstruction, renal failure, than flexible endoscopy, and it can provide excellent biopsy
FIG 29-11 FIG 29-13
E n d o s c o p i c v i e w o f a p o l y p o i d mass in the e s o p h a g u s of a Endoscopic v i e w of the l o w e r e s o p h a g e a l sphincter of a
C h o w . This represents a n a d e n o c a r c i n o m a . d o g w i t h m o d e r a t e l y severe reflux esophagitis s e c o n d a r y to
v o m i t i n g . N o t e the h y p e r e m i c a r e a s .
FIG 29-18
FIG 29-16 Endoscopic v i e w of a gastric ulcer o n the g r e a t e r c u r v a t u r e
V i e w of the l o w e r e s o p h a g e a l sphincter (as seen from the in a C h o w . N o t e that it is o b v i o u s that the m u c o s a is
stomach) of a d o g w i t h a l e i o m y o m a . This lesion w a s e r o d e d to the level of the s u b m u c o s a .
causing v o m i t i n g a n d r e g u r g i t a t i o n a n d w o u l d easily have
been missed if a c a r e f u l , m e t h o d i c a l e x a m i n a t i o n h a d not
been c a r r i e d out. may facilitate passage of the foreign object through the
sphincter.
Gastroduodenoscopy and biopsy are indicated in selected
tension pneumothorax in animals with an esophageal animals with vomiting, apparent upper gastrointestinal
perforation. blood loss, apparent gastroduodenal reflux, or small intesti
Rigid endoscopy is often more useful than flexible endos nal disease. It is more sensitive and specific than radiography
copy in removing esophageal foreign objects. The rigid for detecting mucosal ulcers (Fig. 29-18), erosions (Fig.
endoscope can protect the esophagus during extraction of 29-19), tumors (Fig. 29-20), and inflammatory lesions (Figs.
the object, and it allows the use of rigid forceps that can 29-21 to 29-23). Endoscopy is also quicker and less stressful
grasp the foreign object more tightly. Care must be taken to to the animal than exploratory laparotomy. M a n y foreign
maintain the animal's esophagus as straight as possible when objects in the upper gastrointestinal tract (Fig. 29-24) can be
using a rigid endoscope. If a flexible endoscope is used, it is removed using endoscopy, and multiple biopsy specimens
often helpful to pass it through a rigid scope or tube that can be obtained. Occasionally, unexpected diagnoses (e.g.,
has been passed through the cricopharyngeal sphincter; this Physaloptera infection; Fig. 29-25) may be found. It may be
FIG 29-21
Endoscopic v i e w of the stomach of a cat w i t h diffuse
i n f l a m m a t i o n , e r o s i o n , a n d ulceration of u n k n o w n cause.
FIG 29-19
Endoscopic v i e w o f the gastric m u c o s a of a d o g ' s stomach
that has o b v i o u s b l e e d i n g . This d o g h a d received nonsteroi
d a l d r u g s , a n d the b l e e d i n g represented erosions that c o u l d
not be detected w i t h r a d i o g r a p h s or u l t r a s o n o g r a p h y . (From
Fossum T, e d i t o r : Small animal surgery, St Louis, 1 9 9 7 ,
Mosby.)
FIG 2 9 - 2 2
A f o c a l gastritis near the pylorus of a d o g . N o t e the
r e d d e n e d spots o n the lesion, w h i c h w e r e responsible for
intermittent hematemesis.
FIG 2 9 - 2 0
Endoscopic v i e w of the stomach o f a d o g w i t h a n o b v i o u s
mass in the g r e a t e r c u r v a t u r e . This is a n ulcerated leiomyo
s a r c o m a that w a s successfully r e m o v e d .
not rule out the presence o f significant disease. Strictured ENDOSCOPIC BIOPSY
areas with relatively normal-appearing mucosa are usually Rigid endoscopy usually provides excellent biopsy samples
caused by a submucosal lesion, i n which case biopsying must of the descending colon (i.e., large specimens that include
be aggressive enough to ensure that submucosal tissue is the full thickness o f the mucosa, including some muscularis
included i n the specimen. Cytology can detect histoplasmo mucosa), but the stomach and small intestine cannot be
sis, protothecosis, some neoplasms, and eosinophilic colitis. biopsied with this equipment. Flexible endoscopes can reach
A n adult or a pediatric h u m a n sigmoidoscope is usually more o f the alimentary tract, but the tissue samples obtained
adequate for rigid colonoscopy. The tip o f the rigid biopsy with these scopes may not always be deep enough to allow
forceps should have a shearing action (i.e., one part o f the submucosal lesions to be diagnosed. Ideally, the tissue to be
tip should fit into the other when it is closed, thus acting like biopsied is visualized; however, the clinician may pass the
a pair o f scissors) instead o f a clamshell (also called "double biopsy forceps through the pylorus or ileocolic valve and
spoon") action i n w h i c h the edges o f the top and bottom biopsy the duodenum or ileum blindly if the tip of the endo
jaws simply meet. scope cannot be advanced into these areas.
Ileoscopy is principally indicated i n dogs with diarrhea N o t all laboratories are adept at processing and interpret
and i n cats with v o m i t i n g or diarrhea. It is performed during ing these samples. Endoscopes with 2.8-mm biopsy channel
flexible colonoscopy and requires thorough colonic cleans are generally preferred to those with a 2.0- or a 2.2-mm
channel because the larger forceps allow retrieval of substan the stomach, duodenum, jejunum, ileum, mesenteric l y m p h
tially larger and deeper tissue samples. nodes, and liver (and the pancreas i n cats) should be obtained,
W h e n intestinal or gastric mucosa is biopsied, the tissue regardless of how normal these organs appear, unless an
sample must be handled carefully to m i n i m i z e artifacts and obvious lesion is found (e.g., a large tumor). However, it is
distortion. The tissue should be carefully removed from the wise not to assume that a grossly impressive lesion is respon
biopsy forceps with a 25-gauge needle. A squash preparation sible for the clinical signs; rather, the clinician should perform
of one tissue specimen can be evaluated cytologically, and a biopsy even when the diagnosis seems obvious. Dehiscence
the remaining samples are fixed i n formalin and evaluated is a concern i f the serum albumin concentration is less than
histologically. The cytology slides should be evaluated by a 1.5 g/dl, but the use of nonabsorbable suture material and
pathologist familiar with gastrointestinal cytology. Cytologic serosal patch grafting over intestinal suture lines minimizes
preparations of the gastric mucosa may show adenocarci the risk. The clinician should consider whether gastrostomy
noma, lymphoma, inflammatory cells, or large numbers of or enterostomy feeding tubes should be placed i n emaciated
spirochetes (see Fig. 32-1). Cytologic studies of the intestinal animals before exiting the abdomen.
mucosa may show eosinophilic enteritis, lymphoma, histo
plasmosis, or protothecosis, and occasionally giardiasis,
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In McCarthy TC, editor: Veterinary endoscopy, St Louis, 2005, a component of zinc sulfate flotation examinations, J Am Anim
Elsevier/Saunders. Hosp Assoc 38:22, 2002.
C H A P T E R 30
General Therapeutic
Principles
DRUG DOSAGE*
P e r i p h e r a l l y A c t i n g Drugs
Centrally A c t i n g Drugs
Phenothiazine derivatives
C h l o r p r o m a z i n e (Thorazine) 0 . 3 - 0 . 5 m g / k g I M , IV, o r SC q 8 h
Prochlorperazine ( C o m p a z i n e ) 0.1-0.5 m g / k g IM q8-12h
M e t o c l o p r a m i d e (Region) 0 . 2 5 - 0 . 5 m g / k g P O , I M , o r IV q 8 - 2 4 h
1-2 m g / k g / d a y , constant IV infusion
Serotonin receptor antagonists
Ondansetron (Zofran) 0 . 1 - 0 . 2 m g / k g IV q 8 - 2 4 h
Dolasetron (Anzemet) 0 . 3 - 1 . 0 m g / k g SC o r IV q 2 4 h
Granisetron (Kytril) 0 . 1 - 0 . 5 m g / k g P O ( a n e c d o t a l , d o g s only)
Neurokinin-1 receptor a n t a g o n i s t
M a r o p i t a n t (Cerenia) 1 m g / k g SC q 2 4 h o r 2 m g / k g P O q 2 4 h (dogs only)
T r i m e t h o b e n z a m i d e (Tigan) (poorly effective) 3 m g / k g , I M q 8 h (dogs only)
Antihistamine
D i p h e n h y d r a m i n e (Benadryl) (poorly effective) 2-4 m g / k g P O q 8 h
1-2 m g / k g IV o r I M q 8 - 1 2 h
dehydrated animal. Some data suggest that phenothiazines liminary data suggest that this w i l l be a useful drug i n
may lower the seizure threshold i n animals with epilepsy, but clinical practice.
this is uncertain. Narcotics, such as fentanyl, oxymorphone, and butorpha
Metoclopramide (Reglan) inhibits the chemoreceptor nol, may cause v o m i t i n g initially, but v o m i t i n g is usually
trigger zone and increases gastric tone and peristalsis, both inhibited once the drug penetrates to the medullary vomit
of which inhibit emesis. Rarely, animals show unusual behav ing center. Trimethobenzamide (Tigan) and antihistamines
ior after administration. The drug is excreted i n the urine, are effective i n some animals but generally are unreliable
and severe renal failure makes adverse effects more likely. It antiemetics i n dogs and cats.
rarely worsens vomiting, perhaps because it causes excessive
gastric contractions. The liquid form of metoclopramide
given orally is often not accepted by cats. Because of its pro- ANTACID DRUGS
kinetic activity, the drug is contraindicated i n animals with
a gastric or duodenal obstruction. Metoclopramide may be Antacid drugs (Table 30-4) are indicated when appropriate
more effective in animals with severe vomiting if given intra to lessen gastric acidity (e.g., ulcer disease; acid hypersecre
venously at a dosage of 1 to 2 mg/kg/day by constant rate tion resulting from renal failure, mast cell tumor, or gastri
infusion. noma). A l t h o u g h they are not antiemetics, they apparently
Ondansetron (Zofran) and dolasetron (Anzemet) are may have an "antidyspepsic" effect due to diminishing gastric
serotonin receptor antagonists. Developed for use i n people hyperacidity.
with vomiting resulting from chemotherapy, they are often Antacids, which titrate the gastric acidity, are over-the-
effective i n animals in which vomiting is not controlled with counter preparations that are typically of limited efficacy
phenothiazines or metoclopramide (e.g., severe canine par because o f the way they are administered. C o m p o u n d s
voviral enteritis). Granisetron (Kytril) has been used when containing a l u m i n u m or magnesium tend to be more effec
an oral medication is required, but its efficacy is uncertain. tive and do not cause the gastric acid rebound that some
Maropitant (Cerenia) is a neurokinin-1 receptor antago times occurs i n response to calcium-containing antacids.
nist that has recently been approved for use i n dogs. Pre Antacids should be administered orally every 4 to 6 hours
antagonists are now available as over-the-counter prepara
TABLE 30-4
tions. The m a i n indication for these drugs is the treatment
of gastric and duodenal ulcers. Some clinicians use them
Selected Antacid Drugs
prophylactically i n an attempt to prevent ulceration associ
DRUG DOSAGE* ated with the use of some steroids and some nonsteroidal
antiinflammatory drugs (NSAIDs), but they are most effec
A c i d T i t r a t i n g Drugs
tive i n treating existing ulcers after N S A I D or steroid therapy
Aluminum hydroxide 10-30 m g / k g PO q6-8h has ceased. They are effective i n lessening ulceration associ
(many names)
ated with submaximal exertion. Nizatidine and ranitidine
Magnesium hydroxide 5 - 1 0 ml P O q 4 - 6 h (dogs)
have gastric prokinetic activity. Very rarely, these drugs may
(many names) q 8 - 1 2 h (cats)
cause bone marrow suppression, central nervous system
Gastric A c i d Secretion I n h i b i t o r s problems, or diarrhea. Parenteral administration, especially
H2 receptor antagonists the rapid I V injection o f ranitidine, may cause nausea, vom
Cimetidine (Tagamet) 5 - 1 0 m g / k g P O , I M , o r IV iting, or bradycardia. There is concern that severely i l l or
q6-8h stressed animals may require larger than currently recom
Ranitidine (Zantac) 1-2 m g / k g P O o r IV q 8 - 1 2 h mended doses i n order to suppress gastric acid secretion; this
(dogs) is being investigated.
2 . 5 m g / k g IV o r 3 . 5 m g / k g Proton p u m p inhibitors (i.e., Omeprazole [Prilosec], lan
P O q l 2 h (cats)
soprazole [Prevacid], and pantoprazole [Protonix]) block
N i z a t i d i n e (Axid) 2.5-5 m g / k g q 2 4 h PO
the final c o m m o n pathway o f gastric acid secretion. This
(dogs)
is the most effective class of drugs for decreasing gastric
F a m o t i d i n e (Pepcid, 0 . 5 m g / k g P O o r IV
acid secretion, but m a x i m u m suppression of acid secretion
Pepcid A C ) q12-24h
takes between 2 and 5 days when administered orally.
Proton Pump Inhibitors Omeprazole is a noncompetitive inhibitor primarily used i n
Omeprazole (Prilosec) 0.7-1.5 m g / k g PO q12-24h animals with severe gastroesophageal reflux or gastrinomas
(dogs) (diseases i n which H receptor-antagonists are often inade
2
clear that ranitidine is effective i n dogs. The H receptor 2 often used concurrently i n animals with severe gastrointes-
TABLE 30-5
Pancreatic enzyme supplementation is indicated to treat tinal bacteria from rendering the enzyme supplementation
exocrine pancreatic insufficiency; however, it is often used ineffective. Occasionally, a stomatitis or diarrhea develops i n
empirically without justification i n animals with diarrhea. dogs receiving large amounts o f enzyme supplementation.
There are many products that vary greatly i n their potency.
Although pills may work, powdered preparations tend to be
more effective; enteric-coated pills are particularly ineffec MOTILITY MODIFIERS
tive. Viokase-V ( A . H . Robins Co.) and Pancreazyme (Daniels
Pharmaceuticals) seem to be particularly efficacious. The Drugs that prolong the intestinal transit time are p r i n
powder should be mixed with the food (approximately 1 to cipally used to symptomatically treat diarrhea. Although
2 teaspoons per meal), but allowing the mixture to " i n c u infrequently needed, they are indicated if the diarrhea causes
bate" before feeding has not been found beneficial. Fat is the excessive fluid or electrolyte losses or owners demand control
main nutrient that must be digested i n animals with exocrine of the diarrhea at home. Opiates (Table 30-6) increase resis
pancreatic insufficiency, and feeding them a low-fat diet may tance to flow by augmenting segmental contraction. They
ameliorate diarrhea. Antacid or antibiotic therapy (or both) tend to be more effective than parasympatholytics, which
may occasionally help prevent gastric acidity or small intes paralyze motility i n the intestines (i.e., create ileus). Both
classes o f drugs have antisecretory effects. Because cats do tors. It must be used cautiously because overdose may cause
not tolerate narcotics as well as dogs, opiates should not toxicity accompanied by signs o f parasympathetic overload
be used in this species, although loperamide may be used (e.g., vomiting, miosis, diarrhea). Azathioprine (with or
carefully. without steroids) may be a better long-term treatment for
Loperamide (Imodium) is available as an over-the- myasthenia gravis than pyridostigmine.
counter drug. Use o f loperamide theoretically increases
the risk for bacterial proliferation i n the intestinal lumen,
thus potentially initiating or perpetuating disease; how ANTIINFLAMMATORY AND
ever, this is very rare i n clinical practice. A n overdose can ANTISECRETORY DRUGS
cause narcotic intoxication (i.e., collapse, vomiting, ataxia,
hypersalivation), w h i c h requires treatment with narcotic Intestinal antiinflammatory or antisecretory drugs (or both)
antagonists. are indicated for lessening the fluid losses resulting from
Diphenoxylate (Lomotil) is similar to loperamide but diarrhea or for controlling intestinal inflammation that is
tends to be somewhat less effective. It has more potential for unresponsive to dietary or antibacterial therapy.
toxicity than loperamide. Rarely, a dog responds to it but not Bismuth subsalicylate (Pepto-Bismol, Kaopectate) is an
to loperamide. This drug should not be used i n cats. over-the-counter antidiarrheal agent that is effective i n many
Drugs that shorten the transit time (prokinetic drugs) dogs with acute enteritis (see Table 30-6), probably because
empty the stomach or increase intestinal peristalsis or both. of the antiprostaglandin activity o f the salicylate moiety.
Metoclopramide is a prokinetic drug that is effective only i n The m a i n disadvantages are that the salicylate is absorbed
the stomach and the p r o x i m a l duodenum. However, it can (warranting its cautious use i n cats or in dogs receiving
be administered parenterally. Adverse effects are mentioned other nephrotoxic drugs), it turns stools black (which mimics
under the section o n antiemetics. Cisapride stimulates melena), and it must be administered orally (many animals
normal motility from the lower esophageal sphincter to the dislike its taste). Bismuth is bactericidal for certain organ
anus. It is usually effective unless the tissue has been irrepa isms (e.g., Helicobacter spp.).
rably damaged (e.g., megacolon i n cats). Primarily used for Octreotide (Sandostatin) is a synthetic analog o f soma
the treatment o f constipation, it may also be used for the tostatin that inhibits alimentary tract motility and the secre
management o f gastroparesis (in w h i c h it is usually more tion o f gastrointestinal hormones and fluids. It has had
effective than metoclopramide) and small intestinal ileus. It limited use i n dogs and cats but might be helpful in a few
has rarely been reported to be beneficial i n dogs with mega animals with intractable diarrhea or pancreatitis.
esophagus. Cisapride is no longer available from h u m a n Salicylazosulfapyridine (sulfasalazine [Azulfidine]) is
pharmacies but is generally available from veterinary phar indicated for animals with colonic inflammation. This drug
macies. It is available only as an oral preparation. It has few is generally not beneficial i n animals with small intestinal
significant adverse effects, although intoxication with large problems. It is a combination o f sulfapyridine and 5-amino-
doses may cause diarrhea, muscular tremors, ataxia, fever, salicylic acid. C o l o n i c bacteria split the molecule, and the
aggression, and other central nervous system signs. Erythro 5-aminosalicylic acid (probably the active moiety) is subse
m y c i n stimulates m o t i l i n receptors and enhances gastric quently deposited on diseased colonic mucosa. Dogs gener
motility at doses less than required for antibacterial activity ally receive 50 to 60 mg/kg, divided into three doses daily,
(i.e., 2 mg/kg). It may also increase intestinal motility. but not to exceed 3 g daily. Sulfasalazine may be effective at
Nizatidine and ranitidine are H receptor antagonists that
2 lower-than-expected doses i f used i n combination with glu
also have gastric prokinetic effects at routinely used doses. cocorticoids. Empirically, 15 mg/kg/day, sometimes divided
Bethanechol (Urecholine) is an acetylcholine analog that into twice-daily doses, is often tolerated by cats,
stimulates intestinal motility and secretion. It produces but they must be closely observed for the development of
strong contractions that can cause pain or injure the animal; salicylate intoxication (i.e., lethargy, anorexia, vomiting,
hence, it is infrequently used, except for increasing urinary hyperthermia, tachypnea). Some cats that vomit or become
bladder contractions. Obstruction o f an outflow area can be anorectic may tolerate the medication if it is given i n enteric-
a contraindication to the use o f prokinetic drugs because coated tablets. M a n y dogs with colitis respond to therapy in
vigorous contractions against such a lesion may cause pain 3 to 5 days. However, the drug should be given for 2 weeks
or perforation. Obstruction o f the urinary outflow tract is before deciding that it is ineffective. If signs of colitis resolve,
also a contraindication to the use o f bethanechol. Tegaserod the dose o f the drug should be gradually reduced. If the
(Zelnorm) has prokinetic activity i n the canine colon (0.05 animal cannot be weaned off the drug entirely, the lowest
to 0.1 mg/kg, q l 2 h ) , but there is too little information effective dose should be used and the animal monitored
regarding its effectiveness i n clinical disease to make recom regularly for the development o f drug-induced adverse
mendations about its use. effects (especially those resulting from the sulfa drug). Sul
Pyridostigmine (Mestinon) inhibits acetylcholinesterase fasalazine may cause transient or permanent keratoconjunc
and is used to treat myasthenia gravis (see Chapter 71). It is tivitis sicca. Other possible complications include cutaneous
used for the treatment o f acquired megaesophagus associ vasculitis, arthritis, bone marrow suppression, diarrhea, and
ated with the formation o f antibodies to acetylcholine recep any other problem associated with sulfa drugs or NSAIDs.
Olsalazine and mesalamine contain or are metabolized steroid and dietary therapy. It is also used i n animals with
to 5-aminosalicylic acid but do not have the sulfa, w h i c h is severe disease i n w h i c h it is i n the animal's best interest
responsible for most of sulfasalazine's adverse effects. In to use aggressive therapy initially. These drugs should be
people they are as effective as sulfasalazine but safer. Olsala used only i f the diagnosis has been confirmed histopatho
zine and mesalamine have been used effectively i n dogs. logically. Immunosuppressive therapy can be more efficacious
They are given i n a dose generally about one half that o f than corticosteroid therapy alone and allows corticosteroids
sulfasalazine. Keratoconjunctivitis sicca has also been found to be given at lower doses and for shorter periods, thereby
in dogs receiving mesalamine. decreasing their adverse effects. However, the possibility
Corticosteroids are specifically indicated i n animals with of adverse effects from these drugs usually limits their
chronic alimentary tract inflammation (e.g., moderate to use to animals with severe disease. The reader is referred to
marked inflammatory bowel diseases) that is not responsive Chapter 103 for additional information o n immunosuppres
to well-designed elimination diets. In cats prednisolone sive therapy.
appears to have better activity than prednisone. Relatively Azathioprine (Imuran) is c o m m o n l y used i n dogs (50 mg/
2
high doses (i.e., prednisolone, 2.2 mg/kg/day) are often used m daily or every other day) with severe alimentary tract
initially, and the dose is tapered to find the lowest effective inflammation. Azathioprine should not be used i n cats
dose. Dexamethasone is sometimes effective when predniso because o f the risk for myelotoxicity. For smaller dogs a 50-
lone is not, but dexamethasone has more adverse effects m g azathioprine tablet is typically crushed and suspended i n
than prednisolone. If P O administration is a problem i n a a l i q u i d (e.g., 15 m l o f a v i t a m i n supplement) to allow more
cat, long-lasting steroid injections (e.g., methylprednisolone accurate dosing. The suspension must be mixed well before
acetate) may be tried. each dosing. It may take 2 to 5 weeks before the beneficial
Methyprednisolone appears to be more effective than effects o f this drug are seen. Side effects i n dogs may i n
prednisolone, requiring only 80% o f the dose used for pred clude hepatic disease, pancreatitis, and bone marrow
nisolone. Budesonide (Entocort) is a steroid that is not more suppression.
effective than prednisolone but is largely eliminated by first C h l o r a m b u c i l is an alkylating agent that is used for the
pass metabolism i n the liver, which decreases its systemic same reasons as azathioprine. Chlorambucil, however,
effects. The response may be rapid or take weeks. appears to have fewer adverse effects than azathioprine. A
Corticosteroids are often beneficial i n cats with reasonable starting dose i n cats is 1 m g twice weekly for cats
inflammatory bowel disease, but they may worsen intesti weighing less than 7 lb (3.5 kg) and 2 m g twice weekly for
nal disease in some dogs and cats. Iatrogenic Cushing's syn cats weighing more than that. Beneficial effects may not be
drome is more o f a problem i n dogs but can occur i n seen for 4 to 5 weeks. If a response is seen, the dose should
cats that are grossly overdosed. It is important to have a then be decreased very slowly over the next 2 to 3 months.
histologically based diagnosis before using high-dose The animal should be monitored for myelosuppression.
prednisolone therapy because some diseases that m i m i c Stronger alkylating agents, such as cyclophosphamide, are
steroid-responsive lymphocytic colitis (e.g., histoplasmosis) seldom used for the management o f nonneoplastic gastro
are absolute contraindications to corticosteroid therapy. intestinal tract disease.
Although more c o m m o n i n the southeastern U n i t e d States Cyclosporine (Atopica) is a potent immunosuppressive
and the O h i o River Valley, histoplasmosis has been found i n drug that is sometimes used i n dogs with inflammatory
unexpected states. bowel disease, lymphangiectasia, and perianal fistulas. The
Retention enemas of corticosteroids or 5-aminosalicylic dose is 3 to 5 mg/kg q l 2 h when given orally, but erratic
acid are sometimes indicated i n animals with severe distal bioavailability requires therapeutic drug m o n i t o r i n g and
colitis. The dose is estimated from the h u m a n dose. These subsequent adjusting o f the dose. There is considerable
enemas place large doses of an antiinflammatory agent variation i n the bioavailablity o f different preparations o f
directly on the affected area while m i n i m i z i n g systemic cyclosporine. It may be administered intravenously in v o m
effects. Although effective i n controlling the clinical signs, iting patients, but then the initial dose should probably be
their administration is unpleasant for both clients and decreased by 50%. Because o f its considerable expense, it
animals. Further, the active ingredient may be absorbed i f is sometimes administered with l o w doses o f ketoconazole
there is substantial inflammation and increased mucosal (3 to 5 mg/kg q l 2 h ) , w h i c h inhibits metabolism o f cyclospo
permeability (i.e., animals receiving corticosteroid enemas rine and i n turn allows the use o f lower doses at less expense
can become polyuric and polydipsic). Therapeutic retention to the client.
enemas are typically used until the clinical signs are con
trolled and other therapy (e.g., sulfasalazine, diet) becomes
effective. The contraindications to their use are the same as ANTIBACTERIAL DRUGS
those to the systemic administration o f the active ingredient
of the enema. In dogs and cats with gastrointestinal problems, antibiotics
Immunosuppressive therapy (e.g., azathioprine, chloram are primarily indicated i f aspiration pneumonia, fever, a
bucil, cyclosporine) is indicated i n animals with severe leukogram suggestive o f sepsis, severe neutropenia, antibi
inflammatory bowel disease that is unresponsive to cortico otic-responsive enteropathy, clostridial colitis, symptomatic
Helicobacter gastritis, or perhaps hematemesis or melena is bacteria (e.g., amikacin, 25 mg/kg given intravenously once
found or suspected. Animals with an acute abdomen may daily or enrofloxacin, 15 mg/kg given intravenously once
reasonably be treated with antibiotics while the nature o f the daily) are often effective. T o improve the anaerobic spec
disease is being defined. Acute colitis is a reasonable indica trum, especially i f a cephalosporin is used instead o f ampicil
tion for amoxicillin (22 mg/kg q12h) because clostridial lin, the clinician may include metronidazole (10 mg/kg
colitis is reasonably c o m m o n . However, most animals with given intravenously two or three times daily). Alternatively,
acute enteritis or gastritis o f u n k n o w n cause do not benefit a second-generation cephalosporin (e.g., cefoxitin, 30 mg/kg
from antibiotic therapy. In general, the routine use o f anti given intravenously three or four times daily) may be used.
microbials i n animals with alimentary tract disorders is not In general, it takes at least 48 to 72 hours before the clinician
recommended, unless the animal is at high risk for infection can tell whether the therapy will be effective.
or a specific disorder is being treated. Helicobacter gastritis may be treated with various combi
Nonabsorbable aminoglycosides (e.g., neomycin) are nations o f drugs. Currently, the combination o f an antacid
often used to "sterilize" the intestines. However, they do not (i.e., famotidine or omeprazole; see Table 30-4) and a mac
kill anaerobic bacteria, w h i c h are the predominant type rolide (i.e., erythromycin or azithromycin; see pp. 483-485)
found there. Further, there are a plethora of viral and dietary or amoxicillin seems to be very effective. A d d i n g metronida
causes o f acute enteritis that are not responsive to antibio zole and/or bismuth subsalicylate may enhance efficacy.
tics. Thus aminoglycosides given orally are not indicated However, some patients seem to respond to erythromycin or
unless a specific infection (e.g., campylobacteriosis) is being amoxicillin as a sole agent. If high doses o f erythromycin
considered. (22 mg/kg given twice daily) cause vomiting, the dose may
Broad-spectrum antibiotics effective against aerobes and be lowered to 10 to 15 mg/kg given twice daily. A 10- to 14-
anaerobes may be used for the treatment o f antibiotic- day course o f treatment appears to be adequate for most
responsive enteropathy ( A R E ) . Metronidazole (10 to 15 m g / animals, although recurrence of infection is possible.
kg q24h) may also be used for this purpose (see later discus Metronidazole is a "miscellaneous" drug that is com
sion) but has not been as successful i n this author's experi m o n l y used i n animals with inflammatory bowel disease. It
ence. Tylosin (20 to 40 mg/kg q l 2 h ) is c o m m o n l y used for has antimicrobial activity against anaerobic bacteria (which
this purpose. Tetracycline (22 mg/kg q l 2 h ) has also been predominate i n the gastrointestinal tract) and protozoa
used, and patients w i t h severe disease believed to have A R E (e.g., Giardia). It has been suggested to have some effect on
may be treated with combinations (e.g., metronidazole and the i m m u n e system, as shown by its apparent beneficial
enrofloxacin [7 mg/kg q24h]). Inappropriate antibiotic effects i n people with Crohn's disease. The usefulness of
therapy may hypothetically eliminate enough resident bac metronidazole i n dogs and cats with inflammatory bowel
teria that overgrowth o f pathogenic bacteria i n the colon disease (10 to 15 mg/kg given twice daily) is suspected but
occurs. However, this is rarely a clinical problem i n dogs unproved. Adverse effects are u n c o m m o n but may include
and cats. The clinician should treat the patient for at least 2 salivation (because o f its taste), vomiting, central nervous
to 3 weeks before deciding that therapy for A R E has been system abnormalities (e.g., central vestibular signs), and
unsuccessful. perhaps neutropenia. These adverse effects usually resolve
Pets occasionally have enteritis caused by a specific bac after withdrawing the drug. Cats sometimes accept oral sus
terium. However, even this is not necessarily an indication pensions better than the 250-mg tablets, which must be cut
for antibiotics. Clinical signs resulting from some bacterial and have an unpleasant taste. Some cats diagnosed with
enteritides (e.g., salmonellosis, enterohemorrhagic Esche inflammatory bowel disease respond to metronidazole better
richia coli) generally do not resolve more quickly when the than they do to corticosteroids. Occasionally, dogs with
animal is treated with antibiotics, even those to w h i c h the colitis do likewise.
bacteria are sensitive.
Dogs and cats with viral enteritis but without obvious
systemic sepsis may reasonably be treated with antibiotics i f PROBIOTICS/PREBIOTICS
secondary sepsis is likely to occur (e.g., those with neutro
penia or severe hemorrhagic diarrhea). First-generation The administration o f live bacteria or yeast i n the food with
cephalosporins (e.g., cefazolin) are often effective for such the intent to produce a beneficial effect is called probiotic
use. therapy. The administration o f a specific dietary substance
If systemic or abdominal sepsis is suspected to have orig to specifically increase or decrease the numbers o f specific
inated from the alimentary tract (e.g., septicemia caused by bacteria is called prebiotic therapy. The concurrent use of
parvoviral enteritis, perforated intestine), broad-spectrum probiotics and prebiotics is called symbiotic therapy. Although
antimicrobial therapy is indicated. Antibiotics with a good there is good evidence that these therapies are beneficial for
aerobic gram-positive and anaerobic spectrum o f action specific conditions i n people, there is currently no published
(e.g., ticarcillin plus clavulinic acid [Timentin], 50 mg/kg w o r k showing a clear benefit i n clinically i l l dogs or cats.
given intravenously three to four times daily, or clindamycin, However, this may change with time.
11 mg/kg given intravenously three times daily) combined Lactobacillus, Bifidobacterium, and Enterococcus are the
with antibiotics with excellent activity against most aerobic bacteria typically administered to dogs. These bacteria are
believed to stimulate Toll-like receptors i n the bowel and perforating the colon. Enemas are usually administered to
thereby benefit the patient. The beneficial effect seems to last cats with a soft canine male urinary catheter and a 50-ml
only as long as the bacteria are being administered. There is syringe. If fluid is administered too quickly, however, the cat
no evidence that these bacteria become permanently estab w i l l usually vomit. A suspected or pending colonic perfora
lished i n the gastrointestinal microflora during administra tion is also a contraindication to a cleansing enema.
tion. Not all probiotics sold i n drug or grocery stores contain Hypertonic enemas are potentially dangerous and should
what the label states, which may be at least partially respon be used cautiously (if at all) because they can cause massive,
sible for their failure to have demonstrated efficacy. In fatal fluid and electrolyte shifts (i.e., hyperphosphatemia,
general, large numbers of bacteria appear to be necessary, hypocalcemia, hypokalemia, hyperkalemia). This is espe
which explains why feeding yogurt (which contains relatively cially true for cats, small dogs, and any animal that cannot
modest numbers of Lactobacilli) is ineffective. A t the time o f quickly evacuate the enema because o f obstipation.
this writing, there are two products marketed specifically for Cathartics and laxatives (Table 30-8) should be used only
veterinary use (Fortiflora, Purina C o ) that contains Entero to augment defecation i n animals that are not obstructed.
coccus faecium and Proviable (Nutramax) that contains a They are not routinely indicated i n small animals, except
mixture of several bacteria. perhaps as part o f lower bowel cleansing before contrast-
enhanced abdominal radiography or endoscopy.
Irritative laxatives (e.g., bisacodyl) stimulate defecation
ANTHELMINTIC DRUGS rather than soften feces. They are often used before colono
scopic procedures and i n animals that are reluctant to def
Anthelmintics are frequently prescribed for dogs and cats ecate because o f an altered environment. They are probably
with alimentary tract disease, even i f parasitism is not the not appropriate for long-term use because o f the depen
primary problem. It is often reasonable to use these drugs dence and colonic problems noted i n people who have used
empirically for the treatment of suspected parasitic infec them inappropriately. A glycerin suppository or a lubricated
tions i n animals with acute or chronic diarrhea. Selected match stick is often an effective substitute for an irritative
anthelmintics are listed i n Table 30-7. laxative. These objects are carefully placed i n the rectum to
stimulate defecation.
B u l k and osmotic laxatives include a variety o f prepara
ENEMAS, LAXATIVES, AND CATHARTICS tions: various fibers (especially the soluble ones); magne
sium sulfate; lactulose; and, i n milk-intolerant animals, ice
Enemas are classified as either cleansing or retention. cream or milk. They promote the fecal retention o f water
Retention enemas are given so that the material adminis and are indicated i n animals that have overly hard stools not
tered stays i n the colon until it exerts its desired effects caused by the ingestion o f foreign objects. These laxatives are
(e.g., antiinflammatory retention enemas are used in animals more appropriate for long-term use than the irritative
with inflammatory bowel disease, water i n obstipated cathartics are. Larger doses may be needed i n cats because
animals). Obstipated animals may require frequent a d m i n they retain fluids more effectively than dogs do.
istrations of modest volumes of water (e.g., 20 to 200 m l , Fiber is a bulking agent that is incorporated into the food
depending on the animal's size) so that the water stays i n and can be used indefinitely. C o m m e r c i a l diets relatively
the colon and gradually softens the feces. The clinician high i n fiber may be used, or existing diets may be supple
should avoid overdistending the colon or administering mented with fiber (see pp. 400-401). It is important to
drugs that may be absorbed and produce undesirable effects. supply adequate amounts o f water so that the additional
Suspected or pending colonic rupture is a contraindication fiber does not cause the formation o f harder-than-normal
to the use of enemas, but this outcome is difficult to predict. stools. T o o m u c h fiber may cause excessive stool or inappe
Animals that have undergone neurosurgery (e.g., those that tence resulting from decreased palatability (a danger for fat
have had a hemilaminectomy) and are receiving corticoste cats at risk for hepatic lipidosis). Fiber should not be given
roids (e.g., dexamethasone) may be at increased risk for to animals with a partial or complete alimentary tract
colonic perforation. Animals with colonic tumors or that obstruction because impaction may occur.
have recently undergone colonic surgery or biopsy should Lactulose (Cephulac) was designed to control signs o f
not receive enemas either, unless there is an overriding hepatic encephalopathy, but it is also a very effective osmotic
reason. laxative. It is a disaccharide that is split by colonic bacteria
Cleansing enemas are designed to remove fecal material. into unabsorbed particles. Lactulose is particularly useful for
They involve the repeated administration o f relatively large animals that refuse to eat high-fiber diets. The dose necessary
volumes o f warm water. In dogs the water is administered to soften feces must be determined in each animal, but 0.5
by gravity flow from a bucket or bag held above the animal. or 5 m l may be given two or three times daily to small and
The tube is gently advanced as far as it will easily go into the large dogs, respectively. Cats often need higher dosages (e.g.,
colon. Between 50 and 100 m l is tolerated by most small 5 m l three times daily). If gross overdosing occurs, so m u c h
dogs, 200 to 500 m l by medium-size dogs, and 1 to 2 L by water can be lost that hypernatremic dehydration ensues. There
large dogs. Care should be taken to avoid overdistending or are no obvious contraindications to the use o f lactulose.
TABLE 30-7
Selected Anthelmintics
DRUG DOSAGE* (PO) USE COMMENTS
PO, Orally.
Clinical Features
The condition may cause a painless enlargement of one or
MASSES, PROLIFERATIONS, AND more salivary glands (usually the submandibular). If there is
INFLAMMATION OF THE OROPHARYNX substantial inflammation, animals may be dysphagic. A syn
drome has been reported in which noninflammatory swelling
SIALOCELE is associated with vomiting that is responsive to phenobarbi
tal therapy. This syndrome has no established cause and effect.
Etiology
Sialoceles are accumulations of saliva in subcutaneous tissues Diagnosis
caused by salivary duct obstruction and/or rupture and Biopsy and cytology or histopathology confirm that the mass
subsequent leakage of secretions into subcutaneous tissues. is salivary tissue and determine whether inflammation or
Most cases are probably traumatic, but some are idiopathic. necrosis is present.
Treatment (classically i n Boxers), oral papillomatosis, and eosinophilic
If there is substantial inflammation and pain, surgical granulomas (e.g., i n Siberian Huskies and Cavalier K i n g
removal seems most efficacious. If the patient is vomiting, a Charles Spaniels) also occur.
search should be made for an underlying cause. If a cause is
found, it should be treated and the size of the salivary glands Clinical Features
monitored. If no other cause for vomiting can be found, The most c o m m o n signs of tumors of the oral cavity are
phenobarbital may be administered at anticonvulsant doses halitosis, dysphagia, bleeding, or a growth protruding from
(see Chapter 67). the mouth. Papillomatosis and fibromatous periodontal
hyperplasia are benign growths that may cause discomfort
Prognosis when eating and occasionally cause bleeding, m i l d halitosis,
The prognosis is usually excellent. or tissue protrusion from the mouth. The biologic behaviors
of the different tumors are presented i n Table 31-1.
NEOPLASMS OF THE O R A L CAVITY
IN D O G S Diagnosis
A thorough examination of the oral cavity (which may require
Etiology that the animal be under anesthesia) usually reveals a mass
Most soft tissue masses of the oral cavity are neoplasms, and involving the gingiva, although the tonsillar area, hard palate,
most of these are malignant (i.e., melanoma, squamous cell and tongue can also be affected. Diagnosis requires cytologic
carcinoma, fibrosarcoma). However, acanthomatous amelo or histopathologic analysis, although papillomatosis and
blastomas (previously called epulides), fibromatous epulides melanomas may be strongly suspected o n the basis of their
TABLE 31-1
TYPICAL A P P E A R A N C E / BIOLOGIC
TUMOR LOCATION BEHAVIOR PREFERRED THERAPY
S q u a m o u s Cell Carcinoma
Etiology Etiology
There are many causes o f canine and feline stomatitis (Box A n idiopathic disorder, feline lymphocytic-plasmacytic gin
31 -1). The clinician should always consider the possibility o f givitis might be caused by feline calicivirus or any stimulus
immunosuppression with secondary stomatitis (e.g., F e L V , producing sustained gingival inflammation. Cats appear
FIV, diabetes mellitus, hyperadrenocorticism). to have an excessive oral inflammatory response that can
produce marked gingival proliferation.
Clinical Features
Most dogs and cats with stomatitis have thick, ropey saliva; Clinical Features
severe halitosis; and/or anorexia caused by pain. Some Anorexia and/or halitosis are the most c o m m o n signs.
animals are febrile and lose weight. Affected cats grossly have reddened gingiva around the teeth
and/or posterior pillars o f the pharynx. The gingiva may be
Diagnosis obviously proliferative i n severe cases and bleed easily. Dental
A thorough oral examination usually requires that the animal neck lesions often accompany the gingivitis. Teeth chattering
be under anesthesia. Stomatitis is diagnosed by gross obser- is also occasionally seen.
Diagnosis Prognosis
Biopsy o f affected (especially proliferative) gingiva is needed The prognosis is usually good, but continued medication
for diagnosis. Histologic evaluation reveals a lymphocytic- may be needed.
plasmacytic infiltration. Serum globulin concentrations may
be increased. CRICOPHARYNGEAL A C H A L A S I A /
DYSFUNCTION
Treatment
There is currently no reliable therapy for this disorder. Proper Etiology
cleaning and polishing o f teeth and antibiotic therapy effec The cause o f cricopharyngeal achalasia/dysfunction is
tive against anaerobic bacteria may help. High-dose cortico unknown, but it is usually congenital. There is an incoordi
steroid therapy (prednisolone, 2.2 mg/kg/day) is often useful. nation between the cricopharyngeus muscle and the rest of
In some severe cases, multiple tooth extractions may allevi the swallowing reflex, which produces obstruction at the
ate the source o f the inflammation. However, extraction o f cricopharyngeal sphincter during swallowing (i.e., the
the canine teeth should be delayed. Immunosuppressive sphincter does not open at the proper time). The problem
drugs such as chlorambucil also may be tried i n obstinate has a genetic basis i n Golden Retrievers.
cases.
Clinical Features
Prognosis Primarily seen i n young dogs, cricopharyngeal achalasia
The prognosis is guarded; severely affected animals often do rarely occurs as an acquired disorder. The major sign is
not respond well to therapy. regurgitation immediately after or concurrent with swallow
ing. Some animals become anorexic, and severe weight loss
may occur. Clinically, this condition may be indistinguish
DYSPHAGIAS able from pharyngeal dysfunction.
Treatment Etiology
High-dose prednisolone therapy (2.2 mg/kg/day) with or Pharyngeal dysphagia is primarily an acquired disorder,
2
without azathioprine (50 m g / m q24 h) is usually curative. and neuropathies, myopathies, and junctionopathies (e.g.,
Once control has been achieved, the prednisolone and aza localized myasthenia gravis) seem to be the main cause.
thioprine are administered every 48 hours and then the dose The inability to form a normal bolus o f food at the base of
of prednisolone is tapered to avoid adverse effects. However, the tongue and/or to propel the bolus into the esophagus is
this tapering must be done slowly to prevent recurrence (see often associated with lesions o f cranial nerves IX or X .
the section o n immunosuppressive drugs i n Chapter 103). Simultaneous dysfunction o f the cranial esophagus may
If needed, a gastrostomy tube may be used until the animal cause food retention just caudal to the cricopharyngeal
can eat. sphincter.
Clinical Features Occasionally, coughing and other signs o f aspiration trache
Although pharyngeal dysphagia principally is found i n older itis and/or pneumonia may be the only signs reported by the
animals, young animals occasionally have transient signs. owner.
Pharyngeal dysphagia often clinically mimics cricopharyn
geal achalasia; regurgitation is associated with swallowing. Diagnosis
Pharyngeal dysphagia sometimes causes more difficulty with The clinician usually first determines from the history that
swallowing fluids than solids. Aspiration (especially associ regurgitation appears likely (see p. 353). Then, after radio
ated with liquids) is c o m m o n because the proximal esopha graphic findings show generalized esophageal dilation that
gus is often flaccid and retains food, predisposing to later is not associated with obstruction (see Fig. 29-3, A), the
reflux into the pharynx. clinician can presumptively diagnose esophageal weakness.
Diverticula i n the cranial thorax caused by esophageal
Diagnosis weakness occur occasionally and are often confused with
Fluoroscopy or cinefluoroscopy while the animal is swallow vascular ring obstruction (Fig. 31-1). Congenital, rather
ing barium is typically required for diagnosis. A n experi than acquired, disease is suspected i f the regurgitation and/
enced radiologist is needed to reliably distinguish pharyngeal or aspiration began when the pet was young. If clinical fea
dysphagia from cricopharyngeal dysphagia. W i t h the former tures have been relatively m i l d or intermittent, the diagnosis
condition, the animal does not have adequate strength to might not be made until the animal is older, but consider
properly push boluses of food into the esophagus, whereas ation o f the history should suggest that signs have been
in the latter the animal has adequate strength but the crico present since the animal was young. Endoscopy is not
pharyngeal sphincter stays shut or opens at the wrong time as useful as contrast radiographs for diagnosing this disor
during swallowing, thereby preventing n o r m a l movement o f der. Collies may have dermatomyositis, which also causes
food from the pharynx to the proximal esophagus. It appears esophageal weakness. Some breeds (e.g., M i n i a t u r e Schnau
that some cases may be detected by electromyography o f zers, Great Danes, Dalmatians) appear to be at increased
laryngeal, pharyngeal, and esophageal muscles. risk.
Treatment Treatment
Although cricopharyngeal myotomy is often curative for Congenital esophageal weakness currently cannot be cured
animals with cricopharyngeal achalasia, it may be disastrous or resolved by medical therapy, although cisapride (0.25 m g /
for animals with pharyngeal dysphagias because it allows kg) seemingly ameliorates signs i n rare cases (probably i n
food retained i n the proximal esophagus to more easily patients with substantial gastroesophageal reflux). Conser
reenter the pharynx and be aspirated. The clinician must vative dietary management is used to try to prevent further
either bypass the pharynx (e.g., gastrostomy tube) or resolve dilation and aspiration. Classically, the animal is fed a gruel
the underlying cause (e.g., treat or control myasthenia from an elevated platform that requires the pet to stand o n
gravis). its rear legs. In this manner, the cervical and thoracic esoph
agus is nearly vertical when food is ingested, w h i c h allows
Prognosis gravity to aid food passing through the esophagus and into
The prognosis is guarded because it is often difficult to the stomach. This position should be maintained for 5 to 10
find and treat the underlying cause, and the dog or cat is minutes after the animal has finished eating and drinking. If
prone to progressive weight loss and recurring aspiration the dog cannot stand, it may be backed into a corner, forced
pneumonia. to sit o n its haunches, and have its front legs lifted while the
corner prevents the dog from falling over. Alternatively, it
may be fed o n stairs so that it is at least at a 45-degree angle
ESOPHAGEAL WEAKNESS/ when eating. Feeding several small meals a day also helps
MEGAESOPHAGUS prevent esophageal retention.
Some animals do better i f fed dry or canned dog food free
CONGENITAL E S O P H A G E A L W E A K N E S S choice throughout the day from such a platform. It is impos
sible to predict whether a given dog will respond better to
Etiology gruel or dry dog food. Therefore trial and error are necessary
The cause of congenital esophageal weakness (i.e., congenital to determine the diet that works best for a particular animal.
megaesophagus) is unknown. There is no evidence of demy In some dogs the dilated esophagus may partially return to
elination or neuronal degeneration, and vagal efferent inner n o r m a l size and function. Even i f the esophagus remains
vation appears to be normal. dilated, some dogs may be managed by dietary change and
have a good quality o f life.
Clinical Features Gastrostomy tubes bypass the esophagus and can provide
Affected animals (primarily dogs) are usually presented some relief from regurgitation and/or aspiration. However,
because of "vomiting" (actually regurgitation) with or animals may still regurgitate saliva and, i f there is gastro
without weight loss, coughing, or fever from pneumonia. esophageal reflux, may also regurgitate food. Some animals
FIG 31-1
Lateral contrast t h o r a c i c r a d i o g r a p h of a cat. N o t e l a r g e diverticulum suggestive of
obstruction (arrows). This c a t h a d g e n e r a l i z e d e s o p h a g e a l w e a k n e s s w i t h o u t obstruction.
with gastrostomy tubes respond well for varying periods o f ized esophageal dilation without evidence of obstruction on
time. plain and contrast radiographs (see Fig. 29-3, A). The sever
ity of clinical signs does not always correlate with the mag
Prognosis nitude o f radiographic changes. Some symptomatic animals
The prognosis is guarded to poor; some animals respond have segmental weakness primarily affecting the cervical
well, but most have severe regurgitation and/or aspiration esophagus, just behind the cricopharyngeus muscle. However,
symptoms despite all treatment efforts. Aspiration pneumo normal dogs often have m i n i m a l amounts of barium retained
nia is the major cause o f death. in this location, so it is important to distinguish insignificant
from clinically important retention. It is important to rule
ACQUIRED E S O P H A G E A L W E A K N E S S out lower esophageal spasm and stricture, which, though
very rare, radiographically m i m i c esophageal weakness but
Etiology require surgical treatment. Ideally, fluoroscopy should be
Acquired esophageal weakness in dogs is usually caused by used to look for evidence o f gastroesophageal reflux, which
a neuropathy, myopathy, or junctionopathy (e.g., myasthenia may benefit from prokinetic therapy (e.g., cisapride).
gravis; see B o x 28-5). G e r m a n Shepherds, Golden Retrievers, It is important to search for underlying causes of acquired
and Irish Setters might have increased risk. In cats esopha esophageal weakness (see Box 28-5). The titer o f antibodies
gitis may be a cause of acquired esophageal weakness. to acetylcholine receptors (indicative of myasthenia gravis)
should be measured in dogs. "Localized" myasthenia may
Clinical Features affect only the esophagus and/or oropharyngeal muscles. A n
Acquired esophageal weakness primarily occurs in dogs. adrenocorticotropic hormone ( A C T H ) - s t i m u l a t i o n test is
The patients usually are presented because of "vomiting" indicated to look for otherwise occult hypoadrenocorticism
(actually regurgitation), but some present with a cough (even if serum electrolyte concentrations are normal). Serum
and little or no obvious regurgitation (e.g., regurgitated thyroxine, free thyroxine, and thyroid-stimulating hormone
material is sometimes reswallowed or re-eaten by the animal). (TSH) concentrations may reveal hypothyroidism, which
Weight loss may occur i f the dog regurgitates most o f its can very rarely be associated with esophageal dysfunction.
food. Tests of thyroid gland function must be interpreted carefully
because of potential confusion regarding the euthyroid sick
Diagnosis syndrome (see Chapter 51). Electromyography may reveal
The initial diagnostic step is to document that regurgitation, generalized neuropathies or myopathies. Dysautonomia
rather than vomiting, is occurring (see p. 353). Acquired occurs occasionally and is suspected on the basis of clinical
esophageal weakness is usually diagnosed by finding general signs (i.e., dilated colon, dry nose, dilated pupils, keratocon-
junctivitis sicca, and/or bradycardia that responds poorly to often hyperemic and/or ulcerated; anorexia is the primary
atropine). Gastric outflow obstruction i n cats can cause sign.
vomiting with secondary esophagitis. Other causes are rarely
found (see Box 28-5). If an underlying cause cannot be Diagnosis
found, the disease is termed idiopathic acquired esophageal A history o f vomiting followed by both v o m i t i n g and regur
weakness (i.e., idiopathic acquired megaesophagus). gitation suggests esophagitis secondary to excessive exposure
to gastric acid. This sign may occur i n parvoviral enteritis
Treatment and in various other disorders. Likewise, regurgitation or
Dogs with acquired megaesophagus caused by localized anorexia begining shortly after an anesthetic procedure may
myasthenia gravis or hypoadrenocorticism often respond to indicate esophagitis caused by reflux. Plain and contrast
appropriate therapy (see Chapters 53 and 71). Localized radiographs may reveal hiatal hernias, gastroesophageal
myasthenia seems ultimately to respond best to i m m u n o reflux, or esophageal foreign bodies. Contrast esophagrams
suppressive therapy (e.g., azathioprine), although pyridostig do not reliably detect esophagitis; esophagoscopy with or
mine may help initially. Gastroesophageal reflux may respond without biopsy is needed to establish a definitive diagnosis.
to prokinetic and antacid therapy (cisapride at 0.25 mg/kg
and omeprazole at 0.7 to 1.5 mg/kg are preferred). If the Treatment
disease is idiopathic, conservative dietary therapy as described Decreasing gastric acidity, preventing reflux o f gastric
for congenital esophageal weakness is the only recourse. contents into the esophagus, and protecting the denuded
Although some dogs with congenital esophageal weakness esophagus are the hallmarks o f treatment. H receptor 2
regain variable degrees of esophageal function, this is rare i n antagonists (see Table 30-4) may be used, but proton p u m p
those with idiopathic acquired esophageal weakness. Severe inhibitors (e.g., omeprazole) are superior for decreasing
esophagitis may cause secondary esophageal weakness, which gastric acidity, a critical factor i n these animals. However,
resolves after appropriate therapy (discussed i n more detail because it may take 2 to 5 days for omeprazole to achieve
later in this chapter). Gastrostomy tubes diminish the poten m a x i m u m efficacy, famotidine may be used concurrently
tial for aspiration, ensure positive nitrogen balance, and help during initial therapy. Metoclopramide stimulates gastric
treat esophagitis if present. Some dogs benefit from the long- emptying, resulting i n less gastric volume to reflux into the
term use of a gastrostomy tube, but others continue to regur esophagus, but cisapride (0.25 to 0.5 mg/kg) tends to be
gitate and aspirate as a result o f severe gastroesophageal more effective. Sucralfate (particularly suspensions) might
reflux or simply the accumulation o f large amounts o f saliva protect denuded esophageal mucosa (see Table 30-5), but
in the esophagus. its usefulness is u n k n o w n . Antibiotics effective against
anaerobes (e.g., amoxicillin, clindamycin; see Drugs Used i n
Prognosis Gastrointestinal Disorders, pp. 481-483) have been used but
A l l animals with acquired esophageal weakness are at risk for are o f u n k n o w n value. A gastrostomy feeding tube helps to
aspiration pneumonia and sudden death. If the underlying protect the esophagus while the mucosa is healing and
cause can be treated and the esophageal dilation and weak ensures a positive nitrogen balance. Corticosteroids (e.g.,
ness can be resolved, the prognosis is good because the risk prednisolone, 1.1 mg/kg/day) may be administered i n an
of aspiration is eliminated. The prognosis is guarded i f the attempt to prevent cicatrix, but their efficacy is dubious.
animal with idiopathic megaesophagus responds to dietary Hiatal hernias may need to be surgically repaired.
management (it is still at risk) and very poor i f the animal
does not respond to this protocol. Prognosis
The prognosis depends o n the severity o f the esophagitis
ESOPHAGITIS and whether an underlying cause can be identified and
controlled. Early, aggressive therapy helps to prevent cicatrix
Etiology formation and allows a better prognosis.
Esophagitis is principally caused by gastroesophageal reflux,
persistent vomiting of gastric acid, esophageal foreign HIATAL HERNIA
objects, and caustic agents. Pills (e.g., tetracycline) may be
retained i n the esophagus i f they are not washed down with Etiology
water or food and are thought to cause severe esophagitis i n Hiatal hernia is a diaphragmatic abnormality that allows
cats. A n association between distal esophagitis (ostensibly part o f the stomach (usually the cardia) to prolapse into the
caused by gastroesophageal reflux) and upper respiratory thoracic cavity. In severe cases it allows gastroesophageal
disease in brachycephalic dogs has been suggested. reflux. The condition seems to be primarily congenital.
FIG 31-2
A , Lateral r a d i o g r a p h o f a d o g w i t h a hiatal h e r n i a s h o w i n g the gastric s h a d o w extend
ing c r a n i a l to the d i a p h r a g m (arrows). B , Lateral v i e w of contrast e s o p h a g r a m of a c a t
w i t h hiatal h e r n i a . There is no e v i d e n c e of h e r n i a on this r a d i o g r a p h because it has
a p p a r e n t l y slid b a c k into the a b d o m e n . C , Lateral v i e w of contrast e s o p h a g r a m of the cat
in B . The b o d y of the stomach has n o w slid into the t h o r a c i c c a v i t y (arrows), c o n f i r m i n g
that a hiatal h e r n i a is present. D , A n e n d o s c o p i c i m a g e o f the l o w e r e s o p h a g e a l sphincter
(LES) a r e a of a d o g w i t h a hiatal h e r n i a . G a s t r i c r u g a l folds c a n be seen. ( A , Courtesy
Dr. Russ Stickle, M i c h i g a n State University, East Lansing, M i c h . B a n d C , C o u r t e s y Dr.
Royce Roberts, University o f G e o r g i a , A t h e n s , G a . )
of pupillary light response, dry mucous membranes, weight
loss, constipation, vomiting, poor anal tone, and/or anorexia
have all been reported. There appear to be geographic areas
(e.g., Missouri and surrounding states) that currently have
an increased incidence o f the disease.
Diagnosis
Dysautonomia is usually first suspected clinically by finding
dysuria, dry mucous membranes, and abnormal pupillary
light responses. Radiographs revealing distention of multiple
areas of the alimentary tract (e.g., esophagus, stomach, small
intestine) also are suggestive. A presumptive, antemortem
diagnosis is usually made by observing the effects o f pilocar
pine on pupil size after 1 to 2 drops of 0.05% pilocarpine are
placed i n one eye only. Finding that the treated eye rapidly
constricts whereas the untreated eye does not is consistent
with dysautonomia. Similarly, finding that a dysuric dog
FIG 3 1 - 3
with a large urinary bladder can urinate after subcutaneous E n d o s c o p i c v i e w of a n e s o p h a g e a l lumen constricted b y a n
administration of 0.04 m g bethanechol/kg is also suggestive e x t r a m u r a l v a s c u l a r ring a n o m a l y .
(although not all affected animals respond). Definitive diag
nosis requires histopathology of autonomic ganglia, which
can be obtained only at necropsy.
normal. In rare cases the entire esophagus is dilated (the
Treatment result o f concurrent megaesophagus) except for a narrowing
Treatment is palliative. Bethanechol can be given (1.25 to at the base o f the heart. It has been suggested that i f focal
5 mg once daily) to aid i n urinary evacuation. The urinary leftward deviation o f the trachea is seen at the cranial border
bladder should be expressed as needed. Gastric prokinetics of the heart i n the ventrodorsal or dorsoventral projections,
(e.g., cisapride) may help lessen vomiting. Antibiotics may this is sufficient to diagnose P R A A i n young dogs that are
be administered for aspiration pneumonia secondary to regurgitating food. Endoscopically, the esophagus has an
megaesophagus. extramural narrowing (Fig. 31-3; i.e., not a mucosal prolif
eration or scar) near the base of the heart.
Prognosis
The prognosis is usually grim. Treatment
Surgical resection o f the anomalous vessel is necessary. C o n
servative dietary management (i.e., gruel diet) by itself is
ESOPHAGEAL OBSTRUCTION inappropriate because the dilation will persist and probably
progress. In particular, the animal w i l l be at risk for foreign
VASCULAR RING A N O M A L I E S body occlusion at the site o f the P R A A . Dietary therapy may
benefit some animals postoperatively.
Etiology
Vascular ring anomalies are congenital defects. A n embry Prognosis
onic aortic arch persists, trapping the esophagus i n a ring o f M o s t patients improve dramatically after surgery. However,
tissue. Persistent right fourth aortic arch ( P R A A ) is the most there are exceptions, and the more severe the preoperative
commonly recognized vascular anomaly (see Chapter 5). dilation, the more likely regurgitation will continue postop
eratively. Some dogs have concomitant esophageal weakness.
Clinical Features A guarded prognosis is appropriate. If a postsurgical stric
Vascular ring anomalies occur i n both dogs and cats. Regur ture occurs, esophageal ballooning or a second surgical pro
gitation is the most c o m m o n presenting complaint, although cedure may be considered.
signs of aspiration may occur. Clinical features often begin
shortly after the animal eats solid food for the first time. E S O P H A G E A L FOREIGN OBJECTS
Some animals have relatively m i n o r clinical signs and are not
diagnosed until they are several years old. Etiology
Almost anything may lodge i n the esophagus, but objects
Diagnosis with sharp points (e.g., bones, fishhooks) are probably
Definitive diagnosis is usually made by contrast esophagram most c o m m o n . M o s t obstructions occur at the thoracic
(see Fig. 29-3, B). Typically, the esophagus cranial to the inlet, the base of the heart, or immediately i n front o f the
heart is dilated, whereas the esophagus caudal to the heart is diaphragm.
Clinical Features E S O P H A G E A L CICATRIX
Dogs are more c o m m o n l y affected because of their less
discriminating eating habits. Regurgitation or anorexia Etiology
secondary to esophageal pain is c o m m o n . Acute onset o f Prior esophagitis from any cause may produce a stricture.
regurgitation (as opposed to vomiting) is suggestive o f Severe, deep inflammation of the esophagus (e.g., subse
esophageal foreign body. Clinical signs depend o n where the quent to foreign bodies or severe gastroesophageal reflux) is
obstruction occurs, whether it is complete or partial, and usually required for cicatrix to occur.
whether esophageal perforation has occurred. Complete
obstructions cause regurgitation o f solids and liquids, Clinical Features
whereas partial obstructions may allow passage o f liquids to Esophageal cicatrix occurs i n both dogs and cats. The main
the stomach. If an esophageal foreign object is impinging o n sign is regurgitation (especially o f solids). Some animals
airways, acute dyspnea may occur. Esophageal perforation are clinically anorexic as a result o f pain experienced when
usually causes fever and anorexia; dyspnea may occur as the food becomes lodged at the stricture by forceful esophageal
result of pleural effusion or pneumothorax. Subcutaneous peristalsis.
emphysema rarely occurs.
Diagnosis
Diagnosis Partial obstructions may be difficult to diagnose. Positive-
Plain thoracic radiographs reveal most esophageal foreign contrast esophagrams (often using barium mixed with food)
bodies (see Fig. 29-2), although the clinician may have to are necessary (Fig. 31-4). Esophagoscopy is definitive, but a
search carefully to find poultry bones or other food items partial stricture may not be obvious i n large dogs unless the
that are even less radiodense. It is also important to look for endoscopist is experienced and the esophagus is carefully
evidence o f esophageal perforation (i.e., pneumothorax, inspected.
pleural effusion, fluid i n the mediastinum). Esophagrams are
rarely necessary; esophagoscopy is diagnostic and typically Treatment
therapeutic. Treatment consists o f correcting the suspected cause (e.g.,
esophagitis) and/or widening the stricture by ballooning or
Treatment bougienage. Surgical resection is not recommended because
Foreign objects are best removed endoscopically unless (1) iatrogenic strictures at the anastomotic site are common.
they are too firmly lodged to pull free or (2) radiographs Ballooning is less traumatic, has less chance of perforation,
suggest perforation. Thoracotomy is indicated i n these two
situations, although i n rare cases perforations may be treated
medically. Objects that cannot be moved should not be
pulled on vigorously because of the risk of creating or enlarg
ing a perforation. A n object should be pushed into the
stomach only when the clinician is confident that there are
no sharp edges on the other side of the foreign object. D u r i n g
the procedure the esophagus should be insufflated carefully
to avoid rupturing weakened areas or causing tension pneu
mothorax. After an object has been removed, the esophageal
mucosa should be reexamined endoscopically to evaluate the
damage caused by the object. Thoracic radiographs should
be repeated to look for pneumothorax, an indication o f per
foration. Treatment after foreign body removal may include
antibiotics, H receptor antagonists or proton p u m p inhibi
2
FIG 3 1 - 5
A , Lateral thoracic r a d i o g r a p h of a d o g w i t h a previously unsuspected mass (arrows) not
obviously associated w i t h the e s o p h a g u s . B , Contrast e s o p h a g r a m in the same d o g
demonstrates that the e s o p h a g u s is d i l a t e d (large arrows) a n d that there a r e intraesopha
geal filling defects (small arrows) in this d i l a t e d a r e a . This d o g h a d a p r i m a r y e s o p h a g e a l
carcinoma. ( A from Allen D, editor: Small animal medicine, Philadelphia, 1 9 9 1 , JB Lippincott.)
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disease: clinical signs and radiographic, endoscopic, and histo
pathologic findings, J Am Anim Hosp Assoc 39:161, 2003.
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Vet Med Assoc 220:633, 2002.
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Leib M S et al: Endoscopic b a l l o o n dilation o f benign esophageal
strictures i n dogs and cats, / Vet Intern Med 15:547, 2001.
Mears E A et al: Canine megaesophagus. In Bonagura J D , editor:
Current veterinary therapy XIII, Philadelphia, 2000, W B
FIG 31-6 Saunders.
Endoscopic view of the lower esophageal sphincter of a Melendez L D et al: Suspected doxycyline-induced esophagitis with
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at 3 o'clock to the sphincter. 2000.
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Moses L et al: Esophageal motility dysfunction i n cats: a study of
identifying lower esophageal sphincter leiomyomas and
44 cases, J Am Anim Hosp Assoc 36:309, 2000.
leiomyosarcomas. Niles JD et al: Resolution o f dysphagia following cricopharyngeal
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Treatment N u n n R et al: Association between Key-Gaskell syndrome and
Surgical resection is rarely curative (except for leiomyomas infection by Clostridium botulinum type C / D , Vet Rec 155:111,
at the lower esophageal sphincter) because of the advanced 2004.
nature of most esophageal neoplasms when they are diag O ' B r i e n D P et al: Diagnosis and management o f dysautonomia in
nosed. Resection may be palliative. Photodynamic therapy dogs. In Bonagura J D , editor: Current veterinary therapy XIII,
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esophageal neoplasms.
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Prognosis Diagnosis
The vomiting usually stops as soon as the worms are removed Diagnosing pyloric stenosis requires first finding gastric
or eliminated. outflow obstruction during barium contrast-enhanced
radiographs (Fig. 32-2), ultrasonography, gastroduodenos
OLLULANUS TRICUSPIS copy, and/or exploratory surgery. Infiltrative disease of the
pyloric mucosa then must be ruled out through biopsy.
Etiology Endoscopically, the clinician may see prominent folds of
Ollulanus tricuspis is a nematode with a direct life cycle that normal-appearing mucosa at the pylorus. A t surgery the
is transmitted via vomited material. serosa appears normal, but the pylorus is usually thickened
when palpated. The surgeon can open the stomach and try
Clinical Features to pass a finger through the pylorus to assess its patency.
Cats are the most c o m m o n l y affected species, although dogs Extraalimentary tract diseases causing vomiting (see Box
and foxes are occasionally infected. V o m i t i n g is the principal 28-6) should also be eliminated.
clinical sign, but clinically n o r m a l cats may harbor the para
site. Gross gastric mucosal lesions may or may not be seen Treatment
i n infested cats. Surgical correction is indicated. Pyloroplasty (e.g., a Y - U -
plasty) is more consistently effective than pyloromyotomy.
Diagnosis However, improperly performed pyloroplasty or pyloromy
Cattery situations promote infection because the parasite is otomy can cause perforation or obstruction. Furthermore,
passed directly from one cat to another. However, occasion the clinician should not routinely do a pyloric outflow pro
ally cats with no k n o w n contact with other cats are infected. cedure whenever an exploratory procedure fails to reveal
Looking for parasites in gastric washings or vomited material another cause o f vomiting.
FIG 32-2
A a n d B , V e n t r o d o r s a l contrast r a d i o g r a p h s of a d o g w i t h
a gastric o u t f l o w obstruction. These r a d i o g r a p h s w e r e
o b t a i n e d a p p r o x i m a t e l y 3 hours after b a r i u m a d m i n i s t r a
t i o n . There is i n a d e q u a t e gastric e m p t y i n g despite o b v i o u s
peristalsis. N o t e the smooth c o n t o u r o f b a r i u m in the antrum
(arrows), w h i c h is in contrast to C . This is a case of p y l o r i c
stenosis. C , Dorsoventral contrast r a d i o g r a p h s of a d o g
w i t h gastric a d e n o c a r c i n o m a . The antrum has a n i r r e g u l a r
outline but is not d i s t e n d e d (arrows). This failure to distend
persisted on multiple r a d i o g r a p h s a n d indicates a n infiltra
tive lesion.
Prognosis Clinical Features
Surgery should be curative, and the prognosis is good. Principally found i n older, small-breed dogs, antral hyper
trophy clinically resembles pyloric stenosis (i.e., animals
GASTRIC A N T R A L M U C O S A L usually vomit food, especially after meals).
HYPERTROPHY
Diagnosis
Etiology Gastric outlet obstruction is diagnosed radiographically,
Antral mucosal hypertrophy is idiopathic. Gastric outflow ultrasonographically, or endoscopically; however, definitive
obstruction is caused by excessive, nonneoplastic mucosa diagnosis o f antral mucosal hypertrophy requires biopsy.
that occludes the distal gastric antrum (Fig. 32-3). This dis Endoscopically, the antral mucosa is redundant and may
order is different from benign muscular pyloric stenosis, i n resemble a submucosal neoplasm causing convoluted
which the mucosa is thrown up into folds secondary to the mucosal folds. In some cases the mucosa will be obviously
submucosal thickening. reddened and inflamed. However, the mucosa in dogs with
FIG 3 2 - 3
A , E n d o s c o p i c v i e w o f the p y l o r i c r e g i o n of a d o g that has gastric antral mucosal
h y p e r t r o p h y . If b i o p s y is not p e r f o r m e d , these folds m a y easily be mistaken f o r n e o p l a s i a .
B , Intraoperative p h o t o g r a p h of a d o g ' s o p e n e d pylorus. N o t e the numerous folds of
mucosa that a r e p r o t r u d i n g (arrows) as a result o f gastric antral mucosal h y p e r t r o p h y .
antral hypertrophy is usually not as firm or hard as expected induced (e.g., apomorphine i n the dog, 0.02 or 0.1 mg/kg
in those with infiltrative carcinomas or leiomyomas. If antral administered intravenously or subcutaneously, respectively;
mucosal hypertrophy is seen at surgery, there should be no hydrogen peroxide i n the dog, 1 to 5 m l o f 3% solution/kg
evidence of submucosal infiltration or muscular thickening administered orally; xylazine i n the cat, 0.4 to 0.5 mg/kg
suggestive of neoplasia or benign pyloric stenosis, respec administered intravenously) to eliminate gastric foreign
tively. It is important to differentiate mucosal hypertrophy objects i f the clinician believes that the object will not cause
from these other diseases so that therapeutic recommenda problems during forcible ejection (i.e., it does not have sharp
tions are appropriate (e.g., gastric carcinomas typically have edges or points and is small enough to pass easily). If there
a worse prognosis, and surgery is not always indicated). is doubt as to the safety o f this approach, the object should
be removed endoscopically or surgically.
Treatment Before the animal is anesthetized for surgery or endos
Antral mucosal hypertrophy is treated by mucosal resection, copy, the electrolyte and acid-base status should be evalu
usually combined with pyloroplasty. Pyloromyotomy alone ated. Although electrolyte changes (e.g., hypokalemia) are
may be insufficient to resolve clinical signs from mucosal c o m m o n , they are impossible to predict w i t h any accuracy.
hypertrophy. Hypokalemia predisposes to cardiac arrhythmias and should
be corrected before anesthesia is induced.
Prognosis Endoscopic removal o f foreign objects requires a flexible
The prognosis is excellent. endoscope and appropriate retrieval forceps. The animal
should always be radiographed just before being anesthe
GASTRIC FOREIGN OBJECTS tized to ensure that the object is still i n the stomach. Lacera
tion o f the esophagus and entrapment o f the retrieval forceps
Etiology i n the object should be avoided. If endoscopic removal is
Objects that can pass through the esophagus may become a unsuccessful, gastrostomy should be performed.
gastric or intestinal foreign object. Subsequently, v o m i t i n g
may result from gastric outlet obstruction, gastric distention, Prognosis
or irritation. Linear foreign objects whose orad end lodges The prognosis is usually good unless the animal is debilitated
at the pylorus may cause intestinal perforation with subse or there is septic peritonitis secondary to gastric perforation.
quent peritonitis and must be dealt with expeditiously (see
the section on intestinal obstruction o n p. 464). GASTRIC D I L A T I O N / V O L V U L U S
FIG 3 2 - 4
Lateral r a d i o g r a p h o f a d o g w i t h gastric d i l a t i o n / v o l v u l u s . The stomach is d i l a t e d (large
arrows), a n d there is a "shelf" of tissue (small arrows), d e m o n s t r a t i n g that the stomach is
m a l p o s i t i o n e d . R a d i o g r a p h s o b t a i n e d from the right lateral position seem superior to those
o f other v i e w s in d e m o n s t r a t i n g this shelf. If the stomach w e r e similarly d i s t e n d e d but not
m a l p o s i t i o n e d , the d i a g n o s i s w o u l d b e gastric d i l a t i o n .
immediately performing a laparotomy after decompressing classic G D V . Although occurring i n the same breeds as G D V ,
the stomach but before stabilizing the animal. The decision partial gastric volvulus usually produces a chronic, inter
as to whether to first stabilize the animal or immediately mittent, potentially difficult-to-diagnose problem. It may
perform surgery is based on the condition of the dog at occur repeatedly and spontaneously resolve; dogs may appear
initial presentation and on whether the animal w o u l d be a normal between bouts. Some dogs have persistent, nondis
considerably better anesthetic risk after stabilization. tended volvulus and are asymptomatic.
If the dog has G D V (see Fig. 32-4), surgery is necessary
to reposition the stomach; this is followed by gastropexy to Diagnosis
prevent recurrence. This surgery should be performed as Plain radiographs are usually diagnostic (Fig. 32-5). However,
soon as the animal constitutes an acceptable anesthetic risk diagnosis may require repeated radiographs and/or contrast
because torsion (even when the stomach is deflated) impairs studies. Chronic volvulus will rarely be diagnosed endoscop
gastric wall perfusion and may cause necrosis. Areas of ically. It is possible, i n rare cases, to cause a temporary gastric
gastric wall necrosis should be resected, or preferably invag- volvulus by manipulating the gastroscope i n an air-distended
inated, to prevent perforation and abdominal contamina stomach. Therefore the clinician must differentiate sponta
tion. In dogs with gastric dilation without torsion, gastropexy neous from iatrogenic volvulus.
is optional and may be performed after the dog is completely
recovered from the current episode. Gastropexy almost Treatment
always prevents torsions but does not prevent dilation. If partial or intermittent gastric volvulus is diagnosed, surgi
Postoperatively, the animal should be monitored by elec cal repositioning and gastropexy are usually curative.
trocardiogram (ECG) for 48 to 72 hours. Lidocaine, procain
amide, and/or soltolol therapy may be needed i f cardiac Prognosis
arrhythmias diminish cardiac output (see Chapter 4). H y p o The prognosis is usually good once the problem is identified
kalemia is c o m m o n and makes such arrhythmias refractory and surgically corrected.
to medical control. Therefore hypokalemia should be
resolved. IDIOPATHIC GASTRIC
Prevention is difficult because the cause is u n k n o w n . HYPOMOTILITY
Although preventing exercise after meals and feeding small
meals of softened food w o u l d seem to be useful, there are no Etiology
data to confirm this speculation. Idiopathic gastric hypomotility refers to an anecdotal syn
drome characterized by poor gastric emptying and motility
Prognosis despite the lack of anatomic obstruction, inflammatory
The prognosis depends on how quickly the condition is lesions, or other causes.
recognized and treated. Mortality rates ranging from 20% to
45% have been reported. Early therapy improves the prog Clinical Features
nosis, whereas a delay lasting more than 5 hours between Idiopathic gastric hypomotility has primarily been diag
onset of signs and presentation to the veterinarian's office, nosed i n dogs. Affected dogs usually vomit food several
hypothermia at admission, preoperative cardiac arrhyth hours after eating but otherwise feel well. Weight loss may
mias, increased preoperative blood lactate concentrations, or may not occur.
gastric wall necrosis, severe D I C , partial gastrectomy, sple
nectomy, and postoperative development of acute renal Diagnosis
failure seem to worsen the prognosis. Although rare, gastric Fluoroscopic studies document decreased gastric motility,
dilation may recur after gastropexy. Prophylactic gastropexy but diagnosis requires ruling out gastric outlet obstruction,
may be elected for animals believed to be at increased risk infiltrative bowel disease, inflammatory abdominal disease,
for G D V . Laparoscopy can be used to make prophylactic and extraalimentary tract diseases (e.g., renal, adrenal, or
gastropexy a minimally invasive procedure. hepatic failure; severe hypokalemia or hypercalcemia).
Clinical Features
G U E is more c o m m o n in dogs than i n cats. Anorexia may
be the principal sign. If vomiting occurs, b l o o d (i.e., fresh or
digested) may or may not be present. A n e m i a and/or hypo FIG 3 2 - 6
proteinemia occasionally occur and cause signs (i.e., edema, C o n t r a s t v e n t r o d o r s a l r a d i o g r a p h of a d o g w i t h persistent
pale mucous membranes, weakness, dyspnea). Melena may v o m i t i n g . N o t e the small " s l i v e r " representing retention of
occur i f there is severe b l o o d loss within a short period of b a r i u m in the r e g i o n of the pylorus (arrows). This a r e a of
contrast persisted o n several r a d i o g r a p h s . E n d o s c o p y a n d
time. Most affected dogs, even those with severe G U E , do not
s u r g e r y c o n f i r m e d a l a r g e ulcer that h a d p e r f o r a t e d a n d
demonstrate pain during abdominal palpation. Perforation s p o n t a n e o u s l y s e a l e d . This r a d i o g r a p h demonstrates h o w
is associated with signs o f septic peritonitis (see p. 476). difficult r a d i o g r a p h i c d i a g n o s i s o f gastrointestinal ulceration
Some ulcers perforate and seal over before generalized peri can be.
tonitis occurs. In such cases a small abscess may develop at
the site, causing abdominal pain, anorexia, and/or vomiting.
Treatment
Diagnosis Therapy depends on the severity o f G U E and whether an
A presumptive diagnosis of G U E is usually based on finding underlying cause is detected. Animals with suspected G U E
evidence of gastrointestinal b l o o d loss (e.g., hematemesis, that is not obviously life threatening (i.e., there is no evi
melena, iron-deficiency anemia) i n an animal without a dence of severe anemia, shock, sepsis, severe abdominal pain,
coagulopathy. The history and physical examination may or severe depression) may first be treated symptomatically if
identify an obvious cause (e.g., stress, N S A I D administra the clinician believes that he or she knows the cause.
tion, mast cell tumor). Perforation may cause peritonitis and Symptomatic therapy (e.g., H receptor antagonists, 2
signs of an acute abdomen and sepsis. Because mast cell proton p u m p inhibitors, sucralfate, parenteral fluids, with
tumors may resemble almost any cutaneous lesion, all cuta holding food) is often successful. Eliminating the underlying
neous masses or nodules should be evaluated cytologically. etiology (e.g., N S A I D s , shock) is important, and any gastric
Hepatic failure is usually diagnosed on the basis of the serum foreign objects present should be removed. If appropriate
biochemistry profile. Contrast radiographs are diagnostic for medical therapy is unsuccessful after 5 or 6 days, or i f the
foreign objects and sometimes for G U E (Fig. 32-6). Ultraso animal has life-threatening bleeding despite appropriate
nography sometimes detects gastric thickening (such as medical therapy, the ulcer(s) should usually be resected. The
would be seen in infiltrated lesions) and/or mucosal defects. stomach should be examined endoscopically before surgery
Endoscopy is the most sensitive and specific tool for diagnos to determine the number and location of the ulcers; it is
ing G U E (see Figs. 29-18 to 29-21) and, i n conjunction with surprisingly easy to miss ulcers during laparotomy.
biopsy, can be used to diagnose tumors (see Fig. 29-20), In animals with gastrinomas, H -receptor antagonist 2
foreign bodies (see Fig. 29-24), and inflammation that may therapy is often palliative for months. Animals with high
cause ulcers. Endoscopic findings may also suggest a gastri serum gastrin concentrations may require more potent
noma if duodenal erosions are found. Serum gastrin concen and/or higher doses o f H receptor antagonists (e.g., famoti
2
trations should be measured i f a gastrinoma is suspected or dine) or the more potent proton p u m p inhibitors (see
if there are no other likely causes. Table 30-4).
Prevention of G U E is preferable to treatment, and ratio scopically. W h e n biopsy of such lesions is performed endo
nal N S A I D and steroid therapy are especially important. scopically, the sample must be deep enough to ensure that
Sucralfate (Carafate; see Table 30-5) and H receptor antag
2 submucosal tissue is included. Furthermore, scirrhous
onists (see Table 30-4) have been used i n an attempt to adenocarcinomas may be so dense that the clinician cannot
prevent G U E i n dogs receiving N S A I D s and steroids; however, obtain diagnostic biopsy specimens with flexible endoscopic
there is no good evidence that these drugs are effective for forceps. Mucosal lymphomas and nonscirrhous adenocarci
this purpose i n dogs and cats. M i s o p r o s t o l (see Table 30-5) nomas often produce G U E , and endoscopically obtained
is designed to prevent N S A I D - i n d u c e d ulceration and is tissue samples are usually diagnostic. Polyps are usually
more effective than H receptor antagonists or sucralfate.
2 obvious endoscopically, but a biopsy specimen should always
However, it is not uniformly successful. be obtained and evaluated to ensure that adenocarcinoma is
not present.
Prognosis
The prognosis is favorable i f the underlying cause can be Treatment
controlled and i f therapy prevents perforation of the ulcer. M o s t adenocarcinomas are advanced before clinical signs
are obvious, making complete surgical excision difficult or
impossible. Leiomyomas and leiomyosarcomas are more
INFILTRATIVE GASTRIC DISEASES likely to be resectable than adenocarcinomas. Gastroduode
nostomy may palliate gastric outflow obstruction caused by
NEOPLASMS an unresectable tumor. Chemotherapy is rarely helpful
except for dogs and cats with lymphoma.
Etiology
Neoplastic infiltrations (e.g., adenocarcinoma, lymphoma, Prognosis
leiomyomas, and leiomyosarcomas in dogs; l y m p h o m a i n The prognosis for adenocarcinomas and lymphomas is poor
cats) may produce G U E through direct mucosal disruption. unless they are detected very early. Leiomyomas and leio
Gastric l y m p h o m a is typically a diffuse lesion but can myosarcomas, i f diagnosed relatively early, are often cured
produce masses. The cause and significance of benign gastric surgically. It does not appear to be necessary to resect gastric
polyps are u n k n o w n . They seem to occur more c o m m o n l y polyps unless they are causing outflow obstruction.
in the antrum.
PYTHIOSIS
Clinical Features
Dogs and cats with gastric tumors are usually asymptomatic Etiology
until the disease is advanced. Anorexia (not vomiting) is the Pythiosis is a fungal infection caused by Pythium insidiosum.
most c o m m o n initial sign. V o m i t i n g caused by gastric neo This species is principally found in the G u l f coast area of the
plasia usually signifies advanced disease or gastric outflow southeastern U n i t e d States. A n y area of the alimentary tract
obstruction. Adenocarcinomas are typically infiltrative and or skin may be affected. The fungus typically causes intense
decrease emptying by impairing motility and/or obstructing submucosal infiltration of fibrous connective tissue and a
the outflow tract. Weight loss is c o m m o n l y caused by nutri purulent, eosinophilic, granulomatous inflammation causing
ent loss or cancer cachexia syndrome. Hematemesis occa G U E . Such infiltration prevents peristalsis, causing stasis.
sionally occurs, but leiomyomas seem to be the tumor most
likely to cause severe acute upper gastrointestinal bleeding. Clinical Features
Other bleeding gastric tumors are more likely to cause iron Pythiosis principally affects dogs, typically causing vomiting,
deficiency anemia even i f gastrointestinal blood loss is not anorexia, diarrhea, and/or weight loss. Because gastric
obvious. Polyps rarely cause signs unless they obstruct the outflow obstruction occurs frequently, vomiting is common.
pylorus. Colonic involvement may cause tenesmus and hematochezia.
Diagnosis Diagnosis
Iron deficiency anemia i n a dog or cat without obvious b l o o d Diagnosis requires serology or seeing the organism cyto
loss suggests gastrointestinal bleeding, often caused by a logically or histologically. Enzyme-linked immunosorbent
tumor. Plain and contrast imaging may reveal gastric wall assay (ELISA) and polymerase chain reaction (PCR) tests are
thickening, decreased motility, and/or mucosal irregularities. available to look for antibodies or antigen, respectively.
The only sign of submucosal adenocarcinoma may be failure Biopsy samples should include the submucosa because the
of one area to dilate (see Fig. 32-2, C ) . Ultrasound-guided organism is more likely to be there than in the mucosa. Such
aspiration of thickened areas i n the gastric wall may produce diagnostic biopsy specimens can be procured by way of rigid
cytologic preparations that are diagnostic for adenocarci endoscopy; however, because of the dense nature of the
noma or lymphoma. Endoscopically, such areas may appear infiltrate, a sufficiently deep sample can rarely be obtained
as multiple mucosal folds extending into the lumen without by flexible endoscopy. Cytologic analysis of a tissue sample
ulceration or erosion. Some tumors will be obvious endo obtained by scraping an excised piece of submucosa with a
scalpel blade may be diagnostic; fungal hyphae that do not Graham JP et al: Ultrasonographic features of canine gastrointes
stain and appear as "ghosts" with typical Romanowsky-type tinal pythiosis, Vet Radiol Ultra 41:273, 2000.
stains are strongly supportive of a diagnosis. The organisms Grooters A M et al: Development of a nested polymerase chain
may be sparse and difficult to find histologically, even i n reaction assay for the detection and identification of Pythium
insidiosum, J Vet Intern Med 16:147, 2002.
large tissue samples.
Grooters A M et al: Development and evaluation of an enzyme-
Treatment linked immunosorbent assay for the serodiagnosis of pythiosis
in dogs, / Vet Intern Med 16:142, 2002.
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Liptak JM et al: Gastroduodenal ulceration in cats: eight cases and
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C H A P T E R 33
Disorders of the
Intestinal Tract
BOX 33-1
istration o f a first-generation cephalosporin is reasonable. If noglycosides should not be administered until the patient is
the a n i m a l is i n septic shock (i.e., systemic inflammatory rehydrated and renal perfusion is re-established. C a u t i o n
response syndrome), then an antibiotic c o m b i n a t i o n w i t h a should be used when administering enrofloxacin to young,
broad aerobic and anerobic spectrum is recommended (e.g., large-breed dogs lest cartilage damage occur. Severe vomit
ticarcillin or a m p i c i l l i n plus a m i k a c i n or enrofloxacin). A m i ing complicates therapy and may require administration of
dolasetron, ondansetron, or maropitant (see Table 30-3). If than 5 weeks o f age or those suspected o f incubating or being
esophagitis occurs, H -receptor antagonists may be useful
2 affected with distemper.
(see Table 30-4). H u m a n granulocyte colony-stimulating If parvoviral enteritis develops i n one dog i n a multiple-
factor (G-CSF) (5 g/kg q24h) to increase neutrophil dog household, it is reasonable to administer booster vac
numbers and tamiflu (oseltamivir phosphate) (2 mg/kg q l 2 - cinations to the other dogs, preferably using an inactivated
24h) to combat the virus have been advocated; however, vaccine i n case they are incubating the infection at the time
there is no evidence that either substantively benefits the of i m m u n i z a t i o n . If the client is bringing a puppy into a
patient. Flunixin meglamine has been suggested for patients house with a dog that has recently had parvoviral enteritis,
in septic shock, but care must be taken lest iatrogenic the puppy should be kept elsewhere until it has received its
ulceration/perforation occurs. Recombinant feline IFN- immunizations.
6
(2.5 x 10 units per kg) has been suggested to improve the
chance of survival. Prognosis
If possible, feeding small amounts of liquid diet via a Dogs treated i n a timely fashion with proper therapy
nasoesophageal (NE) tube seems to help the intestines to typically live, especially i f they survive the first 4 days o f
heal more rapidly. A bland diet may be fed once v o m i t i n g clinical signs. The possible sequela o f intussusception
has ceased for 18 to 24 hours. Parenteral nutrition can be may cause persistent diarrhea i n pups recovering from the
life saving for patients that are persistently unable to hold viral infection. Dogs that have recovered from C P V - 2 enter
down oral food. It can be equally critical for patients itis develop long-lived i m m u n i t y that may be lifelong.
unable to accept any enteral nutrition. Partial parenteral Whether i m m u n i z a t i o n against C P V - 1 will be needed is
nutrition is easier and less expensive than total parenteral unknown.
nutrition. The dog should be kept away from other sus
ceptible animals for 2 to 4 weeks after discharge, and the FELINE P A R V O V I R A L ENTERITIS
owner should be conscientious about the disposal o f feces.
Vaccination of other dogs i n the household should be Etiology
considered. Feline parvoviral enteritis (feline distemper, feline panleuko
W h e n trying to prevent the spread o f parvoviral enteritis, penia) is caused by feline panleukopenia virus ( F P V ) , which
the clinician must remember that (1) parvovirus persists for is distinct from C V P - 2 b . However, C P V - 2 a , C P V - 2 b , and
long periods of time (i.e., months) i n the environment, C P V - 2 c can infect cats and cause disease.
making it difficult to prevent exposure; (2) asymptomatic
dogs may shed virulent C P V - 2 ; (3) maternal i m m u n i t y Clinical Features
sufficient to inactivate vaccine virus may be present i n some M a n y infected cats never show clinical signs o f disease. Signs
puppies; and (4) dilute bleach (1:32) is one of the few readily i n affected cats are usually similar to those described for
available disinfectants that kills the virus, but it can take 10 dogs with parvoviral enteritis. Kittens affected in utero may
minutes to achieve effectiveness. develop cerebellar hypoplasia.
Vaccination o f pups should generally commence at 6 to
8 weeks of age. The antigen density and immunogenicity o f Diagnosis
the vaccine as well as the amount o f antibody transferred Diagnosis is similar to that described for canine parvovirus.
from the bitch determine when the pup can be successfully The E L I S A test for fecal C P V is also a good test for feline
immunized. Inactivated vaccines generally are not as suc parvovirus. However, it is important to note that the test may
cessful as attenuated vaccines, and giving a series o f these be positive for only 1 to 2 days after infection, and by the
vaccinations seems best. Attenuated vaccines are generally time the cat is clinically ill, this test may not be able to detect
more successful i n producing a long-lasting immunity. W h e n viral shedding i n the feces.
the immune status o f the pup is u n k n o w n , administering an
attenuated vaccine at 6, 9, and 12 weeks o f age is usually Treatment
successful. If vaccination before 5 to 6 weeks of age is deemed Cats with parvoviral infection are treated m u c h i n the same
necessary, an inactivated vaccine is safer. Regardless o f the way as described for dogs with the disease. A major differ
vaccine used, it appears that there is typically a 2- to 3-week ence between dogs and cats centers o n i m m u n i z a t i o n :
window during which the pup is susceptible to parvovirus Parvoviral vaccine seems to engender a better protective
infection and yet cannot be successfully immunized. A n n u a l response i n cats than i n dogs. However, kittens younger than
revaccination is generally recommended for parvovirus, 4 weeks o f age should not be vaccinated with modified live
although it is possible that vaccination every 3 years may be virus vaccines lest cerebellar hypoplasia occur. Also, the
sufficient after the initial series as a puppy. Adults that were vaccine cannot be administered orally, but intranasal admin
previously not vaccinated usually receive two doses 2 to 4 stration is effective.
weeks apart. There is no strong evidence that parvoviral vac
cination should be given separately from modified-live Prognosis
canine distemper vaccinations. However, modified-live As with dogs, many affected cats live i f overwhelming sepsis
vaccinations should not be administered to patients younger is prevented and they can be supported long enough.
CANINE CORONAVIRAL ENTERITIS by feline parvovirus. The bone marrow and lymph nodes are
not consistently affected as they are i n cats with parvoviral
Etiology enteritis.
Canine coronaviral enteritis occurs when coronavirus
invades and destroys mature cells on the intestinal villi. Clinical Features
Because intestinal crypts remain intact, villi regenerate more C h r o n i c weight loss, vomiting, and diarrhea are c o m m o n .
quickly i n dogs with coronaviral enteritis than i n dogs with The diarrhea often has characteristics of large bowel disease.
parvoviral enteritis; bone marrow cells are not affected. A n e m i a is c o m m o n .
Prognosis Diagnosis
The prognosis for recovery is usually good. Detection o f antibodies to F I V plus severe, purulent colitis
allows presumptive diagnosis.
FELINE CORONAVIRAL ENTERITIS
Infections in adults are often asymptomatic, whereas kittens Treatment
may have m i l d , transient diarrhea and fever. Deaths are rare, Therapy is supportive (e.g., fluids/electrolytes, antiemetics,
and the prognosis for recovery is excellent. This disease is antibiotics, and/or highly digestible bland diets as needed).
important because (1) affected animals seroconvert and may
become positive o n feline infectious peritonitis serologic Prognosis
analysis and (2) mutation by the feline coronavirus may be The long-term prognosis is very poor, although some cats
the cause o f feline infectious peritonitis. can be maintained for months.
Treatment Diagnosis
Treatment consists of symptomatic control o f dehydration, Occasionally, classic Campylobacter forms may be found
vomiting, and diarrhea and elimination o f the rickettsia and during cytologic examination of a fecal smear (i.e., "commas,"
fluke. Tetracycline, oxytetracycline, doxycycline, or chloram "seagull wings"). This cytology is thought to be specific but
phenicol (see Chapter 93) eliminates the rickettsia. The fluke of uncertain sensitivity. Polymerase chain reaction ( P C R )
is killed with praziquantel (see Table 30-7). analysis o f feces is available.
Prognosis Treatment
The prognosis depends on the clinical severity at the time o f If campylobacteriosis is suspected, erythromycin (11 to
diagnosis. Most dogs respond favorably to tetracyclines and 15 mg/kg administered orally q8h) or neomycin (20 mg/kg
supportive therapy. The key to success is awareness o f the administered orally q l 2 h ) is usually effective. -lactam anti
disease. Untreated salmon poisoning has a poor prognosis. biotics (i.e., penicillins, first-generation cephalosporins) are
often ineffective. The length o f treatment necessary for cure
has not been firmly established. The animal should be treated
BACTERIAL DISEASES: for at least 1 to 3 days beyond resolution o f clinical signs;
COMMON THEMES however, antibiotic therapy may not eradicate the bacteria,
and reinfection is likely i n kennel conditions. C h r o n i c infec
The following bacterial diseases all have certain aspects i n tions may require prolonged therapy (e.g., weeks).
common. First, all of these bacteria may be found i n feces This bacterium is potentially transmissible to people, and
from clinically normal dogs and cats. Simply growing the there are cases i n w h i c h there is convincing evidence o f
bacteria or finding toxin produced by the bacteria i n the transmission from pets to people. Infected dogs and cats
patient's feces are insufficient by themselves to definitively should be isolated, and individuals w o r k i n g with the animal
diagnose intestinal disease as being caused by this particular or its environment or wastes should wear protective clothing
organism. Diagnosis can be made only by finding clinical and wash with disinfectants.
disease consistent with a particular organism, evidence of the
organism or its toxin, eliminating other causes o f the clinical Prognosis
signs, and seeing the expected response to appropriate W i t h appropriate antibiotic therapy, the prognosis for recov
therapy. If the clinician undertakes culture, it is crucial to call ery is good.
the laboratory ahead of time, tell staff members what is being
sought through culture, and follow their instructions regard SALMONELLOSIS
ing submission o f the sample.
The problems with making a diagnosis using the previ Etiology
ously mentioned criteria are obvious, and caution is war There are numerous Salmonella serotypes that may cause
ranted before making definitive statements regarding cause disease; Salmonella typhimurium is one o f the serovars that
and effect. In many cases, the best chance o f making a defin is more c o m m o n l y associated with disease. The bacteria may
itive diagnosis involves following the guidelines described originate from animals shedding the organism (e.g., infected
dogs and cats) or from contaminated foods (especially
poultry and eggs).
Clinical Features
Salmonella spp. may produce acute or chronic diarrhea,
septicemia, and/or sudden death, especially i n very young or
geriatric animals. Salmonellosis i n young animals can
produce a syndrome that closely mimics parvoviral enteritis
(including severe neutropenia), which is one reason that
E L I S A testing for parvovirus is useful. The fact that salmo
nellosis occasionally develops during or after canine parvo
viral enteritis makes the situation more confusing.
Diagnosis
Culture of Salmonella spp. from normally sterile areas (e.g, FIG 33-1
blood) confirms that it is causing disease. Identification by Photomicrograph of air-dried canine feces stained with Diff-
P C R can be a sensitive method of diagnosis. Quik. Numerous spores are seen as clear vacuoles in darkly
stained rods. (Magnification x1000.)
Treatment
Treatment depends o n the clinical signs. Animals with diar hemorrhagic diarrhea; or a chronic large bowel or small
rhea as the sole sign may need only supportive fluid therapy bowel (or both) diarrhea (with or without blood or mucus).
(including plasma i n hypoalbuminemic patients). Nonste This clostridial disease is primarily recognized in dogs.
roidal drugs (to lessen intestinal secretion) and lactulose Disease associated with C. difficile is poorly characterized in
have been used i n such patients. Antibiotics are of dubious small animals but may include large bowel diarrhea, espe
value and might promote a carrier state. Septicemic (i.e., cially after antibiotic therapy.
febrile) animals should receive supportive therapy and par
enteral antibiotics as determined by susceptibility testing, Diagnosis
but quinolones, potentiated sulfa drugs, amoxicillin, and In particular, finding spore-forming bacteria on fecal smears
chloramphenicol are often good initial choices (see the (Fig. 33-1) is not diagnostic. Commercially available toxin
discussion of drugs used i n gastrointestinal disorders, assays for C. difficile toxin have not been validated for the
pp. 409-410). Aggressive plasma therapy might be beneficial dog or cat, and results do not necessarily correlate with the
in such patients. patient's clinical condition. Determining that the patient has
Infected animals are public health risks (especially for large bowel diarrhea without weight loss or hypoalbumin
infants and older adults) and should be isolated from other emia, elimination of other causes, and resolution of signs
animals, at least until they are asymptomatic. Even when when treated appropriately (see next paragraph) is typically
signs disappear, reculturing of feces is reasonable to ensure the basis for presumptive diagnosis.
that shedding has stopped. Individuals i n contact with the
animal, its environment, and its waste should wear protective Treatment
clothing and wash with disinfectants such as phenolic c o m If C. perfringens disease is suspected, the animal may be
pounds and bleach (1:32 dilution). treated with tylosin or amoxicillin, and response is expected
shortly. Some animals are cured after a 1- to 3-week course
Prognosis of therapy. However, antibiotic treatment does not necessar
The prognosis is usually good i n animals with only diarrhea ily eliminate the bacteria, and some dogs need indefinite
but guarded i n septicemic dogs and cats. therapy. Tylosin (20 to 80 mg/kg/day, divided, ql2h) or
amoxicillin (22 mg/kg q l 2 h ) seems to be effective and yet
CLOSTRIDIAL DISEASES has m i n i m a l adverse effects i n these animals. Some animals
can eventually be maintained with once daily or every-other-
Etiology day antibiotic therapy. Some dogs with chronic diarrhea
Clostridium perfringens and Clostridium difficile can be found seemingly caused by C. perfringens respond well to fiber-
in clinically normal dogs but appear to cause diarrhea i n supplemented diets. Metronidazole is not as consistently
some. For C. perfringens to produce disease, the bacteria effective as tylosin or amoxicillin. The prognosis is good, and
must possess the ability to produce toxin, and environmen there is no obvious public health risk, although there is anec
tal conditions must be such that toxin is produced. dotal evidence of transmission between people and dogs.
If disease caused by C. difficile is suspected, supportive fluid
Clinical Features and electrolyte therapy may be necessary depending on the
C. perfringens apparently may produce an acute, bloody, self- severity of signs. Metronidazole should be effective in killing
limiting nosocomial diarrhea; an acute, potentially fatal this bacterium, but one must be sure to use a sufficiently
high dose to achieve adequate metronidazole concentrations reticuloendothelial systems, as well as the bones and eyes.
in the feces. Vancomycin is often used to treat people with this Principally found i n animals from the Mississippi and O h i o
disease but has not generally been necessary i n dogs or cats. River valleys, it occurs i n other areas as well.
Prognosis Prognosis
M a n y dogs can be cured i f treated relatively early. M u l t i p l e The prognosis for disseminated disease is poor because no
organ system involvement worsens the prognosis, as does treatment consistently works.
central nervous system ( C N S ) involvement.
FIG 33-4
P h o t o m i c r o g r a p h of a fecal flotation analysis from a d o g , d e m o n s t r a t i n g characteristic o v a
from w h i p w o r m s (W), Toxocara canis (T), a n d Isospora s p p . (I). The r e m a i n i n g o v a a r e
those of an unusual t a p e w o r m , Spirometra sp. ( M a g n i f i c a t i o n x 2 5 0 . ) (Courtesy Dr. Tom
C r a i g , Texas A & M University.)
evaluation. However, these ova are relatively dense and float and migrate against the flow of ingesta. They can cause
only i n properly prepared flotation solutions. Furthermore, inflammatory infiltrates (e.g., eosinophils) in the wall of the
ova are shed intermittently and sometimes can be found only intestine.
if multiple fecal examinations are performed.
Clinical Features
Treatment Roundworms may cause or contribute to diarrhea, stunted
Because of the potential difficulty i n diagnosing T. vulpis, growth, a poor haircoat, and poor weight gain, especially in
it is reasonable to empirically treat dogs with chronic large young animals. Runts with "potbellies" suggest severe round
bowel disease with fenbendazole or other appropriate drugs w o r m infection. Sometimes, roundworms gain access to the
(see Table 30-7) before proceeding to endoscopy. If a dog is stomach, i n which case they may be vomited. If parasites are
treated for whipworms, it should be treated again i n 3 numerous, they may obstruct the intestines or bile duct.
months to kill worms that were not i n the intestinal lumen
at the time of the first treatment. The ova persist i n the Diagnosis
environment for long periods. Diagnosis is easy because ova are produced in large numbers
and are readily found by fecal flotation (Fig. 33-5; see also
Prognosis Fig. 33-4). Occasionally, neonates develop clinical signs of
The prognosis for recovery is good. r o u n d w o r m infestation but ova cannot be found in the feces.
Transplacental migration results in large w o r m burdens,
ROUNDWORMS causing signs i n these animals before the parasites mature
and produce ova.
Etiology
Roundworms are c o m m o n i n dogs {Toxocara canis and Treatment
Toxascaris leonina) and cats {Toxocara cati and Toxascaris Various anthelmintics are effective (see Table 30-7), but pyr
leonina). Dogs and cats can obtain roundworms from antel is especially safe for young dogs and cats, particularly
ingesting the ova (either directly or via paratenic hosts). those with diarrhea. Affected animals should be retreated at
T. canis is often obtained transplacentally from the mother; 2- to 3-week intervals to kill roundworms that were initially
T. cati may use transmammary passage, and T. leonina can in tissues but migrated into the intestinal lumen since the
use intermediate hosts. Tissue migration of immature last treatment.
forms can cause hepatic fibrosis and significant pulmonary High-dose fenbendazole therapy (i.e., 50 mg/kg/day from
lesions. A d u l t roundworms live i n the small intestinal lumen day 40 of gestation until 2 weeks postpartum) has been sug-
FIG 3 3 - 5
P h o t o m i c r o g r a p h o f a fecal flotation analysis from a d o g d e m o n s t r a t i n g characteristic o v a
from h o o k w o r m s (H) a n d Toxocara canis (T). ( M a g n i f i c a t i o n x 4 0 0 . ) (Courtesy Dr. Tom
C r a i g , Texas A & M University.)
gested to reduce the somatic r o u n d w o r m burden i n bitches neous larval migrans). Use o f heartworm preventives con
and lessen transplacental transmission to puppies. N e w b o r n taining pyrantel or milbemycin helps to minimize h o o k w o r m
puppies can be treated with fenbendazole (100 mg/kg for 3 infestations.
days), which kills more than 90% o f prenatal larvae. This
treatment can be repeated 2 to 3 weeks later. Preweaning Prognosis
puppies should be treated at 2, 4, 6, and 8 weeks o f age to The prognosis is good i n mature dogs and cats but guarded
lessen contamination o f the environment because T. canis in severely anemic puppies and kittens. If the puppies or
and T. cati pose a human health risk (i.e., visceral and ocular kittens are severely stunted i n their growth, they may never
larval migrans). Preweaning kittens should be treated at 6, 8, attain their anticipated body size.
and 10 weeks of age.
TAPEWORMS
Prognosis
The prognosis for recovery is good unless the animal is Etiology
already severely stunted when treated, i n w h i c h case it may Several tapeworms infect dogs and cats, the most c o m m o n
never attain its anticipated body size. being Dipylidium caninum. Tapeworms usually have an i n d i
rect life cycle; the dog or cat is infected when it eats an
HOOKWORMS infected intermediate host. Fleas and lice are intermediate
hosts for D. caninum, whereas w i l d animals (e.g., rabbits) are
Etiology intermediate hosts for some Taenia spp.
Ancylostoma spp. and Uncinaria spp. are more c o m m o n i n
dogs than i n cats. Infestation is usually via ingestion o f the Clinical Features
ova or through transcolostral transmission; freshly hatched Aesthetically offensive, tapeworms are rarely pathogenic in
larvae may also penetrate the skin. The adults live i n the small animals, although Mesocestoides spp. can reproduce
small intestinal lumen, where they attach to the mucosa. in the host and cause disease (e.g., abdominal effusion).
Plugs of intestinal mucosa and/or b l o o d is ingested, depend The most c o m m o n sign i n infested dogs and cats is anal
ing on the w o r m species. In severe infestations hookworms irritation associated with shed segments "crawling" on
may be found in the colon. the area. Typically, the owner sees motile tapeworm seg
ments on the feces and requests treatment. Occasionally,
Clinical Features a segment enters an anal sac and causes inflammation.
Dogs are more severely affected than cats. Y o u n g animals V e r y rarely, large numbers o f tapeworms cause intestinal
may have life-threatening b l o o d loss or iron-deficiency obstruction.
anemia, melena, frank fecal blood, diarrhea, and/or failure
to thrive. Older dogs rarely have disease solely caused by Diagnosis
hookworms unless they harbor a massive infestation, but Taenia spp. and especially D. caninum eggs are typically
these worms may still contribute to disease caused by other confined i n segments not detected by routine fecal flotations.
intestinal problems. Echinococcus spp. and some Taenia spp. ova may be found i n
the feces. Tapeworms are usually diagnosed when the owner
Diagnosis reports tapeworm segments (e.g., "rice grains") o n feces or
Finding ova in the feces is diagnostic (see Fig. 33-5) and easy the perineal area.
because hookworms are prolific egg producers. However,
5- to 10-day-old puppies may be exsanguinated by transco Treatment
lostrally obtained hookworms before ova appear i n the feces. Praziquantel and episprantel are effective against all species
Such prepatent infections rarely occur i n older animals that of tapeworms (see Table 30-7). Prevention o f tapeworms
have received a sudden, massive exposure. Diagnosis is sug involves controlling the intermediate hosts (i.e., fleas and lice
gested by signalment and clinical signs i n these animals. Iron for D. caninum). Echinococcus spp. are a h u m a n health
deficiency anemia in a puppy or kitten free of fleas is highly hazard.
suggestive of h o o k w o r m infestation.
STRONGYLOIDIASIS
Treatment
Various anthelmintics are effective (see Table 30-7). Treat Etiology
ment should be repeated i n approximately 3 weeks to kill Strongyloides stercoralis principally affects puppies, especially
parasites entering the intestinal lumen from the tissues. In those i n crowded conditions. These parasites produce motile
anemic puppies and kittens, b l o o d transfusions may be life larvae that penetrate unbroken skin or mucosa; thus the
saving. animal may be infested from its o w n feces even before the
Application o f moxidectin to pregnant bitches on day 55 larvae are evacuated from the colon. In this manner, animals
of pregnancy reduces transcolostral transmission to puppies. can quickly acquire large parasitic burdens. M o s t animals are
Hookworms are a potential human health hazard (i.e., cuta infested after being exposed to fresh feces containing the
motile larvae. H u m a n e shelters and pet stores are likely for 10 to 20 days (see Table 30-7). The sulfa drug does not
sources for infestation. eradicate the coccidia but inhibits it so that body defense
mechanisms can reestablish control. A m p r o l i u m (25 mg/kg
Clinical Features administered orally q24h for 3 to 5 days) can be used in
Infested animals usually have m u c o i d or hemorrhagic diar puppies but is not approved for use i n dogs; it is potentially
rhea and are systemically ill (e.g., lethargy). Respiratory signs toxic in cats. Toltrazuril (15 mg/kg q24h for 3 days) has been
(i.e., verminous pneumonia) occur i f parasites penetrate the found to decrease oocyst shedding, at least temporarily.
lungs.
Prognosis
Diagnosis The prognosis for recovery is usually good unless there are
S. stercoralis is diagnosed by finding the larvae in fresh feces, underlying problems that allowed the coccidia to become
either by direct fecal examination or by Baermann sedimen pathogenic i n the first place.
tation. Strongyloides larvae must be differentiated from
Oslerus spp. larvae. The feces must be fresh because o l d feces CRYPTOSPORIDIA
may contain hatched h o o k w o r m larvae, w h i c h resemble
those o f Strongyloides spp. Etiology
Cryptosporidium parvum may infect animals that ingest the
Treatment sporulated oocysts. These oocysts originate from infested
Fenbendazole (when used for 5 days instead o f 3; see Table animals but may be carried i n water. Thin-walled oocysts are
30-7), thiabendazole, and ivermectin are effective anthel produced, which can rupture in the intestine and produce
mintics. This disease is a h u m a n health hazard because larvae autoinfection. The organism infests the brush border of
penetrate unbroken skin. Immunosuppressed people are at small intestinal epithelial cells and causes diarrhea.
risk for severe disease after being infected.
Clinical Features
Prognosis Diarrhea is the most c o m m o n clinical sign in dogs and cats,
The prognosis is guarded i n young animals with severe diar although many infested cats are asymptomatic. Dogs with
rhea and/or pneumonia. diarrhea are usually under 6 months o f age, but a similar age
predilection has not been recognized for cats.
COCCIDIOSIS
Diagnosis
Etiology Diagnosis requires finding the oocysts or a positive ELISA.
Isospora spp. are principally found i n young cats and dogs. C. parvum is the smallest of the coccidians and is easy to miss
The pet is usually infested by ingesting infective oocysts from on fecal examination. Examination should be performed at
the environment. The coccidia invade and destroy villous x1000 magnification. Use of acid-fast stains on fecal smears
epithelial cells. and fluorescent antibody techniques improves sensitivity. It
is best to submit the feces to a laboratory experienced in
Clinical Features diagnosing cryptosporidiosis. The laboratory must be
Coccidia may be clinically insignificant (especially i n an warned that the feces may contain C. parvum, which is
asymptomatic, older animal), or they may be responsible for potentially infective for people. The ELISA is more sensitive
m i l d to severe diarrhea, sometimes with blood. Rarely, a than fecal examination.
kitten or puppy may lose enough b l o o d to require a b l o o d
transfusion. Treatment/Prognosis
There are no k n o w n reliable treatments. Immunocompetent
Diagnosis people and cattle often spontaneously eliminate the infesta
Coccidiosis is diagnosed by finding oocysts o n fecal flotation tion, but whether small animals do so is unknown. Most
examination (see Fig. 33-4); however, repeated fecal exami young dogs with diarrhea associated with cryptosporidiosis
nations may be needed, and small numbers o f oocysts do not die or are euthanized. M a n y cats have asymptomatic infesta
ensure that the infestation is insignificant. These oocysts tions, and those with diarrhea have an unknown prognosis.
should not be confused with giardial cysts. If a necropsy is
performed, multiple areas o f the intestine should be sampled GIARDIASIS
because the infection may be localized to one area. Occasion
ally, Eimeria oocysts will be seen i n the feces o f dogs that eat Etiology
deer or rabbit excrement. Giardiasis is caused by a protozoan, Giardia sp. Animals are
infected when they ingest cysts shed from infected animals,
Treatment often via water. Organisms are principally found in the small
If coccidia are believed to be causing a problem, sulfadi intestine, where they interfere with digestion through
methoxine or trimethoprim-sulfa should be administered uncertain mechanisms. In people Giardia organisms may
occasionally ascend into the bile duct and cause hepatic occasionally reveal Giardia organisms when other techniques
problems. do not.
FIG 3 3 - 6
Giardia trophozoites (arrows) in a c a n i n e fecal smear that has been stained to e n h a n c e
internal structures. ( M a g n i f i c a t i o n x 1 0 0 0 . ) (Courtesy Dr. Tom C r a i g , Texas A & M
University.)
patient and cleansing the environment can be very impor diluted with warm saline solution is the easiest technique,
tant to successful treatment i n many patients. Quaternary but it is insensitive. Fecal culture using the pouch technique
a m m o n i u m compounds and pine tars are effective disinfec developed for bovine venereal trichomoniasis is more sensi
tants for the premises. Fourth, sometimes other protozoal tive.
agents (e.g, Tritrichomonas) are mistaken for Giardia. V a c
cination is not generally successful as a treatment modality Treatment/Prognosis
for patients that do not respond to the aforementioned Ronidazole (30 to 50 mg/kg q l 2 h for 14 days) is the only
drugs. drug currently k n o w n to safely eliminate Tritrichomonas, but
neurologic signs have been reported with its use. If tricho
Prognosis moniasis is diagnosed, it is still important to look for other
The prognosis for recovery is usually good, although i n some causes of diarrhea (e.g., C. perfringens, diet, Cryptosporidium
cases the organisms are difficult to eradicate. Whether people spp.) because treatment for one of these other causes may
may occasionally be infected with Giardia organisms shed cause resolution of the diarrhea. M o s t affected cats will even
from dogs is u n k n o w n . tually resolve the clinical signs of trichomoniasis, although
diarrhea may recur i f the patient undergoes stressful events
TRICHOMONIASIS (e.g., elective surgery).
Etiology HETEROBILHARZIA
Trichomoniasis i n cats appears to be caused by Tritricho
monas foetus/suis. Animals are probably infected by the fecal- Etiology
oral route. Heterobilharzia americana infects dogs and establishes itself
in the liver. Ova laid i n the veins end up i n the intestinal wall,
Clinical Features where they elicit a granulomatous inflammation. The organ
Trichomoniasis typically is associated with large bowel diar ism is primarily found i n G u l f coast states and the southern
rhea, which rarely contains b l o o d or mucus. Exotic cat breeds Atlantic coast states.
(e.g., Somalis, Ocicats, Bengals) are the breeds primarily
affected with clinical signs. Affected cats are typically other Clinical Features
wise normal, although there may be anal irritation and Large bowel disease is the primary sign, although the ova can
defecation i n inappropriate places. The diarrhea typically be found i n large and small bowel. Diarrhea, hematochezia,
resolves spontaneously, although it may persist for months. and weight loss are typical findings. Protein-losing enter
opathy may occur, and the granulomatous reaction is associ
Diagnosis ated with hypercalcemia i n some dogs. Hepatic disease may
Diagnosis requires identifying the motile trophozoite, but be m i l d or severe.
live Tritrichomonas trophozoites can be mistaken for Giardia
trophozoites (Fig. 33-7). Timely examination of fresh feces Diagnosis
Finding the ova i n feces or i n mucosal biopsy specimens is
diagnostic.
Treatment/Prognosis
Fenbendazole plus praziquantel is successful i n killing the
parasite and the ova. However, the prognosis is seemingly
dependent o n the severity of the granulomatous reaction in
the bowel and liver.
MALDIGESTIVE DISEASE
Etiology
Canine exocrine pancreatic insufficiency (EPI) is caused by
FIG 3 3 - 7 pancreatic acinar cell atrophy or destruction associated with
C o m p a r i s o n of Giardia t r o p h o z o i t e s (small arrows) a n d
pancreatitis.
Tritrichomonas t r o p h o z o i t e s (large arrows) in a smear that
has b e e n stained to e n h a n c e internal structures. N o t e that
the Tritrichomonas trophozoites are larger a n d have one
Clinical Features
large undulating membrane. (Magnification x 1 0 0 0 . ) EPI is principally found i n dogs and rarely i n cats. Chronic
(Courtesy Dr. Tom C r a i g , Texas A & M University.) small intestinal diarrhea, a ravenous appetite, and weight
loss are classic findings. Steatorrhea (i.e., slate-gray stools) tions have questionable sensitivity and specificity for this
is sometimes seen, and animals occasionally have weight disorder. Duodenal mucosal cytology and histopathology are
loss without diarrhea. The diarrhea is classified as a small routinely nondiagnostic for A R E . Because o f these problems
bowel problem (because o f the weight loss and the nature o f in diagnosing A R E , many clinicians treat and observe for
the diarrhea). Physical examination and routine clinical response.
pathologic findings are not diagnostic. The most sensitive
and specific test for canine EPI is measurement o f serum Treatment
trypsin-like immunoreactivity (TLI; i.e., l o w activity i n Because o f the difficulty i n diagnosing A R E , therapy is rea
affected dogs). Finding undetectable levels o f canine pan sonable when this disorder is suspected. Therapy consists o f
creatic lipase immunoreactivity (cPLI) might be suggestive antibiotics and the removal o f potential causes (e.g., b l i n d
of EPI but is not as specific as decreased T L I . Treatment or stagnant loops o f intestine). Because mixed bacterial pop
involves the administration o f pancreatic enzymes with the ulations are expected, broad-spectrum antibiotics effective
food and manipulation o f dietary fat content. The reader is against aerobic and anaerobic bacteria are recommended.
referred to Chapter 40 for more information o n E P I . Tylosin (10 to 40 mg/kg q12h) is often effective. A combina
tion o f metronidazole (15 mg/kg q24h) and enrofloxacin
(7 mg/kg q24h) also seems effective i n many patients. Recent
MALABSORPTIVE DISEASES w o r k suggests that simultaneously feeding a high-quality,
highly digestible or hypoallergenic diet makes the antibiotic
ANTIBIOTIC-RESPONSIVE ENTEROPATHY therapy more effective.
Occasionally, a pure culture o f a specific bacteria will be
Etiology found i n the duodenum, such that a specific antibiotic is
Antibiotic-responsive enteropathy (ARE) is a syndrome i n required. However, such cases appear to be rare. W h e n treat
which the duodenum or jejunum (or both) has high numbers ing dogs with suspected A R E , the clinician should wait 2 to
5
of bacteria (i.e., usually >10 colony forming units/ml) and 3 weeks before deciding that the therapy was not effective.
the host seemingly has an abnormal response to these bac Because there may be an underlying cause that cannot be
teria. The abnormal host response is important, as seen by corrected, some animals need long-term to indefinite anti
the fact that dogs with comparable numbers o f bacteria i n biotic therapy. This may be especially true i n dogs that have
8
their small intestine (i.e., 1 0 / m l o f fasting fluid) do not had repeated episodes of illness since they were a few months
have clinical disease. The bacteria may be present because o f old. It seems as though these patients may have some genetic
(1) an anatomic defect allowing retention o f food (e.g., a predisposition to A R E , probably because o f a defect i n host
partial stricture or an area o f hypomotility), (2) other dis defense mechanisms. The clinician should warn the owner
eases (e.g., intestinal mucosal disease), (3) impaired host that the goal is typically control, not cure. Patients that have
defenses (i.e., hypochlorhydria, IgA deficiency), or (4) no nearly constant diarrhea when not being treated may need
identifiable reason. Bacteria causing A R E are usually present antibiotics and dietary therapy indefinitely. Patients who
in mixed culture, and they probably gain access to the ali have episodes every 2 to 4 months might best be treated
mentary tract by being swallowed (i.e., originating from the when they relapse as opposed to having them o n antibiotics
oral cavity or i n the food). A n y species o f bacteria may be constantly
present, but Escherichia coli, enterococci, and anaerobes such
as Clostridium spp. seem to be especially c o m m o n . Presum Prognosis
ably, enterocytes are damaged by deconjugation of bile acids, The prognosis is usually good for control of A R E , but the
fatty acid hydroxylation, generation o f alcohols, and poten clinician must be concerned with possible underlying
tially other mechanisms. causes.
INTESTINAL LYMPHANGIECTASIA
Etiology
FIG 3 3 - 8
Intestinal lymphangiectasia (IL) is a disorder of the intestinal
Endoscopic i m a g e of the d u o d e n u m of a d o g w i t h l y m p h a n
lymphatic system of dogs. Lymphatic obstruction causes
g i e c t a s i a . The l a r g e w h i t e " d o t s " a r e d i l a t e d lacteals in the
dilation and rupture of intestinal lacteals with subsequent tips of the villi.
leakage of lymphatic contents (i.e., protein, lymphocytes,
and chylomicrons) into the intestinal submucosa, lamina
propria, and lumen. Although these proteins may be digested
and resorbed, excessive loss exceeds the intestine's ability to tic if done appropriately, but surgical biopsies are sometimes
resorb them, thus resulting in hypoalbuminemia. Leakage o f required. If full-thickness surgical biopsies are performed,
lymphatic fat into the intestinal wall may cause granuloma serosal patch grafting and nonabsorbable suture material
formation, which exacerbates lymphatic obstruction. N o t may decrease the risk o f dehiscence. IL may be localized to
reported i n cats, the condition has many potential causes in one area o f the intestines (e.g., ileum).
dogs (e.g., lymphatic obstruction, pericarditis, infiltrative
mesenteric lymph node disease, infiltrative intestinal mucosal Treatment
disease, congenital malformations). M o s t cases o f symptom The underlying cause o f IL is rarely determined, necessitat
atic IL are idiopathic. ing reliance on symptomatic therapy. A n ultra-low-fat diet
essentially devoid o f long-chain fatty acids helps to prevent
Clinical Features further intestinal lacteal engorgement and subsequent
Yorkshire Terriers, Soft Coated Wheaten Terriers, and protein loss. Prednisolone (1.1 to 2.2 mg/kg/day) or azathio
Lundehunds appear to be at higher risk than other breeds. prine (2.2 mg/kg q48h) or cyclosporine (3-5 mg/kg q24h to
Soft Coated Wheaten Terriers also have an unusually high q l 2 h ) sometimes lessens inflammation around the lipogran
incidence of protein-losing nephropathy. The first sign of ulomas and improves lymphatic flow.
disease caused by IL may be transudative ascites. Diarrhea is M o n i t o r i n g serum a l b u m i n concentration may be the
inconsistent and may occur early or late i n the course of the best way o f assessing response to therapy. If the animal
disease, if at all. Intestinal lipogranulomas (i.e., white nodules improves with dietary therapy, it should probably be fed that
in the intestinal serosa or mesentery) are sometimes found diet indefinitely. Azathioprine or cyclosporine therapy might
at surgery. They are probably secondary to IL (i.e., fat leaking help solidify response to dietary therapy and maintain remis
out of dilated lymphatic vessels), but they might worsen sion.
existing IL by further obstructing lymphatics.
Prognosis
Diagnosis The prognosis is variable, but most dogs respond well to
Clinical pathologic evaluation is not diagnostic, but hypoal ultra-low-fat diets, although some require prednisolone i n
buminemia and hypocholesterolemia are expected. Although addition to the diet. A few dogs die despite dietary and pred
panhypoproteinemia is classically attributed to P L E , animals nisolone therapy.
that were initially hyperglobulinemic may lose most of their
serum proteins and still have normal serum globulin con PROTEIN-LOSING ENTEROPATHY IN
centrations. Lymphopenia is c o m m o n but inconsistent. SOFT-COATED WHEATEN TERRIERS
Diagnosis requires intestinal histopathology. Feeding the
animal fat the night before the biopsy seems to make lesions Etiology
more obvious, and classic mucosal lesions may be seen endo Soft Coated Wheaten Terriers (SCWTs) have a predisposi
scopically (Fig. 33-8). Endoscopic biopsies are often diagnos- tion to P L E and protein-losing nephropathy. The cause is
uncertain, although food hypersensitivity has been reported Anticholinergics occasionally are useful (e.g., propantheline,
to be present i n some affected dogs. 0.25 mg/kg; or dicyclomine, 0.15 mg/kg up to q8h, as
needed).
Clinical Features
Individual dogs may have P L E or protein-losing nephropa Prognosis
thy (or both). Typical clinical signs may include vomiting, The prognosis is good; in most animals the signs are con
diarrhea, weight loss, and ascites. Affected dogs are often trolled by diet or medical management.
middle aged when diagnosed.
Clinical Features
FUNCTIONAL INTESTINAL DISEASE Simple intestinal obstructions usually cause vomiting with
or without anorexia, depression, or diarrhea. A b d o m i n a l
IRRITABLE B O W E L S Y N D R O M E pain is u n c o m m o n . The more orad the obstruction is, the
more frequent and severe the vomiting tends to be. If the
Etiology intestine becomes devitalized and septic peritonitis results,
Irritable bowel syndrome (IBS) i n people is characterized by the obstruction becomes complicated and the animal may
diarrhea, constipation, and/or cramping (usually of the large be presented i n a m o r i b u n d state or i n septic shock (systemic
intestines) i n which an organic lesion cannot be identified. inflammatory response syndrome, or SIRS).
It is an idiopathic large bowel disease i n w h i c h all k n o w n
causes of diarrhea have been eliminated and a "functional" Diagnosis
disorder is presumed. IBS i n dogs is different and primarily A b d o m i n a l palpation, plain abdominal radiographs, or
involves an idiopathic, chronic large bowel diarrhea i n w h i c h ultrasonographic imaging can be diagnostic i f they reveal a
parasitic, dietary, bacterial, and inflammatory causes have foreign object, mass, or obvious obstructive ileus (see Fig.
been eliminated. There are probably various causes of this 29-5, A ) . Masses or dilated intestinal loops may be found
syndrome i n dogs. with either technique. A b d o m i n a l ultrasonography tends to
be the most sensitive technique (unless the intestines are
Clinical Features filled with gas) and can reveal dilated or thickened intestinal
C h r o n i c large bowel diarrhea is the principal sign. Fecal loops that are not obvious on radiographs (e.g., poor serosal
mucus is c o m m o n , blood i n the feces is infrequent, and contrast caused by abdominal fluid or lack of abdominal fat)
weight loss is very rare. Some dogs with IBS are small breeds or palpation. If it is difficult to distinguish obstruction from
that are heavily imprinted on a single family member. C l i n physiologic ileus, abdominal contrast radiographs may be
ical signs may develop following separation of the dog from considered. M a n y intestinal foreign bodies cause hypochlo
the favored person. Other dogs with IBS are nervous and remic, hypokalemic metabolic alkalosis, a metabolic change
high-strung (e.g., police or guard dogs, especially German that is supposedly suggestive of gastric outflow obstruction.
Shepherd Dogs). Some dogs have no apparent initiating Finding a foreign object is usually sufficient to establish
cause. a diagnosis. If an abdominal mass or an obvious obstructive
ileus is found, a presumptive diagnosis of obstruction is made,
Diagnosis and ultrasonography or exploratory surgery should be planned.
Diagnosis consists of eliminating k n o w n causes by physical Aspirate cytologic evaluation of masses may be used to diag
examination, clinical pathologic data, fecal analysis, colonos nose some diseases (e.g., lymphoma) before surgery.
copy/biopsy, and appropriately performed therapeutic trials.
Treatment
Treatment Once intestinal obstruction is diagnosed, the clinician should
Treatment with fiber-supplemented diets (i.e., >7% to 9% perform routine preanesthetic laboratory tests (serum
fiber on a dry matter basis) is often helpful (see p. 398). M a n y electrolyte and acid-base abnormalities are c o m m o n i n v o m
animals must receive fiber chronically to prevent relapse. iting animals), stabilize the animal, and promptly proceed to
surgery. V o m i t i n g o f gastric origin classically produces a
hypokalemic, hypochloremic metabolic alkalosis and para
doxical aciduria, whereas vomiting caused by intestinal
obstruction may produce metabolic acidosis and varying
degrees of hypokalemia. However, these changes cannot be
predicted even when the cause o f the vomiting is k n o w n ,
making serum electrolyte and acid-base determinations
important i n therapy planning.
Prognosis
If septic peritonitis is absent and massive intestinal resection
is not necessary, the prognosis is usually good.
INCARCERATED INTESTINAL
OBSTRUCTION
Etiology
Incarcerated intestinal obstruction involves a loop o f intes
tine trapped or "strangulated" as it passes through a hernia
(e.g., abdominal wall, mesenteric) or similar rent. The FIG 3 3 - 9
entrapped intestinal loop quickly dilates, accumulating fluid Lateral a b d o m i n a l r a d i o g r a p h o f a d o g w i t h a r u p t u r e d
in which bacteria flourish and release endotoxins. SIRS p r e p u b i c t e n d o n a n d i n c a r c e r a t e d intestinal obstruction.
occurs rapidly. This is a true surgical emergency, and animals N o t e the d i l a t e d section of intestine in the a r e a of the
h e r n i a (arrows). (From A l l e n D, e d i t o r : Small animal
deteriorate quickly i f the entrapped loop is not removed.
medicine, P h i l a d e l p h i a , 1 9 9 1 , JB Lippincott.)
Clinical Features
Dogs and cats with incarcerated intestinal obstruction typi
cally have acute vomiting, abdominal pain, and progressive M u c h o f the intestine is typically devitalized by the time
depression. Palpation o f the entrapped loop often causes surgery is performed.
severe pain and occasionally vomiting. O n physical examina
tion, "muddy" mucous membranes and tachycardia may be Clinical Features
noted, suggesting endotoxic shock. This u n c o m m o n cause o f intestinal obstruction principally
occurs i n large dogs (especially G e r m a n Shepherd Dogs).
Diagnosis Mesenteric torsion is denoted by an acute onset o f severe
A presumptive diagnosis is made by finding a distended, nausea, retching, vomiting, abdominal pain, and depression.
painful intestinal loop, especially i f the loop is contained Bloody diarrhea may or may not occur. A b d o m i n a l disten
within a hernia. Radiographically, a markedly dilated segment tion is not as evident as it is i n animals with gastric dila
of intestine is detected (Fig. 33-9) that is sometimes obvi tion/volvulus ( G D V ) .
ously outside the peritoneal cavity. Otherwise, an obviously
strangulated loop of intestine will be found at exploratory Diagnosis
surgery. A b d o m i n a l radiographs are often diagnostic and typically
show widespread, uniform ileus (see Fig. 29-6).
Treatment
Immediate surgery and aggressive therapy for endotoxic Treatment
shock are indicated. Devitalized bowel should be resected, Immediate surgery is necessary. The intestines must be prop
with care taken to avoid spillage of septic contents into the erly repositioned, and devitalized bowel must be resected.
abdomen.
Prognosis
Prognosis The prognosis is extremely poor; most animals die despite
The prognosis is guarded. Rapid recognition and prompt heroic efforts. Animals that live may develop short bowel
surgery are necessary to prevent mortality. syndrome i f massive intestinal resection is necessary.
Etiology Etiology
In mesenteric torsion/volvulus, the intestines twist about the Numerous objects can assume a linear configuration i n the
root of the mesentery, causing severe vascular compromise. alimentary tract (e.g., string, thread, nylon stockings, cloth).
The foreign object lodges or fixes at one point (e.g., the base occasionally succeeds, but the clinician must be careful
of the tongue, pylorus), and the rest trails off into the intes because it is easy to rupture devitalized intestine and
tines. The small intestine seeks to propel the object aborally cause peritonitis. If the clinician can pass the tip of the
via peristaltic waves and i n this manner gathers around it endoscope to near the aborad end o f the object and pull
and becomes pleated. A s the intestines continue trying to it out by grabbing the aborad end, surgery is sometimes
propel it aborally, the linear object cuts or "saws" into the unnecessary.
intestines, often perforating them at multiple sites o n the
antimesenteric border. Fatal peritonitis can result. Prognosis
The prognosis is usually good i f severe septic peritonitis is
Clinical Features absent and massive intestinal resection is unnecessary. If a
Linear foreign objects appear to be more frequent i n cats linear foreign object has been present a long time, it may
than i n dogs. V o m i t i n g food, bile, and/or phlegm is c o m m o n , embed itself in the intestinal mucosa, making intestinal
but some animals show only anorexia or depression. A few resection necessary. W h e n massive intestinal resection is nec
(especially dogs with chronic linear foreign bodies) can be essary, short bowel syndrome can result; this condition has
relatively asymptomatic for days to weeks while the foreign a guarded to poor prognosis.
body continues to embed itself in the intestines.
INTUSSUSCEPTION
Diagnosis
The history may be suggestive o f a linear foreign body (e.g., Etiology
the cat was playing with cloth or string). Bunched, painful Intussusception is a telescoping o f one intestinal segment
intestines are occasionally detected by abdominal palpation. (the intussusceptum) into an adjacent segment (the intus
The object is sometimes seen lodged at the base o f the suscipiens). It may occur anywhere in the alimentary tract,
tongue; however, failure to find a foreign object at the base but ileocolic intussusceptions (i.e., the ileum entering the
of the tongue does not eliminate linear foreign body as a colon) seem more c o m m o n . Ileocolic intussusceptions seem
diagnosis. Even when such objects lodge under the tongue, to be associated with active enteritis (especially i n young
they can be very difficult to find despite a careful, thorough animals), which ostensibly disrupts normal motility and
oral examination; some become embedded i n the frenulum. promotes the smaller ileum to intussuscept into the larger
If necessary, chemical restraint (e.g., ketamine, 2 mg/kg diameter colon. However, ileocolic intussusception may
administered intravenously) should be used to allow ade occur i n animals with acute renal failure, leptospirosis, prior
quate oral examination. intestinal surgery, and other problems.
Foreign objects lodged at the pylorus and trailing off into
the d u o d e n u m must be diagnosed by abdominal palpation, Clinical Features
imaging, or endoscopy. The objects themselves are infre Acute ileocolic intussusception causes obstruction of the
quently seen radiographically and only rarely produce dilated intestinal lumen and congestion of the intussusceptum's
intestinal loops suggesting anatomic ileus; the p r o x i m i t y to mucosa. Scant bloody diarrhea, vomiting, abdominal pain,
the stomach and the pleating of the intestines around the and a palpable abdominal mass are c o m m o n . Chronic ileo
object usually prevents the intestines from dilating. Plain colic intussusceptions typically produce less vomiting,
radiographs may reveal small gas bubbles i n the intestines, abdominal pain, and hematochezia. These animals often
especially in the region o f the duodenum, and obvious intes have intractable diarrhea and hypoalbuminemia because of
tinal pleating may occasionally be seen (Fig. 33-10). If con protein loss from the congested mucosa. P L E i n a young dog
trast radiographs are performed, they typically reveal a without hookworms or a puppy that seems to be having an
pleated or bunched intestinal pattern, w h i c h is diagnostic o f unexpectedly long recovery from parvoviral enteritis should
linear foreign body. Finally, these objects are sometimes seen prompt suspicion o f chronic intussusception. Acute jejuno-
endoscopically lodged at the pylorus. jejunal intussusceptions usually do not cause hematochezia.
Mucosal congestion can be more severe than that in ileoco
Treatment lic intussusception; intestinal devitalization eventually
A b d o m i n a l surgery is often needed to remove linear foreign occurs, and bacteria and their toxins gain access to the peri
objects. However, i f the animal is otherwise healthy, i f the toneal cavity.
linear foreign object has been present for only 1 or 2 days,
and if it is fixed under the tongue, the object may be cut loose Diagnosis
to see i f it will now pass through the intestines without Palpation o f an elongated, obviously thickened intestinal
further problem. Surgery is indicated i f the animal does not loop establishes a presumptive diagnosis; however, some
feel better 12 to 24 hours after the object is cut free from its infiltrative diseases produce similar findings. Ileocolic intus
point o f fixation. susceptions that are short and do not extend far into the
If there is doubt as to the length o f time that the object descending colon may be especially difficult to palpate
has been present, or i f it is fixed at the pylorus, surgery is because they are high up and under the rib cage. Occasional
usually a safer therapeutic approach. Endoscopic removal intussusceptions "slide" i n and out of the colon and can be
FIG 3 3 - 1 0
A , Plain a b d o m i n a l r a d i o g r a p h of a c a t w i t h a linear f o r e i g n b o d y l o d g e d at the p y l o r u s .
N o t e the small g a s bubbles in the mass of intestines (arrows). B , Plain a b d o m i n a l r a d i o
g r a p h of a cat with a linear f o r e i g n b o d y . N o t e the o b v i o u s l y p l e a t e d small b o w e l
(arrows). C , Contrast r a d i o g r a p h o f a c a t w i t h a linear f o r e i g n b o d y . N o t e the p l e a t e d ,
b u n c h e d pattern of intestines (arrows). ( A from A l l e n D, editor: Small animal medicine,
P h i l a d e l p h i a , 1 9 9 1 , JB Lippincott.)
missed during abdominal palpation. If the intussusception junal intussusceptions may be easier to palpate because o f
protrudes as far as the rectum, it may resemble a rectal their location. Furthermore, plain abdominal radiographs
prolapse. Therefore i f tissue is protruding from the rectum, may be more likely to demonstrate obstructive ileus (i.e.,
the clinician should perform a careful rectal palpation to gas-distended bowel loops) because the obstruction is not so
ascertain that a fornix exists (i.e., it is a rectal prolapse) as far aborad.
opposed to an intussusception (in which a fornix cannot be A reason for the intussusception (e.g., parasites, mass,
found). enteritis) should always be sought. Fecal examination for
Plain abdominal radiographs infrequently allow the diag parasites and evaluation o f full-thickness intestinal biopsy
nosis of ileocolic intussusceptions because they usually cause specimens obtained at the time o f surgical correction o f the
minimal intestinal gas accumulation. A properly performed intussusception should be performed. In particular, the tip
barium contrast enema may reveal a characteristic colonic of the intussuscepted bowel (i.e., the intussusceptum) should
filling defect caused by the intussuscepted ileum (Fig. 33-11). be examined for a mass lesion (e.g., tumor), w h i c h could
Abdominal ultrasonography is quick and reasonably sensi have served as a focus and allowed the intussusception to
tive and specific for detecting intussusceptions (see Fig. 29-8, occur. Additional diagnostic tests may be warranted depend
B). Colonoscopy can be definitive if the intussuscepted intes ing o n the history, physical examination findings, and results
tine is seen extending into the colon (Fig. 33-12). Jejunoje- of clinical pathologic evaluation.
FIG 3 3 - 1 2
Endoscopic v i e w of the a s c e n d i n g colon of a d o g with an
ileocolic intussusception. N o t e the l a r g e , " h o t dog"-like mass
in the c o l o n i c lumen, w h i c h is the intussusception.
Treatment
Intussusceptions must be treated surgically. Acute ones may
be reduced or resected, whereas chronic ones usually must
be resected. Recurrence (in the same or a different site)
is reasonably c o m m o n . Surgical plication helps prevent
recurrence.
Prognosis
The prognosis is often good i f septic peritonitis has not
occurred and the intestines do not reintussuscept.
SHORT B O W E L S Y N D R O M E
Etiology
Short bowel syndrome occurs when extensive resection of
intestines results i n the need for special nutritional therapy
until the intestines are able to adapt. This is typically an
iatrogenic disorder caused by resection o f more than 75% to
90% o f the small intestine. The remaining intestine is unable
to adequately digest and absorb nutrients. Large numbers of
bacteria may reach the upper small intestines, especially if
the ileocolic valve is removed. However, not all animals with
substantial small intestinal resections develop this syndrome.
Dogs and cats seem better able than people to tolerate loss
FIG 3 3 - 1 1 of a large percentage o f small intestine.
A , Lateral r a d i o g r a p h taken d u r i n g a b a r i u m e n e m a of a
d o g . Contrast m e d i u m outlines the e n d of a l a r g e ileocolic
Clinical Features
intussusception (thin arrows). N o t e that b a r i u m does not fill Affected animals usually have severe weight loss and intrac
up the n o r m a l l y p o s i t i o n e d c o l o n i c lumen because o f a long table diarrhea (typically without mucus or blood), which
filling defect (large arrows). B , Spot r a d i o g r a p h taken
often occurs shortly after eating. Undigested food particles
d u r i n g a b a r i u m e n e m a of a d o g . The c o l o n is d e s c e n d i n g
are often seen in the feces.
o n the left (short arrows), a n d the ileum (long arrows) is
entering the c o l o n . There is a n a r e a in w h i c h b a r i u m is
d i s p l a c e d , representing a n intussuscepted cecum (curved
Diagnosis
arrows). ( A courtesy Dr. A l i c e W o l f , Texas A & M A history o f substantial resection i n conjunction with the
University.) clinical signs is sufficient for diagnosis. It is wise to deter-
mine how m u c h small intestine is left by performing contrast adenopathy (i.e., enlargement) is typical but not invariable,
radiographs; estimates made at surgery can be surprisingly and it is important to note that I B D can cause m i l d to m o d
inaccurate. erate mesenteric lymphadenopathy. Extraintestinal abnor
malities (e.g.,peripherallymphadenopathy) are inconsistently
Treatment found i n dogs and cats with alimentary l y m p h o m a .
The best treatment is prevention. One should avoid massive
resections i f at all possible, even i f it means doing a "second Diagnosis
look" surgery 24 to 48 hours later. If massive resection occurs Diagnosis requires demonstration o f neoplastic l y m p h o
and the animal cannot maintain its body weight with oral cytes, w h i c h may be obtained by fine-needle aspiration,
feedings alone, total parenteral nutrition is needed until imprint, or squash cytologic preparations. However, histo
intestinal adaptation has occurred and treatments have pathologic evaluation o f intestinal biopsy specimens is the
become effective i n controlling clinical signs. It is important most reliable diagnostic method. It is important to biopsy
to continue to feed the animal orally to stimulate intestinal the ileum because many patients (especially cats) do not
mucosal hypertrophy. The diet should be highly digestible have l y m p h o m a i n the duodenum. If endoscopic biopsy
(e.g., low-fat cottage cheese, potato) and should be fed i n samples are obtained, a poor sample or one that is not suf
small amounts, at least three to four times per day. Opiate ficiently deep may cause the erroneous diagnosis o f L P E
antidiarrheals (e.g., loperamide), and H -receptor antagonists
2 instead o f l y m p h o m a . Finding lymphocytes i n the submu
may be useful in lessening diarrhea and decreasing gastric cosa is not specific for l y m p h o m a : Lymphocytes can be
hypersecretion. Antibiotics might be needed to control the found i n the submucosa of cats with I B D . However, cats with
large bacterial populations now present i n the small intestine I B D generally do not have the dramatic numbers that can be
(pp. 409-110). found i n some cases w i t h l y m p h o m a . Occasionally, neoplas
tic lymphocytes are found only i n the serosal layer and full-
Prognosis thickness surgical biopsy specimens are necessary, but this
If intestinal adaptation occurs, the animal may eventually be scenario is extremely u n c o m m o n . A n i m a l s with extremely
fed a near-normal diet. However, some animals w i l l never be well-differentiated lymphocytic l y m p h o m a may be impos
able to resume regular diets, and others die despite all efforts. sible to distinguish from those w i t h L P E using routine his
Animals that are initially malnourished seem to have a worse topathology, even with multiple full-thickness biopsy
prognosis than those that are well nourished. Some dogs samples. This seems to be a particularly important problem
and cats do better than one w o u l d intuitively expect them i n cats. In such cases, diagnosis often depends on finding
to do, despite the loss o f approximately 85% o f the small lymphocytes i n organs where they should not be found (e.
intestines. g., liver) or i n performing immunohistochemical studies to
determine i f the l y m p h o i d population is monoclonal. Para
neoplastic hypercalcemia occasionally occurs but is neither
NEOPLASMS OF THE SMALL INTESTINE sensitive nor specific for l y m p h o m a .
ALIMENTARY L Y M P H O M A Treatment
Chemotherapy is o f questionable value i n dogs; many
Etiology patients become quite i l l i f given aggressive chemotherapy.
Lymphoma is a neoplastic proliferation o f lymphocytes Cats with well-differentiated small cell l y m p h o m a treated
(see Chapter 80) that could also be placed i n the section with prednisolone and chlorambucil may do as well as cats
on malabsorptive diseases. It may be caused by F e L V i n cats, with I B D that receive the same therapy. Treatment protocols
but the etiology i n dogs is u n k n o w n . L P E has been sugges are outlined i n Chapter 80.
ted to be prelymphomatous i n some animals, but the fre
quency of malignant transformation o f L P E to l y m p h o m a is Prognosis
unknown. L y m p h o m a often affects the intestines, although The long-term prognosis is very poor, but some cats with
extraintestinal forms (e.g., l y m p h nodes, liver, spleen) are well-differentiated intestinal l y m p h o m a w i l l live years with
more c o m m o n i n dogs (see Chapter 80). Alimentary l y m therapy.
phoma appears to be more c o m m o n i n cats than i n dogs.
INTESTINAL A D E N O C A R C I N O M A
Clinical Features Intestinal adenocarcinoma is more c o m m o n i n dogs than
Chronic, progressive weight loss, anorexia, small intestinal i n cats. It typically causes diffuse intestinal thickening or
diarrhea, and/or vomiting may occur. Alimentary l y m focal circumferential mass lesions. P r i m a r y clinical signs are
phoma may cause nodules, masses, diffuse intestinal thick weight loss and v o m i t i n g caused by intestinal obstruction.
ening resulting from infiltrative disease (see Fig. 29-9), Diagnosis requires demonstrating neoplastic epithelial cells.
dilated sections of intestine that are not obstructed, and/or Endoscopy, surgery, and ultrasound-guided fine-needle
focal constrictions. It may also be present i n grossly normal- aspiration may be diagnostic. Scirrhous carcinomas have
appearing intestine; P L E may also occur. Mesenteric l y m p h - very dense fibrous connective tissue that often cannot be
adequately biopsied with fine-needle aspiration or a flexible Treatment
endoscope; therefore surgery is sometimes required to obtain Symptomatic therapy is typically sufficient because acute
diagnostic biopsies. The prognosis is good i f c o m p l e t e sur proctitis and colitis are usually idiopathic. Withholding food
gical excision is possible, but metastases to regional l y m p h for 24 to 36 hours lessens the severity of clinical signs. The
nodes are c o m m o n by the time o f diagnosis. Postoperative animal should then be fed small amounts of a bland diet
adjuvant chemotherapy does not appear to be beneficial. (e.g., cottage cheese and rice) with or without fiber. After
resolution o f the clinical signs, the animal may be gradually
INTESTINAL L E I O M Y O M A / returned to its original diet. Areas o f anal excoriation should
LEIOMYOSARCOMA be cleansed, and an antibiotic-corticosteroid ointment
Intestinal leiomyomas and leiomyosarcomas are connective should be applied. M o s t animals recover within 1 to 3 days.
tissue tumors that usually form a distinct mass and are For proctitis, stool softeners and broad-spectrum antimicro
primarily found i n the small intestine and stomach o f bial therapy effective against anaerobic bacteria may also be
older dogs. Primary clinical signs are intestinal hemorrhage, used.
i r o n deficiency anemia, and obstruction. They can also cause
hypoglycemia as a paraneoplastic effect. Diagnosis requires Prognosis
demonstration o f neoplastic cells. Evaluation o f ultrasound- The prognosis for idiopathic disease is good.
guided fine-needle aspirate may be diagnostic, but these
tumors do not exfoliate as readily as many carcinomas or CHRONIC COLITIS
lymphomas, and biopsy is often necessary. Surgical excision For a discussion o f chronic colitis, see p. 459.
may be curative i f there are no metastases. Metastases make
the prognosis poor, although some animals are palliated by
chemotherapy. INTUSSUSCEPTION/PROLAPSE OF THE
LARGE INTESTINE
Diagnosis Treatment
Rectal examination is important; animals with acute colitis Typhlectomy is curative, and the prognosis is good.
may have rectal discomfort and/or hematochezia. E l i m i
nating obvious causes (e.g., diet, parasites) and resolving
the problem with symptomatic therapy allow the clinician RECTAL PROLAPSE
to make a presumptive diagnosis. Colonoscopy and biopsy
are definitive but seldom performed or needed unless Etiology
the initial presentation is unduly severe. Rectal examina Rectal prolapse usually occurs secondary to enteritis or
tion o f animals with acute proctitis may reveal roughened, colitis i n young animals. They begin to strain because of
thick, and/or obviously ulcerated mucosa. Proctoscopy rectal irritation, and eventually some or all o f the rectal
and rectal mucosal biopsy are definitive but seldom mucosa prolapses. M u c o s a l exposure increases irritation and
required. perpetuates straining, which promotes prolapse. Hence a
positive feedback cycle is initiated. M a n x cats appear to be are usually required to diagnose submucosal carcinomas and
predisposed to rectal prolapse. distinguish benign polyps from carcinomas because invasion
of the submucosa is an important feature o f rectal adeno
Clinical Features carcinomas. Because most colonic neoplasms arise i n or near
Dogs and cats (especially juveniles) are affected. The pres the rectum, digital examination is the best screening test.
ence of colonic or rectal mucosa extending from the anus is Colonoscopy is required for masses farther orad. Imaging is
obvious during the physical examination. used to detect sublumbar l y m p h node or pulmonary involve
ment (i.e., metastases).
Diagnosis
The diagnosis is based on physical examination. Rectal Treatment
examination is needed to differentiate rectal prolapse from Complete surgical excision is curative; however, most malig
an intussusception protruding from the rectum (see p. 465). nancies cannot be surgically cured because o f their location
in the pelvic canal, extent o f local invasion, and/or tendency
Treatment to metastasize to regional l y m p h nodes.
Treatment consists o f resolving the original cause of strain
ing if possible, repositioning the rectal mucosa, and prevent Prognosis
ing additional straining/prolapse. A well-lubricated finger is The prognosis for unresectable adenocarcinoma is poor.
used to reposition the mucosa. If it readily prolapses after Preoperative and intraoperative radiotherapy may be
being replaced, a purse-string suture i n the anus is used for palliative for some dogs w i t h nonresectable colorectal
1 to 3 days to hold it in position. The subsequent rectal adenocarcinomas.
opening must be large enough so that the animal can defe
cate. Occasionally, an epidural anesthetic is needed to prevent RECTAL POLYPS
repeated prolapse. If the everted mucosa is so irritated that
straining continues, retention enemas with kaolin or barium Etiology
may provide relief. If a massive prolapse is present or the The cause o f rectal polyps is u n k n o w n .
rectal mucosa is irreversibly damaged, resection may be
necessary. Clinical Features
Principally found i n dogs, hematochezia (which may be con
Prognosis siderable) and tenesmus are the primary clinical signs.
The prognosis is usually good, but some cases tend to Obstruction is rare.
recur.
Diagnosis
Usually detected during rectal examination, some adenoma
NEOPLASMS OF THE LARGE INTESTINE tous polyps resemble sessile adenocarcinomas because they
are so large that the narrow, stalklike attachment cannot be
ADENOCARCINOMA readily discerned. Occasionally, multiple small polyps may
be palpated throughout one segment o f the colon, usually
Etiology within a few centimeters o f the rectum (Fig. 33-13). Histo-
The cause of adenocarcinoma is u n k n o w n . Contrary to ade
nocarcinoma in people, relatively few cases of colonic adeno
carcinoma in dogs have been found to arise from polyps.
These tumors can extend into the lumen or be infiltrative
and produce a circumferential narrowing.
Clinical Features
Principally found in dogs, colonic and rectal adenocarcino
mas are more c o m m o n in older animals. Hematochezia is
common. Infiltrative tumors are likely to cause tenesmus
and/or constipation secondary to obstruction.
Diagnosis
Finding carcinoma cells is necessary for a diagnosis. Histo
pathologic evaluation is often preferable to cytologic analysis
FIG 3 3 - 1 3
because epithelial dysplasia may be present i n benign lesions, E n d o s c o p i c v i e w of the distal c o l o n of a d o g that has
causing a false-positive cytologic diagnosis o f carcinoma. multiple b e n i g n p o l y p s . Biopsy is necessary to d e t e r m i n e
Relatively deep biopsies obtained with rigid biopsy forceps that these a r e not i n f l a m m a t o r y o r m a l i g n a n t .
pathology is required for diagnosis and to distinguish polyps with advanced disease often lose weight. In rare cases there
from malignancies. will be infarction of mucosa or vessels with subsequent isch
emia. Cats are rarely affected.
Treatment
Complete excision via surgery or endoscopy is curative. If Diagnosis
possible, a thorough endoscopic or imaging evaluation Because the lesion is submucosal and very fibrotic, rigid biopsy
of the colon should be done before surgery to ensure that forceps are typically necessary to obtain deep, diagnostic
additional polyps are not present. If they are incompletely samples that include substantial amounts o f submucosa (i.e.,
excised, polyps return and must be excised again. M u l t i p l e where the organism is found; Fig. 33-14). Special stains (e.g.,
polyps w i t h i n a defined area may necessitate segmental Warthin-Starry) are needed to find the organism. Sometimes,
colonic mucosal resection. the organism cannot be found, but a suggestive pyogranulo
matous, eosinophilic inflammation is present. Serologic tests
Prognosis for antigen and antibodies are available (see Chapter 29).
M o s t canine rectal and colonic polyps do not result i n car
cinoma in situ, possibly because they are diagnosed relatively Treatment
sooner than colonic polyps i n people. The prognosis is good. Complete surgical excision is preferred. N o medication has
consistently been effective, although itraconazole or liposo
mal amphotericin B plus/minus terbenifine might be tem
MISCELLANEOUS LARGE INTESTINAL porarily beneficial i n some dogs.
DISEASES
Prognosis
PYTHIOSIS The prognosis is poor unless the lesion can be completely
excised.
Etiology
As discussed i n Chapter 32, pythiosis is caused by Pythium
insidiosum. PERINEAL/PERIANAL DISEASES
Clinical Features PERINEAL HERNIA
Pythiosis o f the large bowel usually occurs at or near the
rectum. However, it can involve any area o f the intestinal Etiology
tract. Rectal lesions often cause partial obstruction. Fistulae Perineal hernia occurs when the pelvic diaphragm (i.e., coc
may develop, resembling perianal fistulae. The dog may be cygeus and levator ani muscles) weakens and allows the
presented for constipation and/or hematochezia. Animals rectal canal to deviate laterally.
FIG 3 3 - 1 4
P h o t o m i c r o g r a p h o f a c o l o n i c b i o p s y s p e c i m e n . The m u c o s a is intact, but g r a n u l o m a s
b e l o w the m u c o s a (arrows) c o n t a i n f u n g a l h y p h a e . These g r a n u l o m a s w o u l d not be f o u n d
by s u p e r f i c i a l mucosal s a m p l i n g . These g r a n u l o m a s a r e c a u s e d b y pythiosis.
Clinical Features 2
prine, 50 m g / m q48h, or topical 0.1% tacrolimus q24h to
This condition is principally found i n older intact male dogs q l 2 h ) with or without antibacterial drugs (e.g., metronida
(especially Boston Terriers, Boxers, Cardigan Welsh Corgis, zole, erythromycin). Administering oral ketoconazole (5 mg/
and Pekingeses); cats are rarely affected. M o s t animals present kg q l 2 h ) may allow a lower dose o f cyclosporine to be effec
because of dyschezia, constipation, or perineal swelling; tive, thus decreasing the client's cost. If cyclosporine is used,
however, urinary bladder herniation into this defect may the clinician should m o n i t o r therapeutic b l o o d levels o f the
cause severe, potentially fatal postrenal uremia with depres drug to ensure that adequate b l o o d levels are present.
sion and vomiting. Hypoallergenic diets may also be beneficial. Rarely, animals
will not respond to medical therapy and w i l l require surgery.
Diagnosis Surgery may cause fecal incontinence. Postoperative care is
Digital rectal examination should detect rectal deviation, important and consists o f keeping the area clean. Fecal soft
lack of muscular support, and/or a rectal diverticulum. The eners are sometimes useful.
clinician should check for retroflexion of the urinary bladder
into the hernia. If such herniation is suspected, it can be Prognosis
confirmed by ultrasonography, radiographs, catheterizing M a n y patients are treated successfully. However, the progno
the bladder, or aspirating the swelling (after imaging) to see sis is guarded, and repeated medical care or surgeries may be
if urine is present. needed.
Treatment A N A L SACCULITIS
Animals with postrenal uremia constitute an emergency; the
bladder should be emptied and repositioned, and intrave Etiology
nous fluids should be administered. The preferred treatment In anal sacculitis the anal sac becomes infected, resulting i n
is surgical reconstruction o f the muscular support; however, an abscess or cellulitis.
surgery may fail, and clients should be prepared for the
fact that their pet may require additional reconstructive Clinical Features
procedures. A n a l sacculitis is relatively c o m m o n i n dogs and occasionally
occurs i n cats. Small dogs (e.g., Poodles, Chihuahuas) prob
Prognosis ably have a higher incidence o f this disorder than other
The prognosis is fair to guarded. breeds. M i l d cases cause irritation (i.e., scooting, licking,
or biting the area). A n a l sacs occasionally bleed onto the
PERIANAL FISTULAE feces. Severe cases may be associated with obvious pain,
swelling, and/or draining tracts. Dyschezia or constipa
Etiology tion may develop because the animal refuses to defecate.
The cause of perianal fistulae is u n k n o w n . Impacted anal Fever may occur i n dogs and cats w i t h severe anal
crypts and/or anal sacs have been hypothesized to become sacculitis.
infected and rupture into deep tissues. A n immune-mediated
mechanism is likely to be involved, as seen by the clinical Diagnosis
response to immunosuppressive drugs. Physical and rectal examination is usually diagnostic. The
anal sacs are often painful; the sac contents may appear
Clinical Features purulent, bloody, or n o r m a l but increased in volume. In
Perianal fistulae occur i n dogs and are more c o m m o n i n severe cases it may be impossible to express the affected sac.
breeds with a sloping conformation and/or a broad base to If the sac ruptures, the fistulous tract is usually i n a 4 o'clock
the tail head (e.g., German Shepherd Dogs). There are typi or 7 o'clock position i n relation to the anus. Occasionally,
cally one or more painful draining tracts around the anus. there is an obvious abscess.
Animals are usually presented because of constipation (caused
by the pain), odor, rectal pain, and/or rectal discharge. Treatment
M i l d cases require only that the anal sac be expressed and an
Diagnosis aqueous antibiotic-corticosteroid preparation be infused.
Diagnosis is made by physical and rectal examination. Care Infusion with saline solution may aid i n expressing impacted
should be taken when examining the patient because the sacs. If clients express the anal sacs at home, they can often
rectal area can be very painful. Draining tracts are sometimes prevent impaction and reduce the likelihood o f severe c o m
absent, but granulomas and abscesses can be palpated via the plications.
rectum. Rectal pythiosis rarely mimics perianal fistulae. Abscesses should be lanced, drained, flushed, and treated
with a hot pack; systemic antibiotics should also be a d m i n
Treatment istered. H o t packs also help soft spots form i n early abscesses.
Most affected dogs are cured with immunosuppressive If the problem recurs, is severe, or is nonresponsive to
therapy (e.g., cyclosporine, 3 to 5 mg/ kg q l 2 h or azathio medical therapy, affected sacs can be resected.
Prognosis Diagnosis
The prognosis is usually good. Cytologic and/or histopathologic evaluation is needed for
diagnosis, but neither reliably distinguishes malignant from
benign masses. Finding metastases (e.g., regional lymph nodes,
PERIANAL NEOPLASMS lungs) is the most certain method o f diagnosing malignancy.
Disorders of the
Peritoneum
tunately, when septic peritonitis is strongly suspected, the of adhesions, resulting in short bowel syndrome (see p. 466),
clinician typically cannot wait for results of abdominal fluid which has substantial morbidity.
culture. At this time, the ability o f canine pancreatic lipase Substantial abdominal contamination may require pro
immunoreactivity determinations to discriminate between tracted drainage. Penrose drains are typically inadequate for
the two is uncertain, especially since dogs with septic peri this purpose. O p e n abdominal drainage may be done, but it
tonitis may have secondary pancreatitis i f the intestinal is very time and labor intensive. A nonabsorbable suture is
perforation is close to the pancreas. Therefore the clinician used to close the abdomen except for a 6- to 8-cm opening
should always warn the client that the patient may or may at its most dependent aspect. This open incision is covered
not need the procedure but that there is no quick, reliable with sterile absorbent dressings (e.g., a sterile sanitary napkin
way to distinguish before surgery. held i n place by sterile cast padding and sterile gauze) that
are changed as needed, usually two to four times per day
Treatment initially. Eventually, only one change per day will be needed.
Animals with spontaneous septic peritonitis usually have an W h e n the dressing is changed, a sterile, gloved hand should
alimentary tract leak and should be surgically explored as explore the opening to ensure that o m e n t u m and intestines
soon as they are stable. A preanesthetic complete b l o o d have not blocked the site. This dressing change regimen is
count ( C B C ) , serum biochemistry profile, and urinalysis are continued until abdominal drainage decreases and most or
desirable; however, surgery usually should not be delayed all o f the peritoneal contamination is gone. Then a second
even i f the laboratory results are. D u r i n g surgery a careful surgery is performed to close the abdomen. The opening
search should be made for intestinal or gastric defects. Biopsy sometimes closes spontaneously. The abdomen should be
of tissue surrounding a perforation should be performed to recultured at the time o f the second surgery. Alternatively,
search for underlying neoplasia or inflammatory bowel closed suction drains have been used postoperatively with
disease (IBD). After the defect is corrected, the abdomen success, and some clinicians advocate closure o f such abdo
should be repeatedly lavaged with large volumes o f w a r m mens without drainage.
crystalloid solutions to dilute and remove debris and bacte Systemic antimicrobial therapy should consist of
ria. The abdomen cannot be adequately lavaged via a drain broad-spectrum, parenteral antibiotics. A combination of
tube or even a peritoneal dialysis catheter except i n the a -lactam drug (e.g., ticarcillin plus clavulinic acid) and
mildest cases. Adhesions re-form quickly; they should not be metronidazole plus an aminoglycoside (e.g., amikacin) is
broken down unless it is necessary to examine the intestines. usually an excellent choice (see the discussion of antibacterial
Intestines should be resected only i f they are truly devital drugs used in gastrointestinal disorders, p. 409). Enrofloxacin
ized. Intestines are sometimes unnecessarily removed because may be substituted for the aminoglycoside, but it must be
FIG 3 4 - 2
A , P h o t o m i c r o g r a p h of peritoneal e x u d a t e from a d o g w i t h septic peritonitis. N o t e bacteria
(small arrows) a n d neutrophils that h a v e d e g e n e r a t e d so much that it is difficult to identify
them as neutrophils (large arrows). ( W r i g h t ' s stain; m a g n i f i c a t i o n x 1 0 0 0 . ) (Courtesy Dr.
C l a u d i a B a r t o n , Texas A & M University.) B , P h o t o m i c r o g r a p h of septic p e r i t o n e a l f l u i d .
There is o n e intracellular b a c t e r i u m (large a r r o w ) a n d t w o things (small, clear a r r o w s ) that
m a y o r m a y not be b a c t e r i a . The neutrophils a r e not n e a r l y as d e g e n e r a t e d as in A .
given over 30 to 40 minutes in a diluted form. A m i n o g l y c o factors is optimal; plasma is given until the A T III concentra
sides and quinolones are dose-dependent drugs; administra tion and the prothrombine time (PT) and partial thrombo
tion of the entire daily dose i n one injection is safer and plastin time (PTT) are normal or clearly much improved.
probably as or more effective than administering smaller Heparin may also be administered; low molecular weight
doses two to three times daily. Cefoxitin (30 mg/kg q6-8h) heparin is believed to be more effective than unfractionated
and meropenem (24 mg/kg once daily) are other -lactam heparin.
drugs that may be used. F l u i d and electrolyte support
helps prevent aminoglycoside-induced nephrotoxicity. Prognosis
Hypoalbuminemia can occur, especially i f open abdominal The prognosis depends on the cause of the leak (e.g., perfo
drainage is used. If disseminated intravascular coagulation rations may be caused by malignancies) and the animal's
(DIC) is present, administration of fresh frozen plasma condition when it is diagnosed. SIRS and D I C worsen the
to replenish antithrombin III ( A T III) and other clotting prognosis.
SCLEROSING, ENCAPSULATING Clinical features
PERITONITIS A b d o m i n a l hemangiosarcoma is principally found i n older
dogs, especially German Shepherd Dogs and Golden Retrievers.
Etiology Anemia, abdominal effusion, and periodic weakness or collapse
Reported causes include bacterial infection, steatitis, and from poor peripheral perfusion are c o m m o n presenting
fiberglass ingestion. This form of peritonitis is rare. complaints. Some animals have bicavity hemorrhagic effusion.
Etiology Diagnosis
A b d o m i n a l hemangiosarcoma often originates i n the spleen Physical examination and radiography rarely help to estab
(see Chapter 82). It can spread throughout the abdomen by lish the diagnosis. Ultrasonography may reveal masses or
implantation, causing widespread peritoneal seepage o f infiltrates i f they are large enough; however, small, miliary
blood, or it can metastasize to distant sites (e.g., liver, lesions can be missed by ultrasound. Fluid analysis reveals a
lungs). nonseptic exudate or a modified transudate; epithelial neo-
plastic cells are occasionally found (see Chapter 36). Lapa inal effusion of FIP is discussed here. Although a major cause
roscopy or abdominal exploratory surgery with histologic of feline abdominal effusion, FIP is not the only cause. Fur
examination of biopsy specimens is usually needed for thermore, not all cats with FIP have effusions. FIP effusions
diagnosis. are classically pyogranulomatous (i.e., macrophages and
nondegenerate neutrophils) with a relatively low nucleated
Treatment cell count (i.e., 10,000/l). However, some cats with FIP
Intracavitary chemotherapy has been palliative for some have effusions that primarily contain neutrophils. A nonsep
animals, although generally there is no effective treatment tic exudate i n a nonazotemic cat suggests FIP until proven
2
for this disorder. Cisplatin (50 to 70 m g / m every 3 weeks) otherwise.
2
and 5-fluorouracil (150 m g / m every 2 to 3 weeks) are fre
quently effective i n decreasing fluid accumulation in dogs Suggested Readings
with carcinomatosis but should not be used i n cats; carbo Boysen SR et al: Evaluation of a focused assessment with sonogra
2
platin (150 to 200 m g / m every 3 weeks) may be effective i n phy for trama protocol to detect free abdominal fluid in dogs
cats. involved in motor vehicle accidents, J Am Vet Med Assoc 225:1198,
2004.
Prognosis Brockman DJ et al: A practical approach to hemoperitoneum in the
The prognosis is grim. dog and cat, Vet Clin N Am 30:657, 2000.
Costello M F et al: Underlying cause, pathophysiologic abnormali
ties, and response to treatment in cats with septic peritonitis: 51
MESOTHELIOMA
cases (1990-2001), J Am Vet Med Assoc 225:897, 2004.
Hinton LE et al: Spontaneous gastroduodenal perforation in 16
Etiology
dogs and seven cats (1982-1999),} Am Anim Hosp Assoc 38:176,
The cause is u n k n o w n . 2002.
Lanz OI et al: Surgical treatment of septic peritonitis without abdo
Clinical Features minal drainage in 28 dogs, J Am Anim Hosp Assoc 37:87, 2001.
Levin G M et al: Lactate as a diagnostic test for septic peritoneal
Mesothelioma often causes bicavity effusion. The tumor may
effusions in dogs and cats, J Am Anim Hosp Assoc 40:364, 2004.
appear as fragile clots adhering to the peritoneal surface of
Merlo M et al: Radiographic and ultrasonographic features of
various organs. retained surgical sponge in eight dogs, Vet Radiol Ultrasound
Diagnosis 41:279, 2000.
Mueller M G et al: Use of closed-suction drains to treat generalized
Imaging reveals only fluid accumulations. F l u i d cytology
peritonitis in dogs and cats: 40 cases (1997-1999), ] Am Vet Med
rarely is beneficial because reactive mesothelial cells are
Assoc 219:789, 2001.
notorious for m i m i c i n g malignancy, and pathologists gener Pintar J et al: Acute nontraumatic hemoabdomen in the dog: a
ally acknowledge the inability to cytologically distinguish retrospective analysis of 39 cases (1987-2001), J Am Anim Hosp
neoplastic cells from nonneoplastic cells i n abdominal fluid. Assoc 39:518, 2003.
Laparoscopy or laparotomy are typically needed to make a Ralphs SC et al: Risk factors for leakage following intestinal anas
definitive diagnosis. tomosis in dogs and cats: 115 cases (1991-2000), J Am Vet Med
Assoc 223:73-77, 2003.
Treatment Saunders WB et al: Penumperitoneum in dogs and cats: 39 cases
(1983-2002), J Am Vet Med Assoc 223:462, 2003.
Intracavity cis-platinum may be attempted. Shales CI et al: Complications following full-thickness small intes
tinal biopsy in 66 dogs: a retrospective study, / Small Anim Pract
Prognosis 46:317, 2005.
The prognosis is grim, but chemotherapy has been reported Sharpe A et al: Intestinal haemangiosarcoma in the cat: clinical and
to prolong survival by several months. pathological features of four cases, / Small Anim Pract 41:411,
2000.
FELINE INFECTIOUS PERITONITIS Smelstoys JA et al: Outcome of and prognostic indicators for dogs
Feline infectious peritonitis (FIP) is a viral disease of cats, and cats with pneumoperitoneum and no history of penetrating
which is discussed i n detail i n Chapter 97. O n l y the abdom trauma: 54 cases (1988-2002), ] Am Vet Med Assoc 225:251, 2004.
Drugs Used i n Gastrointestinal Disorders
Continued
Drugs Used in Gastrointestinal Disorderscont'd
C H A P T E R 35
Clinical Manifestations of
Hepatobiliary Disease
much that details of abdominal organs are obscured during sodium retention by the kidneys and increased circulating
palpation. Whether there is small- or large-volume effusion, fluid volume. This R A A S activation is triggered by a decrease
the general pathogeneses of third-space fluid accumulation i n systemic b l o o d pressure caused by pooling o f a significant
(excessive formation by increased venous hydrostatic pres proportion of the circulating b l o o d volume i n the splanchnic
sure, decreased intravascular oncotic pressure, or altered circulation. It has been observed that, in many cases, overt
vascular permeability and insufficient resorption), singly or ascites does not develop until sodium retention by the
in combination, apply to cats and dogs with hepatobiliary kidneys is increased, altering the balance of fluid formation
diseases. In addition, an important part o f the mechanisms and reabsorption. Therefore aldosterone antagonists play a
of ascites formation in dogs with liver disease is activation key role i n the treatment o f ascites associated with liver
of the renin-angiotensin-aldosterone system (RAAS) with disease.
Intrahepatic portal venous hypertension is the most an inflammatory reaction, with subsequent exudation of
c o m m o n mechanism leading to ascites i n companion l y m p h and fibrin. The fluid may be serosanguineous, hemor
animals, particularly dogs, with hepatobiliary diseases. The rhagic, or chylous i n appearance. Regardless of the gross
formation of abdominal effusion depends on the site, rate, appearance of the fluid, the protein content is variable, and
and degree of defective venous outflow. Sustained resistance the fluid may contain exfoliated malignant cells if the primary
to intrahepatic portal b l o o d flow at the level of the portal neoplasm is a carcinoma, mesothelioma, or lymphoma,
triad favors exudation of fluid from more proximal (in the although often it does not, in which case further investiga
direction of portal b l o o d flow; i.e., intestinal) lymphatics tions are required to diagnose the neoplasm.
into the abdominal cavity. The fluid is generally of low Extravasation of bile from a ruptured biliary tract elicits
protein content and is hypocellular. However, i f the fluid is a strong inflammatory response and stimulates transudation
present i n the abdomen for any amount of time, it becomes of l y m p h by serosal surfaces. In experimental animal models,
"modified" w i t h an increase i n protein content. The excep the damaging component of bile has been identified as bile
tion to this is in the animal with marked hypoalbuminemia acids. U n l i k e with most other causes of abdominal effusion
associated with liver disease i n which the ascites remains a associated with hepatobiliary disease, there may be evidence
low-protein transudate. Inflammatory or neoplastic cellular of cranial abdominal or diffuse abdominal pain identified
infiltrates or fibrosis i n this region of the liver are the patho during physical examination i n cats and dogs with bile peri
logic processes most often responsible for this type of effu tonitis. The fluid appears characteristically dark orange,
sion. Sinusoidal obstruction caused by regenerative nodules, yellow, or green and has a high bilirubin content on analysis,
collagen deposition, or cellular infiltrates causes effusion of and the predominant cell type is the healthy neutrophil,
a fluid composed of a mixture of hepatic and intestinal except when the biliary tract is infected. Because normal bile
l y m p h that has a variable protein content and generally l o w is sterile, the initial phase of bile peritonitis is nonseptic, but
cell count. unless treatment is initiated rapidly, secondary infection,
Prehepatic portal venous occlusion or the presence of a usually with anaerobes, may become life-threatening.
large arteriovenous fistula, leading to portal venous volume
overload, and associated high intrahepatic vascular resis ABDOMINAL MUSCULAR HYPOTONIA
tance triggered by increased portal flow also produces a l o w The presence of a distended abdomen in the absence of
to moderate protein, hypocellular effusion, as w o u l d diffuse organomegaly or abdominal effusion suggests abdominal
mesenteric lymphatic obstruction associated with l y m muscular hypotonia. Either the catabolic effects of severe
phoma. The latter can also sometimes result i n a chylous malnutrition or (more c o m m o n l y in dogs) excess endoge
effusions. Examples of causes of portal venous occlusion nous or exogenous corticosteroids reduce muscular strength,
include intraluminal obstructive masses (e.g., thrombus), giving the appearance of an enlarged abdomen. In both dogs
extraluminal compressive masses (e.g., mesenteric l y m p h and (much less commonly) cats with hyperadrenocorticism,
node, neoplasm), and portal vein hypoplasia or atresia. the combination of generalized hepatomegaly (mild and
Venous congestion from disease of the major hepatic associated with diabetes mellitus i n cats), redistribution of
veins and/or distally (i.e., thoracic caudal vena cava, heart; fat stores to the abdomen, and muscular weakness causes
posthepatic venous congestion) increases formation of abdominal distention.
hepatic lymph, w h i c h exudes from superficial hepatic l y m O n the basis of the physical examination findings, the
phatics. Because the endothelial cell-lined sinusoids are problem of abdominal enlargement should be refined to the
highly permeable, hepatic l y m p h is of high protein content. level of organomegaly, abdominal effusion, or poor muscu
A b d o m i n a l effusion formed under these conditions is more lar tone, as shown i n Fig. 35-2. Additional tests are required
likely to develop i n dogs than i n cats. Reactive hepatic veins to obtain a definitive diagnosis.
that behave as postsinusoidal sphincters have been identified
in dogs and are speculated to add to venous outflow impinge
ment. Concurrent hypoalbuminemia (1.5 g/dl) i n dogs JAUNDICE, BILIRUBINURIA, AND
(and rarely cats) associated with hepatic parenchymal failure CHANGE IN FECAL COLOR
may further enhance movement of fluid into the peritoneal
space. Perivenular pyogranulomatous infiltrates i n the vis By definition, jaundice i n cats and dogs is the yellow staining
ceral and parietal peritoneum of cats with the effusive form of serum or tissues by an excessive amount of bile pigment
of FIP increase vascular permeability and promote exuda or bilirubin (Fig. 35-3); the terms jaundice and icterus may
tion of straw-colored, protein-rich fluid into the peritoneal be used interchangeably. Because the normal liver has the
space. Typically, the fluid is of l o w to moderate cellularity, ability to take up and excrete a large amount of bilirubin,
with a m i x e d cell population of neutrophils and macro there must be either a large, persistent increase i n the pro
phages, and with a moderate to high protein concentration. duction of bile pigment (hyperbilirubinemia) or a major
It is usually classified as an exudate but occasionally is a impairment i n bile excretion (cholestasis with hyperbiliru
modified transudate. binemia) before jaundice is detectable as yellow-stained
Hepatobiliary malignancies or other intraabdominal car tissues (serum bilirubin concentration >2 mg/dl) or serum
cinomas that have disseminated to the peritoneum can elicit (serum bilirubin concentration 1.5 mg/dl).
FIG 35-2
Algorithm for initial evaluation of the cat or dog with abdominal distention.
In normal animals bilirubin is a waste product o f heme tion to various carbohydrates, conjugated bilirubin, n o w
protein degradation. The primary source o f heme proteins water soluble, is excreted into the bile canaliculi. Conjugated
is senescent erythrocytes, with a small contribution by m y o bilirubin is then incorporated into micelles and stored with
globin and heme-containing enzyme systems i n the liver. other bile constituents in the gallbladder until it is discharged
After phagocytosis by cells o f the M P S , primarily in the bone into the duodenum. However, in dogs it has been noted that
marrow and spleen, heme oxygenase opens the protopor only 29% to 53% o f bile produced is stored in the gall
phyrin ring of hemoglobin, forming biliverdin. Biliverdin bladder; the rest is secreted directly into the d u o d e n u m
reductase converts biliverdin to fat-soluble bilirubin IXa, (Rothuizen et al., 1990). After arrival i n the intestine, conju
which is released into the circulation, where it is b o u n d to gated bilirubin undergoes bacterial deconjugation and then
albumin for transport to hepatic sinusoidal membranes. reduction to urobilinogen, with most urobilinogen being
After uptake, transhepatocellular movement, and conjuga resorbed into the enterohepatic circulation. A small fraction
FIG 35-3
Jaundiced mucous membranes in a dog (A, gum, and B, sclera). Note that this dog had
jaundice because of immune-mediated hemolytic anemia and not liver diseasehence the
mucous membranes are pale and yellow (which makes them more easily photographed).
(Photographs courtesy Sara Gould.)
of urobilinogen is then excreted i n the urine, and a small most published resources agree that concentrations over
portion remains in the intestinal tract to be converted to 0.3 mg/dl i n cats and 0.6 mg/dl in dogs are abnormal. W h e n
stercobilin, which imparts normal fecal color. results o f laboratory tests are assessed, species differences in
Inherited abnormalities of bilirubin metabolism have not the formation and renal processing of bilirubin between cats
been identified in cats and dogs; thus i n the absence o f and dogs must be taken into account. Canine renal tubules
massive increases i n bile pigment production by hemolysis, have a low resorptive threshold for bilirubin. Dogs (males to
jaundice is attributable to impaired excretion o f bilirubin a greater extent than females) have the necessary renal
(and usually other constituents o f bile) by diffuse intrahe enzyme systems to process bilirubin to a limited extent;
patic hepatocellular or biliary disease or by interrupted therefore bilirubinuria (up to 2+ to 3+ reaction by dipstick
delivery o f bile to the duodenum. The inability to take up, analysis) may be a normal finding i n canine urine specimens
intracellularly process, or excrete bilirubin into the bile of specific gravity greater than 1.025. Cats do not have this
canaliculi (the rate-limiting step) is the mechanism o f cho ability, and they have a ninefold higher tubular absorptive
lestasis believed to be operational in many primary hepato capacity for bilirubin than dogs. Bilirubinuria in cats is asso
cellular diseases. Jaundice is more likely to be a clinical ciated with hyperbilirubinemia and is always pathologic.
feature i f the liver disorder involves primarily the periportal Because unconjugated and most conjugated bilirubin is
(zone 1) hepatocytes (Fig. 35-4) than i f the lesion involves albumin-bound i n the circulation, only the small amount of
centrilobular (zone 3) hepatocytes. Inflammation and swell nonprotein-bound conjugated bilirubin is expected to
ing o f larger intrahepatic biliary structures could similarly appear in the urine i n physiologic and pathologic states. In
delay bile excretion. dogs with hepatobiliary disease, increasing bilirubinuria
Obstruction o f the bile duct near the d u o d e n u m results often precedes the development of hyperbilirubinemia and
i n increased intraluminal biliary tract pressure, interhepato clinical jaundice and may be the first sign of illness detected
cellular regurgitation o f bile constituents into the circula by owners.
tion, and jaundice. If only one o f the hepatic bile ducts Several nonhepatobiliary disorders impede bilirubin
exiting the liver is blocked or i f only the cystic duct exiting excretion by poorly understood means. Jaundice with evi
the gallbladder is obstructed for some reason, there may be dence o f hepatocellular dysfunction but m i n i m a l histopath
biochemical clues for localized cholestasis, such as high ologic changes i n the liver has been described in septic
serum alkaline phosphatase activity; however, the liver's human, feline, and canine patients. Certain products released
overall ability to excrete is preserved, and jaundice does not by bacteria, such as endotoxin, are k n o w n to reversibly inter
ensue. Traumatic or pathologic biliary tract rupture allows fere with bile flow. As yet unexplained m i l d hyperbilirubine
leakage of bile into the peritoneal space and some absorption mia (2.5 mg/dl) may also be detected in approximately 20%
of bile components. Depending o n the underlying cause and of hyperthyroid cats. Experimental investigations of thyro
the time elapsed between biliary rupture and diagnosis, the toxicosis i n laboratory animals have demonstrated increased
degree o f jaundice may be m i l d to moderate. If biliary production of bilirubin, which has been proposed to be asso
rupture has occurred, the total bilirubin content o f the ciated with increased degradation o f hepatic heme proteins.
abdominal effusion is greater than that o f serum. There is no histologic evidence of cholestasis at the light
Reference ranges for serum total bilirubin concentrations microscopic level in affected cats, and the hyperbilirubine
in dogs and cats may vary from laboratory to laboratory, but mia resolves with return to euthyroidism. Guidelines for
FIG 35-4
A , Rappaport scheme of the hepatic functional lobule (acinus), organized according to
biochemical considerations (1958). For example, zone 1 cells are responsible for protein
synthesis, urea and cholesterol production, gluconeogenesis, bile formation, and cytogen
esis; zone 2 cells also produce albumin and are actively involved in glycolysis and
pigment formation; and zone 3 cells are the major site of liponeogenesis, ketogenesis,
and drug metabolism. Zone 3 hepatocytes, being farther from the hepatic artery and
hepatic portal veins, also have the lowest oxygen supply and are therefore most suscep
tible to hypoxic damage. Conversely, zone 1 hepatocytes, being closest to the hepatic
portal vein, are most susceptible to damage by toxins from the gut. B, Outdated theory of
hepatic functional lobule, as first proposed in 1833. The apparent hexagonal boundaries
have little to do with functional arrangement.
initial evaluation o f the icteric cat or dog are given i n Fig. tion of bile pigments. The true frequency of white bile i n cats
35-5. Finally, lipemia is a c o m m o n cause o f pseudohyper or dogs with severe cholestasis is not k n o w n .
bilirubinemia in dogs as a result o f interference with the
laboratory test.
Acholic feces result from total absence o f bile pigment i n HEPATIC ENCEPHALOPATHY
the intestine (Fig. 35-6). O n l y a small amount of bile pigment
is needed to be changed to stercobilin and yield normal fecal Signs o f abnormal mentation and neurologic dysfunction
color; therefore bile flow into the intestine must be c o m develop i n dogs and cats with serious hepatobiliary disease
pletely discontinued in order to form acholic feces, and this as a result o f exposure o f the cerebral cortex to absorbed
is very rare i n both dogs and cats. In addition to appearing intestinal toxins that have not been removed by the liver.
pale from lack of stercobilin and other pigments, acholic Substances that have been implicated as important i n the
feces are pale because o f steatorrhea resulting from the lack genesis o f hepatic encephalopathy ( H E ) , singly or i n combi
of bile acids to facilitate fat absorption. Mechanical diseases nation, are ammonia, mercaptans, short-chain fatty acids,
of the extrahepatic biliary tract (e.g., unremitting complete skatoles, indoles, and aromatic amino acids. Either there is
extrahepatic bile duct obstruction [ E B D O ] , traumatic bile marked reduction i n functional hepatic mass or portal b l o o d
duct avulsion from the duodenum) are the most c o m m o n flow has been diverted by the development o f portosystemic
causes of acholic feces i n cats and dogs. Total inability to take venous anastomoses, thus preventing detoxification o f gas
up, conjugate, and excrete bilirubin because o f generalized trointestinal (GI) toxins, or there is a combination o f these
hepatocellular failure is theoretically possible. However, two processes. Portosystemic shunting can occur via the
because the functional organization o f the liver is heteroge presence o f a macroscopic vascular pattern that results from
neous (see Fig. 35-4) and because primary hepatic diseases a congenital vascular miscommunication or by a complex o f
do not affect all hepatocytes uniformly, the overall ability o f acquired "relief valves" that open i n response to sustained
the liver to process bilirubin may be altered, although it is portal hypertension secondary to severe primary hepatobi
usually preserved. A condition has been reported rarely i n liary disease (Fig. 35-7). Intrahepatic, microscopic portosys
cats with severe cholangitis i n which bile flow ceases. U n d e r temic shunting or widespread hepatocellular inability to
detoxify noxious enteric substances accounts for H E when
these circumstances, "bile" consists o f only clear, viscous
an abnormal portal vascular pattern cannot be demon
biliary epithelial secretions, and this may result i n the pro
strated. Rarely, i f congenital portovascular anomalies and
duction of acholic feces. A similar finding, k n o w n as "white
severe primary hepatobiliary disease with acquired shunting
bile syndrome," has been associated with prolonged total
have been ruled out, congenital urea enzyme cycle deficiencies
biliary obstruction and is thought to be the result o f resorp
FIG 35-5
Algorithm for preliminary evaluation of the icteric cat or dog. AP, Alkaline phosphatase;
GGT, -glutamyltransferase; ALT, alanine transaminase; EBDO, extrahepatic bile duct
obstruction.
and organic acidemias, in which a m m o n i a cannot be the cerebrospinal fluid (CSF) environment are complex. The
degraded to urea, are considered. H E has also been reported brain is very sensitive to the toxic effects o f N H but does
3
i n congenital cobalamin deficiency i n dogs (Battersby et al., not have a urea cycle, so N H i n the C S F is detoxified to
3
2005). Animals with systemic diseases having hepatic m a n i glutamine. C S F glutamine concentrations in dogs with por
festations do not undergo sufficient loss o f hepatic mass or tosystemic shunts (PSS) correlate better with clinical signs
change in hepatic b l o o d flow to develop signs o f H E . than C S F or b l o o d N H levels (Fig. 35-8). Dogs with
3
The pathogenesis o f this reversible abnormality i n cere congenital PSS also have increased C S F concentrations of
bral metabolism currently is incompletely understood. aromatic amino acids, particularly tryptophan and its
Increased a m m o n i a ( N H ) in the b l o o d remains the most
3 metabolites, and this appears to be directly related to N H 3
important cause of H E . M o s t o f the precipitating factors and concentrations in the C S F because they share an antiport
treatment recommendations for H E primarily affect b l o o d transporter. Also implicated are changes in central nervous
N H 3 concentrations. The effects on neurotransmitters and system ( C N S ) serotonin activity (which is often reduced);
FIG 3 5 - 6
Acholic feces from a 7-year-old spayed female Collie dog
with a strictured bile duct and complete bile duct obstruction
3 weeks after recovery from severe pancreatitis.
FIG 3 5 - 8
Two dogs with similar fasting plasma ammonia concentra
tions, emphasizing the lack of correlation between plasma
ammonia content and severity of encephalopathic signs.
A , Female Miniature Poodle with congenital portosystemic
shunt. The plasma ammonia concentration was 4 5 4 g/dl.
B, Male mixed-breed dog with chronic hepatic failure and
FIG 3 5 - 7 acquired portosystemic shunting. The plasma ammonia
Spectrum of hepatic encephalopathy in cats and dogs concentration was 3 9 0 g/dl.
ranging from pure vascular to pure hepatocellular causes.
*, Clinically relevant only in dogs and cats; , clinically
relevant only in human patients. (Modified from Schafer DF Endogenous hepatic protein metabolism from excess
et al: Hepatic encephalopathy. In Zakim D et a l , editors; dietary protein, G I bleeding, or breakdown of lean
Hepatology: a textbook of liver disease, Philadelphia, body mass
1990, W B Saunders.)
peripheral-type benzodiazepine receptors, and altered astro in animals o n high-protein diets, i n many animals, particu
cyte receptors and handling of glutamate. M o s t o f these larly those with protein-calorie malnutrition, endogenous
changes are related to increased N H .
3 sources o f N H may be more important and further dietary
3
The sources o f increased blood ammonia i n animals protein restriction just worsens the hyperammonemia i n
with liver disease are outlined i n Fig. 35-9 and include the these cases.
following: Subtle, nonspecific signs of H E i n cats and dogs that could
be noted at any time and that represent chronic or subclini
Bacterial breakdown o f undigested amino acids and cal H E include anorexia, depression, weight loss, lethargy,
purines that reach the colon nausea, fever, hypersalivation (particularly in cats), intermit
Bacterial and intestinal urease action o n urea, which tent vomiting, and diarrhea. Certain events might precipitate
freely diffuses into the colon from the blood an acute episode o f H E with severe neurologic signs (see
Small intestinal enterocyte catabolism of glutamine as Chapter 39). Nearly any C N S sign may be observed i n cats
their main energy source and dogs with H E , although typical signs tend to be nonlo-
BOX 35-3
Coagulation Proteins and Inhibitors Synthesized
by the Liver
Proteins C and S
Antithrombin
Fibrinogen
Plasminogen
Vitamin K-dependent factors
II (prothrombin)
VII
IX
X
Factor V
Factor XI
Factor XII
Factor XIII
Pure Clear, colorless <1500/l <2.5 g / d l <1.016 Chronic hepatic failure with
transudates marked hypoalbuminemia
Modified Serosanguineous, <7000/l >2.5 g / d l 1.010-1.031 Chronic hepatic failure, right-sided
transudates amber heart failure, pericardial
disease, caval syndrome, Budd-
Chiari-like syndrome,
intrahepatic portal vein
hypoplasia, chronic portal vein
thrombosis, feline infectious
peritonitis (some cases),
neoplasia (some cases)
Exudates
Septic Cloudy; red, dark >7000/l >2.5 g / d l 1.020-1.031 Perforated duodenal ulcer, bile
yellow, green peritonitis (fluid bilirubin
concentration exceeds serum
bilirubin concentration)
Nonseptic Clear; red, dark >7000/l 2.5 g / d l 1.017-1.031 Feline infectious peritonitis,
yellow, green neoplasia with serosal
involvement, ruptured
hemangiosarcoma, early bile
peritonitis
Chylous Opaque, white to Variable; Variable; 1.030-1.032 Neoplasia (some cases); diseases
effusions pink ("strawberry usually 2.5- obstructing lymphatic drainage
milkshake") 1000- 6.5 g / d l
10,000/l
Hemorrhagic Red Variable; Usually <1.013 Neoplasia (some cases);
effusions usually >3.0 g / d l amyloidosis with hepatic
1500 to capsule rupture; ruptured
1000/l hemangiosarcoma
protein concentration i n a jaundiced dog, especially i f sphe nucleated red b l o o d cells is also detected. M i l d to moderate
rocytes are also identified, indicates hemolytic anemia and nonregenerative anemia is c o m m o n i n cats with many dif
increased bilirubin formation as the cause of jaundice. Cats ferent illnesses, including those of the hepatobiliary tract.
and dogs with hemolytic anemia typically also have high Few changes i n the leukon are expected in cats or dogs
serum liver enzyme activities and bile acid concentrations, with hepatobiliary disease, except when an infectious agent
pointing to hepatic consequences developing secondary to is present as the initiating event (histoplasmosis, bacterial
the effects of marked hemolysis, such as hypoxia and t h r o m cholangitis, or leptospirosis i n dogs); where there is concur
boembolism. rent pancreatitis, which is particularly c o m m o n i n cats (see
Certain red b l o o d cell morphologic changes are consis Chapter 40); or when infection has complicated a primary
tent with serious hepatobiliary disease and are related to hepatobiliary disorder (e.g., gram-negative sepsis in a dog
alterations i n lipoprotein metabolism and irregularities i n with cirrhosis, septic bile peritonitis). Neutrophilic leukocy
red blood cell membrane structure. Acanthocytes, leptocytes, tosis is likely i n such cases, whereas pancytopenia is typical
and codocytes (target cells) are good examples (see Fig. of disseminated histoplasmosis and severe toxoplasmosis in
36-2). Poikilocytosis of u n k n o w n pathogenesis is a consis cats and of early infectious canine hepatitis.
tent finding i n cats w i t h congenital PSS and occasionally
with other hepatobiliary diseases; cats with chronic hepato COAGULATION TESTS
biliary disease frequently have H e i n z bodies i n their red Clinically relevant coagulopathies are unusual i n cats and
b l o o d cells. Fragmented red b l o o d cells or schistocytes con dogs with hepatobiliary disease except for those with acute
stitute an expected finding i n animals with D I C ; hemangio hepatic failure (including acute hepatic lipidosis in cats or
sarcoma is considered when an inappropriate number of hepatic l y m p h o m a i n both species), complete E B D O , or
FIG 36-2
Erythrocyte morphologic changes often associated with hepatobiliary disease in cats and
dogs (Wright-Giemsa stain). A, Microcytic red blood cells (mean corpuscular volume
[MCV] = 4 5 fl) from dog with congenital portosystemic shunt; compare the microcytic red
blood cells with the size of a nearby normal small lymphocyte 6 to 9 m in diameter.
B, Normal canine red blood cells (MCV = 7 0 fl) for comparison. C, Acanthocytes from dog
with severe chronic hepatic passive congestion. D, Poikilocytes from cat with cholangitis.
active D I C . It is more c o m m o n to have subtle prolongation A summary o f laboratory tests for cats and dogs with
of activated partial thromboplastin time ( A P T T ; 1.5 times hepatobiliary disease and interpretation o f their results is
normal), abnormal fibrin degradation products (10 to 40 or given i n Table 36-2.
higher), and variable fibrinogen concentration (<100 to
200 mg/dl) in cats and dogs with severe parenchymal hepatic
disease. Elevated D-dimers are c o m m o n i n patients with DIAGNOSTIC IMAGING
liver disease and do not always indicate D I C i n these cases.
It has been proposed that nonspecific elevation can occur i n SURVEY RADIOGRAPHY
liver disease as a result of reduced clearance by the liver. Radiographic evaluation o f the abdomen is used to c o m
Platelet numbers may be normal or low; m i l d thrombocyto plement physical examination findings and to confirm
penia (130,000 to 150,000 cells/l) is usually associated with suspicions regarding the character and location of the hepa
splenic sequestration or chronic D I C . M o r e severe thrombo tobiliary disease suggested by results o f clinicopathologic
cytopenia (100,000 cells/l) is expected in acute D I C or examination. Survey radiographs provide subjective infor
decompensated chronic D I C . Some animals with severe mation regarding the size and shape o f the liver (see Table
hepatic disease and relatively unremarkable routine coagula 35-1). Optimally, the animal should have an empty gastro
tion test results have high serum activity o f proteins induced intestinal tract at the time the radiographs are obtained. In
by vitamin K antagonism ( P I V K A ) that could impart bleed the n o r m a l dog and cat i n right lateral recumbency, the
ing tendencies. Primary or metastatic cancer o f the liver gastric axis is parallel to the ribs at the tenth intercostal space,
could also cause coagulopathy unrelated to loss of hepatocel and the caudoventral border o f the liver (the left lateral liver
lular ability to make or degrade coagulation proteins. lobe) appears sharp; the image is made possible by the con-
Summary of First- and Second-Line Clinicopathologic Tests Useful in the Diagnosis of Hepatobiliary Disease
SCREENING TEST PRINCIPLE EXAMINED COMMENTS
Serum ALT, AST Integrity of liver cell membranes; Degree of increase roughly correlates with number of
activities escape from cells hepatocytes involved but not severity of disease
Serum AP, G G T Reactivity of biliary epithelium to Increase associated with intrahepatic or extrahepatic
activities various stimuli; increased synthesis cholestasis or drug effect (dogs only): corticosteroids,
and release anticonvulsants (AP only, not GGT)
Serum albumin Protein synthesis Rule out other causes of low concentration (glomerular or
concentration intestinal loss); low value indicates 80% overall hepatic
function loss or negative acute phase response
Serum urea Protein degradation and With low values, rule out prolonged anorexia; dietary
concentration detoxification protein restriction; severe P U / P D ; urea cycle enzyme
deficiency (rare); congenital PSS; severe, acquired
chronic hepatobiliary disease
Serum bilirubin Uptake and excretion of bilirubin Rule out marked hemolysis first; if PCV is normal,
concentration intrahepatic or extrahepatic cholestasis is present
Serum cholesterol Biliary excretion, intestinal High values compatible with severe cholestasis of any
concentration absorption, integrity of the kind; low values suggest congenital PSS; anticonvulsant
enterohepatic circulation drug-induced change; severe, acquired chronic
hepatobiliary disease; or severe intestinal malassimilation
Serum glucose Hepatocellular gluconeogenic or Low values indicate severe hepatocellular dysfunction, PSS,
concentration glycolytic ability; insulin and other or presence of a primary liver tumor
hormone metabolism
Plasma ammonia Integrity of the enterohepatic High fasting or postprandial values suggest congenital or
concentration circulation, hepatic function and acquired PSS or acute hepatocellular inability to detoxify
mass ammonia to urea (massive necrosis)
Serum bile acid Integrity of the enterohepatic High fasting or postprandial values compatible with
concentrations circulation, hepatic function and hepatocellular dysfunction, congenital PSS, or loss of
mass hepatic mass. Elevated in cholestasis independent of
hepatocellular dysfunction or shunting so rule this out
first
Coagulation profile Hepatocellular function, adequacy of Abnormal values may indicate marked hepatocellular
vitamin K absorption and stores dysfunction, acute or chronic DIC, complete EBDO
ALT, Alanine aminotransferase; AST, aspartate aminotransferase; AP, alkaline phosphatase; GGT, -gluramyltransferase; PU/PD, polyuria/
polydipsia; PSS, portosystemic shunting; PCV, packed cell volume; DIC, disseminated intravascular coagulation; EBDO, extrahepatic bile duct
obstruction.
trasting fat-filled falciform ligament (Fig. 36-3). In dog nographic contrast, this is the imaging modality of choice in
breeds with narrow, deep chests, the entire liver shadow may animals with ascites. Poor abdominal detail in emaciated or
be contained within the caudal rib cage. In dogs with wide, very young animals lacking abdominal fat stores also makes
shallow thoracic conformation, the liver may extend slightly detection of subtle hepatic changes difficult.
beyond the costal arch. In the ventrodorsal view the borders In cats and dogs with generalized hepatomegaly, the liver
of the liver are defined by the cranial duodenum and the extends beyond the costal arch; it causes displacement of the
gastric fundus; i n this view the gastric shadow is perpen gastric axis and pylorus caudally and dorsally in the lateral
dicular to the spine. This view is less useful for assessing liver projection and shifting of the gastric shadow caudally and
size unless it is markedly and asymmetrically enlarged. to the left i n the ventrodorsal view (see Fig 36-3). In addition,
Immature animals have a relatively larger liver than do the edges of the liver in the lateral view may appear rounded
adults. The gallbladder and extrahepatic biliary tree are not (see Fig. 36-3). Occasionally, the spleen and liver cannot be
visible separately radiographically i n healthy animals. differentiated when they are i n direct contact, as seen in the
Survey radiography is of minimal to no benefit if there is right lateral view. A ventrodorsal view would help to deter
moderate to marked abdominal effusion because the similar mine the size, shape, and position of each organ. Increased
radiographic opacities of the liver and fluid preclude distinc intrathoracic volume associated with deep inspiration, severe
tion of liver size and shape except by indirect assessment pleural effusion, or overinflation of the lungs may result in
(e.g., malposition of a gas-filled stomach and duodenum; Fig caudal displacement of the liver, giving the erroneous impres
36-4). However, because abdominal fluid increases ultraso sion of hepatomegaly using other radiographic criteria.
FIG 3 6 - 4
Lateral abdominal radiograph of an 8-year-old Bearded
Collie with chronic hepatitis, portal hypertension, and
ascites demonstrating the loss of abdominal detail associ
ated with free abdominal fluid, which renders radiography
unhelpful. (Radiograph courtesy the diagnostic imaging
department, The Queen's Veterinary School Hospital,
University of Cambridge.)
operative mesenteric portography, and operative splenopor hepatic portal vasculature. In addition, it has been shown
tography. The two operative procedures require general that the degree o f intrahepatic portal vessel opacification on
anesthesia and a small abdominal incision; however, little post-ligation portography is predictive for outcome (Lee
sophisticated equipment is needed, and the procedures are et al., 2006).
associated with few complications. A 22-gauge catheter is
placed in the splenic vein or a mesenteric vein (Fig. 36-6), ULTRASONOGRAPHY
and the resting portal venous pressure is measured with a A b d o m i n a l ultrasonagraphy (US) is the preferred diagnostic
water manometer ( N = 6 to 13 c m H O ) . Portal pressure is
2 modality for evaluating the hepatobiliary system in dogs and
measured as soon as possible in the procedure because pro cats. Operating on the principle that a pulse of sound (echo)
longed anesthesia may complicate its interpretation. A n can be reflected when it passes through the interface between
injection o f iodine-based contrast m e d i u m at a dose o f 0.5 two different materials, U S can detect differences between
to 1 m l / k g is then quickly made. Lateral and possibly ventro homogeneous liquids of low echogenicity, such as blood and
dorsal and oblique radiographs are made at the end o f the bile, and more heterogeneous echogenic structures made up
injection. Contrast m e d i u m given to a normal cat or dog of several soft tissues. Whereas abdominal effusion obscures
should flow into the portal vein, enter the liver, and branch abdominal detail on survey radiography, it enhances the
multiple times, opacifying the extrahepatic and intrahepatic ability o f U S to detect abnormalities (Fig. 36-8). However,
portal vasculature. Diversion o f the contrast m e d i u m into bone and gas-filled organs reflect the sound beam com
the systemic circulation indicates PSS (Fig. 36-7). Measure pletely (acoustic shadowing) so that structures beneath
ment o f portal pressure and a liver biopsy can be performed cannot be imaged by U S . The procedure does not require
during the operative techniques; they are required to distin anesthesia, but the patient must be still, and good contact
guish acquired PSS from congenital PSS, w h i c h is essential between the transducer and abdominal skin must be ensured
to rendering an accurate prognosis and developing the by clipping the hair coat and applying acoustic coupling gel.
correct treatment plan. As a general rule, cases o f congenital Animals are usually positioned in dorsal or lateral recum
PSS are usually single whereas acquired PSS are multiple, so bency. The hepatic parenchyma, gallbladder, large hepatic
the mesenteric portography may suggest a diagnosis. It may and portal veins, and adjacent caudal vena cava are all visible
be necessary to repeat the contrast study after congenital PSS i n the liver o f the normal cat and dog. Unlike plain radiog
ligation if there is concern about the adequacy o f the intra raphy, which requires two views to complete the study, US
FIG 36-6
A 22-gauge intravenous catheter attached to an extension
set, three-way stopcock, and water manometer has been
placed in a mesenteric vein in preparation for intraoperative FIG 36-7
measurement of resting portal pressure. The catheter may Operative mesenteric portal venography in a young
also be secured in place and used for operative portal domestic shorthaired cat before (A) and after (B) surgical
venography. correction (note improvement in hepatic portal blood flow in
B with arborization of the contrast material within the
small portal vessels in the liver). (Radiographs courtesy the
diagnostic imaging department, The Queen's Veterinary
School Hospital, University of Cambridge.)
makes many slices through several planes to create a three-
dimensional reconstruction o f the target structures.
Performing U S and interpreting the recorded images are
a blend of technical skill and experience. It is also important
to remember that U S is very sensitive to the presence o f
lesions but does not diagnose what the lesions are (i.e., it
cannot yield a histological diagnosis). W i t h a few exceptions,
which predominantly involve lesions o f the biliary tract and
vessels, the ultrasonographic appearance o f a variety o f both
benign and malignant hepatic lesions can appear very similar
and histology of a liver biopsy is usually required for diag
nosis. A n animal should never be euthanized on the basis of
an ultrasonographically identified "tumor" without histo
logical confirmation because benign nodular hyperplasia or
focal inflammatory lesions can look the same. Table 36-3
outlines the typical appearances o f different hepatic lesions
on ultrasonography.
FIG 36-8
Neoplasia may appear as hyperechoic or hypoechoic
Abdominal ultrasound is enhanced by the presence of
and focal or diffuse. Hepatic l y m p h o m a often appears
ascites. Ultrasound of the abdomen of a dog with chronic
diffusely hypoechoic but can also appear hyperechoic. hepatitis and ascites. (Image courtesy the diagnostic
Some tumors, such as metastatic hemangiosarcomas, have imaging department, The Queen's Veterinary School
a classically nodular hypoechoic appearance (Fig. 36-9). Hospital, University of Cambridge.)
Ultrasonographic Findings in Dogs and Cats with Hepatobiliary Diseases
Parenchyma
Anechogenicity
Focal Cyst(s) may be singular or multiple with septae; thin-walled
Abscess(es) may be poorly demarcated and have a
heterogeneous echo pattern
Hematoma(s) appearance depends on maturity
Lymphoma may look like cyst if solitary
Hypoechogenicity
Focal Focal or multifocal neoplasia
Regenerative nodule formation
Extramedullary hematopoiesis
Normal liver surrounded by hyperechoic liver
Hematoma(s)
Diffuse Abscess(es) or granuloma(s)
Neoplastic or inflammatory cell infiltrates
Passive congestion
Hepatocellular necrosis
Amyloid
Extramedullary hematopoiesis
Hyperechogenicity
Focal Focal or multifocal neoplasia
Nodular hyperplasia
Mineralization (creates shadowing artifact)
Fibrosis
Gas (creates reverberation artifact)
Hematoma or abscess
Diffuse Fatty infiltration (attenuates the sound beam)
Lymphoma
Fibrosis
Neoplastic or inflammatory cell infiltrates
Steroid hepatopathy (dogs only)
Continued
Ultrasonographic Findings i n Dogs and Cats with Hepatobiliary Diseasescont'd
FIG 36-10
FIG 36-9 Ultrasonographic appearance of dilated biliary tract in a
Ultrasonographic appearance of a hepatic hemangiosar cat with chronic cholangitis. (Image courtesy the diagnostic
coma in a dog. Note the multiple hypoechoic nodules. imaging department, The Queen's Veterinary School
(Image courtesy the diagnostic imaging department, Hospital, University of Cambridge.)
The Queen's Veterinary School Hospital, University of
Cambridge.)
PSSs are usually multiple. Use of Doppler color-flow imaging lection of emissions from decaying isotope using a gamma
confirms the location o f the suspicious vessel(s) and the camera focused over the animal's liver region and recorded
direction o f b l o o d flow within it. Doppler imaging can also o n radiographic film. The isotope has a short (6-hour) half-
provide supportive evidence o f intrahepatic portal hyperten life; thus, although the animal must be relatively isolated for
sion by allowing the assessment o f the speed and direction 24 to 48 hours and urinary and fecal waste stored until
of portal flow. Portal b l o o d flow toward the liver (hepatope radioactivity has fallen to background levels, there is minimal
tal) is normal; away from the liver (hepatofugal) is abnormal. radiation hazard to the animal or involved personnel. T o
9 9 m
Whether the lesion is determined to be focal or diffuse, U S distinguish medical from surgical causes of jaundice, Tc
can also be used as a guide to obtain diagnostic specimens is combined with disofenin (Hepatolite). After an intrave
for cytologic or histopathologic evaluation. U S has devel nous injection of radiopharmaceutical, scintigraphic images
oped into a valuable and critically important adjunct to are made sequentially over 3 hours to determine whether the
diagnosis o f hepatobiliary disease of cats and dogs by allow isotope has been taken up by the liver, excreted into the
ing characterization o f structural changes not possible by biliary tract, and expelled into the intestine. In cats and dogs
any other modality and by providing a way to obtain needle with E B D O , no evidence of radiopharmaceutical is detected
liver biopsy specimens and bile duct samples in a visualized i n the gallbladder or intestine.
manner without the need for general anesthesia. Another application o f scintigraphy is used in the diag
nosis o f PSS i n cats and dogs. Following placement of
SCINTIGRAPHY 9 9 m
pertechnetate labeled with T c into the descending colon,
Other imaging modalities, such as scintigraphy (nuclear the vascular path taken by the isotope after absorption is
imaging), magnetic resonance imaging, contrast-enhanced plotted. Time/activity curves determine whether the isotope
harmonic ultrasound, and computed tomography, are avail arrived in the liver first, which is normal, or in the heart and
able primarily through teaching or larger referral institu lungs, which is compatible with any k i n d o f portal venous
tions. O f these imaging modalities, scintigraphy has been bypass of the liver (Fig. 36-12). This approach has the advan
evaluated most thoroughly for diagnosis o f hepatobiliary tage o f specifically evaluating the portal blood supply rather
disease in cats and dogs. The isotope selected most often for than the hepatic mass, which may or may not be reduced in
99m
clinical use is technetium-99m ( T c ) , w h i c h is incorpo animals with congenital PSS or primary hepatobiliary disease
rated into the radiopharmaceutical specific for the planned and acquired PSS. The test results do not provide anatomic
9 9 m
study. For example, T c b o u n d to sulfur colloid, which is detail but only evidence o f the presence or absence of con
phagocytized by monocyte-macrophage cells of the liver and genital or acquired portosystemic shunting. Transcolonic
spleen, is given to assess liver mass. Images are made by col portal scintigraphy is most helpful in confirming the
BOX 36-2
Patient and Operator Considerations for Hepatic Biopsy
Patient
1. Characteristics of the suspected hepatobiliary disorder:
liver size (small, normal, enlarged); texture (fibrotic or
friable); focal, multifocal, or diffuse distribution; pres
ence of abdominal effusion
2. Clinical stability and suitability for anesthesia
3. Coagulation status and platelet count
Operator
1. Available equipment
2. Experience with chosen technique
3. Complication rate for chosen technique
4. Size of specimen needed
5. Access to reliable veterinary pathology laboratory
FIG 36-12
Transcolonic scintigraphy demonstrating the portal vascular
path to the liver. A , Normal dog with isotope following a
direct path to the liver and a small (5%) shunt fraction.
B, Abnormal arrival of isotope in the heart and lungs of 1-
year-old male Miniature Schnauzer with congenital portosys
temic shunt and large (84%) shunt fraction. In each scan
image the dog's head is to the right. (Courtesy Dr. Lisa J.
FIG 36-13
Forrest, North Carolina State University, College of Veteri
nary Medicine.) A 4-year-old spayed female domestic short-haired cat with
suspected hepatic lipidosis positioned in right lateral
recumbency for blind fine-needle aspirate for cytology. With
care taken to avoid the spleen, the needle is directed
presence of a congenital PSS i n a cat or dog with atypical craniomedially into the liver.
clinicopathologic test results, equivocal abdominal ultra
sound findings (e.g., normal-size liver, no identifiable vessel
arising from the portal vein), and no evidence of portal
hypertension (e.g., ascites). cause; (3) determine hepatic involvement i n systemic illness
(although biopsy is not always necessary for this); (4) stage
neoplastic disease; (5) objectively assess response to therapy;
LIVER BIOPSY or (6) evaluate progress of previously diagnosed, not spe
cifically treatable disease. Percutaneous hepatic biopsy is not
General Considerations performed if there is a good chance that the disease can
For many primary hepatobiliary diseases of cats and dogs, a be corrected surgically, such as i n some cases of E B D O or
hepatic biopsy is needed to establish a final diagnosis and congenital PSS; instead, a specimen is obtained at the time
prognosis. In some cases bile culture is also imperative. of surgery to complete the diagnostic evaluation. Several
Biopsy is indicated to (1) explain abnormal results of hepatic approaches are available; choice is dictated by patient and
status and/or function tests, especially i f they persist for operator considerations (Box 36-2). In addition, i n most
longer than 1 month; (2) explain hepatomegaly of u n k n o w n cases of hepatic disease the accuracy of histological diagno-
sis is better with larger (i.e., surgical or laparoscopic) rather to interpret are often the result (Fig. 36-14). There is less than
than smaller (i.e., needle) biopsies. a 40% correlation between 18-gauge needle biopsy and
A l l cats and dogs undergoing hepatic biopsy are fasted for wedge biopsy for certain hepatobiliary diseases (i.e., chronic
at least 12 hours, regardless o f the approach selected. In hepatitis/cirrhosis, cholangitis, portovascular anomaly,
general, percutaneous needle core biopsy or aspiration (for fibrosis). If a needle technique is selected, the largest avail
cytologic analysis) o f a single cavitary or solid lesion highly able instrument is used (preferably 14 gauge; m i n i m u m 16
likely to be n o n l y m p h o i d cancer should be avoided unless gauge) and multiple samples are taken to ensure samples
the owner is unwilling to permit surgery for complete resec adequate for examination.
tion. Fine-needle aspiration o f the liver for cytologic analysis The animal's coagulation status is determined before a
is rarely advisable because o f l o w diagnostic yield and often liver biopsy is performed, regardless of the approach. Ideally,
misleading results. The exceptions to this are for quick diag a complete coagulation profile (one-stage prothrombin time
nosis of hepatic lipidosis i n cats and possibly for suspected [OSPT], A P T T , fibrin degradation products, fibrinogen
hepatic l y m p h o m a , although even then the diagnosis may content, platelet count) is obtained; a platelet count and an
need to be confirmed histologically (Fig. 36-13). However, activated clotting time or whole b l o o d clotting time i n a glass
an overall correlation o f only 30% i n dog and 51% i n cats tube, as a screening test of the intrinsic coagulation cascade,
was found i n one study comparing the cytologic diagnosis are also acceptable. Bleeding after ultrasound-guided biopsy
with the histopathologic diagnosis o f a variety o f liver dis is more likely i f the platelet count is less than 80,000 cells/l
eases (Wang et al., 2004). or i f the O S P T (dogs) or A P T T (cats) is prolonged (Bigge
In an especially small and/or firm fibrotic liver, it is dif et al., 2001). If possible, v o n Willebrand's factor is measured
ficult to obtain a biopsy specimen by percutaneous needle i n susceptible breeds i n advance of biopsy because results
methods; small, fragmented specimens that are challenging of standard coagulation tests are usually normal in affected
FIG 36-14
A , Liver specimen obtained percutaneously (with ultrasound guidance) from a dog with
hepatic fibrosis and nodular regeneration (B). The specimen was difficult to obtain
because the liver was firm and rubbery in texture. C, The resultant sample was difficult to
interpret histologically.
dogs. A buccal mucosa bleeding time test provides indirect needle requires two hands to operate and relies on the tissue
assessment of platelet function (see Chapter 87). In dogs falling into the specimen trough and then being severed by
with von Willebrand's disease, desmopressin acetate the sharp outer cannula (Fig. 36-15). One-handed operat
( D D A V P ) is given (1 g/kg intranasal preparation subcuta able semi-automatic (e.g., Tenmo Evolution biopsy needle,
neously) before surgery to enhance shift of von Willebrand's Cardinal Health; V E T - c o r e biopsy needle, Global Veterinary
factor activity from endothelial cells to the plasma. Products Inc) and automatic (e.g., P r o - M a g Ultra Automatic
M i l d abnormalities i n coagulation test results do not pre biopsy instrument, M a n a n Medical Products; Bard Biopty
clude liver biopsy. In fact, results of routine coagulation tests biopsy instrument and Bard Biopty-Cut biopsy needle, Bard
may not correlate with liver bleeding times, as was found i n Inc) versions of this instrument are also available. These
one study of human patients. Liver biopsy should be delayed biopsy needles are intended for single use. Either the auto
if there is clinical evidence of bleeding or marked abnor matic biopsy instrument or the semi-automatic biopsy
malities in results of coagulation tests. Because animals with needle device can be used to obtain liver biopsies in dogs,
complete E B D O may be vitamin K deficient (manifested by but only the semi-automatic biopsy needle device should be
prolongation of both O S P T and A P T T ) , treatment with used i n cats. A recent study identified a high risk of fatal
vitamin K1 (0.5 to 1.0 mg/kg [maximum of 10 mg] subcuta complications (i.e., unexpected fatal shock reaction) when
neously q l 2 h for 3 treatments) is indicated for 1 or 2 days an automatic biopsy instrument was used to obtain liver
before surgery. V i t a m i n K supplementation can also improve biopsies i n cats (Proot and Rothuizen, 2006).
coagulation times i n animals with other liver disease, par Biopsy can be done of any palpably enlarged lobe as long
ticularly cats. Repeating the O S P T and A P T T within 24 as care is taken to angle the needle to avoid puncturing the
hours after administration of vitamin K1 should demon gallbladder. M o s t often, the animal is placed i n right lateral
strate normal or near-normal values. If not, the dose can be recumbency for this purpose and biopsy of the left lateral
adjusted and the procedure delayed. Although it may not lobe is done. Elevating the head and thorax slightly may
seem rational to give vitamin K1 to animals with severe assist in "presenting" the liver to the operator. T w o or three
parenchymal hepatic disease before surgery, it has been of complete core specimens are obtained; if indicated, one core
benefit to some animals and, i f given properly, can do no specimen is placed i n a sterile container for culture and
harm. These animals may have high serum activity of pro sensitivity testing. Gently rolling a specimen on a slide for
teins induced by vitamin K antagonism ( P I V K A ) that could cytologic assessment is a good way to attempt to identify
impart bleeding tendencies. If there has been m i n i m a l the disease process quickly and inexpensively. Each of the
improvement in coagulation test results after vitamin K has 1 remaining core specimens is placed on a piece of stiff paper
been administered, fresh frozen plasma is administered (e.g., filter paper) i n correct orientation (Fig. 36-16) before
before biopsy. If bleeding is excessive during or after biopsy immersion i n fixative for histologic examination and/or
and cannot be controlled locally with direct pressure special testing.
or application of clot-promoting substances, fresh whole After biopsy, a small bandage is applied to keep the site
blood or plasma is given (see Chapter 83 for transfusion clean during recovery, and the animal is placed i n a position
guidelines). to allow body weight to compress the region of the biopsy
sites in the liver (e.g., left lateral recumbency). Consideration
Techniques should be given to postoperative analgesia; puncture of the
Information gathered before biopsy must support the fact liver capsule can be painful. The animal should be monitored
that the likelihood of acquiring a diagnostic sample without carefully for any evidence of hemorrhage for several hours
complications is high. A specimen procured from any area after the procedure. As long as the biopsy procedure pro
of the liver is considered representative of the disease. Because ceeded smoothly and without unpleasant surprises (animal
only a small stab incision large enough to accommodate the awake and struggling), only basic monitoring of mucous
biopsy needle is needed (a N o . 11 blade is the perfect choice membrane color and the skin puncture site is needed. N a t u
for this purpose), healing i n hypoalbuminemic animals is rally, i f excessive hemorrhage or damage to other organs
not compromised. If the operator is confident with the occurs with this b l i n d technique, detection and treatment
biopsy procedure, there is little time involved and only heavy may be delayed.
sedation is required. If the results are nondiagnostic, a larger Visualized percutaneous needle biopsy, with the aid of
specimen is obtained for histopathologic examination, either U S (Fig. 36-17) or modified laparoscopic equipment
usually by laparoscopy or laparotomy. (Fig. 36-18), allows selection of the site(s) and direct or
Biopsy can be performed blindly i f the cat or dog has indirect inspection after the biopsy. W h e n the procedure is
generalized hepatomegaly and the operator is confident of properly performed, serious complications are few. In an
the path of the needle. The most c o m m o n needle biopsy animal in which diffuse or multifocal hepatobiliary disease
instruments are the T r u - C u t (Cardinal Health) and Jamshidi is suspected, multiple biopsy specimens are obtained safely.
Menghini (Cardinal Health; K o r m e d Inc.) needles. The General anesthesia is usually required for use of a modified
Jamshidi Menghini biopsy needles can be operated with one laparoscope. Aspiration of the gallbladder for cytologic anal
hand, and aspiration is used to sever and contain the speci ysis and culture can be accomplished with U S guidance or
men within the barrel of a 6- or 12-ml syringe. The T r u - C u t by laparoscopy. Bile leakage may occur, even if a small-gauge
FIG 36-15
A , Tru-Cut biopsy needle with the specimen trough exposed (left) and then covered by the
sharp outer cannula (right). B, Liver tissue filling the specimen trough (between arrows).
FIG 36-16
FIG 36-17
Needle biopsy specimen affixed to a stiff piece of paper to
Biopsy gun instrument with accompanying biopsy needle
preserve orientation of the sample during formalin fixation
used for obtaining liver specimens with ultrasonographic
for histopathologic examination.
guidance.
needle is used, so attempts are made to completely evacuate
the gallbladder, and the needle should be placed i n the
gallbladder through the liver parenchyma to help prevent
leakage. Some surgeons prefer to obtain bile during lapa
rotomy when a purse-string suture can be applied to the
aspiration site to prevent seepage. Large-volume abdominal
effusion hinders direct inspection of the liver and associated
structures and must be removed before laparoscopic biopsy
is attempted.
A n operative approach (laparoscopy [Fig. 36-19], lapa
rotomy) is preferred for liver biopsy i f the liver is small, U S
equipment is not available, or the operator is not experi
enced with the aforementioned percutaneous needle
methods. Laparotomy is perfectly acceptable for dogs and
cats that are good anesthetic risks and allows thorough
examination of the liver, biliary tract, and portal vein as well
as other abdominal structures, such as l y m p h nodes. Bile can
be acquired easily and safely. The procedure is more pro
longed, and healing complications may arise i n severely
hypoalbuminemic animals, notably those with intractable
ascites, but larger samples for histopathologic examination
and special staining techniques are obtainable (Fig. 36-20)
and hemorrhage can be arrested directly. Use of nonabsorb
able suture material and small cranial or flank incisions may
lessen incision complications. Obviously, this is the approach
of choice for surgically correctable diseases; a liver biopsy
specimen is obtained concurrently.
As for the percutaneous biopsy techniques, liver and/or
bile specimens for microbiologic culture are aseptically pro
cessed first. Impression smears for cytologic analysis are then
made by gently touching the specimen to a slide before
placing it in fixative. Excess blood is removed by blotting the
sample o n gauze before slides are made. A b n o r m a l popula
tions of cells (e.g., mast cells, lymphoblasts) are readily
detectable using rapid stain systems such as D i f f Q u i k
(Harleco, Gibbstown, N.J.). For routine processing and his
topathologic examination, liver tissue specimens are sub
merged in buffered 10% formalin at a ratio of at least 10
parts formalin to 1 part tissue. Samples for copper histo
chemical staining or tissue quantification are harvested and
fixed or preserved according to the specifications of the
pathology laboratory selected to do the assays. Other special
FIG 36-18
Modified laparoscopic approach for liver biopsy. stains for infectious agents or fibrous tissue, amyloid, glyco
A , Readily available materials needed for the procedure. gen, and other metabolic products are available, and their
B, A Tru-Cut biopsy needle is used for obtaining liver use is discussed with the attending pathologist before the
specimens. C, The liver is first inspected, and then the tissue specimen is obtained. A portion of the specimen can
needle is passed through a sterile otoscope cone into the be frozen for molecular studies (e.g., P C R for organisms or
liver for tissue sampling. See Bunch et a l . (1985) in
tumor clonality).
Suggested Readings for further details on this procedure.
FIG 36-19
A , Laparoscopic liver biopsy. B, Tip of the biopsy instrument that is passed through one
of the preplaced cannulas. C , Intraabdominal view of a dog with chronic hepatic disease
and portal hypertension. Note the prominent, tortuous omental veins.
FIG 36-20
Comparison of liver specimens obtained by different methods and mounted on glass
slides. These samples are adequate for histopathologic examination: percutaneous needle
sample (left); samples obtained intraoperatively by use of an 8-mm skin biopsy punch
(middle) or removal of a wedge specimen (right).
Suggested Readings Koblik PD et al: Transcolonic sodium pertechnetate Tc 99m scin
Balkman CE et al: Evaluation of urine sulfated and nonsulfated bile tigraphy for diagnosis of macrovascular portosystemic shunts in
acids as a diagnostic test for liver disease in dogs, / Am Vet Med dogs, cats, and pot-bellied pigs: 176 cases (1988-1992), J Am Vet
Assoc 222:1368, 2003. Med Assoc 207:729, 1995.
Bexfield NJ et al: Diagnosis of canine liver disease, In Practice Lawler DF et al: Benign familial hyperphosphatasemia in Siberian
28:444, 2006. Huskies, Am J Vet Res 57:612, 1996.
Bigge LA et al: Correlation between coagulation profile findings Lee K C et al: Association of portovenographic findings with
and bleeding complications after ultrasound-guided biopsies: outcome in dogs receiving surgical treatment for single con
434 cases (1993-1996), J Am Anim Hosp Assoc 37:228, 2001. genital portosystemic shunts: 45 cases (2000-2004), J Am Vet Med
Bunch SE et al: A modified laparoscopic approach for liver biopsy Assoc 229:1122, 2006.
in dogs, J Am Vet Med Assoc 187:1032, 1985. Liptak I M : Hepatobiliary tumors. In Withrow SJ, Vail D M , editors:
Clifford C A et al: Magnetic resonance imaging of focal splenic Withrow and MacEwen's small animal clinical oncology, ed 4, St
and hepatic lesions in the dog, / Vet Intern Med 18:330, Louis, 2007, Saunders Elsevier.
2004. Milller PB et al: Effects of long-term phenobarbital treatment on
Cole T et al: Diagnostic comparison of needle biopsy and wedge the liver in dogs, / Vet Intern Med 14:165, 2000.
biopsy specimens of the liver in dogs and cats, / Am Vet Med O'Brien RT: Improved detection of metastatic hepatic hemangio-
Assoc 220:1483, 2002. sarcome nodules with contrast ultrasound in three dogs, Vet
Gallagher AE et al: Hyperphosphatasemia in Scottish Terriers: 7 Radiol Ultrasound 48:146, 2007.
cases, / Vet Intern Med 20:418, 2006. Proot SJ, Rothuizen J: High complication rate of an automatic Tru-
Gaskill CL et al: Serum alkaline phosphatase isoenzyme profiles in Cut biopsy gun device for liver biopsy in cats, / Vet Intern Med
phenobarbital-treated epileptic dogs, Vet Clin Pathol 33:215, 20:1327, 2006.
2004. Sevelius et al: Serum protein electrophoresis as a prognostic marker
Gerritzen-Bruning MJ et al: Diagnostic value of fasting plasma of chronic liver disease in dogs, Vet Rec 137:663, 1995.
ammonia and bile acid concentrations in the identification Toulza O et al: Evaluation of plasma protein C activity for detection
of portosystemic shunting in dogs, / Vet Intern Med 20:13, of hepatobiliary disease and portosystemic shunting in dogs,
2006. J Am Vet Med Assoc 229:1761, 2006.
Hall EJ et al: Laboratory evaluation of hepatic disease. In Villiers E, Trainor D et al: Urine sulfated and nonsulfated bile acids as a diag
Blackwood L, editors: BSAVA manual of canine and feline clinical nostic test for liver disease in cats, / Vet Intern Med 17:145,
pathology, ed 2, Gloucestershire, United Kingdom, 2005, British 2003.
Small Animal Veterinary Association. Walker M C et al: Postprandial venous ammonia concentrations in
Head LL, Daniel GB: Correlation between hepatobiliary scintigra the diagnosis of hepatobiliary disease in dogs, / Vet Intern Med
phy and surgery or postmortem examination findings in dogs 15:463, 2001.
and cats with extrahepatic biliary obstruction, partial obstruc Wang KY, Panciera DL, Al-Rukibat RK, Radi ZA: Accuracy of ultra
tion, and patency of the biliary system: 18 cases (1995-2004), sound-guided fine-needle aspiration of the liver and cytologic
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C H A P T E R 37
Hepatobiliary Diseases in
the Cat
FIG 37-1
Anatomic relationship between pancreas, common bile duct, and duodenum in the cat.
(From Strombeck DR: Small animal gastroenterology, Davis, Calif, 1 9 7 9 , Stonegate
Publishing.)
Important Differences Between Cats and Dogs with Hepatobiliary Disease
Treat any identifiable underlying cause as effectively as such as taurine, arginine, B vitamins, or carnitine to
possible, but also concurrently start other treatment: Do the tube feed, but there is no firm evidence that any
not rely on treating the cause alone to resolve the disease of these are necessary if a balanced feline diet is used.
in secondary cases; in most cases the anorexia will persist Amount to feed: start conservatively with the resting
unless active measures are taken to feed the cat. energy requirement (RER) because cats have had
Institute fluid therapy and nutritional support as soon as prolonged anorexia and complications of feeding are
possible. more common in the first few days. Start with small
Fluid therapy: Intravenous fluid support is necessary in amounts frequently (or even slow-rate constant infusion)
the early stages of therapy (maintenance rates + and gradually build up to higher volumes and lower
replacement for any fluid lost, e.g., in vomiting). frequency over the first week. The calorie intake can
Measure and replace any electrolyte deficits, particu then be gradually increased to the metabolic energy
larly potassium and phosphate. Carefully monitor requirement (MER).
blood glucose and electrolytes, particularly potassium
and phosphate, which may become low during treat RER = 5 0 x B W
ment. Normal saline with added potassium chloride MER = 70 x B W
as necessary is the most useful fluid. Dextrose is Appetite stimulants are not recommended because
avoided because it may worsen hyperglycaemia and they are of very limited efficacy and potentially
lactated Ringer's may be contraindicated with marked hepatotoxic.
hepatocellular dysfunction because the lactate may not Additional vitamins are necessary in some cats: cobal
be metabolized to bicarbonate. There is N O evidence amin (vitamin B ) may be deficient, particularly in cats
12
that adding insulin to the fluids helps; in fact, it with concurrent pancreatic a n d / o r ileal disease (see
increases the risk of serious hypokalaemia and hypo Chapter 40) and should then be supplemented paren
phosphatemia. After the first few days, fluid and elec terally. Vitamin K-responsive coagulopathies are very
trolyte needs can be supplied via the feeding tube. common in cats with lipidosis, and some authors rec
Nutritional support should be instituted as soon as ommend supplementation in all cats at the start of
possible. A nasoesophageal tube can be used for treatment with 0.5 m g / k g given intramuscularly q12h
temporary support for the first few days before general for three doses.
anesthetic for more permanent tube placement. A gas Antiemetics and promotility agents such as ranitidine
trostomy or esophagostomy tube will usually be (2 m g / k g P O or IV twice a day) and metoclopramide
required long term because feeding will be necessary (0.5 mg/kg IM or P O q8h or 1 to 2 m g / k g q24h IV as
in most cases for 4 to 6 weeks. A diet that is as high a slow infusion) may be necessary if the cat is vomiting
in protein as possible should be given, preferably or has delayed gastric empting with reflux of food up the
managing any resultant encephalopathy by other feeding tube.
means such as feeding little and often. This means Antioxidants are also recommended, particularly S-ade
using a diet manufactured for nutritional support of nosylmethionine (20 mg/kg or 2 0 0 mg total once a day)
hypermetabolic sick cats if possible. A diet such as on the basis of some limited but supportive evidence in
Royal-Canin concentration instant diet or Hill's A D cats. There is currently no evidence in support of the use
would be suitable. Some clinicians add extra nutrients of ursodeoyxcholic acid in cats with lipidosis.
should be used if necessary. M a n y cats require vitamin K instituted. Studies have reported between 55% and 80% sur
therapy for coagulopathies [0.5 mg/kg of vitamin K1 (Phy vival i n intensively fed cats, whereas mortality is very high
tomenadione) subcutaneously or intramuscularly q l 2 h for without supportive feeding. One large study (Center et a l ,
3 days]; clinicians should not place any central catheters or 1993) suggested that anemia, hypokalemia, and older age
invasive feeding tubes until hemostasis is normal. There is were poor prognostic indicators for survival and that cats
the potential for serious and undetected bleeding around with secondary hepatic lipidosis may do slightly worse than
a central venous catheter in a cat with a coagulopathy. those with primary disease. However, the differences were
Antioxidant therapy is also indicated i n cats with lipidosis not significant, which suggests that it is well worth treating
because of the associated glutathione depletion i n many cats; cats with secondary lipidosis as aggressively as those with
vitamin E and S-adenosylmethione supplementation should primary disease.
be considered. (S-adenosylmethionine: 20 mg/kg once a day
given whole on an empty stomach, cats and dogs, or 100- to
400-mg total dose daily i n cats. The ideal dose of vitamin E BILIARY TRACT DISEASE
in a cat is unclear, but the authors use 100 I U daily.)
Prognosis for recovery i n cats with hepatic lipidosis is Biliary tract diseases are the second most c o m m o n disorders
reasonably good as long as feeding is rapidly and effectively of the feline liver (see Table 37-1). This contrasts with dogs,
BOX 37-2
Outline of Method of Placement of Feeding Tubes
Nasoesophageal Tube
5. Suture stomach to abdominal wall using simple inter
For short-term nutritional support (<1 week) while stabilizing rupted pattern; you may wrap omentum around tube
cat before placement of esophagostomy or gastrostomy tube. between stomach and body wall.
6. Exit catheter through separate stab incision, and secure
Placement
to skin.
1. Premeasure tube to allow placement in caudal esopha 7. Plug to stop air from filling stomach and food from leaking
gus, not stomach; this minimizes gastric reflux. Premea out, and cover with a dressing/body bandage. Put on
sure to seventh intercostal (IC) space from nose or 7 5 % an elizabethan collar.
of distance from nose to last rib if animal is so obese that 8. Clean stoma regularly, and flush tube regularly with
ribs cannot be counted. (Orogastric: ninth IC space or warm water, even when not in use.
9 0 % of distance nose to last rib.) Mark tube with pen or
piece of tape. Placement endoscopically
2. Apply local anesthetic to nose. M i l d sedation may also This is quicker and less invasive if you are not already doing
be necessary, preferably with buprenorphine or butor a laparotomy, but it is necessary to use a fiberoptic endo
phanol, but often not. scope. (However, it is possible to use gastrostomy introducers
3. Lubricate tube and advance into ventral meatus; it is and do it blind, although there is a higher incidence of
important not to advance into middle or dorsal meatus or traumatic injuries with inexperienced operators, who can
stops at the ethmoturbinates. It may be helpful to raise easily push the tube through visceral surface of stomach and
cat's head slightly to do this. damage or entrap the spleen. It is best to insufflate stomach
4 . Hold cat's head normally as you approach pharynx to first if doing it blind and attempt it only if taught by an exper
prevent tracheal intubation. Allow cat to swallow, and ienced operator and practiced on cadavers first.) Several
advance tube to measured mark or tape. companies make PEG tube kits suitable for veterinary use.
5 . To check that the tube is correctly positioned, instill water 1. Clip and aseptically prepare an area of skin caudal to
and then air and auscultate over left flank for bubbling left costal arch.
in stomach. If still uncertain, perform a radiograph. If tube 2. Pass endoscope through mouth into stomach and inflate
does not have a radiodense line, inject some ionic con stomach.
trast material into tube first. 3. Insert catheter into stomach through stab incision in
6. Pass tube over top of cat's head, and suture or glue tapes shaved area of body wall.
at level of nares and top of head; be careful to avoid 4. Remove stylet, and pass thick nylon suture through
interfering with cat's whiskers. catheter.
7. Put on elizabethan collar. 5. G r a b suture with biopsy instrument of endoscope, and
pull it out of mouth.
8. Flush regularly with warm water before and after feeds.
6. Attach suture to feeding tube as directed by manufac
Gastrostomy Tube turer.
Indicated for longer-term nutritional support (>l-2 weeks). 7. Pull the whole assembly back into the stomach by gentle
The tube must be in at least 5 to 7 days for surgical tubes traction on the nylon where it exits the body wall.
and 14 to 21 days for endoscopically placed tubes to allow 8. Pull the feeding tube out through the body wall, and
adhesions to form between stomach and body wall. secure it with a second stent outside and sutures.
Advantages over nasoesophageal tube of longer-term 9. C a p and cover as directed by manufacturer, and place
support: can feed thicker food; better tolerated by animal, an elizabethan collar to prevent interference.
which is more likely to start eating with tube in place; easier 10. Clean stoma regularly, and flush tube regularly with
to manage; could be managed by owner at home. However, warm water, even when not in use.
it is necessary to use a general anaesthetic for placement. Note on gastrostomy tube removal: Do not remove for at
least 5 to 7 days (surgical) or 14 to 21 days (PEG tubes).
Placement at laparotomy Method of removal depends on tube placed. Always refer
Placement is usually via a left paracostal laparotomy but can to the manufacturer's instructions, and do not attempt simply
be via midline laparotomy. to pull the tube out. Most manufactured tube kits for human
1. Pull stomach to body wall and exteriorize. Pack off area use cannot be pulled out but have to be cut close to the body
between stomach and body wall. wall and the end retrieved from the stomach endoscopically.
2. Lay two concentric purse-string sutures in greater curva (The end can be left to pass through into the feces in medium-
ture of body or fundus of stomach, and incise in center to large-breed dogs but not cats, in which it may act as a
of these. pyloric foreign body.) The Pezzar mushroom-tipped catheters
3. Insert feeding tube or catheter; it is best to use a Pezzar placed surgically can be removed completely by using a
mushroom-tipped catheter and not a foley because the stylet in the tube to flatten out the mushroom.
latter show a propensity to disintegrate too early. Experience with a trained operator is highly recom
4. Tighten purse strings; they should be tight enough to seal mended before attempting surgical placement of a gastros
but not so tight that they cause necrosis of gastric wall. tomy tube or blind placement of a gastrostomy tube.
The nomenclature of biliary tract disease has recently
been standardized by the W o r l d Small A n i m a l Veterinary
Association ( W S A V A ) ; its recommended categorizations of
disease will be used here (Rothuizen et al., 2006; Table 37-3).
A wide variety of alternative names have been used i n the
literature, sometimes blurring the categories and confusing
comparisons between studies. It is to be hoped that a stan
dardized nomenclature will aid i n the search for causes and
treatment of these diseases.
A l l disorders of the biliary tract i n cats can present with
very similar clinical signs, including lethargy, anorexia, and
jaundice. Clinical, clinicopathologic, and diagnostic imaging
findings do not allow differentiation of the types of disease;
in most cases, cytology, culture of bile, and histopathology
of the liver are necessary for accurate diagnosis and most
effective treatment.
CHOLANGITIS
Cholangitis refers to inflammation of the biliary tract, which
in some (but not all) cats may also extend to the surround
ing hepatic parenchyma. It is more c o m m o n in cats than i n
FIG 37-4 dogs, and it is typically divided into three categories, likely
Nasoesophageal tube in place in a cat being fed a liquid associated with different etiologies: neutrophilic cholangitis,
enteral diet. lymphocytic cholangitis, and chronic cholangitis associated
with liver fluke infestation.
Neutrophilic Cholangitis
Neutrophilic cholangitis is also k n o w n as suppurative chol
angitis, exudative cholangitis/cholangiohepatitis, and acute
cholangitis/cholangiohepatitis.
Neutrophilic Suppurative or exudative Likely Acute phase: neutrophils in lumen Cytology and culture of
cholangitis cholangitis/ ascending a n d / o r epithelium of bile ducts. bile aspirates are
cholangiohepatitis bacterial M a y also be edema and necessary for diagnosis.
Chronic phase: some infection neutrophils in periportal area, Ultrasound and
previously reported from small parenchyma, and occasionally histopathology can be
cases of "lymphocytic" intestine hepatic abscess. suggestive but are not
or "chronic" Chronic phase: mixed obligatory, and changes
cholangiohepatitis inflammatory infiltrate in portal may be absent on either
would now fall into this areas, including neutrophils, of these.
category. lymphocytes, plasma cells, and
sometimes some fibrosis and
bile duct proliferation
Lymphocytic Lymphocytic Unknown Infiltration of small lymphocytes Liver histopathology is
cholangitis cholangiohepatitis; may be into the portal regions. Variable necessary for diagnosis.
lymphocytic portal immune- portal fibrosis and bile duct Changes may be found on
hepatitis; chronic mediated proliferation. Lymphocytes may ultrasound and bile
cholangiohepatitis; disease also be present within biliary cytology but will not give
nonsuppurative epithelium. Occasional plasma a definitive diagnosis.
cholangitis: but note cells and eosinophils may be
overlap of these seen. Difficult to differentiate
definitions with the some cases from well-
chronic phase of differentiated lymphoma.
neutrophilic cholangitis
Chronic Liver fluke Dilated larger bile ducts with Ultrasonography of dilated
cholangitis papillary projections and bile ducts + history of
associated marked periductal and portal possible exposure +
with liver fibrosis. Slight to moderate demonstration of fluke
fluke inflammation of portal areas eggs in feces or bile
and ducts with neutrophils and aspirates (see text).
macrophages and limited Histopathology
numbers of eosinophils. Flukes supportive.
and eggs may be seen in ducts.
Data from Rothuizen J et al: WSAVA standards for clinical and histological diagnosis of canine and feline liver diseases, Oxford, UK, 2 0 0 6 ,
Saunders ttd, Elsevier.
Cats typically have signs of biliary stasis and sepsis with A n accurate diagnosis of neutrophilic cholangitis caused
lethargy, pyrexia, and jaundice. by acute ascending infection requires cytology and culture
of bile. Histopathology of the liver alone is not enough i n
Diagnosis this particular disease because i n many cases the disease is
Clinicopathologic and imaging findings show overlap with confined to the biliary tract, and changes on liver pathology
the other diseases of the biliary tract, so a definitive diagno are m i l d and nonspecific. Samples of bile for bacterial culture
sis of neutrophilic cholangitis cannot be made simply from can be taken carefully from the gallbladder during laparot
a characteristic history and clinicopathologic findings. omy or laparoscopy or under ultrasonographic guidance.
However, cats with this acute disease tend to have higher There is a small but definite risk of bile leakage, particularly
segmented and band neutrophil counts, A L T activities, if the gallbladder wall is devitalized and/or there is increased
and total bilirubin concentrations than cats with l y m p h o pressure within it. In these cases it might be safer to obtain
cytic cholangitis. They may have a coarse or nodular texture a sample at laparotomy rather than under ultrasonographic
to the liver on ultrasonography and may develop dilated guidance. In the latter case a general anesthetic is strongly
biliary tracts more chronically, but cats with the truly recommended to prevent patient movement while the needle
acute disease may have no dilation of the biliary tract o n is i n the gallbladder, which greatly increases the risk of bile
ultrasonography. leakage. The needle should be placed i n the gallbladder
Pathogenesis and Etiology
Lymphocytic cholangitis is a slowly progressive chronic
disease characterized by infiltration of the portal areas of the
liver with small lymphocytes. Occasionally, plasma cells and
eosinophils may also be seen. There is often associated pro
liferation of bile ducts, and there may be portal fibrosis. It
particularly affects the larger bile ducts, which may become
irregularly distended with thickened walls but usually remain
patent. In severe cases the m a i n differential diagnosis o n
histology is lymphoma. The cause is u n k n o w n . A n immune-
mediated etiology has been suggested by some researchers,
but the disease does not resolve with immunosuppressive
medication. Other studies have suggested possible infectious
etiologies, such as Helicobacter spp.,or Bartonella spp. ( B o o m -
kens et a l , 2004; Greiter-Wilke et al., 2006; Kordick et al.,
1999), although more evidence is required before infectious
organisms are confirmed as a cause. However, the use of
immunosuppressive medication in these cases is subject to
FIG 37-6
Photomicrograph of liver specimen from a cat with neutro question.
philic cholangitis. Notice the neutrophilic inflammation in
and around bile ducts (large arrow). Biliary ductular Clinical Features
hyperplasia is also present (small arrow) (hematoxylin-eosin
Cats with lymphocytic cholangitis are typically young to
stain).
middle-aged, and Persians appear to be overrepresented.
They tend to have a long history (months to years) of waxing
and waning low-grade illness. M a n y become jaundiced, and
through the hepatic parenchyma further to reduce the risk they often lose weight and have intermittent anorexia and
of leakage. The cat should be monitored carefully for any lethargy, but they are less likely to be pyrexic than cats with
leakage of bile after the procedure; any suspicion of leakage neutrophilic cholangitis. About a third of cats may also present
and bile peritonitis warrants surgery. Cytology of bile usually with a high-protein ascites, reportedly most c o m m o n l y i n
shows bacteria and neutrophils, and culture and sensitivity the United K i n g d o m . This makes differentiation from feline
tests should be performed. infectious peritonitis (FIP) important. Ultimately, the differ
entiation i n these cats can be made only on histopathology.
Treatment and Prognosis
Cats should be treated for 4 to 6 weeks with an appropriate Diagnosis
antibiotic on the basis of the results of culture and sensitiv Diagnosis in these cases relies ultimately on hepatic histopa
ity tests. Amoxycillin is a good initial choice at a dose of thology, although ultrasonographic and clincopathologic
15-20 mg/kg, P O q8h. Ursodeoxycholic acid may be given as findings can support a presumptive clinical diagnosis.
an additional choleretic and antiinflammatory agent at a Increases i n liver enzyme activities are m i l d to moderate and
dose of 15 mg/kg, P O q24h, although there are no studies tend to be less marked than i n cats with neutrophilic chol
demonstrating their benefit in cats. Septic or extremely sick angitis. Peripheral blood neutrophilia is less c o m m o n than
cats may require hospitalization for intravenous (IV) fluid in cats with the acute disease but may be present. A particu
and IV antibiotic administration during the initial stages of lar feature of most cats with lymphocytic cholangitis is an
therapy. Careful attention should be paid to feeding anorexic increase in -globulin concentration, which again may cause
cats to prevent the concurrent development of hepatic l i p i confusion with FIP. Radiographic signs are nonspecific:
dosis; a high-protein diet designed for critical care use, as There may be hepatomegaly (which is often due to enlarge
outlined in the lipidosis section, would be m u c h more appro ment of the larger bile ducts) and i n some cases ascites (Fig.
priate in these animals than a protein-restricted liver diet. The 37-7). Ultrasonography is more helpful and reveals dilation
prognosis is generally good, and these cats usually recover of the biliary tract i n all cases (see Fig. 36-10). The c o m m o n
completely provided they are treated early and appropriately. bile duct typically appears dilated, and there may be dilation
It is thought that the more chronic form of neutrophilic of the gallbladder and "sludge" within it. The main differen
cholangitis may represent long-term persistence of a low- tial diagnosis for these cats is extrahepatic biliary obstruc
grade infection in untreated or only partially treated cats. tion; the ultrasonographer should attempt to rule this out
by carefully imaging the surrounding pancreas, small intes
Lymphocytic Cholangitis tine, and mesentery.
Lymphocytic cholangitis is also k n o w n as lymphocytic chol It is very important to evaluate a hemostasis profile before
angiohepatitis, lymphocytic portal hepatitis, and nonsuppura performing a liver biopsy i n view of how c o m m o n l y coagu
tive cholangitis. lation times are prolonged i n cats with liver disease. V i t a m i n
Treatment and Prognosis
Researchers disagree on the recommended therapy of this
disease, which likely reflects our uncertainty about the etiol
ogy. A number of authors recommend immunosuppressive
doses of corticosteroids. However, although these tend to
ameliorate the acute flare-ups of the disease, they do not lead
to resolution of signs, and the condition invariably recurs.
Antibiotic therapy is wise, at least early i n the treatment,
until an infectious etiology has been ruled out. There is good
logical reason to use ursodeoxycholic acid (15 mg/kg P O
q24h) in these cats for its choleretic and antiinflammatory
effect as well as its effect on modulating the bile acid pool
and reducing toxic bile acids. Use of antioxidants such as
S-adenosylmethionine (20 mg/kg or 200 to 400 mg total
FIG 37-7 once a day on an empty stomach) and vitamin E (approxi
A lateral abdominal radiograph from a cat with lymphocytic mately 100 I U daily) is also logical because bile is a potent
cholangitis and associated ascites. The major differential oxidizing toxin i n the liver. However, none of these therapies
diagnosis in this case would be feline infectious peritonitis. has been critically evaluated in cats with lymphocytic chol
(Courtesy the diagnostic imaging department, The Queen's
angitis. Again, it is important to ensure that affected cats eat
Veterinary School Hospital, University of Cambridge.)
to prevent the development of concurrent hepatic lipidosis;
as discussed i n the preceding sections, a highly digestible,
high-quality diet without protein restriction is indicated. A
diet formulated for feline intestinal disease (such as lam's
feline intestinal or Royal-Canin feline selected protein or
Hills ID) might be the most appropriate because of the rela
tively high prevalence of concurrent inflammatory bowel
disease. Tube feeding should be considered i f necessary, as
outlined i n the section on hepatic lipidosis. Cats with more
acute signs, particularly associated with concurrent intesti
nal and/or pancreatic disease, may require hospitalization
and I V fluid therapy.
The prognosis for cure appears to be poor because the
disease appears to wax and wane chronically i n spite of
treatment. However, few cats with lymphocytic cholangitis
die as a result of their disease. This is likely because, unlike
in dogs, the disease does not generally progress to end-stage
FIG 37-8 cirrhosis.
Photomicrograph of liver specimen from a cat with severe
lymphocytic cholangitis. There is intense mononuclear cell Sclerosing Cholangitis
infiltration in the portal tract (center).
Sclerosing cholangitis, or biliary cirrhosis, involves an end-
stage fibrotic liver, and is very u n c o m m o n i n cats. The con
dition is characterized histologically by diffuse proliferative
K should be given before biopsy (0.5 mg/kg of vitamin K1 fibrosis o f bile duct walls spreading to involve the hepatic
SQ or I M q12h for 3 days) i f there is any concern about clot lobules and disrupting their architecture and circulation. It
ting function; fresh frozen plasma should be available to is thought i n most cases to represent an end stage of chronic
manage postbiopsy bleeding i f it occurs. Bile aspiration is biliary tract disease: usually complete obstruction or chronic
not necessary unless the disease is more acute and there is a severe liver fluke infestation (see the next section). It is very
possibility of neutrophilic cholangitis. Histology is impor unusual for neutrophilic or lymphocytic cholangitis to prog
tant to rule out FIP (see Chapter 97). The typical hepatic ress to sclerosing cholangitis i n cats. Affected cats present
lesion i n cats with FIP is a multifocal pyogranulomatous with typical clinical signs of chronic biliary tract disease, as
reaction with evidence o f vasculitis or perivasculitis, which outlined i n the cholangitis and extrahepatic biliary tract
is quite distinct from the periportal lymphocytic infiltrate obstruction sections. Affected cats may also develop chronic
seen i n cats with lymphocytic cholangitis (Fig. 37-8). Serol portal hypertension, with the resultant development of
ogy or P C R for Bartonella spp. might be considered, although ascites, gastrointestinal ulceration, and/or acquired porto
the importance of this organism in the naturally occurring systemic shunts (PSS) and hepatic encephalopathy (see
disease is unclear. Chapter 39). Acquired PSSs are m u c h less c o m m o n in cats
than in dogs, although they are occasionally recognized. absent in the later stages of disease, and flukes and eggs may
Sclerosing cholangitis is diagnosed on hepatic biopsy; again, not be seen on histology.
it is very important to evaluate hemostasis profiles before
biopsy and to administer vitamin K (0.5 mg/kg SQ or I M Clinical Signs
q l 2 h for up to 3 days) as necessary because vitamin K defi C o m m o n l y , cats with low-grade infestations remain asymp
ciency is c o m m o n in cats with chronic biliary tract obstruc tomatic. However, heavy infestations can be associated with
tion. It should be noted that cats with sclerosing cholangitis severe and often fatal disease (Haney et al., 2006; Xavier
may have hepatomegaly on radiography, which is unexpected et al, 2007). In these cases clinical signs are typically those
(cirrhosis usually results in a small liver i n dogs). Presum of posthepatic jaundice combined w i t h inflammatory liver
ably, this reflects the biliary tract dilation and florid peribil disease (e.g., jaundice, anorexia, depression, weight loss, and
iary fibrosis in these cases. Treatment is supportive, with lethargy). Diarrhea and vomiting have been features of clin
treatment of only the clinical signs associated with portal ical cases but do not occur i n experimental cases; affected
hypertension, as outlined in Chapter 39. cats may also have hepatomegaly and ascites.
BOX 37-3
Formalin-Ether Sedimentation Technique for Detecting Platynosomum concinnum Ova in Feces
1. Mix 1 g of feces in 25 ml saline; filter through a fine 4. A d d 3 ml of cold ether on top of solution and shake
mesh screen. vigorously for 1 min. Centrifuge for 3 min at
2. Centrifuge solution for 5 min at 1500 rpm; discard the 1500 rpm.
supernate. 5. Discard the supernate, resuspend the pellet in several
3. Resuspend the pellet with 7 ml of 10% neutral buffered drops of saline, and prepare slide of solution to
formalin; let stand for 10 min. examine microscopically.
From Bielsa LM et al: tiver flukes (Platynosomum concinnum] in cats, J Am Anim Hosp Assoc 2 1 : 2 6 9 , 1 9 8 5 .
dogs. It may occur alone or i n combination with neutro
philic cholangitis. Ultrasonographically, the gallbladder wall
BOX 37-4
often appears thickened and sometimes irregular; there may
Causes o f Extrahepatic Bile D u c t Obstruction ( E B D O )
be "sludging" o f the bile and/or choleliths. Clinical signs,
i n Cats
diagnosis, and treatment are very similar to those o f neutro
philic cholangitis (see preceding section). Lymphocytic cho Common Causes
lecystitis is also occasionally recognized. O n e or a combination of inflammation of pancreas,
duodenum, or biliary tree (most common)
BILIARY CYSTS Neoplasia, particularly of the biliary tree or pancreas
M o s t cystic lesions i n the feline liver are o f bile duct origin (second most common)
and may be congenital or acquired. Congenital cysts are
Less Common Causes
usually multiple and often present as part o f a polycystic
Stricture of bile duct after inflammation, surgery, or
disease o f several organs, including the kidneys. The cystic
trauma
contents are clear. Persian cats and Persian crosses are at
Diaphragmatic hernia with involvement of the gallblad
increased risk. Cysts may be an incidental finding o n imaging, der/common bile duct and subsequent compression
particularly i f they are small, but large cysts can cause clini Cholelithiasis
cal signs as a result o f destruction o f hepatic tissue and also Usually cholesterol a n d / o r calcium salts secondary
compression o f surrounding bile ducts resulting i n signs o f to cholangitis
biliary tract obstruction (see next section). Treatment is not Occasionally bilirubinassociated with pyruvate
indicated i f they are small and nonprogressive, but i f they kinase deficiency-induced hemolysis in Somali cats
are large and causing problems, they may be treated surgi Cysts (congenital or acquired) compressing biliary tree
cally by removal or omentalization (Friend et a l , 2001). Liver flukes
Acquired hepatic cysts may be single or multiple and may
Note that sepsis distant to the liver can produce an associated
be small or very large. The contents may be clear, bloody, or biliary stasis, which may appear clinicopathologically to be very
bilious. They may occur secondary to trauma, inflammation, similar to EBDO.
or neoplasia (including biliary cystadenomas) or i n rare Note also that biliary tract rupture (usually traumatic) produces
cases caused by liver flukes. Therapy depends on the cause, similar clinicopathological findings to EBDO.
but surgical management may be necessary i f they are large.
EXTRAHEPATIC BILE DUCT choleliths i n a cat should stimulate a search for underlying
OBSTRUCTION hemolytic disease.
TABLE 37-4
Primary Liver Tumors in Cats
TYPE OF TUMOR BEHAVIOR
Bile duct tumors: Most common primary liver tumor in cats (>50%).
Biliary carcinoma (including cystadenocarcinoma) Biliary carcinoma most common malignant feline liver tumor.
Biliary adenoma Aggressive behaviordiffuse intraperitoneal metastases in
Gallbladder tumors 6 7 % to 8 0 % of cases.
Hepatocellular tumors: Recognized but less common than biliary tumors. Adenoma
Hepatocellular carcinoma (HCC) more common than carcinoma.
Hepatocellular adenoma (hepatoblastomavery rare)
Neuroendocrine tumors: Very rare but very aggressive
Hepatic carcinoid
Primary hepatic sarcomas: Uncommon. Most locally aggressive and high MR.
Hemangiosarcoma, leiomyosarcoma, and others Hemangiosarcoma most common primary hepatic sarcoma
in cats.
Note: Benign tumors are more common than malignant tumors in this species.
MR, Metastatic rate.
may also be normal. Some malignant hepatic tumors c o m tumor; however, most cats with l y m p h o m a o f the liver
monly metastasize to the peritoneum and local l y m p h nodes respond to chemotherapy (see Chapter 80).
and less commonly to the lungs. As i n other diseases o f the
liver, ultrasonography is more helpful i n identifying a hepatic
mass and also in evaluating for metastases; it also allows for CONGENITAL PORTOSYSTEMIC SHUNTS
F N A of the mass(es). Hepatic tumors can also be cystic,
particularly cystadenocarcinomas. Cats, unlike dogs, rarely Etiology and Pathogenesis
have benign nodular hyperplasia i n the liver, so this is not a PSSs are abnormal vascular communications between the
differential diagnosis for a hepatic mass. Diffuse hepatic portal and systemic circulation. They may be congenital or
tumors (e.g., lymphoma) may show a diffuse change i n echo acquired secondary to portal hypertension. Those o f the
genicity, or the liver may appear n o r m a l o n ultrasonography. latter type are usually multiple vessels and are very rare i n
Important differential diagnoses for diffuse hepatic tumors cats because they usually occur secondary to severe hepatic
are FIP, lipidosis, and amyloidosis. A thorough abdominal fibrosis and cirrhosis, both u n c o m m o n i n cats. Acquired PSS
ultrasonographic examination should be undertaken to secondary to a congenital hepatic arteriovenous ( A V ) fistula
search for evidence of metastases. It should be kept i n m i n d has been reported i n a young cat, but this is very rare
that because benign tumors are more c o m m o n than malig ( M c C o n n e l l et al., 2006). M o s t cases o f PSS i n cats are there
nant tumors i n cats, no animal should be euthanized on the fore congenital, but even these are recognized less c o m m o n l y
basis of finding a hepatic mass with no evidence of metasta than i n dogs. Congenital PSSs are usually single or at most
ses on ultrasonography. double vessels and may be intrahepatic or extrahepatic i n
A definitive diagnosis is usually obtained using cytology location. Cats may have either type o f PSS (Lipscomb et al.,
or histopathology. In some cases F N A s may be diagnostic, 2007). Extrahepatic PSSs represent abnormal communca
but in others they may be difficult to interpret, particularly tions between the portal vein or one o f its contributors (left
in cats with benign hepatocellular tumors, i n which the gastric, splenic, cranial, or caudal mesenteric or gastroduo
cells look indistinguishable from normal hepatocytes. denal veins) and the caudal vena cava or azygos vein. Intra
Ultrasonography-guided T r u - C u t biopsies are usually diag hepatic PSSs may be left-sided, i n which case they are believed
nostic; alternatively, biopsies can be obtained during lapa to represent a persistence o f the fetal ductus venosus after
roscopy or laparotomy. In the case of an apparently single birth (patent ductus venosus, P D V ; W h i t e and Burton, 2001),
lesion, the clinician may elect to proceed straight to surgical or they may be right-sided or centrally located i n the liver,
removal and an "excisional" biopsy. Hemostasis profiles i n which case they are believed to be anomalous vessels. The
should be evaluated before performing a biopsy. It is unusual reason that congenital PSSs develop at all is u n k n o w n ,
for the one-stage prothrombin time and activated partial although it is assumed that there may be genetic reasons
thromboplastin time to be prolonged i n cats with primary and/or developmental problems i n utero that resulted i n
liver tumors, but they can be markedly prolonged i n cats abnormal development o f the liver vasculature.
with diffuse hepatic infiltration with l y m p h o m a or other The pathophysiology o f congenital PSS largely relates to
diffuse secondary tumors (e.g., mast cell tumors). Biopsies the shunting o f unfiltered b l o o d directly into the systemic
should not be considered i n these cases until clotting circulation, resulting i n hyperammoniemia and hepatic
factors have been replenished with a fresh frozen plasma encephalopathy ( H E ) . The pathophysiology o f H E is out
transfusion. lined i n Chapter 35. The shunting vessel acts as a low-
resistance pathway for some o f the portal blood, bypassing
Treatment the higher resistance intrahepatic portal vasculature. Portal
Treatment of primary hepatic tumors relies o n surgical pressure is therefore lower than n o r m a l i n cats with con
removal i f they are resectable. This is advisable even i n cats genital PSS, w h i c h is an important distinguishing feature
with benign tumors, including biliary adenomas. Treatment from (rare) cases of acquired shunting, i n w h i c h there
of diffuse, nodular, or metastatic tumors may be difficult. is portal hypertension and therefore an increased portal
Primary hepatic tumors generally have a poor response to pressure. Concurrent hepatic microvascular dysplasia or
chemotherapy. It has been suggested that this is because portal vein hypoplasia, which can confuse this differen
hepatocytes, both normal and transformed, have high expres tiation, occurs i n some dogs (see Chapter 38) but has
sion of the multidrug resistance membrane-associated not been reported i n cats. Shunting may also allow bactere
P-glycoprotein and also that hepatocytes are naturally high mia and potentially infections o f hematogenous origin
in detoxifying enzymes. Radiotherapy is not wise because that may present as "pyrexia o f u n k n o w n origin," although
normal liver tissue is very radiosensitive. For additional this is rare. A d d i t i o n a l effects o f portal b l o o d bypassing the
information, please see Chapters 80 (the section on l y m liver are hepatic atrophy and a reduction i n the metabolic
phoma) and 82 (the section on mast cell tumors). activity o f the liver, w h i c h contributes to inefficient use of
dietary components, poor growth, and loss o f lean body
Prognosis mass.
Prognosis of benign tumors is good after resection. Progno Liver atrophy (microhepatia) and changes i n hepatic
sis is very poor for cats with any type of malignant liver organelle function are partly due to changes in hepatic per-
fusion. The portal blood usually provides about 50% of the
liver's oxygen requirement, but this is obviously reduced i n
cats with PSS. Cats with PSS typically have arteriolar hyper
plasia i n an attempt to compensate for the reduced portal
flow, but they often still have some degree of hepatic under
perfusion. In addition, PSS results i n reduced delivery o f
"hepatotrophic factors," such as insulin, to the liver, which
further contributes to hepatic atrophy.
Clinical Features
Persian and Himalayan cats have been reported to be at
increased risk for congenital PSS i n small case series, and
another series noted that purebred cats i n general were over-
represented; however, cats o f any breed, including mixed-
breed cats, can be affected. Both sexes appear to be equally
at risk. There is no reported associated between breed and
shunt types (unlike i n dogs), although i n one study 6 out o f FIG 37-9
13 cats with an intrahepatic PSS were Siamese (Lipscomb et A 6-month-old kitten with a congenital portosystemic shunt,
demonstrating very small size for its age and also copper-
al., 2007). M o s t cases present before 2 years o f age; many are
color irises, which are often noted in kittens with portosys
younger than 1 year old, but old cats with congenital PSSs temic shunts.
are frequently recognized.
The typical clinical signs i n cats with congenital PSS are
gastrointestinal, urinary, or neurological ( H E ) , although the the rare feline cases o f acquired PSS, i n which ascites is more
latter tend to predominate i n cats and, anecdotally, are often c o m m o n because o f portal hypertension.
more severe than i n dogs. Cats typically present with a
history o f waxing and waning neurological signs consistent Diagnosis
with H E rather than a sudden acute H E crisis. The typical A suspicion for congenital PSS can be gained from the history
signs o f H E are outlined i n Box 35-1. Hypersalivation is a of recurrent neurological signs combined with high fasting
c o m m o n sign o f H E i n cats, but it is rare i n dogs. There is and/or postprandial bile acid or ammonia concentrations.
sometimes an association between H E and feeding, which Care should be taken when performing traditional ammonia
may relate to glutamine metabolism by enterocytes releasing tolerance tests, which can precipitate severe H E . Postprandial
ammonia, although not all cats display these signs. Cats i n ammonia or bile acid determinations are safer alternatives.
acute crisis may present comatose or with seizures; cats Serum bile acid concentrations should be measured before
appear to be more susceptible to seizures than dogs, both and 2 hours after feeding. (see Box 36-1). If ammonia is
preoperatively and postoperatively. The reason for this is measured instead, the postprandial sample should be taken
unknown, although it has been suggested that sudden 6 hours after feeding (Walker et al., 2001). Other typical (but
changes i n the concentrations o f a m m o n i a and other metab not pathognomonic) clinicopathologic findings in some
olites i n the blood after surgery or sudden changes i n medical (but not all) cats include low serum urea concentration,
management may destabilize neurotransmitters i n cats. mildly increased liver enzyme activities, and microcytosis.
D r u g intolerance is c o m m o n , particularly prolonged recov Notable differences from dogs are that decreases i n total
ery from routine anesthesia for spaying/neutering. Animals protein or albumin concentrations, hypoglycemia, and
with PSS may also show intermittent vomiting and/or diar anemia are m u c h less c o m m o n i n cats. Urine specific gravity
rhea. Urinary tract signs are due to cystitis associated with is low i n many dogs but occurs i n fewer than 20% of affected
urate calculi and polyuria/polydipsia, but they are less cats. If fasting bile acid concentrations are very high, it is not
c o m m o n i n cats than i n dogs. Impaired urine-concentrating necessary to obtain a postprandial sample, but the diagnos
ability may reflect reduced renal-concentrating gradient sec tic sensitivity o f doing both is higher than just measuring
ondary to low urea concentration and increased blood Cor fasting concentrations. If biliary stasis (which also causes
tisol concentration secondary to reduced hepatic breakdown, high bile acid concentrations) is ruled out and the cat does
although this has been demonstrated only i n dogs thus far. not have hepatic lipidosis (which causes hepatocellular
Cats with congenital PSS also often (but not always) show failure and H E with increases i n bile acid and ammonia
signs o f poor growth compared with their littermates (Fig. concentration i n many cases), it is likely that the cat has a
37-9). There has been a reported high prevalence of copper- congenital PSS because other causes of H E and high bile acid
colored irises i n cats with PSS (see Fig. 37-9), but this is not concentrations are u n c o m m o n i n cats. A b d o m i n a l radio
a consistent feature. graphs show a small liver i n 50% o f cases (Lamb et al., 1996).
Because o f the low portal pressure, ascites is not a feature However, for definitive diagnosis the shunting vessel must be
in cats, which helps i n distinguishing congenital PSS from visualized.
Visualization of the shunting vessel is achieved by ultra
BOX 37-5
sonography or portal venography (see Fig. 36-7, A and B)
Transcolonic portal scintigraphy will also demonstrate por Infectious Diseases with Hepatic Involvement in Cats
tosystemic shunting, but it does not differentiate congenital
Liver fluke (see text for details)
from acquired shunting. A liver biopsy should be taken at
Feline infectious peritonitis
the time of surgery or portovenography (after evaluation of
Toxoplasmosis
hemostasis profiles) to rule out other or concurrent condi
Bartonellosis
tions. This shows histological features very similar to those Histoplasmosis
in dogs and typical of portal venous hypoperfusion with loss Tyzzer's disease
of smaller portal veins, increased numbers of arterioles, Salmonellosis
hepatocellular atrophy with lipogranulomas, and sometimes Infection with Streptococcus groups B and G in neonates
periportal sinusoidal dilation but minimal inflammation. Leptospirosis (extremely rare)
Disseminated mycobacterial infections
Treatment Infection with Cytauxzoon felis
Tularemia (Francisella tularensis)
Treatment involves complete or partial ligation of the shunt
ing vessel using one of several methods, including silk or
Note also that neutrophilic cholangitis is often due to ascending
cellophane or ameroid constrictors; a detailed explanation is bacterial infection from the gut. Bartonella spp. may be involved in
beyond the scope of this book. The procedure is best reserved the etiology of some cases of lymphocytic cholangitis.
for referral centers, particularly in cats, which are more
prone to complications than dogs. The postoperative mor
tality in cats appears to be higher than in dogs, which is often
due to intractable severe neurological signs. Pretreatment long-term prognosis. However, clients should be warned that
with phenobarbital has been attempted, but too few cases short-term mortality rate after surgery is relatively high.
have been reported to assess its value. Propofol infusions are
often used for HE-associated seizures in dogs, but care must
be taken in cats because of their susceptibility to Heinz body HEPATOBILIARY INFECTIONS
anemia when given propofol infusions.
Cats should be managed medically before and for a period Several infectious organisms can infect the liver, either as a
of about 2 months after surgery while the portal vasculature primary target or as part of a more generalized infection.
and liver mass recover. This involves careful mild dietary These are listed in Box 37-5. In addition, neutrophilic chol
protein restriction with additional antibiotics (usually angitis likely has a primary infectious cause in most cats
amoxicillin, 15 to 20 mg/kg PO q8h) and sometimes also a (discussed in more detail in a previous section).
soluble fiber source such as lactulose (2.5 to 5 ml, given PO Hepatic involvement is common in both the dry and
q8h to effect). Some anecdotal data suggest that changes in effusive forms of FIP (see Chapter 97). Because cats with
medical management should be made more gradually in cats effusive FIP can present with the same signs as cats with
than in dogs to prevent the risk of seizures (e.g., change the lymphocytic cholangitis, it is an important differential diag
diet first, then add antibiotics after a week or more, and then nosis for this disease. A liver biopsy may be necessary to dis
add the soluble fiber source later). Details of medical man tinguish them; a diagnosis is occasionally made cytologically.
agement of HE are described in Chapter 39. Cats do not Disseminated toxoplasmosis is uncommon in cats, but
tolerate marked dietary protein restriction because of their when it occurs, the liver is usually involved with intracellular
high obligate protein requirement (see Table 37-2). A diet growth of Toxoplasma gondii during the active clinical
manufactured for cats with liver disease (such as Hills LD) disease, resulting in cell death. Effects of delayed hypersen
is appropriate, and, unlike in dogs, home-made diets based sitivity reactions and immune-complex vasculitis also con
on dairy protein should be avoided in cats because dairy tribute to clinical illness. Infection of the lungs, liver, and
protein is relatively deficient in arginine, which is essential central nervous system (including the eyes) with trophozo
for the urea cycle; deficiency will further predispose to ites is most commonly responsible for clinical signs. As
hyperammonemia. Medical management alone is effective in expected, high serum A L T activity and hyperbilirubinemia
some dogs long term (see Chapter 38), but anecdotally, cats commensurate with the degree of hepatocellular necrosis are
do not do as well with medical management of congenital the typical serum biochemical findings in cats with liver
PSS, probably because of their high obligate protein metab involvement. Cholangiohepatitis resulting from infection of
olism, which would make them more susceptible to hyper the biliary epithelium has been noted occasionally in exper
ammonemia, regardless of the diet fed. imental and spontaneously occurring cases of toxoplasmosis
in cats. The distribution of affected tissues in disseminated
Prognosis histoplasmosis often includes the lung, eye, bone marrow,
The prognosis appears to be good if the PSS can be ligated, spleen, lymph node, skin, bone, and liver. Infection with
although insufficient cases have been reported to assess the Bartonella spp. can cause cholangitis in cats.
TOXIC HEPATOPATHY BOX 37-6
Pathogenesis and Etiology Therapeutic Agents or Environmental Toxins that Can
By definition, toxic hepatopathy refers to a hepatic injury Cause Clinically Relevant Hepatic Toxicity in Cats
directly attributable to exposure to environmental toxins or
certain therapeutic agents. A n y therapeutic agent could Therapeutic Agents
potentially be heptatotoxic as a result o f an idiosyncratic Acetaminophen 120 mg/kg
reaction, but only a limited number o f such drugs have been Griseofulvin
reported i n cats (Box 37-6) i n addition to reported environ Megestrol acetate
mental hepatotoxins. Cats are particularly sensitive to phenol Ketoconazole
Phenazopyridine
toxicity because o f their limited hepatic glucuronide trans
Aspirin >33 m g / k g / d a y
ferase activity. A variety o f essential oils used topically have
Tetracycline
been reported to be hepatotoxic i n cats. Essential oils are Diazepam
absorbed rapidly, both orally and dermally, and are metabo Methimazole
lized by the liver to glucuronide and glycine conjugates; it is Stanozolol
believed that cats are more sensitive than dogs to their hep Nitrofurantoin
atotoxic effects (Means, 2002). Amiodarone
Complete information that could support meaningful MTP inhibitors (off-label use; see text)
conclusions about the frequency, character, and substances Essential oils
that consistently cause hepatotoxicity i n cats is not available. Environmental Toxins
Clinicians therefore must rely o n anecdotal reports, clinical
Pine oil + isopropanol
observations, and data accumulated by central agencies such
Inorganic arsenicals (lead arsenate, sodium arsenate,
as the National A n i m a l Poison C o n t r o l Center in Urbana,
sodium arsenite)
Illinois (888-426-4435; $55 per case via credit card), and the Thallium
U.S. Food and D r u g Administration's Center for Veterinary Zinc phosphide
Medicine, i n Washington, D C (the toll-free telephone White phosphorus
number for reporting suspected adverse drug experiences Amanita phalloides (mushroom)
is 1-888-FDA-VETS). In general, drug- or toxin-induced Aflatoxin
hepatic injury in cats is extremely u n c o m m o n , and most Dry-cleaning fluid (tricholorethane)
reactions are acute (occuring within 5 days o f exposure). The Toluene
character and severity o f the toxic reaction depend on the Phenols
characteristics o f the substance, as well as the dose and the
duration o f exposure.
Three therapeutic agents have been reported to be hepa
totoxic i n certain cats: tetracycline (1 cat), diazepam (17 to 5 o f administration i n cats given diazepam by mouth.
cats), and stanozolol (16 cats). Veterinarians have used these U n t i l there is more information that would improve under
agents for years without k n o w n deleterious effects. For each standing of this lethal and unpredictable hepatic reaction,
drug, clinical and clinicopathologic signs o f hepatotoxicosis use o f other agents for control o f behavior and elimination
developed within 13 days o f daily oral administration at problems i n cats is recommended. Cats that experienced an
recommended dosages. The adverse hepatic reaction to tet adverse reaction to stanozolol were healthy or had chronic
racycline was serious but nonlethal, and the cat recovered renal failure (14 o f 18 cats) or gingivitis/stomatitis (2 of 3
completely after drug discontinuation and 6 weeks o f sup cats; H a r k i n et al., 2000). Serum A L T activity was markedly
portive care (Kaufman et al., 1993). Histologic findings i n increased in most cats given 1 m g orally every 24 hours for
the liver included centrilobular fibrosis, m i l d cholangiohep several months or 4 m g orally every 24 hours (and 25 mg
atitis, and m i l d l i p i d deposition i n hepatocytes. In the cats intramuscularly once) for 3 weeks; all but one survived after
that experienced diazepam-associated hepatic failure, the the drug was discontinued and intensive supportive care
outcome was death in 16 o f 17 despite intensive treatment. given. The histologic lesions were moderate to marked,
The oral dosages of diazepam that cats received, primarily diffuse centrilobular lipidosis and evidence o f intrahepatic
for inappropriate urination, ranged from 1 m g every 24 cholestasis (accumulation o f bile and lipofuscin in hepato
hours to 2.5 m g every 12 hours. The histologic lesions i n the cytes and Kupffer cells).
liver were similar to those observed i n the cat with tetracy The new microsomal triglyceride transfer protein ( M T P )
cline-associated hepatic injury but more severe: massive, inhibitors marketed for weight loss in dogs are known to
predominantly centrilobular necrosis; suppurative cholangi increase liver enzymes reversibly i n that species but could
tis; and m i l d lipid vacuolation i n some cats. Because o f the result i n clinically significant hepatic lipidosis i n cats i f used
severity o f the lesions reported i n cats apparently susceptible off-label i n that species. This has not been reported yet
to diazepam-associated hepatic necrosis, serum liver enzyme because their use in cats is specifically contraindicated;
activities should be evaluated during the w i n d o w o f days 3 however, clinicians should be aware o f the risk.
The discriminatory eating habits of cats may account for HEPATOBILIARY INVOLVEMENT IN CATS
the relatively u n c o m m o n occurrence of hepatotoxicity from WITH SYSTEMIC DISEASE
ingested environmental toxins such as pesticides, household
products, and other chemicals. It is certainly possible that Several feline systemic illnesses have hepatic manifestations
many adverse hepatic reactions to drugs or toxic chemicals that may be identified by physical, clinicopathologic, or
go unnoticed in cats because the first clinical signs of illness radiographic examination, but the major clinical signs can
are vomiting and diarrhea, after which the medication is be attributed to another disease (see Table 37-1). In such
stopped. If the signs resolve, there usually is no further eval cases the hepatic lesion should recede with satisfactory treat
uation and the medication is not readministered to prove ment o f the primary illness.
that the substance caused the reaction. Metastatic neoplasia could be the underlying reason for
abdominal enlargement resulting from hepatomegaly or,
Diagnosis rarely, malignant abdominal effusion, although primary
Clinical evidence that suggests drug- or toxin-induced neoplasia is more c o m m o n than metastatic neoplasia in the
hepatic damage includes supportive history (e.g., k n o w n feline liver. Some of the signs of hyperthyroidism, especially
exposure); normal liver size to m i l d generalized tender hep occasional vomiting, diarrhea, and weight loss, can resemble
atomegaly; laboratory test results consistent with acute liver those of primary hepatobiliary disease. Thyrotoxic cats c o m
injury (e.g., high serum A L T and/or A S T activity, hyperbili monly have high liver enzyme activities; more than 75% of
rubinemia); and, i f the exposure was nonlethal, recovery affected cats have high serum A P activity (twofold to twelve
with discontinuation of the agent and specific or supportive fold), although i n cats it is not k n o w n whether this is of liver
care. There are no pathognomonic histologic changes i n the or bone origin or, as is true for hyperthyroid h u m a n patients,
liver, although necrosis with m i n i m a l inflammation and both. M o r e than 50% of hyperthyroid cats have high serum
lipid accumulation are considered classic findings. In many A L T or A S T activity (twofold to tenfold). M o r e than 90% of
cases all clinical and clinicopathologic markers of a toxic affected cats have high serum activity of at least one of the
liver insult are present, but the inciting chemical cannot be enzymes A P , A L T , and A S T . Approximately 3% are hyper
identified. In the case of hepatotoxicity from therapeutic bilirubinemic. Histopathologic changes are m i n i m a l , and
agents, idiosyncratic reactions can occur that are not dose there appears to be little functional disturbance. It is thought
related, although drug overdose is usually the reason for liver that malnutrition, hepatocellular hypoxia, and the direct
injury. effects of thyroid hormone o n liver cells are responsible for
these liver-related abnormalities. Hepatomegaly associated
Treatment with m i l d to moderate lipid deposition is a c o m m o n physi
In cats with suspected acute hepatotoxicity, the basic p r i n cal examination finding i n cats with diabetes mellitus; a
ciples for treatment of toxicoses are applied: preventing small number of cats may also be icteric. M i l d to moderate
further exposure and absorption, managing life-threatening increases i n liver-specific enzyme activities are typical. M o r e
cardiopulmonary and renal complications, hastening elimi severe clinicopathologic abnormalities might be expected i n
nation of the substance, implementing specific therapy i f cats with more severe hepatic lipidosis. Hyperadrenocortism
possible, and providing supportive care. Because few hepa is rare i n cats, and, unlike i n dogs, obvious liver involvement
totoxins have specific antidotes, the success of recovery often is unusual. The liver is usually n o r m a l i n size o n radiographs,
relies on time and aggressive supportive care. M o r e guidance and it is unusual to identify high serum A P and A L T activi
on supportive treatment of acute toxic hepatopathy is pro ties i n hyperadrenocorticoid cats. U n l i k e dogs, cats do not
vided in Box 38-4. possess a steroid-induced isoenzyme of A L P , and increased
Acetaminophen is one of the few toxins with a specific A L T , when recognized, is probably related to intercurrent
antidote. Acetaminophen is particularly toxic to cats, i n diabetes mellitus.
which the usual hepatic detoxification pathways of sulpha
tion and glucuronidation are particularly limited. Acetamin Suggested Readings
ophen is oxidized to a toxic metabolite that causes Aronson LR et al: Acetaminophen toxicosis in 17 cats, / Vet Emerg
methemoglobinuria within hours of ingestion and H e i n z Crit Care 6:65, 1996.
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of ingestion. N-acetylcysteine is a specific antidote that binds series and review, / Small Anim Pract 44:231, 2003.
the toxic metabolite and increases the glucuronidation Beatty IA et al: Spontaneous hepatic rupture in six cats with sys
process. It should be administered at a dose of 140 mg/kg temic amyloidosis, / Small Anim Pract 43:355, 2002.
Brain P H et al: Feline cholecystitis and acute neutrophilic cholan
intravenously or orally as a loading dose and then continued
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at 70 mg/kg q6h for a total of seven treatments or for up to
ment in six cases, / Feline Med Surg 8:91, 2006.
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Broussard JD et al: Changes in clinical and laboratory findings in
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Center SA et al: Proteins invoked by vitamin K absence and clotting obstruction in cats, / Small Anim Pract 43:247, 2002.
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Cole T L et al: Diagnostic comparison of needle and wedge biopsy vascular abnormalities in two cats, / Small Anim Pract 47:338,
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220:1483, 2002. Means C: Selected herbal hazards, Vet Clin Small Anim 32:367,
Crowe DT et al: Esophagostomy tubes for feeding and decompres 2002.
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Hosp Assoc 33:393, 1997. diagnosis of canine and feline liver diseases, Oxford, U K , 2006,
Friend EJ et al: Omentalisation of congenital liver cysts in a cat, Saunders Ltd Elsevier.
Vet Rec 149:275, 2001. Savary-Bataille K C et al: Percutaneous ultrasound-guided
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C H A P T E R 38
Hepatobiliary Diseases
in the Dog
FIG 38-1
A , Histopathology of normal liver from a middle-aged Yorkshire terrier. Note normal
portal triad with hepatic portal vein, artery, and bile duct and hepatocytes arranged in
neat cords with sinusoids between (white holes in bottom right are a sectioning artefact)
Hematoxylin and eosin x 2 0 0 . B , Histopathology of liver in a 3-year-old female English
Springer Spaniel with severe chronic hepatitis. There is marked distortion of the normal
lobular structure (compare to A) with inflammation and fibrosis and hepatocyte vacuola
tion and necrosis. There is also some ductular hyperplasia and disruption of the limiting
plate. Hematoxylin and eosin x 1 0 0 . (Courtesy the Pathology Department, Department of
Veterinary Medicine, University of Cambridge.)
have been demonstrated in humans with chronic hepatitis mean that chronic hepatitis in all dogs of that breed are due
and some of which have been recognized in other diseases to the same cause. For example, in many Doberman Pin
in dogs. Y o u n g to middle-aged dogs are most c o m m o n l y schers and West Highland White Terriers chronic hepatitis is
affected, and the sex ratio varies among breeds. It should also due to copper accumulation, but in others it is not. In many
be noted that there are some notable geographical differ cases of canine chronic hepatitis, the cause is unknown. This
ences i n breed-related liver diseases, which likely reflect dif contrasts with the situation in human medicine, wherein
ferences i n breeding in different countries: Diseases c o m m o n most cases of chronic hepatitis are viral and some have
in the United States may be unusual in the United K i n g d o m defined and often effective treatments that can reverse the
and vice versa. It is also important to remember that chronic disease process. In dogs chronic viral causes have not been
hepatitis can affect mixed breed as well as purebred dogs and convincingly demonstrated, but the histology in some cases
that recognition of one cause in a breed does not necessarily is suggestive of this and the search for infectious agents con-
inflammation may also result i n bouts o f pyrexia and hepatic
BOX 38-1
pain with associated gastrointestinal (GI) and other signs,
Dog Breeds with a Reported Increased Risk and many dogs with chronic hepatitis develop negative
of Chronic Hepatitis* nitrogen balance and protein-calorie malnutrition. Loss o f
hepatic function accounts for coagulopathies and adverse
Bedlington Terrier (worldwide. Copper storage disease)
drug reactions i n affected dogs.
Dalmatian (U.S., Copper storage disease)
Portal hypertension is an important consequence o f
Labrador Retrievers (worldwide. Copper storage disease in
U.S. and Holland. Not copper associated U.K.) females chronic hepatitis and fibrosis, and its effects contribute to
> males the clinical signs and death o f many affected animals (see
West Highland White Terriers (worldwide. Some copper also Chapter 39). It causes a typical triad o f clinical signs o f
associated and some not; all countries) ascites, G I ulceration, and hepatic encephalopathy ( H E ) . In
Skye Terriers (reports in U.K. onlymay be copper associ a healthy dog the pressure i n the portal vein is lower than
ated. N o recent reports) the pressure i n the caudal vena cava. However, i n association
Doberman Pinschers (worldwide. Some copper storage with obstruction and disruption o f sinusoids by fibrosis and
disease and some not) females > males hepatocyte swelling, portal pressure rises until it exceeds that
American and English Cocker Spaniels (worldwide) males i n the caudal vena cava (portal hypertension). This results i n
> females splanchic congestion with splenic congestion, gut wall edema,
English Springer Spaniels (U.K. and Norway) females >
and eventually ascites. The mechanisms o f ascites formation
males
in dogs with liver disease are complex but involve activation
* N o reported sex ratio unless stated. of the renin-angiotensin-aldosterone system (RAAS) with
sodium retention i n the kidneys and increased circulating
fluid volume.
If the rise i n portal pressure is sustained, multiple acquired
BOX 38-2 PSSs will develop by the opening up o f previously nonfunc
tional vessels; this allows for some o f the portal b l o o d to
Possible Reasons for Breed-related Liver Disease
bypass the liver and enter the portal vein directly (Fig. 38-2).
Increased susceptibility to infectious causes of chronic These acquired PSSs differ from congenital PSSs i n that they
hepatitis and/or chronicity of infection are multiple and exist i n the presence o f increased portal
Mutation in gene involved in metal storage or excretion pressure, whereas i n patients with congenital PSSs the portal
Mutation in gene involved in other metabolic processes pressure is low. Acquired PSSs lead to H E by a similar mech
(e.g., protease inhibitor production)
anism to congenital PSS (see Chapter 39). However, the H E
Increased susceptibility to toxic hepatitis (e.g., impaired
must be medically managed because ligation o f acquired
detoxification of drugs)
PSSs is contraindicated. This is because acquired PSSs are
Susceptibility to autoimmune disease
important escape valves to allow dissipation o f some o f the
portal hypertension; therefore any attempt to ligate them
will result i n fatal splanchic congestion. Acquired PSSs in
tinues. Most cases therefore remain a nonspecific diagnosis humans are also recognized to reduce the risk o f serious G I
of "chronic hepatitis," and the treatment remains nonspecific ulceration associated with portal hypertension; because of
and symptomatic. However, i n a few notable exceptions, this, they are sometimes created surgically i n humans with
such as copper storage disease and toxic hepatitis, the cause cirrhosis to reduce the risk o f serious bleeds. The same is
may be k n o w n and may be treated specifically. These are likely to be true i n dogs: GI ulceration is one o f the most
outlined in separate sections of this chapter. c o m m o n causes o f death i n dogs with chronic hepatitis;
acquired PSSs will help reduce this risk.
IDIOPATHIC CHRONIC HEPATITIS
Clinical Features
Etiology and Pathogenesis Dogs o f any age or breed can be affected with idiopathic
Idiopathic chronic hepatitis likely represents an unidentified chronic hepatitis, but there is an increased suspicion i n
viral, bacterial, or other infection; an unidentified previous middle-aged dogs o f the breeds outlined i n B o x 38-1. The
toxic event; or, in some cases, autoimmune disease. However, functional and structural reserve capacity of the liver implies
because autoimmune chronic hepatitis has not yet been con that dogs with chronic hepatitis usually have no clinical signs
vincingly demonstrated i n dogs, immunosuppressive drugs until late i n the disease process, when more than 75% of liver
should not be used or used only very cautiously. function has gone. By this stage, there is already extensive
The pathogenesis o f chronic hepatitis relates to loss o f destruction o f liver mass and treatment will be less effective
hepatic mass resulting in loss o f function and, late i n the than it w o u l d have been earlier i n the disease (Fig. 38-3). It
disease process, development o f portal hypertension. In is therefore beneficial to diagnose the disease earlier, and
many cases hepatocyte swelling, fibrosis, and portal hyper dogs with persistently high liver enzyme activities (particu
tension also contribute to cholestasis and jaundice. Ongoing larly hepatocellular enzymes such as A L T ) should not be
FIG 38-2
Diagramatic representation of congenital and acquired portosystemic shunts. A , Congeni
tal portocaval shunt. B , Multiple acquired shunts develop only if the pressure in the portal
vein is higher than the pressure in the vena cava.
often overtly thin. They may be depressed, but they are also
often surprisingly alert considering the severity of their
disease.
Diagnosis
Ultimately, a definitive diagnosis requires a liver biopsy, but
suspicion o f disease is gained from the clinical signs and
clinicopathologic features. Clinical signs, clinicopathologic
findings, and imaging may be supportive o f chronic hepati
tis but are not specific. A serum biochemical profile may
show a combination of high activities of hepatocellular
(alanine transaminase [ALT] and aspartate aminotransferase
FIG 38-3
[AST]) and cholestatic (alkaline phosphatase [ALP] and
Liver from a 6-year-old Bearded Collie that had shown
clinical signs for only 1 month before dying from end-stage -glutamyltransferase [GGT]) enzymes, and evidence of
liver disease. The diagnosis was chronic hepatitis with decreased parenchymal liver function (low urea, low albumin,
macronodular cirrhosis and very little normal liver tissue and sometimes high bilirubin and bile acid concentrations).
remaining. Persistent increases in A L T are the most consistent finding
i n dogs with chronic hepatitis, but they can also be found in
other primary and secondary hepatopathies. A high A L P
ignored. If liver enzyme activities are high for several months activity is m u c h less specific i n dogs, particularly because
and other causes have been ruled out (see the section on there is a steroid-induced isoenzyme. Hepatocellular enzymes
secondary hepatopathy), then a liver biopsy should be can become n o r m a l i n end-stage disease because of a lack of
obtained. This is even more important in breeds at high risk liver mass, but by that stage function tests (e.g., ammonia
and i n those predisposed to treatable diseases, such as copper and bile acid concentrations) will be abnormal, and the dog
storage disease. may even be jaundiced.
Once dogs have lost a significant amount o f liver mass, Radiographic findings are nonspecific. Dogs with chronic
they will display clinical signs, but these are typically low- hepatitis often have a small liver (contrasting with cats, in
grade, waxing and waning, and nonspecific, making differ which hepatomegaly is more common), but there is an
ential diagnosis from other diseases a challenge. V o m i t i n g overlap with normal, and the assessment of liver size is
and diarrhea, anorexia, and polydipsia/polyuria are c o m m o n . further confused by the variation in gastric axis in deep-
Jaundice and ascites occur i n some dogs at presentation and chested dogs. If ascites is present, radiographs are not helpful
develop later in others, but not i n all cases. Ascites at presen because the fluid obscures all abdominal detail. Ultrasonog
tation has been identified as a poor prognostic indicator i n raphy is m u c h more useful in assessing hepatic architecture
humans and dogs because it may represent more advanced (see Chapter 36). Dogs with chronic hepatitis often have a
disease with secondary portal hypertension. H E is u n c o m small, diffusely hyperechoic liver on ultrasonography,
m o n and usually seen only i n end-stage disease. The pres although the liver may look ultrasonographically normal in
ence o f H E strongly suggests the development o f acquired some cases. In other cases it may appear nodular because of
PSS. Dogs with chronic hepatitis usually have some degree macronodular cirrhosis and/or concurrent benign nodular
of protein-calorie malnutrition as a result o f chronic hepatic hyperplasia. It is impossible to definitively differentiate
functional impairment and concurrent GI signs. They are benign from malignant nodules on ultrasonographic appear-
ance alone; cytology or biopsy is essential to obtain a defin add to the food is difficult to estimate. It is advisable to
itive diagnosis. start with 1 or 2 tablespoons o f cottage cheese per meal,
End-stage chronic hepatitis with cirrhosis may appear monitor clinical signs and b l o o d protein levels, and adjust
very similar to noncirrhotic portal hypertension from a accordingly.
diagnostic standpoint, and yet the treatment o f the latter is
very different and the long-term prognosis m u c h more Drugs
favorable than with cirrhosis. Therefore a liver biopsy is nec D r u g support i n dogs with idiopathic chronic hepatitis is
essary for a definitive diagnosis and appropriate treatment. nonspecific and attempts to slow progression o f disease and
It is important to perform a hemostasis profile (one stage control clinical signs. Specific drug treatments are reserved
prothrombin time; activated partial thromboplastin time, for patients with an identified underlying cause. W i t h o u t a
and platelet count) before obtaining a biopsy and to address biopsy, nonspecific treatment should consist o f choleretics,
any coagulopathies or thrombocytopenia before the proce antioxidants, and diet. The use of glucocorticoids must be
dure. Fine needle aspirate ( F N A ) cytology is o f limited value reserved for biopsy-confirmed cases only.
in the diagnosis of chronic hepatitis; the most representative G l u c o c o r t i c o i d s . Glucocorticoids are c o m m o n l y used
biopsies are wedge biopsies obtained during laparotomy or i n dogs with idiopathic chronic hepatitis, but they should
laparoscopy, although ultrasonographically guided T r u - C u t never be used without a biopsy. Biopsies are necessary not
needle biopsies can be of some benefit. only to confirm the presumptive diagnosis but also to rule
out any contraindications. There is currently no evidence
Treatment that idiopathic chronic hepatitis is an autoimmune disease,
The aims of treatment of dogs with chronic hepatitis are to so glucocorticoids are used i n this context for their antiin
treat any identified underlying cause (see subsequent sec flammatory and antifibrotic role rather than as i m m u n o s u p
tions), slow progression of the disease if possible, and support pressives. Fibrous tissue is laid d o w n i n the liver by
liver function and the animal's nutritional and metabolic transformed Ito (stellate) cells, and i n dogs these are usually
needs. stimulated indirectly by cytokines produced by inflamma
tory cells to transform to collagen-producing cells. The
Diet chain o f events i n idiopathic chronic hepatitis is therefore
Dietary management is always an important part o f treat usually as outlined i n Fig. 38-4. Glucocorticoids have an
ment in patients with liver disease because the liver is the important role to play early i n the disease process: Their
"first stop" for nutrients on their way from the gut to antiinflammatory effect reduces cytokine formation and Ito
the systemic circulation and it is intimately involved i n the
metabolism of nutrients. This metabolism is compromised
in patients with liver disease; i n addition, dogs with chronic
hepatitis typically have protein-calorie malnutrition, so
excessive restriction of nutrients can be harmful. The nutri
tional requirements i n dogs with liver disease are outlined i n
Table 38-2. The most important consideration is dietary
protein concentration. It is now recognized i n both people
and dogs with liver disease that, i n order to avoid negative
nitrogen balance, dietary protein should not be restricted.
However, it is important to feed a high-quality, highly digest
ible protein to reduce hepatic work and to decrease the
amount of undigested protein that reaches the colon, where
it is converted to ammonia. Most ammonia reaching the
systemic circulation i n the portal b l o o d o f animals with con
genital and acquired PSSs originates not from dietary protein
but from enterocyte catabolism of glutamine as their m a i n
source o f energy. This cannot be avoided without starving
the enterocytes, so other means o f control o f H E are recom
mended in addition to dietary restriction. Clinical diets
available for dogs with liver disease (Hills L D and Royal
Canin-Waltham Hepatic support) are ideally formulated,
except that they have lower protein than is ideal for a dog
with chronic hepatitis. Therefore these diets should be fed as
FIG 38-4
a baseline little and often, with the addition of high-quality
Chain of events in typical idopathic hepatitis in dogs and
protein to the food. Dairy and vegetable protein produce the points for therapeutic intervention (those in brackets are
best results in humans and dogs with liver disease; cottage potential treatments not yet available for clinical use in
cheese is a good choice to add to the diet. The amount to dogs).
Dietary Considerations for Dogs with Liver Disease
The diet should be fed little and often (4-6 times a day) and needs to be palatable. A good and sufficient diet is essential
for hepatic regeneration and optimal hepatic function.
DIETARY C O M P O N E N T RECOMMENDATIONS
Protein Normal amount of high quality (all essential amino acids in optimal amounts), highly digestible
(so none left in colon for bacteria to break down to ammonia), and not in excess or requires
hepatic metabolism resulting in increased blood ammonia.
Low levels of aromatic amino acids and high levels of branched chain amino acids said to be
helpful to reduce hepatic encephalopathy, but evidence is lacking.
Ideal protein to use is dairy or vegetable. Cottage cheese is often used, but it is relatively low
in arginine. The easiest w a y to feed sufficient high-quality protein is to feed a proprietary diet
for canine intestinal or liver disease and adjust the protein level to individual's clinical signs.
Note diets for canine liver disease have slightly reduced protein content so may need to add
more protein e.g., cottage cheese if body weight or blood albumin drops.
Single protein source diet based on dairy or soy protein is recommended after recovery from
acute hepatitis.
Fat N o special advice in liver disease. Should not be excessively restricted as an important source
of calories and fat maldigestion and steatorrhea because of cholestasis and lack of bile salts
very rare. Restrict only if clinical steatorrhea develops. Avoid very high fat diets, particularly
with cholestasis or portal hypertension, in which gastrointestinal signs may be exacerbated.
Optimizing omega 3: Omega 6 may help reduce inflammation (more research necessary).
Carbohydrate The carbohydrate used should be highly digestible as a calorie source, reducing need for
hepatic gluconeogenesis from fat and protein. Carbohydrate metabolism usually disrupted in
hepatic disease. Therefore complex carbohydrates will be better used as an energy source by
the animal with liver disease than glucose.
Fiber Fermentable fiber: may reduce hepatic encephalopathy (conflicting evidence in humans, little
evidence in dogs). Broken down to short chain fatty acids in the colon which trap ammonia
as ammonium ions. Also beneficial effect on colonic bacteria, increasing nitrogen
incorporation into bacteria and reducing ammonia production. (Lactulose is a fermentable
fiber).
Nonfermentable fiber: also important because prevents constipation, which is a potential
predisposing factor for development of encephalopathy; it increases the contact time for
colonic bacteria to act on feces and produce ammonia.
Mixed fiber source in moderate amounts is therefore useful but not too much or it interferes with
the digestion and absorption of nutrients.
Minerals: zinc Zinc deficiency is common in humans with chronic liver disease. Dogs are proposed to be
similar to humans (but little direct evidence exists). Supplementation with zinc proposed to
reduce encephalopathy because it is used in metalloenzymes in the urea cycle and in muscle
metabolism of ammonia. Zinc is also indicated in copper storage disease because it reduces
copper absorption from gut and copper availability in the liver. It may also reduce collagen
lay-down in liver and stabilize lysosomal enzymes and also has some antioxidant activity.
Supplementing zinc is therefore recommended in any chronic hepatitis in dogs or cats.
Minerals: copper Animals with copper storage disease should be maintained on a low-copper, high-zinc diet.
Vitamins: fat soluble Vitamin E supplementation may be cytoprotective especially in copper toxicity because of its
antioxidant effect.
Vitamin K supplementation may be necessary if clotting times are prolonged, especially if
considering biopsies.
Vitamins A and D should not be supplemented. Vitamin A can cause hepatic damage, and
vitamin D supplementation can cause calcification in tissues.
Vitamins: water soluble B vitamins should be supplemented because there is increased loss in polydipsia/polyuria
associated with liver disease. It is recommended that dogs with liver disease receive a double
dose of B-vitamins.
Vitamin C should not be supplemented because ascorbate can increase the tissue damage
associated with copper and iron in liver disease.
cell stimulation, thus reducing fibrous tissue deposition. chronic hepatitis. The recommended dose is 20 mg/kg P O
They are therefore indicated early in the disease process, q24h. There are some studies documenting its use i n dogs,
when there is inflammation and m i n i m a l fibrosis, and once but more are needed to define i n which diseases it is most
infectious etiologies have been ruled out. In these situations useful. S-Adenosylmethionine is a very unstable molecule
they may slow the progression of the disease (although that (because it is a methyl donor) and must therefore be care
has not been proved). The logical dose to use is antiinflam fully packaged and given o n an empty stomach. The phar
matory (equivalent to 0.5 mg/kg of prednisone and gradu mokinetics and GI availability i n dogs are k n o w n for the
ally reducing over several weeks by halving the dose and pure preparation (Denosyl SD4; Nutramax Laboratories),
reducing to every-other-day treatment), although i m m u n o but it is increasingly being marketed as a polypharmacy
suppressive doses also have been used; there is currently nutraceutical in preparations with other nutraceuticals and
insufficient evidence i n dogs to advise which is correct. vitamins mixed together. Pharmacokinetic and absorption
Glucocorticoids are contraindicated later i n the disease, data should be sought from the manufacturers of these prod
when there is portal hypertension and end-stage fibrosis, or ucts to ensure that the S-adenosylmethionine is absorbed in
in conditions with noninflammatory fibrosis (e.g., noncir effective amounts.
rhotic portal hypertension), in which there is no reason for Another antioxidant c o m m o n l y used in dogs with chronic
their use. In these circumstances they are also likely to hepatitis is m i l k thistle (Silybum marianum). The active
shorten the life expectancy by increasing the risk of serious ingredients are flavonoids, c o m m o n l y referred to as silyma
GI ulceration (see Fig. 39-1). Hence glucocorticoids should rin, and the most effective of these is believed to be silybin.
never be used without a histopathologic diagnosis and There are very few studies of the use of flavonoids in dogs,
staging of disease. and the only clinical studies are o n acute toxic hepatitis.
Other antiinflammatory or immunosuppressive Silybin undoubtedly has the potential to be a helpful adjunct
d r u g s . Some of the other drugs used i n dogs with liver to therapy i n some cases, but m u c h more information on
disease also have antiinflammatory activity, particularly zinc, absorption, availability, and ideal dosage is necessary. Silybin
S-adenosylmethionine, and ursodiol (discussed in more is included in many nutraceuticals marketed for dogs with
detail later). Azathioprine has occasionally been used in dogs liver disease. One recent study (Filburn et al., 2007) showed
with chronic hepatitis, but there is no evidence that it is that it had very poor absorption alone but was m u c h more
beneficial; until immune-mediated causes of chronic hepa bioavailable when complexed with phosphatidylcholine.
titis have been proved, it would be wise to avoid the use of Therefore, although antioxidant nutraceuticals have great
this or other potent immunosuppressive medications. potential benefits i n the treatment of chronic liver disease i n
C h o l e r e t i c s . Ursodiol is widely and c o m m o n l y used i n dogs and can be safely used without a biopsy, the clinician
dogs with chronic hepatitis. It is a synthetic hydrophilic bile must be aware of the emerging nature of the information
acid that is choleretic and also modulates the bile acid pool about their bioavailability and efficacy and choose products
in biliary stasis, making the bile less toxic to hepatocytes. It carefully with this in m i n d .
also has antiinflammatory and antioxidant properties, and A n t i f i b r o t i c s . In inflammatory liver disease and early
recent studies suggest that it is synergistic with S-adenosyl fibrosis, glucocorticoids have a potent indirect antifibrotic
methionine and vitamin E. The only absolute contraindica activity by reducing inflammation, as outlined i n the preced
tion is complete biliary obstruction, which is very rare in ing sections. Later i n the disease process, when there is exten
dogs and would usually result in obvious acholic feces. It is sive fibrosis, the direct antifibrotic agent colchicine can be
logical to use it in any dog with chronic hepatitis, particularly used; there is limited but encouraging anecdotal evidence
in those associated with biliary stasis, and it can safely be supporting its effectiveness i n dogs. It is an alkaloid deriva
used without a biopsy. However, as with other drugs used in tive that binds tubulin and has the potential to reverse fibro
canine liver disease, there is very limited (although encour sis. The recommended dose i n dogs is 0.03 mg/kg/day P O .
aging) evidence as to its efficacy. It may be more helpful i n Adverse effects are u n c o m m o n i n dogs but include bone
some diseases than others, but this is not k n o w n yet i n dogs. marrow suppression and anorexia/diarrhea; it is the latter
The recommended dose is 10 to 15 mg/kg q l 2 h (or split into that often limits its use i n clinical cases.
two doses given q l 2 h ) . A n t i b i o t i c s . There is a primary indication for the use of
A n t i o x i d a n t s . A variety of antioxidants are used i n dogs antibiotics in dogs with ascending biliary tract infections or
with chronic hepatitis. The most well-documented are suspected bacterial infection as a cause of the chronic hepa
vitamin E and S-adenosylmethionine. V i t a m i n E appears to titis. The latter is rarely proved, but i f it is possible that
be beneficial at a dose rate of 400 IU/day for a 30-kg dog atypical leptospiral infection may be present (e.g., i f chronic
given as a water-soluble preparation once a day. Doses for hepatitis is seen i n a dog with access to sources of infection
smaller dogs are scaled appropriately. S-Adenosylmethio such as rivers or ditches), a course of appropriate antibiotics
nine is a glutathione precursor and is of particular benefit in w o u l d be wise to rule this out. The recommended therapy
dogs with toxic hepatopathy (discussed i n more detail later) for leptospiral infections is to start with intravenous (IV)
and those with biliary stasis because bile is a potent oxidant. amoxicillin at a dose of 22 mg/kg q12h to terminate replica
It is synergistic with V i t a m i n E and ursodiol, and an argu tion and reduce potentially fatal liver and kidney complica
ment could be made for it being beneficial i n any dog with tions. If leptospiral infection is subsequently confirmed (on
rising titres on serology, dark field microscopy, or P C R of the Zone 3 (perivenous; see Fig. 35-4 for an explanation of
urine for organisms), this should be followed by doxycycline hepatic zonation).
therapy (5 mg/kg P O q l 2 h for 3 weeks) once liver function True copper storage disease likely represents a genetic
is normal to eliminate the chronic renal carrier state. Bar defect i n copper transport and/or storage, but the only breed
tonella spp. have occasionally been associated with chronic in which this has been defined is the Bedlington Terrier. In
liver disease i n dogs. The optimal treatment for Bartonella this breed it is inherited as an autosomal recessive trait, and
spp. i n dogs has not been established. Macrolides (e.g., up to 60% of Bedlington Terriers i n some countries have
erythromycin) or alternatively fluoroquinolones or doxycy been affected in the past, although the prevalence is now
cline have been shown to have some efficacy against some decreasing as a result of selective breeding. The disease is
Bartonella spp. i n dogs. It has been suggested that 4 to confined to the liver, and there appears to be a specific defect
6 weeks of treatment might be necessary to eliminate i n hepatic biliary copper excretion (probably in transport
infection. from the hepatocyte lysosomes to the biliary tract). Recent
Antibiotics are also used as part of supportive treatment work has identified at least one genetic defect associated with
in dogs with H E caused by acquired PSS i n end-stage chronic the disease: a deletion i n the M U R R 1 gene (now C O M M D 1 ;
hepatitis, i n a similar way to dogs with congenital PSS to V a n de Sluis et al., 2002), which codes for a protein of
reduce toxin absorption from the gut and the risk of systemic u n k n o w n function. However, Bedlington Terriers with
infections (see Chapter 39). A m p i c i l l i n is often used long copper storage disease but without a C O M M D 1 deletion
term i n these cases at a dose of 10 to 20 mg/kg, P O or I V are now being reported i n the United States, United Kingdom,
q8-12h. and Australia (Coronado et a l , 2003; Heywood, 2006; H y u n
As with other drugs, the clinician should avoid any et al., 2004), suggesting that there is at least one other muta
antibiotics that increase hepatic w o r k or the risk of hepato tion involved i n the breed that has yet to be identified.
toxicity. Thus tetracyclines, potentiated sulphonamides,
nitrofurantoin, and erythromycin should be avoided unless Clinical Features
necessary (e.g., with confirmed leptospirosis or bartonello Affected Bedlington Terriers can present with either acute or
sis) because they are potentially hepatotoxic. chronic clinical signs, depending on individual factors, such
as the amount of copper i n the diet, and also likely other
COPPER STORAGE DISEASE factors, including concurrent stress and disease. If there is
rapid and marked build-up, dogs may present with acute
Pathogenesis and Etiology fulminant hepatic necrosis and no previous clinical signs.
Copper storage disease has been recognized as a cause of This is usually seen i n young to middle-aged dogs and is
acute and chronic hepatitis i n several breeds, the best often accompanied by acute hemolytic anemia caused by the
researched of which is the Bedlington Terrier (see B o x 38-1). rapid release of copper into the circulation. The prognosis is
Other breeds i n which copper storage disease has been poor, and most animals die within a few days. Fortunately,
reported are Dalmatians (in the U n i t e d States and Canada), this is u n c o m m o n ; most dogs have a more chronic, pro
Labrador Retrievers (in the U n i t e d States and Holland), and tracted course with several years of copper build-up and
some Doberman Pinschers (in H o l l a n d ) , although individ persistently high A L T activity, culminating i n the develop
ual members of all these breeds have also been reported with ment of chronic hepatitis with piecemeal necrosis, inflam
chronic hepatitis without copper accumulation. In addition, mation, and bridging fibrosis. Clinical signs are therefore
copper storage disease has been suspected but not exten recognized i n these individuals only late i n the disease process
sively investigated in West Highland W h i t e Terriers and Skye and are usually those of canine chronic hepatitis. These dogs
Terriers. It is also possible for seemingly n o r m a l dogs without usually present at about 4 years o l d but may be younger (Fig.
a recognized copper storage disease to develop copper-asso 38-5). Eventually, i f not treated, affected dogs will develop
ciated chronic hepatitis if fed a diet very high i n copper, such cirrhosis.
as dry calf feed ( V a n den Ingh et al., 2007). The clinical signs and progression i n other breeds with
Copper is excreted i n the bile and can b u i l d up as a copper storage disease are similar to those i n Bedlington
secondary phenomenon i n any type of chronic hepatitis Terriers. The disease i n Dalmatians is associated with acute
associated with cholestasis. In these cases the accumulation onset, rapid progression, and very high levels of hepatic
is usually m i l d , often i n zone 1 (peribiliary), and the amount copper i n the absence of significant clinical, clinicopatho
of copper does not correlate with the severity of the disease. logical, or histological evidence of cholestasis. Affected dogs
It is unclear whether copper chelation is helpful i n dogs with usually present as young adults with acute onset of GI signs
secondary copper build-up, but probably it is not. The and polydipsia/polyuria, by which time severe liver disease
peribiliary distribution and lack of correlation between is already present. Labrador Retrievers with copper storage
amount of copper b u i l d up and clinical signs helps to dis disease have an average age at presentation of 7 to 9 years
tinguish these cases from "true" copper storage disease, i n (range, 2.5 to 14 years). The clinical signs are relatively mild
which the copper accumulation is the cause rather than an and included anorexia, vomiting, and lethargy. Doberman
epiphenomenon of the disease and accumulation is usually Pinschers appear to have a long phase of subclinical disease
marked, progressive, correlated with disease severity, and i n culminating, i n untreated cases, in an acute-on-chronic
FIG 3 8 - 5
Beddlington Terrier with copper storage disease. (From Hall
FIG 38-6
EJ, Simpson JW, Williams DA, editors: BSAVA manual of
Cytology of hepatocytes from Bedlington terrier with copper
canine and feline gastroenterology, ed 2, Gloucestershire,
storage disease demonstrating copper granules (rubeanic
United Kingdom, 2 0 0 5 , British Small Animal Veterinary
acid stain). (Courtesy Elizabeth Villiers; from Hall EJ,
Association.)
Simpson JW, Williams DA, editors: BSAVA manual of
canine and feline gastroenterology, ed 2, Gloucestershire,
United Kingdom, 2 0 0 5 , British Small Animal Veterinary
disease and rapidly progressive deterioration. However, it is Association.)
unclear how many of the clinically affected Doberman P i n
schers described in the literature had copper storage disease
and how many had idiopathic chronic hepatitis, so the true breeding animal, clinicians should obtain a biopsy when the
presenting signs o f copper storage disease i n this breed are dog is about 12 months o l d , by w h i c h time there will be suf
unclear. Most published studies on true copper storage ficient copper build-up to diagnose the disease. In m u c h
disease i n Doberman Pinschers describe diagnosis and treat older animals, cirrhosis with nodular regeneration can
ment of subclinical disease. develop, and the nodules will have a lower copper content
than the rest of the liver, confusing diagnosis if a regenerative
Diagnosis nodule is inadvertently biopsied.
The magnitude o f increase i n liver enzyme activities and
the diagnostic imaging findings i n dogs with chronic copper Treatment
storage disease are very similar to those of dogs with idio The ideal treatment i n a dog k n o w n to be affected is preven
pathic chronic hepatitis. Therefore a definitive diagnosis tion. Bedlington Terriers with the C O M M D 1 mutation
requires a liver biopsy and estimation of the copper concen should be fed a low-copper, high-zinc diet. The proprietary
tration i n the liver. This can be done qualitatively on forma liver diets formulated for dogs (Royal-Canin Hepatic support
lin fixed sections using rhodanine staining to detect copper; or Hills canine L D ) have low copper and high zinc concen
correlations between quantitative and qualitative estimation trations but are also moderately protein restricted, so it
of copper accumulation have been published (Shih et al., would be wise to supplement with a low-copper protein source
2007). The finding of large accumulations o f copper i n hepa (e.g., cottage cheese) i n growing dogs. It is also important to
tocytes on cytology with rubeanic acid is also very suggestive avoid giving the dog tap water from copper pipes i n soft
of copper storage disease (Fig. 38-6; Teske et a l , 1992). water areas; bottled water should be used instead. B o x 38-3
Quantitative measurement of copper content can also be gives a list o f c o m m o n high-copper foods that should be
performed, but this requires a large biopsy specimen care avoided and high-zinc foods that could be supplemented.
fully taken and stored i n copper-free tubes. In addition to Dogs that present with an acute crisis should be treated
estimating copper content, the liver biopsy will give an i n d i with intensive support in exactly the same way as dogs with
cation of the chronicity and extent o f liver damage, which acute hepatitis (Box 38-4). Blood transfusion may be neces
will affect treatment decisions i n a very similar way to chronic sary i f hemolysis is severe. Copper chelation is unlikely to be
hepatitis. Bedlington Terriers can be tested for the C O M M D 1 beneficial acutely, but chelation with 2,2,2-tetramine (trien
deletion either before breeding or when newly acquired to tine) could be considered (or 2,3,2-tetramine i f obtainable)
assess their risk for this disease, but an absence o f the because this can chelate rapidly. Trientine is available as
C O M M D 1 deletion does not guarantee that the dog will not a drug licensed for humans (Syprine, M e r c k Sharp and
be affected. The genetic test is currently offered via m o u t h Dohme). The recommended dose i n dogs is 10 to 15 mg/kg
swabs at the A n i m a l Health Trust i n Newmarket, U . K . (details P O q l 2 h 30 minutes before a meal. 2,3,2-Tetramine is dif
at http://www.aht.org.uk/sci_diag_disc_genetic_main.htm) ficult to obtain. Penicillamine is not helpful i n an acute crisis
and by Vet G e n in the United States (www.vetgen.com). T o because chelation takes weeks to months. However, it should
rule out copper storage disease through a liver biopsy i n a be noted that there is m u c h less information available about
BOX 38-3 BOX 38-4
Foods Rich in Copper and Zinc Outline of Treatment Recommendations for Acute
Copper Fulminant Hepatitis
FIG 38-8
A , Jaundiced ocular and B , oral mucous membranes in a 6-year-old English Springer
Spaniel with extrahepatic biliary obstruction caused by acute-on-chronic pancreatitis. The
jaundice resolved uneventfully with medical management.
Royal-Canin W a l t h a m intestinal low fat or Eukanuba The most c o m m o n cause o f E B D O in dogs is extraluminal
intestinal diets) with a choleretic (ursodeoxycholic acid 10- obstruction from acute-on-chronic pancreatitis (see Chapter
15 mg/kg total dose daily, preferably split twice daily) and an 40), but intestinal foreign bodies, neoplasia, bile duct involve
anti-oxidant (S-adenosylmethionine 20 mg/kg P O q24h). In ment in a diaphragmatic hernia, and other processes can also
one dog this resulted in resolution of the mucocele, i n two cause E B D O (Fig. 38-8). Bile duct injuries that heal and
dogs the mucocele remained static, one dog died as a result result in stricture formation several weeks later are also seen
of gallbladder rupture, and one dog died as a result o f p u l in dogs; the c o m m o n bile duct ( C B D ) may be compressed
monary thromboembolism, both within 2 weeks o f diagno when carried with the liver into the thorax in dogs with
sis; two dogs were lost to follow-up. It w o u l d seem sensible diaphragmatic hernia. Extraluminal compressive lesions,
also to address the underlying cause o f the dyslipidemia in such as pancreatic, biliary, or duodenal neoplasms, are less
all cases, whether surgically or medically managed. c o m m o n causes, and cholelithiasis as a cause o f E B D O is
rare. T o be considered E B D O , a pathologic process must exist
EXTRAHEPATIC BILE DUCT at the level o f the C B D that impedes bile flow into the duo
OBSTRUCTION denum. O n l y if bile flow has been completely interrupted for
The causes o f extrahepatic bile duct obstruction ( E B D O ) i n several weeks do acholic feces, vitamin K-responsive coagu
dogs are very similar to those i n cats (see B o x 37-4) with lopathy, and repeated absence of urobilinogen in properly
the exception of liver flukes, which are u n c o m m o n in dogs. processed urine specimens occur. If obstruction is incom-
plete, these features are not present and the constellation o f but they may also be found in asymptomatic dogs. These
signs and clinicopathologic test results resembles those o f concretions are radiolucent unless they contain calcium,
other, nonobstructive biliary tract disorders. which occurs about 50% o f the time. Inflammatory abdom
inal effusion is expected i n dogs with bile peritonitis but not
BILE PERITONITIS i n those with most causes o f E B D O (except for effusions
Bile peritonitis results most often from abdominal trauma associated with pancreatitis or pancreatic cancer).
damaging the c o m m o n bile duct (e.g., penetrating injury, The ability to differentiate medical from surgical causes
horse kick, automobile accident) or pathologic rupture o f a of jaundice has been refined with the development o f ultra
severely diseased gallbladder, which sometimes occurs after sonography, although this imaging modality is certainly not
diagnostic ultrasonography-guided aspiration. Early signs foolproof. Dilated and tortuous hepatic bile ducts and C B D ,
of bile peritonitis are nonspecific, but with progression, as well as gallbladder distention, are convincing ultrasono
jaundice, fever, and abdominal effusion are seen. W h e n bile, graphic evidence o f E B D O at the C B D or sphincter of O d d i .
which is normally sterile, comes i n contact with the perito W h e n dilated biliary structures are seen, it might be difficult
neal surface, resultant cell necrosis and changes i n permea to distinguish E B D O that requires surgical intervention from
bility predispose to infection with bacteria that move across resolving, transient E B D O associated with severe acute-on-
the intestinal wall. Hypovolemia and sepsis may occur i n chronic pancreatitis or from nonobstructive biliary disease
animals with undetected bile peritonitis. (e.g., bacterial cholecystitis/cholangitis) unless a source of
obstruction is specifically identified (e.g., pancreatic mass,
Clinical Features cholelith i n the C B D ) . Prolonged fasting causes gallbladder
Presenting clinical signs and clinicopathologic and physical enlargement because o f delayed evacuation and should not
examination findings o f all these disorders may not differ be overinterpreted. In addition, cystic hyperplasia and
greatly unless the underlying condition has caused E B D O epithelial polyp formation are c o m m o n lesions in older
or bile peritonitis. Regardless o f the underlying disorder, dogs, not to be confused with choleliths i n the gallbladder.
typical clinical signs are jaundice, acute or chronic vomiting, A stellate appearance to the contents of the gallbladder is
anorexia, depression, weight loss, and occasionally vague characteristic of gallbladder mucocele. M o n i t o r i n g the serum
cranial abdominal pain. Because o f the protected location o f bilirubin concentration to determine when to intervene sur
the gallbladder in the abdomen, it is rarely possible to be able gically is not worthwhile because it begins to decline over
to palpate it i n a dog with E B D O , unless the gallbladder is days to weeks, without relief o f obstruction, i n both cats
greatly enlarged. and dogs with experimentally induced E B D O . Conversely, i n
some dogs a significant proportion o f bilirubin becomes
Diagnosis irreversibly b o u n d to a l b u m i n i n the circulation ("bilipro
The pattern of clinicopathologic findings typical o f biliary tein"), resulting i n delayed clearance and continued eleva
tract disorders is that o f hyperbilirubinemia, high serum A P tion o f serum bilirubin concentration for up to 2 weeks after
and G G T activities, high fasting and postprandial serum bile the initial insult has resolved.
acid (SBA) concentrations, and less severe changes i n serum
A L T activity. SBA concentrations increase early i n dogs with Treatment and Prognosis
biliary stasis; i n these circumstances the degree of S B A eleva If the distinction between medical and surgical causes o f
tion gives no indication o f liver function. Generally, more jaundice is not clear, it is safer to proceed surgically to avoid
severe cholestatic lesions are associated with more severe excessive delays i n diagnosis. Surgery is required i n dogs with
clinicopathologic changes. Fractionating the total bilirubin persistent E B D O , bile peritonitis, and gallbladder mucocele.
concentration into direct- and indirect-reacting components As with any other form o f liver disease, it is important to
(i.e., the van den Bergh reaction) does not distinguish intra stabilize the patient with fluids and electrolytes and perform
hepatic from extrahepatic cholestasis or obstructive from a hemostasis profile and platelet count before surgery. P r o
nonobstructive cholestasis. Radiographically, there may be longed coagulation times may respond to v i t a m i n K injec
evidence of hepatomegaly and a mass effect i n the area o f tions (1 mg/kg S Q q24h for 24 to 48 hours before and after
the gallbladder on survey abdominal films. Gas shadows surgery), but i f not, a plasma transfusion is advisable before
associated with the gallbladder and other biliary tract surgery to replace clotting factors. If surgery for bile perito
structures could be ascribed to ascending infection with nitis is to be delayed, peritoneal drainage should be estab
gas-forming organisms. Findings consistent with acute-on- lished to remove noxious, bile-containing abdominal fluid
chronic pancreatitis as an underlying cause o f E B D O are loss and for lavage. Should a site o f obstruction or biliary injury
of serosal detail in the area of the pancreas as an indication not be identified, at least tissue (i.e., liver, gallbladder mucosa)
of localized peritonitis, trapped pockets o f gas i n the duode and bile specimens can be obtained for histopathologic and
n u m , and duodenal displacement. However, i n many cases cytologic evaluation and bacterial culture and sensitivity
of chronic pancreatitis imaging findings may be less severe testing. A n y abdominal fluid should be analyzed cytologi
or normal in spite o f extensive fibrosis around the bile duct. cally and cultured for aerobic and anaerobic bacteria. A liver
Choleliths form i n dogs i n a manner similar to the way they biopsy specimen should also be obtained i n all cases. Typical
form i n cats, usually as a sequela to cholestasis and infection, hepatic histopathologic findings i n dogs with early E B D O
are canalicular bile plugs and bile ductular proliferation, result i n the development o f PSSs and asymmetry of hepatic
with degrees o f periportal inflammation and fibrosis i n lobular and vascular supplies; this is likely also true in dogs.
chronic cases. C o n f o u n d i n g biliary infection can incite a This w o u l d explain why it is relatively c o m m o n to see dogs
stronger inflammatory reaction i n the periportal region. with more than one co-existent congenital vascular disorder
However, it is impossible to diagnose a primary biliary tract i n the liver (e.g. a congenital PSS combined with intrahepatic
infection from a liver biopsy alone. Aerobic and anaerobic portal vein hypoplasia or microvascular dysplasia [ M V D ] )
culture and cytological examination o f bile are required to and w o u l d also explain why dogs with congenital PSSs
diagnosis infectious cholangitis. have a higher prevalence o f other congenital defects, such as
Surgical goals are to relieve biliary obstruction or leakage cryptorchidism and cardiac disorders.
and restore bile flow. Reconstructive procedures to divert bile For ease of categorization and because they have different
flow can be performed i f the cause o f E B D O cannot be cor clinical presentations, congenital vascular disorders have
rected. However, because these carry a poor long-term prog been divided into disorders associated with low portal pres
nosis, less invasive procedures such as stenting are preferred sure and those with high portal pressure. However, it is
whenever possible (Amsellem et al., 2006). important to remember than when two or more congenital
Antibiotic therapy is started immediately after bile hepatic defects occur concurrently, the differentiation will be
samples are obtained; ampicillin or amoxicillin (22 mg/kg less obvious.
IV, S Q , or P O q8h), first-generation cephalosporins (22 m g /
kg I V or P O q8h), or metronidazole (7.5 to 10 mg/ kg P O CONGENITAL VASCULAR DISORDERS
q l 2 h ; use lower dose when severe hepatobiliary dysfunc ASOCIATED WITH LOW PORTAL
tion is present) are good empiric choices as single agents PRESSURE: CONGENITAL
initially in animals without a long history o f antibiotic PORTOSYSTEMIC SHUNT
administration.
In cases without complete biliary obstruction (e.g., Etiology and Pathogenesis
ascending cholangitis) or with transient obstruction (e.g., Congenital PSSs are the most c o m m o n congenital portovas
some cases o f acute-on-chronic pancreatitis), medical m a n cular disorder i n dogs. The etiology and pathogenesis are
agement alone is indicated. The choleretic ursodiol is i n d i very similar to those i n cats; the reader is referred to Chapter
cated as additional treatment i n these cases, provided that 37 for more details. M a n y different types o f congenital por
complete E B D O has been ruled out. The recommended dose tovascular anomalies have been reported i n dogs; sometimes
is 10 to 15 mg/kg total daily, preferably split into two doses. they co-exist with intrahepatic or extrahepatic portal vein
In addition, all cases (both medical and surgical) should hypoplasia or intrahepatic M V D (discussed i n more detail
receive antioxidant therapy, preferably with vitamin E later). However, a distinguishing feature of isolated congen
(400 I U for a 30-kg dog, scaled appropriately to the size o f ital PSS is that it results i n low portal pressure, because some
the dog; tablets usually come as 100 I U , 200 I U , or 400 I U ) b l o o d is shunted away from the high resistance sinusoidal
and S-adenosylmethionine (20 mg/kg P O q24h) because it circulation by the shunting vessel. Dogs with isolated con
has been demonstrated that bile reflux i n the liver is a potent genital PSS therefore do not present with ascites unless they
oxidant toxin. Dogs should be fed a high quality diet which are severely hypoalbuminemic. This allows differentiation
is not protein-restricted: i n most cases, a diet designed for from the congenital vascular disorders associated with
critical care feeding is more appropriate than a manufac increased portal pressure, and therefore acquired PSS, out
tured liver support diet, because the dog is suffering an lined below, i n which portal hypertension and associated
inflammatory and/or septic process whereas hepatocyte ascites are c o m m o n at presentation.
function is usually good. Canine congenital PSS can be extrahepatic or intrahe
The prognosis for dogs with E B D O or bile peritonitis patic. Extrahepatic PSSs are anomalous vessels connecting
depends on the underlying cause. If the cause can be the portal vein or one o f its contributors (left gastric, splenic,
addressed without surgical reconstruction, the prognosis is cranial or caudal mesenteric, or gastroduodenal veins) to the
fair to good. If extensive biliary reconstruction is needed, the caudal vena cava or azygos vein. They are most commonly
prognosis is guarded. recognized i n small-breed dogs and have a high prevalence
i n C a i r n Terriers, Yorkshire Terriers, West Highland White
Terriers, Maltese, Havanese, other terriers, and Miniature
CONGENITAL VASCULAR DISORDERS Schnauzers (Fig. 38-9). Intrahepatic PSSs may be left-sided,
i n which case they are thought to represent persistence of the
Congenital disorders o f hepatic vasculature, both intrahe fetal ductus venosus, or they can be right-sided or central, in
patic and extrahepatic, are more c o m m o n i n dogs than i n which case they likely have a different embryological origin.
cats. There are some breed-related tendencies, suggesting a Intrahepatic PSS is more c o m m o n l y seen i n large-breed
genetic basis to some disorders, but it is also assumed that dogs, but Collies also tend to have extrahepatic PSSs, despite
most o f them result from some type o f (as yet undefined) being large dogs. Increased breed prevalence suggests a
insult i n utero. It is k n o w n that experimental reduction i n genetic basis to the disease, but this has only been investi
flow i n the umbilical vein i n sheep and other species can gated i n Irish Wolfhounds, i n which an inherited basis of
FIG 38-9
Typical small-breed dogs with congenital extrahepatic portosytemic shunts. A , An 8-month-
old female Border Terrier. B , A 9-month-old female Miniature Schnauzer.
patent ductus venosus has been demonstrated, and i n C a i r n neurological signs and (in some cases) palpable renomegaly.
Terriers with extrahepatic PSS, i n which an autosomal poly The latter is due to circulatory changes and is not a reflection
genic inheritance or monogenic with variable expression is of renal disease; it is o f no clinical significance and regresses
suspected (Van Straten et a l , 2005). Affected Irish Wolf after shunt ligation. Other congenital defects may be appar
hounds tend to have smaller litters and can also produce ent, particularly cryptorchidism.
more than one puppy with a PSS i n a litter.
One study reported that dogs from breeds that were not Diagnosis
usually recognized as having a high risk of PSS were more Diagnosis o f congenital PSS i n dogs is the same as i n cats
likely to present with unusual anatomical forms o f PSS that (see Chapter 37) and relies on visualizing the shunting vessel
were less often amenable to surgical management (Hunt, ultrasonographically, with portovenography (Fig. 38-10), or
2004). grossly at surgery. Scintigraphy can demonstrate shunting
but is not helpful to differentiate congenital from acquired
Clinical Features PSS, so some other imaging method is necessary for treat
Clinical signs are very similar to those i n cats; neurological, ment decisions. See Chapter 36 for more information on
gastrointestinal, and urinary tract signs predominate (see imaging PSS.
Chapter 37 for more details). A b o u t 75% o f dogs present It is important, i f possible, to try to estimate how well-
before 1 year of age, but some present at an older age, with developed the remaining hepatic portal vasculature is by
some as old as 10 years o f age before signs are recognized. repeating the portovenography after ligation and/or by eval
There is a spectrum of severity of neurological signs ranging uating the histological findings on liver biopsies taken at the
from severely affected young puppies that persistently circle, time o f ligation. This is a work i n progress, but there is a
become centrally blind, and can even have seizures or become strong suspicion that the prognosis postligation may depend
comatose to very mildly affected individuals. It is likely that o n the potential for the intrahepatic vasculature to open up
this variation reflects differences i n shunt fraction and also after surgery and that dogs that do poorly postoperatively
dietary and other environmental differences among dogs. may have concurrent portal vein hypoplasia and/or M V D
Polydipsia and polyuria with hyposthenuric urine are rela (discussed i n more detail later).
tively common; this is largely due to high Cortisol concentra Nonspecific clinicopathologic findings i n more than 50%
tion i n affected dogs (see Chapter 35) and also increases in of affected dogs, regardless o f the type o f vascular anomaly,
antidiuretic hormone and reduced renal medullar concen are microcytosis, hypoalbuminemia, m i l d increases i n serum
trating gradient (see Chapter 35). Urate uroliths are also A P and A L T activities, hypocholesterolemia, and l o w B U N
common and can be renal. Anecdotally, urate renal calculi concentration. Fasting bile acid concentrations may be
seem to be more c o m m o n i n terriers, and dogs presenting normal or high, but postprandial bile acid concentrations
with calculi often do not have prominent neurological signs. are high i n all cases. However, this does not distinguish con
O n physical examination animals are often (but not always) genital PSS from acquired PPS or early cholestasis, which
smaller than their littermates and may have non-localizing also causes increases i n bile acid concentrations. Postpran-
FIG 38-10
A , Portovenogram in a 1-year-old Golden Retriever with an intrahepatic portosystemic
shunt. This was a central divisional shunt and had a venous sinus-like structure, as
demonstrated well in this radiograph. B , Normal portovenogram in a dog for comparison.
(Courtesy the Diagnostic Imaging Department, the Queen's Veterinary School Hospital,
University of Cambridge.)
dial a m m o n i a concentration can also be measured and will aware of the small but definite risk of postoperative mortal
be high, whereas fasting a m m o n i a concentration may be ity as a result o f portal hypertension and/or refractory sei
high or n o r m a l (see B o x 36-1 for details of how to perform zures and of the potential that the PSS may be only partially
an a m m o n i a challenge test). A m m o n i a tolerance or chal and not totally ligated. In fact, it is more c o m m o n to be able
lenge tests are potentially dangerous because they can pre to partially ligate the PSS at the first surgery because the
cipitate an encephalopathic crisis. Other tests have been portal vasculature cannot initially accommodate all the
evaluated for their sensitivity and specificity in the diagnosis shunting blood. In some cases it is possible to repeat
of PSS. Protein C , a liver-derived anticoagulant factor, is also the surgery at a later date to ligate the PSS further, but this
decreased i n dogs with PSS and increases after ligation; this is often not necessary to control clinical signs. A few dogs
can help differentiate PSS from M V D . with partially ligated shunts develop portal hypertension
Puppies o f high-risk breeds could be screened for con and multiple acquired PSS with a recurrence of their clinical
genital PSS by measuring bile acid or ammonia concentra signs. There are several different surgical procedures
tions before they are placed into homes, but there are described for ligation o f PSS, but they are outside the scope
potential false positives with both of these tests and no puppy of this book. In addition to surgical ligation, PSS may be
should be euthanized or labeled as having a definite con attenuated with ameroid constrictors (Fig. 38-11) or embo
genital PSS on the basis o f high bile acid and/or ammonia lized with coils. Laparoscopic ligation of PSS has been
concentrations without further evidence. N o r m a l Irish Wolf reported in two dogs (Miller et a l , 2006). Ligation of a PSS
hounds can have a transiently high b l o o d a m m o n i a concen requires an experienced surgeon.
tration between the ages o f 6 to 8 weeks; this normalizes at Medical management is required to stabilize the patient
3 to 4 months of age. Zandlivet et al. (2007) have demon before surgery and also for about 8 weeks after surgery while
strated that this is due to a clinically insignificant urea cycle the hepatic vasculature and mass recover. This involves
defect. Postprandial bile acid concentrations can be falsely careful dietary management combined, in many cases, with
elevated in Maltese puppies without PSS for u n k n o w n antibiotics and soluble dietary fiber. The details are outlined
reasons, again confusing any efforts at screening tests in this in Chapter 39. In some cases medical management may con
breed (Tisdall et a l , 1995). tinue successfully over the course of the patient's life as an
O n diagnostic imaging the liver is frequently (but not alternative to surgery (Watson et al., 1998). Usually, this is
always) small. Ultrasonography now has a high sensitivity because the client cannot afford referral or is unhappy about
and specificity for the diagnosis o f both intrahepatic and the risks associated with surgery or because the patient has
extrahepatic PSS; furthermore, their anatomy can usually multiple or intrahepatic shunts. M i l d l y affected and older
also be described ultrasonographically. animals are good candidates for medical management; gen
erally, these are the individuals with smaller shunting frac
Treatment and Prognosis tions. Dogs (particularly terriers) that present at an older age
Surgical occlusion o f the anomalous vessel to restore normal with urate stones but no neurological signs, are also good
portal circulation has long been recommended as the treat candidates for medical management alone. In addition, dogs
ment o f choice. In many cases this will restore n o r m a l or with concurrent portal vein hypoplasia and/or M V D tend to
near normal liver function. However, owners need to be have a higher surgical risk and are best managed medically.
of arterioles, and a variable amount o f m i l d fibrosis. There
are some reports o f overt hypoplasia o f the extrahepatic
portal vein, but most reports of noncirrhotic portal hyper
tension and M V D appear to describe portal vein hypoplasia
confined to the intrahepatic vasculature. These diseases may
all be different abnormalities or they may represent different
spectra o f the same abnormalities, but their clinical presen
tation, treatment, and prognosis are similar. A lack o f intra
hepatic or extrahepatic portal vein branches results i n portal
hypertension, with the same potential consequences as those
of chronic hepatitis (see preceding section), including ascites,
gut wall edema, and often G I ulceration and acquired PSS.
Dogs with M V D often do not present with notable portal
hypertension, but it is grouped with these diseases by the
FIG 3 8 - 1 1
W S A V A liver standardization group (Cullen et al., 2006).
Lateral abdominal radiograph of a 3-year-old Miniature
Schnauzer that had an extrahepatic portosystemic shunt Dogs reported with M V D typically have shunting at the level
ligated with an ameroid constrictor 2 years previously. Note of the hepatic lobule but do not have clinical signs of overt
the ameroid is visible as a radiodense ring in the craniodor portal hypertension.
sal abdomen. (Courtesy the Diagnostic Imaging Department, A n y breed can be affected, but M V D particularly affects
the Queen's Veterinary School Hospital, University of small-breed dogs, with Yorkshire Terriers and C a i r n Terriers
Cambridge.)
showing a particularly high incidence.
Clinical Signs
Medical management does not reverse the underlying Dogs with all these conditions typically present at a young
disorder but can result i n good long-term results. Once the age with a combination o f signs o f portal hypertension and
dog has reached adulthood, there is no evidence that the liver PSS, the severity o f w h i c h depends o n that o f their lesions.
progressively atrophies throughout life. Ultimately, more Because o f the acquired PSS seen i n these patients, some of
studies are needed to identify the factors that are most the clinical signs and clinicopathologic findings overlap with
important i n determining prognosis after medical and/or those o f congenital PSS, particularly because all these disor
surgical management and to help identify preoperatively the ders typically present i n young dogs. Therefore presence of
small number of animals that w i l l have a poor outcome after other signs o f portal hypertension (e.g., ascites) is an impor
surgery. tant clinical clue that one of these disorders with acquired
PSS may be present, rather than a congenital PSS.
CONGENITAL VASCULAR Dogs with portal vein hypoplasia or idiopathic noncir
DISORDERS ASSOCIATED WITH HIGH rhotic portal hypertension typically present between 1 and
PORTAL PRESSURE 4 years o f age and are often purebreds o f either gender; large
There are a number of less c o m m o n congenital vascular breeds predominate. Early reports of "congenital" or juvenile
disorders of the liver i n dogs that present with n o r m a l or hepatic fibrosis i n G e r m a n Shepherd Dogs may also have
high portal pressure, rather than the low portal pressure seen represented a form of noncirrhotic portal hypertension. Pre
in association with congenital PSS. Because o f the portal senting signs are typically those o f portal hypertension, with
hypertension, the affected dog may present with the constel abdominal distention associated with effusion; GI signs;
lation of typical clinical signs (see Chapter 39), including polydipsia; weight loss; and, less consistently, signs o f H E .
ascites, and the potential for GI ulceration i n addition to Dogs are often surprisingly alert (Fig. 38-12).
multiple acquired PSS and H E . W i t h the exception o f arte Dogs with M V D present with similar clinicopathological
riovenous fistulae, none of these conditions can be treated findings but usually without overt evidence o f portal hyper
surgically; however, some o f them have a good long-term tension or ascites. M V D tends to affect terriers and thus
prognosis with medical management. overlaps with breeds at high risk for congenital PSS. In addi
tion, some dogs may have both congenital PSS and M V D or
Primary Hypoplasia of The Portal Vein/ portal vein hypoplasia, further confusing the diagnosis.
Microvascular Dysplasia/Noncirrhotic C a i r n Terriers and Yorkshire Terriers i n particular have been
Portal Hypertension reported with M V D . In one breed (the C a i r n Terrier), the
site of anatomic abnormality has been identified as the ter
Etiology and Pathogenesis m i n a l portal veins. In this breed it is believed to be an auto
There are several reports of vascular disorders i n young dogs somal, inherited trait, but the specific mode of inheritance
associated with portal hypertension, usually ascites, and has not been established. Typical signs include vomiting,
characteristic histopathological changes i n the liver o f a diarrhea, and signs o f H E , although the clinical signs, par
reduction i n smaller portal vein branches, increased numbers ticularly the H E , are notably milder i n dogs with M V D than
FIG 38-12
A female German Shepherd Dog with noncirrhotic portal hypertension. A , At 14 months of
age, with ascites and in poor body condition but remarkably alert B, 5 years later on medical
management onlyvery stable and in good body condition with no detectable ascites.
The dog lived for 8 years with a good quality of life before developing a gastroduodenal
ulcer (see Chapter 39). C , Drugs that the dog received long term, in addition to dietary
management. (B and C reproduced by permission from UK Vet, 9(7):41, 2004.)
in those with congenital PSS unless both disorders occur rhotic portal hypertension; it may be possible to visualize
concurrently. Dogs with only M V D are somewhat older, and multiple acquired PSSs ultrasonographically. Dogs with
many have m i l d to no signs of illness. In the case of young M V D alone tend not to have ascites and have less marked
purebred dogs that have been screened for congenital PSS increases i n S B A concentrations than dogs with true con
before sale or that are i l l for nonhepatic reasons, high S B A genital PSS.
concentration may be the only finding. The most important aspects of identifying a dog with
M V D / p o r t a l vein hypoplasia/noncirrhotic portal hyperten
Diagnosis sion are ruling out a surgically correctable PSS, identifying
Diagnosis of M V D / i n t r a h e p a t i c portal vein hypoplasia and portal hypertension (which requires treatment, see Chapter
noncirrhotic portal hypertension relies ultimately o n liver 39), and obtaining a liver biopsy for confirmation or exclu
biopsy findings of intrahepatic portal vein hypoplasia i n sion of other hepatopathies. Portal vein hypoplasia and non
the absence of a grossly demonstrable shunting vessel. The cirrhotic portal hypertension are very similarly clinically, on
liver biopsy findings alone can be indistinguishable from clinical pathology, and on diagnostic imaging to end-stage
the changes that occur secondary to congenital PSS, and chronic hepatitis with cirrhosis, and the only way to differ
therefore the clinical findings of concurrent portal hyper entiate the two is on liver histology. In general, portal vein
tension and ruling out a shunting vessel are important hypoplasia/noncirrhotic portal hypertension carries a much
parts of the final diagnosis. Clinicopathologic findings better long-term prognosis than cirrhosis, so the differentia
are very similar to those i n dogs with congenital PSS and tion is important prognostically.
include microcytosis, evidence of hepatic dysfunction (e.g.,
hypoalbuminemia), and low urine specific gravity. Micro Treatment and Prognosis
hepatia and hypoechogenic abdominal fluid are the notable The prognosis for all these conditions appears to be relatively
abdominal ultrasonographic findings i n dogs with noncir good, provided the clinical signs can be controlled. They are
nonprogressive, and there is no surgical treatment for any of two dogs. Clostridium sp. was the only isolate cultured anaer
them; symptomatic therapy of H E , ascites, and G I ulceration obically from abscess fluid i n 4 of 7 dogs.
(if present) is usually successful (see Chapter 39). It should
be noted that glucocorticoid therapy is absolutely contrain Clinical Features
dicated in these dogs and is likely to worsen the outcome The typical signalment and physical examination findings i n
because of the associated portal hypertension and high risk dogs with hepatic abscesses depend o n the underlying cause.
of GI ulceration. This underlines the importance of liver Dogs over 8 years o l d are most often affected because the
biopsy in these dogs, allowing differentiation from chronic predisposing causes of liver abscesses are seen more c o m
hepatitis. m o n l y i n older dogs. Regardless o f the initiating event,
One study of dogs with noncirrhotic portal hypertension anorexia, lethargy, and v o m i t i n g are consistent presenting
concluded that affected dogs might live as long as 9 years complaints. Expected physical examination findings include
after diagnosis with appropriate symptomatic therapy. A fever, dehydration, and abdominal pain. Hepatomegaly may
few dogs were euthanized because of problems related to be detected i n dogs with diabetes mellitus or hyperadreno
persistent portal hypertension (e.g., duodenal ulceration). corticism and i n some dogs with primary hepatobiliary
Dogs with M V D tend to have milder clinical signs than dogs disease.
with congenital PSS and can be managed medically with
success over the long term. Affected dogs seem to live c o m Diagnosis
fortably i n good to excellent condition for at least 5 years Neutrophilic leukocytosis with a left shift, with or without
(Christiansen et al., 2000). toxic changes, and high serum A L P and A L T activities are
dependable but nonspecific clinicopathologic abnormalities.
Arterioportal Fistula Survey abdominal radiographs may reveal evidence of irreg
Intrahepatic arterioportal fistula, causing marked volume ular hepatomegaly, a mass, or gas opacities within the area
overload of the portal circulation resulting i n portal hyper of the hepatic parenchyma (Fig. 38-13), but ultrasonography
tension, acquired PSSs, and ascites, is seen occasionally. is the imaging modality of choice. One or more hypoechoic
Abdominal ultrasonography with Doppler can frequently or anechoic hepatic masses and perhaps a hyperechoic r i m
detect the tortuous tubular structures representing the con surrounding the mass or masses are characteristic findings.
nection between an artery and overperfused portal vein or If there are multiple masses that w o u l d preclude surgical
veins; sometimes the turbulent b l o o d flow through the fistula removal or i f the owner declines surgery, F N A cytologic
can be auscultated through the body wall. If only one lobe analysis of the contents o f a representative lesion w i l l distin
of the liver is affected, the lobe containing the arterioportal guish an abscess from nodular hyperplasia, neoplasm (e.g.,
fistula can be removed surgically; assuming that there is hemangiosarcoma), or granuloma. Ideally, material should
adequate intrahepatic portal vasculature, acquired PSSs be obtained for cytologic analysis and aerobic and anaerobic
regress once portal overcirculation subsides. M o r e often, bacterial culture from a representative lesion deep i n the liver
multiple liver lobes are involved, making surgical treatment parenchyma to prevent abscess rupture and abdominal con
impossible. tamination. Abscess material should also be obtained by this
approach during surgery so that antibiotic treatment can
be initiated postoperatively. Ultrasound-guided drainage of
FOCAL HEPATIC LESIONS the abscess can also be used as treatment i n combination
with appropriate antibiotics (discussed i n more detail later).
ABSCESSES Results o f the preliminary clinicopathologic and radio
graphic evaluation should be scrutinized for evidence of
Etiology previously mentioned associated or predisposing illnesses.
Hepatic abscesses are usually the result of septic emboliza
tion from an intraabdominal bacterial infection. In puppies Treatment and Prognosis
they are a frequently a consequence of omphalophlebitis, Treatment for liver abscesses consists of surgical removal of
whereas in adult dogs they arise most often subsequent to infected tissue, administration of appropriate antibiotics,
inflammatory conditions of the pancreas or hepatobiliary supportive care, and resolution of underlying predisposing
system. Adult dogs with certain endocrine diseases, such as conditions. Infected liver tissue should be removed, i f pos
diabetes mellitus or hyperadrenocorticism, are also at risk. sible, and submitted for histopathologic examination and
Occasionally, infection arising from a location other than the bacterial culture i f this was not done preoperatively. Fluid,
abdominal cavity, such as the endocardium, lung, or blood, electrolyte, and acid-base abnormalities are addressed.
may disseminate to the liver, causing abscessation. Administration of a combination of antibiotics with a gram-
In a review (Farrar et al., 1996) of 14 dogs with hepatic negative and anaerobic spectrum is initiated until culture
abscesses, aerobic bacteria were isolated i n 9 of 10 cases i n and sensitivity test results are available. Because staphylo
which material from the hepatic lesions was submitted for cocci and Clostridia are the most c o m m o n isolates, amoxicil
culture. Although the most c o m m o n isolates were gram- lin (10 to 20 mg/kg I V q8h) or enrofloxacin (2.5 mg/kg I V
negative organisms, Staphylococcus spp. were identified i n or P O q l 2 h ) combined with metronidazole (10 mg/kg P O
FIG 38-13
A , Lateral abdominal radiograph of a 1-year-old female Great Dane with a liver abscess
[arrows) caused by Clostridium spp.; the cause was undetermined. B , Gross appearance
of the resected liver lobe containing an abscess (arrow).
q8-12h or 7.5 mg/kg P O q8-12h for dogs with hepatic dys change occurs m u c h less frequently and w o u l d be identified
function) or clindamycin (10 mg/kg I V or P O q l 2 h ) is a i n liver biopsy specimens. The lesion consists of increased
good empiric choice. Surgery is not indicated i n animals numbers o f normal to vacuolated hepatocytes with more
with multiple abscesses; ultrasound-guided centesis and mitotic figures and fewer binucleate cells than expected in
abscess evacuation may be a reasonable adjunct to treatment. normal liver; components of normal lobular architecture
Antibiotic treatment is continued on a long-term basis, (e.g., portal tracts, central vein) remain. Adjacent paren
usually for 6 to 8 weeks or until clinicopathologic and ultra chyma is compressed by growth of the nodules; fibrosis,
sonographic indicators of abscessation are resolved. F r o m necrosis, inflammation, and bile ductule hyperplasia are
the limited information available about this rare condition, absent. Because the prognosis for each of these nodular con
it seems that w i t h aggressive medical and surgical manage ditions is different and the margin of the lesion with adjacent
ment the prognosis for dogs with liver abscesses may not be hepatic tissue is important to establish a diagnosis, a wedge
as poor as once thought. biopsy is recommended. Needle specimens are likely to be
too small to confidently differentiate nodular hyperplasia
NODULAR HYPERPLASIA from primary hepatocellular carcinoma or adenoma. The
Hepatic nodular hyperplasia is a benign condition o f older cause o f this lesion is unknown; on the basis of experimen
dogs that does not cause clinical illness; clinicians should be tal development o f nodular hyperplasia in rodent species,
aware o f it, however, because hyperplastic nodules may be some have speculated a dietary role (low protein).
misinterpreted as a more serious condition, such as primary
or metastatic malignancy or regenerative nodules associated NEOPLASIA
with cirrhosis. The prevalence increases with age, and as
many as 70% to 100% o f dogs older than 14 years o f age Etiology
have some microscopic or macroscopic hyperplasia. Affected Primary hepatic neoplasms are rare i n dogs, accounting for
dogs have high serum A L P activity (usually 2.5-fold eleva fewer than 1.5% o f all canine tumors. Unlike in cats, malig
tion but may be as high as fourteenfold), which prompts nant tumors are more c o m m o n than benign tumors, and
investigation for hyperadrenocorticism. There is no evidence metastatic tumors are 2.5 times more c o m m o n than primary
of hepatic dysfunction o n serum biochemical analysis. M a n y tumors i n dogs. Metastases particularly arise from primary
dogs have multiple macroscopic nodules found ultrasono neoplasms i n the spleen, pancreas, and GI tract (Fig. 38-14);
graphically or at surgery, ranging i n size from 2 to 5 c m i n the liver can also be involved in systemic malignancies such
diameter; some dogs have a single nodule. M i c r o n o d u l a r as lymphoma, malignant histiocytosis, and mastocytosis.
Although certain chemicals can induce hepatic neoplasms examination or diagnostic imaging without supportive his
experimentally and infectious hepatitis is also a predisposing tology. The left liver lobes are often affected by hepatocel
cause in other species, the cause o f naturally occurring lular carcinoma which can occur i n three different patterns:
canine hepatic neoplasms is unknown. The types o f primary massive (single, large nodule; most c o m m o n ) , nodular
hepatic tumors seen in dogs and their relative importance (multiple smaller nodules), and diffuse (indistinct nodules
and metastatic potential are outlined in Table 38-3. throughout). The behavior o f each type of tumor tends also
to be different, as outlined i n Table 38-3.
Clinical Features Clinicopathologic abnormalities are likewise not specific
Clinical signs and physical examination findings i n dogs for neoplasia and b l o o d tests may be normal, even i n dogs
with primary or secondary liver tumors are nonspecific, with extensive involvement. Dogs with l y m p h o m a infiltrat
except for diffuse or nodular hepatomegaly. Even this can be ing the liver usually have marked increases i n A L T and A L P
confused with other conditions, such as macronodular cir activities but are rarely jaundiced; moreover, they may have
rhosis or benign nodular hyperplasia, which are also c o m m o n normal liver echotexture. Hypoglycemia has been described
in older dogs. Therefore no dog should be euthanized on the in association with hepatocellular carcinoma in dogs and can
basis of a presumptive diagnosis o f a liver mass on clinical be due to paraneoplastic production o f insulin-like growth
factor. Massive forms of hepatocellular carcinoma have a low
metastatic rate. Metastases from other diffuse and nodular
forms of hepatocellular carcinoma or biliary carcinoma
usually occur early; the most c o m m o n sites are regional
lymph nodes, lung, and peritoneal surfaces. Hepatocellular
adenoma (hepatoma) is a benign tumor that most often
occurs as a single mass that is typically smaller than the
massive form o f hepatocellular carcinoma but can be m u l t i
focal. Histologic features o f hepatocellular adenoma are very
similar to those o f nodular hyperplasia (or indeed normal
liver) except for the presence o f a fine r i m o f reticulin sur
rounding the adenoma and lack o f apparent normal archi
tecture (i.e., few portal tracts, no central veins).
TABLE 38-3
Primary Liver Tumors in Dogs
Note that malignant tumors are more common than benign tumors and that metastases to the liver are more common than
primary liver tumors in dogs.
Hepatocellular tumors: H C C most common primary liver tumor in dogs (50%). Most are
Hepatocellular carcinoma (HCC) massive; some are nodular or diffuse. Miniature Schnauzers and
Hepatocellular adenoma/hepatoma male dogs may be at increased risk. MR 0% to 3 7 % for massive
(Hepatoblastomavery rare) and 9 3 % to 100% for nodular and diffuse forms.
Adenoma uncommon and usually incidental.
Biliary tract tumors: Bile duct carcinomas second most common primary tumor in dogs
Biliary carcinoma (including cystadenocarcinoma) (22% to 4 1 % of malignant canine liver tumors). Labrador Retrievers
Biliary adenoma and females may be at increased risk. Usually aggressive. MR up
Gallbladder tumors to 88%. Adenomas uncommon and gallbladder tumors very rare.
Neuroendocrine tumors: Very rare, but always diffuse or nodular, and very aggressive.
Hepatic carcinoid
Primary hepatic sarcomas: Uncommon. Most locally aggressive, diffuse or nodular and high MR.
Hemangiosarcoma, leiomyosarcoma, and others
SECONDARY HEPATOPATHIES
Secondary (reactive and vacuolar) hepatopathies are very
c o m m o n i n dogs. In fact, i n pathology studies it is clear that
they are more c o m m o n than primary hepatic disease. M a n y
of these hepatopathies result i n elevations i n liver enzymes,
but the liver changes are usually not clinically significant and
usually do not result i n compromised liver function. However,
FIG 38-15 they are often confused with primary liver disease, and it is
Ultrasonographic appearance of the liver of a 6-year-old important to rule out secondary hepatopathies as m u c h as
Border Terrier with hepatocutaneous syndrome secondary to
possible i n the w o r k u p o f dogs with elevated liver enzymes
chronic phenobarbital medication for idiopathic epilepsy.
to allow identification and treatment o f the underlying
Note the typical hypoechoic "holes" in the liver parenchyma
on the left. (Courtesy Diagnostic Imaging Department, Queen's primary disease (e.g., endocrine disease or inflammatory
Veterinary School Hospital, University of Cambridge.) disease elsewhere i n the splanchic bed). It is also important
to be aware that raised liver enzymes i n an o l d dog have
many other causes apart from primary liver disease and to
Treatment a n d Prognosis resist the tendency to immediately put such dogs o n a
The prognosis is very poor unless the underlying cause can protein-restricted diet and other medication for liver disease
be identified and treated; most dogs live for less than 6 before w o r k i n g up the case properly. M a n y dogs with sec
months. There have been reports o f resolution o f disease i f ondary hepatopathies will not have hepatic histopathology
a pancreatic tumor is identified and removed. Dogs with performed because the primary cause will be identified with
phenobarbital-associated hepatocutaneous syndrome may other tests. However, it is convenient from a classification
improve when the drug is withdrawn, although this has point o f view to split secondary hepatopathies into three
not yet been demonstrated. A n alternative nonhepatotoxic groups on the basis o f their appearance histopathologically:
therapy for their epilepsy will need to be instituted; potas secondary hepatopathies associated with hepatocyte swelling
sium bromide might be an alternative choice, but it takes and/or vacuolation, hepatic congestion/edema, and reactive
weeks to reach steady-state. Gabapentin might also be used, hepatitis.
although this is only effective i n some dogs. For additional
information, please see Chapter 67. HEPATOCYTE VACUOLATION
W h e n an underlying cause cannot be identified and Secondary hepatopathies associated with hepatocyte vacu
treated, therapy is symptomatic and supportive. The most olation are divided into steroid-induced hepatopathy and
important aspect is amino acid/protein supplementation; in hepatocellular steatosis (lipidosis/fatty change). Steroid-
a few cases this may lead to long-term survival. There are induced hepatopathy is characterized by hepatocellular gly
single case reports of humans with resolution o f the disease cogen accumulation, which is distinctive from steatosis, i n
after amino acid infusions and/or regular dietary supple which fat (rather than glycogen) accumulates i n hepatocytes.
mentation of egg protein; feeding egg yolks has also been The difference can be demonstrated with special stains (Peri
reported as resulting in a clinical improvement i n some dogs. odic acid Schiff for glycogen and O i l red O or Sudan black
It is unclear whether eggs are beneficial simply because they for fat), but there are some differences also o n routine hema
are a high-quality amino acid supplement or whether there toxylin and eosin staining that help with differentiation:
are other beneficial micronutrients i n the eggs. Dogs with Glycogen vacuoles tend not to displace the nucleus from the
hepatocutaneous syndrome should not be fed proprietary center o f the cell and often contain strands o f eosinophilic
diets for liver disease because these are protein restricted. material, whereas classic steatosis is associated with clear,
Other support included antibiotics for secondary skin infec empty vacuoles (because the fat is lost i n processing) and the
tions (such as cefalexin 20 mg/kg q l 2 h ) and antioxidants nucleus is often displaced to the edge of the cell (Fig. 38-16).
(see the section on the treatment o f chronic hepatitis). In Both types of vacuolar hepatopathy are reversible when
addition, zinc and fatty acid supplementation may be helpful the underlying cause is taken away. The most c o m m o n causes
in some cases. Glucocorticoids should be avoided because are endocrine diseases (see Table 38-1). Steroid-induced
they will precipitate diabetes mellitus. W e have treated two hepatopathy is seen i n hyperadrenocorticism and dogs being
dogs with hepatocutaneous syndrome that survived for given exogenous corticosteroids. It has also been associated
several years on a high-quality digestible diet (marketed for with other hormone therapies and administration o f some
GI disease) supplemented with extra egg and vitamin E and other drugs, such as D-penicillamine. There have been
FIG 38-16
Gross (A) and histological (B) appearance of the liver postmortem in a middle-aged
Miniature Poodle with poorly controlled diabetes mellitus. Note the pale, yellowish
appearance of the liver associated with generalized hepatic steatosis. Histologically, the
hepatocytes are markedly swollen with fat that displaces the nuclei to the edge of the
cells. Portal triad in the center (Hematoxylin and eosin x 200). (Courtesy Pathology
Department, Department of Veterinary Medicine, University of Cambridge.)
reports of idiopathic vacuolar hepatopathy i n Scottish those of the primary cause and not related to the liver.
terriers causing marked elevations in A L P , but the underly However, sometimes there will be an overlap in clinical
ing cause is u n k n o w n . The vacuolation seen as part of the signsnotably with hyperadrenocorticism or diabetes mel
hepatocutaneous syndrome looks very similar to glycogen litus in which the polydipsia, poluria, and abdominal enlarge
vacuolation. Steatosis is classically associated with diabetes ment together with raised liver enzymes might increase the
mellitus in dogs, in which it starts centrilobularly and then suspicion of primary liver disease. Recognizing that there is
spreads. It has also been reported in juvenile hypoglycemia a secondary hepatopathy involves initial pattern recognition
of small-breed dogs. However, although hepatic steatosis can of the enzyme elevation and clinical signs (e.g., i n a dog with
sometimes appear very marked i n dogs, it does not appear polydipsia/polyuria, a pot-belly, and dermatological signs, a
to become a clinically significant disease in its o w n right, pattern of a very marked elevation i n A L P and less marked
unlike i n cats, in which primary or secondary hepatic l i p i elevation in A L T should raise the suspicion of hyperadreno
dosis are important clinical syndromes (Chapter 37). corticism). This is followed by appropriate diagnostic tests
for the underlying condition. Liver biopsies are usually not
HEPATIC CONGESTION/EDEMA indicated or taken. However, there will inevitably be cases
Hepatic congestion is a c o m m o n finding with right-sided with m i l d or nonclassical changes of the primary condition
congestive heart failure and other causes of posthepatic in which liver biopsies will be taken on suspicion of primary
venous congestion, such as heartworm disease. This results hepatopathy. Finding nonspecific secondary changes in the
again i n elevation in liver enzymes. It is usually reversible, liver should then stimulate a repeat search for an underlying
but in a few very chronic cases of congestion associated with cause.
heart disease, it can result in fibrosis and permanent c o m
promise ("hepatic cirrhosis"). Suggested Readings
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C H A P T E R 39
Treatment of
Complications of Hepatic
Disease and Failure
a protein-restricted diet not only is not indicated but will in the gut broken down by bacteria is a source of gut-derived
result in protein-calorie malnutrition. ammonia. However, as has recently been pointed out, gut
Whether it is due to congenital PSS in dogs and cats or bacteria will metabolize only undigested protein that reaches
acquired PSS (mainly i n dogs), treatment o f H E is m u c h the the colon. This should not occur i f the protein in the diet is
same. The m a i n difference is that acquired PSSs are usually very digestible and not i n such excessive amounts that it
the result o f portal hypertension, so treatment o f the other overwhelms the digestive capacity o f the small intestine.
manifestations o f this and the underlying liver disease will There are high amounts o f ammonia in the portal circula
also be necessary in these cases (see the discussion o f portal tion, particularly after a meal, but the main source of these
hypertension below). Recent studies in human medicine is obligate catabolism of glutamine by small intestinal entero
have questioned the actual efficacy of some o f the treatment cytes as their main energy source, and intestinal glutaminase
recommendations for H E , including lactulose. Controlled activity seems to increase for unknown reasons in humans
trials have not been conducted in animals to determine the with cirrhosis, increasing gut ammonia production. Studies
optimal treatment for H E and for each stage (mild, moder in dogs with experimental PSS and animals and humans
ate, severe) o f H E ; therefore current recommendations are with acquired PSS have actually shown a higher protein
based on studies i n h u m a n medicine and on anecdotal requirement than in normal animals or people. Therefore
reports in dogs and cats. the current recommendation is to feed animals with con
genital or acquired PSS normal to only slightly reduced
Diet quantities of protein that is highly digestible and of high
The ideal diet for long-term management o f H E is the same biological value in order to minimize the amounts of undi
as the diet recommended i n chronic liver disease in dogs; gested protein reaching the colon and "wastage" of excess
dietary recommendations are outlined in Table 38-2 and Box nonessential amino acids by transamination or deamination
39-1. Protein restriction has long been recommended in for energy. Some experts recommend that diets should have
patients with H E owing to the fact that undigested protein low amounts o f aromatic amino acids, because these have
been implicated in H E , but i n fact there is no evidence that
BOX 39-1 the ratio of dietary aromatic amino acid : branched chain
amino acid has any effect on H E . Food should be fed i n small
Long-term M e d i c a l Management of Hepatic
amounts and often to avoid overwhelming the ability o f the
Encephalopathy
liver to metabolize it. Diets manufactured for dogs with liver
Dietary Management disease are a good starting point (Hill's canine L D ; Royal-
Feed normal amounts (if possible) of high-quality, highly C a n i n canine hepatic) but are rather protein-restricted, so
digestible protein to minimize the chance that any they should be supplemented with a high-quality protein
protein will reach the colon to be converted into N H 3 . such as cottage cheese or chicken. A n alternative is to feed a
Some veterinarians recommend increasing branched veterinary diet marketed for intestinal disease; these diets
chain amino acids and reducing aromatic amino acids contain high-quality, highly digestible protein sources (Hill's
such as tryptophan, but there is no evidence that chang canine or feline I D ; lam's canine or feline intestinal formula;
ing the dietary levels affects cerebrospinal fluid levels. Royal-Canin canine or feline digestive lowfat). Most, if not
Consider adding ornithine aspartate, which provides
all, dogs with congenital or acquired PSS can tolerate normal
substrates for conversion of NH3 to urea (ornithine) and
protein concentrations i f other measures are also imple
glutamine (aspartate). Restrict protein only if absolutely
mented, as outlined in the subsequent paragraphs and in Box
necessary to control neurologic signs
39-1. A few require more marked restriction i n the short
Prevent protein-calorie malnutrition by avoiding pro
term, but every effort should be made to increase to a normal
longed fasting a n d / o r excessive protein restriction
because this will lead to hyperammonemia from break protein concentration over the long term.
down of body protein
Feed little and often to reduce the amount of liver work Lactulose
required and reduce the potential for undigested food Lactulose (-galactosidoffuctose) is a semisynthetic disaccha
to reach the colon.
ride that is not digestible by mammals and therefore passes
Fat: N o special recommendations, although it should be
into the colon, where it is degraded by bacteria into short
fed in normal amounts and not restricted unless clinical
chain fatty acids ( S C F A ) , particularly lactic and acetic acid.
steatorrhoea develops (rare). Avoid diets that are very
high in fats, particularly with cholestasis or portal These S C F A s help control signs of H E by acidification of the
hypertension in which gastrointestinal signs may be intestinal contents, which traps a m m o n i u m ions i n the colon,
exacerbated. and by promoting osmotic diarrhea. In addition, S C F A s are
Carbohydrates should be highly digestible as a primary used as an energy source by colonic bacteria, allowing them to
calorie source, reducing the need for hepatic gluconeo grow and thus incorporate colonic a m m o n i a into their own
genesis from fat and protein. bacterial protein, which is subsequently lost with the bacteria
Fermentable fiber reduces hepatic encephalopathy in i n the feces (a type of bacterial "ammonia trap").
the same way as lactulose. Nonfermentable fiber is also The dose is adjusted until there are two to three soft stools
important because it prevents constipation and therefore
per day (see Box 39-1); overdosing results i n watery diarrhea.
reduces contact time for colonic bacteria to act on feces
There are no k n o w n complications of chronic lactulose use
and produce ammonia.
i n animals (other than diarrhea). However, the efficacy of
Zinc supplementation may reduce encephalopathy
because zinc is used in many metalloenzymes in the lactulose has never been critically evaluated in dogs and cats
urea cycle and in muscle metabolism of ammonia with H E , and recent studies i n humans suggest that it may
not be as helpful as previously thought. Lactulose can also
Lactulose be given by enema in animals with acute H E (Box 39-2).
Lactulose is a soluble fiber that acidifies colonic contents, M a n y cats and dogs object strongly to the sweet taste of
reducing ammonia absorption, and also increases lactulose; an attractive alternative is lactitol (-galactosidos-
colonic bacterial cell growth, therefore incorporating orbitol), which is a relative of lactulose and can be used as a
ammonia in to bacterial cell walls. Cats should be given powder (500 mg/kg/day i n three to four doses, adjusted to
2.5 to 5 ml P O q8h; dogs 2.5 to 15 ml P O q8h. Start produce two to three soft stools daily). Currently, lactitol is
at the low dose, and titrate to effect (2 to 3 soft stools
available i n the United States as a food sweetener, but it has
a day).
not been studied in dogs and cats with H E
Antibiotics
Amoxicillin (22 mg/kg PO q 12 h) or metronidazole
Antibiotic Treatment
(7.5 mg/kg P O q 12h) to reduce gastrointestinal flora If dietary therapy alone or i n combination with lactulose is
and also protect against bacteremia insufficient to control signs of H E , other medications may
be added. Antibacterial drugs that are effective for anaerobic
Identify and Treat Concurrent Infections/Inflammation
organisms (metronidazole, 7.5 mg/kg administered P O q8-
12h; amoxicillin, 22 mg/kg administered P O q l 2 h ) are pref
erable. Antibiotics effective for gram-negative, urea-splitting
organisms (neomycin sulfate, 20 mg/kg administered P O
q l 2 h ) may also be used, although neomycin is more useful
BOX 39-2 BOX 39-3
SPLANCHNIC CONGESTION AND Corticosteroids have been shown to shorten the life expec
GASTROINTESTINAL ULCERATION tancy o f humans with chronic hepatitis and concurrent
portal hypertension and should not be used in dogs with
Pathogenesis portal hypertension unless there is a very good reason for it.
Splanchnic congestion is a c o m m o n and early complication If they are deemed necessary, the owners should be fully
of portal hypertension, the result of the pooling o f b l o o d in informed o f their potentially serious adverse effects. Other
the splanchnic circulation and reduced flow into the portal triggers for G I ulceration in dogs with portal hypertension
system (see Fig. 39-3). This can cause visible congestion and are sepsis and protein-calorie malnutrition (discussed in
edema o f the gut wall that can be detected either ultrasono more detail later), particularly i f combined with a period of
graphically (where there may be thickening and loss o f layer anorexia (see Fig. 39-1). The small intestine requires luminal
ing o f the gut) or during surgery. It occurs before the onset glutamine and other nutrients to permit effective healing,
of ascites and persists after ascites resolves (see Fig. 39-3). and prolonged anorexia results i n an increased risk of gas
The congested gut wall is at increased risk o f GI ulceration. trointestinal ulceration as a result o f glutamine depletion.
Catastrophic gastrointestinal or esophageal ulceration is the The clinician must be aware that GI ulceration may occur
most c o m m o n cause o f death i n humans with portal hyper acutely i n dogs with splanchic congestion and serious
tension who do not undergo a liver transplant, and it appears clinical deterioration may occur before melena is apparent
also to be the most c o m m o n cause o f death in dogs with because it takes several hours for the blood to pass from the
stable chronic liver disease (see Fig. 39-1). Ulceration associ small to the large intestine. Before this occurs, it is possible
ated with portal hypertension in humans often takes the for the animal to show sudden onset and marked signs of
form o f bleeding esophageal varices, whereas in dogs the H E because blood is a "high-protein meal" in the small intes
ulceration is most c o m m o n l y in the proximal duodenum, tine (see preceding section) or even for the ulcer to perforate
presumably reflecting a difference in the anatomy o f the and cause peritonitis (see Fig. 39-1).
portal system i n the two species. Preventing gastrointestinal
ulceration is therefore vital, and for this reason it is very Treatment
important to refrain from using ulcerogenic drugs (e.g., ste Treatment o f gastrointestinal ulceration largely revolves
roids) in dogs with portal hypertension whenever possible. around its prevention (i.e., avoiding triggers as m u c h as pos-
sible, such as the use of steroids or nonsteroidal antiinflam tubules. This leads to an increase i n circulating fluid volume,
matory drugs, and avoiding hypotension during any surgery). precipitating the formation o f ascites, w h i c h i n turn reduces
It is particularly important that any dog with portal hyper venous return because o f increased pressure o n the caudal
tension that undergoes a prolonged period o f anorexia is fed vena cava and initiates a vicious cycle of renal sodium reten
because these individuals will be at high risk o f gastrointes tion and ascites. Therefore aldosterone antagonists are
tinal ulceration i f they do not receive nourishment (see Fig. usually most effective i n dogs with ascites secondary to
39-1). Parenteral nutrition is not an effective alternative i n portal hypertension, whereas loop diuretics, such as furose
these dogs because it does not supply luminal nutrients for mide used alone, can be ineffective or even, in some cases,
enterocyte healing (in fact, upper gastrointestinal ulceration actually increase the volume o f effusion by causing a further
is a c o m m o n adverse effect of total parenteral nutrition in decrease i n systemic b l o o d pressure as a result o f hemocon
humans, even i n those without portal hypertension), and centration and secondary increases i n R A A S activation.
some form o f enteral support should be instituted as soon
as possible. The use of gastric acid secretory inhibitors ( H 2
Treatment
blockers or proton pump inhibitors) is o f questionable Treatment o f ascites associated with liver failure revolves
benefit in patients with portal hypertension because it is around the use o f diuretics: first aldosterone antagonists
usually the duodenum that is ulcerated (rather than the (spironolactone, 1 to 2 mg/kg administered P O q l 2 h ) , but
stomach); also, there have been reports that the gastric p H then with the addition o f furosemide (2-4 mg/kg adminis
in dogs with liver disease may already be higher than n o r m a l tered P O q l 2 h ) i f necessary i n refractory cases. Spironolac
as a result of changes i n gastrin metabolism. However, i n the tone usually takes 2 or 3 days to reach full effect, and the
face of active ulceration and melena, they are often used i n resolution o f ascites can be monitored by weighing the
the hope that they will help. In these circumstances, cimeti patient daily (any acute changes i n weight w i l l be due to fluid
dine is contraindicated because o f its effect o n hepatic P450 shifts). Dietary sodium restriction has also been recom
enzymes; therefore ranitidine (2 mg/kg administered orally mended, although it is unclear h o w effective or important
or via slow I V administration q l 2 h ) or famotidine (0.5 to this is. However, it is certainly wise to refrain from feeding
1 mg/kg administered P O ql2-24h) are recommended. Like the patient high-salt snacks and treats.
wise, sucralfate (Carafate) is o f questionable efficacy; it is It is very important to m o n i t o r serum electrolyte concen
most effective against gastric ulceration (i.e., i n association trations (mainly s o d i u m and potassium) daily during the
with a low p H ) , but it is often used (at a dosage o f 500 m g first few days o f treatment and every few weeks to months
to 1 g per dog P O q8h). Hemostasis profiles should also be thereafter, depending on h o w stable the dog and drug doses
evaluated, and any coagulopathy treated with vitamin K (see are. Hypokalemia should be avoided because it can precipi
the section on coagulopathy) or plasma transfusions. tate H E (see preceding section), but it is less likely i n a dog
on both aldosterone antagonists and loop diuretics than i n
ASCITES a dog on furosemide alone. Hyponatremia can also occur; i f
it is marked, the diuretics should be stopped and the patient
Pathogenesis given careful intravenous replacement until the sodium is
The development of ascites (defined as the accumulation of normalized.
a transudate or modified transudate i n the peritoneal cavity) Therapeutic paracentesis is indicated only i n patients
is another consequence of portal hypertension (see Fig. with ascites that is severe enough to compromise breathing.
39-3), but the pathogenesis is complex and has really been This is actually unusual and is manifested by severe, d r u m
studied only i n humans; it is assumed that the mechanisms like ascites; the dog is unable to settle and lie down. Paracen
of ascites are similar in dogs. One way i n w h i c h dogs differ tesis should be accompanied by concurrent intravenous
from humans is that dogs do not develop the "spontaneous" administration o f a colloid plasma expander, plasma, or
infection of ascites o f liver origin by extension o f gut bacte albumin; removal o f a large volume of fluid containing
ria into the fluid that results i n peritonitis, which is c o m albumin can result i n a precipitous hypoalbuminemia and
monly reported in people. The presence o f ascites is a poor decrease i n oncotic pressure, leading to pulmonary edema.
prognostic indicator in humans with chronic hepatitis, and This is a real problem i n dogs with chronic liver disease in
the same appears to be true i n dogs. Hypoalbuminemia con which the liver's capacity to manufacture a l b u m i n is reduced.
tributes to the development of ascites but by itself is rarely Clear recommendations for dogs have not been published,
sufficient to cause fluid accumulation; portal hypertension but the recommendations for humans, adapted for dogs, are
is a critical contributing factor. The development o f ascites outlined i n B o x 39-4.
in patients with liver disease also seems to lead to sodium
retention by the kidneys. In many cases there is systemic
hypotension and increased renal sodium retention, partly as COAGULOPATHY
a result of reduced glomerular filtration rate and decreased
sodium delivery to the tubules and partly as a result o f Pathogenesis
increased release of renin-angiotensin-aldosterone (RAAS) The liver plays a central role i n both the coagulation and
that results i n increased sodium retention i n the distal fibrinolytic systems. The liver synthesizes all the coagulation
Coagulopathies can also occur i n dogs and cats with liver
BOX 39-4 disease as a result o f disseminated intravascular coagulation
(DIC) with resultant prolongation o f clotting times and
Guidelines for Therapeutic Paracentesis in Dogs with
thrombocytopenia. D I C is particularly a complication o f
Ascites Resulting from Liver Disease
acute, fulminating hepatitis and also some hepatic tumors;
Reserve for use ONLY in cases with severe, refractory it carries a very poor prognosis.
ascites:
Small volume paracentesis: follow up with intravenous Clinical Features and Diagnosis
plasma expansion with 2 to 5 ml/kg of gelofuscin or
Despite the presence o f hemostatic abnormalities, spontane
hemaccel
ous bleeding is u n c o m m o n i n patients with chronic liver
Large volume paracentesis: volume expand preferably
disease but relatively c o m m o n i n those with acute disease.
with albumin using 8 g albumin/I of ascites removed
(i.e., 1 0 0 ml of 2 0 % albumin per 3 liters of ascites). Because dogs with portal hypertension and gastrointestinal
Failing that, use fresh frozen plasma (10 ml/kg slowly) hemorrhage (see previous section) may also have a coagu
lopathy predisposing to their bleeding, they should be thor
Adapted from Moore et al: Guidelines on the management of oughly evaluated. However, the risk of hemorrhage increases
ascites in cirrhosis, Gut 55 (suppl 6 ) : v i l , 2 0 0 6 . after a challenge to hemostasis, such as liver biopsy; therefore
it is very important to evaluate hemostasis before perform
ing liver biopsy. One study (Bigge et a l , 2001) suggested that
thrombocytopenia was a more significant predictor of bleed
factors with the exception o f factor VIII and also makes the ing complications after ultrasonography-guided biopsies in
inhibitors o f coagulation and fibrinolysis. Factors II, V I I , dogs and cats than prolongation of the O S P T and A P T T .
I X , and X also require hepatic activation by a v i t a m i n In Therefore clinicians must perform a platelet count in dogs
dependent carboxylation reaction. Hemostatic abnormali and cats before performing a liver biopsy. A platelet estimate
ties are quite c o m m o n i n both dogs and cats with liver can be can be done manually on the blood smear (Chapter
disease; i n one study 50% and 75% o f dogs with liver disease 87) The platelet count (per L) can be estimated by counting
had prolongation of the one-stage p r o t h r o m b i n time (OSPT) the number of platelets i n 10 o i l immersion fields and m u l
and activated partial thromboplastin time ( A P T T ) , respec tiplying the average number per field by 15,000 to 20,000.
tively (Badylak et al., 1983). In another study 82% o f cats Prolongation o f coagulation times may also increase the risk
with liver disease had hemostatic abnormalities (Lisciandro of bleeding; i n the same study, prolongation o f the O S P T in
et al., 1998). Cats appear to be particularly susceptible to dogs and the A P T T i n cats was significantly associated with
prolongation of clotting times; this is at least partly due to bleeding complications after biopsy. Ideally, therefore, both
reduced v i t a m i n K absorption. Dogs and cats with v i t a m i n O S P T and A P T T should be evaluated i n cats and dogs before
K-responsive coagulopathies have prolongation of b o t h the hepatic biopsy, however, a practical alternative could be
O S P T and A P T T (and the O S P T may actually be longer than assessment of at least an activated clotting time (ACT) in a
the A P T T ) . V i t a m i n K is a fat-soluble vitamin, and its absorp glass tube containing diatomaceous earth as a contact activa
tion is decreased i n association w i t h biliary tract disease tor, although theoretically this is more useful i n cats than
(which is c o m m o n i n cats); bile acid secretion into the small dogs because it assesses the intrinsic pathway (=APTT) and
intestine is also reduced. Moreover, the inflammatory bowel
final c o m m o n pathway only.
disease c o m m o n l y seen concurrently i n cats with chronic
Because factor depletion must be greater than 70% to
biliary tract disease results i n reduced fat absorption. Finally,
result i n prolongation o f the O S P T or A P T T , many more
some cats with chronic biliary tract disease have concurrent
dogs and cats may have subtle abnormalities in the con
chronic pancreatitis, and as this progresses to exocrine pan
centration o f individual coagulation factors. These can be
creatic insufficiency, fat absorption (and thus v i t a m i n K
detected by more sensitive tests, such as measuring the
absorption) w i l l decline further.
concentration o f individual clotting factors or the P I V K A
In contrast, dogs with chronic liver disease rarely have (proteins induced by vitamin K absence) test, although its
clinically relevant prolongation o f clotting times. However, clinical efficacy in large numbers of dogs and cats is untested.
i n both species severe diffuse liver disease, particularly acute If available, thromboelastography may allow for rapid quan
infiltration such as lipidosis (cats) and l y m p h o m a (cats and tification o f hemostasis (see Chapter 87).
dogs), will cause a decrease i n the activity o f clotting factors In dogs and cats with severe acute liver disease, spontane
i n many cases as a result o f hepatocyte damage and reduced ous bleeding may result from depletion of clotting factors;
synthesis i n the liver. In patients with l y m p h o m a or lipidosis i n addition, there is a potential for developing D I C (see
this decreased activity o f clotting factors is rapidly reversible Chapter 87). In patients with D I C , A P T T and O S P T may be
if the underlying disease can be successfully treated, thus prolonged, but it is impossible to distinguish this from
allowing recovery o f hepatocyte function. In one study o f reduced hepatic production o f clotting factors. However,
cats coagulopathies were seen most c o m m o n l y i n cats with measurement o f increased D-dimers and/or fibrin degrada
hepatic lipidosis and cats with inflammatory bowel disease tion products, combined with decreases in platelet count,
and concurrent cholangitis (Center et al., 2000). increases the index of suspicion for D I C . D-dimer concen-
trations are often mildly to moderately increased i n dogs individual up to 50% o f arterial a m m o n i a is metabolized i n
with liver disease because of reduced clearance i n the liver, skeletal muscle by conversion o f glutamate to glutamine,
and this does not necessarily mean that the dog has a t h r o m so loss o f muscle mass will reduce the ability to detoxify
bus or D I C . M o r e marked elevations are suggestive o f D I C . ammonia. W h a t gives the most cause for concern regarding
protein-calorie malnutrition i n the veterinary patient is that
Treatment it is often partly caused by well-meaning but unhelpful
Dogs and cats with prolonged clotting times associated with manipulations by the clinician or even by a lack o f recogni
chronic liver disease often respond to parenteral v i t a m i n K tion and attention (discussed i n greater detail later). For this
supplementation alone. It is recommended that all patients reason, it is very important that clinicians treating dogs with
receive vitamin K1 (phytomenadione), at a dosage o f 0.5 to chronic liver disease remain alert to the possibility of protein-
2.0 mg/kg administered I M or S Q 12 hours before biopsy calorie malnutrition.
and repeated q12h for 3 days as necessary. M a l n u t r i t i o n can also be seen i n dogs and cats with
It is important to monitor clotting during long-term congenital PSS, both as a result o f reduced liver synthetic
therapy (OSPT + A P T T or P I V K A ) and stop when they capability or as a result of inappropriately severe protein
normalize because it is possible to overdose on v i t a m i n K , restriction by the attending clinician. Cats with chronic liver
which can result i n Heinz body hemolysis. If the coagulopa disease may have negative energy balance, often as a result
thy fails to respond to vitamin K treatment alone or i f there of the effects o f concurrent intestinal and pancreatic disease
are clinical signs of hemorrhage associated with the disease reducing digestion and absorption o f food. In addition, cats
(which is more c o m m o n with acute disease), administration i n negative nitrogen balance are at a particular risk o f devel
of fresh frozen plasma or stored plasma is indicated to oping acute hepatic lipidosis (see Chapter 37) so protein-
replenish depleted clotting factors. A starting dose of 10 m l / calorie malnutrition i n this species requires particularly
kg given slowly is recommended; the dose o f plasma is aggressive management.
titrated on the basis of the results o f the O S P T and A P T T .
Again, liver biopsy, surgery or the placement o f central Clinical Signs and Diagnosis
venous catheters should not be contemplated until coagula W h e n suffering from severe malnutrition, dogs and cats
tion times have been normalized. appear cachectic, with reduced muscle mass. However, loss
The treatment o f D I C is difficult and frequently unsuc of muscle mass occurs relatively late i n the process, and i n
cessful. The most effective treatment is to remove the incit the earlier stages of protein-calorie malnutrition the animal's
ing cause, which i n acute liver failure i n humans means rapid body condition score may be n o r m a l and yet many poten
liver transplant. W i t h o u t this option i n dogs and cats, the tially deleterious effects on the i m m u n e system and gut wall
mortality i n D I C o f acute fulminant hepatitis is likely to be will already be under way. There is no simple b l o o d test that
100%. Recommended therapies include plasma transfusion allows diagnosis o f malnutrition. The most effective means
to replace depleted clotting factors and careful heparin to do this is by taking a careful history as well as performing
therapy during the hypercoagulable phase. However, the effi a clinical examination. A n y animal with liver disease should
cacy of heparin therapy i n D I C has recently been called into be considered as being at risk o f protein-calorie malnutri
question i n humans, and there are no clinical data support tion. A history o f partial or complete anorexia for more than
ing its use i n dogs and cats. 3 days or recent weight loss o f >10% not associated with
fluid shifts should trigger rapid and aggressive nutritional
management.
PROTEIN-CALORIE MALNUTRITION
Treatment
Pathogenesis The treatment is to feed the patient an appropriate diet.
Protein-calorie malnutrition is very c o m m o n i n dogs with Protein restriction should be avoided as m u c h as possible
chronic hepatitis as a result o f reduced intake caused by and i n some cases o f chronic liver disease associated with
anorexia, vomiting, and diarrhea and increased loss/wastage obvious cachexia, supplementation of a maintenance diet
of calories caused by hypermetabolism and poor liver func with extra high-quality protein (such as dairy protein) is
tion. Protein-calorie malnutrition is likely to have a serious even indicated. If the patient will not eat voluntarily, some
impact on both longevity and quality o f life in affected dogs. form of assisted tube feeding should be instituted short term.
There are no studies specifically addressing the effect o f mal This is particularly important i n cats w i t h hepatic lipidosis,
nutrition on survival and infections of dogs with liver disease, which almost invariably refuse to eat independently and require
but in other canine diseases it is k n o w n to increase the risk gastrostomy or esophagostomy tube feeding (see Chapter
of septic complications. This is true i n humans with portal 37). A search should then be made for any underlying cause
hypertension and also likely i n dogs. In humans with portal of anorexia, such as concurrent infections (see Fig. 39-1).
hypertension malnutrition also predisposes to gut ulcer It is very important to avoid iatrogenic malnutrition
ation. In addition, negative nitrogen balance and reduced while the patient is hospitalized. W i t h h o l d i n g food for several
muscle mass predispose to H E . Breakdown o f body protein days to allow multiple tests (e.g., liver biopsy or endoscopy)
results i n more ammonia production, and also i n a n o r m a l is a c o m m o n problem; tests should be spread out over a
longer period i f necessary to allow feeding between them. It Griffen A et al: Evaluation of a canine D-dimer point-of-care test
is also possible for malnutrition to develop unnoticed i n the kit for use in samples obtained from dogs with disseminated
hospital as a result of inadequate record keeping and fre intravascular coagulation, thromboembolic disease, and hemor
quent staff turnover. Finally, feeding an excessively protein- rhage, Am J Vet Res 64:1562, 2003.
Kummeling A et al: Coagulation profiles in dogs with congenital
restricted diet to a dog or cat with liver disease can also result
portosystemic shunts before and after surgical attenuation, / Vet
in negative nitrogen balance.
Intern Med 20:1319, 2006.
Laflamme DP et al: Apparent dietary protein requirement of dogs
Suggested Readings with portosystemic shunt, Am ] Vet Res 54:719, 1993.
Aronson LR et al: Endogenous benzodiazepine activity in the Lisciandro SC et al: Coagulation abnormalities in 22 cats with
peripheral and portal blood of dogs with congenital portosys naturally occurring liver disease, / Vet Intern Med 12:71, 1998.
temic shunts, Vet Surg 26:189, 1997. Mount M E at al: Use of a test for proteins induced by vitamin K
Badylak SF et al: Alterations of prothrombin time and activated absence or antagonism in diagnosis of anticoagulant poisoning
partial thromboplastin time in dogs with hepatic disease, Am J in dogs: 325 cases (1987-1997), / Am Vet Med Assoc 222:194,
Vet Res 42:2053, 1981. 2003.
Badylak SF et al: Plasma coagulation factor abnormalities in dogs Moore et al: Guidelines on the management of ascites in cirrhosis,
with naturally occurring hepatic disease, Am J Vet Res 44:2336, Gut 55 (suppl 6):vil, 2006.
1983. Niles JD et al: Hemostatic profiles in 39 dogs with congenital por
Bigge LA et al: Correlation between coagulation profile findings tosystemic shunts, Vet Surg 30:97, 2001.
and bleeding complications after ultrasound-guided biopsies: Shawcross D et al: Dispelling myths in the treatment of hepatic
434 cases (1993-1996), J Am Anim Hosp Assoc 37:228, 2001. encephalopathy, Lancet 365:431, 2005.
Center SA et al: Proteins invoked by vitamin K absence and clotting Wright G at al: Management of hepatic encephalopathy in patients
times in clinically ill cats, / Vet Intern Med 14:292, 2000. with cirrhosis, Best Pract Res Clin Gastroenterol 21:95, 2007.
C H A P T E R 40
GENERAL CONSIDERATIONS only by the pancreas i n the cat. In the dog the pancreas is the
main source of IF, but a small amount is also secreted by the
The pancreas is located i n the cranial abdomen, with the left gastric mucosa.
limb positioned between the transverse colon and the greater Diseases of the exocrine pancreas are relatively c o m m o n
curvature of the stomach and the right limb running along but often misdiagnosed i n both dogs and cats because of
side the proximal duodenum. A n y or all of these neighboring nonspecific clinical signs and a lack o f sensitive and specific
structures can be affected when there is pancreatic inflam clincopathological tests. Pancreatitis is the most c o m m o n
mation. The exocrine acini make up about 90% of pancreatic disease o f the exocrine pancreas i n both cats and dogs; EPI,
tissue, and the endocrine islets interspersed among the acini although less c o m m o n , is also recognized frequently. U n c o m
make up the other 10% (Fig. 40-1). The close anatomical m o n diseases o f the pancreas include pancreatic abscess,
association between the acini and islets allows subtle signal pseudocyst, and neoplasia.
ing between them to coordinate digestion and metabolism, Recent advances i n the understanding o f the pathophysi
but it also means that there is a complex cause-and-effect ology, prevalence, and potential causes o f pancreatitis i n
relationship between diabetes mellitus and pancreatitis. The dogs and cats may give clues to treatment i n the future,
major function o f the exocrine pancreas is to secrete diges although treatment o f acute pancreatitis remains largely
tive enzymes, bicarbonate, and intrinsic factor (IF) into the nonspecific and supportive i n all species.
proximal duodenum. Pancreatic enzymes are responsible for Important differences i n the anatomy of the pancreas and
the initial digestion o f larger food molecules and require an associated areas between the dog and cat are outlined i n
alkaline p H to function (hence the concurrent bicarbonate Table 40-1.
secretion by pancreatic duct cells). The pancreas secretes
several proteases, phospholipases, ribonucleases, and deoxy
ribonucleases as inactive precursors (zymogens) and also PANCREATITIS
-amylase and lipase as intact molecules. The pancreas is the
only significant source of lipase, and hence steatorrhea (fatty Pancreatitis may be acute or chronic. As with acute and
feces) is a prominent sign o f exocrine pancreatic insuffi chronic hepatitis, the difference is histological and not neces
ciency (EPI). Trypsin is central to the pathogenesis of sarily clinical (Table 40-2 and Fig. 40-2), and there is some
pancreatitis, as outlined i n the subsequent sections, and clinical overlap between the two. C h r o n i c disease may present
with the resulting pancreatic autodigestion, inflammation,
and peripancreatic fat necrosis that leads to focal or more
generalized sterile peritonitis. There is an associated systemic
inflammatory response (SIR) i n even the mildest cases of
pancreatitis. M a n y other organs may be involved, and i n the
most severe cases, there is multiorgan failure and diffuse
intravascular coagulation ( D I C ) . The circulating protease
inhibitors (1-antitrypsin (= -protease inhibitor) and -
1
Anatomy Usually two pancreatic ducts: Usually single major pancreatic duct joining the
(but many variations; large accessory duct from right limb to common bile duct before entering duodenum
some dogs are like minor papilla in duodenum at duodenal papilla 3 cm distal to pylorus
cats and vice versa) small pancreatic duct from left limb to 2 0 % of cats have second, accessory duct;
major duodenal papilla in duodenum occasionally ducts remain separate
beside (but not joining) bile duct Sphincter of O d d i may be as important as in
Sphincter of O d d i unlikely to be of clinical humans
significance
Pancreatic function Intrinsic factor secreted largely by Intrinsic factor secreted entirely by pancreas so
pancreas but also some in stomach; Vitamin B deficiency very common in
12
The clinical signs i n dogs vary with the severity of the causes of acute abdomen, particularly intestinal foreign body
disease from m i l d abdominal pain and anorexia at one or obstruction; the vomiting may be so severe that the dog
end of the spectrum to an "acute abdomen" and potential may undergo an unnecessary laparotomy for a suspected
multiorgan failure and D I C at the severe end of the spec obstruction if a careful workup was not performed first.
trum. Dogs with severe acute disease usually present with Some patients may show the classic "praying stance," with
acute vomiting, anorexia, marked abdominal pain, and the forelegs on the floor and the hindlegs standing (Fig.
varying degrees of dehydration, collapse, and shock. The 40-3), but this is not pathognomonic for pancreatitis and
vomiting is initially typical of delayed gastric emptying can be seen i n association with any pain i n the cranial
resulting from peritonitis, with emesis of undigested food a abdomen, including hepatic, gastric, or duodenal pain. By
long time after feeding progressing to vomiting only bile. contrast, cats with severe, fatal, necrotizing pancreatitis
The main differential diagnoses i n these cases are other usually have surprisingly m i l d clinical signs, such as anorexia
Differences Between Acute and Chronic Pancreatitis in Dogs and Cats
Histopathology Varying degrees of acinar necrosis, edema, Characterized by lymphocytic inflammation and
and inflammation with neutrophils and fibrosis with permanent disruption of
peri-pancreatic fat necrosis architecture
Potentially completely reversible with no Possible to have acute-on-chronic cases with
permanent pancreatic architectural or concurrent neutrophilic inflammation and
functional changes necrosis
Clinical appearance Spectrum from severe and fatal (usually Spectrum from mild, low-grade intermittent
necrotizing) to mild and subclinical gastrointestinal signs (most common) to an
(less common) acute-on-chronic episode indistinguishable from
classical acute pancreatitis
Diagnostic challenge Higher sensitivity of enzyme tests and Lower sensitivity of enzyme tests and
ultrasonography than in chronic disease ultrasonography than in acute disease:
diagnosis much more challenging
Mortality and long- High immediate mortality but no long-term Low mortality except acute-on-chronic bouts
term sequelae sequelae High risk of eventual exocrine and endocrine
insufficiency
TABLE 40-3
Causes of Acute Pancreatitis in Dogs and Cats
From Villiers E, Blackwood L, editors: BSAVA manual of canine and feline clinical pathology, ed 2, Gloucestershire, United Kingdom, 2 0 0 5 ,
British Small Animal Veterinary Association.
and lethargy; vomiting and abdominal pain occur i n fewer ses for this presentation i n dogs as well as cats. Animals that
than half the cases. are still eating may show prominent postprandial discomfort.
At the milder end of the spectrum, dogs and cats may Both cats and dogs with acute pancreatitis can present
present with m i l d gastrointestinal signstypically anorexia with jaundice, either at initial examination or often develop
and sometimes some m i l d vomiting, followed by the passage ing a few days later, when the initial acute signs are resolving.
of some colitic-like feces accompanied by some fresh blood In fact, most, if not all, animals with jaundice have acute-on-
resulting from local peritonitis in the area of the transverse chronic disease (see the section on chronic pancreatitis).
colon. Inflammatory bowel disease, low-grade infectious enter Careful clinical examination should focus on identifica
itis, and chronic hepatitis w o u l d be major differential diagno tion of the degree of dehydration and shock, careful assess-
FIG 40-2
A , Gross appearance of acute pancreatitis in a cat at laparotomy demonstrating
generalized hyperemia. It is also possible for acute pancreatitis to appear normal grossly.
B , Histopathological appearance of acute pancreatitis in a young adult female West
Highland White Terrier. Note prominent edema and inflammation disrupting the acini.
This case was fatal, but it would have been potentially completely reversible if the dog
had survived the acute phase. Hematoxylin and eosin x 1 0 0 . C , Gross appearance of
chronic pancreatitis in a middle-aged Jack Russell Terrier. Note nodular appearance of
pancreas and extensive adhesions to the duodenum obscuring the mesentery. It is also
possible for chronic pancreatitis to appear normal grossly. D , Histological appearance of
chronic pancreatitis from a 10-year-old male Cavalier King Charles Spaniel. Note fibrosis,
mononuclear inflammatory cells, and ductular hyperplasia. Hematoxylin and eosin x 2 0 0 .
E, Histological appearance of end-stage chronic pancreatitis in an 1 1-year-old neutered
female Cavalier King Charles Spaniel with diabetes mellitus and exocrine pancreatic
insufficiency. Note extensive fibrosis (green) and small islands of remaining acini (red).
Massons Trichrome x 4 0 . (A and C , From Villiers E, Blackwood L, editors: BSAVA manual
of canine and feline clinical pathology, ed 2, Gloucestershire, United Kingdom, 2 0 0 5 ,
British Small Animal Veterinary Association.)
ment for any concurrent diseases (particularly endocrine and treatment decisions, as outlined i n the following sec
disease), and careful abdominal palpation. In severe cases tions. A b d o m i n a l palpation should identify pancreatic pain
petechiae or ecchymoses suggestive of D I C may be identi and rule out, if possible, any palpable foreign bodies or intus
fied, and there may be respiratory distress associated with susceptions, although abdominal imaging will be required to
acute respiratory distress syndrome. Careful clinical and rule these out with confidence. In severe cases generalized
clinicopathological assessment of the degree of shock and peritonitis will result i n generalized unmistakable abdominal
concurrent organ damage is important for prognosis pain, whereas i n milder cases careful palpation of the cranial
abdomen is required to identify a focus of abdominal pain, Typical clinicopathologic abnormalities i n dogs and cats
as indicated i n Fig. 40-4. Occasionally, a cranial abdominal with acute pancreatitis are shown i n Table 40-4.
mass may be palpated, particularly in cats, representing a
focus of fat necrosis. More Specific Pancreatic Enzyme Assays
M o r e specific laboratory tests for the pancreas are the
Diagnosis catalytic assays amylase and lipase and the immunoassays
Routine Clinical Pathology trypsinlike immunoreactivity (TLI) and pancreatic lipase
Routine laboratory analysis (i.e., complete b l o o d count immunoreactivity (PLI). Catalytic assays rely on the ability
[ C B C ] , serum biochemical profile, and urinalysis) typically of the molecule to catalyze a reaction in vivo and thus rely
does not help i n arriving at a specific diagnosis, but it is very on presence of active enzyme; however, they are not species
important to perform these in all but the mildest cases specific. In cats amylase and lipase are of very questionable
because they give important prognostic information and aid diagnostic value. Immunoassays, however, use an antibody
in effective treatment, as outlined i n the following sections. against a part of the enzyme molecule distant from the active
site and thus will also measure inactive precursors (e.g., tryp
sinogen) and tend to be organ and species specific. The
advantages and disadvantages of the different assays are out
lined i n Table 40-5. Overall, P L I has the highest sensitivity
and likely the highest specificity i n both species and is the
only reliable test for pancreatitis currently available i n cats.
A SNAP test for canine P L I has recently been released by
I D E X X (see details at http://www.idexx.com/animalhealth/
testkits/snapcpl/index.jsp), which should aid in rapid
diagnosis.
Diagnostic Imaging
The most sensitive way to image the canine and feline pan
creas noninvasively is by ultrasonography. A b d o m i n a l radio
graphs i n patients with pancreatitis usually show m i l d or no
changes, even i n those with severe disease (Fig. 40-5).
However, i n patients with acute disease, abdominal radiog
raphy plays an important role in ruling out acute intestinal
FIG 40-3
obstruction, which w o u l d result i n obvious changes, primar
Dog exhibiting evidence of cranial abdominal pain by
assuming the "position of relief." (Courtesy Dr. William E. ily dilated, gas-filled, stacking loops of intestine. Classical
Hornbuckle, Cornell University, College of Veterinary radiographic changes i n dogs and cats with acute pancreati
Medicine.) tis include focal decrease i n contrast in the cranial abdomen
FIG 40-4
Carefully palpating a Cocker Spaniel for cranial abdominal pain. A , The clinician should
palpate craniodorsally under the rib cage for evidence of focal pancreatic pain (as shown
in this dog by turning of the head). B , With deep-chested dogs it helps to ask an assistant
to elevate the head of the dog to displace the pancreas caudally (effectively achieving the
opposite of the dog in Fig. 40-3).
Typical Clinicopathologic Findings in Dogs and Cats with Acute Pancreatitis
Data from Schaer M : A clinicopathological survey of acute pancreatitis in 3 0 dogs and 5 cats, J Am Anim Hosp Assoc 1 5 : 6 8 1 , 1 9 7 9 ; Hill
RC et al: Acute necrotizing pancreatitis and acute suppurative pancreatitis in the cat: a retrospective study of 4 0 cases (1976-1989), J Vet
Intern Med 7 : 2 5 , 1 9 9 3 ; Hess RS, et al: Clinical. Clinicopathological, radiographic and ultrasonographic abnormalities in dogs with fatal
acute pancreatitis: 7 0 cases (1986-1995), J Am Vet Med Assoc 2 1 3 : 6 6 5 , 1 9 9 8 ; Mansfield C S et al: Review of feline pancreatitis. Part 2:
clinical signs, diagnosis and treatment, J Feline Med and Surgery 3 : 1 2 5 , 2 0 0 1 .
The Use of Specific Catalytic Enzyme Tests and Immunoassays in the Diagnosis of Acute and Chronic Pancreatitis in
Dogs and Cats
Immunoassays
Canine TLI Elevations high specificity for Low sensitivity for diagnosis of pancreatitis (but high
pancreatitis sensitivity for EPI); said to rise and fall more quickly
than lipase or amylase; renally excreted: elevated
2 or 3 times in azotemia
M a y be inappropriately low in severe chronic cases
due to pancreatic depletion loss of tissue mass; no
clear prognostic significance
Feline TLI One of only two assays available for Lower sensitivity and specificity than canine TLI better
cats used for diagnosis of EPI; renally excreted so elevated
in azotemia
Canine PLI Early indications most sensitive and Increased in renal disease but may not be significantly
specific test for canine pancreatitis; so? (Unclear yet if affected by steroids)
organ specific, so no interference
from extrapancreatic sources
N o w available as in-house test
(see URL in text)
Feline PLI Very new test but appears most Very little published data available on its use
sensitive and specific test available
for feline pancreatitis
associated with local peritonitis; a dilated, fixed (C-shaped), dogs. Pancreatic M R I has not been reported in small animal
and laterally displaced proximal duodenum o n ventrodorsal species, and transendoscopic ultrasonography is not widely
views; and caudal displacement of the transverse colon. available, although it w o u l d be expected to be useful
Occasionally, a "mass" effect may be seen i n the region of the insofar as the pancreas can be imaged very closely from the
pancreas, usually the result of fat necrosis. Pancreatic tumors adjacent stomach or duodenum. Because all these techniques
by contrast are usually small, but it is impossible to differen require general anesthesia, they may never become widely
tiate fat necrosis from neoplasia using imaging alone. used i n small animal patients with severe acute pancreatitis.
A b d o m i n a l radiographs appear n o r m a l i n many dogs and Transcutaneous ultrasonography has a high specificity for
cats with acute or chronic pancreatitis. B a r i u m studies pancreatic disease (i.e., i f a lesion is found, it is real) but a
should be avoided, i f possible, because they do not contrib variable sensitivity depending on the skill of the operator
ute to diagnosis and the associated gut filling provides further and the severity of the disease. Ultrasonography has a
stimulus for pancreatic enzyme release. higher sensitivity for classical acute pancreatitis in both
The most sensitive imaging modalities i n humans with dogs and cats because associated edema and peripancreatic
pancreatitis are magnetic resonance imaging ( M R I ) , c o m fat necrosis result i n visible interfaces. The sensitivity is
puted tomography ( C T ) , or transendoscopic ultrasonogra m u c h lower for chronic pancreatitis i n both cats and dogs
phy. C T has so far proved disappointing i n both cats and (Fig. 40-6).
Fluid Analysis cats. However, elevations i n either plasma or urine T A P are
Some dogs and cats with pancreatitis have abdominal effu no more sensitive or specific than currently available blood
sion. Fluid analysis usually reveals serosanguineous sterile tests. In dogs the best prognostic indicator is the modified
exudates, although transudates and chylous effusions have organ score, as shown i n Tables 40-6 and 40-7. This system
also been reported in cats. Amylase and lipase activities i n has been extrapolated from humans, but its use as a prog
the fluid may be higher than in the serum, and elevated nostic and treatment indicator i n cats has not been critically
lipase in the effusion can be diagnostically helpful (Guija de evaluated. O f the individual diagnostic tests, the following
Arespacochaga et al., 2006). Pleural effusions also occur i n a were found to be negative prognostic indicators i n dogs: high
small number of dogs with acute pancreatitis as a result of urinary T A P : creatinine ratio, marked increases in serum
generalized vasculitis. lipase activity, marked increases i n serum creatinine and
The search continues for the ideal diagnostic test for pan phosphate concentrations, and l o w urine specific gravity. In
creatitis. Trypsin-activation peptide ( T A P ) is well conserved cats, the following negative prognostic indicators were found:
between species, so human ELISAs can be used for dogs and low ionized calcium and leukopenia. U r i n a r y or plasma T A P
do not appear to be prognostically useful i n cats, and neither
does the degree o f elevation o f T L I i n either species. The
prognostic significance of degree of elevation of cPLI activ
ity is currently u n k n o w n .
Histopathology
Definitive diagnosis of acute pancreatitis can be achieved
only via histopathology of a pancreatic biopsy, but this is
invasive and not indicated i n most cases. However, i f the
animal has a laparotomy during its investigation, the clini
cian should always remember to visually inspect the pan
creas and also, preferably, to obtain a small biopsy. The
pancreas usually appears grossly inflamed and may have a
FIG 40-5 masslike appearance. The latter is usually due to fat necrosis
Lateral abdominal radiograph from a 7-year-old Jack Russell and/or fibrosis and not neoplasia; therefore no animal should
Terrier with acute pancreatitis. There are minimal changes be euthanized on the basis of a tumorlike appearance in the
apparent apart from a mild loss of abdominal contrast, in
pancreas without supportive cytology or pathology because
spite of the severity of the disease. This does, however, help
to rule out acute obstruction because the intestinal loops are most large masses i n the pancreas are not tumors. As i n the
not dilated and gas filled. (Courtesy the Diagnostic Imaging small intestine, it is possible for the pancreas to appear
Department, Queen's Veterinary School Hospital, University grossly n o r m a l despite having clinically relevant disease, par
of Cambridge.) ticularly i n cats and i n dogs and cats with low-grade chronic
FIG 40-6
A , Typical ultrasonographic appearance of acute pancreatitis in a Miniature Schnauzer
with a diffusely hypoechoic pancreas (white arrows) with surrounding hyperechoic mesen
tery. B , Typical ultrasonographic appearance of chronic pancreatitis in an English Cocker
Spaniel. There is a masslike effect displacing the duodenum. Many dogs and cats with
chronic pancreatitis have an unremarkable abdominal ultrasound. (Courtesy the Diagnostic
Imaging Department, Queen's Veterinary School Hospital, University of Cambridge.)
disease. Pancreatic biopsy is safe and does not carry a high intravenous fluids and analgesia, and patients with mild
risk of postoperative pancreatitis, provided that the pancreas disease can sometimes be managed on an outpatient basis.
is handled gently and the b l o o d supply is not disrupted. It is The easiest and most practical way to scale treatment and
best to take a small biopsy f r o m the tip of a lobe and not to prognosis in dogs is to use the organ-scoring system m o d i
ligate any vessels, particularly o n the right limb, which shares fied f r o m h u m a n medicine by Ruaux and Atwell (1998) and
a b l o o d supply with the proximal duodenum. Ruaux (2000; see Tables 40-6 and 40-7). Cats, even those
However, in most cases a biopsy will not be performed with severe disease, are more difficult to assess because of
and diagnosis is based o n a combination of clinical suspicion, their m i l d clinical signs and because the utility of the organ-
specific enzyme tests, and diagnostic imaging. N o one n o n scoring system has not yet been assessed in this species. It
invasive test is 100% sensitive and specific for pancreatitis in therefore seems prudent to assume that all cats have severe
dogs and cats; in a few cases of even severe disease, all the disease unless proved otherwise and treat them intensively,
tests may be negative. with the intent of preventing hepatic lipidosis and other fatal
complications.
Treatment and Prognosis The inciting cause of the pancreatitis should be treated or
The treatment and prognosis of dogs and cats with acute removed i n the few cases where it is known (e.g., hypercal
pancreatitis depends o n the severity of the condition at pre cemia or drug-induced), and every effort should be made
sentation. Severe acute pancreatitis is a very serious disease, during treatment to avoid further potential triggers, as out
has a very high mortality, and requires intensive manage lined in Table 40-3. M o s t cases of pancreatitis are, however,
ment, whereas more moderate disease can be managed with idiopathic, and treatment is largely symptomatic. The one
TABLE 40-6
Modified Organ Scoring System for Treatment and Prognostic Decisions in Acute Pancreatitis
SEVERITY A N D DISEASE S C O R E * PROGNOSIS EXPECTED MORTALITY %
Mild 0 Excellent 0
Moderate 1 G o o d to fair 11
2 Fair to poor 20
Severe 3 Poor 66
4 Grave 100
*The severity scoring system is based on the number of organ systems apart from the pancreas showing evidence of failure or compromise at
initial presentation; see Table 40-7 for details on scoring. This scoring system was developed for acute pancreatitis in dogs. It is unclear
whether this system can be applied to cats or to acute-on-chronic pancreatitis in dogs.
From Ruaux C G et al: A severity score for spontaneous canine acute pancreatitis, Austr Vet J 7 6 : 8 0 4 , 1 9 9 8 ; and Ruaux C G : Pathophysiology
of organ failure in severe acute pancreatitis in dogs, Compend Cont Edu Small Anim Vet 2 2 : 5 3 1 , 2 0 0 0 .
TABLE 40-7
Criteria to Assess Organ System Compromise for Severity Scoring System in Canine Acute Pancreatitis
Buprenorphine Most generally useful IV, S C , IM: 0.01- IV, S C , IM as Concerns about effects on
analgesic in hospitalized 0.02 m g / k g dogs Sphincter of O d d i largely
case Orally in cats unfounded
Cats (but not dogs) may (Robertson
be dosed orally at home et a l . , 2003)
Butorphanol Authors have very limited 0.05-0.6 m g / k g IM, As dogs At analgesic doses in humans
experience of its use S C , or IV q6-8h; it increases pulmonary
other opiates preferred 0.1-0.2 m g / k g / h artery pressure and cardiac
in acute pancreatitis as a CRI work, unlike the other
because of O r a l : 0.5-1 m g / k g analgesics in the table, so
butorphanol's q6-12h other opiates preferred
cardiovascular effects
(see notes)
Meperidine Meperidine by injection 5 mg/kg S C , IM 3-5 mg/kg S C , Painful on injection
(Demerol) only, hence hospitalized q2h IM q2h Is derived from atropine and
animals therefore, in contrast to the
N O T for IV administration other opioids, is a
spasmolytic agent on
smooth musclemight be
useful for the gut
Methadone Little nausea or vomiting so 0.2-0.4 m g / k g SC 0.2 m g / k g S C Can produce dysphoria
more useful than or IM q4-6h or as or IM q4-6h
morphine required or as required
Hydromorphone 0.05 mg/kg IV q4h; 0.1 mg/kg IM Can produce dysphoria
0.1-0.4 m g / k g IM q7h
Fentanyl patches Very useful, care with 2-4 g/kg/h patch 25 (g/h patch 24-hour onset and 72-hour
home discharge with half duration in dogs; 7-hour
exposed onset and 72-hour duration
in cats
Tramadol Authors have no personal Oral: 2-5 mg / k g Oral: 2-4 m g / Tramadol also decreases
experience of using this q8-12h kg q 8-12 h cardiac contractility; should
in acute pancreatitis but not be used in acute phase
may be a useful drug for when myocardial depressant
home use orally for mild factor may be released.
to moderate pain. N o published studies on
pharmacokinetics in small
animals so doses empirical.
Dysphoria more likely in cats
Ketamine infusion Severe refractory pain in 2 g/kg/min As dogs Useful as adjunct, probably
hospitalized patient not suitable as sole
analgesic; can produce
dysphoria at higher
infusion rates
Lidocaine infusion Excellent analgesic for Bolus of 1 m g / k g IV 0.1 m g / k g / h Use with caution in cats
hospitalized patients followed by because of lidocaine
2 0 g/kg/min toxicity
infusion
Acetaminophen Mainstay nonsteroidal in 10 mg/kg orally D O N O T USE Should not be used if
(Paracetamol) human pancreatitis; q12h as is toxic significant concurrent liver
often neglected in dogs, disease
but useful because it
does not have the same
deleterious effects on the
gastrointestinal tract and
kidneys
TABLE 40-8
Details of Analgesics Used on Acute Pancreatitiscont'd
DOSE A N D DOSE A N D
ANALGESIC INDICATIONS A N D CAUTIONS ROUTE: D O G S ROUTE: CATS NOTES
Carprofen and Mainly for home use; Used Carprofen: 4 mg/kg Carprofen: Underestimated efficacy
other with great care because S C , IV, or orally 2 mg/kg S C , C O X 1:2 inhibition ratio of
nonsteroidal of potential gut and renal q 2 4 h ; maintain on IV, or orally; 65
antiinflammatory side effects in pancreatitis; 2 m g / k g q12h maintain on
drugs not for use in acute 2 mg/kg
disease or in the
presence of concurrent
hyperadrenocorticism or
steroid treatment
(With thanks to Dr. Jackie Brearley, Senior Lecturer in Veterinary Anaesthesia, the Queen's Veterinary School Hospital, University of
Cambridge, UK.)
IV, Intravenous; S C , subcutaneous; IM, intramuscular.
Recent studies and metaanalyses of studies of nutrition in experimental acute pancreatitis but not yet in clinical pan
human acute pancreatitis have led to changes in advice for creatitis in dogs, although the experiences from early
best-practice feeding in these cases (Meier and Beglinger, enteral feeding in other gastrointestinal diseases in this
2006). Note that early enteral nutrition is p a r t i c u l a r l y species, such as parvovirus enteritis (Mohr et al., 2003),
indicated in severe disease, which is perhaps unexpected suggest that the recommendations may be similar. Most
and counter to our current practice in dogs. recently, it has been suggested that feeding may even be
A negative nitrogen balance is common in acute pancre given safely intragastrically in humans with acute pancre
atitis and is associated with a tenfold increase in mortal atitis, although more studies are needed to confirm this.
ity, although there have been no studies looking at Type of diet used: In humans, elemental diets have been
association of disease severity with nitrogen balance. This used in most cases and usually by continuous infusion.
is also likely to be true in small animals but has not been N o studies have really assessed whether less elemental
specifically investigated. diets would also work. Recent studies looking at immune-
IV feeding of glucose, protein, or lipids does not stimulate modulating micronutrients in the diets, such as glutamine,
pancreatic secretions. However, whether feeding is IV or fiber, arginine, omega-3 fatty acids, and probiotic bacte
enteral, blood glucose should be kept normal because ria, have been encouraging (Pearce et al., 2006), but
hypoglycemia or hyperglycemia is associated with a more studies are needed before definite conclusions can
negative outcome. Insulin is used if the patient becomes be drawn. N o similar studies have been undertaken in
hyperglycemic on feeding, but this should be done only dogs and cats.
carefully in an intensive care situation with regular (hourly) In m i l d acute pancreatitis in humans current best practice
monitoring of blood glucose. is to withhold food in many cases for a little longer. Fluids,
Intrajejunal infusion of elemental diets in humans and electrolytes, and analgesics are delivered for 2 to 5 days,
experimental canine models of pancreatitis does not and then a diet rich in carbohydrate and moderate in fat
stimulate pancreatic enzyme release significantly. and protein is initiated with discharge on a normal diet
Early o r a l feeding after acute pancreatitis in humans is within 4 to 7 days. A g a i n , there are no specific recom
associated with increased pain, whereas jejunal feeding mendations for mild acute disease in dogs and cats.
is not. This has not been assessed in small animals. In c a t s : Current anecdotal recommendations are to feed
I m p o r t a n t : e a r l y i n t r a j e j u n a l f e e d i n g is p r e f e r r e d immediately in mild, moderate, and severe pancreatitis,
o v e r t o t a l p a r e n t e r a l n u t r i t i o n in p a t i e n t s w i t h preferably via a jejunostomy tube, although again it has
acute pancreatitis, particularly severe disease. been suggested that gastrostromy tubes with multiple low-
Results of metaanalysis in humans show that intrajejunal volume feeds should also be safe. There is just one case
feeding after 48 hours significantly reduced incidences of report of using an endoscopically placed J-tube in a
infections, reduced surgical interventions, and reduced cat with acute pancreatitis (Jennings et al., 2001). The
length of hospital stay and cost over total parenteral nutri emphasis on early feeding in cats comes from the risk of
tion. These findings have also been replicated in dogs with hepatic lipidosis.
although frequent small-volume feeds of a low-fat food via administered intramuscularly, subcutaneously, or orally
a gastrostomy tube is also well tolerated i n most dogs and three times a day, or 1 to 2 mg/kg, administered intrave
cats with moderate pancreatitis. A good initial choice is baby nously over 24 hours as a slow infusion), but its effect on
rice mixed with water followed by a low-fat proprietary vet stimulating gastric motility may increase pain and pancre
erinary diet (such as Eukanuba Intestinal Formula; H i l l ' s atic enzyme release i n some animals. A phenothiazine anti
i/d; Royal-Canin-Waltham Digestive low fat or Purina E N - emetic such as chlorpromazine may be more effective in
formula) (Fig. 40-7). Concurrent antiemetics are also essen some patients, but phenothiazines have sedative and hypo
tial to allow effective feeding i n many cases (see next section). tensive effects, which may be particularly marked if they are
In patients in which enteral nutrition is not possible or when used together with opioid analgesia, so care should be taken
only a small percentage of the daily caloric requirements can i n these cases. 5 - H T receptor antagonists such as ondanse
3
be given enterally, some form of supplemental parenteral tron are useful i n other forms of vomiting in dogs (such as
nutrition should be considered. This is most practically chemotherapy-induced emesis) but are best avoided in pan
administered as peripheral parenteral nutrition (see creatitis because they have occasionally been reported to
Chandler et a l , 2000). trigger pancreatitis i n humans. The newly available NK1
receptor antagonist maropitant, licensed for use in dogs, has
Antiemetics both central and peripheral antiemetic effects and is showing
Antiemetics are often necessary to manage acute vomiting i n promise as an antiemetic i n dogs with pancreatitis, although
dogs and cats with pancreatitis. Metoclopramide has been it is not licensed for use i n cats. (Maropitant is available as
used successfully i n dogs with pancreatitis (0.5 to 1 mg/kg, Cerenia (Pfizer) in either an injectable solution (10 mg/ml)
FIG 40-7
Baby rice is a good first choice for feeding dogs with acute pancreatitis because it
contains no fat and protein. It comes as a finely ground rice powder (A) that can then be
mixed with water and, if desired, a gravy substitute such as Bovril to enhance the flavor
for feeding (B).
or tablets (16 mg, 24 mg, and 60 mg). The dose of injection Treatment of Biliary Tract Obstruction
is 1 mg/kg (i.e., 1 m l per 10 kg body weight once a day for Associated with Pancreatitis
up to 5 days). The dose of the tablets is 2 mg/kg once a day M o s t cases of extrahepatic biliary obstruction secondary to
for up to 5 days. acute-on-chronic pancreatitis resolve with conservative
management, and surgical or needle decompression of the
Gastroprotectants gallbladder and stenting of the bile duct are usually unneces
Patients with acute pancreatitis have an increased risk of sary i n dogs and cats. In humans it has n o w been demon
gastroduodenal ulceration caused by local peritonitis; they strated that there is no advantage to surgical intervention i n
should be monitored carefully for evidence of this (melena, most patients and no difference i n the severity and chronic
hematemesis) and treated as necessary with sucralfate and ity of secondary liver disease between those treated medically
acid secretory inhibitors ( H blockers such as cimetidine,
2 and those treated surgically, provided the jaundice resolves
famotidine, ranitidine, or nizatidine or the proton p u m p within a m o n t h (Addallah et al 2007). N o such study has
inhibitor omeprazole). Cimetidine should be avoided i n been done i n small animals, so treatment advice has to be
animals with concurrent liver disease because of its effect on empirical: If the feces remain colored (not white or acholic,
the cytochrome P450 system. Ranitidine can be used instead which implies complete biliary obstruction) and the jaun
in these animals, but its additional gastric prokinetic effect dice gradually resolves over a week to 10 days, then surgical
can cause vomiting in some individuals; it should be discon intervention is not indicated and conservative management
tinued if this occurs. Because famotidine does not have these with antioxidants and ursodeoxycholic acid are advised (see
prokinetic effects, it may be preferable. Chapters 37 and 38).
Clinical Features
Dogs with chronic pancreatitis, regardless of the cause, most
c o m m o n l y present with m i l d intermittent gastrointestinal
signs. Typically, they have bouts of anorexia, occasional v o m
iting, m i l d hematochezia, and obvious postprandial pain,
which often goes on for months to years before a veterinar
ian is consulted. The trigger for finally seeking veterinary
attention is often an acute-on-chronic bout or the develop
ment o f D M or E P I . The m a i n differential diagnoses in the
low-grade cases are inflammatory bowel disease and primary
gastrointestinal motility disorders. Dogs may become more
playful and less picky with their food when they are switched
FIG 4 0 - 8 to a low-fat diet, which suggests that they previously had
A n 8-year-old neutered m a l e English C o c k e r S p a n i e l with postprandial pain. C h r o n i c epigastric pain is a hallmark of
c h r o n i c pancreatitis. the h u m a n disease and is sometimes severe enough to lead
to opiate addiction or surgery, so it should not be overlooked there is less edema than i n those with acute disease. A variety
or underestimated in small animal patients. In more severe, of ultrasonographic changes may be seen i n patients with
acute-on-chronic cases, the dogs are clinically indistinguish chronic pancreatitis, including a n o r m a l pancreas, a mass
able from those with classical acute pancreatitis (see preced lesion, a mixed hyperechoic and hypoechoic appearance to
ing section), with severe vomiting, dehydration, shock, and the pancreas, and sometimes an appearance resembling that
potential multiorgan failure. The first clinically severe bout of classical acute pancreatitis with a hypoechoic pancreas
tends to come at the end o f a long (often years) subclinical and a bright surrounding mesentery (Watson et al 2006b;
phase of quietly progressive and extensive pancreatic destruc see Fig. 40-6). In addition, i n patients with chronic disease
tion in dogs. It is very important for clinicians to be aware adhesions to the gut may be apparent, and the anatomy o f
of this because these dogs are at m u c h higher risk for devel the pancreatic and duodenal relationship may be changed
oping exocrine and/or endocrine dysfunction than those by these adhesions. Some patients (particularly Cocker
with truly acute pancreatitis; in addition, they usually already Spaniels) have large mass-like lesions associated w i t h fibrosis
have protein-calorie malnutrition at presentation, w h i c h and inflammation; some cases have tortuous and dilated,
makes their management even more challenging. It is also irregular ducts; and many cases have completely n o r m a l
relatively c o m m o n for dogs with chronic pancreatitis to first pancreatic ultrasonographic findings i n spite o f severe
present with signs of D M and a concurrent acute-on-chronic disease.
bout of pancreatitis resulting i n a ketoacidotic crisis. In some Likewise, clinical pathology can be helpful, but the results
dogs there are no obvious clinical signs until the develop may also be normal. Increases i n pancreatic enzyme a c t i v i
ment o f EPI, D M , or both. The development o f E P I in a ties are most likely to be seen during an acute-on-chronic
middle-aged to older dog of a breed not typical for pancre bout than during a quiescent phase o f disease (very similar
atic acinar atrophy has to increase the index o f suspicion for to the waxing-and-waning increases i n liver enzyme activi
underlying chronic pancreatitis. The development o f EPI or ties i n patients w i t h ongoing chronic hepatitis). Again,
D M i n a dog or cat with chronic pancreatitis requires the similar to the situation i n hepatic cirrhosis, in end-stage
loss of approximately 90% o f exocrine or endocrine tissue chronic pancreatitis there may not be enough pancreatic
function, respectively, which implies considerable tissue tissue left to produce increases i n enzyme activities, even i n
destruction and end-stage disease. acute flare-ups. O n the other hand, occasionally serum T L I
In cats the clinical signs of chronic pancreatitis are usually can temporarily increase into or above the n o r m a l range i n
very mild and nonspecific. This is not surprising considering dogs with E P I as a result o f end-stage chronic pancreatitis,
that cats display m i l d clinical signs, even i n association with confusing the diagnosis o f E P I i n these dogs. cPLI appears
acute necrotizing pancreatitis. One study showed that the to have the highest sensitivity for the diagnosis o f canine
clinical signs o f histologically confirmed chronic nonsup chronic pancreatitis, but even this has a lower sensitivity
purative pancreatitis i n cats were indistinguishable from than i n acute disease. The diagnostic sensitivity o f feline P L I
those of acute necrotizing pancreatitis (Ferreri et a l , 2003). for chronic pancreatitis i n cats is u n k n o w n .
However, chronic pancreatitis in this species is significantly It is important to measure serum B concentrations i n
12
more often associated with concurrent disease than acute dogs and cats with chronic pancreatitis. The gradual devel
pancreatitis, particularly inflammatory bowel disease, chol opment of EPI, combined often w i t h concurrent ileal disease
angiohepatitis, hepatic lipidosis, and/or renal disease. The particularly i n cats, predisposes to cobalamin deficiency, as
clinical signs o f these concurrent diseases may predominate, outlined i n the section o n E P I . If serum B concentration
1 2
further confusing diagnosis. Nevertheless, some cats will is low, cobalamin should be supplemented parenterally
eventually develop end-stage disease with resultant EPI (0.02 mg/kg, administered intramuscularly or subcutane
and/or D M . ously every 2 weeks i n dogs and cats until serum concentra
Chronic pancreatitis is the most c o m m o n cause o f extra tion is normalized).
hepatic biliary obstruction i n dogs (see Chapter 38), and
dogs and cats with acute-on-chronic pancreatitis frequently Biopsy
develop jaundice. The diagnosis o f chronic pancreatitis can be very difficult i n
dogs and cats, and difficulties i n diagnosis likely result i n
Diagnosis under-recognition o f the disease. Establishing a definitive
Noninvasive Diagnosis diagnosis relies o n obtaining a pancreatic biopsy. However,
In the absence o f a biopsy, which is the gold standard, the this w i l l not be indicated i n most cases until there are effec
clinician must rely on a combination o f clinical history, tive treatments because a biopsy is a relatively invasive
ultrasonography, and clinical pathology. The findings o n procedure, the results o f w h i c h do not alter treatment or
diagnostic imaging and clinical pathology are similar to outcome. However, with the potential for some more specific
those outlined in the section on acute pancreatitis and Tables therapies, routine biopsy may be indicated i n the future. In
40-4 and 40-5. However, changes tend to be less marked i n humans the preferred method is needle-biopsy via transen
dogs and cats with chronic pancreatitis, and the diagnostic doscopic ultrasonographic guidance. Transendoscopic ultra
sensitivity of all tests is lower. Ultrasonography has a lower sonography is very expensive and o f limited availability i n
sensitivity in dogs and cats with chronic disease because veterinary medicine, so i n dogs and cats surgical or laparo-
scopic biopsies remain the most applicable. Cytology o f EXOCRINE PANCREATIC INSUFFICIENCY
ultrasound-guided transcutaneous fine needle aspirates o f
the pancreas may help differentiate neoplasia or dysplasia EPI is a functional diagnosis that results from a lack o f pan
from inflammation, but veterinary experience i n this area is creatic enzymes. As such, unlike pancreatitis, it is diagnosed
very limited. If the clinician is performing a laparotomy to o n the basis o f clinical signs and pancreatic function tests
obtain other biopsies, it makes perfect sense to obtain a and not primarily the results of pancreatic histopathology,
pancreatic biopsy at that time as well. Pancreatitis is not a although finding a marked reduction in pancreatic acinar
risk, provided the pancreas is handled gently and the b l o o d mass on histology is supportive of a diagnosis of EPI. The
supply is not disrupted. However, the biopsy should be small pancreas is the only significant source o f lipase, so fat
and from the tip o f a lobe and may therefore miss the area maldigestion with fatty feces (steatorrhea) and weight loss
of disease, which is usually patchy, particularly early on, and are the predominant signs o f EPI.
can also be centered on large ducts. Unfortunately therefore,
even biopsy has its limitations. Pathogenesis
Pancreatic acinar atrophy ( P A A ) is believed to be the pre
Treatment and Prognosis dominant cause o f EPI i n dogs, but recent work has shown
Dogs and cats with chronic, intermittent pancreatitis may that end-stage chronic pancreatitis is also important i n this
have intermittent bouts o f m i l d gastrointestinal signs and species (Fig. 40-9; Watson and Herrtage, 2006a; Batchelor
anorexia, and the owner's primary concern is often that the et al., 2007a). P A A has not been recognized in cats; end-stage
pet has missed a meal. These animals can be managed at pancreatitis is the most c o m m o n cause o f feline EPI (Fig.
home, as long as anorexia is not long lasting, and the owner 40-10). The development o f clinical EPI requires approxi
should be reassured that a short period o f self-induced star mately a 90% reduction i n lipase production and thus exten
vation is actually beneficial because it provides pancreatic sive loss o f pancreatic acini. It is therefore extremely unlikely
rest. to occur after a severe bout o f pancreatitis; it tends to result
As i n patients with acute pancreatitis, the current prefer from chronic, ongoing disease. However, the chronic disease
ence is for symptomatic treatment. Dogs and cats with acute may be largely subclinical or only present as occasional clin
flare-ups require the same intensive treatment as dogs and ical acute-on-chronic episodes, so the degree of underlying
cats w i t h classical acute pancreatitis and have the same risk pancreatic damage may be underestimated.
of mortality (see preceding section). The difference from P A A is particularly recognized i n young German Shep
isolated acute pancreatitis is that if the animal recovers from herd Dogs (see Fig. 40-9, A) , i n which an autosomal mode
the acute bout, it is likely to remain with considerable exo of inheritance has been demonstrated, and has also been
crine and/or endocrine functional impairment. In the milder described i n Rough Collies, suspected in English Setters, and
cases symptomatic treatment can make a real difference i n sporadically reported i n other breeds. A recent large study of
the animal's quality o f life. Changing to a low-fat diet (such EPI i n the U . K . reported that young C h o w Chows were over-
as H i l l ' s I D , R o y a l - C a n i n - W a l t h a m Digestive l o w fat, or represented (Batchelor et al., 2007a). The pathogenesis was
Eukanuba Intestinal) apparently reduces postprandial pain u n k n o w n , but the juvenile onset suggested P A A or perhaps
and acute flare-ups i n many cases. Owners often underesti a congenital defect i n this breed.
mate the effects o f fatty treats, w h i c h can precipitate recur Histological studies i n German Shepherd Dogs suggest
rences i n susceptible individuals. Some animals need that P A A is an autoimmune disease directed against the
analgesia, either intermittently or continuously (see section acini (Wiberg et al., 2000). Therefore the islets are spared,
o n acute pancreatitis and Table 40-8). A c c o r d i n g to anec and dogs with P A A are not typically diabetic. However,
dotal reports, short courses o f metronidazole (10 mg/kg, P O affected dogs do not respond to immunosuppressive therapy.
q l 2 h ) seem to help some patients after acute bouts M o s t dogs develop the disease i n young adulthood, but a
presumably because they develop secondary bacterial over proportion o f G e r m a n Shepherd Dogs remain subclinical
growth as a result o f a "stagnant l o o p " phenomenon i n for a prolonged period o f time and present only late in
the adjacent duodenum. Serum B concentration should
1 2
life.
be measured regularly, and cobalamin should be supple In contrast, many dogs with end-stage chronic pancreati
mented parenterally as necessary (0.02 mg/kg, administered tis also develop D M either before or after EPI as a result of
intramuscularly 2 to 4 weeks until serum concentration concurrent islet cell destruction (Watson, 2003; Watson
normalizes). et al., 2006a). The situation is similar i n cats with end-stage
Treatment o f extrahepatic biliary tract obstruction asso chronic pancreatitis. There is no breed relationship in cats,
ciated with acute-on-chronic disease should be as outlined but dogs with E P I as a result of end-stage chronic pancreati
i n the acute pancreatitis section. tis tend to be middle-aged to older m e d i u m - or small-breed
In patients with end-stage disease, exocrine and/or endo dogs, particularly Cavalier K i n g Charles Spaniels, English
crine deficiency may develop. Dogs and cats w i t h E P I and/or Cocker Spaniels, and Collies (see Fig. 40-8). Interestingly,
D M are managed with enzymes (discussed i n more detail although Boxers i n the U . K . were reported to have an
later) and insulin as necessary i n the usual way (see Chapter increased prevalence o f chronic pancreatitis in one study,
52), and most do surprisingly well long term. they have also been reported to be significantly under-
FIG 40-9
A , Physical appearance of a 2-year-old male German Shepherd Dog with exocrine
pancreatic insufficiency (EPI). B , An 11-year-old neutered female English Springer Spaniel
with EPI caused by end-stage chronic pancreatitis. This dog also had diabetes mellitus
(DM) but was still losing weight in spite of good control of the D M . EPI had not initially
been suspected, but once it was diagnosed and treated with enzyme supplements, the
dog returned to normal weight and coat condition within 6 months (C). (A, Courtesy Dr.
William E. Hornbuckle, Cornell University, College of Veterinary Medicine. B , From
Journal of Small Animal Practice vol. 4 4 , 2003.)
A low serum TLI (<2.5 g/l in dogs) in a dog with com In another proportion of dogs (about 10%), the TLI will
patible clinical signs, particularly in a high-risk breed, is decrease to the level diagnostic of EPI and in some it
diagnostic of EPI may remain in the grey area.
A repeat blood sample to confirm diagnosis in a few In an older dog that is not a German Shepherd Dog,
weeks to months is recommended in cats and in older TLI values may fluctuate as described below and
dogs that are not German Shepherd Dogs. Occasion samples should be repeated when there is no clinically
ally, a single TLI may be low in a dog with pancreati acute flare-up
tis as a result of a temporary reduction in enzyme A normal TLI in a German Shepherd Dog rules out EPI
production. resulting from PAA, and a search should be made for
A low serum TLI (<2.5 g/1 in dogs) with no compatible another cause of the presenting clinical signs.
clinical signs (i.e., no weight loss or diarrhea) is not A single normal or high TLI in an older nonGerman Shep
diagnostic of EPI but should be repeated herd Dog with suspicious clinical signs does not rule out
A dog with persistently low TLI but no steatorrhea or EPI. TLI can transiently and intermittently increase into or
weight loss should be considered to have subclinical above the normal range in dogs with EPI secondary to
EPI and should not be treated but monitored for any chronic end-stage pancreatitis if it is measured during a
evidence of clinical disease. A TLI stimulation test may bout of inflammation. This is understandable because EPI
give more information about the status of the animal reduces TLI but pancreatitis elevates it, so the two condi
but is rarely performed. Subclinical EPI has been tions occurring concurrently interfere with interpretation
reported in a small number of German Shepherd Dogs of the test. This is likely to be true in cats as well, although
with PAA (Wiberg et al 1999) but has not yet been it has not been well documented in that species. Therefore
reported in cats. It is uncommon. in any animal with suspected EPI secondary to chronic
A TLI in the gray area (2.5-5.0 g/1 in dogs) is not diag pancreatitis, TLI measurements should be repeated, pref
nostic of EPI and should be repeated in a few weeks to erably when the animal is showing no clinical signs of
months pancreatitis. Alternatively, a test for enzyme activity in the
In a proportion of dogs (45% in one study: Wiberg gut such as a fecal elastase test could be used in these
et al., 1999), the TLI will return to the normal range. animals.
Note: A TLI stimulation test could be used in animals with subclinical EPI (low TLI but no clinical signs) or animals with a TLI persistently in
the grey area. Pancreatic enzyme output is stimulated either with intravenous cholecystokinin and secretin or with a test meal, and TLI
concentrations are measured before and after stimulation (Wiberg et al., 1999). Animals with true clinical EPI show no stimulation, whereas
animals with subclinical EPI still have enough enzyme activity to increase their TLI after stimulation. The value of a stimulation test in clinical
cases is limited because the decision to treat is based on the clinical signs. It is of more value in monitoring progression of disease for clinical
research.
EPI, Exocrine pancreatic insufficiency; PAA, pancreatic acinar atrophy.
Fecal tests for EPI are rarely used because of low sensitiv on three days or using a cut-off value for diagnosis of EPI,
ity and specificity compared with serum tests. Measuring which is below this variation i n most dogs.
fecal trypsin activity has a very low sensitivity and specificity
for EPI, as do assessment of fecal proteolytic activity or OTHER DIAGNOSTIC TESTS
microscopic examination of feces for undigested fat, starch, It is also advisable to measure serum cobalamin concentra
and muscle fibers. A l l these tests have been superseded by tion in animals with EPI because cobalamin concentration
measurement of serum T L I and cPLI. Measurement of fecal is often reduced because of a deficiency of pancreatic intrin
elastase may have some utility in dogs with EPI as a result of sic factor, as previously explained. If serum B concentration
1 2
chronic pancreatitis or duct blockage, in which T L I results is low, it should be supplemented parenterally. (0.02 mg/kg,
may be misleading. Elastase appears to have higher sensitiv administered intramuscularly every 2 to 4 weeks until serum
ity and specificity than the other fecal tests for the diagnosis concentration normalizes).
of EPI in dogs. Elastase is a pancreatic enzyme, and a species- Serum folate concentrations are high i n about a third of
specific ELISA for canine elastase has been developed and is dogs with EPI. This may indicate SIBO, although the sensi
available for commercial use i n dogs (Spillman et a l , 2000 tivity and specificity of high serum folate concentration for
and 2001). As with canine T L I , because there is no cross- the diagnosis of SIBO is poor. The definition and diagnosis
reaction with elastase from other species, dogs can remain of SIBO is problematic, and it is better to assume that a
on enzyme supplementation while the test is performed. newly diagnosed dog with EPI has SIBO and treat it appro
There is marked variation in elastase levels in normal canine priately than to rely o n the results of diagnostic tests. The
feces compared with humans. The sensitivity and specificity importance of SIBO i n cats with EPI is u n k n o w n . Occasion
of the test are improved by taking three separate fecal samples ally i n dogs and cats with EPI, serum folate concentration
may be low; this can suggest either dietary deficiency or gain may be very difficult to achieve with a low-fat diet.
concurrent inflammatory or infiltrative disease i n the There is no convincing evidence i n the literature that long-
jejunum. U n l i k e cobalamin, there is no clear evidence that term feeding o f a low-fat diet improves outcome i n dogs
folate should be supplemented i n dogs when it is low. with P A A , although there is some evidence that it may result
i n faster resolution o f clinical signs. However, high-fat diets
Treatment (such as proprietary renal diets) should obviously be avoided.
DRUGS W e therefore recommend that dogs with P A A be fed a normal
A l l dogs and cats w i t h clinical EPI require enzyme supple- to moderately fat-restricted, highly digestible diet with rea-
mentation for life. In most cases this is provided as a powder sonable calorie density. The diet should also be low in fiber
or in the form o f a capsule, which is opened and then sprin- because fiber impairs the activity of pancreatic enzymes and
kled on the food. Fresh raw pancreas (which can be frozen soluble fiber may actually absorb pancreatic enzymes. Fiber
i n aliquots) may be used as an alternative and can be very may also reduce small intestinal absorption and activity of
effective, but there is also the potential for acquiring gastro- brush border enzymes. The proprietary veterinary diets mar-
intestinal infections (such as Salmonella and C a m p y l o - keted for gastrointestinal disease i n dogs (e.g., Hill's ID,
bacter). The dose o f enzymes is initially as recommended by Royal-Canin Digestive l o w fat H E , and Eukanuba Intestinal
the manufacturer and then titrated to the individual. A large or Dermatosis FP) fulfill these requirements and are recom-
proportion o f enzyme activity is lost i n the acid p H o f the mended, at least for initial stabilization. In the long term,
stomach (up to 83% o f lipase activity and 65% o f trypsin after the gut wall recovers, these dogs can be maintained on
activity). T o overcome this, either the dose o f enzymes given a normal fat level in most cases and can often return to their
is increased or an H blocker is administered concurrently to
2 normal diet. In some individuals with P A A extra calories can
increase gastric p H . Preincubating enzymes with the food is be added to the diet between meals i n the form of medium
not indicated because they require the alkaline environment chain triglycerides, such as coconut oil. They should not be
of the small intestine to work properly. In the long term it is used i n cats and should not be given in overly high doses i n
often possible to decrease the dose o f enzymes given (but not dogs because o f the risk o f osmotic diarrhea. The recom-
stop altogether). This may be due to resolution o f the sec- mended daily amount is to 4 teaspoons i n dogs in divided
ondary bacterial overgrowth and the effects o f chronic m a l - doses. M e d i u m chain triglycerides also cannot carry fat-
nutrition and cobalamin deficiency on enterocytes and brush soluble vitamins, will cause vomiting in some individuals,
border enzymes. Reports suggest that enzyme replacement and are contraindicated i n dogs with liver disease because
may be reduced over the long term by between 6% and 58% they may worsen encephalopathy.
but not stopped altogether. In dogs with EPI as a result of C P , dietary advice is slightly
Dogs and cats with EPI and concurrent SIBO require different. M a n y of these dogs benefit from long-term feeding
courses o f appropriate antibiotics (oxytetracycline, tylosin, of a low-fat diet, which seems to reduce postprandial pain
or metronidazole). It is advisable to administer prophylactic and acute flare-ups o f disease (Hill's I D ; Royal-Canin Diges-
medication for presumed SIBO i n all newly diagnosed cases tive l o w fat, or Eukanuba Intestinal). Therefore proprietary
for 3 to 4 weeks i n view o f the high prevalence o f concurrent low-fat diets w o u l d be preferred i n these patients. The use of
bacterial overgrowth and the difficulty i n diagnosing it, m e d i u m chain triglycerides is not recommended in dogs
although it remains unclear whether initial antibiotic therapy with chronic pancreatitis, but fortunately these are often
improves prognosis. small-breed dogs with less cachexia than the German
Dogs and cats with documented hypocobalaminemia will Shepherd Dogs with P A A .
require parenteral vitamin B injections (0.02 mg/kg, a d m i n -
1 2 It is best to feed two or more meals a day, each with
istered intrumuscularly every 2 to 4 weeks until serum con- enzymes added, and the dog should not be allowed to scav-
centration normalizes). It is relatively c o m m o n for G e r m a n enge. This is often difficult because they are polyphagic, but
Shepherd Dogs with P A A to have concurrent inflammatory scavenging, especially o f fatty foods, causes recurrence of
bowel disease, and this must also be addressed. Animals with diarrhea and sets back recovery.
EPI as a result o f chronic pancreatitis may require insulin Cats with EPI are often best managed on a hypoallergenic
therapy for concurrent D M and other therapies for acute intestinal type diet (e.g., H i l l ' s D D , Eukanuba dermatosis
flare-ups, including analgesics, as outlined i n the section o n L B , or Royal-Canin limited ingredient diets) because there
pancreatitis. is a high incidence o f concurrent inflammatory bowel
disease. If they are also diabetic, it is unclear whether they
DIET should be fed an intestinal diet or a proprietary feline dia-
Disruption of fat digestion is the most important feature o f betes diet (e.g., H i l l ' s M D , Royal-Canin diabetic diet, or
EPI. A low-fat food has therefore been traditionally recom- Purina D M ) .
mended, but it may not contain enough calories to feed a
large-breed dog (e.g., a G e r m a n Shepherd Dog) effectively. Prognosis
Fat usually contributes a significant proportion o f daily The prognosis for dogs with EPI is good because the disease
energy intake because it is more energy-dense than carbohy- can be treated. However, a surprising number of dogs (19%
drates. In large-breed dogs with EPI and cachexia, weight i n one recent study) are euthanized within the first year of
treatment because o f poor response to therapy (Batchelor Neuroendocrine tumors such as insulinomas and gastri
et al., 2007b). The same study showed that the median sur nomas appear to be more c o m m o n than pancreatic adeno
vival time o f dogs that responded to treatment was very carcinomas i n dogs and tend to be seen i n different breeds
good, at 1919 days. This underlines the importance of sched of dog, predominantly large breeds (Watson et al., 2007).
uling regular follow-up appointments, particularly i n the These are tumors o f the endocrine pancreas that produce
initial stages o f therapy, to evaluate progress and change clinical signs related to secretion o f hormones and are
management as necessary. Prognosis for dogs and cats with therefore outside the scope o f this chapter.
EPI as a result o f end-stage chronic pancreatitis is surpris
ingly good i n most cases, even i f it is complicated by concur
rent D M , with survival times o f several years i n most cases. PANCREATIC ABSCESSES, CYSTS,
AND PSEUDOCYSTS
EXOCRINE PANCREATIC NEOPLASIA Pancreatic abscesses, cysts, and pseudocysts are u n c o m m o n l y
reported i n dogs and cats and are usually a complication or
Neoplasms of the exocrine pancreas are u n c o m m o n i n both sequela o f pancreatitis. Pancreatic cysts may be congenital
cats and dogs. Pancreatic adenocarcinomas have a very (e.g., as part o f the polycystic renal disease i n Persian cats)
aggressive biological behavior and have usually disseminated or secondary to cystic neoplasia, but the most c o m m o n are
widely by the time o f diagnosis. They are often subclinical pseudocysts secondary to pancreatitis. A pancreatic pseudo
until they have disseminated, but they can result i n single or cyst is a collection o f fluid containing pancreatic enzymes
repeat bouts o f pancreatitis and/or the development o f EPI. and debris i n a nonepithelialized sac. Pseudocysts have been
Some pancreatic tumors have been associated with paraneo recognized i n association with pancreatitis i n both cats and
plastic syndromes such as sterile panniculitis i n dogs, alope dogs, although they appear to be rare, and microscopic
cia with shiny skin i n cats, and hypercalcemia. C h r o n i c acinar cysts were found frequently i n feline chronic pancre
pancreatitis is a risk factor for the development of pancreatic atitis. Pseudocysts are not associated with any distinct c l i n i
adenocarcinomas i n humans, and this may also be true i n copathological findings other than those associated with the
dogs because the published reports o f these tumors i n dogs underlying pancreatitis. Analysis o f fluid obtained from a
show a predominance o f Cocker and Cavalier K i n g Charles pseudocyst by fine needle aspiration generally shows a m o d
spaniels. ified transudate. The activities o f amylase and lipase can be
Pancreatic adenomas are rare i n small animals but have measured i n the pseudocyst fluid. In humans the enzymes
been reported i n cats. N o d u l a r hyperplasia o f the exocrine are higher i n pseudocysts associated with pancreatitis than
pancreas is also c o m m o n i n older dogs and cats. This usually i n those associated with cystic carcinomas, but the value o f
presents as multiple small masses, whereas pancreatic tumors this measurement i n small animals is u n k n o w n . Cytology
are usually single, but histopathology or cytology is neces can differentiate a pseudocyst from a true abscess because a
sary to definitively differentiate hyperplasia from neoplasia. pseudocyst contains amorphous debris; some neutrophils
Both dogs and cats with acute and chronic pancreatitis and macrophages; and, rarely, small numbers o f reactive
sometimes present with a large pancreatic "mass" as a result fibroblasts, whereas an abscess contains many degener
of fat necrosis and/or associated fibrosis, and it is important ative neutrophils and variable numbers o f pancreatic acinar
not to confuse these with neoplasia. Again, histopathology is cells, which may appear very atypical as a result o f
required to differentiate these conditions. Ultrasound-guided inflammation.
fine needle aspiration cytology has been suggested as a useful A true pancreatic abscess is a collection o f septic exudate
means of differentiating inflammatory and neoplastic lesions that results from secondary infection o f necrotic pancrea
of the pancreas (Bjorneby and Kari, 2002). Clinical use i n tic tissue or a pancreatic pseudocyst. They are associated
dogs and cats is limited, but it has been reported to be helpful with a poor prognosis but fortunately are rare i n dogs and
in diagnosis i n some studies (Bennet et al., 2001). cats.
Pancreatic tumors are not associated with any specific Treatment o f pancreatic pseudocysts can be surgical or
clinicopathological changes and may cause no changes i n medical. M e d i c a l treatment by ultrasound-guided cyst aspi
enzymes at all. Alternatively, they can result i n recurrent ration has had a reasonable success rate. Pancreatic abscesses
bouts o f pancreatitis with typical associated b l o o d changes, should be treated surgically with omentalization or open
and EPI can develop. In some cases biliary tract obstruc peritoneal drainage. Both carry a high mortality rate, but a
tion may occur with associated jaundice and marked eleva recent study suggested that omentalization may be preferable
tions i n liver enzyme activities. Occasionally, pancreatic (Johnson et a l , 2006).
tumors have been reported associated with marked
hyperlipasemia. Suggested Readings
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exocrine pancreatic insufficiency, / Small Anim Prac 32:613, Spillmann T et al: A n immunoassay for canine pancreatic elastase
1991. 1 as an indicator of exocrine pancreatic insufficiency in dogs,
Ferreri JA et al: Clinical differentiation of acute necrotizing / Vet Diagnost Invest 13:468, 2001.
from chronic non-suppurative pancreatitis in cats: 63 cases Steiner J M et al: Serum canine lipase immunoreactivity in dogs
(1996-2001), J Am Vet Med Assoc 223:469, 2003. with exocrine pancreatic insufficiency, / Vet Intern Med 15:274,
Gerhardt A et al: Comparison of the sensitivity of different 2001.
diagnostic tests for pancreatitis in cats, / Vet Intern Med 15:329, Swift N C et al: Evaluation of serum feline tryspin-like immunore
2001. activity for diagnosis of pancreatitis in cats, J Am Vet Med Assoc
Guija de Arespacochaga A et al: Comparison of lipase activity in 217:37, 2000.
peritoneal fluid of dogs with different pathologiesa comple Watson PJ: Exocrine pancreatic insufficiency as an end stage of
mentary diagnostic tool in acute pancreatitis? / Vet Med 53:119, pancreatitis in four dogs, / Small Anim Pract 44:306, 2003.
2006. Watson PJ et al: A prospective observational study of 30 cases of
th
Hall EJ et al: A survey of the diagnosis and treatment of canine canine chronic pancreatitis. Proceedings of the 16 ECVIM-CA
exocrine pancreatic insufficiency, / Small Anim Prac 32:613, Congress Amsterdam, and published in the Journal of Veterinary
1991. Internal Medicine, 20:1519, 2006a.
Hess RS, et al: Clinical, clinicopathological, radiographic and ultra Watson PJ et al: Prevalence and breed distribution of chronic
sonographic abnormalities in dogs with fatal acute pancreatitis: pancreatitis at post-mortem examination in first opinion dogs.
70 cases (1986-1995), J Am Vet Med Assoc 213:665, 1998. / Small Anim Prac 48:609, 2007.
Hess RS et al: Evaluation of risk factors for fatal acute pancreatitis Watson PJ et al: Chronic pancreatitis in cocker spaniels shows
in dogs, J Am Vet Med Assoc 214:46, 1999. features of human autoimmune pancreatitis.Proceedings of
th
Hill RC et al: Acute necrotizing pancreatitis and acute suppurative the 16 E C V I M - C A Congress Amsterdam, and published in
pancreatitis in the cat: a retrospective study of 40 cases (1976- the Journal of Veterinary Internal Medicine, 20:1518, 2006b.
1989), / Vet Intern Med 7:25, 1993. Weiss DJ et al: Relationship between inflammatory hepatic disease
Jennings M et al: Successful treatment of feline pancreatitis using and inflammatory bowel disease, pancreatitis and nephritis in
an endoscopically placed gastrojejunostomy tube, / Am Anim cats, J Am Vet Med Assoc 206:1114, 1996.
Hosp Assoc 37:145, 2001. Westermarck E et al: Exocrine pancreatic insufficiency in dogs,
Johnson M D et al: Treatment for pancreatic abscesses via omental- Vet Clin Nh Am Small Anim Pract 33:1165, 2003.
ization with abdominal closure versus open peritoneal drainage Wiberg M E : Pancreatic acinar atrophy in German shepherd dogs
in dogs: 15 cases (1994-2004), / Am Vet Med Assoc 228:397, and rough-coated collies. Etiopathogenesis, diagnosis and treat
2006. ment. A review, Vet Q 26:61, 2004.
Kimmel SE et al: Incidence and prognostic value of low plasma Wiberg M E et al: Cellular and humoral immune responses in atro
ionised calcium concentration in cats with acute pancreatitis: 46 phic lymphocytic pancreatitis in German shepherd dogs and
cases (1996-1998),} Am Vet Med Assoc 219:1105, 2001. rough-coated collies, Vet Immunol Immunopathol 76:103, 2000.
Mansfield CS et al: Trypsinogen activation peptide in the diagnosis Wiberg M E et al: Serum trypsinlike immunoractivity measurement
of canine pancreatitis, / Vet Intern Med 14:346, 2000. for the diagnosis of subclinical exocrine pancreatic insufficiency,
Mansfield CS et al: Review of feline pancreatitis. Part 2: clinical / Vet Intern Med 13:426, 1999.
signs, diagnosis and treatment, / Feline Med Surg 3:125, Williams DA, Batt R M : Sensitivity and specificity of radioimmuno
2001. assay of serum trypsin-like immunoreactivity for the diagnosis
Meier RF et al: Nutrition in pancreatic diseases, Best Pract Res Clin of canine exocrine pancreatic insufficiency, / Am Vet Med Assoc
Gastroenterol 20:507, 2006. 192:195, 1988.
DRUG N A M E (TRADE NAME) DOSAGE INDICATIONS A N D C O M M E N T S
Continued
D R U G N A M E (TRADE N A M E ) DOSAGE INDICATIONS A N D C O M M E N T S
Maropitant Dogs only: 1 mg/kg S C q24h for Centrally acting antiemetic in new class (NK1 receptor
(Cerenia) up to 5 days or 2 m g / k g orally antagonist); antiemetic of choice in canine
q24h for up to 5 days pancreatitis as no obvious prokinetic effect; used
with care in liver disease because metabolized in
the liver, so do not use if significant liver
dysfunction; not licensed for cats
Ondansetron Cats and dogs: 0.5 mg/kg IV Refractory vomiting; may be contraindicated in
(Zofran) loading dose followed by pancreatitis because it has been reported to trigger
0.5 mg/kg/hour infusion q6h or it in humans
0.5-1 mg/kg P O q12-24h
ANTIENCEPHALOPATHIC
Lactulose 5-15 ml P O q8h (dogs) Hepatic encephalopathy with acquired or congenital
0.25-1 ml P O q8h (cats) portosystemic shunts; overdose produces diarrhea;
C a n also be given as retention titrate to effect (= 2-3 soft bowel movements a day)
enema in acute encephalopathy
Antibiotics (e.g., ampicillin, See antibacterial section
metronidazole, neomycin)
Propofol Constant rate infusion; rate Drug of choice for seizures because of liver disease/
calculated by giving an initial hepatic encephalopathy; should not be used in
bolus to effect (usually about pancreatitis because it is a lipid vehicle
1 mg/kg) and timing duration of
action; usually about 0.1-
0.2 m g / k g / m i n
Phenobarbital 5-10 m g / k g P O q24h Can be used prophylactically before and immediately
preoperatively followed by 3- after surgery to reduce risk of postoperative
5 m g / k g q12h postoperatively seizures after ligation of PSS, but evidence of
for 3 weeks effectiveness is anecdotal
ANTIINFLAMMATORY and
ANTIFIBROTIC
Prednisolone (prednisone) Antiinflammatory dose: 0.5 m g / k g Antiinflammatory or immunosuppressive doses in
q 2 4 h ; immunosuppressive dose: lymphocytic cholangitis in cats and chronic hepatitis
1-2 m g / k g q24h. Taper at in dogs and in suspected immune-mediated
0.5 m g / k g q24h or eod pancreatitis in English Cocker spaniels
Avoid in suppurative cholangitis; avoid in portal
hypertension or animals with ascites (potential G l
ulceration); avoid use of dexamethasone because
very ulcerogenic
Colchicine Dogs only 0.03 m g / k g / d a y P O Antifibrotic of choice in moderate hepatic fibrosis in
dogs, but efficacy unclear; monitor blood samples
for bone marrow suppression; G l side effects
common and most likely reason to stop therapy
ANTIOXIDANTS
S-adenosylmethionine Dogs: 2 0 m g / k g P O q24h or Indicated in any liver disease but particularly hepatic
(SAM-e) higher; cats: 2 0 m g / k g or lipidosis in cats and toxic hepatitis and diseases
(Denosyl) 200-400 mg total daily causing biliary stasis in dogs and cats; tablets must
be given whole on an empty stomach for effective
absorption
Sylmarin (silymarin, silibin) 50-200 m g / d o g P O q24h Antioxidant derived from milk thistle; likely effective
and safe, but very limited studies to base dose
advice on in dogs; studies were in toxic hepatitis
Vitamin E (tocopherol) 4 0 0 IU per day for medium-sized Indications as S A M e but including any chronic
dogs (titrate accordingly for hepatitis in dogs
other sizes) or 5-25 l U / k g P O
daily dogs and cats
DRUG N A M E (TRADE NAME) DOSAGE INDICATIONS A N D COMMENTS
Continued
D R U G N A M E (TRADE N A M E ) DOSAGE INDICATIONS A N D C O M M E N T S
DIURETIC
Furosemide 2 mg/kg P O q8-12h dogs and Use as additional diuretic where necessary in ascites
cats of liver disease; always use concurrent
spironolactone to avoid compensatory increase
aldosterone action with further water retention and
hypokalaemia
Spironolactone 2-4 mg/kg day in divided doses Diuretic of choice in ascites of liver disease (see text
dogs and cats Chapter 39); Gradual onset of action over 2-3
days; may be combined with furosemide for more
marked diuresis
TREATMENT O F
COAGULOPATHIES
Fresh frozen plasma Dogs and cats: starting dose of Replenish depleted clotting factors in severe acute or
10 ml/kg; the dose of plasma is chronic liver disease, particularly if prolonged OSPT
titrated based on the results of a n d / o r APTT and no response to vitamin K
the OSPT and APTT treatment alone
Vitamin K1 (Phytomenadione) 0.5-2 mg/kg SC or IM 12 hours Treatment of coagulopathy associated with liver
(Konakion) before biopsy and then q12h for disease, particularly if concurrent biliary stasis a n d /
3 days or gut disease reducing vitamin K absorption;
treatment of coagulopathy before liver biopsy
VITAMINS
Vitamin B 12 Dogs and cats: 0.02 m g / k g IM or Treatment of vitamin B deficiency, particularly
12
(Cyanocobalamin) SC every 2-4 weeks until serum associated with EPI and lack of pancreatic intrinsic
concentration normalizes (oral factor
dosing ineffective in EPI because
of ineffective absorption)
Vitamin K1 (Phytomenadione) See treatment of coagulopathy
section
Vitamin E See antioxidant section
Vitamin C (ascorbic acid) Cats and dogs oxidant toxins: Indicated only as supportive treatment for oxidant
30-40 mg/kg S C q6h for 7 toxins affecting the liver (e.g., acetaminophen)
treatments Not indicated in other cases of hepatitis or copper
storage disease because increases absorption and
hepatic build-up of metals
PO, By mouth; SC, subcutaneous; IV, intravenous; GI, gastrointestinal; PSS, portosystemic shunt; IM, intramuscular; EPI, exocrine pancreatic
insufficiency.
PART FIVE URINARY TRACT DISORDERS
G r e g o r y F. G r a u e r
C H A P T E R 41
Clinical Manifestations of
Urinary Disorders
TABLE 41-1
Numbers of Bacteria per Milliliter Considered Significant According to Method of Urine Collection in Dogs and Cats
patients with a functional obstruction, whereas an anatomic or a midstream catch during voiding. However, the number
obstruction w i l l result i n "grating," difficult passage or the of organisms isolated i n a normal dog or cat varies according
inability to pass the catheter. If there is any question, a pos to the technique used (Table 41-1). Ideally, urine should be
itive contrast retrograde urethrogram w i l l confirm the pres obtained by cystocentesis, and urine specimens should be
ence o f an anatomic lesion or obstruction. If a complete plated w i t h i n 30 minutes o f collection. If this is not possible,
urethral obstruction exists, the degree o f postrenal azotemia the urine sample should be refrigerated i n a closed container
and hyperkalemia should be assessed immediately. H y p e r k a because bacteria may double their numbers i n urine every
lemia can cause life-threatening cardiac arrhythmias and 45 minutes at r o o m temperature, resulting i n false-positive
should be treated p r o m p t l y (see Fig. 41-1). culture findings. O n the other hand, false-negative urine
culture results may be obtained i f the urine has been frozen
URINARY TRACT INFECTION or refrigerated for 12 to 24 hours or more.
U r i n e for urinalysis and bacterial culture may be obtained A n i m a l s with recurrent or refractory urinary tract infec
by antepubic cystocentesis, urinary bladder catheterization, tions (UTIs) should undergo ultrasonography or contrast-
enhanced radiography i n a search for underlying anatomic urease-producing bacteria are present); cystine uroliths
disorders. Bladder tumors or polyps, uroliths, pyelonephri with an acidic urine; and oxalate, urate, and silicate uroliths
tis, prostatitis, ureteroceles, and urachal remnants are with a neutral-to-acidic urine. Crystalluria may be observed
common causes o f recurrent or unresponsive U T I s . In depending o n the urine concentration, p H , and temperature.
some cases, systemic disorders such as hyperadrenocorti Although crystalluria may exist i n the absence o f uroliths,
cism, chronic kidney disease, and diabetes mellitus may be and uroliths may be present i n the absence of crystalluria, i f
associated with recurrent UTIs, as can long-term corticoste the two coexist, the identity of the crystals is usually the same
roid treatment. UTIs are discussed i n greater depth i n as that o f the urolith (Figs. 41-2 to 41-6). Exceptions do
Chapter 45. occur, however; for example, a urease-producing bacterial
infection could generate struvite crystals i n the presence o f
TRANSITIONAL CELL CARCINOMA silicate or calcium oxalate uroliths. Bacterial urine culture
Transitional cell carcinoma ( T C C ) is the most c o m m o n and sensitivity testing should be performed i n all animals
malignant bladder tumor in dogs and should be suspected with urolithiasis to identify and properly treat any concur
in older dogs with hematuria, pollakiuria, and dysuria- rent U T I . If a cystotomy is performed to remove stones,
stranguria. T C C s are rare i n cats, where they are usually a small piece o f the bladder mucosa or urolith should be
detected as a diffuse thickening of the bladder wall during
palpation or imaging. T C C s most frequently arise i n the
bladder trigone region; therefore rectal palpation can often
detect their presence. U r i n a r y bladder ultrasonography or
double contrast-enhanced cystography will confirm that a
bladder mass exists. In some cases, unilateral or bilateral
hydroureter-hydronephrosis is observed as a result of obstruc
tion o f one or both ureters at the vesicoureteral junction.
T u m o r biopsy and histopathologic evaluation should be done
to confirm the tumor type and stage and to direct the nature
of specific treatment. The bladder tumor antigen test ( V -
B T A test: www.polymedco.com) is usually not recommended
as a diagnostic aid because it does not reliably differentiate
dogs with bladder cancer from dogs with L U T I resulting
from other causes. In some specialty practices, cystoscopy
provides a simple method to obtain a diagnostic sample for
histopathology and assess the extent of bladder involvement
FIG 4 1 - 3
in dogs and cats with infiltrative bladder diseases.
Struvite crystals in urine sediment. These crystals a r e
normally colorless. (From G r a u e r GF: C a n i n e urolithiasis. In
UROLITHIASIS Allen D G , editor: Small animal medicine, Philadelphia,
Urinary bladder and urethral uroliths can often be palpated 1 9 9 1 , JB Lippincott.)
during abdominal or rectal examination; however, a full
bladder or a thickened, inflamed bladder wall may obscure
small uroliths. In male dogs with dysuria, the urethra should
be palpated subcutaneously from the ischial arch to the os
penis i n a search for urethral uroliths. Ultrasonography
or plain or contrast-enhanced radiography of the urinary
tract may be necessary to confirm the presence o f uroliths.
Calcium oxalate and struvite uroliths are the most radiodense,
whereas urate uroliths are relatively radiolucent, and c o n
trast-enhanced radiographs may be required for their diag
nosis. Silicate and cystine uroliths have an intermediate
radiodensity, and unless the stones are small (<5 m m i n
diameter), they can usually be observed o n plain film
radiographs.
Urinalysis findings i n dogs and cats with urolithiasis often
indicate the presence of urinary tract inflammation (e.g.,
hematuria, pyuria, increased numbers of epithelial cells, and
FIG 4 1 - 3
proteinuria). The urine p H varies depending o n the stone
M o n o h y d r a t e calcium oxalate crystals in urine sediment.
type, on the presence or absence o f a concurrent bacterial These crystals a r e normally colorless. (From G r a u e r GF:
infection, and on the animal's diet. In general, struvite uro C a n i n e urolithiasis. In Allen D G , editor: Small animal
liths are associated with an alkaline urine (especially i f medicine, Philadelphia, 1 9 9 1 , JB Lippincott.)
FIG 4 1 - 4 FIG 4 1 - 6
Dihydrate calcium oxalate crystals in urine sediment. These Cystine crystals in urine sediment. These crystals a r e
crystals a r e normally colorless. (From G r a u e r GF: C a n i n e normally clear to light yellow. (From Grauer GF: Canine
urolithiasis. In Allen D G , editor: Small animal medicine, urolithiasis. In Allen D G , editor: Small animal medicine,
Philadelphia, 1 9 9 1 , JB Lippincott.) Philadelphia, 1 9 9 1 , JB Lippincott.)
Struvite
Urine is usually a c i d i c to neutral.
8 0 % to 9 7 % of uroliths in female d o g s are struvite. Uroliths a r e relatively radiolucent.
Uroliths in d o g s y o u n g e r than 1 year of a g e are usually Increased incidence in d o g s w i t h severe hepatic insuffi
struvite. ciency (e.g., portosystemic shunts in M i n i a t u r e Schnau
There is a high incidence of concurrent u r i n a r y tract infec zers a n d Yorkshire Terriers).
tion (especially Staphylococcus or Proteus spp.).
Urine is usually alkaline. Silicate
Uroliths are radiodense. Increased prevalence in male d o g s (especially G e r m a n
Increased prevalence in M i n i a t u r e Schnauzers, M i n i a t u r e Shepherd Dogs, G o l d e n Retrievers, a n d Labrador
Poodles, Bichon Frises, Cocker Spaniels. Retrievers).
Urine is usually a c i d i c to neutral.
Calcium O x a l a t e Urolith r a d i o d e n s i t y is v a r i a b l e .
Increased prevalence in older male d o g s (especially M i n H i g h d i e t a r y intake o f silicates p r o b a b l y predisposes
iature Schnauzers, M i n i a t u r e Poodles, Yorkshire Terriers, (corn gluten a n d s o y b e a n hulls).
Lhasa Apsos, Bichon Frises, a n d Shih Tzus).
Cystine
Urine is usually acidic to neutral.
Uroliths are radiodense. Increased prevalence in male d o g s (especially Dachs
Hypercalcemia m a y b e a contributing factor. hunds, Basset H o u n d s , Bulldogs, Yorkshire Terriers, Irish
Terriers, C h i h u a h u a s , Mastiffs, a n d Rottweilers).
A m m o n i u m Acid Urate
Urine is usually a c i d i c .
Increased prevalence in male d o g s (especially Dalma Urolith r a d i o d e n s i t y is v a r i a b l e .
tians a n d Bulldogs).
congested and it may protrude from the prepuce. Occasion Because the urine strip reagents detect hemoglobin and
ally, a urethral plug is seen extending from the urethral myoglobin, a positive " b l o o d " test i n a urine dipstick does
orifice, and i n some cases the cat may lick its penis until it not necessarily mean that the patient has hematuria, and the
becomes excoriated and bleeds. sediment should be evaluated microscopically (discussed i n
A history of acute onset of pollakiuria, dysuria- more detail later). Hematuria occurring i n conjunction with
stranguria, and hematuria i n an otherwise healthy cat i n d i pollakiuria and dysuria-stranguria is usually associated with
cates L U T D . Physical examination should include digital L U T I . Conversely, hematuria that occurs i n the absence o f
rectal palpation o f the caudal bladder and urethra i n an other clinical signs often originates from the upper urinary
attempt to determine whether there are masses or calculi, as tract. Hematuria may be gross (macroscopic hematuria) or
well as abdominal palpation o f the bladder before and after occult (microscopic hematuria). Occult hematuria (more
voiding to determine the residual urine volume and whether than five red b l o o d cells per high-power field) is often present
there are intraluminal masses or uroliths. The m i n i m a l diag in dogs and cats with pollakiuria and dysuria-stranguria.
nostic workup i n cats with pollakiuria and dysuria-strangu The diagnostic w o r k u p i n dogs and cats with hematuria is
ria should always include a complete urinalysis. The urine directed toward identifying the origin o f the hemorrhage as
should preferably be obtained by cystocentesis; however, i f well as the underlying disease.
manipulation o f the bladder during abdominal palpation In most cases hematuria is caused by inflammation,
results i n voiding, a sample obtained from a clean tabletop trauma, or neoplasia o f the urogenital tract; however, hema
may be used to assess urine p H and sediment. turia may also be caused by systemic bleeding disorders,
A n extensive diagnostic evaluation o f the unobstructed strenuous exercise, heat stroke, or renal infarcts. The renal
cat is usually not warranted. In most o f these cases the urine telangiectasia that occurs i n Cardigan Welsh Corgis may also
is bacteriologically sterile, and clinical signs respond to cause hematuria, as can the renal hematuria i n Weimaraners.
canned food dietary therapy. However, if clinical signs persist The timing o f gross hematuria during voiding may provide
beyond 5 to 7 days o f instituting dietary therapy, a second clues as to the source o f the hemorrhage. Hematuria that
urinalysis with a urine culture and sensitivity, radiography occurs at the beginning o f voiding (initial hematuria) is sug
of the abdomen, ultrasonography, and/or contrast-enhanced gestive o f hemorrhage originating from the lower urinary
cystography-urethrography should be performed (Fig. 41-7). tract (bladder neck, urethra, vagina, vulva, penis, or prepuce).
Extraurinary causes such as proestrus, metritis, pyometra,
HEMATURIA prostatic disease, or neoplasia o f the genital tract may also
Hematuria, the presence of red blood cells i n the urine, is cause initial hematuria (Table 41-2). H e m a t u r i a that occurs
frequently encountered i n clinical veterinary medicine. at the end o f voiding (terminal hematuria) usually results
FIG 41-7
D i a g n o s t i c p l a n for feline l o w e r u r i n a r y tract i n f l a m m a t i o n s y n d r o m e .
TABLE 4 1 - 2
U R I N A R Y CAUSES E X T R A U R I N A R Y CAUSES
Initial hematuria
Urethral causes S p o n t a n e o u s b l e e d i n g unassociated w i t h v o i d i n g m a y also occur w i t h
Trauma the f o l l o w i n g :
Infection Prostatic: i n f e c t i o n , cyst, abscess, tumor
Urolithiasis Uterine: i n f e c t i o n , tumor, proestrus, subinvolution
Neoplasia V a g i n a l : tumor, t r a u m a
G r a n u l o m a t o u s urethritis P r e p u t i a l / p e n i l e : tumor, t r a u m a
Bladder trigone region
Neoplasia
Pseudohematuria
Kidney, ureter, b l a d d e r Prostatic (see a b o v e )
Trauma B l e e d i n g disorders
Infection H e a t stroke
Urolithiasis Exercise-induced
Tumor
Parasitism
Drug i n d u c e d ( c y c l o p h o s p h a m i d e )
Feline l o w e r u r i n a r y tract i n f l a m m a t i o n s y n d r o m e
Renal infarct
Renal t e l a n g i e c t a s i a
I d i o p a t h i c renal h e m a t u r i a
from hemorrhage originating from the upper u r i n a r y tract hematuria), the hemorrhage usually originates i n the bladder,
(bladder, ureters, or kidneys). In this case the hemorrhage ureters, or kidneys. Pseudohematuria may be caused by myo
may be intermittent, w h i c h allows the red b l o o d cells to settle globin or h e m o g l o b i n , drugs, and natural or artificial food
i n the bladder and be expelled w i t h the last o f the bladder dyes i n the urine. In cases o f pseudohematuria, the urine
contents. If hematuria occurs throughout voiding (total supernate remains discolored after centrifugation.
In dogs and cats with hematuria caused by inflammation, the pelvic inlet. In larger female dogs digital vaginal palpa
trauma, or neoplasia o f the lower urinary tract, concurrent tion and the use of a vaginal speculum or scope allow for the
clinical signs usually include pollakiuria and dysuria- urethral orifice to be evaluated; vaginal masses, strictures,
stranguria. Hematuria associated with upper urinary tract and lacerations can be ruled i n or out i n this way. In male
disease may be associated with systemic signs, including dogs the perineal urethra should be palpated subcutaneously
depression, lethargy, anorexia, vomiting, diarrhea, weight from the ischial arch to the os penis, and the penis should
loss, and abdominal pain, or it may be asymptomatic. In be extruded from the prepuce and examined to determine
some cases upper urinary tract hemorrhage can result i n the whether there are masses, signs o f trauma, or urethral pro
formation of blood clots i n the bladder, leading to subse lapse. Finally, catheterization o f the urethra i n dysuric
quent dysuria-stranguria. If hemorrhage from the genital animals allows assessment o f urethral patency; when i n d i
tract is causing hematuria, spontaneous bleeding not associ cated, positive contrast retrograde urethrography or ultraso
ated with voiding may also be observed. A d d i t i o n a l signs nography can be employed to outline urethral anatomic
indicating that the genital tract is the source o f hemorrhage abnormalities.
include a purulent vaginal or urethral discharge independent C o m p a r i s o n o f urine obtained by cystocentesis with
of voiding, behavioral changes (e.g., proestrus), or straining voided urine may help differentiate lower urinary tract or
to defecate i n association with a stilted gait (e.g., prostatic genital tract disease from upper urinary tract disease. Cysto
disease). centesis prevents the urine from being contaminated with
A complete physical examination often helps localize the bacteria, cells, and debris from the urethra, vagina, vulva,
source of the hematuria. If possible, the kidneys should be prepuce, or uterus; however, prostatic disease may alter the
palpated and assessed i n terms o f their size, shape, consis characteristics o f urine obtained by cystocentesis (as a result
tency, and symmetry and for the presence o f pain. The of the reflux of fluid into the bladder). A b n o r m a l urinalysis
urinary bladder should be palpated before and after voiding, findings i n urine collected by cystocentesis indicate involve
because, as already noted, a full bladder may obscure intra ment o f the bladder, ureters, kidneys, or prostate. It should
luminal masses, uroliths, or wall thickening. Observation o f be remembered, however, that catheterization or bladder
voiding should also be part of the physical examination and expression, and to a greater extent cystocentesis, may result
provides the opportunity to obtain a voided urine sample in traumatic microscopic hematuria.
(Fig. 41-8). In addition, the timing o f the hematuria can be Urinalysis should be performed as soon as possible after
confirmed and the character o f the urine stream, as well as urine collection. In addition to evaluating the urine sedi
the presence or absence of dysuria, can be noted. Rectal ment for red b l o o d cells, the clinician should look for white
palpation allows evaluation of the prostate i n male dogs and b l o o d cells, epithelial cells, t u m o r cells, casts, crystals, para
of the pelvic urethra i n dogs and cats of both sexes. The site ova, and bacteria. If urine remains at r o o m temperature
trigone region o f the bladder can also be palpated rectally i n for more than 30 minutes, urease-producing bacteria can
small dogs and cats; this is facilitated by concurrent abdom proliferate, resulting i n an increase i n the urine p H , w h i c h
inal palpation, with the examiner pushing the bladder toward may cause red and white b l o o d cells and casts to fragment
FIG 4 1 - 8
Diagnostic a p p r o a c h to d o g s a n d cats w i t h h e m a t u r i a .
and lyse and may alter the crystal composition. In addition, is unilateral or bilateral. Nuclear medicine (technetium
hyposthenuria can result i n the lysis o f red and white b l o o d labeled red b l o o d cells) can also be used to localize renal
cells, and lysed red b l o o d cells i n urine may create confusion hematuria to one individual kidney.
between hemoglobinuria and hematuria. Refrigeration is
the easiest way to preserve the stability o f a urine sample.
A l t h o u g h overnight refrigeration i n a closed sterile container DISORDERS OF MICTURITION
is acceptable for urine to be used for bacterial culture samples,
it is not recommended for urine intended for chemical and Disorders o f micturition include both urine retention and
cellular analysis. urine leakage (incontinence). Incontinence, the inappropri
Reagent strips used to detect b l o o d i n urine do so by ate passage o f urine, may be caused by congenital abnor
detecting the peroxidase-like activity o f hemoglobin from malities or acquired disorders. In evaluating an animal with
lysed cells. The test can detect approximately 0.05 to 0.3 m g incontinence, the clinician may find it helpful to determine
of hemoglobin per deciliter of urine (equivalent to 10,000 whether the urinary bladder is distended, small, or normal
lysed red b l o o d cells per milliliter o f urine, or approximately in size (Table 41-3). Distended bladders are associated with
three lysed red b l o o d cells per high-power field). These urine retention and are usually caused by either detrusor
reagent test strips also show a positive reaction for b l o o d i n hypocontractility or increased outflow resistance. Increased
the presence o f myoglobinuria. outflow resistance may be anatomic (e.g., urethral urolith)
A C B C and serum biochemistry profile should be evalu or functional (e.g., reflex dyssynergia). Urinary incontinence
ated i n dogs and cats with hematuria and concurrent w i l l occur with a primary urine retention disorder when
systemic signs. A n inflammatory leukogram is compatible intravesicular pressure overcomes outflow resistance pres
with metritis-pyometra, acute bacterial pyelonephritis, or sure. This type of incontinence is termed paradoxic.
prostatitis. Azotemia occurring i n association with hematu M o r e commonly, however, incontinence is associated with a
ria usually indicates the presence o f renal parenchymal small or normal-sized bladder that is typically caused by
disease or a rent i n the urinary excretory pathway; how either decreased outflow resistance or increased detrusor
ever, prerenal causes o f azotemia should also be ruled out. contractility.
If the b l o o d loss caused by hematuria is severe or i f signs
of generalized bleeding exist, a hemostasis profile, platelet Initial Evaluation
count, and bleeding time s h o u l d be evaluated (see The age of onset, reproductive status, age at neutering,
Chapter 87). current medications, and history of trauma or previous
Plain and contrast-enhanced radiography, ultrasonogra urinary tract disorders are important anamnestic points to
phy, and/or cystoscopy w i l l often help show the location and cover when obtaining the history i n an animal with disorders
cause o f hematuria. In some cases, abdominal exploratory of micturition. The physical examination should include an
surgery and biopsy may be necessary to arrive at a diagnosis. evaluation o f the perineum for evidence of urine scalding or
Biopsy specimens may be obtained from the kidneys, bladder, staining. Thorough palpation o f the bladder to assess its size
and prostate gland; i f indicated, individual ureteral catheter and wall thickness and a rectal examination to assess anal
ization through a cystotomy or visualization through a cys tone, the prostate gland, the pelvic urethra, and the trigone
toscope may be performed to determine i f renal hematuria region o f the bladder should be performed i n all cases. A
TABLE 4 1 - 3
DISORDERS CLINICAL S I G N S
Large bladder
Lower motor neuron lesions D r i b b l i n g of urine; distended b l a d d e r that is easily expressed; history of trauma or surgery
in pelvic region
U p p e r motor neuron lesions Distended b l a d d e r that is difficult to express; possible presence o f paresis or paralysis
Reflex dyssynergia O f t e n , large-breed male d o g ; distended b l a d d e r that is difficult to express but easy to
catheterize; urine stream initiated a n d then interrupted
O u t f l o w tract obstruction Usually male animals; dysuria-stranguria, d r i b b l i n g of urine; distended bladder that is
difficult to express a n d catheterize
Small bladder
Urethral sphincter mechanism M i d d l e - a g e d or older neutered or spayed d o g s ; d r i b b l i n g of urine usually occurring w h e n
incompetence a n i m a l is relaxed o r asleep, normal v o i d i n g otherwise
Detrusor h y p e r r e f l e x i a / i n s t a b i l i t y Pollakiuria, dysuria-stranguria, hematuria, bacteriuria
C o n g e n i t a l abnormalities Young a n i m a l ; constant d r i b b l i n g o f urine possible, v o i d i n g possibly normal otherwise
digital vaginal examination is indicated, and vaginoscopy bladder helps localize the lesion and classify the injury as an
may be used to help identify congenital defects (e.g., vaginal upper motor neuron ( U M N ) lesion (located above the fifth
strictures, ectopic ureters) i n female dogs. lumbar vertebral body) or a lower motor neuron ( L M N )
A neurologic examination should include evaluation o f lesion (located at or below the fifth lumbar vertebral body).
the perineal and bulbospongiosus reflexes. The perineal The most characteristic sign o f an L M N lesion to the bladder
reflex causes the anal sphincter to contract and the tail to is a distended bladder that is easily expressed. A n L M N injury
ventroflex i n response to pinching o f the perineal skin. The affecting innervation to the bladder creates both sphincter
bulbospongiosus reflex causes the anal sphincter to contract and detrusor hyporeflexia; i f the lesion involves the S1-S3
in response to gentle compression o f the bulb o f the penis spinal cord segments, both perineal and bulbospongiosus
or the vulva. Both of these reflexes are dependent on an reflexes are absent.
intact pudendal nerve (sensory and motor) and intact sacral A n i m a l s with U M N lesions to the bladder characteristi
spinal cord segments S1-S3. If both reflexes are normal, the cally have a large, distended bladder that is difficult to express;
pudendal reflex arc is intact. Because the pelvic nerve (sensory the U M N lesion may also cause paresis or paralysis. A n i m a l s
and motor parasympathetic innervation to the detrusor with a U M N lesion have no voluntary control o f micturition,
muscle) arises from the same sacral cord segments, damage and the urethral sphincter shows reflex hyperexcitability
to the pudendal nerve may also affect the pelvic nerve. because there is a lack o f inhibition to the somatic efferents
Dogs should be walked outside so that the voiding posture i n the pudendal nerve, making expression o f the bladder
and urine stream size and character can be observed. Imme difficult. W i t h time, U M N bladders may develop reflex c o n
diately after the animal has attempted to void, the bladder traction and partial emptying i n response to detrusor stretch
should be palpated to estimate the residual volume (normal ing. This "automatic" emptying occurs without control or
residual volume is approximately 0.2 to 0.4 ml/kg). Catheter sensation.
ization to quantify the residual volume is indicated i f a large Reflex dyssynergia or detrusor-urethral dyssynergia is a
bladder is palpable after voiding (in male dogs behavioral condition observed p r i m a r i l y i n large-breed male dogs. The
urine marking can make it difficult to assess the true residual cause is usually difficult to determine but may include any
urine volume). of several neurologic lesions o f the spinal cord or autonomic
A urinalysis should be performed i n all animals with ganglia. Reflex dyssynergia results from active contraction o f
urinary incontinence. If a bacterial urine culture is indicated, the detrusor without relaxation o f the internal or external
as noted earlier, cystocentesis is the preferred method o f col urethral sphincters. Characteristic signs o f reflex dyssynergia
lection; however, dogs and cats with a distended bladder include a n o r m a l or near-normal initiation o f voiding, fol
should ideally be catheterized to empty the bladder and lowed by a narrowed urine stream. U r i n e may be delivered
prevent the possibility of urine from leaking from the cysto i n spurts, or flow may be completely disrupted and the
centesis site. animal w i l l often strain to produce urine. After a while, the
dog lowers his leg and then often begins dribbling urine as
Pharmacologic Testing and Treatment he walks away. A l t h o u g h it is difficult to express urine from
Frequently, the diagnosis o f disorders of micturition (see the bladder o f a dog with reflex dyssynergia, urethral cath
Chapter 48) is based to some degree on the animal's response eterization is usually easy.
to pharmacologic testing and therapy. For example, detrusor Incontinence i n an animal w i t h urinary outflow tract
hypocontractility should improve i n response to a parasym obstruction is called paradoxic incontinence. It occurs because
pathomimetic drug such as bethanechol, and urethral hypo intravesical pressure exceeds the pressure within the urethra,
tonicity should respond to - a d r e n e r g i c agents such as allowing urine to leak past the obstruction before a urethral
phenylpropanolamine or hormone replacement therapy. or bladder rupture occurs. C l i n i c a l signs associated with an
Urethral hypertonicity is treated with - s y m p a t h o l y t i c s anatomic urethral obstruction include dribbling of urine,
(e.g., phenoxybenzamine) and striated muscle relaxants straining to urinate without producing urine, restlessness,
(e.g., diazepam). Detrusor hypercontractility often responds and abdominal pain. The most c o m m o n causes o f urethral
to treatment o f the underlying inflammatory process (e.g., obstruction are calculi and neoplasia i n dogs and urethral
bacterial cystitis or urolithiasis); however, smooth muscle plugs i n cats; however, urethral strictures and granuloma
antispasmodics (e.g., oxybutynin) and parasympatholytics tous urethritis can also create obstructions to urine flow.
(e.g., propantheline) may be useful i n cases o f severe Prostatic disease i n dogs may cause an outflow tract obstruc
inflammation. tion. Older male dogs with benign prostatic hyperplasia may
be evaluated because o f stranguria and tenesmus; however,
DISTENDED BLADDER prostatic neoplasia and prostatic abscess formation are more
Causes of incontinence that are typically associated with a likely causes o f urinary outflow tract obstruction i n such
distended bladder include neurogenic disorders (lower and animals.
upper motor neuron lesions and reflex dyssynergia) and
urine outflow tract obstructive disorders (paradoxic i n c o n SMALL OR NORMAL-SIZED BLADDER
tinence; see Table 41-3). If neurologic lesions or deficits are Causes o f urinary incontinence i n animals with a small or
detected during a neurologic examination, the status o f the normal-size bladder include urethral sphincter mechanism
incompetence ( U S M I ) , detrusor hyperreflexia or instability, The most c o m m o n clinical sign i n an animal with ectopic
and congenital abnormalities. Estrogen and testosterone are ureters is a constant dribbling o f urine, although dogs and
believed to contribute to the integrity o f urethral muscle cats with a unilateral ectopic ureter may void normally.
tone by increasing its responsiveness to - a d r e n e r g i c inner Because 70% o f ectopic ureters i n dogs terminate i n the
vation. Thus middle-aged to older, spayed female dogs are vagina, vaginoscopy may allow visualization of the opening
prone to the development o f incontinence associated with of the ectopic ureter; however, the opening can be difficult
decreased estrogen concentrations. This incontinence is to see, even i f the vagina is fully distended with air. Intrave
most pronounced when the animal is asleep or relaxed and nous urography, retrograde vaginourethrography, and cys
often responds to estrogen replacement therapy. Less fre toscopy are additional diagnostic tests for characterizing the
quently, incontinence develops i n male dogs after castration; defect. In contrast to the incontinence associated with ectopic
the condition seems to occur most c o m m o n l y i n dogs cas ureters, that associated with a vaginal stricture is often inter
trated at an older age and often responds to intramuscular mittent, occurring with changes i n body position. Vaginal
testosterone administration. Diagnosis o f both processes is strictures can be diagnosed using digital vaginal examina
based on the history, physical examination, and urinalysis tion, vaginoscopy, or contrast-enhanced vaginography.
findings (no evidence o f L U T I ) and o n the response to Incontinence may also be caused by cognitive dysfunc
therapy. Frequently, - a d r e n e r g i c treatment (e.g., phenyl tion, decreased bladder capacity, or decreased mobility i n
propanolamine) is effective i n both male and female dogs senior animals. Polyuric-polydipsic disorders such as chronic
with U S M I incontinence, and i n severe cases may be c o m kidney disease and diabetes mellitus i n senior animals also
bined with hormone replacement treatment. Testosterone often exacerbate incontinence. Likewise, diuretic and corti
treatment is contraindicated i n dogs that were neutered costeroid therapy should be avoided i n incontinent animals
because o f behavioral, prostatic, or perineal problems. because o f their negative effects o n urine concentration.
In these cases - a d r e n e r g i c treatment should be used;
- a d r e n e r g i c treatment should be used with caution (or not
at all) i n patients with hypertension. POLYDIPSIA AND POLYURIA
Detrusor hyperreflexia or instability is the inability to
control voiding because o f a strong urge to urinate. Increased thirst and urine production are frequent present
Inflammation o f the bladder or urethra may create a sensa ing complaints i n small animals. Polydipsia (PD) and poly
tion o f bladder fullness, w h i c h triggers the voiding reflex. uria (PU) i n the dog and cat have been defined as a water
Clinical signs o f this type o f incontinence include pollaki consumption greater than 80 to 100 ml/kg/day and a urine
uria, dysuria-stranguria, and frequently hematuria. Bacterial production greater than 40 to 50 ml/kg/day, respectively.
U T I is the most c o m m o n cause i n the dog, and sterile L U T D However, it is possible for thirst and urine production to be
is the most c o m m o n cause i n cats. A urinalysis that reveals w i t h i n the n o r m a l range and yet be abnormal i n individual
evidence of U T I or inflammation (e.g., bacteriuria, pyuria, animals. Polydipsia and polyuria usually co-exist, and deter
or hematuria) initially supports a tentative diagnosis o f urge m i n i n g the primary component o f the syndrome is one of
or inflammatory incontinence. If clinical signs persist after the initial diagnostic considerations i n an animal showing
appropriate treatment for the urinary tract inflammation increased water consumption and urine production.
has been initiated, further diagnostic testing, including ultra Thirst is stimulated primarily by osmotic factors. Hyperos
sonography, contrast-enhanced radiography, and/or cystos molality of the extracellular fluid usually occurs secondary to
copy, are indicated because infiltrative disease o f the bladder water loss, or it may result from the ingestion or intravenous
(e.g., neoplasia, chronic cystitis), polyps, uroliths, or urachal infusion of hypertonic solutions. This hyperosmolality results
remnants can also result i n pollakiuria and stranguria. It i n the dehydration of osmoreceptors, which stimulate thirst.
should also be noted that detrusor hyperreflexia/instability Nonosmotic factors, including decreased arterial blood pres
may also be a primary or idiopathic disorder that is not sure, increased body temperature, pain, and certain drugs, can
associated with bladder or urethral inflammation. also stimulate thirst. Thirst is inhibited by expansion of the
U r i n a r y incontinence i n a young animal may be associ extracellular fluid volume, increased arterial blood pressure,
ated with a variety o f congenital defects o f the urinary and drinking, and fullness o f the stomach. Thirst is abnormally
genital systems. The most c o m m o n defects are ectopic ureters stimulated i n animals with primary polydipsia, resulting i n
and vaginal strictures, but a patent urachus, urethrorectal water consumption that exceeds physiologic need. Renal func
and urethrovaginal fistulas, and female pseudohermaphro tion i n these animals is usually normal, and secondary poly
ditism have also been associated with urinary incontinence. uria occurs to r i d the body of the excess water.
Ectopic ureters are most c o m m o n l y observed i n female dogs. The kidneys maintain body fluid composition and volume
Breeds at high risk for ectopic ureters include Siberian by resorbing water and solutes from the glomerular filtrate.
Huskies, M i n i a t u r e and T o y Poodles, Labrador Retrievers, The resorption o f solute i n excess o f water results i n the
Smooth Fox Terriers, West H i g h l a n d W h i t e Terriers, Collies, formation o f dilute urine. Conversely, the resorption of
and Cardigan Welsh Corgis. Ectopic ureters are rarely seen water i n excess o f solute results i n the formation of concen
i n cats, but the gender predisposition is reversed; the preva trated urine. For concentrated urine to form, antidiuretic
lence is higher i n males than i n females. hormone ( A D H ) must be produced and released, and the
renal tubules must be responsive to the A D H . For the latter p h o m a with hypercalcemia); perineal mass (anal sac adeno
to occur, the renal medullary interstitium must be hyper carcinoma with hypercalcemia); cataracts (diabetes mellitus);
tonic and at least one third o f the total nephron population symmetric truncal alopecia (hyperadrenocorticism); vaginal
must be functional. A D H is synthesized i n the supraoptic discharge (pyometra); and small, irregular kidneys (chronic
and paraventricular nuclei of the hypothalamus and is stored kidney disease). A m i n i m u m w o r k u p consisting o f a C B C ,
in the posterior pituitary gland. Its release is stimulated by serum biochemistry profile, urinalysis, thoracic radiography,
the same factors that stimulate thirst. In the presence of and abdominal radiography or ultrasonography may confirm
A D H , the distal portion of the distal convoluted tubule and or suggest a diagnosis i n many animals with primary poly
the collecting duct become permeable to water, and water is uria (e.g., hypercalcemia and mediastinal lymphadenopathy
resorbed from the tubular lumen. The hypertonicity o f the in dogs with l y m p h o m a or increased serum alkaline phos
renal medullary interstitium produces the osmotic pressure phatase activity i n dogs with hyperadrenocorticism). Fre
that drives the water resorption. A primary polyuria associ quently, further specific tests are necessary to confirm a
ated with a relative or absolute lack of A D H is termed central diagnosis (e.g., l y m p h node aspiration or biopsy for l y m
or pituitary diabetes insipidus (CDI), whereas a polyuria p h o m a and an A C T H - s t i m u l a t i o n test for hyperadrenocor
caused by nonresponsiveness to A D H is termed nephrogenic ticism [Table 41-4]).
diabetes insipidus (NDI; Box 41-2). The urine specific gravity may also be helpful i n deter
Even though P U and P D usually occur together, the m i n i n g the underlying cause o f the syndrome and i n
owner may not be aware of one or both components, depend confirming whether the pet is actually polyuric. U r i n e specific
ing on their severity and how closely the animal is observed. gravity is usually divided into four ranges: hyposthenuric
Conversely, owners frequently confuse pollakiuria with poly urine has a specific gravity o f between 1.001 and 1.007; isos
uria. Polyuria is often manifested by nocturia, pollakiuria thenuric urine has the same specific gravity as plasma, 1.008
and incontinence, whereas polydipsia is often manifested by to 1.012; m i n i m a l l y concentrated urine has a specific gravity
a constantly empty water bowl and drinking from unusual of between 1.013 and 1.030 i n dogs and 1.013 and 1.035 i n
sources, including toilets and puddles, and eating snow. It is cats; and hypersthenuric urine has a specific gravity o f more
relatively easy for most pet owners to measure 24-hour water than 1.030 i n dogs and more than 1.035 i n cats. The animal's
consumption i n a single-pet household, and this is a good hydration status, serum urea nitrogen and creatinine c o n
way to confirm the presence o f polydipsia; measuring water centrations, and current medications must be k n o w n i n
consumption i n a multipet household is relatively difficult, order to interpret r a n d o m urine specific gravity values. For
unless the patient can be isolated. example, a normally hydrated dog may have a urine specific
A complete history and physical examination may suggest gravity i n the isosthenuric range and a cat receiving furose
the underlying cause i n animals with polydipsia and polyuria mide may be somewhat dehydrated and still have m i n i m a l l y
(Fig. 41-9); these include lymphadenopathy i n dogs (lym concentrated urine; however, n o r m a l dogs and cats should
produce hypersthenuric urine i n response to clinically
detectable dehydration.
BOX 4 1 - 2 It is unusual for dogs and cats with P D and/or P U to have
a urine specific gravity consistently i n the hypersthenuric
Potential Causes of Polydipsia and Polyuria range; this finding warrants the measurement o f water c o n
sumption to confirm i f the patient actually has either c o n d i
P r i m a r y Polydipsia
tion. Animals with primary polydipsia or with C D I usually
Psychogenic have urine specific gravities i n the hyposthenuric range,
Hepatic insufficiency o r portosystemic shunt whereas animals with nephrogenic diabetes insipidus are
P r i m a r y Polyuria most likely to be isosthenuric or to have m i n i m a l l y concen
trated urine. If the history, physical examination, and
Pituitary diabetes insipidus
m i n i m a l diagnostic w o r k u p findings are unrewarding, spe
N e p h r o g e n i c diabetes insipidus
cialized diagnostic tests, including determination o f the
Renal insufficiency o r failure
Hyperadrenocorticism plasma osmolality, gradual water deprivation testing, and
Hypoadrenocorticism determination o f the animal's response to exogenous A D H ,
Hepatic insufficiency may be necessary to arrive at a diagnosis (see Chapter 42 and
Pyometra Fig. 41-9).
Hypercalcemia
Hypokalemia
Postobstructive diuresis PROTEINURIA
Diabetes mellitus
Normoglycemic glucosuria
N o r m a l l y , the urine o f dogs and cats contains only a small
Hyperthyroidism
amount o f protein because the selective permeability o f the
Iatrogenic or drug induced
Renal medullary solute w a s h o u t glomerular capillary wall restricts the filtration of most
plasma proteins o n the basis o f protein weight and charge.
FIG 4 1 - 9
D i a g n o s t i c a p p r o a c h to d o g s a n d cats w i t h p o l y d i p s i a a n d p o l y u r i a .
TABLE 4 1 - 4
Ancillary Diagnostic Tests that May Be Used to Evaluate Dogs and Cats with Polydipsia and Polyuria
ACTH, Adrenocorticotropic hormone; ADH, antidiuretic hormone; PSS, portosystemic shunt; PTH, parathyroid hormone; PTHrp, parathyroid
hormone-related peptide.
with quaternary a m m o n i u m compounds, or i f the dipstick
TABLE 4 1 - 5
is left i n contact w i t h the urine long enough to leach out the
Approximate Molecular Weights of Various citrate buffer that is incorporated i n the filter paper pad.
Plasma Proteins False-negative results may occur i n the setting o f Bence Jones
proteinuria or dilute or acidic urine. The dipstick test can
MOLECULAR WEIGHT
detect approximately 30 to 1000 m g o f protein per deciliter.
P L A S M A PROTEIN (DALTONS)
The dipstick method is not affected by urine turbidity;
6,000
however, the supernatant from centrifuged urine samples
Insulin
Parathyroid h o r m o n e 9,000 should ideally be used for all physiochemical analyses.
Lysozyme 14,000 The sulfosalicylic acid test is performed by m i x i n g equal
Myoglobin 17,000 quantities o f urine supernate and 3% to 5% sulfosalicylic
Growth hormone 22,000 acid, and subjectively grading the turbidity that results from
Bence Jones proteins (monomer) 22,000 precipitation o f protein o n a 0 to 4 scale. This test is also
Amylase 50,000 more sensitive to a l b u m i n than globulins, but Bence Jones
Hemoglobin 64,500
proteinuria can be detected. False-positive results may occur
Antithrombin 65,000
if the urine contains radiographic contrast agents, penicillin,
Albumin 69,000
cephalosporins, sulfisoxazole, or the urine preservative
Immunoglobulin G 160,000
thymol. The protein content may be overestimated with the
Immunoglobulin A (dimer) 300,000
Fibrinogen 400,000 sulfosalicylic acid test i f uncentrifuged urine or t u r b i d urine
Immunoglobulin M 900,000 is analyzed. False-negative results may occur i f the urine is
markedly alkaline or diluted. Because the varying degrees o f
turbidity are not standardized, results may also vary among
laboratories. This test can detect approximately 5 to 5000 m g
Proteins with a molecular weight greater than 60,000 to of protein per deciliter. Further information on such tests is
65,000 daltons are normally not present i n large quantities contained i n Chapter 42.
in normal glomerular filtrate (Table 41-5). The negatively Proteinuria detected by these semiquantitative methods
charged glomerular capillary wall further impedes the should always be interpreted i n light o f the urine specific
passage of negatively charged proteins such as albumin. In gravity and urine sediment. For example, a 2 proteinuria
addition, smaller-molecular-weight proteins, as well as those with a 1.010 urine specific gravity is suggestive o f a m u c h
positively charged proteins that do pass through the glo greater urine protein loss on a 24-hour basis than is a 2
merular capillary wall, are largely resorbed by the p r o x i m a l proteinuria with a 1.040 urine specific gravity. Because the
tubular epithelial cells. Such resorbed proteins may be broken urine protein concentration is frequently increased i n
down and used by the epithelial cells or returned to the b l o o d animals with L U T I or hemorrhage, proteinuria should also
stream. Renal proteinuria most c o m m o n l y arises because o f be assessed i n the context o f urine sediment changes indica
glomerular capillary wall lesions that allow increased filtra tive o f inflammation or hemorrhage (e.g., bacteria and
tion o f plasma proteins into the glomerular filtrate. Tubular increased numbers o f white and red b l o o d cells and epithe
lesions that result i n decreased reabsorption o f filtered lial cells i n the urine sediment). The evaluation o f the animal
proteins (primarily albumin) are another source o f renal with proteinuria is further discussed i n Chapter 42.
proteinuria. Although glomerular lesions result i n greater Once persistent proteinuria has been documented, the
magnitude of proteinuria compared with tubular lesions, next step is to identify its source. Proteinuria may be caused
proteinuria associated with both types o f lesions tends to be by physiologic or pathologic conditions (Table 41-6). Physi
persistent and serves as an important marker o f kidney ologic or benign proteinuria is often transient and abates
disease. when the underlying cause is corrected. Strenuous exercise,
Proteinuria is routinely detected by semiquantitative seizures, fever, exposure to extreme heat or cold, and stress
methods, including the dipstick colorimetric test and the are examples o f conditions that may cause physiologic pro
sulfosalicylic turbidimetric test. The dipstick test is inexpen teinuria. The pathophysiology o f physiologic proteinuria is
sive and easy to use; amino groups o f proteins b i n d to the not completely understood; however, relative renal vasocon
indicator incorporated i n the filter paper o n the dipstick and striction, ischemia, and congestion are thought to be
cause a color change. The color change is graded by compar involved. Decreased physical activity may also affect urine
ing it to a standard, but the comparison is subjective. protein excretion i n dogs; one study showed that urinary
However, automated dipstick analyzers that use reflectance protein loss is higher i n dogs confined to cages than i n dogs
photometry to consistently read the color change and provide with n o r m a l activity. This is different from the postural or
a printout of results are available (Idexx VetLab U A Analyzer, orthostatic proteinuria that occurs i n people. In the latter
I D E X X Laboratories, Westbrook, Maine). The dipstick test condition, m i l d proteinuria occurs when the person is stand
is most sensitive to albumin because a l b u m i n has more free ing or active but diminishes when the person is recumbent.
amino groups than globulins. False-positive results may be Pathologic proteinuria may be caused by urinary or n o n -
obtained i f the urine is alkaline, i f it has been contaminated urinary abnormalities. N o n u r i n a r y disorders associated
result i n the decreased resorption of filtered protein (e.g.,
TABLE 4 1 - 6
Fanconi's syndrome and chronic kidney disease).
Classification of Proteinuria Prerenal (physiologic and pathologicnonurinary) and
postrenal (pathologic urinarynonrenal) proteinuria, as
TYPE CAUSES
well as inflammatory renal proteinuria, can usually be
identified on the basis o f history and physical examination
Physiologic Strenuous exercise
findings and the urine sediment changes. Renal proteinuria
Seizures
Fever caused by abnormal tubular resorption may be accompanied
Exposure to heat o r cold by normoglycemic glucosuria and an abnormal urinary loss
Stress of electrolytes, which can help differentiate tubular from
Decreased activity level (strict c a g e rest) glomerular proteinuria. It is important to identify the source
Pathologic of the proteinuria because the quantification of renal pro
Nonurinary Bence Jones proteinuria teinuria can be a helpful prognostic tool, although it is not
Hemoglobinuria or myoglobinuria useful i n animals with prerenal or postrenal proteinuria.
Congestive heart failure
G e n i t a l tract inflammation
Urinary
AZOTEMIA
Nonrenal Cystourolithiasis
Bacterial cystitis
Trauma o r h e m o r r h a g e Azotemia is defined as increased concentrations of urea and
Neoplasia creatinine (and other nonproteinaceous nitrogenous sub
Drug-induced cystitis (e.g., stances) i n the blood. The interpretation of serum urea
cyclophosphamide) nitrogen and creatinine concentrations as a measure of renal
Renal G l o m e r u l a r lesions function requires a knowledge o f the production and excre
A b n o r m a l tubular resorption tion of these substances. Urea is synthesized i n the liver from
Renal parenchymal inflammation or ammonia, which is i n turn generated from the catabolism of
hemorrhage ingested and endogenous proteins. Urea production is
increased i n the settings o f a high dietary protein intake,
upper gastrointestinal tract hemorrhage, and catabolic states
that result i n the breakdown of body proteins (e.g., fever and
with proteinuria often involve the production o f s m a l l - corticosteroid administration). Conversely, urea production
molecular-weight proteins that are filtered by the glomeruli is decreased i n the settings of a low dietary protein intake,
and that subsequently overwhelm the resorptive capacity o f use o f anabolic steroids, decreased hepatic function, or
the p r o x i m a l tubule. Examples o f this include the produc decreased delivery o f a m m o n i a to the liver (e.g., portosys
tion o f i m m u n o g l o b u l i n light chains (Bence Jones proteins) temic shunt). Urea has a small molecular weight (60 daltons)
by neoplastic plasma cells or lymphocytes and the release o f and is a permeate solute that readily diffuses throughout all
hemoglobin from damaged red b l o o d cells, w h i c h then body fluid compartments; its concentration is similar in
exceeds the b i n d i n g capacity of haptoglobin (in this case intracellular and extracellular fluid and i n plasma, serum,
centrifuged urine w o u l d be discolored by the pigment). and b l o o d . Urea that diffuses into the intestinal lumen is
Renal congestion secondary to congestive heart failure can degraded by enteric organisms to ammonia, which is then
also result i n pathologic nonurinary proteinuria, as can reabsorbed into the portal circulation and again converted
genital tract inflammation (e.g., prostatitis or metritis). to urea by the liver. Urea is principally excreted by the
Pathologic urinary proteinuria may be renal or nonrenal kidneys; it is freely filtered through the glomeruli and pas
in origin. N o n r e n a l proteinuria most frequently occurs i n sively resorbed by the renal tubules. The tubular resorption
association with L U T I or hemorrhage. Changes seen i n the of urea is increased and the net excretion decreased when
urine sediment usually reflect the underlying cause (e.g., tubular flow rates and volumes are decreased, as it occurs i n
urolithiasis, neoplasia, trauma, bacterial cystitis). O n the patients with dehydration. Conversely, the tubular resorp
other hand, renal proteinuria is most often caused by glo t i o n o f urea is decreased and the excretion is increased i n the
merular lesions. Glomerulonephritis and amyloidosis alter presence o f diuresis. Decreased renal blood flow (prerenal
the selective permeability o f the glomerular capillaries and causes, such as dehydration or decreased cardiac output) and
frequently result i n a proteinuria greater than 50 mg/kg/24 h decreased excretion o f urine (postrenal causes, such as ure
or urine protein: creatinine ratios greater than 2.0 (see thral obstruction or ruptured bladder), as well as primary
Chapter 42). The occurrence o f persistent proteinuria with renal dysfunction, will result i n decreased excretion of urea.
a n o r m a l urine sediment or accompanied by hyaline cast Creatinine is irreversibly formed by the nonenzymatic
formation is strongly suggestive o f glomerular disease. metabolism of creatine and phosphocreatine i n muscle. Cre
Besides glomerular disease, renal proteinuria may be caused atinine production is relatively constant and proportional to
by inflammatory or infiltrative disorders o f the kidney (e.g., muscle mass; animals with a large muscle mass produce
neoplasia, pyelonephritis) or by tubular abnormalities that more creatinine each day than do animals with a small
muscle mass. For example, serum creatinine concentration Postrenal azotemia is usually caused by an obstruction to
in Greyhounds is higher than i n dogs of other breeds. Muscle urine outflow or a rupture o f the urine outflow tract. Similar
trauma and inflammation do not increase the production o f to prerenal azotemia, i n postrenal azotemia the kidneys are
creatinine. In comparison with the urea nitrogen concentra initially normal; however, the urine specific gravity varies
tion, the creatinine concentration is relatively unaffected by depending o n the animal's hydration status. In patients with
the dietary protein level; however, serum creatinine concen urethral obstruction, catheterization is difficult and dysuria
trations can increase after the ingestion o f meat and the and stranguria are c o m m o n clinical signs. Rupture o f the
subsequent increased absorption of creatinine from the gas urinary tract that results i n azotemia usually involves the
trointestinal tract. The molecular weight o f creatinine is 113 bladder or urethra, is more c o m m o n i n male than female
daltons; therefore it diffuses throughout body fluid compart animals, and frequently results i n abdominal effusion or sub
ments more slowly than urea does. Some creatinine diffuses cutaneous fluid accumulation. F l u i d obtained by abdomino
into the intestinal lumen, is degraded by enteric bacteria, and centesis is usually sterile and contains a higher concentration
is excreted from the body i n the feces; however, most creati of creatinine than the serum does. Even though creatinine is
nine is excreted by the kidneys. Creatinine is freely filtered a small molecule and equilibrates rapidly, the concentration
by the glomeruli and is not significantly resorbed or secreted of creatinine i n the abdominal fluid is higher than that of
by the renal tubules. Because the production o f creatinine is serum i f the kidneys are producing urine that is draining
relatively constant, an increase i n the serum creatinine con into the abdomen. Positive contrast-enhanced urethrogra
centration is indicative o f decreased renal excretion. It is phy or cystography is the best way to confirm a rupture o f
important to remember, however, that prerenal and postre the urethra or bladder.
nal factors influence renal function and, therefore, the Renal azotemia occurs as a result o f nephron loss or
excretion o f creatinine. Disproportionate increases i n blood damage. A diagnosis o f renal azotemia is confirmed i f the
urea nitrogen ( B U N ) relative to creatinine can be caused azotemia is persistently associated with isosthenuria or m i n
by high-protein diets, upper gastrointestinal hemorrhage, imally concentrated urine (see Table 41-7). Inasmuch as
and increased tubular reabsorption o f urea nitrogen associ urine is usually stored i n the bladder for several hours, it is
ated with prerenal azotemia. Conversely, a disproportion important not to evaluate the specific gravity of urine pro
ately low B U N can be observed with decreased liver function, duced before the onset o f the azotemia. For example, pre
portosystemic shunts, low-protein diets, and prolonged renal azotemia may occur i n response to acute, severe
diuresis. dehydration; however, the animal may appear to have renal
Rule outs for azotemia include prerenal, renal, and postre azotemia i f the hypersthenuric urine being produced i n
nal causes. A n y condition that causes a decrease i n renal response to the dehydration is diluted by a larger volume
blood flow may result i n prerenal azotemia, and this includes of previously formed, less concentrated urine. The differ
hypovolemia (e.g., dehydration, hypoadrenocorticism), entiation o f prerenal from renal azotemia can be a diag
hypotension (e.g., anesthesia, cardiomyopathy), and aortic nostic challenge i n some animals. Prerenal dehydration
or renal arterial thrombus formation. Initially, the kidneys causing azotemia and accompanied by a decreased urine-
are structurally and functionally n o r m a l i n dogs and cats concentrating ability can be confused with renal azotemia.
with prerenal azotemia, and they respond to the decreased Examples of conditions that can cause this syndrome include
renal blood flow by conserving water and sodium. Hyper furosemide treatment, w h i c h causes dehydration, and hyper
sthenuric urine (i.e., specific gravity greater than 1.030 i n calcemia, w h i c h compromises the urine-concentrating ability
dogs and greater than 1.035 i n cats) with a relatively l o w and results i n dehydration secondary to vomiting. A l t h o u g h
concentration of sodium and a high concentration o f cre fluid therapy is often implemented initially i n animals with
atinine is produced (Table41-7). Elimination of the underly either prerenal or renal azotemia to manage the dehydration,
ing disorder (e.g., fluid therapy to correct hypovolemia) the prognosis is quite different. Frequently, the response to
results i n rapid resolution o f the azotemia unless the under fluid therapy is the best way to differentiate prerenal from
lying disorder has persisted long enough or is severe enough renal azotemia; renal azotemia does not completely resolve
to have caused renal parenchymal damage. i n response to fluid therapy alone.
TABLE 4 1 - 7
nine concentration is considerably increased, the effect o f S e r u m ] / [ U r i n e : S e r u m ] ) . A timed urine collection is not
S Cr Cr
necessary to determine the F C o f a solute. Some solutes, of the inflammatory disorder. The urine p r o t e i n : creatinine
including glucose and amino acids, are normally highly con ratio cannot be used to differentiate between renal protein
served, whereas electrolytes such as sodium, chloride, potas uria and proteinuria associated with lower urinary tract
sium, calcium, and phosphorus are variably conserved. In inflammation or hemorrhage. The urine proteinxreatinine
normal dogs and cats the FCs o f sodium, chloride, and ratio provides a noninvasive way to follow progression o f
calcium are less than 1%; however, the FCs o f potassium and disease or response to treatment. The variation i n urine
phosphorus are more variable and may be as high as 20% p r o t e i n : creatinine observed i n dogs with stable proteinuria
and 39%, respectively. Examples o f situations i n w h i c h a suggests that the ratio should differ by 80%, especially with
knowledge o f the F C o f electrolytes may be helpful include lower range proteinuria, i n order to conclude that a signifi
(1) the diagnosis of primary hyperparathyroidism, i n which cant change has occurred. In cats the urine p r o t e i n : creati
the F C of phosphorus is increased; (2) the diagnosis o f nine variation within the reference range suggests that the
tubular dysfunction, such as Fanconi's syndrome, i n w h i c h ratio should differ by 90% to conclude that a significant
the FCs of all electrolytes are increased; and (3) the differ increase or decrease i n proteinuria has occurred. Typically,
entiation of prerenal azotemia, i n which the F C of s o d i u m quantitative measurement o f urine protein and creatinine
is decreased, from acute renal failure, i n which the F C o f (mg/dl) is performed at reference laboratories and teaching
sodium is increased (>2%; see Table 41-3). In many cases, hospitals; however, in-house quantitative urine p r o t e i n : cre
however, the correlation between spot urine sample and 24- atinine measurement has recently become available (Idexx
hour urine sample F C is poor. In addition, the amount o f VetTest Chemistry Analyzer, I D E X X Laboratories, West-
dietary intake o f the electrolyte i n question can influence brook, M a i n e ) , and results appear to correlate well with stan
results, and there tends to be large intrapatient and interpa dard quantitative methodologies.
tient variation i n results. Moreover, the F C may also be breed Antigen capture enzyme-linked immunosorbent assays
dependent; for example, F C o f most electrolytes is signifi (ELISA) used to detect l o w levels o f a l b u m i n i n canine and
cantly different i n Greyhounds than i n other dog breeds. For feline urine (microalbuminuria [ M A ] ) are commercially
these reasons, the clinical usefulness o f F C of electrolytes is available (E.R.D.-Screen, Heska Corp., Fort Collins, C o l o
limited. rado). M A is usually defined as a urine a l b u m i n concentra
tion between 1.0 and 30 mg/dl. These are concentrations too
low to be routinely detected by standard dipstick screening
QUANTIFICATION OF PROTEINURIA tests. It is interesting to note that the presence o f M A has
been shown to be an accurate predictor o f subsequent renal
If the results of the dipstick or sulfosalicylic acid test for disease i n h u m a n beings with both systemic hypertension
proteinuria (see Chapter 41) indicate the presence o f persis and diabetes mellitus, and it has also been observed i n h u m a n
tent proteinuria and the urine sediment examination findings beings with systemic diseases that are associated with glo
are normal (i.e., renal proteinuria is suspected), urine protein merulopathy. Studies i n dogs have shown the prevalence o f
excretion should be quantified. This helps i n evaluating the M A i n apparently healthy dogs and Soft Coated Wheaten
severity of renal lesions and assessing the response to treat Terriers genetically predisposed to developing glomerular
ment or the progression of disease. The trichloroacetic acid- disease to be 19% and 76%, respectively (Jensen et al., 2001;
N-Ponceau S, Coomassie brilliant blue, or benzethonium Vaden et al., 2001). In additional studies, development o f
chloride tests are the most c o m m o n methods used to quan M A preceded the development o f overt albuminuria i n dogs
tify urine protein and are available at referral centers and with experimentally induced heartworm disease (Grauer
reference laboratories. et a l , 2002) and i n dogs with X - l i n k e d hereditary nephrop
The urine protein: creatinine ratio i n canine and feline athy (Lees et al., 2002). M A testing should be used when
urine samples has been shown to accurately reflect the quan conventional screening tests for proteinuria are negative and
tity of protein excreted i n the urine over a 24-hour period. increased sensitivity is desired (e.g., screening for early
Both urine creatinine and urine protein concentrations are kidney disease i n young animals that may have heritable
affected by urine volume and urine concentration, but the kidney disease or screening for acquired chronic kidney
ratio of the urine protein to urine creatinine is not. This disease i n older animals). A positive M A test o f suspected
allows quantitation of proteinuria without the need to collect renal origin should be pursued with a three-step paradigm
a timed urine sample, and therefore the test has greatly facil of (1) monitoring, (2) investigating, and (3) intervening. The
itated the diagnosis o f kidney disease i n small animals. A initial step o f m o n i t o r i n g involves determining i f the albu
urine protein: creatinine ratio of less than 0.4 and less than m i n u r i a is persistent or transient. It is important to note that
0.5 is considered normal i n cats and dogs, respectively. A the sensitivity o f M A assays makes it likely that some positive
complete urinalysis should always be performed before or results w i l l be caused by benign or physiologic proteinuria.
along with determination of the urine protein: creatinine In these cases, follow-up assays should be negative, confirm
ratio because hematuria or pyuria may indicate the presence ing that the M A was transient. Transient M A is likely to be
of nonglomerular proteinuria. If there is evidence o f of little or no consequence. O n the other hand, persistent
inflammation (e.g., pyuria, bacteriuria), the protein concen proteinuria/albuminuria o f renal origin indicates the pres
tration should be measured again after successful treatment ence o f kidney disease. Persistent proteinuria/albuminuria
can be defined as positive test results o n >2 occasions, >2 teins i n the serum indicate the presence of severe glomerular
weeks apart. Because persistent proteinuria/albuminuria can proteinuria and the nephrotic syndrome.
be constant or increase or decrease i n magnitude over time,
m o n i t o r i n g should use quantitative methods to determine
disease trends and/or response to treatment. Quantitative PLASMA AND URINE OSMOLALITY,
albuminuria assays or the urine protein/creatinine ratio are WATER DEPRIVATION TEST, AND
used to document changes i n the magnitude of the a l b u m i n RESPONSE TO EXOGENOUS
uria once its persistence has been confirmed. Changes i n the ANTIDIURETIC HORMONE
magnitude o f proteinuria should always be interpreted i n
light o f the patient's serum creatinine concentration because Measurement o f plasma osmolality may aid i n the determi
albuminuria may decrease i n association with progressive nation o f the primary component o f the polydipsia/polyuria
renal disease as the number o f functional nephrons decrease. ( P D / P U ) syndrome. N o r m a l plasma osmolality i n dogs and
Decreasing albuminuria i n the face o f a stable serum creati cats is 280 to 310 m O s m / k g . Plasma osmolality i n animals
nine concentration suggests improvement i n renal function, with primary P D is usually low (275 to 285 mOsm/kg),
whereas decreasing albuminuria i n the face o f an increasing reflecting the dilutional effect of excessive water consump
serum creatinine suggests disease progression. tion. In contrast, animals with a primary P U often have high
Once persistent proteinuria has been documented by plasma osmolalities (305 to 315 mOsm/kg) because of their
monitoring, the appropriate response depends o n the mag inability to concentrate urine and the resultant dehydration
nitude o f the proteinuria and the health status o f the patient (see Fig. 41-9). However, there can also be considerable
(e.g., the presence or absence o f azotemia and/or hyperten overlap i n randomly obtained plasma osmolalities between
sion). The second step o f investigation refers to performing animals with primary polydipsic disorders and those with
new or additional tests to diagnose an underlying/concur primary polyuric disorders.
rent infectious, inflammatory, or neoplastic disease process Determination o f a urine: plasma osmolality ratio allows
or to more completely define the patient's renal disease. a more precise determination o f urine concentration than
Examples o f such further investigation may include a c o m does urine specific gravity alone because specific gravity
plete m i n i m u m database, urine culture, measurement o f measures the density o f urine rather than the number of
blood pressure, serology for immune-mediated or infectious particles i n solution. For example, moderate-to-marked glu
diseases, radiographs/ultrasound, and renal biopsy. cosuria or proteinuria increases urine specific gravity more
In cases o f persistent proteinuria, where an underlying than the urine osmolality. In response to dehydration, normal
disorder cannot be identified or treated, the need for treat dogs and cats should be able to form urine that is five to six
ment o f the proteinuria depends o n its magnitude and the times more concentrated than plasma. Plasma and urine
presence or absence o f azotemia. In the absence o f azotemia, osmolality may be determined using either a vapor pressure
proteinuria resulting i n urine p r o t e i n : creatinine ratios >1.0 or freezing point depression osmometer, and measurement
to 3.0 should be treated, whereas continued m o n i t o r i n g and is available at a reasonable cost at most veterinary teaching
patient investigation should be the primary focus i n cases hospitals and reference laboratories.
with lesser-magnitude proteinuria. Treatment recommenda Water deprivation causes dehydration and plasma hyper
tions i n these cases usually include decreased dietary protein osmolality and allows the neurohypophyseal-renal axis to be
intake (early renal failure diets), n-3 fatty acid supplementa evaluated. Water deprivation tests are used to differentiate
tion (early renal failure diets), low-dose aspirin (0.5 mg/kg diabetes insipidus from primary P D and should be per
q24h administered orally), and angiotensin-converting formed only after other causes of P U and P D have been ruled
enzyme ( A C E ) inhibitors (e.g., enalapril, benazepril; 0.5 to out o n the basis of the findings from physical examination
1.0 mg/kg q24h administered orally), although it is difficult and a m i n i m u m database. It should be noted that water
to separate the effects o f individual treatments when they are deprivation tests are potentially dangerous. They should
used i n combination. Treatment for persistent proteinuria i n therefore be performed only under close observation and
azotemic dogs and cats should be initiated when the urine after water intake has been gradually reduced (see later dis
proteinxreatinine ratio is 0.5 and 0.4, respectively. Treat cussion) because failure to produce concentrated urine (i.e.,
ment recommendations i n this case usually include A C E diabetes insipidus) may result i n severe dehydration and
inhibition and renal failure diets. potential ischemic renal injury. Increases i n plasma osmolal
U r i n e and serum protein electrophoresis may help i n ity o f 1% to 2% above n o r m a l levels stimulate the release of
identifying the source o f the proteinuria and i n establishing antidiuretic hormone ( A D H ) , and normal kidneys should
a prognosis. For example, proteinuria associated with hem respond to this A D H by producing hypersthenuric urine.
orrhage into the urinary tract has an electrophoretic pattern The water deprivation test is complete when the animal loses
very similar to that o f serum. Early glomerular damage 5% o f its body weight as a result o f dehydration, becomes
usually results principally i n albuminuria; however, as the azotemic, becomes hyperosmolemic (plasma osmolality
glomerular disease progresses, an increasing amount o f >320 m O s m / k g ) , or produces hypersthenuric urine (specific
globulin may be lost as well. M a r k e d hypoalbuminemia and gravity 1.030 i n dogs or 1.035 i n cats). It is important to
increased concentrations o f larger-molecular-weight pro obtain accurate baseline values and ensure that the bladder
is emptied each time the urine specific gravity or osmolality deprivation. The lack o f a response to water deprivation and
is measured so that urine produced between evaluations is exogenous A D H administration after gradual water reduc
not diluted by previously formed urine. Plasma osmolality tion suggests that N D I unrelated to medullary washout is the
constitutes a good measure o f hydration status during water cause o f the P D / P U .
deprivation, and, i n fact, a water deprivation test may not be
necessary i f it is measured at baseline. The finding o f a base
line plasma osmolality of 320 m O s m / k g or greater i n a BLADDER AND URETHRAL FUNCTION
clinically nondehydrated dog or cat with hyposthenuria or
isosthenuria indicates a failure o f the neurohypophyseal- Several specialized diagnostic tests, including urethral pres
renal axis. Similarly, a water deprivation test should not be sure profilometry, cystometry, and uroflowmetry, may help
performed i n an animal that is clinically dehydrated or azo categorize bladder and urethral function i n dogs and cats
temic and that has hyposthenuria, isosthenuria, or m i n i with disorders o f micturition. These tests are available at
mally concentrated urine because these conditions already many referral centers. The urethral pressure profile ( U P P )
demonstrate a failure o f the neurohypophyseal-renal axis. assesses the perfusion pressure or m i n i m a l distention pres
The time it takes to reach the end-point o f a water depriva sure w i t h i n the bladder and urethra during the storage phase
tion test is variable; small dogs and cats may dehydrate of micturition. The functional urethral length (the length o f
within several hours, whereas significant dehydration may the urethra that has a pressure greater than the intravesical
not occur i n large dogs for 36 to 48 hours. A n i m a l s that fail pressure) and the functional urethral closure pressure (the
to produce hypersthenuric urine i n response to water greatest urethral pressure minus the intravesical pressure)
deprivation have either pituitary or nephrogenic diabetes can be determined o n the basis o f a U P P . Electromyography
insipidus. may be combined with a U P P to define the portion o f ure
A pharmacologic dose o f A D H may be administered to thral resistance contributed to by periurethral striated muscle
differentiate pituitary diabetes insipidus (lack o f A D H ) from (external sphincter). The U P P can be used to assess urethral
nephrogenic diabetes insipidus (no response to A D H ) . sphincter tone i n animals with suspected urethral sphincter
Aqueous A D H (3 to 5 U given intramuscularly) is c o m m o n l y incompetence or functional urethral obstruction and ure
used for diagnostic testing, although synthetic desmopressin thral spasm. In addition, the U P P can be used to evaluate
acetate nasal spray, given as drops i n the conjunctival sac, sphincter response to treatment with -adrenergic drugs or
or an injectable preparation o f desmopressin acetate, given estrogens. Finally, the U P P should be determined preopera
subcutaneously (3 to 5 U ) , may also be used. The A D H tively to evaluate urethral sphincter function i n dogs and cats
should be administered immediately at the end-point o f with ectopic ureters or vaginal strictures because o f the
the water deprivation test, before water is made available, increased incidence o f sphincter incompetence i n animals
in animals that do not respond to water deprivation. It is with these congenital anomalies. A cystometrogram records
important that the bladder be empty immediately before the changes i n intravesical pressure during bladder filling and
administration of A D H so that the urine produced i n detrusor contraction. It evaluates the detrusor reflex,
response to A D H is not diluted by previously formed urine. m a x i m a l detrusor contraction pressure, and bladder cap
Animals with central diabetes insipidus ( C D I ) usually acity and compliance i n animals w i t h suspected detrusor
respond by producing urine that is hypersthenuric or at least atony, instability, and decreased capacity or compliance.
1.025 within 1 to 2 hours. The absence o f an increase i n Uroflowmetry measures urine flow during the voiding phase
urine specific gravity i n response to both water deprivation o f m i c t u r i t i o n and defines the relationship between urine
and exogenous A D H administration indicates the presence flow and detrusor contraction. The presence o f normal,
of nephrogenic diabetes insipidus ( N D I ) . increased, or decreased urethral resistance can be established
Renal medullary hypertonicity may be lost after pro with uroflowmetry.
longed P U (primary or secondary). Therefore medullary
washout may develop i n animals with primary P D or C D I ,
making them appear to have N D I . Water intake may be BACTERIAL ANTIBIOTIC
gradually reduced over 10 to 14 days to correct renal m e d u l SENSITIVITY TESTING
lary washout before the water deprivation test is performed.
In addition to gradually limiting the dog's or cat's water The majority o f simple, uncomplicated urinary tract infec
intake (10% reduction every other day u n t i l the animal is tions i n female dogs can be effectively treated with an anti
drinking 80 to 90 ml/kg/day), a high-protein diet that is biotic chosen o n the basis o f urine sediment G r a m staining
lightly salted (unless the patient is hypertensive) should be or culture and sensitivity based o n the disk-diffusion/Kirby
fed to the animal to facilitate reestablishment o f n o r m a l Bauer method. If disk-diffusion sensitivity testing shows that
medullary tonicity. Water restriction should be discontinued the organism is highly resistant to antibiotics (e.g., suscep
if the animal becomes overly aggressive i n its desire for water tible only to aminoglycosides), m i n i m u m inhibitory concen
or becomes lethargic or weak. The response to water depri tration ( M I C ) sensitivity testing can be helpful because o f
vation and, i f necessary, the response to exogenous A D H differences i n the serum and urine concentrations o f antibi
should be evaluated after 10 to 14 days o f this gradual water otics. In these cases, i n vivo sensitivity may exist even though
TABLE 42-1
Urine Concentration of Selected Antimicrobial Agents in Healthy Dogs with Normal Renal Function
* Dosages are the same for cats, except that the dosage or chloramphenicol in cats is 20 mg/kg q8h for 1 week.
PO, Orally.
Imaging Procedure and Potential Findings in Cats and Dogs with Urinary Disorders
PROCEDURE POTENTIAL F I N D I N G S
Plain a b d o m i n a l r a d i o g r a p h y R a d i o p a q u e uroliths
Increased o r d e c r e a s e d k i d n e y size
A b d o m i n a l mass(es)
Bladder distention
Emphysematous cystitis
Enlarged uterus
Enlarged prostate
Lymphadenopathy
Renal ultrasonography Tissue architecture (diffuse versus focal disease, echodense versus echolucent lesions)
Pyelonephritis
Perirenal fluid, renal cysts, o r abscesses
H y d r o n e p h r o s i s , hydroureter
Excretory u r o g r a p h y Renal p a r e n c h y m a l filling defects
Renal pelvic dilatation o r filling defects
Hydronephrosis o r hydroureter
Ureteral obstruction
Ectopic ureter(s)
Extravasation o f contrast material
Contrast-enhanced cy st ogr a phy Radiolucent uroliths
Intraluminal mass(es)
W a l l thickening
U r a c h a l remnant
Extravasation o f contrast material
Enlarged prostate
Reflux o f contrast material into ureters*
Bladder ultrasonography Intraluminal masses (uroliths, b l o o d clots, tumors, polyps)
W a l l thickening
Prostatic lesions
Sublumbar l y m p h a d e n o p a t h y
Contrast-enhanced urethrography Intraluminal filling defects
Extraluminal compression
Extravasation o f contrast material
Enlarged prostate
Reflux o f contrast material into p r o s t a t e *
can show a normal or hyperechoic echotexture depending becomes more difficult as azotemia increases. I V urography
on chronicity. Renal l y m p h o m a can make the renal cortices should be avoided i n dehydrated animals and i n those receiv
appear hypoechoic or hyperechoic (Fig. 42-3). H y d r o n e ing potentially nephrotoxic drugs.
phrosis and hydroureters are easily and noninvasively diag If the ureters are normal, they cannot be visualized o n
nosed on the basis o f ultrasonographic findings (Fig. 42-4). plain radiographs. N o r m a l ureters appear as radiopaque
Resistance to renal b l o o d flow (resistive index), which can be lines that extend from the kidneys to the trigone region o f
calculated with the use o f color flow Doppler imaging, is the bladder o n I V urograms (see Fig. 42-5, B). The n o r m a l
increased i n association with several renal diseases. ureteral diameter is 1 to 2 m m , and apparent filling defects
A n intravenous urogram (Box 42-2) can also aid i n the are frequently caused by peristaltic contractions that propel
evaluation of renal structures, specifically the renal vessels, urine and contrast material to the bladder. Indications for
parenchyma, and pelvis, as well as the ureters (Fig. 42-5). intravenous urography to evaluate the ureters include sus
Potential indications for I V urography include kidney abnor pected obstructive uropathy (Fig. 42-6), trauma (rupture or
malities noted on plain radiographs or ultrasonograms, laceration), calculi, ectopic ureters (Fig. 42-7), neoplasia, and
inability to visualize one or both kidneys on plain radio ureterocele.
graphs or ultrasonograms, and hematuria o f suspected renal The size, shape, and position o f the urinary bladder can
origin. In addition, I V urography qualitatively assesses i n d i usually be evaluated and any radiopacities detected on
vidual kidney excretory function; therefore it should be per plain abdominal radiographs and ultrasonograms (Fig.
formed before nephrectomy or nephrotomy i f other means 42-8). However, retrograde contrast-enhanced radiographic
of assessing G F R are not available. The utility o f I V urogra studies are easy to perform and are used to visualize the
phy diminishes if azotemia exists, and good renal opacification entire bladder and its relationship to other structures i n the
FIG 4 2 - 2 FIG 4 2 - 4
Ultrasonographic i m a g e s o f t h e k i d n e y a n d s p l e e n in a d o g Ultrasonographic image of a hydronephrotic kidney.
s h o w i n g the increased echogenicity of the spleen (upper ( C o u r t e s y Dr. Phillip S t e y n , C o l o r a d o State University, Fort
BOX 4 2 - 2
1. Patient preparation:
N o f o o d for 2 4 hours; w a t e r a v a i l a b l e , free choice
One or more enemas at least 2 hours before
radiography
Assess hydration status; d o not proceed if a n i m a l is
dehydrated.
2. Evaluate survey r a d i o g r a p h s for effectiveness o f e n e m a s .
3. U s e s e d a t i o n o n l y if n e c e s s a r y .
4. Infuse contrast solution intravenously via jugular or
cephalic vein as bolus injection.
8 8 0 m g / k g i o d i n e ; d o s e c a n b e d o u b l e d if r e n a l f u n c t i o n
is p o o r .
Nonionic iodinated contrast solutions are safest but
more expensive.
5. Obtain abdominal r a d i o g r a p h s as follows:
Ventrodorsal views a t 5 to 2 0 seconds, 5 minutes, 20
minutes, a n d 4 0 minutes after injection
Lateral v i e w at 5 minutes
FIG 4 2 - 3
Oblique views at 3 to 5 minutes to assess ureteral
Ultrasonographic i m a g e o f a feline kidney with lymphoma.
t e r m i n a t i o n in b l a d d e r
( C o u r t e s y Dr. Phillip S t e y n , C o l o r a d o State University, Fort
Collins, Colo.)
FIG 42-5
R a d i o g r a p h i c a p p e a r a n c e of n o r m a l c a n i n e kidneys d u r i n g (A) the n e p h r o g r a m stage of
a n i n t r a v e n o u s p y e l o g r a m a n d (B) t h e p y e l o g r a m s t a g e o f a n i n t r a v e n o u s pyelogram.
FIG 42-6
Intravenous p y e l o g r a m of a d o g w i t h a transitional cell c a r c i n o m a of the b l a d d e r and
unilateral hydroureter. ( C o u r t e s y Dr. Phillip S t e y n , C o l o r a d o S t a t e U n i v e r s i t y , Fort C o l l i n s ,
Colo.)
FIG 4 2 - 7
Intravenous p y e l o g r a m of a d o g with a unilateral ectopic
FIG 4 2 - 9
ureter. ( C o u r t e s y Dr. Phillip S t e y n , C o l o r a d o State Univer
P o s i t i v e c o n t r a s t - e n h a n c e d c y s t o g r a m in a m a l e d o g
sity, F o r t C o l l i n s , Colo.)
s h o w i n g a small u r a c h a l r e m n a n t . ( C o u r t e s y Dr. Phillip
S t e y n , C o l o r a d o State University, Fort C o l l i n s , Colo.)
obtain urine samples and perform retrograde pyelography. temic hypertension, and renal lesions associated with fluid
Cystoscopy is used to evaluate patients with lower urinary accumulation (e.g.,hydronephrosis, renal cysts and abscesses).
tract inflammation, to evaluate potential anatomic abnor In addition, renal biopsy should not be attempted by inex
malities i n animals with recurrent urinary tract infections perienced clinicians or i n animals that are not adequately
(e.g., urolithiasis, polyps, urachal remnants) and animals restrained.
with urine retention or incontinence, to evaluate and obtain Renal biopsy specimens can be obtained percutaneously
a biopsy specimen of bladder or urethral masses, and to dif using the keyhole technique or under laparoscopic or ultra
ferentiate unilateral from bilateral renal hematuria. sonographic guidance. In many cases the best way to obtain
a specimen is at laparotomy, when both kidneys can be visu
alized, because postbiopsy hemorrhage can then be accu
RENAL BIOPSY rately assessed and treated and an adequate biopsy specimen
ensured. The cortical region o f the kidney should be biop
The biopsy and histopathologic evaluation o f renal tissue is sied to obtain an adequate number o f glomeruli i n the
a valuable diagnostic and prognostic tool. Renal biopsy specimen and to avoid renal nerves and major vessels i n the
should be considered i f the diagnosis is i n question (e.g., medullary region. Most animals w i l l have microscopic
immune complex glomerulonephritis versus amyloidosis i n hematuria for 1 to 3 days after the biopsy procedure, and
dogs with proteinuria), i f treatment may be altered on the overt hematuria is not u n c o m m o n . In a retrospective study
basis of results (e.g., confirmation and culture o f bacterial by V a d e n (2007) o f renal biopsies i n 283 dogs and 65 cats,
pyelonephritis), or i f the prognosis may be altered on the complications were reported i n 13.4% and 18.5% of dogs
basis of results (e.g., evidence o f reversible tubular lesions i n and cats, respectively. The most c o m m o n complication was
a dog or cat with acute tubular necrosis). A specific diagnosis severe hemorrhage; hydronephrosis and death were u n c o m
is required to implement specific treatment in most animals m o n . Dogs that developed complications after renal biopsy
with renal disease, and a biopsy frequently must be per were more likely to have been 4 to <7 years o f age and >9
formed for a specific diagnosis to be obtained. In addition, years, to weigh <5 kg, and to have serum creatinine concen
the prognosis for animals with renal disease is most accurate trations >5 mg/dL. The majority o f biopsies from both dogs
if it is based on three variables: the severity o f dysfunction, (87.6%) and cats (86.2%) were considered to be o f satisfac
the response to treatment, and the renal histopathologic tory quality. Biopsies from dogs were more likely to be o f
findings. high quality i f they were obtained when the patient was
Renal biopsy should be considered only after less invasive under general anesthesia and more likely to contain only
tests have been done and the blood clotting ability has been renal cortex i f they were obtained by surgery. It was c o n
assessed. Absolute or relative contraindications to renal cluded that renal biopsy is a relatively safe procedure, with
biopsy include a solitary kidney, a coagulopathy, severe sys- a l o w frequency o f severe complications.
FIG 42-11
A a n d B, U l t r a s o n o g r a p h i c i m a g e s of the b l a d d e r of d o g s with b e n i g n polyps.
(A c o u r t e s y Dr. Phillip S t e y n , C o l o r a d o State U n i v e r s i t y , Fort C o l l i n s , Colo.)
FIG 42-12
Ultrasonographic i m a g e of the b l a d d e r of a d o g w i t h a
transitional cell carcinoma.
FIG 42-13
Positive c o n t r a s t - e n h a n c e d urethrogram in a d o g w i t h an
i n t r a l u m i n a l u r o l i t h . ( C o u r t e s y Dr. Phillip S t e y n , Colorado
State University, Fort C o l l i n s , Colo.)
FIG 42-14
Positive c o n t r a s t - e n h a n c e d u r e t h r o g r a m in a d o g w i t h a n o b s t r u c t i v e u r o p a t h y associated
with prostatic neoplasia.
Glomerulonephropathies
FIG 4 3 - 2
Glomerular response to the presence of immune complexes.
BOX 43-1
Dogs
Familial
Infectious
Nonimmunologichyperfiltration?
Canine adenovirus I Diabetes mellitus
Bacterial e n d o c a r d i t i s
Cats
Brucellosis
Infectious
Dirofilariasis
Ehrlichiosis Feline leukemia virus
Leishmaniasis Feline i m m u n o d e f i c i e n c y virus
Pyometra Feline infectious peritonitis
Borelliosis M y c o p l a s m a polyarthritis
Chronic bacterial infections (gingivitis, p y o d e r m a ) C h r o n i c b a c t e r i a l infections
Rocky M o u n t a i n spotted fever
Trypanosomiasis Neoplasia
Inflammatory
Septicemia
Helicobacter? Pancreatitis
Systemic lupus erythematosus
Neoplasia
Other immune-mediated diseases
Inflammatory
C h r o n i c skin disease
Pancreatitis
Various Types
Systemic lupus erythematosus
Other immune-mediated diseases Idiopathic
Prostatitis Familial
Hepatitis Nonimmunologichyperfiltration?
Diabetes mellitus
Inflammatory b o w e l disease
Various Types
Hyperadrenocorticism a n d long-term, high-dose corticosteroids?
Idiopathic
FIG 4 3 - 3
Proposed pathogenesis o f progressive loss o f n e p h r o n s s e c o n d a r y to a p r i m a r y
glomerulonephropathy.
hypertension i f present, may further contribute to glomeru of the acute-phase reactant protein, serum amyloid A protein
lar hyalinization and sclerosis. Although it has not been (SAA), and is produced by hepatocytes i n response to tissue
documented i n dogs with naturally occurring G N , hyperfil injury. Cytokines (e.g., interleukins, tumor necrosis factor)
tration and proteinuria i n remnant nephrons may result i n released from macrophages after tissue injury stimulate
progressive nephron loss, independent of the primary disease hepatocytes to produce S A A . Amyloidosis is usually associ
process. ated with an underlying inflammatory or neoplastic process;
Although glomerular amyloidosis is less c o m m o n than however, no predisposing factors can be identified i n many
G N , it is a progressive disease that also frequently leads to dogs and cats with amyloidosis. Amyloidosis has been asso
C K D . It is characterized by the extracellular deposition o f ciated with cyclic neutropenia and with ciliary dyskinesia
nonbranching fibrillar proteins that stack into a specific (3- and recurrent respiratory tract infections i n dogs. Renal
pleated sheet conformation and exhibit green birefringence amyloidosis is a familial disease i n the Abyssinian cat; it
under polarized light when stained with Congo red (Fig. 43-4). results i n medullary (not glomerular) amyloid deposition as
Amyloidosis i n dogs and cats is the reactive systemic form, a part o f systemic amyloidosis. A similar form of suspected
i n which amyloid may be deposited i n several organs besides familial medullary amyloidosis resulting i n renal failure has
the kidneys. Reactive systemic amyloid deposits contain been observed i n Chinese Shar-Pei dogs. Intermittent fever
amyloid protein A A , which is an amino-terminal fragment that occurs i n association with tibiotarsal joint swelling
and that resolves regardless of treatment is often observed
i n these dogs. The staining characteristics o f the amyloid
i n Chinese Shar-Peis indicate that the amyloid is an inflam
matory type. This amyloidosis syndrome i n Chinese Shar-
Peis is similar to that observed i n people with familial
Mediterranean fever. The medullary deposition of amyloid
i n Abyssinian cats and Chinese Shar-Pei dogs makes pro
teinuria u n c o m m o n ; renal failure, however, is a c o m m o n
sequela.
Clinical Features
There may be no clinical signs associated with low level
proteinuria; alternatively, i f signs are present they are usually
m i l d and nonspecific (e.g., weight loss and lethargy). If pro
teinuria is severe and results i n serum albumin concentra
tion <1.5 to 1.0 mg/dl, edema and/or ascites may occur
(Table 43-1). If the glomerular disease process causes loss of
FIG 4 3 - 4
Typical a p p e a r a n c e of glomerular a m y l o i d (green birefrin more than three quarters of the nephrons, clinical signs
g e n c e ) w h e n r e n a l t i s s u e is s t a i n e d w i t h C o n g o red a n d consistent with advanced stage C K D may be present (e.g.,
viewed under polarized light. polydipsia-polyuria, anorexia, nausea, vomiting, weight
TABLE 43-1
*Microalbuminuria, as discussed in Chapter 42, may precede proteinuria and therefore be an early diagnostic tool.
P c o , Partial pressure of carbon dioxide.
2
loss). Occasionally, clinical signs associated with an underly A n t i t h r o m b i n works i n concert with heparin to inhibit serine
ing infectious, inflammatory, or neoplastic disease may be proteases (clotting factors II, I X , X , X I , and XII) and nor
the reason owners seek veterinary care. Rarely, dogs may be mally plays a vital role i n modulating t h r o m b i n and fibrin
presented with acute dyspnea or severe panting caused by a production. Finally, impaired fibrinolysis caused by aldoste
pulmonary thromboembolism or may have signs associated rone-induced production o f PAI-1 further enhances b l o o d
with thromboembolism elsewhere (e.g., lameness from clotting. The pulmonary arterial system is the most c o m m o n
aortic thromboembolism). location for a thromboembolic disease i n dogs with glo
Persistent proteinuria may lead to clinical signs o f merular lesions. Dogs with pulmonary thromboembolism
nephrotic syndrome, which is usually defined as a combina are usually dyspneic and hypoxemic and have m i n i m a l p u l
tion of proteinuria, hypoalbuminemia, ascites or edema, and monary parenchymal radiographic abnormalities. Treatment
hypercholesterolemia. Decreased plasma oncotic pressure of pulmonary thromboembolism is difficult, often expen
and hyperaldosteronism activity causing sodium retention sive, and frequently unrewarding; therefore early prophylac
are thought to be the primary cause o f ascites and edema. It tic treatment to prevent thrombus formation is important.
has also been hypothesized that intrarenal mechanisms, There is increasing suspicion that proteinuria may cause
independent o f aldosterone, may contribute to sodium glomerular and tubulointerstitial damage that can lead to
retention. The hypercholesterolemia associated with the progressive nephron loss i n dogs and cats. Plasma proteins
nephrotic syndrome probably occurs because o f a combina that have crossed the glomerular capillary wall can accumu
tion of decreased catabolism o f proteins and lipoproteins late w i t h i n the glomerular tuft and stimulate mesangial cell
and increased hepatic synthesis of proteins and lipoproteins. proliferation and increased production o f mesangial matrix.
This results i n the accumulation o f large-molecular-weight, In addition, excessive amounts o f protein i n the glomerular
cholesterol-rich lipoproteins, which are not as easily lost filtrate can damage tubular epithelial cells and lead to inter
through the damaged capillary wall as are the smaller- stitial inflammation, fibrosis, and cell death. Mechanisms for
molecular-weight proteins, such as albumin. the tubulointerstitial lesions associated with proteinuria
In addition to the previously mentioned clinical signs, include tubular cell lysosomal damage/rupture, peroxidative
systemic hypertension and hypercoagulability are frequent and immune-mediated damage, increased production o f
complications i n dogs with nephrotic syndrome. A combina growth factors, cytokines and vasoactive agents, and
tion of activation o f the R A A S and decreased renal produc transdifferentiation o f tubular cells to myoepithelial cells
tion of vasodilators, coupled with increased responsiveness that can produce collagen.
to normal vasopressor mechanisms, are likely involved i n the In dogs with naturally occurring C K D , proteinuria result
pathogenesis of the systemic hypertension. Systemic hyper ing i n a urine p r o t e i n : creatinine ratio 1.0 was associated
tension has been c o m m o n l y associated with i m m u n e - with a threefold greater risk o f developing uremic crises and
mediated G N , glomerulosclerosis, and amyloidosis, and i n death compared with dogs with urine protein: creatinine
one study, 84% of dogs with glomerular disease were found ratio <1.0. The relative risk o f adverse outcome was approx
to be hypertensive. Retinal changes, including hemorrhage, imately 1.5 times higher for every 1 unit increase i n urine
detachment, and papilledema, can be consequences o f sys protein: creatinine ratio. In addition, dogs with urine pro
temic hypertension; occasionally, blindness may be the pre tein: creatinine ratio 1.0 had a decrease i n renal function
senting sign i n hypertensive dogs. In most cases, the systemic that was greater i n magnitude than that observed i n dogs
hypertension is thought to occur secondary to the kidney with urine p r o t e i n : creatinine ratio <1.0. In cats with natu
disease rather than being a primary entitiy that causes the rally occurring C K D , proteinuria appears to be very highly
kidney disease. Systemic hypertension can be transmitted related to survival. The hazard ratios (95% confidence inter
into the glomerular capillaries, especially as autoregulation vals) for death or euthanasia were 2.9 and 4.0 for urine
fails, resulting i n intraglomerular hypertension. This protein: creatinine ratio 0.2 to 0.4 and >0.4, respectively,
increased hydrostatic pressure within glomerular capillaries compared w i t h the baseline group with a urine protein: cre
can exacerbate loss o f plasma proteins across the already atinine ratio <0.2. O n the basis o f this evidence, it is possible
abnormal capillary wall or sufficiently damage the wall to that proteinuria is not only a marker o f C K D i n the dog and
induce nascent glomerular protein loss. B l o o d pressure mea cat but also a mediator o f progressive renal injury. A t t e n u
surement should be part o f the evaluation and management ation o f p r o t e i n u r i a should be a major treatment objective
of dogs with glomerular disease because it is likely that i n dogs and cats with C K D .
control of systemic hypertension may slow the progression
of glomerular disease. Diagnosis
Hypercoagulability and thromboembolism associated Persistent, severe proteinuria with a n o r m a l urine sediment
with the nephrotic syndrome occur secondarily to several (hyaline casts may be observed) is the hallmark clinicopath
abnormalities i n hemostasis. In addition to m i l d thrombo ologic sign o f glomerulonephropathies. The urine pro
cytosis, a hypoalbuminemia-related platelet hypersensitivity tein : creatinine ratio is used to quantify the magnitude o f the
increases platelet adhesion and aggregation proportionally urine protein loss. M i c r o a l b u m i n u r i a may precede overt
to the magnitude of hypoalbuminemia. Loss o f antithrom proteinuria i n many cases (see the section o n proteinuria i n
bin (AT) i n urine also contributes to hypercoagulability. Chapter 42). Protein-losing nephropathies are definitively
diagnosed o n the basis o f renal cortical histopathologic study by V a d e n (1995) cyclosporine treatment was found to
findings. (See sections o n proteinuria and renal biopsy i n be o f no benefit i n reducing proteinuria associated with G N
Chapters 41 and 42.) i n dogs. The association between hyperadrenocorticism or
long-term exogenous corticosteroid administration and G N
Treatment and thromboembolism i n the dog, as well as the lack of
Inasmuch as i m m u n e complexes usually initiate G N , primary consistent therapeutic response to corticosteroids, raises
treatment objectives include (1) identification and elimina questions about use of these drugs i n dogs with G N . In a
tion of causative/associated antigens and (2) reduction of the retrospective study o f dogs with naturally occurring G N ,
glomerular response to the i m m u n e complexes. treatment with corticosteroids appeared to be detrimental,
E l i m i n a t i o n o f the source o f antigenic stimulation is the leading to azotemia and worsening o f proteinuria. Similarly,
treatment o f choice for G N . For example, proteinuria associ prednisone increased the urine protein: creatinine level from
ated with dirofilariasis i n dogs often improves or resolves 1.5 to 5.6 i n carrier female dogs with X - l i n k e d hereditary
after successful treatment o f parasitic infection. U n f o r t u nephropathy. Consequently, routine use of corticosteroids to
nately, elimination of the antigen source often is not possible treat G N i n dogs is not recommended. Treatment with cor
because the antigen source or underlying disease may not be ticosteroids may be indicated, however, i f the underlying
identified or may be impossible to eliminate (e.g., neoplasia). disease process is k n o w n to be steroid responsive (e.g., sys
In a retrospective study by C o o k (1996) o f 106 dogs with temic lupus erythematosus). It is likely that there are specific
G N , 4 3 % had no identifiable concurrent disease or disorder subtypes o f canine i m m u n e complex G N (e.g., minimal
and 19% had neoplasia. Infection, polyarthritis, hepatitis, change G N ) that are steroid responsive i f they are appropri
hyperadrenocorticism, and immune-mediated hemolytic ately identified and treated.
anemia are additional c o m m o n l y identified concurrent If an underlying or concurrent disease process cannot be
medical problems (Box 43-2). identified and treated, or i f immunosuppressive treatment is
Immunosuppressive drugs have been recommended i n deemed inappropriate, treatment may be aimed at decreas
dogs with G N , but despite these recommendations, there has ing the glomerular response to the presence of immune
been only one controlled clinical trial i n veterinary medicine complexes. Platelets appear to play an important role i n the
assessing the effects of immunosuppressive treatment. In this glomerular response to i m m u n e complexes, and therefore
aspirin treatment is often recommended. Appropriate dosage
is probably important i f nonspecific cyclooxygenase inhibi
tors, such as aspirin, are used to decrease glomerular inflam
mation and platelet aggregation. A n extremely low dosage of
BOX 4 3 - 2 aspirin (0.5 mg/kg administered orally once a day) may
selectively inhibit platelet cyclooxygenase without prevent
T r e a t m e n t Guidelines f o r Dogs a n d Cats
ing the beneficial effects of prostacyclin formation (e.g.,
with Glomerulonephritis
vasodilation, inhibition of platelet aggregation). Low-dose
1 . Identity a n d eliminate a n y underlying diseases aspirin is easily administered o n an outpatient basis and does
2 . Immunosuppressive treatment (usually not r e c o m m e n d e d not require extensive monitoring. Because fibrin accumula
for dogs) tion within the glomerulus is a frequent and irreversible
2
a. C y c l o p h o s p h a m i d e , 5 0 m g / m P O q 4 8 h (dogs) o r consequence of G N and thromboembolic disorders can
2
2 0 0 to 3 0 0 m g / m P O q 3 w k (cats) o r complicate the management of protein-losing nephropa
2
b. A z a t h i o p r i n e , 5 0 m g / m P O q 2 4 h x 7 days, then thies, antiplatelet/anticoagulant treatment with aspirin may
q 4 8 h (dogs only) o r
serve several purposes.
c. C y c l o s p o r i n e A , 1 5 m g / k g P O q 2 4 h (dogs only)
Treatment with angiotensin-converting enzyme inhibitors
d . Prednisone, 1.0 to 2 . 0 m g / k g P O q l 2 - 2 4 h (cats
only) (ACEIs) can reduce proteinuria and slow disease progres
3. A n t i i n f l a m m a t o r y - h y p e r c o a g u l a b i l i t y treatment: a s p i r i n , sion. In dogs with unilateral nephrectomy and experimen
0 . 5 to 5 . 0 m g / k g P O q l 2 h (dogs); 0 . 5 to 5 . 0 m g / k g tally induced diabetes mellitus, A C E I administration reduced
PO q 4 8 h (cats) glomerular transcapillary hydraulic pressure and glomerular
4 . Supportive care cell hypertrophy as well as proteinuria. In another study by
a. Dietary: sodium restriction, h i g h - q u a l i t y - l o w - q u a n t i t y Grodecki (1997) A C E I treatment o f Samoyed dogs with X -
protein linked hereditary nephritis decreased proteinuria, improved
b. Hypertension: d i e t a r y sodium reduction; ACEIs (e.g., renal excretory function, decreased glomerular basement
enalapril, 0 . 5 m g / k g PO q 1 2 - 2 4 h , or benazepril,
membrane splitting, and prolonged survival compared with
0 . 2 5 to 0 . 5 m g / k g P O q 2 4 h ; ACEIs often have
control dogs. A double-blind, multicenter, prospective clini
antiproteinuric effects as well) a n d / o r calcium
cal trial assessed the effects o f enalapril ( E N ) versus standard
channel blockers
care i n dogs with naturally occurring, idiopathic G N . The
c. Edema a n d ascites: d i e t a r y sodium restriction; furo
semide, 2 . 2 m g / k g P O q 8 - 2 4 h , if necessary enalapril treatment group had decreased proteinuria, systolic
b l o o d pressure, and stable renal function compared with the
PO, By mouth; ACEIs, angiotensin-converting enzyme inhibitors. placebo-treated group. In prospective randomized, con-
trolled clinical trials (King, 2006; M i z u t a n i , 2006) i n cats that D M S O has a similar amyloid-dissolving effect i n domes
with spontaneous C K D , benazepril has been shown to reduce tic animals. The antiinflammatory effects o f D M S O may also
proteinuria, delay C K D progression, and extend survival serve to decrease production o f the acute-phase reactant
time. S A A and the inflammation associated w i t h an underlying
Treatment with A C E I probably decreases proteinuria and disease. Decreased urinary protein excretion was observed i n
preserves renal function associated with glomerular disease one dog w i t h amyloidosis treated w i t h D M S O ; however, the
by several mechanisms. In dogs administration o f lisinopril effects o f D M S O were difficult to determine because two
decreases efferent glomerular arteriolar resistance, w h i c h potential underlying causes (interdigital pyoderma and a
results i n decreased glomerular transcapillary hydraulic Sertoli cell tumor) were eliminated before the D M S O treat
pressure and decreased proteinuria. In rats administration ment. The dosage o f D M S O used i n that dog was 80 mg/kg
of E N prevents the loss of glomerular heparan sulfate that administered subcutaneously three times per week; the treat
can occur with glomerular disease. Administration o f A C E I ment was continued for more than a year without apparent
also is thought to attenuate proteinuria by decreasing the size adverse effects. Other studies assessing the effects o f D M S O
of glomerular capillary endothelial cell pores i n people. In in dogs w i t h amyloidosis, however, have shown the treat
addition, the antiproteinuric and renal protective effects o f ment to be ineffective.
A C E I i n people may be, i n part, associated w i t h improved Colchicine is another drug that is frequently mentioned
lipoprotein metabolism. Decreased production o f angioten for the treatment o f amyloidosis. It prevents the production
sin and aldosterone may also result i n decreased renal fibro of S A A by hepatocytes and has been shown to prevent amy
sis. Finally, administration of A C E I i n dogs slows glomerular loidosis i n humans and mice i f used early i n the disease.
mesangial cell growth and proliferation that can alter the A l t h o u g h colchicine has been recommended to prevent
permeability of the glomerular capillary wall and lead to medullary amyloidosis i n Chinese Shar-Pei dogs w i t h
glomerulosclerosis. fever and tibiotarsal joint swelling, no controlled studies o f
Supportive therapy is important i n the management of its use i n this setting have been performed. The dosage
dogs with G N and should be aimed at alleviating systemic of colchicine that has been recommended for the pro
hypertension, decreasing edema/ascites, and reducing the phylactic treatment o f amyloidosis is 0.025 mg/kg given
risk of thromboembolism. A C E I s are recommended as the orally q24h. Increasing the dose to 0.025 mg/kg, given orally
first line of treatment for proteinuric, hypertensive dogs. In q12h, may be considered i f the animal tolerates the initial
those cases wherein systemic hypertension is refractory to dose well for 2 weeks. However, because adverse effects
A C E I treatment, a calcium channel blocker should be added of colchicine include bone marrow toxicity, the patient
to the antihypertensive regimen. A l t h o u g h similar studies should be monitored closely w i t h periodic complete b l o o d
have not been performed i n dogs or cats, i n people the c o m counts.
bination o f A C E I and an aldosterone receptor antagonist
(e.g., spironolactone) have had additive effects i n reducing Monitoring
proteinuria and renal disease progression. It is important to m o n i t o r the urine protein: creatinine ratio
Cage rest and restriction o f dietary sodium should be the after initiating treatment. Immunosuppressive treatment
primary treatment considerations for patients with edema could alter the ratio of antigen to antibody, thus exacerbating
and/or ascites. Paracentesis and diuretics should be reserved the glomerular lesions and the proteinuria (i.e., a decrease
for those dogs with respiratory distress or abdominal dis i n antibody formation leading to a m i l d excess o f antigen or
comfort. Overzealous use of diuretics may cause dehydration equal amounts o f antigen and antibody i n the i m m u n e c o m
and acute renal decompensation. Plasma transfusions w i l l plexes), i n w h i c h case treatment should be altered or discon
provide only temporary benefit i n terms of increasing oncotic tinued. In addition, corticosteroids can induce proteinuria
pressure resulting from the addition o f albumin. In the past, owing to a number o f mechanisms, so an increase i n the
dietary protein supplementation was recommended to offset urine protein: creatinine ratio can be iatrogenic, not neces
the effects o f proteinuria and reduce edema and ascites; sarily a result o f the progression o f the disease. Lack o f
however, recent studies i n proteinuric heterozygous female response to A C E I treatment may suggest the need for increas
dogs with X - l i n k e d nephropathy suggest that reduced dietary ing the dosage or adding one or more drugs.
protein is associated with reduced proteinuria. N - 3 fatty acid In addition, b l o o d pressure and serum creatinine and
supplementation may also be beneficial; i n dogs w i t h surgi urea nitrogen concentrations should be monitored i n animals
cally reduced remnant kidneys, dietary supplementation with G N . In cases i n w h i c h the glomerular filtration rate
with fish o i l reduced proteinuria, intraglomerular pressures, depends o n s o d i u m retention and volume expansion, treat
and glomerular lesion and maintained the glomerular filtra ment w i t h A C E I s can be associated w i t h a decrease i n renal
tion rate. excretory function. Finally, although proteinuria then
Similar to the treatment of G N , the primary treatment for occurs before the onset o f azotemia, G N can lead to C K D .
amyloidosis, i f possible, should be the identification and W i t h the development o f C K D , the glomerular filtration
treatment of any underlying inflammatory process. Dimeth rate decreases and the proteinuria therefore usually also
ylsulfoxide ( D M S O ) has been shown to dissolve amyloid decreases. Management guidelines for C K D are presented i n
fibrils in vitro and in vivo i n mice. It has been hypothesized Chapter 44.
Prognosis Grauer G F et al: Effects o f enalapril vs placebo as a treatment for
canine idiopathic glomerulonephritis, / Vet Intern Med 14:526,
The prognosis for dogs w i t h G N is variable and is best based
2000.
on consideration of the following factors: severity o f dys
Grauer G F : Management o f glomerulonephritis. In Elliott JA,
function (i.e., the magnitude o f the proteinuria and the pres
Grauer G F , editors: BSAVA manual ofcanine and feline nephrology
ence or absence o f azotemia), the response to therapy, and and urology, ed 2, Gloucester, England, 2007, British Small
the assessment o f renal histopathology. C l i n i c a l experience A n i m a l Veterinary Association.
suggests that the disease is progressive i n m a n y cases, but G r o d e c k i K et al: Treatment o f X - l i n k e d hereditary nephritis i n
decreases i n the urine p r o t e i n : creatinine ratio and increases Samoyed dogs w i t h angiotensin-converting enzyme ( A C E )
i n a l b u m i n and A T concentration can occur i n dogs w i t h inhibitor, / Comp Pathol 117:209, 1997.
i m m u n e - m e d i a t e d G N treated w i t h diet, A C E I s , and l o w - l o c o b F et al: Evaluation o f the association between initial pro
dose aspirin. In selected cases, immunosuppressive treatment teinuria a n d m o r b i d i t y rate or death i n dogs w i t h naturally
occurring chronic renal failure, J Am Vet Med Assoc 226:393-400,
w i t h corticosteroids and azathioprine may be o f benefit.
2005.
Inasmuch as glomerular a m y l o i d deposition results i n
K i n g J N et al: Tolerability a n d efficacy o f benazepril i n cats
severe proteinuria, w i t h its attendant effects, the disease is
with chronic kidney disease, / Vet Intern Med 20:1054,
relentlessly progressive, often resulting i n C K D and uremia;
2006.
and given that no specific treatment has proved to be effec Lees G E , et al: Assessment a n d management o f proteinuria i n dogs
tive, the prognosis for animals w i t h renal amyloidosis is a n d cats: 2004 A C V I M F o r u m Consensus Statement (Small
guarded to poor. A n i m a l ) , / Vet Intern Med 19:377, 2005.
M i z u t a n i H et al: Evaluation o f the clinical efficacy o f benazepril i n
Suggested Readings the treatment o f chronic renal insufficiency i n cats, / Vet Intern
B r o w n S et al: Guidelines for the identification, evaluation, a n d Med 20:1074, 2006.
management o f systemic hypertension i n dogs a n d cats, / Vet Syme H M et al: Survival o f cats w i t h naturally occurring chronic
Intern Med 21:542, 2007. renal failure is related to severity o f proteinuria, / Vet Intern Med
C o o k A K et al: C l i n i c a l a n d pathologic features o f protein-losing 20:528, 2006.
glomerular disease i n the dog: A review o f 137 cases, J Am Anim V a d e n S L et al: T h e effects o f cyclosporin versus standard care i n
Hosp Assoc 32:313-322, 1996. dogs w i t h naturally occurring glomerulonephritis, / Vet Intern
D a m b a c h D M et al: M o r p h o l o g i c , i m m u n o h i s t o c h e m i c a l , a n d Med 9:259, 1995.
ultrastructural characterization o f a distinctive renal lesion i n V a d e n SL: G l o m e r u l a r diseases. In Ettinger SJ, Feldman E C , editors:
dog putatively associated w i t h Borrelia burgdorferi infection: 49 Textbook of veterinary internal medicine, ed 6, St Louis, 2005,
cases (1987-1992), Vet Pathol 34:85, 1997. Elsevier/Saunders.
C H A P T E R 44
Therapeutic Agents
Antimicrobials Chloroform
Pesticides
Aminoglycosides Herbicides
Cephalosporins Solvents
Nafcillin (especially in c o m b i n a t i o n w i t h anesthesia)
Polymyxins Pigments
Sulfonamides Hemoglobin
Tetracyclines Myoglobin
Antifungals Intravenous Agents
Amphotericin B R a d i o g r a p h i c contrast agents
Anthelmintics Chemotherapeutic Agents
Thiacetarsamide Cisplatin
Analgesics Methotrexate
Doxorubicin
Nonsteroidal antiinflammatory drugs
Anesthetics
H e a v y Metals
Methoxyflurane
Lead
Mercury Miscellaneous A g e n t s
Cadmium Hypercalcemia
Chromium
Snake v e n o m
Organic C o m p o u n d s Raisins/grapes
Ethylene glycol
C a r b o n tetrachloride
over 10 minutes can help assess the possibility o f a subse Provide caloric requirements ( 7 0 to 1 0 0 k c a l / k g / d a y ) .
quent volume overload. The C V P should not increase by
more than 2 c m of water if the patient's cardiovascular func
tion is normal. Because measurement o f C V P is not always
accurate or reproducible, results should always be inter assessment o f body weight, C V P , packed cell volume, and
preted i n light o f other paramenters (e.g., patient's body plasma total solids w i l l help detect early overhydration. A n
weight, hematocrit, plasma total solids, and physical exami increase i n the C V P of 5 to 7 c m o f water over baseline
nation findings). The purpose of replacing volume deficits values suggests the likelihood of overhydration. Physical
over the first 4 to 6 hours rather than over the n o r m a l 12 to manifestations o f overhydration include increased broncho-
24 hours is to rapidly improve renal perfusion and decrease vesicular sounds or overt crackles and wheezes, tachycardia,
the likelihood of continued ischemic damage. N o r m a l saline restlessness, chemosis, and serous nasal discharge; however,
(0.9% solution) is the fluid o f choice for rehydration unless these signs tend to be observed after the development of
the patient is hypernatremic, i n which case a 0.45% saline pulmonary edema. Overhydration i n dogs and cats with oli
with 2.5% dextrose solution should be used. The amount o f goanuric A R F is a c o m m o n complication that is extremely
fluid required to restore extracellular fluid deficits can be difficult to correct.
calculated by multiplying the estimated percentage o f dehy U r i n e production should be measured and electrolyte
dration by the patient's body weight i n kilograms. and acid-base status assessed during the period o f rehydra
D u r i n g this rapid rehydration phase the patient should tion. U r i n e production (ml/kg/hour) should be measured so
be closely observed for signs of overhydration. Frequent that maintenance fluid needs can be accurately administered.
0.9% saline solution) are effective i n lowering serum calcium
TABLE 4 4 - 2
concentration and do not affect the clinician's ability to diag
nose the primary cause of hypercalcemia. Conversely, sig
Hypothetical Examples of Daily Maintenance Fluid
nificant hypocalcemia can be observed i n dogs and cats with
Requirements in Does and Cats
A R F associated with ethylene glycol intoxication.
NORMAL Oliguric A R F patients are at risk for hyperkalemia. Serum
URINE OLIGURIC NONOLIGURIC
potassium concentrations greater than 6.5 to 7.0 m E q / L can
PRODUCTION ARF ARF
cause cardiac conduction disturbances (bradycardia, atrial
standstill, idioventricular rhythms, ventricular tachycardia,
Insensible 20 20 20
ventricular fibrillation, asystole) and electrocardiographic
loss ( m l / k g )
Urine v o l u m e 40 10 160 changes (peaked T waves, prolonged P R intervals, widened
(ml/kg) Q R S complexes, or the loss o f P waves). M i l d to moderate
Total ( m l / k g ) 60 30 180 hyperkalemia typically resolves with administration of
potassium-free fluids (dilution) and improved urine flow
ARF, Acute renal failure. (increased excretion). M o r e severe hyperkalemia (>7-8 m E q /
L) or hyperkalemia resulting i n electrocardiographic ( E C G )
abnormalities should be treated with agents that rapidly
Because approximately two thirds o f normal maintenance decrease serum potassium concentrations or counteract the
fluid needs are due to fluid loss i n urine, oliguric and nono effects o f hyperkalemia on cardiac conduction. Sodium
liguric patients can have large variations i n their mainte bicarbonate (see discussion o f dosage later i n this chapter)
nance fluid needs (see Table 44-2). Metabolism cages, urinary helps correct metabolic acidosis and lower serum potassium
catheters, and manual collection of voided urine are methods concentration by exchanging intracellular hydrogen ions for
used to collect and measure urine volume. W i t h regard potassium. Insulin can also be used to increase intracellular
to indwelling urinary catheters, strict aseptic technique shifting o f potassium. Regular insulin is administered intra
and closed collection systems must be used. Because o f the venously at a dosage o f 0.1 to 0.25 U / k g , followed by a
possibility o f urinary tract infection, intermittent u r i n glucose bolus o f 1 to 2 g per unit o f insulin given. Blood
ary bladder catheterization is usually recommended over glucose m o n i t o r i n g should be maintained for several hours
indwelling catheterization for timed urine volume collec after administration o f insulin because hypoglycemia may
tions. In cats weighing the litter pan before and after voiding occur. Ten percent calcium gluconate (0.5-1.0 ml/kg admin
is a useful, although less accurate, method for assessing urine istered intravenously over 10 to 15 minutes) will counteract
production. If an indwelling urinary catheter or a metabo the cardiotoxic effects o f hyperkalemia without lowering the
lism cage is not available, patients should be weighed i n the serum potassium and can be used i n emergency situations.
same scale two or three times a day to assess fluid gain or The effects o f the aforementioned regimens are short-lived,
loss. and fluid and acid-base therapy to initiate and maintain a
Initially, most patients with A R F have n o r m a l serum diuresis and maintain b l o o d p H and bicarbonate within
s o d i u m and chloride concentrations o n account o f iso the normal range (discussed i n more detail later i n this
natremic fluid loss. However, hypernatremia can develop chapter) are important to maintain potassium excretion and
after several days o f therapy with fluids containing large normokalemia.
amounts o f s o d i u m (0.9% N a C l , lactated Ringer's solution, M i l d to moderate metabolic acidosis also generally res
and N o r m o s o l ) and/or i n association with sodium bicarbon olves after fluid therapy, and specific treatment is usually not
ate treatment o f metabolic acidosis. If hypernatremia occurs, necessary unless the b l o o d p H is less than 7.2 or the total
the use 0.45% N a C l w i t h 2.5% dextrose fluids w i l l usually C O / C O H is less than 12 m E q / L . Bicarbonate requirements
2 3
correct the problem. can be calculated using the base deficit as determined from
Disorders o f calcium balance can also occasionally occur arterial b l o o d gas, or an estimated base deficit [body weight
i n patients with A R F . If moderate to severe hypercalcemia is (kg) x 0.3 x base deficit or (20 - T C O ) = m E q bicarbonate
2
observed, a primary hypercalcemic disorder (e.g., neoplasia required]. Optimally, one half the calculated bicarbonate
or vitamin D intoxication) should be considered as the
3 dosage should be administered intravenously over 15 to 30
cause o f the renal failure. In most cases assessment o f the minutes, and then acid-base parameters reassessed. Over-
ionized calcium concentration is preferable to measurement zealous bicarbonate administration may result i n ionized
of the total calcium concentration. Immediate treatment for hypocalcemia, paradoxical cerebral spinal fluid (CSF) acido
hypercalcemia includes rehydration with 0.9% N a C l fol sis, and/or cerebral edema.
lowed by diuresis induced with furosemide. Glucocorticoids If signs of overhydration are not present and oliguria
w i l l also help lower calcium concentrations by decreasing persists after apparent rehydration, m i l d volume expansion
intestinal absorption and facilitating excretion, but their use (3% to 5% o f the patient's body weight i n fluid) may be
may interfere with the diagnosis o f the underlying disorder initiated inasmuch as dehydration of this magnitude is dif
(e.g., lymphoma). Intravenous bisphosphonates (pamidro ficult to detect clinically. If volume expansion is attempted,
nate-Aredia, 1 mg/kg as a constant rate infusion (CRI) i n the possibility o f inducing overhydration increases and close
patient observation is necessary. Unfortunately, most patients 3 times a day on the same scale. If hypernatremia and hyper
that have oliguria will remain oliguric after rehydration and kalemia are not present and a diuresis has been established,
volume expansion. polyionic maintenance fluids (e.g., lactated Ringer's solu
In the past, diuretic therapy was frequently recommended tion, N o r m o s o l ) should be used. In the recovery phase of
in patients that were persistently oligoanuric despite appro A R F , urine volume and electrolyte losses can be great. Potas
priate fluid therapy. Compared with those patients with sium supplementation may be necessary, especially i f the
diminished urine production, polyuric A R F patients are patient is v o m i t i n g or anorectic.
thought to have less severe tubular injury, improved excre C o n t r o l o f nausea and v o m i t i n g i n dogs and cats with
tion of solutes that are reabsorbed or secreted (e.g., urea A R F is important to facilitate caloric intake. In addition, the
nitrogen and potassium), and less risk o f developing over inability to control v o m i t i n g is discouraging to owners and
hydration and pulmonary edema. There is, however, no evi may result i n a hastened decision for euthanasia. (Please see
dence that diuretic therapy w i l l hasten the recovery from the section o n management o f chronic kidney disease for
A R F or decrease mortality associated with A R F . In humans specific recommendations for the treatment of nausea and
with established A R F , there is increasing evidence that vomiting.)
diuretic therapy may actually be associated with increased W h e n fluid therapy is successful i n i n d u c i n g or maintain
risk of death and nonrecovery of renal function. If the choice ing diuresis, the daily volume of fluid administered to the
is to use diuretics i n dogs or cats with A R F , they should be patient w i l l eventually need to be decreased. Indications for
used only after dehydration has been corrected and the tapering I V fluid volume include the following: (1) signifi
patient has been volume expanded. Furosemide and m a n cant decreases i n B U N and phosphorus concentrations, (2)
nitol are probably the diuretics o f choice. Dopamine is not control o f v o m i t i n g and diarrhea, and (3) i m p r o v e d m o o d
recommended because o f its unpredictable effects on renal and renewed interest i n eating and drinking. These indica
blood flow and G F R . tions rarely occur before 5 or 6 days o f intense fluid therapy/
Furosemide blocks the reabsorption o f chloride and diuresis and may require 10 or more days o f treatment.
sodium i n the thick ascending limb o f Henle, resulting i n Gradually reducing maintenance fluid requirements by 25%
natriuresis and osmotic diuresis. The dose recommended for each day is usually recommended for fluid tapering. If the
oligoanuric dogs and cats is 2 to 6 mg/kg I V q8h; however, patient loses weight or increases i n packed cell volume, total
in healthy dogs C R I o f furosemide with a 0.66 mg/kg I V protein, and B U N and/or creatinine concentrations are
loading dose followed by 0.66 mg/kg/h resulted i n more observed, fluid therapy tapering should be discontinued and
diuresis, natriuresis, and calciuresis and less kaliuresis than the previous maintenance volume reinstated for at least 48
did intermittent bolus infusion. hours.
Mannitol, i n a 10% or 20% solution, has been recom Peritoneal or hemodialysis should be considered i n
mended as an osmotic diuretic at a dose o f 0.5 to 1.0 g/kg, patients with severe, persistent uremia, acidosis, or hyperka
given intravenously as a slow bolus over 15 to 20 minutes. lemia. Dialysis may also be used to treat overhydration and
Urine output should increase within 1 hour i f the treatment hasten elimination o f dialyzable toxicants. Renal biopsy
is effective. A second bolus may be attempted, but the poten should be performed i f the diagnosis is i n doubt, i f the
tial for volume overexpansion and complications such as patient does not respond to therapy w i t h i n 3 to 5 days, or i f
pulmonary edema increases considerably i f urine produc dialysis is considered. The long-term prognosis for dogs or
tion does not increase. As an osmotic agent, mannitol may cats with A R F is usually fair to good i f the patient survives
decrease tubular cell swelling, increase tubular flow, and the period o f renal tubular regeneration and compensation;
help prevent tubular obstruction or collapse. In healthy cats however, several weeks may be required for renal function to
the renal effects of mannitol, when used as an adjunct to improve. A n i m a l s with moderate to severe renal damage may
fluid therapy, are superior to those o f furosemide and require many weeks for renal repair, and the prolonged time
dopamine combination. The use o f mannitol is contraindi required for recovery results i n a poor prognosis. The sever
cated in an overhydrated patient because the resultant ity o f the initial azotemia/uremia, the response to fluid
increase i n intravascular volume may precipitate pulmonary therapy, and assessment o f renal histopathologic lesions are
edema. the most important prognostic indicators early i n the course
Whether or not diuresis can be established, fluid therapy of A R F .
should be tailored to match urine volume and other losses,
including insensible losses (e.g., water loss caused by respira
tion) and continuing losses (e.g., fluid loss caused by vomit CHRONIC KIDNEY DISEASE
ing or diarrhea). Insensible losses are estimated at 20 ml/kg/day.
Urine output is quantitated for 6- to 8-hour intervals, and Etiology and Pathogenesis
that amount is replaced over an equivalent subsequent time U n l i k e A R F , the cause o f C K D is usually difficult to deter
period. The volume o f fluid loss resulting from v o m i t i n g mine. Because o f the interdependence of the vascular and
and/or diarrhea is estimated, and that amount is added to tubular components o f the nephron, the end-point o f irre
the 24-hour fluid needs of the patient. Fluid losses or gains versible glomerular or tubular damage is the same. A m o r
can also be indirectly estimated by weighing the patient 2 to phologic heterogeneity among nephrons exists i n the
BOX 4 4 - 6 BOX 4 4 - 7
I m m u n o l o g i c Disorders A m i n o acids
Ammonia
Systemic lupus erythematosus A r o m a t i c a n d aliphatic amines
Glomerulonephritis Creatinine
Vasculitis (e.g., feline infectious peritonitis)
Cyclic adenosine m o n o p h o s p h a t e
Amyloidosis Gastrin
Neoplasia Glucagon
Growth hormone
Primary
Guanidinium compounds
Secondary
Indoles
Nephrotoxicants Parathyroid h o r m o n e
Renal Ischemia Peptides
I n f l a m m a t o r y o r Infectious Causes Phenols
Phosphate
Pyelonephritis
Polyols
Leptospirosis
Purine a n d p y r i m i d i n e derivatives
Renal calculi
Renin
H e r e d i t a r y a n d Congenital Disorders Ribonuclease
Urea
Renal h y p o p l a s i a o r dysplasia Uric a c i d
Polycystic kidneys
Familial nephropathies (Lhasa A p s o s , Shih Tzus, N o r w e
g i a n Elkhounds, Rottweilers, Bernese M o u n t a i n Dogs,
C h o w C h o w s , N e w f o u n d l a n d s , Bull Terriers, Pembroke
Welsh C o r g i s , Chinese Shar-Peis, D o b e r m a n Pinschers, of these substances. Components of the uremic syndrome
Samoyeds, G o l d e n Retrievers, S t a n d a r d Poodles, Soft include sodium and water imbalance, anemia, carbohydrate
C o a t e d W h e a t e n Terriers, Cocker Spaniels, Beagles, intolerance, neurologic disturbances, gastrointestinal tract
Keeshonds, Bedlington Terriers, C a i r n Terriers, Basenjis, disturbances, osteodystrophy, immunologic incompetence,
Abyssinian cats) and metabolic acidosis.
In addition to excreting metabolic wastes and maintain
Urinary O u t f l o w Obstruction
ing fluid and electrolyte balance, the kidneys also function
Idiopathic
as endocrine organs and catabolize several peptide hor
mones. Therefore h o r m o n a l disturbances also play a role i n
the pathogenesis o f C K D . For example, the decreased pro
duction o f erythropoietin ( E P O ) and calcitriol i n animals
chronically diseased kidney, with the changes ranging from with C K D contributes to the development of nonregenera
severe atrophy and fibrous connective tissue replacement to tive anemia and hyperparathyroidism. Conversely, decreased
marked hypertrophy. The histopathologic changes are not metabolism and increased concentrations o f parathyroid
process-specific, and therefore the cause is usually u n k n o w n . hormone ( P T H ) and gastrin contribute to the development
Nevertheless, recent studies have shown that primary glo of hyperparathyroidism and gastritis, respectively.
merular disorders are a major cause o f C K D i n the dog. Some o f the pathophysiologic changes that occur i n C K D
Because glomerular filtration in toto is uniformly reduced, are brought about by compensatory mechanisms. The
C K D may be considered a single pathologic entity, although osteodystrophy of C K D occurs secondary to hyperparathy
many diverse pathways can lead to this end-point. Potential roidism, which develops i n an attempt to maintain normal
causes o f C K D are listed i n B o x 44-6. plasma calcium and phosphorus concentrations. Similarly,
The pathophysiology o f C K D can be considered at both the G F R o f intact hypertrophied nephrons increases in
the organ and systemic level. A t the level o f the kidney, the animals with C K D i n an attempt to maintain adequate renal
fundamental pathologic change that occurs is a loss o f neph function; however, proteinuria and glomerulosclerosis i n
rons and decreased G F R . Reduced G F R , i n turn, results i n these individual nephrons, leading to additional nephron
increased plasma concentrations o f substances that are nor damage and loss, may be consequences of this hyperfiltration
mally eliminated from the body by renal excretion. M a n y (Fig. 44-3).
substances have been shown to accumulate i n the plasma of
patients with C K D (Box 44-7). The constellation o f clinical Clinical Features and Diagnosis
signs k n o w n as the uremic syndrome is thought to occur, at Unlike A R F , C K D develops over a period of months or years,
least i n part, as a result o f increasing plasma concentrations and its clinical signs are often relatively m i l d for the magni-
tude of the azotemia. Unique signs o f C K D include a history STAGING CHRONIC KIDNEY DISEASE
of weight loss, polydipsia-polyuria, poor body condition, Once a diagnosis o f C K D has been established and fluid
nonregenerative anemia, and small and irregularly shaped therapy has resolved any prerenal azotemia, staging the
kidneys. A diagnosis of C K D is usually based on a combina disease process can help clinicians focus their diagnostic and
tion of compatible historical, physical examination, and therapeutic efforts. The International Renal Interest Society
clinicopathologic findings. Plain radiographs can confirm (IRIS) was created to advance the scientific understanding
the presence o f small kidneys. Renal ultrasonography will of kidney diseases i n small animals at the Eighth A n n u a l
usually show diffusely hyperechoic renal cortices with loss o f Congress o f the European Society o f Veterinary Internal
the normal corticomedullary boundary. The increased corti Medicine i n Vienna, Austria i n 1998. Seventeen independent
cal echogenicity results from replacement o f the irreversibly veterinary nephrologists from eight countries serve o n the
damaged nephrons with fibrous connective tissue. Radio IRIS Board, w i t h the mission o f helping practitioners better
graphic studies and ultrasonography can also help identify diagnose, understand, and treat canine and feline renal
or rule out potentially treatable causes o f C K D , such as disease. Table 44-3 was developed by the IRIS Board as guide
pyelonephritis and renal urolithiasis. Renal biopsy is not to staging canine and feline C K D .
routinely performed i n animals with C K D unless the diag Serum creatinine concentrations must always be inter
nosis is i n question. Renal histopathologic preparations will preted i n light of the patient's urine specific gravity and
show some combination o f a loss o f tubules with replace physical examination findings to rule out prerenal and
ment fibrosis and mineralization, glomerulosclerosis and postrenal causes o f azotemia. The C K D stages are further
glomerular atrophy, and foci of mononuclear cells (small classified by the presence or absence o f proteinuria and sys
lymphocytes, plasma cells, and macrophages) within the temic hypertension (Table 44-4).
interstitium i n association with fibrous connective tissue The classic diagnosis o f renal failure based o n renal azo
replacement. temia (persistent azotemia superimposed on the inability to
TABLE 4 4 - 4
URINE PROTEIN:CREATININE
RATIO CLASSIFICATION
<140 Normotensive
140-160 Borderline hypertensive
>160 Hypertensive
FIG 4 4 - 3
Proposed pathogenesis of progressive loss of nephrons in IRIS, International Renal Interest Society; CKD, chronic kidney
chronic kidney disease. disease.
TABLE 44-3
FIG 4 4 - 4
Prioritization o f d i a g n o s t i c a n d treatment efforts b a s e d o n the stage of chronic k i d n e y
disease. The larger the a r r o w h e a d , the higher the priority.
is not performed unless an obstruction develops. C o n c u r
TABLE 4 4 - 5
rent pyelonephritis that cannot be resolved with antibiotic
treatment is another potential indication for surgical Risk of Target Organ Damage Associated with
intervention. Hypertension in Dogs and Cats
Similar to bacterial pyelonephritis, hypertension ( H T )
SYSTOLIC B L O O D DIASTOLIC B L O O D
can cause or complicate C K D . Gradual reduction o f dietary
PRESSURE ( M M H G ) PRESSURE ( M M H G ) RISK LEVEL
salt intake is often recommended as the first line of treat
ment for H T ; however, no studies document the efficacy of <150 <95 Minimal
dietary salt reduction i n lowering b l o o d pressure i n dogs or 150-159 95-99 Low
cats. In many cases vasodilators ( A C E I and calcium channel 160-179 100-119 Moderate
blockers [CCBs]) may be necessary to control hypertension. 180 120 High
Although ACEIs are usually recommended for H T associated
with C K D i n dogs, amlodipine is often recommended as the
first-choice antihypertensive medication for cats. Recent
studies, however, have raised the concern that amlodipine as phosphorus reduction, serum phosphorus concentrations
a monotherapy i n animals with renal disease may expose the remain high, enteric phosphate-binding gels containing
glomeruli to higher pressures because o f efferent arteriolar calcium acetate, calcium carbonate, or a l u m i n u m hydroxide
constriction caused by local increases i n renin-angiotensin- should be administered with meals (initial dosage o f 30 m g /
aldosterone system activity. If so, cats with renal disease kg b o d y weight with the dosage increased as needed to
should benefit from therapy with both A C E I s and C C B s . achieve normophosphatemia).
Cats with C K D are m i l d to moderate H T should be treated Hyperphosphatemia i n patients with C K D occurs as a
with an A C E I (e.g., benazepril: 0.5 to 1.0 mg/kg q24h) result o f decreased renal excretion o f phosphates. C o n c u r
because of the positive effects on intraglomerular hyperten rently, decreased renal production o f the active form o f
sion and proteinuria. In cats with severe H T (systolic b l o o d vitamin D decreases intestinal absorption of calcium, which,
3
pressure >180 m m Hg) or cats i n which H T persists despite i n conjunction with impaired renal reabsorption of calcium,
A C E I treatment, amlodipine (0.625 to 1.25mg/cat q24h) decreases plasma ionized calcium concentrations. Decreased
treatment should be initiated. Several studies have docu vitamin D and serum calcium concentrations stimulate
3
mented renoprotective effects of A C E I s i n dogs and cats with P T H secretion, which facilitates renal excretion of phospho
naturally occurring C K D . rus and increases serum calcium concentrations by increas
Direct-acting vasodilator drugs such as A C E I s and C C B s ing renal calcium reabsorption and calcium absorption from
are the most successful i n achieving acute reduction o f blood bones and the gastrointestinal tract. The disadvantages o f
pressure, but sympathetic nervous system-mediated increases this hyperparathyroidism, however, can be severe and include
in heart rate and aldosterone-mediated sodium and water osteodystrophy, bone m a r r o w suppression, and soft tissue
retention may modulate the effects o f the vasodilation over mineralization. Soft tissue mineralization occurs p r e d o m i
time. C o m b i n i n g antihypertensive treatments with different nantly i n damaged tissue, and i f mineralization occurs i n
modes of action may block the compensatory effects caused renal tissue, the result may be a progressive decline i n renal
by one medication when used alone. For example, diuretics, function. If the product o f the serum calcium and phospho
aldosterone antagonists, and -blockers, which may have rus concentrations is greater than 50 to 70 mg/dl, the patient
minimal antihypertensive effect alone, may produce additive is at risk for soft tissue mineralization. Studies i n dogs and
effects when given i n combination with A C E I s or C C B s . cats with remnant kidney C K D have shown that n o r m a l
Overall, the risk o f target organ damage i n the eyes, brain, dietary phosphorus intake is associated with microscopic
kidneys, and heart is thought to be m i n i m a l i f systolic b l o o d renal mineralization and fibrosis, and these changes were
pressure is <150 m m H g (Table 44-5). prevented by reducing dietary phosphorus. Similarly, i n dogs
In many dogs and cats with stage II to I V C K D , renal and cats with naturally occurring C K D , feeding a diet spe
lesions progress and renal function deteriorates (see Figure cifically formulated to meet their needs, together with phos
44-1). Progressive loss o f function as well as the rate of phate-binding drugs, ifrequired, controls hyperphosphatemia
decline are monitored by longitudinal measurement o f and secondary renal hyperparathyroidism and is associated
serum creatinine concentrations. In addition to the antihy with a prolonged survival time. Physiologic doses o f cal
pertensive treatment discussed previously, A C E I s (to control citriol may also be beneficial i n dogs and cats with hyper
intraglomerular hypertension and proteinuria) and dietary parathyroidism and hyperphosphatemia associated with
phosphorus restriction are examples of so-called renopro C K D . In a prospective, randomized, controlled clinical trial
tective treatments. Reduction of dietary phosphorus is one i n dogs with spontaneous C K D (stages III and I V ) , calcitriol
of the cornerstones of management o f C K D and can be treatment (initial dose o f 2.5 ng/kg/day that was adjusted
accomplished by feeding specifically formulated diets for w i t h i n the range o f 0.75 to 5.0 ng/kg/day according to serial
C K D . F r o m a practical standpoint, dietary phosphorus determination o f ionized calcium and P T H concentrations)
reduction is combined with dietary protein reduction (dis resulted i n decreased all-cause mortality and prolonged sur
cussed i n more detail later). If, after 3to 4 weeks o f dietary vival compared with placebo treatment. Calcitriol should
not be administered until hyperphosphatemia has been con animal can tolerate at his/her level of renal function. A favor
trolled with diet and enteric binders. In addition, i f the C a able response to therapy consists of stable body weight and
X Phos product exceeds 60 to 70 mg/dl, calcitriol should not serum creatinine and albumin concentrations and decreas
be used because o f the risk o f soft tissue mineralization. ing serum urea nitrogen and phosphorus concentrations.
Serial serum calcium determinations are recommended i n Moderate dietary protein reduction should be employed
dogs and cats receiving calcitriol to help prevent hypercalce early i n the course o f renal failure, and use of markedly
mia, especially i f the patient is also receiving a calcium-con reduced protein diets should be reserved for patients that are
taining enteric phosphorus binder. refractory to moderate dietary protein reduction.
Diagnosis and management o f proteinuria i n dogs and Most diets for C K D are alkalinizing diets; however, potas
cats with C K D should be accomplished i n a step-wise fashion. sium citrate or sodium bicarbonate, given orally to effect,
Because the specificity o f the dipstick screening test for pro may be indicated if the patient remains acidemic (total C O 2
teinuria in both dogs and cats is poor, confirmation o f pro < 12 m E q / L ) 2 to 3 weeks after diet change. Oral potassium
teinuria should be accomplished with a more specific citrate supplementation may also prevent hypokalemia and
follow-up test, such as the sulfosalicylic acid (SSA) turbidi potassium depletion i n cats with C K D . Anorexia; high-
metric test, urine p r o t e i n : creatinine ratio, or canine or feline protein, acidifying diets; polyuria-polydipsia; and vomiting
specific albuminuria assay (see Chapter 42). The second step can all contribute to potassium depletion; however, only
in assessment o f proteinuria is to determine its origin. P r o 20% to 30% o f cats with C K D have hypokalemia as an initial
teinuria o f renal origin can adversely affect the prognosis o f clinicopathologic finding. Potassium is predominantly an
dogs and cats with C K D , and therefore physiologic or benign intracellular cation, and approximately 95% of total body
proteinuria and prerenal and postrenal proteinuria should potassium is present i n skeletal muscle; therefore serum
be ruled out. Subsequently, via serial monitoring, the clini potassium concentrations may not accurately reflect total
cian should determine whether the proteinuria is persistent body potassium stores, especially in the early stages of potas
or transient. Persistent proteinuria is defined as at least two sium depletion. It has been documented that cats with C K D
positive tests at 2-week intervals. Relatively m i l d proteinuria have lower muscle potassium concentrations and higher
in dogs and cats with spontaneous chronic renal failure serum potassium concentrations than do normal cats. This
appears to be a negative predictor o f survival. In azotemic data may suggest the need for oral potassium supplementa
patients persistent proteinuria o f renal origin with a urine tion early i n the course o f C K D i n cats. Generalized muscle
protein: creatinine ratio > 0.4 (cats) or > 0.5 (dogs) should weakness is the primary clinical sign associated with hypo
be treated with an A C E I and/or dietary protein reduction kalemia/potassium depletion. Muscle weakness usually
(discussed i n more detail later). resolves within 1 to 5 days after initiation of oral potassium
Symptomatic treatment becomes a higher priority i n the supplementation.
later stages o f C K D , when the renal failure and uremia have V o m i t i n g and anorexia are c o m m o n i n dogs and cats with
a more pronounced effect o n the patient's quality o f life. In C K D and can often result i n decreased caloric intake. Causes
addition to phosphorus restriction, dietary management of vomiting and anorexia include (1) stimulation of chemo
includes protein reduction (dietary protein is reduced not receptor trigger zone by uremic toxins, (2) decreased excre
restricted in these diets; restriction of any dietary component tion o f gastrin and increased gastric acid secretion (plasma
generally means feeding less than the daily requirements), gastrin concentrations i n cats with chronic renal failure may
salt reduction, n-3 fatty acid supplementation, and alkalini be as high as 20 times the normal concentrations), and (3)
zation. Feeding specifically formulated renal failure diets not gastrointestinal irritation secondary to uremia. V o m i t i n g
only may allow the animal to live more comfortably with may be treated with metoclopramide, which blocks the che
decreased renal function but also may significantly prolong moreceptor trigger zone. Metoclopramide also increases
survival. Ideally, dietary protein reduction allows all essential gastric motility and emptying without causing gastric acid
amino acid requirements to be met without excesses. This is secretion and is the drug of choice for vomiting associated
accomplished by feeding smaller quantities o f high biologi with renal failure. H receptor blockers (famotidine or ranit
2
cal value protein and results i n a decreased need for renal idine) have been shown to effectively decrease gastric acid
clearance o f urea and other nitrogenous metabolites. W h e n secretion, which may attenuate vomiting in C K D . Oral ulcers,
feeding reduced protein diets, the clinician must remember stomatitis, and glossitis may occur as a result of gastritis and
that the energy requirements o f the body have a higher vomiting or the effect o f uremic toxins on mucosal mem
priority than does protein anabolism; therefore, i f the branes and w i l l often also result i n anorexia. If vomiting has
available carbohydrates and fats are insufficient to meet been controlled but anorexia persists, placement of a gas
caloric requirements, endogenous proteins w i l l often be used trostomy or esophagostomy tube will often facilitate the
as a source o f energy. Catabolism of endogenous proteins for maintenance o f caloric intake and hydration status. In many
energy increases the nitrogenous waste that the kidney must cases without feeding tubes, fluid therapy with polyionic
excrete and exacerbates the clinical signs o f renal failure. solutions, given intravenously or subcutaneously in the hos
A good recommendation for dietary protein reduction pital or subcutaneously by owners at home (10 to 50 ml/kg
for both dogs and cats is to feed the m a x i m u m amount of subcutaneously every 1 to 3 days), will help improve the
high biological value, highly digestible protein that the patient's quality o f life.
The nonregenerative anemia observed i n dogs a n d cats B r o w n S et al: Guidelines for the identification, evaluation, a n d
with C K D occurs as a result of a combination o f decreased management o f systemic hypertension i n dogs a n d cats, / Vet
E P O production, shortened red b l o o d cell survival, gastro Intern Med 21:542, 2007.
C o w g i l l L D , Francey T: A c u t e uremia. I n Ettinger SJ, F e l d m a n E C ,
intestinal tract b l o o d loss, and the effects o f uremic toxins
editors: Textbook of veterinary internal medicine, ed 6, St Louis,
such as P T H on erythropoiesis. In addition, nutritional defi
2005, Elsevier/Saunders.
ciencies (e.g., vitamins B and B , niacin, and folic acid) and
6 1 2
D i B a r t o l a SP: F a m i l i a l renal disease i n dogs a n d cats. In Ettinger SJ,
iron depletion can contribute to the anemia associated w i t h
F e l d m a n E C , editors: Textbook of veterinary internal medicine, ed
C K D . Anabolic steroids are usually o f little benefit; however, 6, St Louis, 2005, Elsevier/Saunders.
treatment with recombinant h u m a n E P O i n dogs and cats Elliott JA: Staging chronic k i d n e y disease. I n Elliott J A , Grauer G F ,
with C K D and anemia has generally been successful. editors: BSAVA manual of canine and feline nephrology and
Although not approved for use i n veterinary medicine, the urology, ed 2, Gloucester, E n g l a n d , 2007, British Small A n i m a l
dosage that has been recommended is 100 U / k g o f recombi Veterinary Association.
nant E P O given subcutaneously three times weekly. The dose Fischer JR: Peritoneal a n d hemodialysis. I n Elliott JA, Grauer G F ,
interval is lengthened once a target packed cell volume is editors: BSAVA manual of canine and feline nephrology and
achieved (approximately 40% i n dogs a n d 35% i n cats). urology, ed 2, Gloucester, England, 2007, British Small A n i m a l
Veterinary Association.
Usually, a dosage of 75 to 100 U / k g once or twice weekly is
Grauer G F : M a n a g e m e n t o f acute renal failure. I n Elliott JA, Grauer
sufficient for maintenance. This treatment, i n addition to
G F , editors: BSAVA manual of canine and feline nephrology and
increasing the packed cell volume, often results i n increased
urology, ed 2, Gloucester, E n g l a n d , 2007, British Small A n i m a l
appetite, weight gain, increased strength, and an improved Veterinary Association.
sense o f well-being. It should be noted, however, that anti Jacob F et al: Association between initial systolic b l o o d pressure and
bodies may form i n dogs and cats treated with h u m a n risk o f developing a u r e m i c crisis or o f d y i n g i n dogs w i t h chronic
recombinant products. Studies show that antirecombinant renal failure, I Am Vet Med Assoc 222:322, 2003.
EPO-binding antibodies will develop i n approximately 25% Jacob F et al: Evaluation o f the association between initial
to 30% of dogs and cats and that these antibodies may also proteinuria a n d m o r b i d i t y rate o r death i n dogs w i t h naturally
react with endogenous E P O , making the animal transfusion occurring chronic renal failure, / Am Vet Med Assoc 226:393,
the rapid initiation o f erythropoiesis and marginal depletion diets, Vet Rec 157:185, 2005.
P o l z i n D J et al: C h r o n i c k i d n e y disease. I n Ettinger SJ et al, editors:
of iron stores that occur i n animals with C K D . U n t i l canine
Textbook of veterinary internal medicine, ed 6, Philadelphia, 2005,
and feline recombinant E P O become commercially available,
W B Saunders.
treatment with human recombinant products should be
Ross SJ et al: A case-control study o f the effects o f nephrolithiasis
reserved for those animals with weakness and lethargy attrib i n cats w i t h chronic k i d n e y disease, J Am Vet Med Assoc 230:1854,
utable to their anemia. 2007.
Stepien R L , Elliott JA: Measurement o f b l o o d pressure. I n Elliott
Suggested Readings JA, Grauer G F , editors: BSAVA manual of canine and feline
A d i n D B et al: Intermittent bolus injection versus continuous infu nephrology and urology, ed 2, Gloucester, England, 2007, British
sion of furosemide i n n o r m a l adult greyhound dogs, / Vet Intern Small A n i m a l Veterinary Association.
Med 17:632, 2003. Syme H M et al: Survival o f cats w i t h naturally o c c u r r i n g chronic
Behrend E N et al: Hospital-acquired acute renal failure i n dogs: 29 renal failure is related to severity o f proteinuria, / Vet Intern Med
cases (1983-1992), J Am Vet Med Assoc 208:537, 1996. 20:528, 2006.
Brown SA: Management o f chronic kidney disease. In Elliott JA, V a d e n S L et al: Retrospective analysis o f 106 dogs w i t h acute renal
Grauer G F , editors: BSAVA manual of canine and feline nephrology failure, / Vet Intern Med 9:209, 1995.
and urology, ed 2, Gloucester, England, 2007, British Small W o r w a g S et al: Retrospective, acute renal failure i n cats: 25 cases
A n i m a l Veterinary Association. (1997-2002) (abstract), / Vet Intern Med 18:416, 2004.
C H A P T E R 45
Approximate Percentages of Bacterial Isolates in Dogs Host Defense Mechanisms and Abnormalities that May
with Urinary Tract Infections Lead to Complicated Urinary Tract Infections
treatment for a U T I . Antibiotic treatment should control the cus spp., amoxicillin; Enterobacter spp., trimethoprim-sulfa
pathogenic bacterial growth for enough time to allow host or enrofloxacin; Klebsiella spp., first-generation cephalospo
defense mechanisms to prevent colonization o f the urinary rins or enrofloxacin; and Pseudomonas spp., tetracycline
tract without the need for further antibiotic administration. (Table 45-3). It should be noted, however, that it is often
A l t h o u g h it is advisable to evaluate the bacterial sensitivity difficult to predict the sensitivity o f gram-negative enteric
to antimicrobial drugs, the treatment o f acute, u n c o m p l i bacteria. If the identity of the bacteria is unknown, treatment
cated U T I s is often dictated by economic and time consid should be determined o n the basis o f the Gram's staining
erations. If bacterial sensitivity results are not available, characteristics (i.e., ampicillin, amoxicillin, or amoxicillin-
the antibiotic should be chosen o n the basis o f bacterial clavulanic acid for gram-positive bacteria and trimethoprim-
identification or the Gram's staining characteristics o f the sulfa or enrofloxacin for gram-negative bacteria).
bacteria (Fig. 45-1). C l i n i c a l experience at several veterinary The steps to follow in the management of a U T I are given
teaching hospitals has shown that intelligent guesses can be in B o x 45-3, and a flow diagram is shown in Fig. 45-1. The
made regarding bacterial susceptibility to antibiotics. In the duration o f therapy for a lower U T I must be individualized
absence o f bacterial sensitivity testing, the following are and should be based on the cessation of clinical signs and
the drugs o f choice for the treatment o f infection w i t h the elimination o f the abnormal urine sediment as well as nega
bacteria listed: E. coli, trimethoprim-sulfa or enrofloxacin; tive urine culture results. In general, uncomplicated lower
Proteus, amoxicillin; Staphylococcus, amoxicillin; Streptococ UTIs should be treated for 2 weeks, whereas complicated
TABLE 45-3 BOX 4 5 - 3
Antimicrobial Agents to Which More than 90% of Ideal Steps to Follow in the Management of Urinary Tract
Urinary Isolates Are Susceptible In Vitro at Infections in Dogs and Cats
Concentrations Less than One Fourth of the Expected
D i a g n o s i s should b e d e t e r m i n e d o n t h e basis o f history;
Urinary Concentration
urine sediment; a n d , ideally, urine culture a n d sensitivity
ORGANISM ANTIMICROBIAL AGENTS findings.
Select a n a n t i m i c r o b i a l a g e n t .
E. coli* Trimethoprim-sulfa Reculture urine in 3 t o 5 d a y s t o ascertain effectiveness o f
Fluoroquinolone selected a n t i m i c r o b i a l a g e n t .
Amoxicillin-clavulanic acid E x a m i n e urine sediment 3 t o 4 d a y s b e f o r e d i s c o n t i n u i n g
Coagulase-positive Amoxicillin a n t i b i o t i c treatment.
Staphylococcus spp. Chloramphenicol Repeat urinalysis a n d culture 1 0 t o 1 4 d a y s after cessation
Trimethoprim-sulfa of antibiotic therapy.
C e p h a l o s p o r i n s (first g e n e r a t i o n ) Patients w i t h recurrent u r i n a r y tract infections should u n d e r g o
Proteus mirabilis Amoxicillin contrast-enhanced radiography and/or ultrasonogra
Fluoroquinolone phy, a c o m p l e t e b l o o d c o u n t , a n d serum b i o c h e m i s t r y
C e p h a l o s p o r i n s (first, s e c o n d , p r o f i l e t o d e t e r m i n e w h e t h e r they h a v e u n d e r l y i n g pre
third generations) d i s p o s i n g factors.
Amoxicillin-clavulanic acid It m a y b e necessary t o treat frequent reinfections w i t h pro
Klebsiella C e p h a l o s p o r i n s (first, s e c o n d , p h y l a c t i c doses o f a n t i b i o t i c s after the initial i n f l a m m a
pneumoniae* third generations) tion has b e e n c l e a r e d u p in response t o s t a n d a r d - d o s e
Fluoroquinolone a n t i b i o t i c treatment.
Amoxicillin-clavulanic acid
Trimethoprim-sulfa
Streptococcus spp. Amoxicillin
Amoxicillin-clavulanic acid BOX 4 5 - 4
Chloramphenicol
C e p h a l o s p o r i n s (first, s e c o n d , Reasons for Poor Therapeutic Response in Dogs and Cats
t h i r d generations) with Urinary Tract Infections
Pseudomonas Tetracycline
aeruginosa Fluoroquinolone Use o f ineffective d r u g s o r ineffective d u r a t i o n o f t h e r a p y
Carbenicillin Failure o f o w n e r t o a d m i n i s t e r p r e s c r i b e d d o s e a t p r o p e r
Enterobacter spp.* Trimethoprim-sulfa intervals
Fluoroquinolone Gastrointestinal tract d i s e a s e o r c o n c u r r e n t o r a l intake o f
Enterococcus spp. Fluoroquinolone f o o d a n d d r u g , resulting i n d e c r e a s e d d r u g a b s o r p t i o n
Trimethoprim-sulfa I m p a i r e d a c t i o n o f d r u g s , either b e c a u s e b a c t e r i a a r e not
Chloramphenicol m u l t i p l y i n g o r b e c a u s e they a r e sequestered in a n inac
Tetracyline cessible site ( e . g . , prostate o r uroliths)
Failure t o r e c o g n i z e a n d e l i m i n a t e p r e d i s p o s i n g causes
* These bacteria are capable of major changes in their Presence o f m i x e d b a c t e r i a l infections in w h i c h o n l y o n e o f
susceptibility to antibiotics and are therefore less predictable. the p a t h o g e n s is e r a d i c a t e d b y a n t i m i c r o b i a l t h e r a p y
Iatrogenic reinfection c a u s e d b y c a t h e t e r i z a t i o n
D e v e l o p m e n t o f d r u g resistance in b a c t e r i a
mucosal lesions o f the bladder, or urolithiasis. In intact male urine sediment. L o n g - t e r m (4 to 6 weeks) antibiotic treat
dogs semen and prostatic wash cytologic and culture studies ment is required for patients w i t h complicated U T I s , and
as well as ultrasonography should be done to rule out or careful follow-up examinations s h o u l d be performed i n such
identify bacterial prostatitis. Excretory urographic, ultraso- animals (see B o x 45-3). W h e n antibiotic treatment is used
for this period o f time, the adverse effects o f long-term people. These products should not be used i n cats, however,
antibiotic therapy should also be considered. Keratocon because methylene blue has the potential to cause Heinz
junctivitis sicca and folate deficiency anemia may occur i n bodies and hemolytic anemia. Similarly, phenazopyridine, a
association with long-term use o f trimethoprim-sulfa urinary tract analgesic, should not be used i n cats.
(although they are rare), and nephrotoxicity is always a Cranberry juice extracts, glycosaminoglycans, and vac
concern i n animals receiving aminoglycosides, even for a cines directed against bacterial fimbria are additional adjunc
short time. tive treatments that can decrease bacterial adherence to
The prognosis for an animal with a complicated U T I , as uroepithelium i n other species but require further evalua
opposed to an uncomplicated U T I , is always guarded. The tion i n the dog before clinical recommendations can be
single most important treatment for a complicated U T I is made.
correction of the underlying defect i n the host defense mech
anisms. If predisposing factors cannot be identified or elim Suggested Readings
inated, relapses and reinfections are c o m m o n . Low-dose A d a m s L G , Syme H M : C a n i n e lower urinary tract diseases. In
(one t h i r d to one half o f the conventional daily dose) anti Ettinger SJ, Feldman E C , editors: Textbook of veterinary internal
microbial treatment administered at bedtime (after the last medicine, ed 6, St Louis, 2005, Elsevier/Saunders.
evening void) may be recommended for animals with fre Bartges J W : U r i n a r y tract infections. In Ettinger SJ, Feldman E C ,
editors: Textbook of veterinary internal medicine, ed 6, St Louis,
quent infections associated with host defense mechanism
2005, Elsevier.
problems that cannot be cured. This allows the drug to be
C o h n L A et al: Trends i n fluoroquinolone resistance o f bacteria
present i n the bladder overnight, supplementing the animal's
isolated from canine urinary tracts, / Vet Diag Invest 15:338,
defense mechanisms. Penicillins are recommended for the 2003.
treatment o f recurrences caused by gram-positive bacteria, C r a w f o r d JT et al: Influence o f vestibulovaginal stenosis, pelvic
whereas trimethoprim-sulfa or enrofloxacin is recommended bladder, a n d recessed vulva o n response to treatment for clinical
for the treatment o f recurrences caused by gram-negative signs o f lower urinary tract disease i n dogs: 38 cases (1990-1999),
bacteria. It should be noted, however, that low-dose, long- J Am Vet Med Assoc 221:995, 2002.
term antibiotic treatment can predispose the animal to the Forrester S D et al: Retrospective evaluation o f urinary tract infec
development o f a very resistant U T I . t i o n i n 42 dogs w i t h hyperadrenocorticism or diabetes mellitus
or both, / Vet Intern Med 13:557, 1999.
U r i n a r y acidification ( a m m o n i u m chloride) has been
Hess RS et al: C o n c u r r e n t disorders i n dogs w i t h diabetes mellitus:
advocated as adjunctive therapy for lower U T I s because
221 cases (1993-1998), J Am Vet Med Assoc 217:1166, 2000.
acidic urine provides a less favorable environment for bacte
L i n g G V : Bacterial infections o f the urinary tract. In Ettinger SJ
rial growth. However, the antimicrobial activity o f acidic
et al, editors: Textbook of veterinary internal medicine, Philadel
urine is inferior to that o f antibiotics and should not be phia, 2000, W B Saunders.
expected to eradicate infection; a m m o n i u m chloride should L i n g G V et al: Interrelations o f organism prevalence, specimen col
be used only i n conjunction w i t h other modes o f therapy. lection method, and host age, sex, and breed a m o n g 8,354 canine
U r i n a r y acidification may also be an effective adjunctive urinary tract infections (1969-1995), / Vet Intern Med 15:341,
therapy to adjust the urine p H and thereby optimize the 2001.
efficacy o f certain antibiotics (penicillin, ampicillin, carben N o r r i s C R et al: Recurrent a n d persistent urinary tract infections
icillin, tetracycline, nitrofurantoin). A m m o n i u m chloride i n dogs: 383 cases (1969-1995), / Am Anim Hosp Assoc 36:484,
Canine Urolithiasis
RADIOGRAPHIC COMMONLY
DENSITY USUAL U R I N A R Y TRACT GENDER C O M M O N L Y AFFECTED AFFECTED CLINICOPATHOLOGIC
U R O L I T H TYPE ( 1 . 0 - 3 . 0 scale) URINE p H INFECTION PREDISPOSITION BREEDS AGES ( y r ) ABNORMALITIES
Magnesium 2.5 Neutral to Very c o m m o n , Female (>80%) Miniature Schnauzers, 1-8 Usually n o n e
ammonium alkaline e s p e c i a l l y urease- B i c h o n Frises, C o c k e r
phosphate producing Spaniels, Miniature
(struvite) bacteria (e.g., Poodles
Staphylococcus,
Proteus)
Calcium oxalate 3.0 A c i d i c to Rare M a l e (>70%) Miniature Schnauzers, 5-12 Occasional
neutral M i n i a t u r e Poodles, hypercalcemia
Yorkshire Terriers, Lhasa
A p s o s , Bichon Frises, Shih
Tzus, C a i r n Terriers
Urate 1.0 A c i d i c to Uncommon M a l e (>90%) D a l m a t i a n s , English B u l l d o g s , 1-4 D e c r e a s e d serum u r e a ,
neutral M i n i a t u r e Schnauzers nitrogen, a n d albumin
(PSS), Yorkshire Terriers concentrations a n d
(PSS) abnormal preprandial
a n d postprandial bile
a c i d c o n c e n t r a t i o n s in
d o g s w i t h PSS
Cystine 1.5 Acidic Rare M a l e (>95%) D a c h s h u n d s , Basset H o u n d s , 1-7 Usually n o n e
English B u l l d o g s , Yorkshire
Terriers, Irish Terriers,
Rottweilers, C h i h a u h a u s ,
M a s t i f f s , Tibetan Spaniels
Silicate 2.5 Acidic to Uncommon M a l e (>95%) G e r m a n Shepherd Dogs, 4-9 Usually n o n e
neutral G o l d e n Retrievers,
L a b r a d o r Retrievers, O l d
English S h e e p d o g s
lence o f calcium oxalate uroliths i n dogs has increased allantoin has been found to be decreased i n them, even
significantly over the past 10 years and may be related to the though hepatocyte uricase activities are often adequate. The
increased use of urine-acidifying diets or other unidentified decreased production of allantoin seen i n these breeds results
environmental factors. i n the increased urinary excretion of uric acid. Normally,
Approximately 70% o f calcium oxalate uroliths are found allantoin, which is produced through the oxidation of uric
i n male dogs, and M i n i a t u r e and Standard Schnauzers, acid by uricase, is the major metabolite generated during
Miniature Poodles, Yorkshire Terriers, Lhasa Apsos, Bichon purine metabolism. In comparison with uric acid, allantoin
Frises, and Shih Tzus are the breeds c o m m o n l y affected. is quite soluble i n urine.
Obesity also appears to increase the risk o f calcium oxalate In addition to a decreased hepatic metabolism of uric
urolithiasis. The increased prevalence i n male dogs may be acid, the proximal tubular resorption of uric acid appears to
related to an increase i n the hepatic production o f oxalate be decreased i n Dalmatians. This increases the uric acid and
mediated by testosterone. Conversely, estrogens i n female sodium urate (the salt o f uric acid) concentrations i n urine.
dogs may increase the urinary excretion of citrate. C a l c i u m Although urinary uric acid excretion i n Dalmatians is
oxalate uroliths frequently occur i n older dogs (mean age: approximately 10 times that of other dogs, urate stones form
8 to 12 years), and a concurrent U T I appears to be rare. i n only a small percentage. For u n k n o w n reasons, male Dal
C a l c i u m oxalate solubility is increased i n urine with a p H matians are at greater risk o f having urate stones than are
above 6.5, whereas a urine p H o f less than 6.5 favors calcium female Dalmatians. In one published study the male : female
oxalate crystal formation. ratio for urate stone-forming Dalmatians was reported to be
Urate uroliths. M o s t urate uroliths are composed o f 16.4:1. Approximately 60% of urate uroliths occur in Dal
a m m o n i u m acid urate; 100% uric acid and sodium urate matians, and, conversely, approximately 75% of the uroliths
uroliths are relatively rare (Fig. 46-3). U r i c acid is derived i n Dalmatians are urate uroliths. In addition to Dalmatians,
from the metabolic degradation o f endogenous purine ribo English Bulldogs have an increased incidence of urate
nucleotides and dietary nucleic acids. It is hypothesized that uroliths.
the hepatic transport o f uric acid is defective i n Dalmatians Another possible cause o f urate stone formation is a
and some English Bulldogs because uric acid conversion to decreased glycosaminoglycan concentration i n the urine.
Glycosaminoglycans i n urine may combine with urate salts, silicate solubility, and secondary UTIs may occur as a result
resulting i n an overall negative charge and reduced crystal of mucosal irritation caused by these jack-shaped uroliths.
lization. H i g h dietary protein is usually associated w i t h an Cystine uroliths. Cystinuria, an inherited disorder of
increase i n the urinary excretion o f both uric acid and renal tubular transport, is thought to be the primary cause
ammonium ions. A m m o n i a , w h i c h is produced by renal of cystine uroliths. The tubular resorptive defect involves
tubular cells from glutamine, diffuses into the tubular l u m e n cystine and, i n some cases, other amino acids (tubular
and serves as a buffer for secreted hydrogen ions, thereby resorption o f cysteine, the immediate precursor o f cystine,
forming a m m o n i u m ions. A m m o n i u m ions are relatively glycine, ornithine, carnitine, arginine, and lysine, may also
lipid insoluble and therefore become trapped within the be decreased). A l t h o u g h the plasma cystine concentrations
tubular fluid. U r i c acid crystallization is facilitated i n acidic are normal i n these dogs, the concentration of plasma methi
urine, whereas an alkaline urine appears to favor a m m o n i u m onine, a precursor o f cystine, may be increased. Plasma
urate crystallization. A m m o n i u m acid urate stones may also cystine is freely filtered through the glomeruli and is actively
form i n any dog with hepatic insufficiency (e.g., hepatic resorbed by p r o x i m a l tubular epithelial cells i n normal dogs.
cirrhosis, microvascular dysplasia, or portosystemic shunt Were it not for the relative insolubility o f cystine i n urine
[PSS]) as a result of increased renal excretion o f a m m o n i u m and the potential for uroliths to form, cystinuria w o u l d be
urates. PSSs are c o m m o n i n Miniature Schnauzers, Yorkshire of little consequence. Cystine is most soluble i n alkaline solu
Terriers, and Pekingese dogs; therefore a m m o n i u m acid tions; therefore cystine stones usually form i n acidic urine.
urate uroliths are more c o m m o n i n these breeds. UTIs, espe Interestingly, cystine uroliths do not form i n all dogs with
cially those with urease-producing bacteria, may facilitate cystinuria; therefore cystinuria is a predisposing, rather than
ammonium acid urate crystallization by increasing urine a primary, causative factor. Cystine uroliths (Fig. 46-5) are
ammonia concentrations. A U T I may also occur secondary most frequently observed i n male dogs, and Dachshunds are
to urolith-induced mucosal irritation. the breed principally affected, but Basset H o u n d s , Tibetan
Silicate uroliths. Silicate uroliths were first reported i n Spaniels, English Bulldogs, Yorkshire Terriers, Irish Terriers,
the United States i n 1976 i n association with crystallographic Chihuahuas, Mastiffs, and Rottweilers also appear to be at
analysis o f uroliths. Silicate uroliths frequently, but not increased risk for cystine urolithiasis.
always, have a jack shape (Fig. 46-4), although not all jack- For u n k n o w n reasons, cystine uroliths usually do not
stones are silicates ( a m m o n i u m urate and struvite uroliths form i n young dogs; the average age at detection is 3 to 6
may also be jack shaped; see Fig. 46-1, B). The factors respon years. The prevalence o f cystine urolithiasis i n dogs i n the
sible for the pathogenesis o f silicate uroliths are u n k n o w n , U n i t e d K i n g d o m has been reported to be m u c h higher than
but their formation is probably related to the dietary intake that seen i n dogs i n the U n i t e d States, probably reflecting
of silicates, silicic acid, or magnesium silicate. There appears the increased popularity o f affected breeds i n the U n i t e d
to be a link between the formation o f silicate uroliths and K i n g d o m . UTIs may occur secondarily; however, infection is
the consumption of large amounts o f corn gluten or soybean not thought to play a primary role i n the pathogenesis o f
hulls, which can be high i n silicates. M a n y o f the reported cystine uroliths.
silicate uroliths i n the U n i t e d States have occurred i n male
German Shepherd Dogs, O l d English Sheepdogs, and G o l d e n Clinical Features and Diagnosis
and Labrador Retrievers. M o s t silicate uroliths are diagnosed The clinical features o f urolithiasis depend on the number,
in dogs 6 to 8 years of age. Alkaline urine appears to increase type, and location o f the stones i n the urinary tract. Because
FIG 4 6 - 4 FIG 4 6 - 5
Typical a p p e a r a n c e of a silicate stone. Typical a p p e a r a n c e of cystine stones.
most uroliths are located i n the urinary bladder, clinical signs with unilateral renal uroliths may be asymptomatic, or they
of cystitis (hematuria, pollakiuria, dysuria-stranguria) are may have hematuria and chronic pyelonephritis. Frequently,
frequently observed. M u c o s a l irritation is relatively severe i n chronic kidney disease develops i n animals with bilateral
dogs w i t h jack-shaped uroliths, as opposed to that seen i n renal uroliths, especially i f pyelonephritis is also present.
dogs with solitary, smooth stones. Incomplete v o i d i n g (i.e., Dogs with ureteral uroliths may also be asymptomatic, or
urine retention), mucosal hyperplasia leading to polyp for they may have hematuria and abdominal pain. Unilateral
mation, and sequestration o f bacteria w i t h i n the stone are obstruction o f a ureter often results i n unilateral hydrone
additional complications associated with urolithiasis. In phrosis without evidence o f decreased renal function.
male dogs smaller uroliths may pass into the urethra, causing Canine urolithiasis is usually diagnosed on the basis of a
partial or complete obstruction w i t h signs o f bladder disten combination o f historical, physical examination, and radio
tion, dysuria-stranguria, and postrenal azotemia (depres graphic or ultrasonographic findings (Fig. 46-7). In male
sion, anorexia, vomiting). Uroliths frequently lodge i n the dogs with dysuria and stranguria caused by urethral stones,
male urethra at the caudal aspect o f the os penis (Fig. 46-6). attempted passage o f a urinary catheter will often be met
Occasionally, the urinary bladder or urethra may rupture with a "gritty feeling" of resistance. Regardless o f the ease of
and result i n an abdominal effusion or subcutaneous peri catheter passage, the diagnosis can usually be confirmed with
neal fluid accumulation and postrenal azotemia. A n i m a l s retrograde positive contrast-enhanced urethrography. In
some cases cystouroliths can be detected during abdominal
palpation i n dogs with signs o f cystitis. Plain film radio
graphs w i l l usually confirm the presence o f cystouroliths
unless the stones are radiolucent or very small. Double-
contrast-enhanced cystography is a more sensitive diag
nostic tool for detecting radiolucent cystouroliths. Finally,
ultrasonography can be used to visualize radioopaque or
radiolucent uroliths and is the imaging method of choice for
diagnosing renoliths and hydronephrosis-hydroureter that
can be associated with renoliths.
Treatment
General principles for the treatment of urolithiasis include
the relief o f any urethral obstruction and decompression of
the bladder, if necessary. This can usually be accomplished
by the passage of a small-bore catheter, cystocentesis, or dis
lodgment of the urethral calculi by retrograde hydropulsion.
FIG 46-6
O n l y rarely will an emergency urethrotomy be necessary.
R a d i o g r a p h of a male d o g with a n o p a q u e urethral calculus
at the c a u d a l a s p e c t of the os penis. N o t e the d i s t e n d e d Fluid therapy should be initiated to restore water and elec
b l a d d e r associated with the obstructive uropathy a n d the trolyte balance i f postrenal azotemia exists. Hyperkalemia is
staples from a previous cystotomy for urolith removal. a potentially life-threatening electrolyte disturbance that
may occur i n association with postrenal azotemia caused by
urethral obstruction or rupture of the urinary bladder or
urethra. The serum potassium concentration as well as the
blood urea nitrogen and creatinine concentrations should be
measured i n patients with a suspected obstruction. Alter
natively, bradycardia and electrocardiographic findings of
flattened P waves, a prolonged P R interval, widened Q R S
complexes, and tall or spiked T waves are suggestive o f
hyperkalemia and indicate the need for aggressive treatment
to lower the serum potassium concentration. Hyperkalemia
should be promptly treated according to the regimen out
lined i n B o x 46-1.
The medical dissolution o f struvite, urate, and cystine
uroliths has been shown to be effective (Table 46-2); however,
the choice between the surgical removal of uroliths and
medical dissolution is not always clear. Disadvantages of
surgery include the need for anesthesia, the invasiveness of
FIG 46-7
Typical a p p e a r a n c e of r a d i o p a q u e cystouroliths o n plain the procedure (potential surgical complications), the possi
film r a d i o g r a p h s . ( C o u r t e s y Dr. Philip S t e y n , C o l o r a d o State bility o f incomplete removal o f uroliths, and the persistence
University, Fort Collins, Colo.) of underlying causes. Inasmuch as the underlying cause is
M e d i c a l treatment decreases the concentration of calcu
BOX 46-1 logenic salts i n the urine, increases salt solubility i n urine,
and increases urine volume, which produces urine with a
Electrocardiographic Findings and Treatment
lower concentration o f calculogenic salts. The major disad
Recommendations for Dogs and Cats with Hyperkalemia
vantage o f the medical treatment o f urolithiasis is that c o n
ECG Findings siderable owner compliance is required for several weeks to
1. Bradycardia months. The cost of medical dissolution is comparable to the
2. Flattened waves cost o f surgery because multiple urinalyses, bacterial cul
3. Prolonged PR interval tures, and frequent radiographs are required for follow-up.
4. W i d e n e d QRS complexes Animals with urolith-induced obstructive uropathy cannot
5. Tall or spiked T w a v e s be treated medically, and some uroliths (calcium oxalate,
6. Arrhythmias calcium phosphate, silicate, and mixed-composition uro
Treatment Recommendations liths) do not respond to medical dissolution. In addition to
the medical dissolution of uroliths, voiding urohydropropul
1. Fluid therapy w i t h 0 . 9 % saline solution
sion or catheter u r o l i t h retrieval can be used to remove
2. Slow IV bolus of regular insulin ( 0 . 2 5 - 0 . 5 U / k g ) , fol
l o w e d by 5 0 % dextrose (4 m l / U of administered insulin), cystouroliths nonsurgically i n some animals (Box 46-2;
or see also L u l i c h et a l , 1992, 1993, for detailed instructions).
3. Slow IV bolus o f sodium b i c a r b o n a t e (1-2 m E q / k g ) , o r Lithotripsy, available at some referral centers, has also been
4 . Slow IV bolus o f 1 0 % calcium gluconate ( 0 . 5 - 1 . 0 m l / k g used successfully to treat nephroliths and, less c o m m o n l y ,
while monitoring the ECG) ureteroliths i n dogs.
General preventive measures to be taken i n addition
ECG, Electrocardiogram; IV, intravenous. to the surgical or medical management o f uroliths include
the induction o f diuresis and the eradication o f UTIs.
Diuresis is important because it lowers the urine specific
gravity and the urinary concentration o f calculogenic salts.
usually not eliminated, surgery typically does not lead to Feeding canned food w i l l help increase water intake. In
a decrease i n the rate o f urolith recurrence. Advantages general, the maintenance o f a urine specific gravity o f less
of surgery include the fact that the urolith type can be than 1.020 is ideal, and dogs should be allowed frequent
definitively diagnosed, any concurrent or predisposing ana opportunities to void. The urine sediment and p H should
tomic abnormalities (e.g., urachal remnants, urinary bladder be monitored routinely, and UTIs should be treated pro
polyps) can be corrected, and urinary bladder mucosal mptly on the basis o f bacterial culture and sensitivity results
samples can be obtained for bacterial culture i f the urine (see specific instructions i n discussion of each type o f
yields no growth on culture. urolith).
TABLE 4 6 - 2
removing the urolith surgically. ciency, / Vet Intern Med 15:94, 2001.
Seaman R et al: Canine struvite urolithiasis, Compend Contin Educ
U r o l i t h s recur in up to 25% o f dogs, and it is not u n c o m
Pract Vet 23:407, 2001.
m o n for i n d i v i d u a l dogs to have three or more episodes o f
Stevenson A R et al: Effects o f dietary potassium citrate supplemen
urolithiasis i n their lifetimes. The l i k e l i h o o d o f recurrence
tation o n urine p H and urinary relative supersaturation of
appears to be greatest i n dogs w i t h metabolic uroliths
c a l c i u m oxalate and struvite i n healthy dogs, Am } Vet Res 61:430,
(calcium oxalate, urate, and cystine uroliths) or a familial 2000.
predisposition (e.g., M i n i a t u r e Schnauzers w i t h struvite u r o W e i c h s e l b a u m R C et al: Evaluation o f the m o r p h o l o g i c character
liths). Therefore appropriate preventive measures and fre istics and prevalence o f canine urocystoliths from a regional
quent reevaluations are important i n such dogs. u r o l i t h center, Am J Vet Res 59:379, 1998.
C H A P T E R 47
Diagnostic and Therapeutic Plan for Cats with Lower Urinary Tract Inflammation
1 . Rule out urethral o b s t r u c t i o n ; relieve o b s t r u c t i o n , if present 5. O b t a i n a urine sample in cats with non-struvite
with n o . 2 below. associated FLUTD o r in cats w i t h struvite-associated FLUTD
2 . Assess d e g r e e o f h y p e r k a l e m i a w i t h a n e l e c t r o c a r d i o w i t h persistent o r r e c u r r i n g clinical signs:
gram; measure serum urea nitrogen, creatinine, a n d a. If there is n o e v i d e n c e o f u r i n a r y tract infection,
potassium c o n c e n t r a t i o n s ; a n d initiate IV f l u i d t h e r a p y if e x a m i n e the b l a d d e r using r a d i o g r a p h y o r ultrasonog
cat is obstructed a n d d e p r e s s e d . raphy o r e x a m i n e the b l a d d e r a n d urethra using
3. In both obstructed a n d unobstructed cats, o b t a i n a urine contrast-enhanced r a d i o g r a p h y o r cystoscopy.
s a m p l e b y cystocentesis, if possible, for the e v a l u a t i o n o f b. If there is e v i d e n c e o f u r i n a r y tract infection, p e r f o r m
urine p H a n d urine sediment. Culture urine if there is b a c t e r i a l culture a n d sensitivity testing a n d treat w i t h
evidence o f a u r i n a r y tract infection (pyuria, bacteriuria). an a p p r o p r i a t e a n t i b i o t i c . If signs persist or recur,
4 . M a n a g e cats w i t h suspected struvite-associated FLUTD e x a m i n e the b l a d d e r using r a d i o g r a p h y o r ultrasonog
using a diet c o n t a i n i n g less than 2 0 mEq o f m a g n e s i u m raphy or examine the b l a d d e r a n d urethra with
per 1 0 0 k C a l , a n d a c i d i f y urine ( b e t w e e n 6 . 2 a n d 6 . 4 ) contrast-enhanced r a d i o g r a p h y o r cystoscopy.
w i t h a m m o n i u m c h l o r i d e o r m e t h i o n i n e , if necessary. 6. In cases of idiopathic FLUTD, try antiinflammatory treatment.
FIG 4 7 - 2
Diagnostic a n d therapeutic f l o w chart for unobstructed cats with lower urinary tract disease.
of young cats with F L U T D have sterile urine and that the mended for the treatment o f F L U T D i n cats; however, no
same results could be obtained by treating with numerous controlled studies have demonstrated the efficacy o f any o f
placebos. these agents. O x y b u t y n i n and propantheline are antispas
If the initial urinalysis reveals an alkaline urine with stru m o d i c drugs that may alleviate pollakiuria i n some cats, and
vite crystalluria, imaging o f the urinary tract to rule out buprenophine (0.005 to 0.01 mg/kg administered intrave
struvite uroliths is indicated. U r i n e culture and sensitivity nously or intramuscularly q4-8h) or butorphanol (0.2 to
tests should be performed if pyuria or bacteriuria is observed 0.8 mg/kg administered intravenously or subcutaneously q2-
in the urine sediment, and appropriate antibiotics should be 6h or 1.5 mg/kg administered orally q4-8h) can be used as
administered i f urine cultures are positive. Cystocentesis is an analgesic. It must be kept i n m i n d that i n controlled
the ideal way to obtain urine for bacterial culture; i f urine is studies, more than 70% o f cats w i t h idiopathic F L U T D have
obtained by any other method, a quantitative urine culture appeared to respond to placebo treatments (e.g., lactose,
should be performed. Several sources o f fresh water should wheat flour).
be made available to the cat. The litter boxes should also be In cats that w i l l accept the change, switching from a dry
cleaned frequently and placed i n convenient locations. diet to a canned diet to help increase water intake and
Hill's Feline Prescription Diet s/d can be used to effec decrease urine concentration is often associated with
tively dissolve struvite uroliths. It takes an average o f 36 days improvement. Decreasing stress and i m p r o v i n g quality o f
for sterile struvite uroliths to dissolve, whereas struvite uro life may also be very important factors i n the management
liths associated with urease-producing bacterial infections i n of cats w i t h idiopathic F L U T D . Increasing the number o f
cats take an average o f 79 days to dissolve. Antibiotic treat litter boxes and keeping them clean may help decrease stress
ment i n cats with struvite urolithiasis and a concurrent bac in multiple cat households. Similarly, providing access to
terial urinary tract infection should be determined o n the several sources o f fresh food and water may help. Cats may
basis o f urine culture and sensitivity results and continued also benefit from increased play activities and increased
throughout the period o f dissolution. The diet should be fed access to private space. Finally, pheromone therapy (Feliway
for 30 days beyond the point when the uroliths are no longer C E V A A n i m a l Health, Libourne, France) may produce a
visible i n radiographs. calming effect and help reduce stress.
If struvite crystalluria and alkaline urine recur repeatedly Obstructed cats. In cats w i t h a urethral obstruction, the
in cats with previous struvite uroliths, longer-term dietary relative urgency for relieving the obstruction depends o n the
therapy is warranted. Examples o f diets that can be used to physical status of the cat. Cats that are alert and not azotemic
treat struvite-associated F L U T D as well as prevent recur may be sedated for urethral catheterization without further
rence include Hill's Feline Prescription Diet c/d (canned or diagnostic tests or treatment; however, i n a depressed cat
dry), Science Diet Feline Maintenance (canned or dry), lams with urethral obstruction, the serum potassium concentra
pH/S, Purina U R - F o r m u l a Feline Diet, and W a l t h a m Vet tion should be measured in-house or an electrocardiograph
erinarium Feline C o n t r o l p H o r m u l a Diet. The composition rhythm strip should be evaluated to assess the degree o f
of many over-the-counter cat foods is not constant; therefore hyperkalemia (see B o x 46-1) and an intravenous (IV) cath
it is difficult to make recommendations regarding their use. eter should be placed for the administration o f n o r m a l
Ideally, the urine p H , measured 4 to 8 hours after feeding, (0.9%) saline solution before establishing urethral patency.
should be maintained between 6.2 and 6.4. The aforemen If the electrocardiogram or b l o o d tests confirm the presence
tioned prescription diets are metabolized to form acid ions, of hyperkalemia, the cat should be treated aggressively
which are excreted i n the urine; it is rare, therefore, for these to decrease serum potassium concentrations or counteract
prescription diets not to maintain an acidic urine i n cats. A the effects o f hyperkalemia o n cardiac conduction (see
urease-producing bacterial infection and dietary indiscre Box 46-1).
tion should be identified or ruled out i f alkaline urine is The degree o f restraint required for urethral catheteriza
found to persist during dietary therapy. tion depends o n the cat's temperament and physical status.
In most cases o f F L U T D , the urine is acidic and no stru Physical restraint i n a towel or cat bag, w i t h or without the
vite crystals are observed; therefore magnesium-restricted, topical application o f lidocaine, may be all that is required
acidifying diets are not recommended. In cats with persistent i n a severely depressed cat. In cats requiring more restraint,
or recurrent clinical signs, a urine sample should be obtained ketamine H C 1 (1 to 2 mg/kg administered intravenously),
by cystocentesis for urine culture, and plain abdominal an ultra-short-acting barbiturate (IV thiamylal s o d i u m or
radiography or ultrasonography, contrast-enhanced radio thiopental sodium, 1 mg/kg titrated to effect), or propofol
graphic studies of the bladder and urethra, or cystoscopy 6.6 mg/kg administered I V slowly over 60 seconds) may be
should be performed to identify or rule out anatomic abnor used to effect. Because ketamine is eliminated by the kidneys,
malities i f the urine is bacteriologically sterile (see B o x 47-2 low I V doses (10 to 20 m g total) are frequently adequate for
and Fig. 47-2). Numerous agents, including antibiotics, tran restraint. The administration of additional doses o f ketamine
quilizers, anticholinergics, analgesics, antispasmodics, gly should be avoided i n severely azotemic cats.
cosaminoglycans, amitriptyline, and antiinflammatory drugs A urethral obstruction may be relieved i n some cases by
(e.g., dimethylsulfoxide, glucocorticoids, and nonsteroidal penile massage and gentle expression o f the bladder. If this
antiinflammmatory drugs [NSAIDs]), have been recom does not result i n urine flow, palpation o f the urethra per
rectum may dislodge a urethral plug or calculus. Sterile iso the degree o f azotemia and the response to treatment, to
tonic saline solution, administered through well-lubricated ensure the adequate recovery of renal function. Occasionally,
catheters or cannulas, should be used to hydropulse urethral hypokalemia occurs i n a cat with a prolonged and severe
plugs into the bladder. A variety o f cannulas and catheters diuresis. In addition, i f severe hematuria persists, the hema
may be used for this purpose; however, nonmetal catheters tocrit should be monitored once or twice daily.
with smooth, open ends are preferred to prevent iatrogenic Detrusor atony is fairly c o m m o n i n cats obstructed for
damage to the urethral mucosa. Use o f a strict aseptic tech more than 24 hours and is associated with bladder over-
nique is essential to prevent bacterial U T I s . If catheterizing distention. If the bladder can be expressed four to six times
the bladder proves difficult, cystocentesis with a 22-gauge or per day, an indwelling catheter may not be necessary. If the
small needle may be performed to decrease the intravesical bladder cannot be expressed at least four times per day, an
pressure and allow for the urethral obstruction to be indwelling catheter is indicated. Bethanechol (2.5 m g q8h
backflushed into the bladder. administered orally) may be administered to stimulate detru
Indications for the placement o f indwelling urinary cath sor contractility only after the finding o f a wide urine stream
eters i n male cats with obstructions that have just been or the placement o f an indwelling urinary catheter has
relieved include the following: (1) an inability to restore a confirmed that the urethra is patent. Acepromazine and
n o r m a l urine stream, (2) an abundance o f debris that cannot phenoxybenzamine can significantly lower intraurethral
be extracted via repeated bladder lavage, (3) evidence o f pressures i n anesthetized, healthy, intact male cats, and
detrusor atony i n cats that cannot be manually expressed therefore these drugs may also be helpful i n the management
four to six times per day, or (4) intensive care o f critically i l l of a functional urethral obstruction i n cats with F L U T D .
animals i n which urine formation is being monitored as a Perineal urethrostomy is rarely required for the emer
guide to fluid therapy requirements. W h e n an indwelling gency relief o f a urethral obstruction. If the obstruction
urinary catheter is necessary, again, strict aseptic technique cannot be relieved by medical means, the condition of uremic
should be used during placement. A soft red rubber feeding cats must be stabilized before surgery is performed. Repeated
tube (3F to 5F) should be used; placing the feeding tube i n cystocentesis should be done to keep the bladder empty until
the freezer for 30 minutes before use facilitates its passage. hyperkalemia, acidosis, and uremia resolve. Elective perineal
The catheter should be inserted only as far as the neck o f the urethrostomies are occasionally advisable i n male cats with
bladder; catheter passage should be stopped as soon as urine recurrent obstructions to decrease the likelihood of death
can be aspirated from the catheter. A closed urine-collection from postrenal azotemia. However, a perineal urethrostomy
system should be used, and the catheter should be sutured does not decrease the risk o f recurrence o f clinical signs of
to the prepuce and left i n place for as short a time as possible cystitis, and it has been documented that cats with cystitis
(2 to 3 days is the average). A n Elizabethan collar or tape that undergo perineal urethrostomies are more susceptible
hobbles are needed to prevent the cat from chewing out the to bacterial U T I s .
sutures and removing the catheter. Phenoxybenzamine or Probably the most important aspect of long-term patient
prazosin treatment is often initiated at this time to decrease monitoring is ensuring that the owner recognizes both the
urethral spasms that can be stimulated by the indwelling significance and the clinical signs o f urethral obstruction.
catheter. Prophylactic antibiotic treatment is not recom Owners o f male cats with urinary obstruction must be
mended; however, the urine sediment should be examined warned o f the risks o f reobstruction, especially during
daily for bacteria and white b l o o d cells, and the urine cul the first 24 to 48 hours after the relief of an obstruction or
tured i f necessary. Secondary bacterial U T I s are c o m m o n i n the removal of an indwelling urinary catheter. Allowing the
cats with indwelling urinary catheters receiving I V fluids to owner to palpate the distended bladder during the initial
promote diuresis. examination is a good way to teach h i m or her how to dif
The degree o f postrenal azotemia should be assessed by ferentiate pollakiuria, dysuria-stranguria, and an obstruc
measuring the serum urea nitrogen, creatinine, and potas tion. A n y straining i n the litter box should be cause for alarm
sium concentrations. I V fluid therapy is indicated, especially in a male cat with a history o f urethral obstruction, and
in cats with azotemia. Maintenance therapy (approximately careful observation for continued voiding of urine is essen
60 to 70 ml/kg/day) and replacement therapy (percentage of tial for the early detection of a recurrence.
dehydration x body weight [in kilograms] = liters to a d m i n Follow-up urinalysis and urine culture should be per
ister) should be administered intravenously over 24 hours. formed 5 to 7 days after catheterization i n all cats that have
The subcutaneous administration o f a balanced electrolyte been catheterized to relieve a urethral obstruction. Because
solution is an acceptable mode o f fluid therapy i n some cats n o r m a l host defenses are bypassed when a catheter is intro
once the initial uremic crisis is under control. Measurement duced into the bladder, UTIs are c o m m o n after catheteriza
of the urine volume every 4 to 8 hours w i l l facilitate the tion, especially i f an indwelling urinary catheter has been
administration o f correct replacement therapy. A large- used. A follow-up urinalysis and urine culture should also
volume, postobstructive diuresis may develop i n some cats, be performed i n all cats receiving corticosteroids because
and I V fluid replacement therapy is essential i n these animals. these may decrease i m m u n e system function (and decrease
Serum urea nitrogen, creatinine, and serum electrolyte con inflammation-related changes i n the urine sediment) and
centrations should be reassessed as needed, depending o n predispose cats to the development of bacterial UTIs. Ascend-
ing pyelonephritis is a significant concern i n cats with any Buffington C A T et al: C l i n i c a l evaluation o f cats w i t h nonobstruc
UTI, and it is a potential complication o f F L U T D , especially tive urinary tract diseases, J Am Vet Med Assoc 210:46, 1997.
if corticosteroids are used. Urethral obstruction caused by Buffington C A T et al: Feline interstitial cystitis, J Am Vet Med Assoc
215:682, 1999.
struvite uroliths or struvite-containing mucous plugs should
Buffington C A T et al: C V T update: idiopathic (interstitial) cystitis
be managed with dietary treatment designed to either dis
in cats. In Bonagura J D , editor: Current veterinary therapy XIII,
solve the urolith or prevent recurrence, as previously
Philadelphia, 2000, W B Saunders.
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Buffington C A T , C h e w D J : Management o f non-obstructive i d i o -
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diet to prevent recurrent episodes. The urine p H 4 to 8 hours BSAVA manual of canine and feline nephrology and urology, ed 2,
after eating should be 6.4 or less. Yearly urinalysis and bacte Gloucester, England, 2007, British Small A n i m a l Veterinary
rial culture are especially important i n cats w i t h perineal Association.
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nisms of the lower urethra have been surgically removed i n tract disease: therapeutic rights a n d wrongs. In Bonagura J D ,
these cats. editor: Current veterinary therapy XIII, Philadelphia, 2000, W B
Saunders.
The prognosis for male cats w i t h recurrent urethral
Kruger J M et al: R a n d o m i z e d controlled trial o f the efficacy o f
obstruction is guarded, and perineal urethrostomy should
short-term amitripyline administration for treatment o f acute,
be considered, especially i f the second obstruction occurs
nonobstructive, idiopathic lower u r i n a r y tract disease i n cats,
during medical management designed to prevent recurrence. ] Am Vet Med Assoc 222:749, 2003.
The prognosis for cats w i t h recurrent nonobstructed Lekcharoensuk C et al: Association between dietary factors and
F L U T D is fair to good, inasmuch as this syndrome is rarely c a l c i u m oxalate and magnesium a m m o n i u m phosphate u r o l i
life-threatening. Pyelonephritis, renal urolithiasis, and thiasis i n cats, J Am Vet Med Assoc 219:1228, 2001.
C K D are potential sequelae o f recurrent nonobstructed Lekcharoensuk C et al: E p i d e m i o l o g i c study o f risk factors for lower
FLUTD. urinary tract disease i n cats, / Am Vet Med Assoc 218:1429, 2001.
Osborne C A et al: Feline urologic syndrome, feline lower urinary
tract disease, feline interstitial cystitis: what's i n a name? J Am Vet
Suggested Readings Med Assoc 214:1470, 1999.
Bartges J W et al: Bacterial urinary tract infection i n cats. In W e s t r o p p JL et al: Feline lower urinary tract disease. In Ettinger SJ,
Bonagura J D , editor: Current veterinary therapy XIII, Philadel Feldman E C , editors: Textbook of veterinary internal medicine,
phia, 2000, W B Saunders. ed 6, St Louis, 2005, Elsevier/Saunders.
C H A P T E R 48
Disorders of Micturition
the bladder and involuntarily inhibited by a spinal reflex that tion that produces compression, damage, or degeneration of
tightens the external urethral sphincter when there is a sharp the spinal cord or pelvic nerve. Overdistention of the bladder
increase i n intraabdominal pressure (e.g., during abdominal for a prolonged time may also cause a neurogenic inconti
palpation or bladder expression, barking, coughing, sneez nence by decreasing bladder detrusor muscle tone (a type o f
ing, retching). Urinary incontinence occurs i f the intravesi L M N disorder). Dysautonomia i n dogs and cats, an auto
cal pressure exceeds the pressure exerted by the urethral n o m i c polyganglionopathy, also produces an L M N inconti
sphincters. nence that is associated with weak and ineffective detrusor
Stretch receptors i n the bladder send impulses through activity. O n the other hand, urine leakage or incontinence
the pelvic nerve and spinal cord pathways to the thalamus disorders are usually associated with a small or normal-size
and cerebral cortex when the urinary bladder fills and intra bladder caused by increased detrusor contractility or
mural tension exceeds the threshold. V o l u n t a r y control o f decreased urethral outflow resistance. Congenital abnor
voiding is mediated by the cerebral cortex through the pons malities o f the urinary system (e.g., ectopic ureters, vaginal
(main micturition center), the cerebellum, and the reticulo strictures) can also result i n urinary incontinence associated
spinal tracts to the sacral nuclei. The voiding phase o f m i c with a small or normal-sized urinary bladder. It should be
turition is characterized by parasympathetic activity. In this noted that urine leakage can occur with urine retention dis
phase the detrusor muscle contracts secondary to choliner orders when intravesical pressure exceeds outflow resistance.
gic stimulation of the motor portion o f the pelvic nerve. It This type o f urine leakage is referred to as paradoxic or over
is important to note that during this cholinergic-mediated flow incontinence (discussed i n greater detail later).
detrusor contraction, the a and -adrenergic input to the
internal and external urethral sphincters is reflexly inhibited
at the level of the pons. W h e n the bladder is empty, the DISTENDED BLADDER
normal sympathetic domination resumes and the detrusor
muscle relaxes to allow filling to occur. The n o r m a l residual Big, distended urinary bladders are usually easily palpated
volume of urine after complete voiding is approximately on physical examination, and the ease o f bladder expression
0.2 to 0.4 ml/kg (with a m a x i m u m o f 10 ml) i n both dogs is an important part o f patient assessment. If the distended
and cats. bladder is easy to express, the underlying p r o b l e m is usually
decreased detrusor contractility. Conversely, if the bladder is
Etiology and Clinical Features of difficult to express, increased outflow resistance should be
Disorders of Micturition suspected. Both functional (e.g., increased urethral tone
Disorders of micturition can be divided into two major cat caused by increased sympathetic tone or urethral spasm) and
egories: those associated with a large or distended bladder anatomic (e.g., urethral uroliths or trigonal masses) prob
and those associated with a small or normal-sized bladder lems can cause increased outflow resistance. Urethral cath
(Table 48-1). Urine retention disorders associated with dis eterization and/or positive contrast urethrography can be
tended bladders include neurogenic disorders (upper [ U M N ] used to differentiate functional and anatomic causes of
and lower [ L M N ] motor neuron disease, functional urethral increased outflow resistance.
obstruction, reflex dyssynergia) and anatomic obstructive If neurologic lesions or deficits are detected during neu
disorders. Neurologic disorders may be caused by any condi rologic examination, the status o f the bladder helps localize
TABLE 48-1
Disorders of Micturition
DISORDER CAUSES
Distended Bladder
Neurogenic
Lower motor neuron disease Lesion to S1 to S3 spinal c o r d segment (at o r b e l o w fifth lumbar
vertebral b o d y ) , n e o p l a s i a , t r a u m a , c a u d a e q u i n a syndrome
Trauma to pelvic nerve, detrusor atony, canine a n d feline dysautonomia
U p p e r motor neuron disease Lesion cranial t o S1 spinal c o r d segment (above fifth lumbar vertebral
b o d y ) , intervertebral disk protrusion, n e o p l a s i a , trauma,
fibrocartilaginous infarct, meningitis
C e r e b r a l disease, cerebellar disease, brainstem disease
Reflex dyssynergia (detrusor-urethral dyssynergia) Unknown
Functional urethral obstruction Urethral muscular spasm, often associated with urethral inflammation o r
trauma
A n a t o m i c outflow tract obstruction Urethral stricture, n e o p l a s i a , cystic o r urethral calculi, granulomatous
urethritis, prostatic disease
Small o r N o r m a l - S i z e d B l a d d e r
Urethral sphincter mechanism incompetence Deficient b l a d d e r / u r e t h r a l support, hormone-responsive
Detrusor hyperreflexia o r instability Bladder irritation, urethral irritation
C o n g e n i t a l incontinence Ectopic ureters, patent urachus, urethral fistula (rectal o r vaginal),
p s e u d o h e r m a p h r o d i t i s m , v a g i n a l strictures
the lesion and classify the injury as either a U M N lesion urine while walking away. It is difficult to express urine from
(above the fifth lumbar vertebral body) or an L M N lesion the bladder of a dog with reflex dyssynergia, but urethral
(at or below the fifth lumbar vertebral body). The most catheterization is usually easily accomplished. W i t h reflex
characteristic sign o f an L M N lesion affecting the bladder is dyssynergia, increased outflow resistance occurs when the
a distended bladder that is easily expressed. A n L M N injury dog tries to initiate voiding. A similar type of functional
affecting the bladder causes both sphincter and detrusor urethral obstruction has been described i n three male dogs
hyporeflexia; if the lesion involves spinal cord segments S1 in which resting outflow resistance was increased (Lane,
to S3, both perineal and bulbospongiosus reflexes o f the 2000). Prostatitis and a history o f urethral calculi were asso
pudendal nerve are usually absent. ciated with the functional urethral obstruction i n two cases,
U M N lesions affecting the bladder result i n a large, dis respectively; the t h i r d case was diagnosed as idiopathic.
tended bladder that is difficult to express but easy to cathe Anatomic outflow obstruction results i n a big, distended
terize. Thoracolumbar spinal c o r d lesions causing paresis or bladder that is usually both difficult to express and catheter
paralysis are frequent causes o f U M N bladder disorders. A n ize. In some cases a catheter may be passed around an ana
animal with a U M N lesion has no voluntary control o f m i c tomic urethral lesion relatively easily, and a positive contrast
turition, and the urethral sphincter shows reflex hyperexcit retrograde urethrogram may be necessary to confirm the
ability because the somatic efferents i n the pudendal nerve presence of a lesion.
are not inhibited, making expression difficult. Incontinence i n an animal with a primary urine retention
Reflex dyssynergia, or detrusor-urethral dyssynergia, is problem is called paradoxic or overflow incontinence. Urine
seen p r i m a r i l y i n large-breed male dogs. The cause is usually leakage occurs i n this case when intravesical pressure exceeds
difficult to determine but may include any o f several neuro outflow resistance. Clinical signs associated with a functional
logic lesions of the spinal cord or autonomic ganglia. Patho or anatomic urethral obstruction include dribbling of urine,
physiologically, reflex dyssynergia results from the active straining to urinate without producing urine, restlessness,
contraction o f the detrusor without relaxation o f the inter and abdominal pain. The most c o m m o n causes of anatomic
nal or external urethral sphincters. Characteristic signs o f urethral obstruction are calculi and neoplasia i n dogs, and
reflex dyssynergia include n o r m a l or near-normal initiation struvite/mucous plugs i n cats; however, trigonal masses, ure
of voiding, followed by a narrowed urine stream. U r i n e may thral strictures, and granulomatous urethritis can also create
be delivered i n spurts, or flow may be completely disrupted obstructions to urine flow. A n y type of prostatic disease i n
and the dog w i l l often strain to produce urine. After a while dogs may produce an outflow tract obstruction. Older male
the dog will lower its leg and then often begins dribbling dogs with benign prostatic hyperplasia may be evaluated
because of stranguria and tenesmus; however, bacterial pros the dog under anesthesia has been identified i n bitches with
tatitis, prostatic neoplasia, and prostatic abscesses are more U S M I . This is thought to be due to deficient bladder and
likely causes of a urinary outflow tract obstruction. In urethral support mechanism i n these dogs. Estrogen and
patients with decreased detrusor contractility, paradoxic testosterone are believed to contribute to the integrity of
incontinence occurs earlier and at lower intravesicular pres urethral muscle tone by augmenting its responsiveness to
sures compared with patients that have either functional or - a d r e n e r g i c innervation. Thus middle-age to older, spayed
anatomic outflow resistance problems. female dogs are prone to incontinence because o f decreased
estrogen concentrations. This incontinence is most pro
nounced when the animal is asleep or relaxed and often
SMALL OR NORMAL-SIZE BLADDER responds to estrogen replacement or - a d r e n e r g i c therapy.
Less frequently, incontinence develops i n male dogs after
Causes of urinary incontinence associated with a small or castration; the condition seems to occur most c o m m o n l y
normal-size bladder include increased detrusor contractility i n dogs castrated at an older age and often responds to
and decreased outflow resistance. Increased detrusor c o n - a d r e n e r g i c treatment or hormone replacement. B o t h
tractility is generally associated with bladder and or urethral processes are diagnosed o n the basis o f history, physical
irritation/inflammation that creates an urge to v o i d that examination findings, urinalysis (lack o f evidence o f lower
overcomes normal house-trained behavior. These patients urinary tract inflammation), and the animal's response to
often exhibit pollakiuria, dysuria, and stranguria and have therapy. Frequently, - a d r e n e r g i c treatment (e.g., phenyl
inflammatory or hemorrhagic urine sediment findings. propanolamine) may be combined with hormone replace
Conversely, i n patients with decreased urethral outflow resis ment treatment i n severe cases o f U S M I .
tance, urine leakage is often most pronounced when the U r i n a r y incontinence i n a young animal with a small or
animal is asleep or relaxed. The voiding phase of micturition normal-size bladder may be associated with a variety o f c o n
is usually normal i n these patients, as is the urinalysis (unless genital defects o f the urinary or genital systems. The most
complicated by an ascending urinary tract infection). c o m m o n defects are ectopic ureters and vaginal strictures,
Detrusor muscle hypercontractility (also referred to but patent urachus, urethrorectal and urethrovaginal fistulae,
as detrusor instability or urge incontinence) is the inability and female pseudohermaphroditism have also been associ
to control voiding owing to a strong urge to urinate. ated with urinary incontinence. Ectopic ureters are most
Inflammation of the bladder or urethra may trigger the c o m m o n l y observed i n female dogs. Breeds i n which the
voiding reflex by creating a sensation o f bladder fullness. prevalence of ectopic ureters is high include Siberian Huskies,
Clinical signs of this type o f incontinence include pollaki Miniature and T o y Poodles, Labrador Retrievers, Fox
uria, dysuria-stranguria, and frequently hematuria. A bacte Terriers, West H i g h l a n d W h i t e Terriers, Collies, and C a r d i
rial urinary tract infection is the most c o m m o n cause i n the gan and Pembroke Welsh Corgis. Ectopic ureters are rarely
dog, and sterile inflammation o f the lower urinary tract is seen i n cats, but the gender predisposition is reversed (i.e.,
the most c o m m o n cause i n cats. Evidence o f a urinary tract the prevalence is higher i n male than i n female cats). U S M I
infection or inflammation revealed by urinalysis (e.g., bac is a frequent concurrent problem i n dogs with ectopic ureters
teriuria, pyuria, or hematuria) initially supports the tentative or vaginal strictures.
diagnosis of urge or inflammatory incontinence. If clinical The most c o m m o n clinical sign associated with ectopic
signs persist after appropriate treatment for the urinary tract ureters is constant dribbling o f urine, although dogs and cats
inflammation has been initiated, further diagnostic studies, with a unilateral ectopic ureter also may v o i d normally.
including ultrasonography, contrast-enhanced radiography, Because 70% o f ectopic ureters i n dogs terminate i n the
and cystoscopy, are indicated because infiltrative disease o f vagina, vaginoscopy may allow visualization o f the opening
the bladder (e.g., neoplasia, chronic cystitis), polyps, uro of the ureter; however, the orifice may be difficult to see
liths, or urachal remnants can result i n pollakiuria and stran even i f the vagina is fully distended with air. Intravenous
guria. It should also be noted that detrusor hyperreflexia/ urography and retrograde vaginourethrography are excellent
instability may be a primary or idiopathic disorder that is diagnostic tests for characterizing the defect, although a
not associated with bladder or urethral inflammation. recent study suggested that contrast computed tomography
The preferred terminology for decreased urethral outflow (CT) is the test o f choice for the diagnosis of ectopic
resistance is urethral sphincter mechanism incompetence ureters. In contrast to the incontinence seen i n animals with
(USMI). This urethral sphincter dysfunction is most often ectopic ureters, incontinence associated with a vaginal stric
observed i n spayed, m e d i u m - to large-breed female dogs. ture is often intermittent, occurring with changes i n body
Decreased tone i n collagenous supporting structures o f the position. Vaginal strictures can be diagnosed by digital
urogenital tract caused by aging and/or decreased estrogen vaginal examination, vaginoscopy, or contrast-enhanced
concentrations is thought to be the primary cause o f U S M I . vaginography.
Additional causes/complications may include abnormal Incontinence may also be caused by cognitive disorders
bladder/urethral position (e.g., pelvic bladder), decreased (CDs), decreased bladder capacity, or decreased mobility i n
responsiveness of - a d r e n e r g i c urethral receptors, and senior animals. Polyuric-polydipsic disorders, such as chronic
obesity. Recently, abnormal caudad bladder movement with kidney disease ( C K D ) i n senior animals, also often exacer-
bate incontinence. Likewise, use o f diuretic and corticoste and U M N and L M N disorders result i n large, distended
roid medications should be avoided, if possible, i n incontinent bladders.
animals because o f their negative effects on urine- As noted earlier, incontinence i n senior animals may be
concentrating ability. caused by C D s , a decreased bladder capacity, or decreased
physical control. Physical problems i n such animals, espe
Diagnosis cially polyuric disorders and disabilities that impair mobility,
Clinical features o f disorders o f m i c t u r i t i o n often help should be identified and treated. Polyuria and polydipsia can
the clinician discern the underlying problem. For example, trigger urge incontinence by placing continual stress on the
if c o n t i n u o u s urinary incontinence has been present bladder wall and urethral sphincter; however, i n these cases
from birth, the likely underlying problem is a congenital the urine volume is large. A normally completely house-
anomaly. Incontinence associated with hematuria, pollaki broken animal with polyuria and polydipsia may start uri
uria, and dysuria-stranguria usually indicates the presence nating i n the house i f it does not have frequent access to the
of inflammation o f the bladder, urethra, or both. Inappro outdoors. If increased thirst and large urine volume are
priate dribbling o f urine during sleep or relaxation indicates described by the owner, appropriate diagnostic tests should
U S M I , and leakage o f urine i n female dogs associated with be performed to identify conditions that cause polydipsia
postural changes may point to the pooling o f urine behind and polyuria (e.g., diabetes mellitus, pyometra, C K D , hyper
a vaginal stricture. Dogs with pelvic bladders, which is a adrenocorticism, hypercalcemia).
more caudal abdominal location i n which the bladder neck Owners frequently mistake submissive urination, which
is caudal to the pecten o f the pubic bone (Fig. 48-2), can also may be a normal behavioral pattern o f young dogs, with
have urethral sphincter incompetence that results i n urinary urinary incontinence. Other voiding patterns that are con
incontinence. A l l these forms o f incontinence are usually strued by some owners as incontinence are the urine marking
associated with a small or normal-size bladder. used by male and occasionally female animals and inappro
Dysuria and stranguria that occur i n association with an priate elimination behavior problems. The owner's descrip
abnormal or absent urine stream are typical of an obstruc tion o f the animal's voiding pattern may reveal a behavioral
tive uropathy. Urethral obstructions may be caused by basis for the abnormal micturition, although a complete
anatomic (e.g., uroliths, tumors) or functional (e.g., reflex physical examination and a urinalysis should always be per
dyssynergia) problems. U r i n a r y incontinence that occurs formed to identify or rule out a urinary tract disorder.
i n association w i t h trauma or pelvic surgery is usually
neurogenic i n origin ( L M N disease); i f paresis or paralysis
is present, the lesion is usually above the fifth lumbar verte INITIAL EVALUATION
bral body and is a U M N lesion. Obstructive uropathies
The age o f onset, reproductive status of the animal, age at
neutering, current medications, and history of trauma or
previous urinary tract disorders are important anamnestic
points to cover during the history-taking i n an animal with
any disorder of micturition. The physical examination should
include evaluation o f the perineum for evidence of urine
scalding or staining. A thorough palpation of the bladder to
assess its size and wall thickness and a rectal examination to
assess anal tone, the prostate gland, the pelvic urethra, and
the trigone region o f the bladder should be performed i n all
cases. A digital vaginal examination is also indicated, and
vaginoscopy may be used to help identify congenital defects
(e.g., vaginal strictures, ectopic ureters) i n larger female dogs.
A neurologic examination should include evaluation of
the perineal and bulbospongiosus reflexes. The perineal
reflex causes the anal sphincter to contract and the tail to
ventroflex i n response to pinching the perineal skin. The
bulbospongiosus reflex causes the anal sphincter to contract
i n response to gentle compression o f the bulb of the penis
or the vulva. Both these reflexes depend on an intact puden
dal nerve (sensory and motor) and spinal cord segments S1
to S3. If both reflexes are normal, the pudendal reflex arc is
intact. Because o f their c o m m o n origin, injury to the puden
FIG 48-2
Double-contrast-enhanced cystogram showing a pelvic dal nerve may also affect the pelvic nerve.
bladder in a 2-year-old spayed female Doberman Pinscher Dogs should be walked outside so that the voiding posture
with urethral sphincter mechanism incompetence. and urine stream size and character can be observed. Imme-
diately after the animal has attempted to void, the bladder Care should be taken to prevent urine scalding by applying
should be palpated to determine the residual volume (normal petroleum jelly to the perivulvar or peripreputial and abdom
residual volume is approximately 0.2 to 0.4 ml/kg). Catheter inal skin. Bethanechol may be administered to increase detru
ization is indicated to quantify the residual volume i f a large sor contractility i f the urethra is confirmed to be patent by
bladder is palpable after voiding (in male dogs, however, bladder expression (5-15 mg/dog P O q8h; 1.25-5 mg/cat P O
behavioral urine marking can make assessment o f residual q8h). Adverse effects o f bethanechol include salivation, v o m
urine volume difficult). iting, diarrhea, or coliclike signs that indicate intestinal
Urinalysis should be performed i n all animals with urinary cramping. These signs usually appear w i t h i n 1 hour o f drug
incontinence. If a urine culture is indicated, cystocentesis is administration; if they are observed, the dose of bethanechol
the preferred method o f collection; however, animals with a should be decreased.
distended bladder should be catheterized instead to empty T o manage detrusor atony, the bladder must be expressed
the bladder and prevent the problem o f urine leaking from or urinary catheterization done intermittently to keep the
the cystocentesis site. Additional diagnostic testing that can bladder empty for a period o f days to weeks. A closed urine-
be accomplished at many referral centers includes cystoscopy collection system should always be used with indwelling
and urethral pressure profilometry ( U P P ) . Cystoscopy allows catheters. Urinalysis should be performed every 3 or 4 days
direct visualization of the urethral and bladder mucosa and and a urine bacterial culture and antibiotic sensitivity testing
the ability to obtain mucosal specimens for culture and his done i f there is any evidence o f urinary tract inflammation.
tology. The functional length o f the urethral sphincter and Bethanechol may be administered to increase detrusor c o n
the urethral closure pressure can be determined via U P P , tractility but only after increased outflow resistance has been
which is usually performed i n conscious patients. A flexible ruled out.
catheter with a side port is passed through the urethra, and
after the bladder has been emptied, the catheter is connected
to a pressure transducer and a withdrawal arm (that pulls UPPER MOTOR NEURON DISORDERS
catheter back through the urethra at a constant rate). Saline
is then infused through the catheter as it is withdrawn, and The nature o f the management o f animals w i t h a U M N
the resistance to flow (pressure) is recorded versus distance lesion affecting the bladder depends o n whether the animal
traveled. (See additional descriptions of bladder and urethral has an autonomic bladder. A reflex, or autonomic, bladder
function testing i n Chapter 42.) often develops 5 to 10 days after a spinal cord injury, and it
occurs because stretching o f the bladder wall stimulates a
local reflex arc that results i n detrusor contraction. There is
PHARMACOLOGIC TESTING no cortical perception or voluntary control, and initially
voiding is usually incomplete, resulting i n a large urine resid
Frequently, the diagnosis of disorders o f micturition is based ual volume. Treatment i n an animal before an autonomic
to some degree o n the animal's response to pharmacologic bladder develops should include aseptic catheterization three
testing or therapy. For example, detrusor hypocontractility times per day. The use o f corticosteroids for the treatment
should improve i n response to a parasympathomimetic drug of neurologic disease may cause polyuria, necessitating more
(e.g., bethanechol), and decreased urethral tone should frequent catheterization to prevent overdistention o f the
respond to - a d r e n e r g i c agents (e.g., phenylpropanolamine) bladder. Corticosteroids also predispose animals to urinary
or hormone replacement therapy. Increased urethral tone is tract infections. D u r i n g the initial stages o f treatment, u r i
treated with -sympatholytics (e.g., phenoxybenzamine) nalysis or urine sediment examination should be performed
and striated muscle relaxants (e.g., diazepam). Detrusor every 3 or 4 days, and urine bacterial culture and antibiotic
hypercontractility often responds to treatment o f the under sensitivity testing should be performed i f there is evidence
lying inflammatory process, such as bacterial cystitis or of urinary tract inflammation (corticosteroids frequently
urolithiasis; however, smooth muscle antispasmodics (e.g., mask signs o f inflammation). Because these animals are
oxybutynin) and parasympatholytics (e.g., propantheline) usually i n pain and reluctant to move, it is important to
may be useful i n cases o f severe inflammation. prevent urine scalding. The use o f elevated racks or absor
bent bedding is indicated, and petroleum jelly applied around
Treatment the perineum or prepuce may m i n i m i z e urine scalding.
After an autonomic bladder develops, the bladder should
LOWER MOTOR NEURON DISORDERS be palpated after urination to determine the residual urine
volume. It may still be necessary to catheterize the bladder
Animals with L M N diseases resulting from sacral spinal cord two or three times per day to m i n i m i z e urine stasis. U r i
lesions or dysautonomia require expression or strict aseptic nalyses should continue to be done o n a monthly schedule
catheterization o f their bladder at least three times per day. (weekly if the animal is receiving corticosteroids), and owners
Urinalysis or examination o f the urine sediment should be should be instructed to b r i n g i n a urine sample i f a change
performed weekly, and a urine bacterial culture should be i n urine color or odor is noted. N u r s i n g care to prevent urine
performed if there is any evidence of a urinary tract infection. scalding should be continued.
REFLEX DYSSYNERGIA URETHRAL SPHINCTER
MECHANISM INCOMPETENCE
Reflex dyssynergia often responds to pharmacologic m a n
agement; however, a therapeutic response may not be seen The treatment o f urinary incontinence associated with
for several days. Drugs c o m m o n l y used include an -blocker decreased sphincter tone includes hormone replacement or
(e.g., prazosin or phenoxybenzamine), a somatic muscle -adrenergic drugs (or both). The usual induction therapy
relaxant (e.g., diazepam), and occasionally bethanechol. for estrogen-responsive incontinence consists of diethylstil
Intermittent urinary catheterization should be performed bestrol (DES; 0.1 to 1.0 m g total administered orally q24h
as necessary to keep the bladder small and combat for 3 to 5 days). The frequency o f administration is then
detrusor atony that may be caused by overdistention of the decreased to the lowest possible dose that will maintain con
bladder. tinence. Some dogs can be successfully tapered to a very low
Phenoxybenzamine has a slow onset o f action, and the maintenance schedule (e.g., 0.1 to 1.0 m g per dog every 7 to
dose should be increased only at 3- to 4-day intervals. 10 days). Phenylpropanolamine (1.5 to 2.0 mg/kg adminis
The urine stream should be evaluated to gauge drug tered orally q8h) may be used as an alternative drug or i n
effectiveness. If the stream is weak but continuous and o f addition to DES. Owners o f dogs receiving phenylpropanol
n o r m a l diameter, bethanechol may be used to increase detru amine should be cautioned to observe their dog for hyper-
sor contractility; however, it must not be used u n t i l the func excitability, panting, or anorexia and to decrease the dose i f
tional urethral obstruction has been relieved. If the urine these signs develop. Although initially administered three
stream is intermittent or narrowed, increased doses o f diaz times per day, i n some animals the dosing frequency of
epam or phenoxybenzamine or both may be required. timed-release or precision-release phenylpropanolamine
Because diazepam has a very short duration o f action can be decreased to a once- or twice-daily schedule. Careful
(approximately 1 to 2 hours when administered orally), observation by the owner for recurrence o f signs usually
administering it 30 minutes before walking the animal some reveals when the dose needs to be increased. Dogs with
times aids i n the management o f reflex dyssynergia. It may increasing resistance to D E S pose the greatest worry because
be several weeks before a correct combination o f drugs is the development o f estruslike signs and bone marrow toxic
determined, however, and drug dosages may have to be ity are possible adverse effects o f higher-dose D E S therapy.
modified over time. Periodic urinalyses are indicated to Endocrine alopecia is another possible adverse effect. If DES-
detect urinary tract inflammation or infection at an early resistant dogs are not concurrently receiving phenylpropa
stage. nolamine, a trial o f it should be instituted before the DES
Hypotension is the major adverse effect of phenoxyben dose exceeds recommended levels. -Adrenergic drugs are
zamine, and the dose should be decreased immediately i f contraindicated i n patients with systemic hypertension,
the animal shows any indication o f lethargy, weakness, or mitral regurgitation, and anxiety disorders.
disorientation. In most cases the dosage o f phenoxy Urethral sphincter incompetence i n neutered male
benzamine should be increased only i f a favorable response dogs is best treated with -adrenergic drugs. If testosterone
is not observed after 3 or 4 days; rapid dose changes is to be used, it should be parenterally administered because
should be avoided. Nausea is an adverse effect that can be most testosterone administered orally undergoes rapid
m i n i m i z e d by administering the medication w i t h a small hepatic degradation. Depository forms injected intramuscu
meal. G l a u c o m a is a rare complication o f phenoxybenza larly may be effective for 4 to 6 weeks. Male dogs receiving
mine treatment i n people; it is u n k n o w n i f this occurs i n testosterone should have regular rectal examinations to
dogs. evaluate prostate size. Testosterone should not be used
in dogs that were previously neutered because of a testo
sterone-responsive disease (e.g., benign prostatic hyper
FUNCTIONAL URETHRAL OBSTRUCTION trophy, perianal adenomas) or behavioral disorders (e.g.,
aggression).
Nonneurogenic functional urethral obstruction, i n w h i c h In those patients with U S M I refractory to hormone
resting as well as voiding urethral pressures are abnormally replacement and/or -adrenergic therapy, alternative treat
high, has been associated with prostatic disease; urinary tract ments include gonadotropin-releasing hormone ( G n R H )
infection; urethral muscular spasm; and urethral inflam analogues and urethral bulking and surgical procedures.
mation, hemorrhage, or edema i n dogs and cats. Affected Increased concentrations o f luteinizing hormone ( L H ) and
animals have clinical signs and histories similar to those i n follicle-stimulating hormone (FSH) have been documented
dogs with reflex dyssynergia. Resting urethral pressure in spayed dogs, and G n R H analogues w i l l downregulate
profilometry is usually necessary to differentiate these two production/secretion of L H and F S H . Submucosal collagen
syndromes. W h e n treatment o f the underlying disorder injections at the level o f the internal urethral sphincter via
fails to decrease the increased outflow resistance, -blockers urethroscopy can also be used as an adjunct treatment to
(e.g., prazosin or phenoxybenzamine) and skeletal muscle increase urethral sphincter tone. Finally, surgical procedures
relaxants (e.g., diazepam) can be used. such as colposuspension, cystourethropexy, and formation
of seromuscular urethral slings may benefit patients with plasia, partial or complete prostatectomy or radiotherapy
U S M I that is nonresponive to medical management. may be beneficial; however, prostatectomy is difficult and
frequently results i n neurologic damage and U S M I .
C H A P T E R 49
Disorders of the
Hypothalamus and
Pituitary Gland
Endocrine Disorders Causing Polyuria and Polydipsia in the Dog and Cat
C / C , Cortisol/creatinine; ACTH, Adrenocorticotropic hormone; PTH, parathyroid hormone; GH, growth hormone; IGF-I, Insulin-like growth
factor-l; CT, computed tomographic; MR, magnetic resonance.
TABLE 49-2
Results of Urinalysis in Dogs with Selected Disorders Causing Polyuria and Polydipsia
URINE SPECIFIC
GRAVITY
NO. OF PROTEINURIA WBC (>5/HPF) BACTERIURIA
DISORDER DOGS MEAN RANGE (%) (%) (%)
m i l d renal insufficiency without azotemia, and m i l d hepatic veterinary hospital for determination of urine specific
insufficiency, most notably with portosystemic shunts. gravity. U r i n e specific gravity varies widely among healthy
Hyperadrenocorticism, renal insufficiency, and hepatic dogs and can range from 1.006 to greater than 1.040 within
insufficiency should be ruled out before performing diag a 24-hour period. W i d e fluctuations i n urine specific gravity
nostic tests for diabetes insipidus or psychogenic P D . Diag have not been reported i n healthy cats. If the urine specific
nostic tests to consider include evaluating the range o f urine gravity is consistently i n the isosthenuric range (1.008 to
specific gravities obtained from several urine samples (dis 1.015), renal insufficiency should be considered the primary
cussed i n more detail below), tests for hyperadrenocorticism differential diagnosis, especially i f the blood urea nitrogen
(e.g., urine Cortisol: creatinine ratio, low-dose dexametha and serum creatinine concentration are high normal or
sone suppression test), liver function tests (e.g., measure increased (i.e., 25 m g / d l or more and 1.6 m g / d l or more,
ment o f preprandial and postprandial bile acid levels), respectively). Isosthenuria is relatively c o m m o n i n dogs with
determination o f the urine p r o t e i n : creatinine ( P / C ) ratio, hyperadrenocorticism, psychogenic water consumption,
and abdominal ultrasonography. Ideally, all realistic causes hepatic insufficiency, pyelonephritis, and partial diabetes
of secondary acquired nephrogenic diabetes insipidus should insipidus with concurrent water restriction, but urine specific
be ruled out before performing tests (especially the modified gravities above (e.g., hyperadrenocorticism, pyelonephritis,
water deprivation test) for primary pituitary and nephro hepatic insufficiency, psychogenic water consumption) or
genic diabetes insipidus and psychogenic P D . below (e.g., hyperadrenocorticism, hepatic insufficiency,
Critical evaluation o f urine specific gravity measured partial diabetes insipidus) the isosthenuric range also occur
from several urine samples obtained by the client at different with these disorders. If urine specific gravities less than 1.005
times o f the day for 2 to 3 days may provide clues to the (i.e., hyposthenuric) are identified, renal insufficiency and
underlying disorder (Table 49-2). U r i n e samples should be pyelonephritis are ruled out and diabetes insipidus, psycho
stored i n the refrigerator u n t i l they can be brought to the genic water consumption, hyperadrenocorticism, and hepatic
insufficiency should be considered. Primary pituitary and
nephrogenic diabetes insipidus are ruled out i f the urine
specific gravity exceeds 1.020. Urine specific gravities that
Recognized Causes of Diabetes Insipidus in Dogs and Cats
range from less than 1.005 to greater than 1.030 are sugges
tive of psychogenic P D . CENTRAL DIABETES NEPHROGENIC
INSIPIDUS DIABETES INSIPIDUS
CENTRAL DIABETES INSIPIDUS Primary intracranial tumors that are associated with dia
Central diabetes insipidus ( C D I ) is a polyuric syndrome that betes insipidus i n dogs and cats include craniopharyngioma,
results from insufficient secretion o f A V P to concentrate pituitary chromophobe adenoma, and pituitary c h r o m o
urine for water conservation. This deficiency may be abso phobe adenocarcinoma. Metastatic m a m m a r y carcinoma,
lute or partial. A n absolute deficiency o f A V P , referred to as lymphoma, malignant melanoma, and pancreatic carcinoma
complete CDI, causes persistent hyposthenuria and severe have been reported to cause C D I i n dogs through their pres
diuresis. The urine specific gravity i n dogs and cats with ence i n the pituitary gland or hypothalamus. Metastatic
complete C D I remains hyposthenuric (i.e., 1.005 or less), neoplasia has not yet been reported to be a cause o f C D I i n
even with severe dehydration. A partial deficiency o f A V P , cats.
referred to as partial CDI, also causes persistent hyposthe
nuria and a marked diuresis as long as the dog or cat has NEPHROGENIC DIABETES INSIPIDUS
unlimited access to water. D u r i n g periods o f water restric Nephrogenic diabetes insipidus ( N D I ) is a polyuric disorder
tion the urine specific gravity can increase into the isosthe that results from impaired responsiveness o f the nephron to
nuric range (i.e., 1.008 to 1.015), but typically the urine A V P . Plasma A V P concentrations are n o r m a l or increased i n
cannot be concentrated to more than 1.015 to 1.020 even animals w i t h this disorder. N D I is classified as either primary
when the animal is severely dehydrated. In any dog or cat (familial) or secondary (acquired). P r i m a r y N D I is a rare
with partial C D I the m a x i m u m urine-concentrating ability congenital disorder i n dogs and cats, with only a few reports
during dehydration is inversely related to the severity o f the in the literature. The etiology of primary N D I i n dogs and
deficiency i n A V P secretionthat is, the more severe the cats is u n k n o w n , although decreased b i n d i n g affinity o f
A V P deficiency, the less concentrated the urine specific A V P receptors was identified i n a family o f Siberian Huskies.
gravity during dehydration. Affected puppies showed antidiuretic responses to high
C D I may result from any condition that damages the doses o f synthetic vasopressin (desmopressin [ d D A V P ] ) .
neurohypophyseal system (Box 49-1). Idiopathic C D I is the
most c o m m o n form, appearing at any age, i n any breed, and Clinical Features
affecting animals of either sex. Necropsies performed i n dogs
and cats with idiopathic C D I fail to identify an underlying SIGNALMENT
reason for the A V P deficiency. Although C D I is well docu There is no apparent breed-, sex-, or age-related predilection
mented in kittens and puppies, a hereditary form o f C D I has for C D I . In one study the age at the time o f the diagnosis o f
not yet been documented. The most c o m m o n identifiable C D I i n dogs ranged from 7 weeks to 14 years, with a median
causes of C D I in dogs and cats are head trauma (accidental of 5 years. Similarly, most cats with C D I are domestic short-
or neurosurgical), neoplasia, and hypothalamic-pituitary and long-haired cats, although the disorder has also been
malformations (e.g., cystic structures). Head trauma may documented i n Persians and Abyssinians. The age at the time
cause a transient (typically lasting 1 to 3 weeks) or perma of diagnosis of C D I i n cats ranged from 8 weeks to 6 years,
nent C D I , depending on the viability o f the cells i n the with a mean o f 1.5 years. Primary N D I has been identified
supraoptic and paraventricular nuclei. only i n puppies, kittens, and young adult dogs and cats
younger than 18 months o f age. P U and P D have been Chapter 55). Hyposthenuria i n the presence of persistent
present since the clients acquired these pets. hypernatremia should raise suspicion for diabetes insipidus.
FIG 49-1
U r i n e specific g r a v i t y m e a s u r e d in 3 0 d o g s with central d i a b e t e s insipidus at the time of
initial presentation to the v e t e r i n a r i a n . (From F e l d m a n E C , N e l s o n R W : Canine and feline
endocrinology and reproduction, e d 3 , St Louis, 2 0 0 4 , W B Saunders.)
the causes for acquired secondary N D I have been ruled lary solute washout may prevent a dog or cat with C D I from
out. forming concentrated urine i n response to only one or two
administrations. Clients should notice a decrease i n P U and
MODIFIED WATER DEPRIVATION TEST P D by the end o f the treatment period i f the P U and P D are
The technique, interpretation, contraindications, and c o m caused by C D I . U r i n e specific gravity should be measured
plications of the modified water deprivation test are described
in Chapter 42. The test consists of two phases. In phase I the
A V P secretory capabilities and renal distal and collecting
tubule responsiveness to A V P are evaluated by assessing the
effects of dehydration (i.e., water restriction until the animal
loses 3% to 5% o f its body weight) o n urine specific gravity.
The normal dog and cat, as well as those with psychogenic
water consumption, should be able to concentrate urine to
greater than 1.030 (1.035 i n the cat) i f dehydrated. Dogs and
cats with partial and complete C D I and primary N D I have
an impaired ability to concentrate urine i n the face o f dehy
dration (Table 49-3 and Fig. 49-2). The time required to
attain 3% to 5% dehydration can sometimes be helpful i n
establishing the diagnosis. It often takes less than 6 hours
for dogs and cats with complete C D I to attain 3% to 5%
dehydration, whereas it often takes more than 8 to 10 hours
for dogs and cats with partial C D I , and especially those
with psychogenic water consumption, to attain 3% to 5%
dehydration.
Phase II of the water deprivation test is indicated for dogs
and cats that do not concentrate urine to greater than 1.030
during phase I of the test. Phase II determines the effect, i f
any, that exogenous A V P has on the renal tubular ability to
concentrate urine in the face o f dehydration (see Fig. 49-2).
This phase differentiates impaired A V P secretion from
impaired renal tubular responsiveness to A V P (see Table 49-3).
TABLE 49-3
Central Dl
Complete < 1.006 < 1.006 > 1.008 4 3-7
Partial <1.006 1.008-1.020 >1.015 8 6-11
Primary n e p h r o g e n i c D l <1.006 <1.006 <1.006 5 3-9
Primary p o l y d i p s i a 1.002-1.020 >1.030 NA 13 8-20
FIG 4 9 - 3
R a n d o m p l a s m a o s m o l a l i t y in 1 9 d o g s with c o m p l e t e central d i a b e t e s insipidus, 12 d o g s
with p a r t i a l central d i a b e t e s i n s i p i d u s , 9 d o g s with p r i m a r y n e p h r o g e n i c d i a b e t e s insipi
d u s , a n d 11 d o g s with p r i m a r y (psychogenic) p o l y d i p s i a . N o t e the o v e r l a p in values
b e t w e e n g r o u p s of d o g s . Dashed lines, U p p e r a n d l o w e r limits for n o r m a l p l a s m a
osmolality. (From F e l d m a n E C , N e l s o n RVV: Canine and feline endocrinology and
reproduction, e d 3 , St Louis, 2 0 0 4 , W B Saunders.)
obtained while the dog or cat has free access to water suggests
the presence of psychogenic P D , whereas a plasma osmolal
ity greater than 280 m O s m / k g is consistent with C D I , N D I ,
Therapies Available for Polydipsic/Polyuric Dogs and Cats
or psychogenic P D .
with Central Diabetes Insipidus, Nephrogenic Diabetes
Insipidus, or Primary (Psychogenic) Polydipsia
ADDITIONAL DIAGNOSTIC TESTS
Neoplasia i n the region o f the pituitary and hypothalamus A . Central diabetes insipidus (severe)
should be considered i n the older dog or cat i n which C D I 1. dDAVP (desmopressin acetate)
a. Effective
develops. A complete neurologic evaluation, including c o m
b. Expensive
puted tomographic ( C T ) or magnetic resonance ( M R ) scan
c. O r a l tablets or drops of nasal solution in
may be warranted before idiopathic C D I is arbitrarily diag
conjunctival sac
nosed, especially i f the client is willing to consider radio
2. LVP (lypressin [Diapid])
therapy or chemotherapy should a t u m o r be identified. a. Short duration of action; less potent than dDAVP
Similarly, a more complete evaluation o f the kidney (e.g., b. Expensive
creatinine clearance studies, intravenous pyelogram, C T or c. Requires drops into nose or conjunctival sac
M R scan, renal biopsy) may be warranted i n the older dog 3. N o treatmentprovide continuous source of water
or cat tentatively considered to have primary N D I . B. Central diabetes insipidus (partial)
1. dDAVP
Treatment 2. LVP
3. Chlorpropamide
Therapeutic options for dogs and cats with diabetes insipi
a. 30%-70% effective
dus are listed i n Box 49-2. The synthetic analog o f vasopres
b. Inexpensive
sin, d D A V P , is the standard therapy for C D I . d D A V P has
c. Pill form
almost three times the antidiuretic action o f A V P , with
d. Takes 1-2 weeks to obtain effect of drug
minimal-to-no vasopressor or oxytocic activity. The intrana e. M a y cause hypoglycemia
sal d D A V P preparation ( d D A V P nasal drops, 2.5- and 5.0-ml 4. Thiazide diuretics
bottles containing 100 g d D A V P / m l ) is used most c o m a. Mildly effective
monly for treating C D I i n dogs and cats. Administration o f b. Inexpensive
medication to animals via the intranasal route is possible but c. Pill form
not recommended. The d D A V P nasal preparation may be d. Should be used with low-sodium diet
transferred to a sterile eye dropper bottle and drops placed 5. Low-sodium diet (NaCl < 0.9 g / 1 0 0 0 kcal/ME)
into the conjunctival sac o f the dog or cat. Although the 6. N o treatmentprovide continuous source of water
C . Nephrogenic diabetes insipidus
solution is acidic, ocular irritation rarely occurs. One drop
1. Thiazide diuretics
of d D A V P contains 1.5 to 4 g o f d D A V P , and a dosage o f
2. Low-sodium diet (NaCl < 0.9 g / 1 0 0 0 kcal/ME)
one to four drops administered once or twice daily controls
3. N o treatmentprovide continuous source of water
signs of C D I i n most animals. D. Primary (psychogenic) polydipsia
Oral d D A V P ( d D A V P tablets, 0.1 and 0.2 mg) can be used 1. Water restriction at times
to treat C D I , although the clinical response is variable. The 2. Water limitation
bioavailability o f oral d D A V P is approximately 5% to 15% 3. Change in environment or daily routine; excercise;
of the intranasal dose i n humans. Similar information is not increased contact with humans or dogs
available for dogs and cats. The initial oral d D A V P dose is
ME, Metabolizable energy
0.1 mg (dogs) and 0.05 m g (cats) given three times a day. The
dose is gradually increased to effect i f unacceptable P U and
P D persist 1 week after therapy is initiated. Decreasing the
frequency o f administration to twice a day, decreasing the expense becomes a limiting factor. The medication may be
dose of d D A V P , or both can be tried once clinical response administered exclusively i n the evening as insurance against
has been documented. T o date, most dogs have required 0.1 nocturia.
to 0.2 m g of d D A V P two to three times a day, and most cats Chlorpropamide, thiazide diuretics, and oral s o d i u m
have required 0.025 to 0.05 m g o f d D A V P two to three times chloride restriction have a limited efficacy i n the treatment
a day to control P U and P D . Treatment should be switched of N D I . d D A V P may control the clinical signs i f adminis
to the intranasal d D A V P preparation i f there is m i n i m a l to tered i n massive amounts (i.e., five to ten times the amount
no response to 0.2 m g (dog) or 0.05 m g (cat) o f oral d D A V P used for the treatment o f C D I ) , but the cost o f the drug
administered three times a day. obviously detracts from the attractiveness o f this therapeutic
The maximal effect o f d D A V P , regardless o f the route o f approach. Fortunately, therapy for C D I or N D I is not man
administration, occurs from 2 to 8 hours after administra datory as long as the dog or cat has unlimited access to water
tion, and the duration o f action varies from 8 to 24 hours. and is housed i n an environment that cannot be damaged
Larger doses o f d D A V P appear both to increase its antidi by severe P U . A constant water supply is o f paramount
uretic effects and to prolong its duration o f action; however, importance because relatively short periods o f water restric-
tion can have catastrophic results (i.e., the development of water should be divided into several aliquots, with the last
hypernatremic, hypertonic dehydration and neurologic aliquot given at bedtime. Oral salt (1 g/30 kg q l 2 h ) and/or
signs). oral sodium bicarbonate (0.6 g/30 kg q l 2 h ) may also be
administered for 3 to 5 days to help reestablish the renal
Prognosis medullary concentration gradient. Changes i n the dog's
Dogs and cats with idiopathic or congenital C D I become environment or daily routine should be considered, such as
relatively asymptomatic i n response to appropriate therapy, initiating a daily exercise routine; bringing a second pet into
and with proper care these animals have an excellent life the home; providing some distraction, such as a radio playing
expectancy. P U and P D frequently resolve i n dogs and cats when the clients are not home; or moving the dog to an area
with trauma-induced C D I , often within 2 weeks of the trau with an increased amount of contact with humans.
matic incident. The prognosis i n dogs and cats with hypo
thalamic and pituitary tumors is guarded to grave. Neurologic
signs typically develop within 6 months after the diagnosis ENDOCRINE ALOPECIA
of C D I , and clinical response to radiotherapy and chemo
therapy is variable and unpredictable. Symmetric alopecia without historical or clinical evidence of
The prognosis for animals with primary N D I is guarded inflammation usually results from hair cycle arrest induced
to poor because of limited therapeutic options and the gen by hormonal diseaseshence the term endocrine alopecia
erally poor response to therapy. The prognosis for animals (Fig. 49-4). H a i r follicles are atrophic, hairs are easily epi
with secondary N D I depends on the prognosis of the primary lated, the skin is often thin and hypotonic, and hyperpig
problem. mentation is c o m m o n . Other dermatologic lesions, such as
scales, crusts, and papules, are absent. Seborrhea and pyo
derma may develop, depending on the underlying cause.
PRIMARY (PSYCHOGENIC) POLYDIPSIA Causes of endocrine alopecia are listed i n Table 49-4. In
dogs the most c o m m o n causes are hypothyroidism and glu
Primary P D is defined as a marked increase i n water intake cocorticoid excess (iatrogenic or spontaneous). Feline endo
that cannot be explained as a compensatory mechanism for crine alopecia is perhaps the most c o m m o n endocrine
excessive fluid loss. In humans primary P D results from a alopecia i n cats. The diagnostic evaluation for endocrine
defect i n the thirst center or may be associated with mental alopecia begins with a complete history, physical examina
illness. Primary dysfunction of the thirst center resulting i n tion, and routine blood and urine tests, (i.e., C B C , serum
compulsive water consumption has not been reported i n the biochemistry panel, and urinalysis). Results of these tests will
dog or cat, although an abnormal vasopressin response to often provide evidence for hypothyroidism and hyperadre
hypertonic saline infusion has been reported i n dogs with nocorticism, and appropriate diagnostic tests can then be
suspected primary P D . A psychogenic or behavioral basis for performed to confirm these diagnoses (see Chapters 51 and
compulsive water consumption does occur i n the dog but 53, respectively).
has not been reported i n the cat. Psychogenic P D may be
induced by concurrent disease (e.g., hepatic insufficiency,
hyperthyroidism) or may represent a learned behavior fol
lowing a change i n the pet's environment. P U is compensa
tory to prevent overhydration.
Dogs (and presumably cats) with primary or psychogenic
P D have an intact hypothalamic-pituitary-renal axis for con
trolling fluid balance and variable severity of renal medullary
solute washout. Because A V P production and renal tubular
response to A V P are normal, these dogs can concentrate
urine i n excess of 1.030. Depending on the severity of renal
medullary solute washout, a period of 24 hours or longer of
water deprivation may be necessary to attain concentrated
urine. Psychogenic P D is diagnosed by exclusion of other
causes of P U and P D and by demonstrating that the dog or
cat can concentrate urine to a specific gravity i n excess of
1.030 during water deprivation.
Treatment is aimed at gradually limiting water intake to FIG 4 9 - 4
E n d o c r i n e a l o p e c i a , thin skin, a n d severe obesity in a
amounts i n the high-normal range. The client should deter
7-year-old m a l e castrated P o m e r a n i a n with iatrogenic
mine the dog's approximate water intake i n a 24-hour period h y p e r a d r e n o c o r t i c i s m c a u s e d b y c h r o n i c administration of
when free-choice water is allowed, and this volume of water p r e d n i s o n e for a s e i z u r e d i s o r d e r . N o t e the symmetric
is then reduced by 10% per week until water volumes of 60 truncal a l o p e c i a with s p a r i n g of the h e a d a n d distal
to 80 ml/kg/24 h are reached. The total 24-hour volume of extremities.
TABLE 49-4
COMMON CLINICOPATHOLOGIC
DISORDER ABNORMALITIES DIAGNOSTIC TESTS
nonregenerative anemia
Hyperadrenocorticism Stress leukogram, increased ALP, Urine Cortisol/creatinine ratio, low-dose
hypercholesterolemia, hyposthenuria, dexamethasone suppression test,
proteinuria, urinary tract infection abdominal US
Hyperestrogenism
Functional Sertoli cell tumor in None (bone marrow depression Physical findings, abdominal US,
male dog uncommon) cytologic or histopathologic findings,
plasma estrogen concentration
Hyperestrogenism in intact None (bone marrow depression Vaginal cytology, abdominal US, plasma
female dog uncommon) estrogen concentration, response to
ovariohysterectomy
Hyperprogesteronism None Physical findings, abdominal US, serum
progesterone concentration
Increased adrenocortical steroid None Measure adrenocortical steroid hormone
hormone intermediates (adrenal intermediates before and after A C T H
hyperplasia-like syndrome, administration
Alopecia-X)
Growth hormone deficiency None Signalment, physical findings, growth
pituitary dwarfism hormone response test
Growth hormone-responsive None Growth hormone response test, response
dermatosisadult dog to growth hormone replacement therapy
Castration-responsive dermatosis None Response to castration
Hypoestrogenism (?)
Estrogen-responsive dermatosis None Response to estrogen therapy
of spayed female dogs
Hypoandrogenism (?)
Testosterone-responsive None Response to testosterone therapy
dermatosismale dog
Feline endocrine alopecia None Response to progestin therapy
Telogen defluxion (effluvium) None History of recent pregnancy or diestrus
Diabetes mellitus Hyperglycemia, glycosuria Blood and urine glucose measurement
T , Tetraiodothyronine; TSH, thyroid-stimulating hormone; ALP, alkaline phosphatase; US, ultrasonography; ACTH, adrenocorticotropic
4
hormone.
Once hypothyroidism and hyperadrenocorticism have of a C B C may reveal aplastic anemia. Histologic assessment
been ruled out, the next diagnostic step is to rule out an of a skin biopsy specimen can be used to identify nonspecific
excess of one of the sex hormones or one of the adrenocor endocrine-related alterations and support the diagnosis of
tical steroid hormone intermediates. Dermatologic mani endocrine alopecia (Table 49-5). There are no pathogno
festations are similar for most sex h o r m o n e - i n d u c e d m o n i c histologic changes for sex h o r m o n e - i n d u c e d derma
dermatoses and include endocrine alopecia that initially toses. The identification of an increased plasma estrogen
begins in the perineal, genital, and ventral abdominal regions (i.e., estradiol) concentration w o u l d support the presence of
and spreads cranially; dull, dry, easily epilated hair; failure of a functional Sertoli cell t u m o r i n the dog and hyperestrogen
the haircoat to regrow after clipping; and variable presence ism i n the bitch (assuming that the bitch is not i n proestrus
of seborrhea and hyperpigmentation. Additional clinical or early estrus). A b d o m i n a l ultrasound may identify ovarian
signs of hyperestrogenism may include gynecomastia, a pen cysts or neoplasia i n the bitch with hyperestrogenism, and
dulous prepuce, the attraction of other male dogs, squatting abdominal and testicular ultrasound may identify testicular
to urinate, and unilateral testicular atrophy (contralateral to neoplasia i n the male dog. Hyperestrogenism and endocrine
the testicular tumor) i n the male dog and vulvar enlarge alopecia w i l l resolve after surgical removal o f the ovarian
ment and persistent proestrus or estrus in the bitch. Results cyst, ovarian tumor, or testicular tumor.
TABLE 49-5
FIG 4 9 - 6
A a n d B, E n d o c r i n e a l o p e c i a in a 6-year-old P o m e r a n i a n w i t h suspected adult-onset, G H -
responsive d e r m a t o s i s . N o t e the symmetric truncal a l o p e c i a w i t h lesser involvement of the
extremities a n d s p a r i n g of the h e a d .
TABLE 49-6
PO, By mouth.
FELINE ACROMEGALY
Etiology
C h r o n i c excessive secretion o f G H in adult cats results in
acromegaly, a disease characterized by overgrowth of con FIG 4 9 - 7
nective tissue, bone, and viscera. In cats acromegaly is caused M a g n e t i c resonance i m a g e of the pituitary region of a 6-year-
o l d m a l e , castrated domestic short-haired cat with insulin-
by a functional adenoma o f the somatotropic cells o f the
resistant d i a b e t e s mellitus a n d a c r o m e g a l y (see F i g . 4 9 - 8 , A ) .
pituitary pars distalis that secretes excess G H (Fig. 49-7). In A mass is evident in the hypothalamic-pituitary region (arrow).
most cats the pituitary tumor is a macroadenoma that
extends dorsally above the sella turcica. Progestogen-induced
acromegaly has not been documented i n the cat. Progesto medroxyprogesterone acetate) or late in life after years of
gens, including megestrol acetate, do not appear to stimulate endogenous progesterone secretion during the diestrual
G H or IGF-I secretion in the cat. In contrast, acromegaly in phase o f the estrous cycle i n the intact bitch.
the dog is seen most c o m m o n l y after prolonged exposure C h r o n i c excess secretion o f G H has catabolic and ana
to progestogens, either exogenously administered (e.g., bolic effects. The anabolic effects are caused by increased
concentrations of IGF-I. The growth-promoting effects of
IGF-I result i n proliferation of bone, cartilage, and soft
tissues and i n organomegaly, most notably o f the kidney and Clinical Signs Associated with Acromegaly i n Dogs and Cats
heart. These anabolic effects are responsible for producing
Anabolic, IGF-l-lnduced
the classic clinical manifestations o f acromegaly (Box 49-3).
The catabolic effects of G H are a direct result o f G H - i n d u c e d Respiratory*
insulin resistance that ultimately results i n carbohydrate Inspiratory stridor, stertor
Transient apnea
intolerance, hyperglycemia, and the development of diabetes
Panting
mellitus that quickly becomes resistant to insulin treatment.
Exercise intolerance
Most but not all cats with acromegaly have diabetes mellitus
Fatigue
at the time acromegaly is diagnosed, and most eventually
Dermatologic
develop severe resistance to exogenously administered Myxedema
insulin. Excessive skin folds
Hypertrichosis
Clinical Features Conformational*
Acromegaly typically occurs i n male, mixed-breed cats that Increased size
are 8 years o f age or older. Clinical signs result from the Increased soft tissue in oropharyngeal/laryngeal area
catabolic, diabetogenic effects of G H , the anabolic actions o f Enlargement of:
chronic IGF-I secretion by the liver, and growth o f the p i t u Abdomen
Head*
itary macroadenoma (see Box 49-3). The earliest clinical
Feet
signs are usually P U , P D , and polyphagia resulting from
Viscera*
concurrent diabetes mellitus. Polyphagia can become quite
Broad face*
intense. Weight loss varies and depends i n part o n whether Prominent jowls*
the anabolic effects of IGF-I or the catabolic effects of u n c o n Prognathia inferior*
trolled diabetes predominate. M o s t cats initially lose weight Increased interdental space*
and then experience a period of stabilization followed by a Rapid toenail growth
slow, progressive gain i n body weight as the anabolic effects Degenerative polyarthropathy
of IGF-I begin to dominate the clinical picture. Severe insulin
Catabolic, GH-lnduced
resistance eventually develops. Insulin dosages i n cats with
acromegaly frequently exceed 2 to 3 U / k g o f body weight Polyuria, polydipsia*
Polyphagia*
twice a day, with no apparent decline i n the b l o o d glucose
concentration. Iatrogenic
Clinical signs related to the anabolic actions of excess G H
Progestins
secretion (see Box 49-3) may be evident at the time diabetes Mammary nodules
mellitus is diagnosed. M o r e commonly, however, they Pyometra
become apparent several months after diabetes has been
diagnosed, often i n conjunction with the realization that Neoplasia-lnduced
hyperglycemia is difficult to control with exogenous insulin Lethargy, stupor
therapy. Because o f the insidious onset and slowly progres Adipsia
sive nature of the anabolic clinical signs, clients are often not Anorexia
aware of the subtle changes i n the appearance of their cat Temperature deregulation
Papilledema
until the clinical signs are quite obvious. Anabolic changes
Circling
in acromegalic cats include an increase i n body size, enlarge
Seizures
ment of the abdomen and head, development o f prognathia
Pituitary dysfunction
inferior, and weight gain (Fig. 49-8). Weight gain i n a cat Hypogonadism
with poorly regulated diabetes mellitus is an important diag Hypothyroidism
nostic clue to acromegaly. W i t h time, organomegaly, espe Hypoadrenocorticism
cially of the heart, kidney, liver, and adrenal gland, develop.
Diffuse thickening of soft tissues i n the pharyngeal region IGF-I, Insulin-like growth factor-l; GH, growth hormone.
can lead to extrathoracic upper airway obstruction and *Common findings.
respiratory distress.
Neurologic signs may develop as a result of pituitary pituitary gland. Papilledema may be evident during an o p h
tumor growth and the resultant invasion and compression thalmic examination. Peripheral neuropathy causing weak
of the hypothalamus and thalamus. Signs include stupor, ness, ataxia, and a plantigrade stance may develop as a result
somnolence, adipsia, anorexia, temperature deregulation, of poorly controlled diabetes mellitus. Other endocrine and
circling, seizures, and changes i n behavior. Blindness is not metabolic abnormalities resulting from the compressive
common because the optic chiasm is located anterior to the effects o f the t u m o r o n the pituitary are u n c o m m o n .
Clinical Pathology
Concurrent, poorly controlled diabetes mellitus is respon
sible for causing most of the abnormalities identified on a
serum biochemistry panel and urinalysis, including hyper
glycemia, glycosuria, hypercholesterolemia, and a mild
increase i n alanine transaminase and alkaline phosphatase
activities. Ketonuria is an infrequent finding. M i l d erythro
cytosis, persistent m i l d hyperphosphatemia without concur
rent azotemia, and persistent hyperproteinemia (total serum
protein concentration of 8.2 to 9.7 mg/dl) with a normal
pattern of distribution on protein electrophoretic studies
may also be found. Renal failure is a potential sequela of
acromegaly and, if present, will be associated with azotemia,
isosthenuria, and proteinuria.
Diagnosis
Clinical suspicion for acromegaly is based on the identifica
tion of conformational alterations (e.g., increased body size,
large head, prognathia inferior, organomegaly) associated
with acromegaly and a stable or progressive increase in
body weight i n a cat with insulin-resistant diabetes mellitus.
Measurement of serum IGF-I concentration provides
further evidence for the diagnosis of acromegaly. Measure
ment of serum IGF-I is commercially available (e.g., Diag
nostic Endocrinology Laboratory, College of Veterinary
Medicine, Michigan State University, East Lansing, M I
48909-7576). Concentrations are usually increased in acro
megalic cats, but values may be in the reference range in the
early stages of the disease (Fig. 49-9). Repeat measurements
FIG 49-9
B o x plots of serum concentrations of insulin-like growth factor-l
(IGF-I) in 3 8 healthy cats, 15 well-controlled d i a b e t i c cats, 4 0
FIG 49-8 p o o r l y controlled d i a b e t i c cats, a n d 1 9 p o o r l y controlled
A , A 6-year-old m a l e , castrated domestic short-haired cat with d i a b e t i c cats with a c r o m e g a l y . For e a c h b o x plot, T-bars
insulin-resistant d i a b e t e s mellitus a n d a c r o m e g a l y . N o t e the represent the m a i n b o d y of d a t a , w h i c h in most instances is
b r o a d face a n d mildly protruding mandible (prognathia inferior). e q u a l to the range. Each b o x represents the interquartile range
B a n d C, A n 8-year-old m a l e , castrated domestic short-haired (twenty-fifth to seventy-fifth percentile). The horizontal b a r in
cat with insulin-resistant diabetes mellitus a n d a c r o m e g a l y . N o t e e a c h box is the median. Asterisks represent outlying data points,
the b r o a d h e a d , mildly protruding m a n d i b l e , a n d p r o g n a t h i a (a) P < 0 . 0 0 0 1 , c o m p a r e d with healthy cats a n d well-controlled
inferior with d i s p l a c e m e n t of the l o w e r c a n i n e teeth. (From a n d poorly controlled diabetic cats. (From Berg RIM et a l : Serum
F e l d m a n E C , N e l s o n R W : Canine and feline endocrinology insulin-like g r o w t h factor-l concentration in cats with diabetes
and reproduction, e d 3 , St Louis, 2 0 0 4 , W B S a u n d e r s . ) mellitus a n d a c r o m e g a l y , J Vet intern Med 2 1 : 8 9 2 , 2 0 0 7 . )
performed 4 to 6 months later will usually demonstrate Treatment
an increase in serum IGF-I i f acromegaly is present. The Radiotherapy is currently considered the most viable treat
increase i n serum IGF-I typically coincides with develop ment option for acromegaly i n cats. Cobalt teletherapy
ment and growth of the pituitary somatotropic adenoma. involves the administration o f a total dose o f 45 to 48 G y i n
Increased serum IGF-I concentrations have been identified daily fractions five days per week for 3 to 4 weeks. The
in a small number o f poorly controlled diabetic cats i n clinical response to cobalt teletherapy is unpredictable and
which the poor control was not caused by acromegaly. ranges from no response to a dramatic response, character
Interpretation o f serum IGF-I test results should always take ized by shrinkage o f the tumor; elimination o f hypersomato
into consideration the status o f control o f the diabetic tropism; resolution o f insulin resistance; and, in some cats,
state, the presence and severity o f insulin resistance, and the reversion to a subclinical diabetic state (see Fig. 49-7). T y p i
index of suspicion for acromegaly based on review o f the cally, t u m o r size and plasma G H and serum IGF-I concen
history, physical examination, and results o f routine b l o o d trations decrease and insulin responsiveness improves after
and urine tests and diagnostic imaging. Identifying an cobalt teletherapy, although this improvement may take 6
increased serum IGF-I concentration i n a poorly controlled months or longer to occur after radiation treatment. In most
diabetic cat with insulin resistance and clinical features sug treated cats that respond to radiation therapy, diabetes
gestive of acromegaly supports the diagnosis and provides mellitus and/or insulin resistance recurs 6 months or longer
justification for C T or M R imaging of the pituitary gland. after treatment, although growth o f the pituitary mass is
Documenting a pituitary mass by C T or M R scanning (see often not evident o n C T or M R imaging.
Fig. 49-7) adds further evidence for the diagnosis and is Microsurgical transsphenoidal hypophysectomy has been
indicated whenever the client is considering radiation treat shown to be effective for the treatment o f feline pituitary-
ment. It is usually necessary to administer a positive contrast dependent hyperadrenocorticism, but use o f this specialized
agent to visualize a pituitary mass using C T or M R surgical technique for the treatment o f acromegaly has not
imaging. been reported. Successful use o f transsphenoidal cryother
A definitive diagnosis of acromegaly requires documenta apy of a pituitary tumor has been described i n a cat with
tion of an increased baseline serum G H concentration. Base acromegaly. A n effective medical treatment for acromegaly
line serum G H concentration i n cats with acromegaly in cats has not been identified.
typically exceeds 10 ng/ml (normal concentration is less than
5 ng/ml). Unfortunately, a commercial G H assay is not avail Prognosis
able for cats. The short- and long-term prognosis for cats with tumor-
induced acromegaly is guarded to good and poor, respec
A C R O M E G A L Y VERSUS tively. The survival time has ranged from 4 to 60 months
HYPERADRENOCORTICISM (typically 1.5 to 3 years) from the time the diagnosis o f
Hyperadrenocorticism and acromegaly are u n c o m m o n dis acromegaly is established. The GH-secreting pituitary t u m o r
orders that occur in older cats, have a strong association usually grows slowly, and neurologic signs associated with an
with diabetes mellitus, can cause severe insulin resistance, expanding tumor are u n c o m m o n until late in the disorder.
and are often caused by a functional pituitary macrotumor. Diabetes mellitus is difficult to control, even with the a d m i n
Clinical signs related to poorly controlled diabetes mellitus istration o f large doses o f insulin (20 U or more/injection)
are c o m m o n in cats with hyperadrenocorticism and acro given twice daily. A d m i n i s t r a t i o n o f large doses o f insulin
megaly. Additional clinical signs differ dramatically between is not recommended. The severity o f insulin resistance
these two disorders. Hyperadrenocorticism is a debilitating fluctuates unpredictably i n cats w i t h acromegaly, and severe,
disease that results in progressive weight loss leading to life-threatening hypoglycemia may suddenly develop after
cachexia and dermal and epidermal atrophy leading to months o f insulin resistance and b l o o d glucose concentra
extremely fragile, thin, easily torn and ulcerated skin (i.e., tions in excess o f 400 mg/dl. T o prevent severe hypoglycemia,
feline fragile skin syndrome). In contrast, conformational insulin doses should not exceed 12 to 15 units per injection.
changes caused by the anabolic actions of chronic IGF-I M o s t cats with acromegaly eventually die or are euthanized
secretion dominate the clinical picture i n acromegaly, most because of the development of severe congestive heart failure,
notably an increase in body size, prognathia inferior, and renal failure, respiratory distress, the neurologic signs o f
weight gain despite poorly regulated diabetes mellitus. Feline an expanding pituitary tumor, or coma caused by severe
fragile skin syndrome does not occur with acromegaly. hypoglycemia.
W i t h both disorders most o f the abnormalities identified on
routine blood and urine tests are caused by concurrent
poorly controlled diabetes mellitus. A b d o m i n a l ultrasound PITUITARY DWARFISM
may also reveal m i l d bilateral adrenomegaly with both
disorders. Ultimately, the differentiation between the two Etiology
diseases is based on results of tests of the pituitary- Pituitary dwarfism results from a congenital deficiency o f
adrenocortical axis (see Chapter 53) and serum G H and/or G H . Studies i n G e r m a n Shepherd D o g dwarfs suggest that
IGF-I concentrations. congenital G H deficiency is caused by primary failure o f
differentiation of the craniopharyngeal ectoderm into
normal tropic hormone-secreting pituitary cells. Pituitary
cysts are c o m m o n l y identified with diagnostic imaging of the C l i n i c a l Signs Associated with Pituitary Dwarfism
pituitary region using C T or M R imaging and may enlarge
Musculoskeletal
as the pituitary dwarf ages. However, current belief is that
pituitary cysts develop secondary to primary failure of ante Stunted growth*
rior pituitary formation i n most pituitary dwarfs. Pituitary Thin skeleton, immature facial features*
Square, chunky contour (adult)*
dwarfism is encountered most often as a simple, autosomal
Bone deformities
recessive inherited abnormality in the German Shepherd
Delayed closure of growth plates
Dog. A similar mode of inheritance has been reported i n
Delayed dental eruption
Carnelian Bear dogs. Inherited pituitary dwarfism may be
due to isolated G H deficiency or may be part of a combined Reproduction
pituitary hormone deficiency. Concurrent deficiency i n Testicular atrophy
thyroid-stimulating hormone ( T S H ) and prolactin are most Flaccid penile sheath
c o m m o n l y identified i n affected German Shepherd Dogs; Failure to have estrous cycles
A C T H secretion is preserved. Kooistra et al. (2000) hypoth
Other Signs
esize that the disorder is caused by a mutation i n a develop
mental transcription factor that precludes effective expansion Mental dullness
of a pituitary stem cell after differentiation of the cortico Shrill, puppylike bark*
Signs of secondary hypothyroidism
tropic cells that produce A C T H . Pituitary dwarfism resulting
Signs of secondary adrenal insufficiency (uncommon)
from a mutant G H or an insensitivity to G H owing to a lack
of or defect i n G H receptors (e.g., Laron-type dwarfism i n Dermatologic
h u m a n beings) has not been documented i n dogs or cats. Soft, wooly haircoat*
Retention of lanugo hairs*
Clinical Features Lack of guard hairs*
Alopecia*
SIGNALMENT Bilaterally symmetric
Pituitary dwarfism occurs primarily i n German Shepherd Trunk, neck, proximal extremities
Dogs, although pituitary dwarfism i n other dog breeds, Hyperpigmentation of the skin*
including the Weimaraner, Spitz, Miniature Pinscher, Carne Thin, fragile skin
Wrinkles
lian Bear dog, and Labrador Retriever, and i n cats has also
Scales
been observed. There does not appear to be a sex-related
Comedones
predilection. Papules
Pyoderma
CLINICAL SIGNS Seborrhea sicca
The most c o m m o n clinical manifestations of pituitary
dwarfism are lack of growth (i.e., short stature), endocrine *Common finding.
alopecia, and hyperpigmentation of the skin (Box 49-4).
Affected animals are usually normal i n size during the first 2 but becomes hyperpigmented, thin, wrinkled, and scaly.
to 4 months of life but after that grow more slowly than their Comedones, papules, and secondary pyoderma frequently
litter mates. By 5 to 6 months of age, affected dogs and cats develop i n the adult dwarf. Secondary bacterial infections are
are obviously runts of the litter and do not attain full adult c o m m o n long-term complications.
dimensions. Dwarfs with an isolated G H deficiency typically Hypogonadism may also develop, although normal repro
maintain a normal body contour and body proportions as they ductive function has been observed i n some animals with
age (i.e., proportionate dwarfism), whereas dwarfs with c o m pituitary dwarfism. In the male animal cryptorchidism, tes
bined deficiencies (most notably T S H ) may acquire a square ticular atrophy, azoospermia, and a flaccid penile sheath are
or chunky contour typically associated with congenital hypo typical; i n the female persistent anestrus is c o m m o n with
thyroidism (i.e., disproportionate dwarfism; Fig. 49-10). impaired secretion of pituitary gonadotropins.
The most notable dermatologic sign is retention of the
lanugo or secondary hairs, with concurrent lack of the Clinical Pathology
primary or guard hairs. As a result, the haircoat i n a dwarf Results of a C B C , serum biochemical panel, and urinalysis
is initially soft and wooly. The lanugo hairs are easily epi are usually normal i n animals with uncomplicated pituitary
lated, and a bilateral symmetric alopecia gradually develops. dwarfism and isolated G H deficiency. Concurrent deficiency
Initially, hair loss is confined to areas of wear, such as the of T S H may result i n clinicopathologic abnormalities affili
neck (collar) and posterolateral aspects of the thighs (from ated with hypothyroidism, such as hypercholesterolemia and
sitting). Eventually, the entire trunk, neck, and proximal anemia (see Chapter 51). Deficiency of G H , IGF-I, and T S H
limbs become alopecic, with primary hairs remaining only may also affect kidney development and function, resulting
on the face and distal extremities. The skin is initially normal in azotemia.
FIG 49-10
A, A 9-month-old m a l e domestic short-haired c a t with pituitary d w a r f i s m . The s i z e of the
pituitary d w a r f cat w a s similar to that of a n 8-week-old kitten. N o t e the n o r m a l b o d y
contour a n d juvenile a p p e a r a n c e . B a n d C, A 7-month-old f e m a l e G e r m a n S h e p h e r d D o g
with pituitary d w a r f i s m . N o t e the n o r m a l b o d y contour, p u p p y h a i r c o a t , a n d juvenile
a p p e a r a n c e . D, A 2-year-old f e m a l e s p a y e d L a b r a d o r Retriever with pituitary d w a r f i s m
sitting next to a n a g e - m a t c h e d n o r m a l L a b r a d o r Retriever to illustrate the small stature a n d
juvenile a p p e a r a n c e of the pituitary d w a r f . A l l of the pituitary d w a r f s presented with the
p r i m a r y o w n e r c o m p l a i n t of failure of their pet to g r o w .
Nonendocrine Causes
Treatment
The therapy for pituitary dwarfism relies on the administra
Malnutrition
Gastrointestinal tract disorders tion of G H . Unfortunately, an effective G H product is not
Megaesophagus available for use i n dogs. Canine G H is not available for
Inflammatory diseases therapeutic use, G H antibody formation and legal restric
Infectious diseases tions preclude the use of biosynthetic h u m a n G H , and the
Heavy intestinal parasitism concentration of biosynthetic bovine G H i n commercial
| Exocrine pancreatic insufficiency products for use i n cattle precludes its use i n dogs. The
Hepatic disorders
amino acid sequence of porcine G H is identical to canine
Portosystemic vascular shunt G H , but porcine G H is difficult to find. If available, the rec
Glycogen storage disease
o m m e n d e d subcutaneous dose is 0.1 to 0.3 I U / k g three times
Renal disease and failure
per week for 4 to 6 weeks. Because of the synergistic influ
Cardiovascular disease, anomalies
Skeletal dysplasia; chondrodystrophy ence of G H and thyroid hormone on growth processes, sub
Mucopolysaccharidoses n o r m a l concentrations of thyroid hormone may diminish
Hydrocephalus the effectiveness of G H therapy. Dogs and cats with sus
pected concurrent T S H deficiency should be treated with
daily thyroid hormone supplementation, as discussed i n
Chapter 51.
TABLE 49-7
Hypersensitivity reactions (including angioedema), car A n increase i n body size and regrowth of a complete
bohydrate intolerance, and overt diabetes mellitus are the haircoat has been reported i n pituitary dwarfs treated with
primary adverse reactions associated with G H injections. medroxyprogesterone acetate at doses o f 2.5 to 5.0 mg/kg
Frequent monitoring o f urine for glycosuria and b l o o d for body weight, initially at 3-week intervals and subsequently
hyperglycemia should be done, and G H therapy should be at 6-week intervals. Progestogens induce the expression o f
stopped i f either develops. Regrowth o f hair, thickening of the G H gene i n the m a m m a r y gland o f dogs, resulting i n G H
the skin, and changes i n serum IGF-I and glucose concentra secretion from foci o f hyperplastic ductular epithelial cells
tions are used to monitor therapy. A beneficial response i n and increased plasma concentrations o f G H and IGF-I.
the skin and haircoat usually occurs within 6 to 8 weeks of Adverse reactions with progestogen treatment include recur
the start of G H and thyroid hormone supplementation. The rent pruritic pyoderma, abnormal skeletal development,
hair that grows back is lanugo or secondary hairs; the growth mammary tumors, diabetes mellitus, acromegaly, and cystic
of primary or guard hairs is variable and may occur spo endometrial hyperplasia. Female dogs should be ovariohys
radically over the body. A n increase i n height is dependent terectomized before progestogen treatment. Serum IGF-I
on the status o f the growth plates at the time treatment is and glucose concentrations should be monitored.
initiated. A significant increase i n height may occur i f the
growth plates are open, and m i n i m a l to no change i n height Prognosis
will occur i f the growth plates have closed or are about to The long-term prognosis for animals with pituitary dwarfism
close at the time treatment is initiated. is poor. M o s t animals die by 5 years o f age despite therapy.
Death is usually a result of infections, degenerative diseases, Frank LA et al: Steroid hormone concentration profiles in healthy
neurologic dysfunction, or renal failure. intact and neutered dogs before and after cosyntropin adminis
tration, Domest Animl Endocrinol 24:43, 2003.
Frank LA et al: Retrospective evaluation of sex hormones and
Suggested Readings steroid hormone intermediates in dogs with alopecia, Vet Derm
Feldman EC, Nelson RW: Canine and feline endocrinology and 4:91, 2003.
reproduction, ed 3, St Louis, 2004, WB Saunders. Paradis M : Melatonin therapy for canine alopecia. In Bonagura JD,
editor: Kirk's current veterinary therapy XIII, Philadelphia, 2000,
DIABETES INSIPIDUS
W B Saunders.
Aroch I et al: Central diabetes insipidus in five cats: clinical presen Schmeitzel LP et al: Congenital adrenal hyperplasia-like syndrome.
tation, diagnosis and oral desmopressin therapy, / Eel Med Surg In Bonagura JD, editor: Kirk's current veterinary therapy XII,
7:333, 2005. Philadelphia, 1995, W B Saunders.
Harb M F et al: Central diabetes insipidus in dogs: 20 cases (1986- Scott D W et al, editors: Muller and Kirk's small animal dermatology,
1995), J Am Vet Med Assoc 209:1884, 1996. ed 6, Philadelphia, 2001, WB Saunders.
Nichols R: Clinical use of the vasopressin analogue dDAVP for the
diagnosis and treatment of diabetes insipidus. In Bonagura JD, FELINE ACROMEGALY
editor: Kirk's current veterinary therapy XIII, Philadelphia, 2000, Berg R I M et al: Serum insulin-like growth factor-I concentration
W B Saunders. in cats with diabetes mellitus and acromegaly, / Vet Intern Med
van Vonderen IK et al: Intra- and interindividual variation in urine 21:892, 2007.
osmolality and urine specific gravity in healthy pet dogs of Goossens M M C et al: Cobalt 60 irradiation of pituitary gland tumors
various ages, / Vet Intern Med 11:30, 1997. in three cats with acromegaly, J Am Vet Med Assoc 213:374,1998.
van Vonderen IK et al: Disturbed vasopressin release in 4 dogs Reusch CE, et al: Measurements of growth hormone and insulin
with so-called primary polydipsia, / Vet Intern Med 13:419, like growth factor 1 in cats with diabetes mellitus, VetRec 158:195,
1999. 2006.
van Vonderen IK et al: Vasopressin response to osmotic stimulation Starkey SR et al: Investigation of serum IGF-I levels amongst dia
in 18 young dogs with polyuria and polydipsia, / Vet Intern Med betic and nondiabetic cats, / Feline Med Surg 6:149, 2004.
18:800, 2004.
PITUITARY DWARFISM
ENDOCRINE ALOPECIA Kooistra HS et al: Progestin-induced growth hormone (GH) pro
Ashley PF et al: Effect of oral melatonin administration on sex duction in the treatment of dogs with congenital G H deficiency,
hormone, prolactin, and thyroid hormone concentrations in Domest Anim Endocrinol 15:93, 1998.
adult dogs, J Am Vet Med Assoc 215:1111, 1999. Kooistra HS et al: Combined pituitary hormone deficiency in
Frank LA: Growth hormone-responsive alopecia in dogs, J Am Vet German Shepherd dogs with dwarfism, Domest Anim Endocrinol
Med Assoc 226:1494, 2005. 19:177, 2000.
C H A P T E R 50
Disorders of the
Parathyroid Gland
NET EFFECT
HORMONE BONE KIDNEY INTESTINE SERUM CA SERUM PO 4
FIG 50-1
A , S u r g i c a l site in a 12-year-old d o g with p r i m a r y h y p e r p a r a t h y r o i d i s m (PHP). A parathy
roid a d e n o m a (arrow) c a n b e seen in the thyroid l o b e . B, G r o s s a p p e a r a n c e of parathy
roid a d e n o m a (arrow) a n d thyroid l o b e after r e m o v a l from the d o g in A .
PTH, Parathyroid hormone; LSA, lymphosarcoma; PTHrp, parathyroid hormone-related peptide; ACTH, adrenocorticotropic hormone;
FIP, feline infectious peritonitis.
FIG 5 0 - 4
A , U l t r a s o u n d i m a g e of the left t h y r o i d l o b e of a n 12-year-old K e e s h o n d with h y p e r c a l c e
m i a . A mass is in the r e g i o n of the p a r a t h y r o i d g l a n d (arrow), a n d a n e e d l e has b e e n
inserted into the mass using ultrasound g u i d a n c e b e f o r e heat a b l a t i o n of the mass.
B, H e a t is b e i n g a d m i n i s t e r e d to the mass, c a u s i n g h y p e r e c h o g e n i c i t y of the mass (arrow).
parathyroid gland (Fig. 50-3). In 185 dogs with P H P none the parathyroid glands appear enlarged or i f all appear small,
had serum P T H concentration below the reference range, the diagnosis of P H P must be questioned and hypercalcemia
45% were in the lower half of the reference range (2.3 to stemming from occult neoplasia or P T H production by a
7.9 pmol/L), 28% were in the upper half of the reference range parathyroid tumor i n an ectopic site (e.g., cranial mediasti
(8.0 to 13.0 p m o l / L ) , and 27% had increased serum P T H num) or by a nonparathyroid tumor should be considered.
concentrations (13 to 121 pmol/L; Feldman et a l , 2005). Chemical (i.e., ethanol) and heat ablation of abnormal
parathyroid tissue performed under ultrasound guidance are
Treatment also effective treatments for P H P (Fig. 50-4). Surgery is
Surgical removal of the abnormal parathyroid tissue is the avoided, anesthetic time is significantly reduced, and there
treatment of choice. Slatter (2003) and Fossum (2007) have are no incisions or issues related to w o u n d healing. However,
adequately described the surgical techniques for the thyro the management of the dog after chemical or heat ablation
parathyroid complex (see Suggested Readings). Almost all is identical to the management after surgical removal of the
dogs and cats with P H P have a solitary, easily identified parathyroid mass. In a recent retrospective study surgical
parathyroid adenoma (see Fig. 50-1). Enlargement of more removal, heat ablation, and chemical ablation of the para
than one parathyroid gland indicates the presence of either thyroid mass were successful i n controlling hypercalcemia in
multiple adenomas or parathyroid hyperplasia. If none of 94%, 90%, and 72% of dogs treated for P H P , respectively
(Rasor et al., 2007). N o t all dogs are candidates for chemical therapy can be initiated 24 to 36 hours before surgery or
or heat ablation. Surgery is indicated i f more than one para ablation because o f the k n o w n delay i n the onset of vitamin
thyroid mass is identified with cervical ultrasound, the para D's action.
thyroid mass is less than 4 m m or greater than 15 m m i n Therapy for hypocalcemia includes the administration of
m a x i m u m width, a parathyroid mass is not identified, intravenous calcium to control immediate clinical signs and
the parathyroid mass is too close to the carotid artery, or the long-term oral administration o f calcium and vitamin D
cystic calculi are identified with abdominal radiographs or supplements to maintain low-normal blood calcium con
ultrasound. centrations while the parathyroid gland atrophy resolves.
A n attempt must be made to ensure that at least one (See Chapter 55 and Box 55-7 for details about the manage
parathyroid gland remains intact to maintain calcium ment of hypocalcemia.) The goal of calcium and vitamin D
homeostasis and prevent permanent hypocalcemia. Removal therapy is to maintain the serum calcium concentration
or ablation o f the parathyroid tumor results i n a rapid within the l o w to l o w - n o r m a l range (9 to 10 mg/dl). M a i n
decline i n circulating P T H and a decrease i n serum calcium. taining the serum calcium concentration i n the low-normal
In the early stages of P H P the remaining parathyroid glands range prevents development of clinical signs of hypocalce
may secrete P T H i n response to the decrease i n serum mia, minimizes the risk o f hypercalcemia, and stimulates a
calcium, thereby preventing development o f severe hypocal return o f function i n the remaining atrophied parathyroid
cemia. In dogs with more advanced P H P , atrophy o f the glands. Once the parathyroid glands regain control of calcium
normal parathyroid glands may prevent a response to the homeostasis and the serum calcium concentration is stable
decrease i n serum calcium, leading to severe hypocalcemia i n the dog or cat i n the home environment, the calcium and
and clinical signs within 7 days o f surgery or ablation. In vitamin D supplements can be gradually withdrawn over a
these dogs intravenous and oral calcium and oral vitamin period o f 3 to 6 months. This gradual withdrawal allows time
D therapy must be initiated to correct and/or prevent for the parathyroid glands to become fully functional and
hypocalcemia. thereby prevents hypocalcemia. V i t a m i n D therapy is with
There are two approaches for managing the dog (and cat) drawn by gradually increasing the number o f days between
once the parathyroid t u m o r has been removed with surgery administrations. The dosing interval should be increased by
or ablation. One approach is to arbitrarily treat all dogs with 1 day every 2 to 3 weeks, after the serum calcium concentra
oral calcium and vitamin D at the time the parathyroid tion has been measured and found to be 9 mg/dl or greater.
t u m o r is removed, and another approach is to w i t h h o l d V i t a m i n D therapy can be discontinued once the dog or cat
calcium and vitamin D therapy until the serum calcium is clinically normal, the serum calcium concentration is
concentration decreases below a safe concentration, typically stable between 9 and 11 mg/dl, and the vitamin D dosing
a serum calcium or ionized calcium concentration of 9.0 m g / interval is every 7 days.
dl and 0.9 m m o l / L , respectively, and before clinical signs o f
hypocalcemia develop. Regardless o f w h i c h approach is Prognosis
taken, serum total or ionized calcium should be monitored The prognosis for dogs and cats undergoing surgical or abla
once or twice a day until the serum calcium concentration tion therapy for P H P is excellent, assuming severe hypocal
is stable and i n the reference range. I prefer to w i t h h o l d cemia is avoided postoperatively and P H P is caused by a
calcium and v i t a m i n D therapy i n dogs i n w h i c h I suspect parathyroid adenoma. Hypercalcemia may recur weeks to
parathyroid gland atrophy is m i l d and calcium and vitamin months after surgery i n dogs and cats with P H P caused by
D therapy may not be needed. The higher the preoperative parathyroid hyperplasia i f one or more parathyroid glands
serum calcium concentration or the more chronic the hyper have been left i n situ.
calcemic condition, or both, the more likely the dog will
become clinically hypocalcemic after removal o f the abnor
mal parathyroid gland or glands. As a general rule, I do not
PRIMARY HYPOPARATHYROIDISM
initially treat hyperparathyroid dogs with oral calcium and
vitamin D i f the serum calcium or ionized calcium concen Etiology
tration before surgery or ablation is less than 14 mg/dl or
Primary hypoparathyroidism develops as a result of an abso
1.6 m m o l / L , respectively, and hypercalcemia has been present
lute or relative deficiency i n the secretion of P T H . This
for less than 6 months. Serum calcium or ionized calcium
deficiency ultimately causes hypocalcemia and hyperphos
concentrations greater than 14 m g / d l and 1.6 m m o l / L ,
phatemia because o f a loss of the effects o f P T H on bone,
respectively, and hypercalcemia that has been present for
kidney, and intestine (see Table 50-1). The major signs of
greater than 6 months suggest the existence o f significant
hypoparathyroidism are directly attributable to the decreased
atrophy o f the remaining parathyroid glands and a high
concentration o f ionized calcium i n the blood, which leads
probability for the development o f signs o f hypocalcemia
to increased neuromuscular activity.
after surgery or ablation. In these dogs oral calcium and
Spontaneous primary hypoparathyroidism is uncommon
vitamin D therapy is started at the time P H P is treated. In
i n dogs and cats. M o s t cases are classified as idiopathic (i.e.,
dogs with severe hypercalcemia (total calcium or ionized
there is no evidence of trauma, malignant or surgical destruc
calcium >18 m g / d l and 2.0 m m o l / L , respectively), vitamin D
tion, or other obvious damage to the neck or parathyroid
glands). The glands are difficult to locate visually and show
microscopic evidence o f atrophy. Histologic evaluation o f
the parathyroid gland may reveal a diffuse lymphocytic, Clinical Signs of Primary Hypoparathyroidism in Dogs
plasmacytic infiltration and fibrous connective tissue, sug
Nervousness
gesting an underlying immune-mediated cause o f the
Generalized seizures
disorder.
Rear leg cramping or pain
Iatrogenic hypoparathyroidism after performance o f
Focal muscle fasciculations, twitching
bilateral thyroidectomy for the treatment o f hyperthyroid Ataxia, stiff gait
ism is c o m m o n i n cats. The parathyroid tissue i n such Facial rubbing (intense)
animals may be excised or traumatized, or its b l o o d supply Aggressive behavior
may be compromised during surgery. This form o f hypo Panting
parathyroidism may be transient or permanent, depending Weakness
on the viability o f the parathyroid gland or glands saved Inappetence
at the time of surgery. O n l y one viable parathyroid Listlessness, lethargy
gland is needed to maintain a n o r m a l serum calcium Biting, licking paws (intense)
concentration.
Transient hypoparathyroidism may develop secondary to
severe magnesium depletion (serum magnesium concentra
tion <1.2 mg/dl). Severe magnesium depletion may suppress clinical hypocalcemia are interspersed w i t h relatively n o r m a l
P T H secretion without parathyroid destruction, increase periods, lasting minutes to days. Interestingly, hypocalcemia
end-organ resistance to P T H , and impair the synthesis o f the persists during these clinically " n o r m a l " periods.
active form o f vitamin D (i.e., calcitriol). The end result is
mild hypocalcemia and hyperphosphatemia. Magnesium PHYSICAL E X A M I N A T I O N
repletion reverses the hypoparathyroidism. Serum magne The most c o m m o n physical examination findings are related
sium concentrations in dogs and cats w i t h spontane to muscular tetany and include a stiff gait; muscle rigidity; a
ous primary hypoparathyroidism usually have been n o r m a l tense, splinted abdomen; and muscle fasciculations. Fever,
when measured. (See Chapter 55 for more information o n panting, and nervousness, often so pronounced that they
magnesium.) interfere w i t h the examination, are also c o m m o n . Potential
cardiac abnormalities include bradycardia, paroxysmal
Clinical Features tachyarrhythmias, muffled heart sounds, and weak femoral
pulses. Cataracts have been noted i n a few dogs and cats w i t h
SIGNALMENT primary hypoparathyroidism. Cataracts were small, punc
The age at which the clinical signs o f hypoparathyroidism tate-to-linear, white opacities that were randomly distrib
appear in dogs ranges from 6 weeks to 13 years, w i t h a mean uted i n the anterior and posterior cortical subcapsular region
of 4.8 years. There may be a sex-related predisposition i n of the lens; there was no loss of vision. The physical examina
female dogs. There is no apparent breed-related predisposi tion is occasionally normal, despite the previous history o f
tion, although T o y Poodles, Miniature Schnauzers, Labrador neuromuscular disorders.
Retrievers, German Shepherd Dogs, and Terriers are c o m
monly affected breeds. However, this increased prevalence Diagnosis
may merely reflect the popularity o f these breeds. O n l y a few Primary hypoparathyroidism should be suspected i n a dog
cases of naturally acquired primary hypoparathyroidism i n or cat w i t h persistent hypocalcemia, hyperphosphatemia,
cats have been reported. T o date, these cats have been young and n o r m a l renal function. The serum calcium concentra
to middle-aged (6 months to 7 years), o f several breeds, and tion is usually less than 7 mg/dl, the serum ionized calcium
usually male. is usually less than 0.8 m m o l / L , and the serum phosphorus
is usually greater than 6 mg/dl. L o w serum calcium and high
CLINICAL SIGNS serum phosphorus concentrations can also be encountered
The clinical signs and physical examination findings i n dogs during nutritional and renal secondary hyperparathyroid
and cats with primary hypoparathyroidism are similar. The ism, after phosphate-containing enema, and during tumor
major clinical signs are directly attributable to hypocalcemia, lysis syndrome. The diagnosis o f primary hypoparathyroid
most notably its effects on the neuromuscular system. N e u ism is established by identifying an undetectable serum P T H
romuscular signs include nervousness, generalized seizures, concentration i n the face o f severe hypocalcemia i n a dog or
focal muscle twitching, rear-limb cramping or tetany, ataxia, cat i n which other causes o f hypocalcemia have been ruled
and weakness (Box 50-2). Additional signs include lethargy, out (Table 50-3). M o s t causes o f hypocalcemia can be
inappetence, intense facial rubbing, and panting. The onset identified after evaluation of the history, findings o n physical
of clinical signs tends to be abrupt and severe and to occur examination, and results o f routine b l o o d and urine tests
more frequently during exercise, excitement, and stress. and an abdominal ultrasound. The history and physical
Clinical signs also tend to occur episodically. Episodes o f examination findings are essentially unremarkable i n dogs
TABLE 50-3
Primary hypoparathyroidism History, serum PTH concentration, rule out other causes
Idiopathic
Posthyroidectomy
Puerperal tetany History
Renal failure Serum biochemistry panel, urinalysis
Acute
Chronic
Ethylene glycol toxicity History, urinalysis
Acute pancreatitis Physical findings, abdominal ultrasound, serum PLI
Intestinal malabsorption syndromes History, digestion and absorption tests, intestinal biopsy
Hypoproteinemia or hypoalbuminemia Serum biochemistry panel
Hypomagnesemia Serum total and ionized M g
Nutritional secondary hyperparathyroidism Dietary/History
Tumor lysis syndrome History
Phosphate-containing enemas History
Anticonvulsant medications History
N a H C O 3 administration History
Laboratory error Repeat calcium measurement
and cats with primary hypoparathyroidism, other than those two phases. The first phase (i.e., acute therapy) should ini
findings caused by hypocalcemia. The only relevant abnor tially control hypocalcemic tetany and involves the slow
malities identified o n routine b l o o d and urine tests are severe administration of calcium gluconate (not calcium chloride)
hypocalcemia and, i n most dogs and cats, hyperphosphate intravenously, to effect. Once clinical signs of hypocalcemia
mia. The serum total protein, albumin, urea nitrogen, are controlled, calcium gluconate should then be adminis
creatinine, and magnesium concentrations are normal. tered by continuous intravenous infusion until orally admin
A b d o m i n a l ultrasound is also normal. istered calcium and vitamin D therapy (i.e., second phase of
Measurement of serum P T H concentration helps confirm therapy) becomes effective. C a l c i u m gluconate is initially
a diagnosis of primary hypoparathyroidism. B l o o d for P T H administered at a dose of 60 to 90 mg/kg per day (approxi
determination should be obtained before the initiation of mately 2.5 m l / k g of 10% calcium gluconate added to the
calcium and vitamin D therapy while the animal is still infusion solution and administered every 6 to 8 hours).
hypocalcemic. The two-site I R M A assay system is currently C a l c i u m should not be added to solutions containing
used by most veterinary laboratories and is considered the lactate, bicarbonate, acetate, or phosphates because of the
most reliable assay system for P T H quantification i n dogs potential for precipitation problems. Serum calcium concen
and cats. Interpretation of the serum P T H concentration trations should be monitored twice a day and the rate of
must be done i n conjunction with the serum calcium con infusion adjusted as needed to control clinical signs and
centration. If the parathyroid gland is functioning normally, maintain the serum calcium concentration greater than
the serum P T H concentration should be increased i n the 8 mg/dl.
face o f hypocalcemia because of the stimulatory effects of a The second phase of therapy (i.e., maintenance therapy)
decreased serum ionized calcium concentration o n parathy should maintain the blood calcium concentration between
r o i d gland function. A low-to-undetectable serum P T H con 8 and 10 m g / d l through the daily administration of vitamin
centration i n a hypocalcemic dog or cat is strongly suggestive D and calcium. These calcium concentrations are above the
of primary hypoparathyroidism (see Fig. 50-3). Dogs and level at which there is a risk for clinical hypocalcemia and
cats with nonparathyroid-induced hypocalcemia should below the level at which hypercalciuria (risk of calculi for
have n o r m a l or high serum P T H concentrations; the excep mation) or severe hypercalcemia and hyperphosphatemia
tions are those disorders causing severe hypomagnesemia. (risk of nephrocalcinosis and renal failure) may occur. M a i n
tenance therapy should be initiated once the hypocalcemic
Treatment tetany is controlled with intravenous calcium therapy. The
The therapy for primary hypoparathyroidism involves the onset of action of vitamin D varies depending on the for
administration of vitamin D and calcium supplements (see mulation of vitamin D that is administered. In general, 1,25-
Chapter 55 and B o x 55-7). Therapy is typically divided into dihydroxy-vitamin D (calcitriol) has the fastest onset of
3
action and is preferred for treating hypoparathyroidism. The of preventing extremes in the concentration and the better
initial dosage of calcitriol is 0.02 to 0.03 (g/kg/day. Dogs and the chance of a normal life expectancy.
cats should ideally remain hospitalized until their serum
calcium concentration remains between 8 and 10 mg/dl Suggested Readings
without parenteral support. Serum calcium concentrations
Feldman EC, Nelson RW: Canine and feline endocrinology and
should be monitored weekly, with the vitamin D dose
reproduction, ed 3, St Louis, 2004, WB Saunders.
adjusted to maintain a concentration of 8 to 10 mg/dl. The Fossum TW: Small animal surgery, ed 3, St Louis, 2007, Mosby.
aim of therapy is to prevent hypocalcemic tetany and not Slatter D: Textbook ofsmall animal surgery, ed 3, Philadelphia, 2003,
induce hypercalcemia. Serum calcium concentrations o f W B Saunders.
more than 10 mg/dl are unnecessary to prevent tetany and
PRIMARY HYPERPARATHYROIDISM
only increase the likelihood of unwanted hypercalcemia.
Bolliger AP et al: Detection of parathyroid hormone-related protein
Once the serum calcium concentration has stabilized,
in cats with humoral hypercalcemia of malignancy, Vet Clin Path
attempts can be made to slowly taper the dose of oral calcium
31:3, 2002.
and then vitamin D to the lowest dose that maintains the Feldman EC et al: Pretreatment clinical and laboratory findings in
serum calcium concentration between 8 and 10 mg/dl. dogs with primary hyperparathyroidism: 210 cases (1987-2004),
Vitamin D is critical for establishing and maintaining a J Am Vet Med Assoc 227:756, 2005.
normal blood calcium concentration. M o s t dogs and cats Gear RNA et al: Primary hyperparathyroidism in 29 dogs: diagno
with primary hypoparathyroidism require permanent sis, treatment, outcome and associated renal failure, / Small Anim
vitamin D therapy. The calcium supplement can often be Pract 46:10, 2005.
gradually tapered over a period of 2 to 4 months and then Goldstein RE et al: Inheritance, mode of inheritance, and candidate
stopped once the animal's serum calcium concentration is genes for primary hyperparathyroidism in Keeshonden, / Vet
Intern Med 21:199, 2007.
stable between 8 and 10 mg/dl. Calcium i n the diet is often
Long C D et al: Percutaneous ultrasound-guided chemical parathy
sufficient for maintaining the calcium needs of the animal.
roid ablation for treatment of primary hyperparathyroidism in
Supplementing the diet with calcium-rich foods (e.g., dairy
dogs, J Am Vet Med Assoc 215:217, 1999.
products) helps ensure an adequate source of dietary calcium. Pollard RE et al: Percutaneous ultrasonographically guided radio-
Once the animal's serum calcium concentration is stable and frequency heat ablation for treatment of primary hyperparathy
maintenance therapy has become established, reevaluation roidism in d o g s , / A m Vet Med Assoc 218:1106, 2001.
of the serum calcium concentration every 3 to 4 months is Rasor L et al: Retrospective evaluation of three treatment methods
advisable. for primary hyperparathyroidism in dogs, J Am Anim Hosp Assoc
43:70, 2007.
Prognosis Tebb AJ et al: Canine hyperadrenocorticism: effects of trilostane on
The prognosis depends on the dedication of the client. The parathyroid hormone, calcium and phosphate concentration,
/ Small Anim Pract 46:537, 2005.
prognosis is excellent if proper therapy is instituted and
timely reevaluations are performed. Proper management PRIMARY HYPOPARATHYROIDISM
requires close monitoring of the serum calcium concentra Barber PJ: Disorders of the parathyroid glands, / Pel Med Surg
tion. The more frequent the rechecks, the better the chance 6:259, 2004.
C H A P T E R 51
Disorders of the
Thyroid Gland
Primary Hypothyroidism
Lymphocytic thyroiditis
Idiopathic atrophy
Neoplastic destruction
Iatrogenic
Surgical removal
Antithyroid medications
Radioactive iodine treatment
Drugs (e.g., sulfamethoxazole)
Secondary Hypothyroidism
Pituitary malformation
Pituitary cyst
Pituitary hypoplasia
Pituitary destruction
Neoplasia
Pituitary thyrotropic cell suppression
Naturally acquired hyperadrenocorticism
Euthyroid sick syndrome
Iatrogenic causes
FIG 51-1
The hypothalamic-pituitary-thyroid gland axis. TRH, Thyrotro Drug therapy, most notably glucocorticoids
pin-releasing hormone; TSH, thyrotropin; T , thyroxine;T
4
Radiation therapy ,3,5,3'-triiodothyronine; rT , 3,3',5'-triio
3 3
Tertiary Hypothyroidism
Congenital hypothalamic malformation (?)
Acquired destruction of hypothalamus (?)
disorder or represent an end stage of autoimmune l y m p h o
Congenital Hypothyroidism
cytic thyroiditis.
Secondary hypothyroidism results from failure of pitu Thyroid gland dysgenesis (aplasia, hypoplasia, ectasia)
itary thyrotrophs to develop (pituitary hypoplasia causing Dyshormonogenesis: iodine organification defect
Deficient dietary iodine intake
pituitary dwarfism; see Chapter 49) or from dysfunction
within the pituitary thyrotropic cells causing impaired secre
tion of thyroid-stimulating hormone (TSH) and a "second
ary" deficiency i n thyroid hormone synthesis and secretion. recessive fashion i n the family of Giant Schnauzers. Develop
Follicular atrophy in the thyroid gland gradually develops ment of an enlarged thyroid gland (i.e., goiter) depends o n
owing to lack of T S H . Secondary hypothyroidism could also the etiology. If the hypothalamic-pituitary-thyroid gland
result from destruction of pituitary thyrotrophs (e.g., p i t u axis is intact (e.g., as occurs with an iodine organification
itary neoplasia [rare]) or suppression of thyrotroph function defect), goiter w i l l develop, and i f it is not intact (e.g., as
by hormones or drugs (e.g., glucocorticoids [common]; see occurs with pituitary T S H deficiency), goiter w i l l not
Box 51-1). develop.
Tertiary hypothyroidism is a deficiency i n the secretion
of thyrotropin-releasing hormone ( T R H ) by peptidergic Clinical Features
neurons i n the supraoptic and paraventricular nuclei of Clinical signs of the more c o m m o n forms of primary hypo
the hypothalamus. Lack of T R H secretion should cause a thyroidism usually develop during middle age (i.e., 2 to 6
deficiency in T S H secretion and secondary follicular atrophy years). Clinical signs tend to develop at an earlier age i n
in the thyroid gland. Tertiary hypothyroidism has not been breeds at increased risk than i n other breeds (see Table 51-1).
reported i n dogs. There is no apparent sex-related predilection.
Congenital primary hypothyroidism is u n c o m m o n i n C l i n i c a l signs are quite variable and depend i n part on the
dogs and has been caused by deficient dietary iodine intake, age of the dog at the time a deficiency i n thyroid hormone
dyshormonogenesis (i.e., an iodine organification defect), develops (Box 51-2). Clinical signs may also differ between
and thyroid dysgenesis. Secondary hypothyroidism resulting breeds. For example, truncal alopecia may dominate i n some
from an apparent deficiency of T S H has also been reported breeds, whereas thinning of the haircoat dominates i n other
in a family of Giant Schnauzers and i n a Boxer. Pedigree breeds. In adult dogs the most consistent clinical signs of
analysis showed that it may be inherited i n an autosomal hypothyroidism result from decreased cellular metabolism
TABLE 51-1
Pointer 3.61
English Setter 3.44
English Pointer 3.31
S k y e Terrier 3.04
G e r m a n W i r e h a i r e d Pointer 2.72
O l d English S h e e p d o g 2.65
Boxer 2.37
Maltese 2.25
Kuvasz 2.18
Petit Basset G r i f f o n V e n d e e n 2.16
A m e r i c a n Staffordshire Terrier 1.84
Beagle 1.79
A m e r i c a n Pit Bull Terrier 1.78
Dalmatian 1.74
Giant Schnauzer 1.72
Rhodesian Ridgeback 1.72
G o l d e n Retriever 1.70
Shetland S h e e p d o g 1.69
C h e s a p e a k e B a y Retriever 1.56
Siberian Husky 1.45
Brittany S p a n i e l 1.42
Borzoi 1.39
Australian Shepherd 1.28
D o b e r m a n Pinscher 1.24
Malamute 1.22
Cocker Spaniel 1.17
Mixed 1.05
and its effects o n the dog's mental status and activity. Most
dogs with hypothyroidism show some mental dullness, leth
FIG 51-2
argy, exercise intolerance or unwillingness to exercise, and a
H i s t o l o g i c section of a t h y r o i d g l a n d from a healthy d o g
(A), from a d o g with l y m p h o c y t i c thyroiditis a n d hypothy
propensity to gain weight without a corresponding increase
r o i d i s m (B), a n d from a d o g with i d i o p a t h i c a t r o p h y of the in appetite or food intake. These signs are often gradual in
thyroid g l a n d a n d h y p o t h y r o i d i s m (C). N o t e the m o n o n u onset, subtle, and not recognized by the client until after
c l e a r cell infiltration, disruption of the n o r m a l architecture, thyroid hormone supplementation has been initiated. A d d i
a n d loss of c o l l o i d - c o n t a i n i n g follicles in B a n d the small tional clinical signs o f hypothyroidism typically involve the
s i z e of the g l a n d , d e c r e a s e in follicular s i z e a n d c o l l o i d
skin and, less commonly, the neuromuscular system.
content, a n d lack of a cellular infiltration in C, c o m p a r e d
with A . (A a n d B, H e m a t o x y l i n a n d e o s i n stain; m a g n i f i c a
tion x 2 5 0 ; C, h e m a t o x y l i n a n d eosin stain; m a g n i f i c a t i o n
DERMATOLOGIC SIGNS
x 4 0 ) . (From F e l d m a n E C , N e l s o n R W : Canine and feline Alterations i n the skin and haircoat are the most common
endocrinology and reproduction, e d 3 , St Louis, 2 0 0 4 , W B observable abnormalities in dogs with hypothyroidism. The
Saunders.) classic cutaneous signs include bilaterally symmetric, non
pruritic truncal alopecia that tends to spare the head and
extremities (Fig. 51-3). Alopecia may be local or generalized
and symmetric or asymmetric, it may involve only the tail
(i.e., "rat tail"), and it often initially starts over sites of wear
Clinical Manifestations of Hypothyroidism in the Adult Dog
Metabolic
Ataxia
Lethargy* Circling
Mental dullness* Vestibular signs
Inactivity* Facial nerve paralysis
Weight g a i n * Seizures
Cold intolerance Laryngeal paralysis (?)
Dermatologic Ocular
Endocrine alopecia* Corneal lipid deposits
Symmetric or asymmetric Corneal ulceration
"Rat tail" Uveitis
Dry, brittle haircoat
Hyperpigmentation Cardiovascular
Seborrhea sicca or oleosa or dermatitis* Decreased contractility
Pyoderma* Bradycardia
Otitis externa Cardiac arrythmias
Myxedema
Gastrointestinal
Reproductive Esophageal hypomotility (?)
Persistent anestrus Diarrhea
Weak or silent estrus Constipation
Prolonged estrual bleeding
Inappropriate galactorrhea or gynecomastia
Hematologic
Testicular atrophy (?) Anemia*
Loss of libido (?) Hyperlipidemia*
Coagulopathy
Neuromuscular
Weakness*
Behavior Abnormalities (?)
Knuckling
* Common.
and friction. Although nonpruritic endocrine alopecia is not dermis, b i n d water, and cause skin to thicken. Referred to as
pathognomonic for hypothyroidism (see Chapter 49), hypo myxedema, the condition causes the skin to thicken pre
thyroidism is certainly the most likely diagnosis i n an affected dominantly i n the forehead and face of dogs, resulting i n
dog with lethargy, weight gain, and no polyuria-polydipsia. rounding of the temporal region of the forehead, puffiness
Seborrhea and pyoderma are also c o m m o n signs of and thickening of the facial skin folds, and drooping of the
hypothyroidism. Depletion of thyroid hormone suppresses upper eyelids.
humoral immune reactions, impairs T-cell function, and
reduces the number of circulating lymphocytesdefects N E U R O M U S C U L A R SIGNS
that can be reversed by exogenous thyroid hormone therapy. Neurologic signs may be the predominant problem i n
A l l forms of seborrhea (i.e., sicca, oleosa, dermatitis) are some dogs with hypothyroidism (see B o x 51-2). Hypothy
possible. Seborrhea and pyoderma may be focal, multifocal, roidism-induced segmental demyelination and axonopathy
or generalized. Because both frequently result i n pruritus, may cause signs referable to the central or peripheral ner
hypothyroid dogs with secondary pyoderma or seborrhea vous system. Clinical signs referable to the central nervous
may initially be brought to the veterinarian because of a system ( C N S ) may also appear after mucopolysaccharide
pruritic skin disorder. accumulates i n the perineurium and endoneurium or
The haircoat i n dogs with hypothyroidism is often dull, after cerebral atherosclerosis, transient ischemia or brain
dry, and easily epilated. H a i r regrowth is slow. Hyperkera infarctions, or the development o f severe hyperlipidemia
tosis leads to the development of scales and dandruff. and include seizures, ataxia, circling, weakness, and pro
Variable degrees of hyperpigmentation may also be noted. prioceptive and postural reaction deficits. These signs are
Chronic otitis externa has been noted i n some dogs with often present i n conjunction with vestibular signs (e.g., head
hypothyroidism. In severe cases of hypothyroidism acidic tilt, nystagmus) or facial nerve paralysis. Peripheral neu
and neutral mucopolysaccharides may accumulate i n the ropathies include facial nerve paralysis, weakness, and
FIG 51-3
A , A 6-year-old f e m a l e s p a y e d S a m o y e d with h y p o t h y r o i d i s m ; a dry, lusterless h a i r c o a t ;
h y p e r p i g m e n t a t i o n ; a n d e n d o c r i n e a l o p e c i a . B a n d C, A 2-year-old f e m a l e s p a y e d
G o l d e n Retriever with h y p o t h y r o i d i s m , diffuse thinning of the h a i r c o a t , a n d d e v e l o p m e n t
of a "rat t a i l . " In both d o g s note the truncal distribution of the d e r m a t o l o g i c p r o b l e m with
s p a r i n g of the h e a d a n d distal extremities. D, A n 8-year-old m a l e castrated B e a g l e with
h y p o t h y r o i d i s m , obesity, a n d m y x e d e m a of the f a c e . N o t e the " t r a g i c f a c i a l e x p r e s s i o n "
a n d " m e n t a l d u l l n e s s " evident from the d o g ' s f a c i a l e x p r e s s i o n . E, A 7-month-old f e m a l e
M a l a m u t e with c o n g e n i t a l h y p o t h y r o i d i s m . N o t e the retention of the p u p p y h a i r c o a t a n d
small stature of the d o g .
knuckling or dragging of the feet, with excessive wear a variable and sometimes deleterious effect o n the b l o o d
of the dorsal part of the toenail. Muscle wasting may also concentration of v o n Willebrand factor i n euthyroid dogs
be evident, although myalgia is not c o m m o n . Thyroxine with v o n Willebrand's disease.
responsive unilateral forelimb lameness has also been A cause-and-effect relationship between hypothyroidism
observed in dogs. The relationship between hypothyroidism and behavioral problems (e.g., aggression) has not been well
and laryngeal paralysis or esophageal hypomotility remains established i n dogs. T o date, most reports have been anec
controversial, i n part because it is difficult to prove a cause- dotal and based o n improvement i n behavior following i n i
and-effect relationship between these disorders and because tiation of thyroid hormone treatment. A n inverse relationship
treatment of hypothyroidism often does not improve the between development o f aggression and serotonin activity i n
clinical signs caused by laryngeal paralysis or esophageal the C N S has been documented i n several species, including
hypomotility. dogs. Serotonin turnover and sympathetic activity i n the
C N S increase i n rats made hypothyroid after surgical thy
REPRODUCTIVE SIGNS roidectomy, dopamine receptor sensitivity is affected by
Historically, hypothyroidism was believed to cause lack of thyroid hormone i n rats, and thyroid hormone potentiates
libido, testicular atrophy, and oligospermia to azoospermia the activity of tricyclic antidepressants i n humans suffering
in male dogs. However, work by Johnson et al. (1999) i n from certain types of depression. These studies suggest that
Beagles failed to document any deleterious effect of experi thyroid hormone may have an influence on the serotonin-
mentally induced hypothyroidism on any aspect of male dopamine pathway i n the C N S , regardless of the functional
reproductive function. Although other classic clinical signs status o f the thyroid gland. The benefits, i f any, of using
and clinicopathologic abnormalities of hypothyroidism thyroid hormone to treat behavioral disorders such as aggres
developed i n dogs studied, libido, testicular size, and total sion i n dogs remain to be clarified.
sperm count per ejaculate remained normal. These findings
indicate that hypothyroidism may, at best, be an u n c o m m o n MYXEDEMA COMA
cause of reproductive dysfunction i n male dogs, assuming Myxedema coma is an u n c o m m o n syndrome of severe
that the Beagle is representative of other dog breeds. hypothyroidism characterized by profound weakness, hypo
Clinical experience has shown that hypothyroidism can thermia, bradycardia, and a diminished level of conscious
cause prolonged interestrus intervals and failure to cycle i n ness that can rapidly progress to stupor and then coma.
the bitch. Additional reproductive abnormalities include Physical findings include profound weakness; hypothermia;
weak or silent estrous cycles, prolonged estrual bleeding nonpitting edema of the skin, face, and jowls (i.e., myx
(which may be caused by acquired problems i n the coagula edema); bradycardia; hypotension; and hypoventilation.
tion system), and inappropriate galactorrhea and gyneco Laboratory findings may include hypoxemia, hypercarbia,
mastia. A n association between hypothyroidism and fetal hyponatremia, and hypoglycemia i n addition to the typical
resorption, abortion, and stillbirth has been suggested i n the findings of hyperlipidemia, hypercholesterolemia, and n o n -
bitch; however, published documentation of this association regenerative anemia. Serum thyroid hormone concentra
is lacking. Maternal hypothyroidism has also been suggested tions are usually extremely l o w or undetectable; serum T S H
to result i n the birth of weak puppies that die shortly after concentration is variable but typically increased. Treatment
birth. consists of intravenous levothyroxine (5 g/kg q12h) and
supportive care aimed at correcting hypothermia, hypo
MISCELLANEOUS CLINICAL SIGNS volemia, electrolyte disturbances, and hypoventilation. Once
Ocular, cardiovascular, gastrointestinal, and clotting abnor the dog has stabilized, oral levothyroxine can be started
malities are u n c o m m o n clinical manifestations of hypothy (see p. 741).
roidism (see Box 51-2). M o r e commonly, biochemical or
functional abnormalities of these organ systems are identified CRETINISM
in dogs exhibiting the more c o m m o n clinical signs of hypo Hypothyroidism i n puppies is termed cretinism. As the age
thyroidism. Echocardiography may identify a decrease i n of onset increases, the clinical appearance of animals with
cardiac contractility that is usually m i l d and asymptomatic cretinism merges imperceptibly with that o f adult hypothy
but that may become relevant during a surgical procedure roidism. Retarded growth and impaired mental development
requiring prolonged anesthesia and aggressive fluid are the hallmarks of cretinism (Box 51-3). Dogs with cretin
therapy. ism have a disproportionate body size, with large, broad
A reduction i n the activity of factor VIII-related antigen heads; thick, protruding tongues; wide, square trunks; and
(von Willebrand factor) activity has been inconsistently short limbs (Fig. 51-4). This is i n contrast to the proportion
documented i n dogs with hypothyroidism, and the develop ate dwarfism caused by growth hormone deficiency. Cretins
ment of clinical signs of a bleeding disorder i n hypothyroid are mentally dull and lethargic and do not show the typical
dogs is uncommon. A n evaluation of the coagulation cascade playfulness seen i n normal puppies. Persistence of the puppy
or von Willebrand factor activity is not indicated i n dogs haircoat, alopecia, inappetence, delayed dental eruption, and
with untreated hypothyroidism unless there are concurrent goiter are additional signs. Differential diagnoses for failure
bleeding problems. Thyroid hormone supplementation has to grow include endocrine (e.g., dwarfism) and nonendo-
crine causes (see B o x 49-4 and Fig. 49-11). The presence ing that lymphocytic thyroiditis may occur i n conjunction
of goiter is variable and dependent on the underlying with other immune-mediated endocrinopathies. Presum
etiology. ably, the immune-mediated attack is directed against anti
gens shared by the endocrine system. In human beings
A U T O I M M U N E POLYENDOCRINE autoimmune polyglandular syndrome type II (Schmidt's
SYNDROMES syndrome) is the most c o m m o n o f the immunoendocri
Because autoimmune mechanisms play an important role i n nopathy syndromes, and it usually consists of primary
the pathogenesis o f lymphocytic thyroiditis, it is not surpris- adrenal insufficiency, autoimmune thyroid disease, and
type 1 diabetes mellitus. A u t o i m m u n e polyendocrine syn
dromes are u n c o m m o n i n dogs and should be suspected
i n a dog found to have multiple endocrine gland failure.
Hypothyroidism; hypoadrenocorticism; and, to a lesser
BOX 51-3
extent, diabetes mellitus, hypoparathyroidism, and lympho
C l i n i c a l Signs o f C r e t i n i s m cytic orchitis are recognized combined syndromes. In most
affected dogs each endocrinopathy is manifested separately,
Disproportionate dwarfism
with additional disorders ensuing one by one after variable
Short, b r o a d skull
periods (months to years). Diagnostic tests and treatment
Shortened mandible
are directed at each disorder as it is recognized because it
Enlarged cranium
is not possible to reliably predict or prevent any of these
S h o r t e n e d limbs
Kyphosis problems. Immunosuppressive drug therapy is not indicated
M e n t a l dullness for animals with these syndromes because the adverse
Constipation effects o f immunosuppressive therapy and the difficulty
Inappetence posed by suppression of the immune destruction of affected
G a i t abnormalities endocrine glands outweigh the potential benefits o f such
D e l a y e d d e n t a l eruption therapy.
Alopecia
"Puppy haircoat" Clinical Pathology
Dry hair
The most consistent clinicopathologic findings in dogs with
Thick skin
hypothyroidism are hypercholesterolemia and hypertriglyc
Lethargy
eridemia; the latter is identified as lipemia. Hypercholester
Dyspnea
Goiter olemia is identified i n approximately 75% o f hypothyroid
dogs, and the cholesterol concentration can exceed 1000 mg/
including vacuolated and/or hypertrophied arrector p i l i most of the thyroid hormone secreted by the thyroid gland,
muscles, increased dermal m u c i n content, and thickened with only small quantities of 3,5,3'-triiodothyronine (T ) 3
dermis. A variable inflammatory cell infiltrate may be present and m i n o r amounts of 3,3',5'-triiodothyronine (reverse T 3
if a secondary pyoderma has developed. [rT ]) released. Once secreted into the circulation, more than
3
FIG 5 1 - 5
A , U l t r a s o u n d i m a g e of the n o r m a l - a p p e a r i n g left t h y r o i d l o b e (arrows) of a healthy a d u l t
G o l d e n Retriever. B, U l t r a s o u n d i m a g e of the left t h y r o i d l o b e (arrows) of a n a d u l t G o l d e n
Retriever d o g with p r i m a r y h y p o t h y r o i d i s m . N o t e the significant reduction in the s i z e of
the thyroid l o b e in the d o g with h y p o t h y r o i d i s m , c o m p a r e d with the t h y r o i d l o b e i m a g e
from the healthy d o g .
99% o f T is b o u n d to plasma proteins, which serves as a
4 deiodinated to form either T or r T , depending on the met
3 3
reservoir and buffer to maintain a steady concentration o f abolic demands o f the tissues at that particular time. T is 3
itary T S H secretion (see Fig. 51-1), and is capable o f entering hormone that induces physiologic effects.
cells throughout the body (Fig. 51-7). W i t h i n the cell f T is 4 A l l serum T , both protein b o u n d and free, comes from
4
C o m p a r i s o n of u l t r a s o n o g r a p h i c characteristics of the serum T are also available, are economical, quick, and easy
4
thyroid g l a n d in healthy small-, medium-, a n d l a r g e - b r e e d to perform, and allow the clinician to make recommenda
d o g s , Am J Vet Res 6 7 : 7 0 , 2 0 0 6 . ) tions the same day the dog (or cat) is evaluated. In a recent
FIG 5 1 - 7
Intracellular m e t a b o l i s m of free T to either T o r reverse T b y 5 ' - or 5 - m o n o d e i o d i n a s e ,
4 3 3
d o g s with h y p o t h y r o i d i s m , a n d 3 0 euthyroid d o g s with T fraction by RIA. The Diasorin 2-step f T assay uses two
4 4
(Kemppainen and Birchfield, 2006). For most laboratories is approximately 0.5 to 0.8 ng/dl (6 to 10 p m o l / L ) in dogs.
the lower limit of the reference range for serum T in dogs 4 Measurement o f serum f T is usually reserved for those
4
is approximately 0.8 to 1.0 g/dl (10 to 13 n m o l / L ) , although dogs with suspected hypothyroidism and a nondiagnostic
in some breeds the normal range may extend to as l o w as serum T test result, severe concurrent illness, or both. E D
4
0.5 g/dl (6 nmol/L) (see the discussion o f breed variations, assays for serum f T concentration have comparable sensitiv
4
p. 740). ity but higher specificity than assays for serum T concentra 4
Theoretically, the interpretation o f baseline serum T 4 tion. Similar studies have not been reported for the 2-step
concentration should be straightforward i n that dogs with RIA. Serum f T is more resistant to the suppressive effects
4
hypothyroidism should have low values compared with the of nonthyroidal illness and medications than serum T , 4
values in healthy dogs. Unfortunately, the serum T concen 4 although severe illness can cause serum f T concentrations 4
tration range i n hypothyroid dogs overlaps with that in to decrease below 0.5 ng/dl. In addition, serum T autoanti 4
pressed by a variety of factors, most notably nonthyroidal Interpretation o f serum fT test results is similar to that used
4
illness and medications (Table 51-2). Clinicians often find it to interpret serum T test results (see Table 51-3). Serum f T
4 4
difficult to judge the effect that extraneous factors, especially values greater than 1.5 ng/dl (20 p m o l / L ) are consistent with
concurrent illness, have on the serum T concentration. 4 euthyroidism; values less than 0.5 ng/dl (6.5 p m o l / L ) are
Because these variables can suppress a baseline serum T 4 supportive o f hypothyroidism, assuming the history, physi
concentration to less than 0.5 g/dl i n a euthyroid dog and cal examination, and results o f routine b l o o d work are con
hypothyroid dogs rarely have a serum T concentration 4 sistent with hypothyroidism and severe systemic illness is
Diagnostic Tests for Evaluating Thyroid Gland Function in the Dog
The decision to assess thyroid gland function should be Provides additional evidence for or against the diagnosis of
based on results of the history, physical examination, and hypothyroidism
results of routine blood work (complete blood count, serum False positive and false negative serum TSH test results are
biochemistry panel, urinalysis). common
Serum TSH should not be used, by itself, to diagnose hypo
Serum Thyroxine (T ) 4
thyroidism
Most commonly used initial screening test for hypothyroidism
Serum 3,5,3'-Triiodothyronine (T )
Normal serum T rules out hypothyroidism
4
3
Autoantibody Tests
Usually measured in dogs with nondiagnostic serum T test 4
results, severe nonthyroidal illness, or both; common com Common component of canine thyroid panels
ponent of canine thyroid panels Tests of thyroid gland pathology, not thyroid gland function
Normal serum IT4 rules out hypothyroidism Used to identify lymphocytic thyroiditis and explain unusual
Low serum fT does not, by itself, confirm hypothyroidism;
4 serum T and T test results
4 3
severe nonthyroidal illness and drugs can suppress serum Should never be used to diagnose hypothyroidism
fT to below the reference range
4
TABLE 51-2
Variables that May Affect Baseline Serum Thyroid Hormone Function Test Results in the Dog
FACTOR EFFECT
Breed
Sight hounds (e.g., Greyhounds) T and free T lower than normal range established for dogs; no difference for TSH
4 4
Surgery/anesthesia Decreased T 4
Concurrent illness* Decreased T and free T ; depending on illness, TSH may increase, decrease or
4 4
not change
Moderate/severe osteoarthritis N o effect on T , free T , or TSH
4 4
Hypothyroidism*
SERUM T CONCENTRATION
4 SERUM FT CONCENTRATION
4 PROBABILITY OF HYPOTHYROIDISM
* Interpretation based on lower end of the reference range for serum T and fT being 0.8 g/dl and 0.8 ng/dl, respectively, without regard
4 4
for breed of dog. The lower end of the reference range for serum T and fT may be as low as 0.5 g/dl and 0.5 ng/dl, respectively, for
4 4
some breeds such as sight hounds (e.g., Greyhounds) and Nordic breeds (e.g., Siberian Huskies).
Assuming that a severe systemic illness is not present.
not present; and values between 0.5 and 1.5 ng/dl are not what percentage o f these dogs progress to clinical hypothy
diagnostic. roidism. Clinical signs o f hypothyroidism are usually not
evident i n these dogs, presumably because serum T and 4
Baseline Serum TSH Concentration fT concentrations are i n the reference range. Treatment
4
Measurement of serum T S H provides information o n the with levothyroxine is not indicated. Rather, assessment
interaction between the pituitary and thyroid gland. In of thyroid gland function should be repeated i n 3 to 6
theory, serum T S H concentration should be increased i n months, especially i f antibody tests for lymphocytic thy
dogs with hypothyroidism. In dogs serum T S H can be mea roiditis are positive. If progressive destruction o f the
sured using immunoradiometric, chemiluminescent immu thyroid gland is occurring, serum T and f T concentrations
4 4
nometric, and enzyme i m m u n o m e t r i c assays. In one study w i l l gradually decrease and clinical signs w i l l eventually
the highest precision for canine T S H analysis was obtained develop.
with the chemiluminescent assay, although the correlation
between the three assays for measuring canine serum T S H TSH and TRH Stimulation Tests
was satisfactory (Marca et al., 2001). M o s t clinical laborato T S H and T R H stimulation tests evaluate the thyroid gland's
ries use a serum T S H concentration o f 0.6 n g / m l as the responsiveness to exogenous T S H and T R H administration,
upper limit of the reference range. The lower limit o f the respectively. The p r i m a r y advantage of these tests is that they
reference range is currently below the sensitivity o f these help differentiate between hypothyroidism and nonthyroidal
assays; differentiation between l o w and n o r m a l serum T S H illness i n dogs with low serum T and f T concentrations.
4 4
dogs with histologically confirmed hypothyroidism and concentration obtained before and 6 hours after rhTSH
increased i n euthyroid dogs with concurrent nonthyroidal administration. In a euthyroid dog serum T concentration 4
illness or dogs receiving drugs such as phenobarbital (Fig. should be 2.5 g/dl (30 n m o l / L ) 6 hours after rhTSH
51-9). In most studies the sensitivity and specificity o f the administration and the 6-hour p o s t - r h T S H serum T c o n 4
T S H assay has ranged from 63% to 87% and 82% to 93%, centration should be 1.5 times the baseline serum T c o n 4
respectively. Serum T S H test results should always be inter centration. Reconstituted r h T S H can be stored at 4 C for 4
preted i n conjunction with results o f serum T , f T , or both
4 4 weeks and at - 2 0 C for 8 weeks without loss o f biological
and should not be used alone i n the diagnosis o f hypothy activity.
roidism. Serum T S H test results increase the likelihood o f
euthyroidism or hypothyroidism when results are consistent Antibody Tests for Lymphocytic Thyroiditis
with results of serum T and f T tests. A n o r m a l serum T
4 4 4 Circulating thyroglobulin (Tg) and thyroid hormone ( T 3
tration occur i n the early stages o f primary hypothyroidism phocytic thyroiditis i n dogs. Tests for the presence o f Tg, T , 3
in humans. Although similar thyroid hormone and T S H and T autoantibodies i n the serum o f dogs can be used to
4
test results have been identified i n dogs, it is not k n o w n identify lymphocytic thyroiditis, to explain unusual serum
FIG 51-9
B o x plots of serum c o n c e n t r a t i o n s of thyrotropin (TSH) in 2 2 3 d o g s with n o n t h y r o i d a l
d i s e a s e stratified a c c o r d i n g to severity of d i s e a s e . For e a c h b o x plot T-bars represent the
m a i n b o d y of d a t a , w h i c h in most instances is e q u a l to the r a n g e . E a c h b o x represents a n
interquartile r a n g e (twenty-fifth to seventy-fifth percentile). The h o r i z o n t a l b a r in e a c h b o x
is the m e d i a n . O p e n circles represent outlying d a t a points. N u m b e r s in parentheses
i n d i c a t e the numbers of d o g s in e a c h g r o u p . S h a d e d a r e a is the n o r m a l r a n g e . (From
K a n t r o w i t z LB et a l : S e r u m total t h y r o x i n e , total triiodothyronine, free thyroxine, a n d
thyrotropin c o n c e n t r a t i o n s in d o g s with n o n t h y r o i d a l d i s e a s e , J Am Vet Med Assoc
219:765,2001.)
test for hypothyroidism caused by lymphocytic thyroiditis. typically have autoantibodies against Tg, but the converse is
Autoantibodies predominantly develop against Tg. T and 3 not true. As such, the better screening test for lymphocytic
T are haptens and not antigenic by themselves. T g is the
4 thyroiditis is the Tg autoantibody test. ELISAs for detection
protein that provides the antigenic stimulus. Because T and 3 of T g autoantibodies are sensitive and specific for identifica
T are attached to the T g molecule, autoantibodies develop
4 tion of Tg autoantibodies in dogs and are commercially
available. Results are reported as negative, positive, and The most c o m m o n factors that result i n lower baseline
inconclusive. thyroid hormone concentrations i n euthyroid dogs are non
A positive T g autoantibody test suggests the possibility of thyroidal illness (i.e., euthyroid sick syndrome), drugs (espe
lymphocytic thyroiditis but does not provide information on cially glucocorticoids, phenobarbital, and sulfonamide
the severity or progressive nature of the inflammatory antibiotics; see Table 51-2), and variation i n the reference
process. T g autoantibody is not a thyroid function test. Pos range between breeds (most notably sight hounds).
itive results increase the suspicion for hypothyroidism i f
serum T and fT concentrations are low but have no bearing
4 4
Nonthyroidal Illness
on generation of clinical signs if serum T and fT concentra
4 4
(Euthyroid Sick Syndrome)
tions are normal. T g autoantibodies should not be used Euthyroid sick syndrome refers to suppression of serum
alone i n the diagnosis of hypothyroidism. Dogs with con thyroid hormone concentrations i n euthyroid dogs i n
firmed hypothyroidism can be negative and euthyroid dogs response to concurrent illness. A decrease i n serum thyroid
can be positive for T g autoantibodies. Identification of T g hormone concentrations may result from a decline in T S H
autoantibodies would support hypothyroidism caused by secretion secondary to suppression of the hypothalamus or
lymphocytic thyroiditis i f the dog has clinical signs, physical pituitary gland, from decreased synthesis of T , from 4
findings, and thyroid hormone test results consistent with decreased concentration or b i n d i n g affinity of circulating
the disorder. Positive serum T and T autoantibody test
4 3 binding proteins (e.g., thyroid binding globulin), from i n h i
results are interpreted i n a similar manner. bition of the deiodination of T to T , or any combination
4 3
The value of serum T g autoantibodies as a marker for of these factors. The subsequent decrease in serum total T 4
eventual development of hypothyroidism remains to be and, i n many cases, f T concentrations is believed to repre
4
clarified. A 1-year prospective study found that approxi sent a physiologic adaptation by the body, with the purpose
mately 20% of 171 dogs with positive T g autoantibody being to decrease cellular metabolism during periods of
and normal fT and T S H test results developed changes
4 illness. It is not indicative of hypothyroidism, per se. Gener
in fT , T S H , or both test results consistent with hypothy
4 ally, the type and magnitude of most alterations i n serum
roidism; 15% reverted to a negative T g autoantibody test thyroid hormone concentrations are not unique to a specific
with no change i n fT and T S H test results; and 65% remained
4 disorder but reflect the severity of the illness or the catabolic
Tg autoantibody positive or had an inconclusive result state and appear to represent a c o n t i n u u m of changes. Sys
with no change in f T and T S H test results 1 year later
4 temic illness has more of an effect in lowering serum thyroid
(Graham et a l , 2001). Currently, a positive T g autoanti hormone concentrations than do, for example, dermatologic
body test is considered suggestive of lymphocytic thyroiditis disorders. In addition, the more severe the systemic illness,
and supports retesting thyroid gland function i n 3 to 6 the more suppressive the effect on the serum thyroid
months. hormone concentration (Fig. 51-10).
Testing for serum T or T g autoantibodies is indicated i n
4 Unfortunately, euthyroid dogs with concurrent illness can
dogs with unusual serum T values. T autoantibodies may
4 4 have serum T concentrations that often fall between 0.5 and
4
system used i n the R I A . Falsely low results are obtained i f more variable and probably depend i n part o n the patho
nonspecific separation methods are used (e.g., a m m o n i u m physiologic mechanisms involved i n the illness. In general,
sulfate, activated charcoal); falsely increased values are serum f T concentrations tend to be decreased i n dogs with
4
obtained i f single-step separation systems using antibody- concurrent illness but to a lesser extent than total T concen
4
ing from clinically relevant concentrations of thyroid dl i f severe illness is present. T S H concentrations may be
hormone antibody account for less than 1% of such results normal or increased depending, i n part, o n the effect of the
from commercial endocrine laboratories. Serum f T mea 4 concurrent illness on f T concentrations and o n pituitary
4
FUNCTION TESTS can easily exceed 1.0 n g / m l i n dogs with euthyroid sick
There are many factors that affect baseline thyroid hormone syndrome.
and endogenous T S H concentrations (see Table 51-2). Treatment of euthyroid sick syndrome should be aimed
Unfortunately, most of these factors decrease baseline thyroid at the concurrent illness. The serum thyroid hormone con
hormone concentrations and may increase endogenous T S H centrations return to n o r m a l once the concurrent illness is
in euthyroid dogs, potentially causing misdiagnosis of hypo eliminated. Treatment of euthyroid sick syndrome with
thyroidism i f the clinician accepts the results out of context. sodium levothyroxine is not recommended.
FIG 5 1 - 1 0
B o x plots of serum total T (A) a n d free T (B) c o n c e n t r a t i o n s in 2 2 3 d o g s with nonthyroi
4 4
should be suspected of affecting thyroid hormone test results, is variable but usually within the reference range. The mag
especially i f the history, clinical signs, and clinicopathologic nitude and duration o f suppression of serum thyroid
FIG 5 1 - 1 0 , cont'd
hormone concentrations depend on the type o f glucocorti exception are dogs receiving relatively high dosages of glu
coid, dosage, route of administration, and duration o f glu cocorticoids for prolonged periods to treat chronic steroid-
cocorticoid administration. The higher the dosage, the longer responsive disorders (e.g., immune-mediated diseases). In
the administration, and the more potent the glucocorticoid these dogs glucocorticoid-induced secondary hypothyroid
administered, the more severe the suppression o f serum ism may become clinical and require treatment with syn
thyroid hormone concentrations. If glucocorticoids have thetic levothyroxine.
been administered i n the recent past, assay of serum thyroid P h e n o b a r b i t a l . In dogs phenobarbital treatment at
hormone concentrations should be delayed or must be inter therapeutic dosages decreases serum T and fT concentra
4 4
preted carefully. Ideally, glucocorticoids should be discontin tions into the range consistent with hypothyroidism. A
ued and serum thyroid hormone and T S H concentrations delayed increase i n the serum T S H concentration may occur
assessed 4 to 8 weeks later. secondary to loss o f negative feedback as serum T and fT
4 4
Typically, the administration o f exogenous glucocorti concentrations decline. Increased serum T S H concentra
coids does not result i n clinical signs of hypothyroidism. The tions quickly return to the reference range after discontinu-
breeds may be as low as 0.4 g/dl and 0.4 ng/dl, respectively.
TABLE 51-4 Serum T and fT concentrations that are consistent with
4 4
Propylthiouracil
may be affected by thyroid hormone deficiency, but clinical
Decreased T and free T ; increased TSH
4 4
concentrations may take up to 4 weeks to return to pretreat initial screening test for thyroid gland function. It is impor
ment values. Potassium bromide treatment does not seem to tant to remember that serum T concentrations can be sup
4
T S H concentrations can increase above the reference range A low serum T concentration (ideally less than 0.5 g/dl
4
within 2 to 3 weeks after initiating sulfonamide therapy. [6 n m o l / L ] ) i n conjunction with hypercholesterolemia and
Clinical signs o f hypothyroidism can develop with chronic clinical signs strongly suggestive of the disease supports the
sulfonamide administration. The increase i n the serum diagnosis o f hypothyroidism, especially i f systemic illness is
T S H concentration occurs secondary to loss o f negative not present. The definitive diagnosis must then rely on
feedback as serum T and f T concentrations decline and can
4 4 response to trial therapy with synthetic levothyroxine. A d d i
lead to thyroid hyperplasia and goiter. Alterations i n results tional tests o f thyroid gland function are warranted i f the
of thyroid gland function tests may resolve w i t h i n 1 to 2 serum T concentration is less than 0.8 to 1.0 g/dl but clin
4
weeks or last as long as 8 to 12 weeks after cessation o f the ical signs and physical examination findings are not strongly
antibiotic. supportive o f the disease and hypercholesterolemia is not
present, i f severe systemic illness is present and the potential
Breed Variations for the euthyroid sick syndrome is high, or i f medications
Current reference ranges were established i n large popula k n o w n to decrease serum T concentration are being
4
but not T S H concentration is lower i n sight hounds, most T S H , and T g autoantibody provides a more informative
notably Greyhounds, and N o r t h e r n breeds such as the Sibe analysis o f the pituitary-thyroid axis and thyroid gland func
rian H u s k y and may be lower i n other breeds as well. The tion, can be used as the initial screening test for hypothyroid
lower end of the reference range for serum T and f T i n these 4 4 ism, and should be used when serum T concentration alone
4
fails to establish the diagnosis. L o w serum T and f T , and
4 4
DIAGNOSIS IN A PREVIOUSLY
increased serum T S H concentrations i n a dog with appropri TREATED D O G
ate clinical signs and clinicopathologic abnormalities strongly Occasionally, a clinician wants to determine i f a dog receiv
support the diagnosis o f hypothyroidism. Concurrent pres ing thyroid hormone supplementation is i n fact hypothy
ence of T g autoantibodies suggests lymphocytic thyroiditis roid. The exogenous administration o f thyroid hormone,
as the underlying etiology. either T or T , will suppress pituitary T S H secretion and
4 3
Unfortunately, discordant test results are c o m m o n . W h e n cause pituitary thyrotroph atrophy and subsequently thyroid
this occurs, the appropriateness of clinical signs, clinico gland atrophy i n a healthy euthyroid dog. Serum T , fT , and4 4
pathologic abnormalities, and clinician index of suspicion T S H concentrations are decreased or undetectable; the sever
become the most important parameters when determining ity o f the decrease is dependent on the severity of thyroid
whether to treat the dog with levothyroxine. Serum f T con 4
gland atrophy induced by the thyroid supplement. Serum T 4
centration measured using E D or the 2-step R I A is the most and f T results are often suggestive o f hypothyroidism, even
4
accurate test of thyroid gland function and carries the highest in a previously euthyroid dog, i f testing is performed within
priority, followed by serum T concentration. Results of T S H
4
a m o n t h o f discontinuing treatment. T h y r o i d hormone sup
concentration increase the likelihood o f euthyroidism or plementation must be discontinued and the pituitary-thyroid
hypothyroidism when T S H test results are consistent with axis allowed to regain function before meaningful baseline
results of serum fT , but T S H test results should not be used
4
serum thyroid hormone concentrations can be obtained.
as the sole indicator o f hypothyroidism. L o w serum f T and 4
The time between discontinuation o f thyroid hormone sup
normal T S H test results occur i n approximately 20% o f dogs plementation and acquisition o f meaningful test results
with hypothyroidism, and high T S H test results occur i n depends on the duration o f treatment, the dose and fre
euthyroid dogs with nonthyroidal illness and with medica quency of administration of the thyroid hormone supple
tions such as phenobarbital and sulfonamides (see Tables ment, and individual variability. As a general rule, thyroid
51-2 and 51-4). N o r m a l serum f T and high T S H may suggest
4
hormone supplements should be discontinued for a
early compensated hypothyroidism, but one has to wonder m i n i m u m o f 4 weeks, preferably 6 to 8 weeks, before thyroid
why clinical signs w o u l d develop when the serum f T con4
gland function is critically assessed.
centration is normal. Positive T g autoantibody findings
merely suggest the possibility of lymphocytic thyroiditis; T g DIAGNOSIS IN PUPPIES
autoantibody determination is not a thyroid function test. A n approach similar to that discussed i n the previous
Positive results increase the suspicion for hypothyroidism i f section is used to diagnose congenital hypothyroidism.
serum T or fT concentrations are low but have no bearing
4 4 However, serum T S H concentrations are dependent on
on the generation of clinical signs i f serum T and f T con
4 4 the etiology. T S H concentrations will be increased i n dogs
centrations are normal. W h e n faced with discordant test with primary dysfunction o f the thyroid gland (e.g.,
results, the clinician must decide whether to initiate trial iodine organification defect) and an intact hypothalamic-
therapy with synthetic levothyroxine or repeat the tests pituitary-thyroid gland axis. T S H concentrations will be
sometime in the futurea decision that I usually base o n the within the n o r m a l range or undetectable i n dogs with
appropriateness of clinical signs and results o f the f T mea
4 pituitary or hypothalamic dysfunction as the cause o f the
sured using E D or the 2-step R I A . hypothyroidism.
Admittedly, interpretation o f serum T , fT , and T S H
4 4
only when thyroid hormone supplementation does not The initial treatment and m o n i t o r i n g recommendations are
pose a risk to the patient. Response to trial therapy with summarized i n B o x 51-5. Synthetic levothyroxine is the
sodium levothyroxine is nonspecific. A dog that has a posi treatment o f choice for hypothyroidism. Its administration
tive response to therapy either has hypothyroidism or orally should result i n normal serum concentrations o f T , 4
"thyroid-responsive disease." Because o f its anabolic nature, T , and T S H , which attests to the fact that these products can
3
thyroid supplementation can create an effect i n a dog be converted to the more metabolically active T by periph
3
without thyroid dysfunction, especially regarding quality o f eral tissues. A sodium levothyroxine product approved for
the haircoat. Therefore, if a positive response to trial therapy use i n dogs is recommended. L i q u i d and tablet formulations
is observed, thyroid supplementation should be gradually are effective. The initial dosage is 0.02 mg/kg body weight
discontinued once clinical signs have resolved. If clinical (0.1 mg/10 lb) with a m a x i m u m initial dose o f 0.8 mg.
signs recur, hypothyroidism is confirmed and the supple Twice-daily administration is recommended initially unless
ment should be reinitiated. If clinical signs do not recur, a the levothyroxine product has been specifically formulated
thyroid-responsive disorder or a beneficial response to con for once-daily administration. Because o f the variability in
current therapy (e.g., antibiotics, flea control) should be its absorption and metabolism, the dose and frequency may
suspected. have to be adjusted before a satisfactory clinical response is
BOX 51-5 BOX 51-6
Recommendations for the Initial Treatment and Potential Reasons for Poor Clinical Response to
Monitoring of Hypothyroidism in Dogs Treatment with Sodium Levothyroxine (Synthetic T ) 4
Initial Monitoring
Response to treatment should be critically evaluated 4 to 8
weeks after initiating treatment. FAILURE T O RESPOND TO S O D I U M
Serum T and TSH concentrations should be measured 4 to
4
LEVOTHYROXINE THERAPY
6 hours after administration of levothyroxine. Problems with levothyroxine therapy should be suspected if
Serum T should be in the reference range or increased.
4
clinical improvement is not seen by 8 weeks after initiating
Serum TSH concentration should be in the reference
therapy. A n inappropriate diagnosis of hypothyroidism is
range.
the most obvious. Hyperadrenocorticism can be mistaken
Measuring serum T concentration immediately before levo
4
for hypothyroidism i f other clinical signs (e.g., polyuria,
thyroxine administration (i.e., trough level) is optional
but is recommended if levothyroxine is being given once
polydipsia) c o m m o n l y associated with hyperadrenocorti
a day. cism are not present because o f the suppressive effects of
The trough concentration of serum T should be in the refer
4
Cortisol on serum thyroid hormone concentrations (see
ence range. p. 738). Failure to recognize the impact o f concurrent illness
on thyroid hormone test results is another c o m m o n reason
TSH, Thyroid-stimulating hormone. for misdiagnosing hypothyroidism. Concurrent disease (e.g.,
allergic skin disease, flea hypersensitivity) is c o m m o n i n dogs
with hypothyroidism and may affect the clinical impression
observed; this variability is one reason for m o n i t o r i n g of response to levothyroxine therapy if the disease is not
therapy i n dogs. recognized. Other possible reasons for a poor response
to therapy are listed i n Box 51-6. Whenever a dog shows a
RESPONSE TO S O D I U M poor response to levothyroxine therapy, the history, physical
LEVOTHYROXINE THERAPY examination findings, and diagnostic test results that
T h y r o i d hormone supplementation should be continued prompted the initiation o f levothyroxine therapy should be
for a m i n i m u m o f 4 weeks before critically evaluating the critically reevaluated and serum thyroid hormone concen
effectiveness o f treatment. W i t h appropriate therapy all clin trations measured.
ical signs and clinicopathologic abnormalities associated
with hypothyroidism are reversible. Improvement in mental THERAPEUTIC M O N I T O R I N G
alertness and activity usually occurs w i t h i n the first week Therapeutic monitoring includes evaluation o f the clinical
of treatment; this is an important early indicator that the response to levothyroxine treatment, measurement of serum
diagnosis o f hypothyroidism was correct. A l t h o u g h some T and T S H concentrations before or after levothyroxine
4
hair regrowth usually occurs w i t h i n the first m o n t h i n dogs administration, or both. These concentrations should be
with endocrine alopecia, it may take several months for measured 4 weeks after initiating therapy, whenever signs of
complete regrowth and a marked reduction i n hyperpig thyrotoxicosis develop, or i n the event that there has been
mentation o f the skin to occur. Initially, the haircoat may m i n i m a l or no response to therapy. Concentrations should
worsen as large amounts o f hair i n the telogen stage o f the also be measured 2 to 4 weeks after an adjustment in
hair cycle are shed. Improvement i n neurologic manifesta levothyroxine therapy in dogs showing a poor response to
tions is usually evident w i t h i n days o f initiating treatment; treatment.
complete resolution o f neurologic signs is unpredictable and Serum T and T S H concentrations are typically evaluated
4
may take 4 to 8 weeks or longer o f treatment before it 4 to 6 hours after the administration of levothyroxine in dogs
occurs. receiving the medication twice daily and just before and 4 to
6 hours after administration in dogs receiving it once a day. the reference range. Postdosing serum T and T S H concen 4
in the dose or frequency o f administration of levothyroxine and undetectable serum T S H concentrations supports the
is indicated i f clinical manifestations of hypothyroidism diagnosis. However, serum T and f T concentrations can
4 4
persist, the serum T S H concentration remains increased, or occasionally be w i t h i n the reference range i n a dog with signs
both, but it is not necessarily indicated if the clinical response of thyrotoxicosis and are c o m m o n l y increased in dogs with
to treatment is good and the serum T S H concentration is i n no signs of thyrotoxicosis. Adjustments in the dose or fre-
FIG 51-11
Initial therapeutic a p p r o a c h a n d monitoring r e c o m m e n d a t i o n s for d o g s with h y p o t h y r o i d i s m .
quency o f administration o f levothyroxine, or both mea
sures, are indicated i f clinical signs o f thyrotoxicosis develop
in a dog receiving thyroid hormone supplements. Supple Clinical Manifestations of Feline Hypothyroidism
mentation should be discontinued for a few days i f clinical
Adult-Onset Hypothyroidism
signs are severe. Signs of thyrotoxicosis should resolve w i t h i n
1 to 3 days i f they are due to the thyroid medication and the Lethargy
adjustment in treatment has been appropriate. Inappetence
Obesity
Prognosis Dermatologic
Seborrhea sicca
The prognosis for adult dogs w i t h primary hypothyroidism
Dry, lusterless haircoat
that are receiving appropriate therapy is excellent. The prog
Easily epilated hair
nosis for puppies w i t h hypothyroidism (i.e., cretinism) is Poor regrowth of hair
guarded and depends on the severity o f skeletal and joint Endocrine alopecia
abnormalities at the time treatment is initiated. Although Alopecia of pinnae
many o f the clinical signs resolve w i t h therapy, musculo Thickened skin
skeletal problems, especially degenerative osteoarthritis, may Myxedema of the face
develop owing to abnormal bone and joint development. Reproduction
The prognosis for dogs with secondary hypothyroidism Failure to cycle
Dystocia
caused by congenital malformation of the pituitary gland
Bradycardia
(i.e., pituitary dwarfism) is guarded to poor because o f the
Mild hypothermia
multiple problems that develop i n early life (see Chapter 49).
The prognosis for dogs w i t h acquired secondary hypothy Congenital Hypothyroidism
roidism caused by suppression of pituitary function by med Disproportionate dwarfism
ications (e.g., glucocorticoids) is excellent, although treatment Failure to grow
with levothyroxine may be necessary i f the medication can Large head
not be discontinued. The prognosis for dogs with acquired Short, broad neck
secondary hypothyroidism caused by destruction o f the Short limbs
region by a space-occupying mass is grave. Lethargy
Mental dullness
Constipation
Hypothermia
HYPOTHYROIDISM IN CATS
Bradycardia
Retention of kitten haircoat
Etiology
Retention of deciduous teeth
Iatrogenic hypothyroidism is the most c o m m o n cause o f
hypothyroidism i n cats and can result from bilateral thyroid
ectomy, radioactive iodine treatment, or an overdose of anti
thyroid drugs. Naturally acquired adult-onset primary
hypothyroidism is rare. Congenital primary hypothyroidism of hair; and alopecia. Bradycardia and m i l d hypothermia
causing disproportionate dwarfism is recognized more fre may be additional findings on physical examination.
quently i n cats than adult-onset hypothyroidism. Reported The clinical signs o f congenital hypothyroidism are
causes of congenital hypothyroidism include a defect i n similar to those i n dogs (see p. 729). Affected kittens typically
thyroid hormone biosynthesis, most notably an iodine appear n o r m a l at birth, but delayed growth usually becomes
organification defect, and thyroid dysgenesis. Goiter is evident by 8 weeks of age. Disproportionate dwarfism devel
c o m m o n i n cats w i t h defects i n thyroid hormone biosynthe ops over the ensuing months, with large heads; short, broad
sis because the hypothalamic-pituitary-thyroid gland axis necks; and short limbs developing i n affected kittens (Fig.
remains intact. A suspected autosomal recessive inherited 51-12). Additional findings include lethargy, mental dull
defect i n iodine organification was documented i n a family ness, constipation, hypothermia, bradycardia, and prolonged
of Abyssinian cats w i t h congenital hypothyroidism. A l t h o u g h retention o f deciduous teeth. The haircoat may consist
rare, iodine deficiency may cause hypothyroidism in kittens mainly o f an undercoat with primary guard hairs scattered
fed a strict all-meat diet. thinly throughout.
terless, unkempt haircoat; easily epilated hair; poor regrowth surement o f serum T S H concentration using the canine T S H
Asymptomatic cats with a low serum T concentration fol
4
small size of the pituitary d w a r f . N o t e the s q u a r e , c h u n k y after 4 to 8 weeks o f treatment but there is m i n i m a l or
contour of the h e a d a n d the dull f a c i a l e x p r e s s i o n of the no clinical response, the clinician should reassess the
c a t f i n d i n g s that a r e suggestive of cretinism (see F i g . 4 9 - diagnosis.
1 0 , for c o m p a r i s o n ) . The c a t h a d concurrent g r o w t h
hormone a n d thyroid h o r m o n e d e f i c i e n c y . (From F e l d m a n Prognosis
E C , N e l s o n R W : Canine and feline endocrinology and
reproduction, e d 3 , St Louis, 2 0 0 4 , W B S a u n d e r s . ) The prognosis for adult cats with hypothyroidism that are
receiving appropriate therapy is excellent. The prognosis for
kittens with congenital hypothyroidism is guarded and
depends o n the severity o f the skeletal changes at the
assay should also be considered. Abnormalities identified on time treatment is initiated. Although many o f the clinical
routine blood and urine tests include hypercholesterolemia signs resolve with therapy, musculoskeletal problems may
and a m i l d nonregenerative anemia. Serum T concentration 4 persist or develop owing to abnormal bone and joint
is often used as the initial screening test o f thyroid gland development.
function. A normal serum T concentration indicates that
4
primary hypothyroidism is rare and l o w serum T concen 4 the thyroid gland and is almost always a result o f chronic
trations in adult cats is almost always caused by nonthyroidal intrinsic disease i n one or both thyroid lobes. One or more
illness (see Fig. 51-13) or some other nonthyroidal factor, the usually small, discrete thyroid masses are palpable i n the
diagnosis of hypothyroidism should never be made solely on ventral region o f the neck i n most cats with hyperthyroid
the basis of the serum T concentration i n an adult cat that
4 ism. M u l t i n o d u l a r adenomatous hyperplasia is the most
has not been previously treated for hyperthyroidism. D o c u c o m m o n histologic finding. Less c o m m o n are thyroid ade
menting a low serum f T and high serum T S H concentration
4 nomas that cause the lobes to be enlarged and distorted;
and failure of serum T to increase following administration
4 thyroid carcinoma accounts for fewer than 5% o f clinical
of r h T S H adds further evidence for the diagnosis o f hypo cases.
thyroidism. The definitive diagnosis relies on the cat's One or both thyroid lobes can be affected i n thyrotoxic
response to trial therapy with levothyroxine. cats. Approximately 20% o f hyperthyroid cats have involve
ment o f a single thyroid lobe (Fig. 51-14). The nondiseased
Treatment thyroid lobe is nonfunctioning and atrophied because of
Treatment of hypothyroidism i n cats is similar to that used the suppressive effects o f the hyperactive thyroid tissue on
in dogs, which is described i n detail on p. 741. Treatment T S H secretion. M o r e than 70% o f hyperthyroid cats have
with levothyroxine is indicated for cats with congenital and involvement of both thyroid lobes (Fig. 51-15). O f these cats
naturally acquired adult-onset hypothyroidism and for cats the thyroid lobes are symmetrically enlarged i n 10% to 15%
with iatrogenic hypothyroidism following treatment for and asymmetrically enlarged i n the remainder. A p p r o x i
hyperthyroidism that are symptomatic for the disease. mately 3% to 5% o f thyrotoxic cats have hyperactive thyroid
FIG 5 1 - 1 3
B o x plots of serum total T (A) a n d free T (B) c o n c e n t r a t i o n s in 2 2 1 cats with nonthyroi
4 4
tissue i n the anterior mediastinum, with or without a pal content, isoflavones from soybeans, and chemicals lining
pable mass i n the neck (Fig. 51-16). Presumably, this tissue pop-top canned foods (specifically bisphenol A ) that have
represents ectopic thyroid tissue. Functional thyroid carci migrated into the food during storage have been proposed
noma is the most likely diagnosis i f more than two thyroid as potential dietary and chemical goitrogens. Epidemiologic
masses are present (see Fig. 51-16). Some of these cats i n i studies suggest that environmental factors such as use of
tially have only one or two thyroid masses, emphasizing the kitty litter may be involved. Recent studies have identified
importance of histologic evaluation of surgically removed overexpression of the c-ras oncogene in areas of nodular
tissue. follicular hyperplasia in feline thyroid glands, suggesting that
The pathogenesis o f adenomatous hyperplastic changes mutations in this oncogene may play a role in the etiopatho
of the thyroid gland remains unclear. It has been postulated genesis of hyperthyroidism in cats (Merryman et al., 1999).
that immunologic, infectious, nutritional, environmental, or In the normal cell activation of the ras protein leads to
genetic factors may interact to cause pathologic changes. mitosis. Mutations of the ras oncogene produce mutated ras
Epidemiologic studies have identified consumption of c o m proteins that are not subject to the normal cellular feedback
mercial canned cat foods as a risk factor for development of mechanisms that prevent uncontrolled mitosis. Altered
hyperthyroidism, suggesting that a goitrogenic c o m p o u n d expression of G proteins involved in the signal transduction
may be present in the diet. Excessive or deficient iodine pathway that stimulates growth and differentiation of thyroid
FIG 5 1 - 1 3 , cont'd
cells has also been identified in adenomatous thyroid glands the most frequently affected breeds. Siamese and Himalayans
obtained from hyperthyroid cats ( W a r d et al., 2005). have a decreased risk for development of hyperthyroidism.
Decreased inhibitory G protein expression has been identi
fied, a decrease that creates a relative increase i n stimulatory CLINICAL SIGNS
G protein expression that may stimulate unregulated mito Clinical signs are a result o f excessive secretion o f thyroid
genesis and thyroid hormone production in hyperthyroid hormone by the thyroid mass. Rarely, a client will seek vet
cells. Further studies are necessary to clarify the significance erinary care because of an observed mass i n the ventrocervi
of these findings and the relationships among abnormalities cal region o f the neck. The classic clinical signs o f
identified in thyroid cells from hyperthyroid cats, potential hyperthyroidism are weight loss (which may progress to
dietary or chemical goitrogens identified in canned cat foods, cachexia), polyphagia, and restlessness or hyperactivity.
and the development of hyperthyroidism in cats. Additional clinical signs include haircoat changes (patchy
alopecia, matted hair, m i n i m a l or excessive grooming
Clinical Features behavior), polyuria, polydipsia, vomiting, and diarrhea
(Table 51-5). Some cats show aggressive behavior that
SIGNALMENT resolves i n response to successful treatment o f the hyperthy
Hyperthyroidism is the most c o m m o n endocrine disease roid state. In some cats lethargy, weakness, and anorexia are
affecting cats older than 8 years. The average age at the time the dominant clinical features, i n addition to weight loss.
of initial presentation to the veterinarian is 13 years, with a Because of the multisystemic effects o f hyperthyroidism, the
range of 4 to 20 years. Fewer than 5% of cats with this dis variable clinical signs, and its resemblance to many other
order are younger than 8 years. There is no sex-related pre diseases o f the cat, hyperthyroidism should be suspected in
disposition; domestic short-haired and long-haired cats are any aged cat with medical problems.
FIG 51-14
A , S o d i u m pertechnetate s c a n of the h e a d , neck, a n d p r o x i m a l t h o r a x of a healthy cat.
N o t e that the uptake of pertechnetate (i.e., darkness) is c o m p a r a b l e b e t w e e n the two
t h y r o i d lobes (solid arrow) a n d the s a l i v a r y g l a n d s (broken arrow). B, S o d i u m pertechne
tate s c a n of the h e a d , neck, a n d p r o x i m a l t h o r a x of a c a t with h y p e r t h y r o i d i s m c a u s e d b y
unilateral d i s e a s e affecting the right t h y r o i d l o b e (arrow). N o t e the difference in uptake of
pertechnetate b e t w e e n the h y p e r f u n c t i o n i n g t h y r o i d l o b e a n d the s a l i v a r y g l a n d s .
include an increase i n serum activities of alanine amino on palpation of the ventral thorax; and, less frequently, pulse
transferase, alkaline phosphatase, and aspartate aminotrans deficits, gallop rhythms, cardiac m u r m u r , and muffled heart
ferase; the increase is typically i n the m i l d to moderate range sounds resulting from a pleural effusion. Electrocardio
(i.e., 100 to 400 I U / L ) . One or more of these liver enzymes graphic abnormalities include tachycardia; an increased R-
are increased in approximately 90% of hyperthyroid cats. wave amplitude i n lead II; and, less commonly, a right
Additional evaluation of the liver should be considered i f bundle-branch block, a left anterior fascicular block, widened
liver enzyme activities are greater than 500 I U / L . Increased QRS complexes, and atrial and ventricular arrhythmias.
serum urea nitrogen and creatinine concentrations are Thoracic radiographs may reveal cardiomegaly, pulmonary
identified i n approximately 25%, and hyperphosphatemia i n edema, or a pleural effusion. Echocardiographic abnormali
20%, of hyperthyroid cats at our clinicfindings that have ties identified in cats with hypertrophic thyrotoxic cardio
important implications regarding treatment (see the discus myopathy include left ventricular hypertrophy, thickening of
sion of renal insufficiency). U r i n e specific gravity ranges the interventricular septum, left atrial and ventricular dila
from 1.008 to greater than 1.050. M o s t hyperthyroid cats tion, and myocardial hypercontractility. Those seen i n cats
have urine specific gravities greater than 1.035. The remain with dilative thyrotoxic cardiomyopathy include subnormal
der of the urinalysis is usually unremarkable unless concur myocardial contractility and marked ventricular dilation.
rent diabetes mellitus or urinary tract infection exists. Either form of cardiomyopathy may result i n the development
of congestive heart failure. Hypertrophic thyrotoxic cardio
C O M M O N CONCURRENT PROBLEMS myopathy is usually reversible once the hyperthyroid state is
Thyrotoxic Cardiomyopathy corrected, whereas dilative thyrotoxic cardiomyopathy is not.
Hypertrophic and, less commonly, dilative thyrotoxic car
diomyopathy may develop in cats with hyperthyroidism. Renal Insufficiency
Cardiovascular abnormalities detectable during physical Hyperthyroidism and renal insufficiency are c o m m o n dis
examination include tachycardia; a pounding heartbeat noted eases of older cats and often occur concurrently. Identification
FIG 5 1 - 1 6
A , S o d i u m pertechnetate s c a n of the h e a d , neck, a n d p r o x i m a l t h o r a x of a cat with
h y p e r t h y r o i d i s m c a u s e d b y metastatic thyroid a d e n o c a r c i n o m a with multiple masses
present in the h e a d , neck, a n d a n t e r i o r m e d i a s t i n u m (solid arrows). H e a r t (broken arrow).
B, S o d i u m pertechnetate s c a n of the h e a d , neck, a n d p r o x i m a l t h o r a x of a cat with
h y p e r t h y r o i d i s m c a u s e d b y t w o h y p e r f u n c t i o n i n g masses: o n e l o c a t e d in the neck (broken
arrow) a n d o n e in the a n t e r i o r m e d i a s t i n u m (i.e., e c t o p i c site) (solid arrow). H e a r t (broken
1 3 1
arrow). l t h e r a p y is the treatment of c h o i c e for both forms of h y p e r t h y r o i d i s m illustrated
in this figure.
of small kidneys o n physical examination, increased serum renal failure after treatment for hyperthyroidism, suggesting
urea nitrogen and creatinine concentrations, and urine that urine specific gravity is a poor predictor of renal func
specific gravity between 1.008 and 1.020 should raise sus tion i n cats with hyperthyroidism. For these reasons cats
picion for concurrent renal insufficiency i n a cat with with hyperthyroidism should initially be given reversible
hyperthyroidism. Unfortunately, hyperthyroidism increases therapy (i.e., oral antithyroid drugs) until the impact of
glomerular filtration rate ( G F R ) , renal blood flow, and renal establishing euthyroidism on renal function can be deter
tubular resorptive and secretory capabilities i n normal mined (see p. 749).
and compromised kidneys. Renal perfusion and G F R may
acutely decrease and azotemia or clinical signs of renal Urinary Tract Infections
insufficiency become apparent or significantly worsen after Urinary tract infections are relatively c o m m o n in untreated
treatment of the hyperthyroid state. It is not easy to deter hyperthyroid cats, with a reported prevalence of 12% to
mine what impact the hyperthyroid state is having on 22%. The most c o m m o n bacterial isolate is Escherichia
renal function i n cats. The clinical and biochemical manifes coli. U r i n e culture is indicated i n hyperthyroid cats with
tations of renal failure may be masked i n cats with both lower urinary tract signs or presence of bacteriuria, pyuria,
thyroid and renal disease i n which renal perfusion is or both o n urinalysis. Unfortunately, most hyperthyroid
enhanced by the circulatory dynamics produced by hyper cats are asymptomatic for urinary tract infection, suggesting
thyroidism. Thomas Graves, at the University of Illinois, that urine culture should be a routine part of the complete
has recently described a group of hyperthyroid cats with diagnostic evaluation of cats with newly diagnosed
urine specific gravities greater than 1.040 that developed hyperthyroidism.
TABLE 51-6
PROBABILITY O F
SERUM T CONCENTRATION
4 HYPERTHYROIDISM
roidism and results from the effects of increased -adrencr- the diagnosis o f hyperthyroidism, especially i f appropriate
gic activity o n heart rate, myocardial contractility, systemic clinical signs are present, and a l o w serum T concentration
4
vasodilation, and activation o f the renin-angiotensin-aldo rules out hyperthyroidism, except i n extremely u n c o m m o n
sterone system. Hypertension caused by hyperthyroidism is situations when severe life-threatening nonthyroidal illness
usually clinically silent. Retinal hemorrhages and retinal is present (Table 51-6). Serum T concentrations that fall
4
detachment are the most c o m m o n clinical complications of within the upper half of the normal range (i.e., 2.5 to 5.0 g/
systemic hypertension i n hyperthyroid cats, but i n general, dl) create a diagnostic dilemma, especially i f clinical signs are
ocular lesions are not commonly identified. suggestive o f hyperthyroidism and a nodule is palpable i n
the ventral region of the neck. This combination o f findings
Gastrointestinal Tract Disorders is referred to as occult hyperthyroidism and is most c o m
Gastrointestinal tract signs are c o m m o n i n cats with hyper monly identified i n cats i n the early stages of hyperthyroid
thyroidism and include polyphagia, weight loss, anorexia, ism. Serum T concentrations are more likely to be influenced
4
vomiting, diarrhea, increased frequency o f defecation, and by nonthyroidal factors such as concurrent illness and are
increased volume of feces. Intestinal hypermotility and mal more likely to randomly fluctuate into the reference range in
assimilation have been documented i n some cats with hyper cats with m i l d hyperthyroidism, compared with cats with
thyroidism and are responsible for producing some of the more advanced disease (Fig. 51-18; see also Fig. 51-13). The
gastrointestinal tract signs. Inflammatory bowel disease is a diagnosis of hyperthyroidism should not be excluded on the
common concurrent gastrointestinal tract disorder that basis of one " n o r m a l " serum T test result, especially i n a cat
4
should be considered i n any hyperthyroid cat that has per with appropriate, albeit often m i l d , clinical signs and a pal
sistence of gastrointestinal signs after correction o f the pable mass i n the neck. Additional diagnostic factors to con
hyperthyroid state (see Chapter 33). Intestinal neoplasia, sider include measurement o f serum free T (fT ), the T 4 4 3
most notably lymphoma, is perhaps the most important dif suppression test, sodium pertechnetate thyroid scan, or rep
ferential diagnosis i n cats seen because o f polyphagia and etition of the serum T test 3 to 6 months later. It is impor
4
weight loss. The abdomen should be carefully palpated i n a tant to remember that the thyroid nodule m a y also be
search for thickening of the intestinal tract and mesenteric nonfunctional and the clinical signs may be the result of
lymphadenopathyfindings that may be the only clues for another disease (see Chapter 54).
FIG 51-18
B o x plots of serum total T (A) a n d free T (B) concentrations in 1 7 2 c l i n i c a l l y n o r m a l
4 4
2-step R I A (see p. 733) is the current recommendation of tration i n conjunction with a low-normal or low serum T 4
choice to confirm hyperthyroidism i n a cat with nondiag concentration is supportive o f the euthyroid sick syndrome
nostic serum T test results. Measurement o f serum f T is a
4 4 rather than hyperthyroidism.
more reliable means o f assessing thyroid gland function than
serum T concentration, i n part because nonthyroidal illness
4
T Suppression Test
3
with suspected hyperthyroidism i n which T values are non 4 T S H secretion in euthyroid cats, resulting in a decrease
diagnostic. Concurrent illness may increase the serum fT4 in circulating T (Fig. 51-19). In contrast, pituitary T S H
4
concentration in cats, an increase that can exceed the refer secretion is already suppressed in cats with hyperthyroidism,
ence range (see Fig. 51-18). For this reason serum fT4 con oral administration o f T will not cause further suppression,
3
centration should always be interpreted i n conjunction with and serum T will not decrease following T administration.
4 3
Methimazole, Long-term therapy for all forms None Daily therapy required; no
propylthiouracil, of hyperthyroidism; initial effect on growth of
carbimazole therapy to stabilize cat's thyroid; mild adverse
condition and assess renal reactions common;
function before thyroidectomy severe reactions possible
or radioactive iodine
Thyroidectomy Unilateral lobe involvement; Ectopic thyroid lobe; metastatic Anesthetic risks; relapse of
bilateral lobe involvement, carcinoma; bilateral, disease; postoperative
asymmetrical sizes symmetric, large lobes (high complications, especially
risk of hypocalcemia); severe hypocalcemia
systemic signs; cardiac
arrhythmias or failure; renal
insufficiency
131
Radioactive iodine ( l) Therapy for all forms of Renal insufficiency Limited availability;
hyperthyroidism; treatment of hospitalization time;
choice for ectopic thyroid potential for retreatment;
lobe and thyroid carcinoma hazardous to humans
readily available, relatively safe, and effective i n the treatment evaluated 2 weeks later. The dosage should continue to be
of hyperthyroidism i n cats. They inhibit the synthesis o f increased every 2 weeks by 2.5 mg/day increments until the
thyroid hormone by blocking the incorporation o f iodine serum T concentration is between 1 and 2 g/dl or adverse
4
into the tyrosyl groups i n thyroglobulin and by preventing reactions develop. Serum T concentrations decline into the
4
the coupling of these iodotyrosyl groups into T and T . 3 4 reference range w i t h i n 2 weeks once the cat is receiving an
Antithyroid drugs do not block the release o f stored thyroid effective dose o f methimazole; clinical improvement is
hormone into the circulation and do not have antitumor usually noted by clients w i t h i n 2 to 4 weeks once good
actions. Oral antithyroid drugs do not interfere with results control o f serum T concentration is achieved. M o s t cats
4
of pertechnetate scanning or radioactive iodine therapy. respond to 5 to 7.5 m g o f methimazole per day, and the drug
Indications for oral antithyroid drugs include (1) test treat is most effective when given twice a day. Attempts at decreas
ment to normalize serum T concentrations and assess the
4 ing the daily dosage, frequency o f administration, or both
effect o f resolving hyperthyroidism o n renal function, (2) can take place once clinical signs have resolved and a euthy
initial treatment to alleviate or eliminate any medical prob roid state is attained, especially for cats receiving chronic
lems associated with the syndrome before thyroidectomy is methimazole treatment.
performed or before the hospitalization required for radio Rarely, cats are encountered that seem particularly resis
active iodine treatment, and (3) long-term treatment o f tant to methimazole, requiring as m u c h as 20 mg/day. The
hyperthyroidism. most c o m m o n cause for apparent resistance to methimazole
Methimazole (Tapazole; E l i Lilly & Co.) is currently the is the inability o f some clients to administer the drug to their
antithyroid drug o f choice because the incidence o f adverse cats. One alternative is to have a c o m p o u n d i n g pharmacy
reactions associated with its use is lower than that associated incorporate methimazole into tasty kitty treats. Another
with the use o f propylthiouracil (Table 51-8). Adverse reac alternative is the topical application o f methimazole to the
tions are less likely to occur when the dosage o f methimazole pinna o f the ear. C o m p o u n d i n g veterinary pharmacies offer
is started low (typically at subtherapeutic dose initially) and transdermal methimazole i n a pluronic lecithin organogel
gradually increased to effect. The recommended initial dose ( P L O ) formulation. Creams can be made with methimazole
of methimazole is 2.5 m g administered orally twice a day for at any concentration and are usually provided i n 1 -cc syringes
2 weeks. If adverse reactions are not observed by the client, that allow the client to place the appropriate dose o n the
if the physical examination reveals no new problems, i f fingertip and rub the cream into the p i n n a o f the cat's ear.
results of a C B C and platelet count are w i t h i n reference The client must wear gloves to avoid absorption o f m e t h i m
limits, i f the serum creatinine and urea nitrogen concentra azole, should alternate ears, and should wipe away any resid
tions have not increased, and i f serum T concentration is
4
ual cream 30 to 60 minutes after each administration. The
greater than 2 g/dl after 2 weeks o f therapy, the dose is dosage and frequency o f administration is as discussed with
increased by 2.5 m g per day (i.e., 5 m g i n the m o r n i n g and oral methimazole treatment. The bioavailability o f transder
2.5 mg in the evening) twice daily and the same parameters mal methimazole is more variable, the overall effectiveness
TABLE 51-8
Clinical Signs
Anorexia 11 24 1-78
Vomiting 11 22 7-60
Lethargy 9 24 1-60
Excoriations 2 21 6-40
Bleeding 2 31 15-50
Clinical Pathology
Positive Antinuclear antibody titer 22 91 10-870
Eosinophilia 11 57 12-490
Lymphocytosis 7 25 14-90
Leukopenia 5 23 10-41
Thrombocytopenia 3 37 14-90
Agranulocytosis 2 62 26-95
Hepatopathy 2 39 15-60
Adapted from Peterson ME, Kintzer PP, Hurvitz Al: Methimazole treatment of 262 cats with hyperthyroidism, J Vet Intern Med 2:150, 1988.
is not as good, and the prevalence o f gastrointestinal adverse cations develop, methimazole treatment should be discon
effects is lower, compared w i t h oral methimazole. One tinued and supportive care given. Adverse reactions typically
important concern w i t h using transdermal methimazole is resolve within 1 week after methimazole treatment is discon
the lack o f regulation o f c o m p o u n d i n g pharmacies; consis tinued. It is c o m m o n for these potentially life-threatening
tency between products created can vary considerably. adverse reactions to recur, regardless o f the dose or type of
Adverse reactions to methimazole typically occur within antithyroid drug used; thus alternative therapy (i.e., surgery,
the first 4 to 8 weeks o f therapy (see Table 51-8). The cat radioactive iodine) is recommended.
should be examined every 2 weeks during the initial 3 months Carbimazole (NeoMercazole; A m d i p h a r m ) is an antithy
o f methimazole treatment and a C B C , platelet count, assess r o i d drug that is converted to methimazole i n vivo; it is an
ment o f kidney function, and serum T concentration evalu
4 effective alternative treatment i f methimazole is not avail
ated at each visit. After the initial 3 months of therapy a C B C , able. The dosage and frequency o f administration are the
platelet count, serum biochemistry panel, and serum T con 4 same as those i n oral methimazole treatment. Long-term,
centration should be evaluated every 3 to 6 months. U s i n g twice-daily schedules are effective i n controlling hyperthy
the dosing protocol described above, lethargy, vomiting, and roidism. Adverse reactions are similar to those seen i n
anorexia occur i n fewer than 10% o f cats; these m i l d adverse cats receiving methimazole, but they occur less frequently.
reactions are usually transient and often resolve despite con Cats being treated with carbimazole should be monitored
tinued administration o f the drug. M i l d methimazole- i n the same manner as that suggested for cats receiving
induced hematologic changes occur i n fewer than 10% o f methimazole.
cats and include eosinophilia, lymphocytosis, and transient
leukopenia. M o r e worrisome but less c o m m o n (fewer than Surgery
5% o f cats) alterations include facial excoriations, thrombo Thyroidectomy is an effective treatment but should always
3
cytopenia (platelet counts less than 75,000/mm ), leukope be considered an elective procedure. Surgery is not indicated
3
nia (total white b l o o d cell counts less than 2000/mm ), and if the risk o f anesthesia i n the cat is unacceptable, its renal
immune-mediated hemolytic anemia. Apparent hepatic tox function is questionable, the likelihood o f postoperative
icity or injury occurs i n fewer than 2 % o f cats receiving hypocalcemia is great, ectopic thyroid tissue is present i n the
methimazole and is characterized by clinical signs o f liver thorax, or thyroid carcinoma with metastasis is suspected.
disease (i.e., lethargy, anorexia, vomiting), icterus, and Treatment with methimazole for 1 to 2 months before thy
increased serum alanine transaminase and alkaline phospha roidectomy is recommended for reasons previously dis
tase activities. Some cats test positive for antinuclear anti cussed. If possible, an ultrasound examination o f the ventral
bodies, but the importance o f this finding is not k n o w n . neck or a radionuclide scan should be performed before
Development o f myasthenia gravis has also been reported surgery to identify the location of the abnormal thyroid
with methimazole treatment. If any o f these serious c o m p l i tissue, differentiate unilateral from bilateral lobe involve-
becomes severe (i.e., serum total or ionized calcium concen
BOX 51-8
tration less than 8 m g / d l and 0.8 m m o l / L , respectively). A
Complications of Thyroidectomy in Cats decline i n the b l o o d calcium concentration is not an absolute
with Hyperthyroidism indication to begin therapy because the remaining parathy
roid glands may respond before clinical signs or severe hypo
Transient or permanent hypoparathyroidism causing hypo
calcemia develop.
calcemia:
The persistence o f hypoparathyroidism is unpredictable.
Restlessness
Irritability
Parathyroid function may recover after days, weeks, or
Abnormal behavior months o f vitamin D and calcium supplementation. W h e n
Muscle cramping, pain ever resolution o f hypoparathyroidism is observed, it is
Muscle tremors, especially of ears and face assumed that reversible parathyroid damage occurred, acces
Tetany sory parathyroid tissue may be starting to compensate for
Convulsions glands damaged or removed at surgery, or the parathyroid
Laryngeal paralysis autotransplant (if performed at surgery) has revascularized
Horner's syndrome and become functional. It is also possible that calcium-regu
Hypothyroidism
lating mechanisms are functioning i n the absence o f para
Exacerbation of concurrent renal insufficiency
thyroid hormone. Because it is difficult to predict the
N o amelioration of the hyperthyroidism
long-term requirement for vitamin D therapy i n any cat, an
attempt should be made to gradually wean all treated cats
off medication while m o n i t o r i n g the serum calcium concen
tration. The tapering process should extend over a period o f
ment, and provide some insight into the probability of hypo at least 12 to 16 weeks. The goal is to maintain the serum
calcemia developing postoperatively (see Fig. 51-15). Similar calcium concentration between 8.5 and 10.0 mg/dl. If hypo
information can also be gained by direct visualization at the calcemia recurs, therapy w i t h v i t a m i n D and calcium must
time of surgery. be reinstituted.
Postoperative complications are listed i n B o x 51-8. The H y p o t h y r o i d i s m may develop i n some cats after bilateral
most worrisome is hypocalcemia. There is a direct correla thyroidectomy. The clinical signs, diagnosis, and treatment
tion between the size of the thyroid lobes, the inability to are discussed o n p. 744. The decision to initiate levothyrox
visualize the external parathyroid glands, and the risk o f ine treatment should be based on the presence or absence o f
hypocalcemia. Care must be taken to preserve at least one, clinical signs, not o n the serum T concentration, per se.
4
preferably both, external parathyroid glands and their asso Serum T concentrations c o m m o n l y decrease after surgery,
4
ciated blood supply. A "subcapsular" thyroidectomy affords often to less than 0.5 g/dl, but thyroid function returns i n
the best chance o f retaining functional parathyroid glands. most cats before clinical signs become apparent. T h y r o i d
(See Suggested Readings for thyroidectomy procedures.) If hormone supplementation should be initiated i n cats that
all four parathyroid glands are inadvertently removed, the develop clinical signs i n conjunction with a l o w serum T 4
two external parathyroid glands should be removed from concentration. Because thyroid replacement therapy may
their respective thyroid lobes, minced, and placed within the not be needed long term i n some o f these cats, thyroid
muscle belly of one of the sternohyoideus muscles by bluntly replacement therapy should be tapered slowly and then dis
dissecting parallel to the muscle fibers. Hypoparathyroidism continued after 1 to 3 months to determine the continued
usually resolves within a month o f surgery i f revasculariza need for treatment.
tion of the parathyroid autotransplant occurs. If clinical signs o f hyperthyroidism persist despite
Serum calcium concentration should be assessed at least thyroidectomy, the serum T concentration should be mea
4
once daily for 5 to 7 days i f a bilateral thyroidectomy has sured. If the serum T concentration is l o w - n o r m a l or l o w
4
been performed. Clinical signs o f hypocalcemia typically (i.e., <2.0 g/dl), another disorder should be suspected. If
develop within 72 hours of surgery, although signs may not the serum T concentration is high-normal or high (i.e.,
4
develop for 7 to 10 days. These signs include lethargy, >4.0 g/dl), ectopic abnormal thyroid tissue, metastatic
anorexia, reluctance to move, facial twitching (especially the thyroid carcinoma, or, i f unilateral thyroidectomy was per
ears), muscle tremors and cramping, tetany, and convulsions. formed, abnormal tissue i n the remaining thyroid lobe
If all four parathyroid glands are removed at surgery, appro should be suspected. Ectopic thyroid tissue w o u l d most
priate calcium and vitamin D supplementation should be likely be i n the mediastinum, cranial to the heart (see Fig.
initiated once the cat has recovered from anesthesia (see 51-16). T h y r o i d scanning is recommended to identify ectopic
p. 735). If at least one parathyroid gland has been spared, or metastatic thyroid tissue. Alternatively, oral methimazole
transient hypocalcemia may still develop and last for several or radioactive iodine therapy can be considered. Clinical
days to weeks, probably as a result o f disruption o f b l o o d signs o f hyperthyroidism may also recur months to years
flow to the parathyroid gland after surgical manipulation. In after thyroidectomy. The serum T concentration should be
4
these cats oral vitamin D and calcium therapy should be monitored once or twice a year i n all cats successfully treated
initiated only i f clinical signs develop or i f hypocalcemia with surgery.
become euthyroid within 3 monthsmost within 1 week
and more than 95% of treated cats are euthyroid at 6 months.
In one study by Peterson et al. (1995), clinical signs and
laboratory data consistent with hypothyroidism developed
131
in approximately 2% of 254 I-treated cats, 2% to 4%
131
required a second I treatment, and hyperthyroidism
recurred in 2% within 1 to 6 years of treatment. C h u n et al.
(2002) found no correlation between pretreatment serum T 4
Prognosis
The prognosis is excellent for most cats with hyperthyroid
ism, assuming concurrent disease can be managed and
FIG 51-21 131
Nonfunctional
Swelling or mass in neck
Dyspnea
Cough
Lethargy
Dysphagia
Regurgitation
Anorexia
Weight loss
Horner's syndrome
Change in bark
Facial edema
Functional (Hyperthyroid)
Swelling or mass in neck
Polyphagia and weight loss
Hyperactivity
Polyuria and polydipsia
Panting
Change in behavior
Aggression
FIG 5 1 - 2 2
A , A 13-year-old male Labrador Retriever was presented to
the veterinarian because the client noticed a mass in the with large invasive tumors that destroy both thyroid lobes.
neck (arrows). The mass was a thyroid adenocarcinoma. Clinical signs of hyperthyroidism occur i n approximately
B, Thyroid adenocarcinoma in an 1 1-year-old mixed-breed
10% of dogs with thyroid tumors and are similar to those
dog. Clinical signs included dysphagia, coughing, and a
visible mass in the ventral region of the neck. seen in hyperthyroid cats (see p. 748).
M o s t thyroid tumors are firm, asymmetric, lobulated, and
nonpainful masses located close to the typical thyroid region
in the neck. The mass is usually well embedded in surround
retropharyngeal and cervical l y m p h nodes and lungs is ing tissue and not freely movable. Additional physical exam
common. Metastasis to other locations such as the liver, ination findings may include dyspnea, cough, cachexia,
kidney, bone, and brain is also possible. lethargy, Horner's syndrome, and dehydration. A dry, luster-
Most dogs with thyroid tumors are euthyroid or hypothy less haircoat is c o m m o n , but alopecia is rare. M a n d i b u l a r or
roid; approximately 10% of dogs have functional thyroid cervical l y m p h nodes (or both) may be enlarged as a result
tumors that secrete excess thyroid hormone, causing hyper of tumor spread or lymphatic obstruction. Dogs with func
thyroidism. Clinical signs of hyperthyroidism may predom tional thyroid tumors may be restless, thin, and panting, and
inate in these dogs. Hyperthyroidism may be caused by auscultation of the heart frequently reveals tachycardia. Sur
functional thyroid adenomas and carcinomas. Adenomatous prisingly, many dogs are found to be remarkably healthy on
hyperplasia is the most c o m m o n cause of hyperthyroidism physical examination.
in cats but has not been described in dogs. C B C , serum biochemistry panel, and urinalysis findings
usually do not help establish the diagnosis. A m i l d normo
Clinical Features cytic, normochromic, nonregenerative anemia, hypercholes
Thyroid tumors occur i n middle-aged to older dogs, with an terolemia, and hypertriglyceridemia causing lipemia may be
average age of 10 years. There is no sex-related predilection. present i n dogs with concurrent hypothyroidism. A m i l d
Although any breed can be affected, Boxers, Beagles, and increase in the blood urea nitrogen concentration and liver
Golden Retrievers may be at an increased risk. enzyme activities has been identified i n less than 35% of
Dogs with nonfunctional thyroid tumors are usually dogs; however, the latter changes were not found to be indic
brought to veterinarians because the client has seen or felt a ative of hepatic metastasis. Hypercalcemia has also been
mass in the ventral region of the dog's neck (Fig. 51-22). noted in a few dogs.
Clinical signs may develop as a result of the mass compress Baseline serum T and f T concentrations are increased
4 4
ing on adjacent structures (e.g., dyspnea, dysphagia) or as a and serum T S H is undetectable in dogs with a functional
result of metastasis (e.g., exercise intolerance, weight loss; thyroid tumor causing hyperthyroidism. However, most
Box 51-9). Clinical signs of hypothyroidism may develop canine thyroid tumors are nonfunctional, and most of these
FIG 51-23
U l t r a s o u n d i m a g e of a mass in the r e g i o n of the right
thyroid l o b e (straight arrow), the c a r o t i d artery (broken
arrow), a n d the t r a c h e a (curved arrow) in a n 1 1-year-old FIG 51-24
f e m a l e s p a y e d L a b r a d o r m i x . A small r e g i o n of m i n e r a l i z a M a g n e t i c r e s o n a n c e i m a g e of a right-sided thyroid mass
tion c a u s i n g a s h a d o w i n g effect is e v i d e n t within the mass. (solid arrow) a d j a c e n t to the trachea (broken arrow) in a
The mass w a s a n u n e x p e c t e d f i n d i n g d u r i n g a routine 10-year-old m a l e castrated G o l d e n Retriever that w a s
p h y s i c a l e x a m i n a t i o n . T h y r o i d a d e n o c a r c i n o m a w a s the presented for a s w e l l i n g in the neck. The histopathologic
h i s t o p a t h o l o g i c d i a g n o s i s after s u r g i c a l r e m o v a l of the mass. d i a g n o s i s w a s thyroid C-cell c a r c i n o m a with v a s c u l a r
i n v a s i o n . The affected r e g i o n of the neck w a s treated with
r a d i a t i o n after thyroidectomy.
Surgical excision of thyroid adenomas and small, well-encap body surface area intravenously every 3 to 6 weeks is the
sulated, movable thyroid carcinomas is likely to be curative. historic treatment o f choice. The response o f canine thyroid
Surgical removal o f a fixed, invasive thyroid carcinoma, tumors to doxorubicin is variable. In most dogs doxorubicin
regardless of size, carries a guarded to poor prognosis for prevents further growth o f the t u m o r and may cause the
complete excision of the tumor. Megavoltage irradiation is t u m o r to shrink, but total remission is u n c o m m o n . C o m b i
the treatment of choice for these tumors. Chemotherapy is nation chemotherapy with 5-fluorouracil, cyclophospha
indicated i f distant metastasis is identified. Surgical debulk mide, and/or vincristine may enhance the effectiveness o f
ing of fixed, invasive tumors is indicated to relieve tumor- doxorubicin. Cisplatin or carboplatin should be considered
induced problems such as dysphagia or dyspnea and allow i n dogs that fail to respond to or have recurrence o f disease
more time for other therapies to work. Surgical debulking with doxorubicin therapy. The response to cisplatin has been
may also be considered after megavoltage irradiation or che reported to be similar to the response to doxorubicin,
motherapy has caused the size o f large invasive tumors to although several cisplatin-treated dogs were previously
shrink. Aggressive attempts at surgical removal, especially o f treated w i t h doxorubicin (Fineman et al., 1998). (See Chap
bilateral tumors, threaten the integrity o f recurrent laryngeal ters 77 and 78 for a discussion o f the use o f these chemo
nerves, parathyroid glands, and normal thyroid tissue. It is therapeutic agents.)
important to monitor serum calcium concentrations before
1 3 1
and for 7 to 10 days after surgery i f there is any chance that RADIOACTIVE IODINE ( l)
the parathyroid glands have been excised or damaged. Recent retrospective studies suggest that I therapy will131
V i t a m i n D and calcium therapy should be initiated i f any prolong survival times when used as sole therapy or i n
evidence of hypoparathyroidism is found (see p. 735). Serum combination with surgery for the treatment o f thyroid
T , fT , and T S H concentrations should be monitored 2 to 3
4 4 tumors i n dogs. W o r t h et al. (2005) reported a median sur
weeks after surgery and, depending on clinical signs, replace vival time o f 30 months for dogs treated with radioiodine
ment therapy implemented accordingly (see p. 741). (See alone, 34 months when radioiodine was combined with
Slatter [2003] and Fossum [2007] for information o n surgi surgery, and 3 months for dogs that d i d not receive treat
cal techniques for the thyroparathyroid complex.) ment. Turrell et al. (2006) reported a median survival time
of 839 days for dogs with local or regional tumors (i.e., stage
MEGAVOLTAGE IRRADIATION II and III disease) and 366 days for dogs with metastasis.
Megavoltage irradiation is the treatment of choice for locally T u m o r site (cervical versus ectopic), age, body weight, treat
131
advanced thyroid carcinoma. Megavoltage irradiation can be ment protocol ( I alone or with surgery), and serum T 4
used alone or i n conjunction with surgery or chemotherapy. concentration were not significantly associated with survival
There is a slow regression rate o f thyroid carcinoma after time. Iodine 131 therapy is useful for any thyroid tumor
radiation therapy i n dogs. In one study involving 25 dogs tissue that can accumulate organic iodine, including meta
with unresectable differentiated thyroid carcinoma and no static sites. Kinetic studies to evaluate the ability of the t u m o r
evidence of metastasis, the time to attain m a x i m u m reduc to trap iodine should be conducted before considering
131
radioactive iodine treatment. Large doses o f I (i.e., 30 to Kyfe JC et al: Congenital hypothyroidism with goiter in Toy Fox
150 m C i ) are typically administered intravenously or subcu Terriers, / Vet Intern Med 17:50, 2003.
taneously to treat canine thyroid tumors. Potential adverse Marca M C et al: Evaluation of canine serum thyrotropin (TSH)
reactions include esophagitis, tracheitis, and bone marrow concentration: comparison of three analytical procedures, / Vet
Diag Invest 13:106, 2001.
suppression.
Nachreiner RF et al: Prevalence of serum thyroid hormone autoan
tibodies in dogs with clinical signs of hypothyroidism, / Am Vet
O R A L ANTITHYROID D R U G S
Med Assoc 220:466, 2002.
Oral antithyroid drugs are used as palliative therapy to Peterson M E et al: Measurement of serum total thyroxine, triiodo
control the clinical signs of hyperthyroidism i n dogs with thyronine, free thyroxine, and thyrotropin concentrations for
functional thyroid tumors. O r a l antithyroid drugs are not diagnosis of hypothyroidism in dogs, / Am Vet Med Assoc
used as a primary treatment because they are not cytotoxic. 211:1396, 1997.
The therapeutic approach is similar to that used i n hyper Pullen W H , Hess RS: Hypothyroid dogs treated with intravenous
thyroid cats (see p. 754), beginning with 2.5 m g of methim levothyroxine, / Vet Intern Med 20:32, 2006.
azole administered twice a day, with subsequent increases i n Schachter S et al: Comparison of serum free thyroxine concentra
the dosage and frequency o f administration as needed to tions determined by standard equilibrium dialysis, modified
equilibrium dialysis, and 5 radioimmunoassays in dogs, / Vet
control clinical signs and maintain the serum T concentra4
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tion w i t h i n the reference range.
Scott-Moncrieff JCR et al: Lack of association between repeated
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Prognosis
Med 20:818, 2006.
The prognosis for thyroid adenomas is excellent after surgi Stegeman JR et al: Use of recombinant human thyroid-stimulating
cal removal. The prognosis is guarded to good for dogs hormone for thyrotropin-stimulation testing of euthyroid cats,
that undergo surgical resection of small, well-encapsulated Am] Vet Res 64:149, 2003.
carcinomas. Unfortunately, most dogs have relatively large
thyroid masses, which have frequently invaded surrounding FELINE HYPERTHYROIDISM
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aggressive therapy using multiple treatments can alleviate hyperthyroid cats, Vet Radiol Ultrasound 43:587, 2002.
Court M H et al: Identification and concentration of soy isoflavones
the clinical signs and i n some cases dramatically reduce the
in commercial cat foods, Am I Vet Res 63:181, 2002.
tumor burden. The long-term prognosis, however, remains
Fischetti AJ et al: Effects of methimazole on thyroid gland uptake
guarded to poor, with survival times typically ranging 99m
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Feldman EC, Nelson RW: Canine and feline endocrinology and Hoffman SB et al: Bioavailability of transdermal methimazole in a
reproduction, ed 3, St Louis, 2004, WB Saunders. pluronic lecithin organogel (PLO) in healthy cats, / Vet Intern
Fossum TW: Small animal surgery, ed 3, St Louis, 2007, Mosby. Med 16:359, 2002.
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CANINE AND FELINE HYPOTHYROIDISM Martin K M et al: Evaluation of dietary and environmental risk
Bromel C et al: Ultrasound of the thyroid gland in healthy, hypo factors for hyperthyroidism in cats, ] Am Vet Med Assoc 217:853,
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Graham PA et al: A 12-month prospective study of 234 thyro- Milner RJ et al: Survival times for cats with hyperthyroidism treated
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C H A P T E R 52
Disorders of the
Endocrine Pancreas
I N S U L I N - S E C R E T I N G -CELL N E O P L A S I A
CHAPTER OUTLINE
Signalment
Clinical Signs
HYPERGLYCEMIA
Physical Examination
HYPOGLYCEMIA
Clinical Pathology
DIABETES MELLITUS IN D O G S
Overview of Treatment
Signalment
Perioperative Management of Dogs Undergoing Surgery
History
Postoperative Complications
Physical Examination
Medical Treatment for C h r o n i c Hypoglycemia
Overview of Insulin Preparations
GASTRIN-SECRETING NEOPLASIA
Storage and D i l u t i o n of Insulin
Initial Insulin Recommendations for Diabetic Dogs
Diet
Exercise HYPERGLYCEMIA
Identification and C o n t r o l of Concurrent Problems
Protocol for Identifying Initial Insulin Requirements Etiology
History and Physical Examination Hyperglycemia is present i f the blood glucose concentration
Single B l o o d Glucose Determination is greater than 130 mg/dl, although clinical signs of hyper
Serum Fructosamine Concentration glycemia do not develop until the renal tubular threshold for
Urine Glucose M o n i t o r i n g the resorption of glucose is exceeded. In dogs this typically
Serial B l o o d Glucose Curves occurs whenever the blood glucose concentration exceeds
Insulin Therapy D u r i n g Surgery 180 to 220 mg/dl. The threshold for glucose resorption
Complications of Insulin Therapy appears to be more variable i n cats, ranging from 200 to
C h r o n i c Complications of Diabetes Mellitus 280 mg/dl. Glycosuria causes an osmotic diuresis, which in
DIABETES MELLITUS I N C A T S turn causes polyuria and polydipsia, the hallmark clinical
Signalment signs of severe hyperglycemia (greater than 180 mg/dl in
History dogs and greater than 200 to 280 mg/dl i n cats). The most
Physical Examination c o m m o n cause of hyperglycemia and glycosuria is diabetes
Initial Insulin Recommendations for Diabetic Cats mellitus. Severe hyperglycemia without glycosuria also
Diet occurs c o m m o n l y in cats with stress-induced hyperglycemia,
Identification and C o n t r o l of Concurrent Problems presumably resulting from the secretion of catecholamines
Oral Hypoglycemic Drugs and possibly lactate. Transient glycosuria (typically less than
Identifying Initial Insulin Requirements 1% on urine glucose test strips) may occur i n some cats with
Insulin Therapy D u r i n g Surgery severe or prolonged stress-induced hyperglycemia.
Complications of Insulin Therapy
C h r o n i c Complications of Diabetes Mellitus Clinical Features
DIABETIC K E T O A C I D O S I S Hyperglycemia of between 130 and 180 mg/dl (possibly as
Fluid Therapy high as 280 mg/dl i n cats) is clinically silent and is often an
Insulin Therapy unsuspected finding encountered during blood testing for
Concurrent Illness another reason. If a dog or cat with m i l d hyperglycemia (less
Complications o f Therapy for Diabetic Ketoacidosis than 180 mg/dl) and no glycosuria is seen because of poly-
BOX 52-1 BOX 52-2
Causes of Hyperglycemia i n Dogs and Cats Causes o f Hypoglycemia i n Dogs and Cats
Breeds Recognized to Have H i g h and L o w Risk for Developing Diabetes Mellitus Based on Analysis of the Veterinary
M e d i c a l Database ( V M D B ) from 1970 to 1993.*
BREEDS WITH HIGH RISK O D D S RATIO BREEDS WITH L O W RISK ODDS RATIO
From Guptill L et al: Is canine diabetes on the increase? In Recent advances in clinical management of diabetes mellitus, lams Company,
Dayton, Ohio, 1999, p. 24. Mixed-breed dogs were used as the reference group (Odds Ratio 1.00] for comparison with other breeds.
*The VMDB comprises medical records of 24 veterinary schools in the United States and Canada. VMDB case records analyzed included
those from first hospital visits of 6078 dogs with a diagnosis of diabetes mellitus and 5,922 randomly selected dogs with first hospital visits
for any diagnosis other than diabetes mellitus seen at the same veterinary schools in the same year. Only breeds with more than 25 cases of
diabetes mellitus are included.
Breeds also identified with significant high or low risk for developing diabetes in a study by Hess RS et al: Breed distribution of dogs with
diabetes mellitus admitted to a tertiary care facility, J Am Vet Med Assoc 21 6:1414, 2000.
HISTORY
The history in virtually all diabetic dogs includes polydipsia,
polyuria, polyphagia, and weight loss. Polyuria and polydip
sia do not develop until hyperglycemia results i n glycosuria.
Occasionally, a client brings i n a dog because of sudden
blindness caused by cataract formation (Fig. 52-1). The
typical clinical signs of diabetes were either unnoticed or
considered irrelevant by the client. If the clinical signs asso
ciated with uncomplicated diabetes are not observed by the
client and impaired vision caused by cataracts does not
develop, a diabetic dog is at risk for the development of
systemic signs of illness as progressive ketonemia and meta
bolic acidosis develop. The time sequence from the onset of
initial clinical signs to the development of diabetic ketoaci
dosis ( D K A ) is unpredictable, ranging from days to weeks.
FIG 52-1
PHYSICAL E X A M I N A T I O N Bilateral c a t a r a c t s c a u s i n g blindness in a d i a b e t i c d o g .
Physical examination findings depend on the presence and (From F e l d m a n E C , N e l s o n R W : Canine and feline endocri
severity of D K A , on the duration of diabetes before its diag nology and reproduction, e d 3 , St Louis, 2 0 0 4 , W B
Saunders.)
nosis, and on the nature of any other concurrent disorder.
The nonketotic diabetic dog has no classic physical examina
tion findings. M a n y diabetic dogs are obese but are otherwise brittle and lusterless; and scales from hyperkeratosis may be
in good physical condition. Dogs with prolonged untreated present. Diabetes-induced hepatic lipidosis may cause hepa
diabetes may have lost weight but are rarely emaciated unless tomegaly. Lenticular changes consistent with cataract forma
concurrent disease (e.g., pancreatic exocrine insufficiency) is tion are c o m m o n . Additional abnormalities may be identified
present. The haircoat may be sparse; the hairs may be dry, if D K A is present (see p. 796).
Diagnosis
The diagnosis of diabetes mellitus is based o n three findings:
appropriate clinical signs, persistent fasting hyperglycemia, Clinicopathologic Abnormalities Commonly Found in
and glycosuria. Measurement of the blood glucose concen Dogs and Cats with Uncomplicated Diabetes Mellitus
tration using a portable b l o o d glucose-monitoring device
Complete Blood Count
and testing for the presence of glycosuria using urine reagent
test strips (e.g., KetoDiastix; Ames Division, Miles Laborato Typically normal
ries) provides rapid confirmation of diabetes mellitus. C o n Neutrophilic leukocytosis, toxic neutrophils if pancreatitis or
current documentation of ketonuria establishes a diagnosis infection present
laboratory evaluation should include a C B C , serum bio Normal or increased if pancreatitis present
Baseline serum insulin concentration
chemistry panel, measurement of serum pancreatic lipase
IDDM: low, normal
immunoreactivity, and urinalysis with bacterial culture.
NIDDM: low, normal, increased
Serum progesterone concentration should be determined i f
Insulin resistance induced: low, normal, increased
diabetes mellitus is diagnosed i n an intact bitch, regardless
of her cycling history. If available, abdominal ultrasound is IDDM, Insulin-dependent diabetes mellitus; NIDDM, non-insulin-
indicated to assess for pancreatitis, adrenomegaly, pyometri dependent diabetes mellitus.
tis in an intact bitch, and abnormalities affecting the liver
and urinary tract (e.g., changes consistent with pyelonephri
tis or cystitis). Measurement o f baseline serum insulin con plication o f therapy. Hypoglycemia is most apt to occur
centration or an insulin response test is not routinely done. as the result o f overzealous insulin therapy. The veter
Additional tests may be warranted after obtaining the history, inarian must balance the benefits o f tight glucose control
performing the physical examination, or identifying keto obtainable with aggressive insulin therapy against the risk o f
acidosis. Potential clinical pathologic abnormalities are listed hypoglycemia.
in Box 52-4.
O V E R V I E W OF INSULIN
Treatment PREPARATIONS
The primary goal of therapy is elimination of client-observed Types o f insulin typically used for the home treatment of
clinical signs of diabetes. Persistence o f clinical signs and diabetes i n dogs and cats include intermediate-acting insulin
development of chronic complications (Box 52-5) are ( N P H , lente) and long-acting basal insulin (PZI, insulin
directly correlated with the severity and duration o f hyper glargine; (Table 52-2). N P H ( H u m u l i n N, E l i Lilly) is a
glycemia. In the diabetic dog establishing control o f hyper recombinant h u m a n insulin, lente (Vetsulin, Intervet) is a
glycemia can be accomplished with insulin, diet, exercise, purified pork-source insulin, and P Z I (PZI Vet, I D E X X ) is
prevention or control o f concurrent insulin antagonistic dis a beef/pork-source insulin with approximately 90% being
eases, and discontinuation of medications that cause insulin beef-source insulin. Insulin glargine (Lantus, Aventis Phar
resistance. The veterinarian must also guard against develop maceuticals) is a long-acting insulin analog i n w h i c h the
ment of hypoglycemia, a serious and potentially fatal c o m - amino acid sequence has been altered, compared with h u m a n
insulin, making glargine more soluble at a slightly acidic p H
BOX 52-5
and less soluble at a physiological p H than human insulin.
Complications of Diabetes Mellitus in Dogs and Cats The solution in the bottle o f glargine is acidic, which keeps
glargine soluble and suspended in the solution (i.e., the solu
Common
tion is clear, and the bottle does not need to be rolled before
Iatrogenic hypoglycemia the insulin is drawn into the syringe). Because of this depen
Persistent or recurring polyuria, polydipsia, weight loss dency o n p H , glargine cannot be diluted or mixed with any
Cataracts (dog) thing that may change the p H of the solution. Glargine forms
Lens-induced uveitis (dog)
microprecipitates i n the subcutaneous tissue at the site of
Bacterial infections, especially involving the urinary tract
injection, from which small amounts of insulin glargine are
Chronic pancreatitis
slowly released and absorbed into the circulation. In humans
Recurring ketosis, ketoacidosis
Hepatic lipidosis
the slow, sustained release of insulin glargine from these
Peripheral neuropathy (cat) microprecipitates results i n a relatively constant concentra
Systemic hypertension (dog) tion/time profile over a 24-hour period with no pronounced
peak i n serum insulin. Insulin glargine is currently recom
Uncommon
mended as a basal insulin (i.e., sustained long-acting insulin
Peripheral neuropathy (dog) used to inhibit hepatic glucose production) administered
Diabetic nephropathy once a day at bedtime and used i n conjunction with either
Significant proteinuria prandial insulin analogs or oral hypoglycemic drugs in
Glomerulosclerosis
h u m a n diabetics.
Retinopathy
Exocrine pancreatic insufficiency
S T O R A G E A N D DILUTION OF INSULIN
Gastric paresis
Intestinal hypomotility and diarrhea Freezing, heating, and shaking the insulin bottle inactivate
Diabetic dermatopathy (i.e., superficial necrolytic dermatitis) insulin i n the bottle. Although keeping the substance at
" r o o m temperature": does not inactivate insulin, I instruct
clients to store insulin i n the door of the refrigerator to
maintain a consistent environment and prolong the life of
TABLE 52-2
Commonly Used Insulin Preparations for Treating Diabetes in Dogs and Cats
TYPICAL DURATION OF
ADMINISTRATION EFFECT (hr)
Correct obesity and maintain body weight in an acceptable range (see Chapter 54).
Control daily caloric intake.
Increase daily exercise.
Avoid excessive amounts of insulin.
Maintain consistency in the timing and caloric content of the meals.
Feed within the time frame of insulin action.
Feed one half the daily caloric intake at the time of each insulin injection with q12h insulin therapy or at the time of the
insulin injection and 8 to 10 hours later with q24h insulin therapy.
Minimize the impact of food on postprandial blood glucose concentrations.
Avoid monosaccharides and disaccharides, propylene glycol, and corn syrup.
Let "nibbler" cats and dogs nibble throughout the day and night; ensure that other pets do not have access to the food.
Increase the fiber content of the diet (dogs).
Feed high-protein, low-carbohydrate diets (cats).
Veterinary Diets for Diabetic Dogs Veterinary Diets for Diabetic Cats
Hill's Prescription Diet w / d High-protein, low-carbohydrate diets:
Hill's Prescription Diet r / d (obese diabetic dog) Purina D M
Purina D C O Hill's Prescription Diet M D
Purina O M (obese diabetic dog) Royal-Canin Diabetic DS 4 4
Royal Canin Diabetic HF
Royal Canin Calorie Control C C High Fiber Fiber-containing diets:
(obese diabetic dog) Hill's Prescription Diet w / d
lams Optimum Weight Control Hill's Prescription Diet r/d (obese diabetic cat)
Purina O M (obese diabetic cat)
Royal-Canin Calorie Control C C
High Fiber (obese diabetic cat)
betic dog. A thorough history, physical examination, and ress of therapy; and, if possible, the b l o o d glucose concentra
complete diagnostic evaluation are imperative i n the newly tions range between 100 and 250 m g / d l throughout the day.
diagnosed diabetic dog (see the section on diagnosis, p. 769). The client is informed at the time insulin therapy is initiated
that it w i l l take approximately 1 m o n t h to establish a satisfac
PROTOCOL FOR IDENTIFYING INITIAL tory insulin treatment protocol, assuming unidentified
INSULIN REQUIREMENTS insulin-antagonistic disease is not present. The goals of
Diabetic dogs require several days to equilibrate to changes therapy are also explained to the client. D u r i n g this m o n t h
in insulin dose or preparation. Therefore newly diagnosed changes i n insulin dose, type, and frequency o f administra
diabetic dogs are typically hospitalized for no more than 24 tion are c o m m o n and should be anticipated by the client. A t
to 48 hours to finish the diagnostic evaluation o f the dog and each evaluation the client's subjective o p i n i o n o f water
begin insulin therapy. D u r i n g hospitalization b l o o d glucose intake, urine output, and overall health o f the pet is dis
concentrations are typically determined at the time insulin cussed; a complete physical examination is performed;
is administered and 3, 6, and 9 hours later. The intent is to change i n body weight noted; and serial b l o o d glucose mea
identify hypoglycemia (i.e., b l o o d glucose less than 80 m g / surements obtained over an 8- to 12-hour period after
dl) i n those dogs that are unusually sensitive to the actions insulin administration are assessed. Adjustments i n insulin
of insulin. If hypoglycemia occurs, the insulin dose is therapy are based o n this information, the pet is sent home,
decreased before sending the dog home. The insulin dose is and an appointment is scheduled for the next week to reeval
not adjusted i n those dogs that remain hyperglycemic during uate the response to any change i n therapy. If the dog remains
the first few days of insulin therapy. The objective during this poorly controlled, the dose o f insulin is gradually increased
first visit is not to establish perfect glycemic control before by 1 to 5 U/injection (depending o n the size o f the dog) each
sending the dog home. Rather, the objective is to begin to week until control is attained. This gradual increase i n dose
reverse the metabolic derangements induced by the disease, helps prevent hypoglycemia and the Somogyi response.
allow the patient to equilibrate to the insulin and change i n C o n t r o l o f glycemia can be established i n most dogs using
diet, teach the client how to administer insulin, and give the insulin doses i n the range o f 1.0 U o f insulin/kg or less
client a few days to become accustomed to treating the dia administered twice each day. If the insulin dose exceeds
betic dog at home. Adjustments i n insulin therapy are made 1.5 U/kg/injection without adequate glycemic control, then
on subsequent evaluations, once the client and pet have further investigations to determine the reason for treatment
become accustomed to the treatment regimen. failure are indicated (see the section on complications o f
Diabetic dogs are typically evaluated once weekly until an insulin therapy, p. 779). If hypoglycemia is noted either clin
effective insulin treatment protocol is identified. Glycemic ically or biochemically at any time, the insulin dosage should
control is attained when clinical signs o f diabetes have be decreased and further adjustments i n the insulin dose
resolved; the pet is healthy and interactive i n the home; its performed as needed to attain glycemic control.
body weight is stable (unless the dog is undergoing weight M a n y factors affect the dog's glycemic control from day
loss to correct obesity); the client is satisfied with the prog to day, including variations i n insulin administration and
absorption, dietary indiscretions and caloric intake, amount mia supports insulin overdosage and the need to decrease
of exercise, and variables that affect insulin responsiveness the insulin dose, especially i f glycemic control is poor (see
(e.g., stress, concurrent inflammation, infection). As a con the discussion of the Somogyi response, p. 780). In contrast,
sequence, the insulin dosage required to maintain glycemic documenting an increased blood glucose concentration does
control typically changes with time. Initially, a fixed dose of not, by itself, confirm poor control of glycemia. Stress or
insulin is administered at home and changes are made only excitement can cause marked hyperglycemia, which does not
after the client consults with the veterinarian. A s the insulin reflect the dog's responsiveness to insulin and can lead to the
dose range required to maintain glycemic control becomes erroneous belief that the diabetic dog is poorly controlled. If
apparent and as confidence is gained in the client's ability to a discrepancy exists between the history, physical examina
recognize signs of hypoglycemia and hyperglycemia, the tion findings, and blood glucose concentration or i f the dog
client is eventually allowed to make slight adjustments in the is fractious, aggressive, excited, or scared and the blood
insulin dose at home on the basis of clinical observations of glucose concentration is k n o w n to be unreliable, measure
the pet's well-being. However, the client is instructed to stay ment of serum fructosamine concentration should be done
within the agreed-upon insulin dose range. If the insulin to further evaluate status of glycemic control. In addition, a
dose is at the upper or lower end of the established range single blood glucose concentration is not reliable for evaluat
and the pet is still symptomatic, the client is instructed to ing the effect of a given insulin type and dose in a poorly
call the veterinarian before making further adjustments i n controlled diabetic dog (see the section on serial blood
the insulin dose. glucose curve).
Sample Handling, Methodology, and Normal Values for Serum Fructosamine Concentrations Measured
in Our Laboratory
FRUCTOSAMINE
lower half of the normal reference range (i.e., less than dog i n which clinical manifestations of hyperglycemia or
300 mol/L) or below the normal reference range should hypoglycemia have developed. Reliance o n history, physical
raise concern for significant periods of hypoglycemia i n the examination, body weight, and serum fructosamine concen
diabetic dog. Increased serum fructosamine concentrations tration to determine when a b l o o d glucose curve is needed
(i.e., >500 mol/L) suggest poor control of glycemia and a helps reduce the frequency with which blood glucose curves
need for insulin adjustments but do not identify the under must be performed, thereby m i n i m i z i n g the animal's aver
lying problem. sion to these evaluations and i m p r o v i n g the chances of
obtaining meaningful results when a b l o o d glucose curve is
URINE GLUCOSE MONITORING needed.
Occasional monitoring of urine for glycosuria and ketonuria W h e n a b l o o d glucose curve is being generated, the insulin
is helpful in diabetic dogs that have problems with recurring and feeding schedule used by the client should be m a i n
ketosis or hypoglycemia to identify ketonuria or persistent tained, the dog dropped off at the hospital early in the
negative glycosuria, respectively. The client is instructed not morning, and blood obtained every 1 to 2 hours throughout
to adjust daily insulin doses on the basis of m o r n i n g urine the day for glucose determination. It is more important to
glucose measurements, except to decrease the insulin dose i n maintain the pet's daily routine than to risk inaccurate blood
dogs with recurring hypoglycemia and persistent negative glucose results caused by inappetence i n the hospital or
glycosuria. The vast majority of diabetic dogs develop c o m insulin administration at an unusual time (Fig. 52-2). If
plications because clients were misled by m o r n i n g urine there are concerns regarding the client's technique for a d m i n
glucose concentrations. Persistent glycosuria throughout the istering insulin, the client can administer insulin (using his
day and night suggests inadequate control of the diabetic or her o w n insulin and syringe) i n the hospital after the
state and the need for a more complete evaluation of diabetic initial blood glucose is obtained or can demonstrate his or
control using other techniques discussed i n this section. her technique using sterile saline after arriving to pick up the
pet at the end of the day. The veterinarian or a veterinary
SERIAL BLOOD GLUCOSE CURVES technician should closely evaluate the entire insulin a d m i n
If an adjustment i n insulin therapy is deemed necessary after istration procedure. By measuring b l o o d glucose concentra
review of the history, physical examination, changes i n body tion every 1 to 2 hours throughout the day, the clinician w i l l
weight, and serum fructosamine concentration, then a serial be able to determine i f the insulin is effective and identify
blood glucose curve should be generated to provide guid the glucose nadir, time of peak insulin effect, duration of
ance in making the adjustment, unless b l o o d glucose mea insulin effect, and severity of fluctuation i n blood glucose
surements are unreliable because of stress, aggression, or concentrations i n that particular dog. Determining the
excitement. The serial blood glucose curve provides guide glucose nadir and the time of the glucose nadir i n relation
lines for making adjustments i n insulin therapy. Evaluation to the time of insulin administration is critical for assessing
of a serial blood glucose curve is mandatory during the the duration of insulin effect. If the glucose nadir has not
initial regulation of the diabetic dog and is necessary i n the been identified by the time of the next insulin injection, the
glucose curve should be continued, the scheduled insulin betic state often stems from misinterpretation of the effects
injection aborted, and the dog fed its evening meal (see the of insulin that is based o n assessment o f only 1 or 2 blood
discussion o f the prolonged duration o f insulin effect, glucose concentrations.
p. 781). Obtaining only 1 or 2 blood glucose concentrations Blood glucose concentrations are typically determined by
has not been reliable for evaluating the effect o f a given a point-of-care glucose analyzer or hand-held portable blood
insulin dose (Fig. 52-3). Persistent poor control o f the dia- glucose monitoring device. Commercially available portable
blood glucose-monitoring devices provide blood glucose
concentrations that are reasonably close to those obtained
with reference methods, although results often overestimate
or underestimate actual glucose values. Blood glucose values
determined by most portable blood glucose monitoring
devices are typically lower than actual glucose values deter
mined b y reference methods (Fig. 52-4). This may result i n
an incorrect diagnosis of hypoglycemia or the misperception
that glycemic control is better than it actually is. Failure to
consider this error could result i n insulin underdosage and
the potential for persistence of clinical signs despite appar
ently acceptable blood glucose results. One exception is the
AlphaTRAK by Abbott Laboratories. Accuracy of this por
table glucometer is very good, but glucose values may be
higher or lower than glucose values measured by benchtop
FIG 5 2 - 2 methodologies o n the same blood sample, forcing the vet
M e a n b l o o d g l u c o s e c o n c e n t r a t i o n s in eight d i a b e t i c d o g s erinarian to accept the blood glucose concentration at face
after the a d m i n i s t r a t i o n of N P H insulin (T) a n d the f e e d i n g value.
of e q u a l - s i z e d meals at 8 A M a n d 6 P M (blue line) or Insulin therapy is adjusted according to interpretation of
f e e d i n g them nothing (red line) d u r i n g the 2 4 hours of a single serial blood glucose curve, and the impact of the
blood sampling.
change is initially assessed by client perceptions of clinical
response and change i n serum fructosamine concentration.
If problems persist, the blood glucose curve can be repeated.
If possible, performing blood glucose curves o n multiple,
consecutive days should be avoided because it promotes
stress-induced hyperglycemia. Information gained from a
prior serial b l o o d glucose curve should never be assumed to
be reproducible o n subsequent curves. Lack of consistency
in the results o f serial blood glucose curves is a source of
frustration for many veterinarians. This lack of consistency
is a direct reflection of all the variables that affect the blood
glucose concentration i n diabetics. Daily self-monitoring of
blood glucose concentrations and adjustments i n insulin
dose are used i n h u m a n diabetics to minimize the effect of
these variables o n control of glycemia. A similar approach
for diabetic dogs and cats will undoubtedly become more
c o m m o n i n the future, as home glucose monitoring tech
niques are refined. For now, initial assessment of control of
FIG 5 2 - 3 glycemia is based o n the client's perception of the diabetic
B l o o d g l u c o s e c o n c e n t r a t i o n c u r v e in a D a c h s h u n d r e c e i v i n g
pet's health combined with periodic examinations by the
0 . 8 U of r e c o m b i n a n t h u m a n lente insulin p e r k i l o g r a m of
b o d y w e i g h t t w i c e a d a y (solid line), a M i n i a t u r e P o o d l e
veterinarian. Serial blood glucose measurements are indi
r e c e i v i n g 0 . 6 U of r e c o m b i n a n t h u m a n lente insulin p e r cated i f poor control o f glycemia is suspected. The goal of
kilogram of b o d y weight twice a d a y (dashed line), a n d a serial b l o o d glucose measurements is to obtain a glimpse of
Terrier-mix r e c e i v i n g 1.1 U of r e c o m b i n a n t h u m a n lente the actions o f insulin i n that diabetic animal and identify a
insulin p e r k i l o g r a m of b o d y w e i g h t t w i c e a d a y (dotted possible reason that the diabetic dog is poorly controlled.
line). Insulin a n d f o o d w a s g i v e n to e a c h d o g at 8 A M .
Interpretation of the b l o o d g l u c o s e curves suggest short
Protocol for Generating the Serial Blood
d u r a t i o n of insulin effect in the D a c h s h u n d , insulin underdos
ing in the M i n i a t u r e P o o d l e , a n d the S o m o g y i r e s p o n s e in
Glucose Curve at Home
the Terrier-mix. The b l o o d g l u c o s e concentrations w e r e similar Hyperglycemia induced by stress, aggression, or excitement
in a l l d o g s at 2 P M a n d 4 P M ; the g l u c o s e results at these is the single biggest problem affecting accuracy of the serial
times d o not establish the d i a g n o s i s in a n y of the d o g s . blood glucose curve, especially in cats (Fig. 52-5). The biggest
FIG 5 2 - 4
Scatter plots of blood glucose concentrations obtained with two portable blood-glucose
meters versus concentrations obtained using a reference method. Data represent 110
blood samples from 3 4 dogs. Shaded areas represent concentrations greater than or less
than the concentrations that can be detected by each meter. The dashed line represents
the theoretical line of equality. Note that one glucose meter tends to read higher (A) and
one glucose meter tends to read lower (B) than the reference concentration. (From Cohn
LA ef al: Assessment of five portable blood glucose meters, a point-of-care analyzer, and
color test strips for measuring blood glucose concentration in dogs, J Am Vet Med Assoc
2 1 6 : 1 9 8 , 2000.)
factors inducing stress-induced hyperglycemia are hospital decrease i n the b l o o d glucose concentration after insulin
ization and multiple venipunctures. A n alternative to hospi administration. Assessment of duration of insulin effect may
tal-generated blood glucose curves is to have the client not be valid when the b l o o d glucose decreases to less than
generate the blood glucose curve at home using the ear or 80 mg/dl or decreases rapidly because of the potential induc
lip prick technique and a portable home glucose-monitoring tion of the Somogyi response, which can falsely decrease the
device that allows the client to touch the drop of b l o o d o n apparent duration o f insulin effect (see p. 780). A rough
the ear or lip with the end o f the glucose test strip. This approximation o f the duration o f effect o f insulin can be
technique is usually reserved for diabetic dogs i n which the gained by examining the time of the glucose nadir. For most
reliability of blood glucose results generated i n the veterinary well-controlled diabetic dogs, the initial b l o o d glucose con
hospital is questionable. The reader is referred to p. 792 for centration near the time o f insulin administration is less
more information o n monitoring b l o o d glucose concentra than 300 m g / d l and the glucose nadir occurs 8 to 10 hours
tions at home. after injection of insulin. A n initial b l o o d glucose concentra
tion greater than 300 mg/dl, combined with a glucose nadir
Interpreting the Serial Blood Glucose Curve occurring less than 8 hours after insulin administration and
A n overview of interpreting results of a serial b l o o d glucose subsequent b l o o d glucose concentrations exceeding 250 mg/
curve is provided i n Fig. 52-6. The ideal goal is to maintain dl, is supportive o f short duration o f insulin effect (see
the blood glucose concentration between 100 m g / d l a n d p. 781). A glucose nadir occurring 12 hours or longer after
250 mg/dl throughout the day and night, although many insulin administration is supportive o f prolonged duration
diabetic dogs do well despite blood glucose concentrations of insulin effect (see p. 781). Dogs may develop hypoglyce
consistently i n the high 100's to l o w 300's. Typically, the mia or the Somogyi response if the duration of insulin effect
highest blood glucose concentrations occur at the time o f is greater than 14 hours and the insulin is being administered
each insulin injection, but this does not always occur. If the twice a day (Fig. 52-7).
blood glucose nadir is greater than 150 mg/dl, the insulin
dose may need to be increased, and i f the nadir is less than Role of Serum Fructosamine in Aggressive,
80 mg/dl, the insulin dose should be decreased. Excitable, or Stressed Dogs
Duration o f insulin effect can be assessed i f the glucose Blood glucose curves are unreliable i n aggressive, excitable,
nadir is greater than 80 mg/dl and there has not been a rapid or stressed dogs because of problems related to stress-induced
hyperglycemia. In these dogs the clinician must make an
educated guess as to where the problem lies (e.g., wrong type
of insulin, low dose), make an adjustment i n therapy, and
rely on changes in serum fructosamine to assess the benefit
of the change i n treatment. The reader is referred to p. 792
for more information o n the use of serum fructosamine in
diabetic pets with stress-induced hyperglycemia.
FIG 5 2 - 6
A l g o r i t h m for interpreting results of a b l o o d g l u c o s e c o n c e n t r a t i o n c u r v e .
W h e n the blood glucose concentration exceeds 300 mg/dl,
the dextrose infusion should be discontinued and the blood
glucose concentration evaluated 30 and 60 minutes later. If
the b l o o d glucose concentration remains greater than
300 mg/dl, regular crystalline insulin is administered intra
muscularly at approximately 20% of the dose of long-acting
insulin being used at home. Subsequent doses o f regular
crystalline insulin should be given no more frequently than
every 4 hours, and the dose should be adjusted o n the basis
of the effect of the first insulin injection on the blood glucose
concentration.
O n the day after surgery the diabetic dog or cat can
usually be returned to the routine schedule of insulin admin
istration and feeding. A n animal that is not eating can be
maintained with I V dextrose infusions a n d regular crystal
FIG 5 2 - 7 line insulin injections given subcutaneously every 6 to 8
B l o o d g l u c o s e concentration curves o b t a i n e d from three hours. Once the animal is eating regularly, it can be returned
d i a b e t i c d o g s treated with r e c o m b i n a n t h u m a n lente insulin to its normal insulin and feeding schedule.
twice a d a y , illustrating a difference b e t w e e n d o g s in the
duration of insulin effect. The insulin is effective in l o w e r i n g COMPLICATIONS O F INSULIN THERAPY
the b l o o d g l u c o s e c o n c e n t r a t i o n in a l l d o g s , a n d the b l o o d
Hypoglycemia
g l u c o s e n a d i r is b e t w e e n 1 0 0 a n d 1 7 5 m g / d l for the d o g s .
H o w e v e r , the d u r a t i o n of insulin effect is a p p r o x i m a t e l y 1 2 Hypoglycemia is a c o m m o n complication of insulin therapy.
hours (solid line) in o n e d o g with g o o d control of g l y c e m i a Signs o f hypoglycemia are most apt to occur after sudden
(ideal duration of effect), a p p r o x i m a t e l y 8 hours (dotted large increases i n the insulin dose, with excessive overlap of
line) in o n e d o g with persistently p o o r control of g l y c e m i a insulin action i n dogs receiving insulin twice a day, after
(short duration of effect), a n d greater than 1 2 hours (dashed
prolonged inappetence, during unusually strenuous exercise,
line) in o n e d o g with a history of g o o d d a y s a n d b a d d a y s
following sudden improvement i n concurrent insulin resis
of g l y c e m i c control ( p r o l o n g e d d u r a t i o n of effect)a history
suggestive of the S o m o g y i response (see F i g . 5 2 - 8 ) . tance, a n d i n insulin-treated cats that have reverted to a
non-insulin-dependent state (see p. 785). In these situations
severe hypoglycemia may occur before glucose counterregu
lation (i.e., secretion of glucagon, epinephrine, Cortisol, and
severe hyperglycemia and minimize ketone formation. T o growth hormone) is able to compensate for a n d reverse
compensate for the lack of food intake and prevent hypogly hypoglycemia. The occurrence and severity of clinical signs
cemia, the amount of insulin administered during the peri is dependent o n the rate o f blood glucose decline and the
operative period is decreased and I V dextrose is administered severity o f hypoglycemia. In many diabetic dogs signs o f
when needed. hypoglycemia are not apparent to clients, and hypoglycemia
The following protocol is used during the perioperative is identified during evaluation of a serial blood glucose curve
period in dogs and cats undergoing surgery. The day before or suspected when a low serum fructosamine concentration
surgery the dog or cat is given its normal dose o f insulin is identified. Clinical signs and treatment o f hypoglycemia
and fed as usual. Food is withheld after 10 PM. O n the are discussed on p. 765. If clinical signs of hypoglycemia have
morning o f the procedure the b l o o d glucose concentra occurred, insulin therapy should be stopped until hypergly
tion is measured before the dog or cat is given insulin. If the cemia and glycosuria recur. The adjustment i n the insulin
blood glucose concentration is less than 100 mg/dl, insulin dose is somewhat arbitrary; as a general rule o f thumb,
is not given and an I V infusion o f 2.5% to 5% dextrose is the insulin dose initially should be decreased 25% to 50%
initiated. If the blood glucose concentration is between 100 and subsequent adjustments i n the dose based o n clinical
and 200 mg/dl, one quarter o f the animal's usual m o r n i n g response and results of blood glucose measurements. Failure
dose o f insulin is given and an I V infusion o f dextrose is of glycosuria to recur after a hypoglycemic episode suggests
initiated. If the blood glucose concentration is more than reversion to a non-insulin-dependent diabetic state or
200 mg/dl, one half o f the usual morning dose o f insulin impaired glucose counterregulation.
is given but the I V dextrose infusion is withheld until
the blood glucose concentration is less than 150 mg/dl. In Recurrence of Clinical Signs
all three situations the blood glucose concentration is Recurrence or persistence o f clinical signs is perhaps the
measured every 30 to 60 minutes during the surgical proce most c o m m o n complication o f insulin therapy i n diabetic
dure. The goal is to maintain the blood glucose concentra dogs. This is usually caused by problems with client tech
tion between 150 and 250 mg/dl during the perioperative nique i n administering insulin; problems with insulin
period. A 2.5% to 5% dextrose infusion is administered therapy relating to the insulin type, dose, species, or fre
intravenously as needed to correct or prevent hypoglycemia. quency of administration; or problems with responsiveness
to insulin caused by concurrent inflammatory, infectious, hypoglycemia-induced stimulation of hepatic glycogenolysis
neoplastic, or h o r m o n a l disorders (i.e., insulin resistance). and secretion o f diabetogenic hormones, most notably epi
Problems with client administration a n d insulin nephrine and glucagon, increase the blood glucose concen
activity. Failure to administer an appropriate dose o f tration, m i n i m i z e signs o f hypoglycemia, and cause marked
biologically active insulin w i l l result i n recurrence or persis hyperglycemia within 12 hours of glucose counterregulation.
tence of clinical signs. C o m m o n reasons include administra The marked hyperglycemia that occurs after hypoglycemia
tion ofbiologically inactive insulin (e.g., outdated, overheated, is due, i n part, to an inability o f the diabetic dog to secrete
previously frozen, destroyed by shaking the bottle), a d m i n sufficient endogenous insulin to dampen the rising blood
istration o f diluted insulin, use o f inappropriate insulin glucose concentration. By the next m o r n i n g the blood
syringes for the concentration o f insulin (e.g., U100 syringe glucose concentration can be extremely elevated (greater
with U 4 0 insulin), or problems with insulin administration than 400 mg/dl), and the m o r n i n g urine glucose concentra
technique (e.g., failure to correctly read the insulin syringe, tion is consistently 1 to 2 g m / d l as measured with urine
inappropriate injection technique). These problems are glucose test strips. Unrecognized short duration of insulin
identified by evaluating the client's insulin administration effect, combined with insulin dose adjustments based on
technique and by administering new, undiluted insulin and m o r n i n g urine glucose concentrations, is historically the
measuring several b l o o d glucose concentrations throughout most c o m m o n cause for the Somogyi response i n dogs.
the day. Clinical signs o f hypoglycemia are typically m i l d or not
Problems with the insulin treatment regimen. The recognized by the client; clinical signs caused by hyperglyce
most c o m m o n problems with the insulin treatment regimen mia tend to dominate the clinical picture. The insulin dose
in the dog include insulin underdosage, insulin overdosage that induces the Somogyi response is variable and unpredict
causing the Somogyi response, short duration o f effect o f able. The Somogyi response is often suspected i n poorly
lente or N P H insulin, and once-daily insulin administration. controlled diabetic dogs i n which insulin dosage is approach
The insulin treatment regimen should be critically evaluated ing 2.2 U / k g body weight/injection but can also occur at
for possible problems i n these areas and appropriate changes insulin dosages less than 0.5 U/kg/injection. T o y and minia
made i n an attempt to improve insulin effectiveness, espe ture breeds o f dogs are especially susceptible to development
cially i f the history and physical examination do not suggest of the Somogyi response with lower-than-expected doses of
a concurrent disorder causing insulin resistance. insulin.
Diluted insulin. D i l u t e d insulin should be replaced with The diagnosis o f the Somogyi response requires demon
full-strength insulin. In some dogs insufficient amounts o f stration o f hypoglycemia (less than 80 mg/dl) followed by
insulin are administered when diluted insulin is used, despite hyperglycemia (greater than 300 mg/dl) after insulin admin
appropriate dilution and insulin administration techniques. istration (Fig. 52-8). The Somogyi response should also be
These inadequacies are corrected when full-strength insulin suspected when the b l o o d glucose concentration decreases
is used. rapidly regardless o f the glucose nadir (e.g., a drop from 400
Insulin underdosing. C o n t r o l o f glycemia can be to 100 m g / d l i n 2 to 3 hours). If the duration of insulin effect
established i n most dogs using less than 1.0 U o f insulin/kg is greater than 12 hours, hypoglycemia often occurs at night
of body weight administered twice daily. A n inadequate after the evening dose o f insulin and the serum glucose
dose o f insulin i n conjunction with once-daily insulin concentration is typically greater than 300 mg/dl the next
therapy is a c o m m o n cause for persistence of clinical signs. morning. Unfortunately, the diagnosis of the Somogyi
In general, insulin underdosing should be considered i f the response can be elusive, i n part because of the effects of the
insulin dose is less than 1.0 U / k g and the animal is receiving diabetogenic hormones on b l o o d glucose concentrations
insulin twice a day. If insulin underdosing is suspected, the after an episode o f glucose counterregulation. Secretion of
dose o f insulin should be gradually increased by 1 to 5 U / diabetogenic hormones during the Somogyi response may
injection (depending on the size o f the dog) per week. The induce insulin resistance, which can last 24 to 72 hours after
effectiveness o f the change i n therapy should be evaluated by the hypoglycemic episode (Fig. 52-9). If a serial blood glucose
client perception o f clinical response and measurement o f curve is obtained o n the day glucose counterregulation
serum fructosamine or serial b l o o d glucose concentrations. occurs, hypoglycemia w i l l be identified and the diagnosis
Other causes for insulin ineffectiveness, most notably the established. However, i f the serial b l o o d glucose curve is
Somogyi response, should be considered once the insulin obtained o n a day when insulin resistance predominates,
dose exceeds 1.0 to 1.5 U/kg/injection, the insulin is being hypoglycemia w i l l not be identified and the insulin dose may
administered every 12 hours, and control of glycemia remains be incorrectly increased i n response to the high blood glucose
poor. values. A cyclic history o f one or two days of good glycemic
Insulin overdosing a n d the S o m o g y i response. control followed by several days o f poor control should raise
The Somogyi response results from a n o r m a l physiologic suspicion for insulin resistance caused by glucose counter-
response to impending hypoglycemia induced by excessive regulation. Serum fructosamine concentrations are unpre
insulin. W h e n the b l o o d glucose concentration declines to dictable but are usually increased (>500 mol/L)results
less than 65 m g / d l or when the b l o o d glucose concentration that confirm poor glycemic control but do not identify the
decreases rapidly regardless o f the glucose nadir, direct underlying cause.
FIG 5 2 - 9
Schematic of the change in the results of blood glucose
curves obtained on sequential days after induction of the
FIG 5 2 - 8 Somogyi response to hypoglycemia induced by an overdose
Blood glucose concentration curves obtained from three
of insulin. Hypoglycemia and the Somogyi response occur
poorly controlled diabetic dogs treated with recombinant
on day 1. The secretion of diabetogenic hormones in
human lente insulin twice a day, illustrating the typical
response to the hypoglycemia causes insulin resistance and
blood glucose curves suggestive of the Somogyi response.
increased blood glucose concentrations on day 2. Insulin
In one dog (solid line) the glucose nadir is less than 8 0 m g / resistance gradually wanes over the ensuing couple of days
dl and is followed by a rapid increase in the blood glucose
(days 3 and 4), eventually resulting in hypoglycemia and
concentration. In one dog (dashed line) a rapid decrease in the Somogyi response (day 5) as sensitivity to insulin returns
the blood glucose concentration occurs within 2 hours of
to normal. The same dose of insulin is administered each
insulin administration and is followed by a rapid increase in
day (arrow).
the blood glucose concentration; the rapid decrease in
blood glucose stimulates glucose counterregulation, despite
maintaining the blood glucose nadir above 80 m g / d l . In
one dog (dotted line) the blood glucose curve is not periods o f hyperglycemia and persistence of clinical signs
suggestive of the Somogyi response, per se. However, the (Fig. 52-10). A diagnosis o f short duration o f insulin effect
insulin injection causes the blood glucose to decrease by is made b y demonstrating an initial b l o o d glucose concen
approximately 3 0 0 m g / d l during the day, and the blood tration greater than 300 mg/dl combined with a glucose
glucose concentration at the time of the evening insulin nadir above 80 mg/dl that occurs less than 8 hours after
injection is considerably lower than the 8 A M blood glucose
insulin administration and recurrence o f hyperglycemia
concentration. If a similar decrease in the blood glucose
occurs with the evening insulin injection, hypoglycemia and
(greater than 250 mg/dl) w i t h i n 10 hours o f the insulin
the Somogyi response would occur at night and would injection (see Fig. 52-7). Treatment involves changing to a
explain the high blood glucose concentration in the morning longer-acting insulin (e.g., switching to insulin glargine; Fig.
and the poor control of the diabetic state. 52-11) or increasing the frequency of insulin administration
(e.g., initiating therapy q8h). P Z I insulin of beef/pork source
should not be used i n dogs because o f potential problems
Establishing the diagnosis may require several days o f with insulin antibodies (discussed later).
hospitalization and serial blood glucose curves, an approach Prolonged duration of insulin effect. In some dia
that eventually leads to problems with stress-induced hyper betic dogs the duration o f effect o f lente or N P H insulin is
glycemia. A n alternative, preferable approach is to arbitrarily greater than 12 hours, and twice-daily insulin administra
reduce the insulin dose 1 to 5 units and have the client tion creates problems with hypoglycemia and the Somogyi
evaluate the dog's clinical response over the ensuing 2 to 5 response. In these dogs the glucose nadir after the m o r n i n g
days. If clinical signs o f diabetes worsen after a reduction i n administration o f insulin typically occurs near or after the
the insulin dose, another cause for the insulin ineffectiveness time of the evening insulin administration, and the m o r n i n g
should be pursued. However, i f the client reports no change blood glucose concentration is usually greater than 300 mg/
or improvement i n clinical signs, continued gradual reduc dl (see Fig. 52-7). The effectiveness of insulin i n lowering the
tion of the insulin dose should be pursued. Alternatively, blood glucose concentration is variable from day to day,
glycemic regulation of the diabetic dog could be started over presumably because of varying concentrations o f diabeto
using an insulin dose of 0.25 U / k g given twice daily. genic hormones, the secretion of which was induced by prior
Short duration of insulin effect. For most dogs, the hypoglycemia. Serum fructosamine concentrations are vari
duration of effect of lente and N P H insulin is 10 to 14 hours able but usually greater than 500 mol/L. A n effective treat
and twice-daily insulin administration is effective i n control ment depends, i n part, o n the duration o f effect o f the
ling blood glucose concentrations. However, i n some dia insulin. A 24-hour blood glucose curve should be generated
betic dogs the duration of effect of lente and N P H insulin is after administration of insulin once i n the m o r n i n g and
less than 10 hours, a duration that is too short to prevent feeding the dog at the normal times o f the day. This will
FIG 5 2 - 1 0
M e a n b l o o d g l u c o s e (blue line) a n d serum insulin (red line) c o n c e n t r a t i o n s in eight d o g s
with d i a b e t e s mellitus treated with a beef-pork source N P H insulin subcutaneously o n c e
d a i l y . The d u r a t i o n of N P H effect is t o o short, resulting in p r o l o n g e d p e r i o d s of hypergly
c e m i a b e g i n n i n g shortly after the e v e n i n g m e a l . T, Insulin i n j e c t i o n ; * , e q u a l - s i z e d meals
consumed.
water into the lens, leading to swelling and rupture o f the Diabetic Nephropathy
lens fibers and the development o f cataracts. Cataract forma Although diabetic nephropathy has occasionally been
tion is an irreversible process once it begins, and it can occur reported i n the dog, its clinical recognition appears to be low.
quite rapidly. Diabetic dogs that are poorly controlled and Histopathologic findings include membranous glomerulo
have problems with wide fluctuations i n the b l o o d glucose nephropathy, glomerular and tubular basement membrane
concentration seem especially at risk for rapid development thickening, an increase i n the mesangial matrix material, the
of cataracts. Blindness may be eliminated by removing the presence o f subendothelial deposits, glomerular fibrosis, and
abnormal lens. V i s i o n is restored i n approximately 75% to glomerulosclerosis. The pathogenic mechanism of diabetic
80% o f diabetic dogs that undergo cataract removal. Factors nephropathy is u n k n o w n . Clinical signs depend on the
that affect the success o f surgery include the degree o f gly severity o f glomerulosclerosis and the functional ability of
cemic control preceding surgery, presence o f retinal disease, the kidney to excrete metabolic wastes. Initially, diabetic
and presence of lens-induced uveitis. Acquired retinal degen nephropathy is manifested as proteinuria, primarily albu
eration affecting vision is more o f a concern i n older diabetic minuria. As glomerular changes progress, glomerular filtra
dogs than is diabetic retinopathy. Fortunately, acquired tion becomes progressively impaired, resulting i n the
retinal degeneration is unlikely i n an older diabetic dog with development of azotemia and eventually uremia. W i t h severe
vision immediately before cataract formation. If available, fibrosis of the glomeruli, oliguric and then anuric renal
electroretinography should be performed before surgery to failure develops. There is no specific treatment for diabetic
evaluate retinal function. nephropathy apart from meticulous metabolic control of the
diabetic state, conservative medical management of the renal
Lens-Induced Uveitis insufficiency, and control o f systemic hypertension.
D u r i n g embryogenesis the lens is formed w i t h i n its o w n
capsule, and its structural proteins are not exposed to the Systemic Hypertension
i m m u n e system. Therefore i m m u n e tolerance to the crystal Diabetes mellitus and hypertension commonly co-exist in
line proteins does not develop. D u r i n g cataract formation dogs. Struble et al. (1998) found the prevalence of hyperten-
sion to be 46% i n 50 insulin-treated diabetic dogs, i n which of amylin i n the islets as amyloid (Fig. 52-12). IAPP-derived
hypertension was defined as systolic, diastolic, or mean amyloid fibrils are cytotoxic and associated with apoptotic
blood pressure greater than 160, 100, and 120 m m H g , cell death of islet cells. If deposition of amyloid is progres
respectively. The development of hypertension was associ sive, as occurs with a sustained demand for insulin secretion
ated with the duration of diabetes and an increased albu in response to persistent insulin resistance, islet cell destruc
min : creatinine ratio i n the urine. Diastolic and mean b l o o d tion progresses and eventually leads to diabetes mellitus. The
pressure were higher i n dogs with longer duration of disease. severity of islet amyloidosis and cell destruction deter
A correlation between control of glycemia and b l o o d pres mines, i n part, whether the diabetic cat has I D D M or
sure was not identified. Treatment for hypertension should N I D D M . Total destruction of the islets results i n I D D M and
be initiated i f the systolic blood pressure is consistently the need for insulin treatment for the rest of the cat's life.
greater than 160 m m H g . Partial destruction of the islets may or may not result i n
clinically evident diabetes, insulin treatment may or may not
Prognosis be required to control glycemia, and diabetes may or may
The prognosis is dependent on the presence and reversibility not revert to a noninsulin-requiring state once treatment is
of concurrent diseases, ease of regulation of the diabetic state initiated. If amyloid deposition is progressive, the cat will
with insulin, and client commitment toward treating the progress from subclinical diabetes to N I D D M and ultimately
disease. The mean survival time i n diabetic dogs is approxi to I D D M . Current research regarding the etiopathogenesis
mately 3 years from the time of diagnosis. This survival time of diabetes i n the cat suggests that the difference between
is somewhat skewed because dogs are often 8 to 12 years o l d I D D M and N I D D M is primarily a difference i n severity of
at the time of diagnosis and a relatively high mortality rate loss o f cells and severity and reversibility of concurrent
exists during the initial 6 months because of concurrent life- insulin resistance. Cats may have I D D M or N I D D M at the
threatening or uncontrollable disease (e.g., ketoacidosis, time diabetes is diagnosed, cats with N I D D M may progress
acute pancreatitis, renal failure). Diabetic dogs that survive to I D D M with time, cats with apparent I D D M may revert to
the initial 6 months can easily maintain a good quality of life a noninsulin requiring state after initiation of treatment, and
for longer than 5 years with proper care by the clients, timely cats may flip back and forth between I D D M and N I D D M as
evaluations by the veterinarian, and good client-veterinarian severity of insulin resistance and impairment o f cell func
communication. tion waxes and wanes.
Approximately 20% of diabetic cats become transiently
diabetic, usually within 4 to 6 weeks after the diagnosis of
DIABETES MELLITUS IN CATS diabetes has been established and treatment has been initi
ated. In these cats hyperglycemia, glycosuria, and clinical
Etiology signs of diabetes resolve, and insulin treatment can be dis
C o m m o n histologic abnormalities i n cats with diabetes mel continued. Some diabetic cats may never require insulin
litus include islet-specific amyloidosis, -cell vacuolation treatment once the initial bout of clinical diabetes mellitus
and degeneration, and chronic pancreatitis. The cause of has dissipated, whereas others become permanently insulin
-cell degeneration is not k n o w n . Other diabetic cats have a dependent weeks to months after the resolution of a prior
reduction in the number of pancreatic islets and/or insulin- diabetic state. Studies suggest that cats with transient diabe
containing B cells on immunohistochemical evaluation, sug tes mellitus are i n a subclinical diabetic state that becomes
gesting additional mechanisms may be involved i n the clinical when the pancreas is stressed by exposure to a con
physiopathology of diabetes mellitus i n cats. A l t h o u g h l y m current insulin-antagonistic drug or disease, most notably
phocytic infiltration of islets, i n conjunction with islet amy glucocorticoids, megestrol acetate, and chronic pancreatitis
loidosis and vacuolation, has been described i n diabetic (Fig. 52-13). U n l i k e healthy cats, those with transient diabe
cats, this histologic finding is very u n c o m m o n , and B cell and tes mellitus have a reduced population of (3 cells, dysfunc
insulin autoantibodies have not been identified i n newly tional cells, or both, which impairs the ability of the
diagnosed diabetic cats. The role of genetics remains to be pancreas to compensate for concurrent insulin resistance. A n
determined. inadequate insulin response results i n hyperglycemia. Persis
Noninsulin-dependent type 2 diabetes may be identified tent hyperglycemia can, i n turn, cause hypoinsulinemia by
in as many as 50% to 70% of newly diagnosed diabetic cats. suppressing function of remaining cells and can induce
Islet amyloidosis and insulin resistance are important factors insulin resistance by promoting downregulation of glucose
in the development of noninsulin-dependent type 2 diabetes transport systems and causing a defect in posttransport
in cats. Islet-amyloid polypeptide (IAPP), or amylin, is the insulin action. This phenomenon is referred to as glucose
principal constituent of amyloid i n adult cats with diabetes, toxicity. cells have an impaired response to stimulation by
is stored in -cell secretory granules, and is co-secreted with insulin secretagogues, thereby m i m i c k i n g I D D M . The effects
insulin by the cell. Stimulants of insulin secretion also of glucose toxicity are potentially reversible u p o n correction
stimulate the secretion of amylin. C h r o n i c increased secre of the hyperglycemic state. The clinician makes a correct
tion of insulin and amylin, as occurs with obesity and other diagnosis of diabetes mellitus, insulin and treatment of
insulin-resistant states, results i n aggregation and deposition insulin-antagonistic disorders improve hyperglycemia and
FIG 5 2 - 1 2
A , S e v e r e islet a m y l o i d o s i s (straight arrow) in a cat with initial noninsulin-dependent
d i a b e t e s mellitus ( N I D D M ) that p r o g r e s s e d to insulin-dependent d i a b e t e s mellitus (IDDM).
A p a n c r e a t i c b i o p s y s p e c i m e n w a s o b t a i n e d w h i l e the a n i m a l w a s in the I D D M state.
R e s i d u a l cells c o n t a i n i n g insulin (red arrows) a r e a l s o present. ( I m m u n o p e r o x i d a s e stain,
x 1 0 0 . ) B, S e v e r e v a c u o l a r d e g e n e r a t i o n of islet cells. P a n c r e a t i c tissue w a s e v a l u a t e d at
n e c r o p s y 2 8 months after d i a b e t e s w a s d i a g n o s e d a n d 2 0 months after c a t p r o g r e s s e d
from N I D D M to I D D M , r e q u i r i n g insulin to control b l o o d g l u c o s e c o n c e n t r a t i o n s . The c a t
d i e d from metastatic e x o c r i n e p a n c r e a t i c a d e n o c a r c i n o m a . ( H & E , x 5 0 0 . )
C, S e v e r e c h r o n i c pancreatitis with fibrosis in a d i a b e t i c cat with I D D M . The cat w a s
e u t h a n i z e d b e c a u s e o f persistent p r o b l e m s with lethargy, i n a p p e t e n c e , a n d p o o r l y
control led d i a b e t e s mellitus. ( H & E , x 1 0 0 . ) (A from F e l d m a n E C , N e l s o n R W : Canine and
feline endocrinology and reproduction, e d 3 , St Louis, 2 0 0 4 , W B Saunders.)
insulin resistance, glucose toxicity and cell function position has been discovered, although Burmese cats may be
improve, insulin secretion returns, and an apparent I D D M overrepresented i n Australia.
state resolves. The future requirement for insulin treatment
depends o n the underlying abnormality i n the islets. If the HISTORY
abnormality is progressive (e.g., amyloidosis), eventually The history i n virtually all diabetic cats includes polydipsia,
enough cells will be destroyed and I D D M will develop. polyuria, polyphagia, and weight loss. A c o m m o n complaint
of cat owners is the constant need to change the litter and
Clinical Features an increase i n the size of the litter clumps. Additional clinical
signs include lethargy; decreased interaction with family
SIGNALMENT members; lack of grooming behavior and development of a
Although diabetes mellitus may be diagnosed i n cats of any dry, lusterless, unkempt, or matted haircoat; and decreased
age, most diabetic cats are more than 9 years old (mean 10 jumping ability, rear limb weakness, or development of a
years) at the time of diagnosis. Diabetes mellitus occurs pre plantigrade posture (Fig. 52-14). If the client does not notice
dominantly i n neutered male cats; no apparent breed predis clinical signs associated with uncomplicated diabetes, a dia-
FIG 52-13
S e q u e n c e of events in the d e v e l o p m e n t a n d resolution of a n
insulin-requiring d i a b e t i c e p i s o d e in cats with transient
diabetes. (From F e l d m a n E C , N e l s o n R W : Canine and
feline endocrinology and reproduction, e d 3 , St Louis,
2 0 0 4 , W B Saunders.)
PHYSICAL EXAMINATION
Physical examination findings depend on the presence and FIG 52-14
severity of D K A and the nature of other concurrent disor A , P l a n t i g r a d e posture in a cat with d i a b e t e s mellitus a n d
ders. The nonketotic diabetic cat has no classic physical e x o c r i n e p a n c r e a t i c insufficiency. B, Resolution of h i n d limb
w e a k n e s s a n d p l a n t i g r a d e posture after i m p r o v i n g g l y c e m i c
examination findings. M a n y diabetic cats are obese but oth
control b y adjusting insulin t h e r a p y a n d initiating p a n c r e a t i c
erwise in good physical condition. Cats with prolonged
e n z y m e r e p l a c e m e n t therapy. C, S e v e r e d i a b e t i c n e u r o p a
untreated diabetes may have lost weight but are rarely ema thy in a cat with d i a b e t e s mellitus. N o t e the p a l m i g r a d e a n d
ciated unless concurrent disease (e.g., hyperthyroidism) is p l a n t i g r a d e posture. The more severe a n d the m o r e c h r o n i c
present. Newly diagnosed and poorly controlled diabetic cats the neuropathy, the less likely the n e u r o p a t h y w i l l i m p r o v e
often stop grooming and develop a dry, lusterless haircoat. after i m p r o v e m e n t in d i a b e t i c control.
Diabetes-induced hepatic lipidosis may cause hepatomegaly.
Impaired ability to jump, weakness i n the rear limbs, ataxia,
or a plantigrade posture (i.e., the hocks touch the ground malities may be identified i n the ketoacidotic diabetic cat
when the cat walks) may be evident if the cat has developed (see p. 796).
diabetic neuropathy. Distal muscles of the rear limbs may
feel hard on digital palpation, and cats may object to palpa Diagnosis
tion or manipulation of the rear limbs, presumably because Establishing the diagnosis of diabetes mellitus is similar for
of pain associated with the neuropathy. Additional abnor cats and dogs and is based on identification of appropriate
clinical signs, persistent hyperglycemia, and glycosuria (see Treatment
p. 769). Transient, stress-induced hyperglycemia is a c o m m o n The significant incidence o f N I D D M i n cats raises interest
problem i n cats and can cause the b l o o d glucose concentra ing questions regarding the need for insulin treatment. Gly
tion to increase above 300 mg/dl. Unfortunately, stress is a cemic control can be maintained i n some diabetic cats with
subjective state that cannot be accurately measured, is not dietary changes, oral hypoglycemic drugs, control of current
always easily recognized, and may evoke inconsistent diseases, discontinuation o f insulin-antagonistic drugs, or a
responses among individual cats. Glycosuria usually does combination o f these. The ultimate differentiation between
not develop i n cats with transient stress-induced hypergly I D D M and N I D D M is usually made retrospectively, after the
cemia but can be present i f stress is prolonged (i.e., hours). clinician has had several weeks to assess the response of the
For this reason, presence of appropriate clinical signs, per cat to therapy and to determine the cat's need for insulin.
sistent hyperglycemia, and glycosuria should always be doc The initial treatment strategy is based on the severity of
umented when establishing a diagnosis o f diabetes mellitus clinical signs and physical abnormalities, presence or absence
i n cats. If the clinician is i n doubt, the stressed cat can be of ketoacidosis, general health of the cat, and client wishes.
sent home with instructions for the client to monitor the For most newly diagnosed diabetic cats, treatment includes
urine glucose concentration with the cat i n the nonstressed insulin, adjustments i n diet, and correction or control of
home environment. Alternatively, a serum fructosamine concurrent insulin resistance.
concentration can be measured (see p. 774). Documenting
an increase i n the serum fructosamine concentration sup INITIAL INSULIN RECOMMENDATIONS
ports the presence of sustained hyperglycemia; however, a FOR DIABETIC CATS
serum fructosamine concentration i n the upper range o f Diabetic cats are notoriously unpredictable in their response
n o r m a l can occur i n symptomatic diabetic cats i f the diabe to exogenous insulin. N o single type of insulin is routinely
tes developed shortly before presentation o f the cat to the effective i n maintaining control of glycemia, even with twice-
veterinarian. daily administration. The initial insulin of choice ultimately
Clinical signs develop when hyperglycemia causes glycos is based on personal preferences and experiences. C o m
uria and are the same regardless o f the functional status o f m o n l y used insulin preparations for the long-term manage
pancreatic islets. Information used to establish the diagnosis ment o f diabetic cats include human recombinant N P H ,
of diabetes mellitus does not provide information o n the porcine lente, beef/pork P Z I , and the insulin analog glargine
status o f pancreatic islet health, presence o f glucose toxicity, (see the section on overview of insulin preparations, p. 769;
ability o f the cat to secrete insulin, or the severity and revers see Fig. 52-11). A l l have potential problems in diabetic cats,
ibility o f concurrent insulin resistance. Unfortunately, mea primarily related to duration o f insulin effect, not species of
surements o f baseline serum insulin concentration or serum insulin and insulin antibody formation. Although lente and
insulin concentrations after administration o f an insulin N P H insulin are consistently and rapidly absorbed after sub
secretagogue have not been consistent aids i n differentiating cutaneous administration, the duration of effect of lente and
I D D M and N I D D M i n the cat. Identification o f a baseline especially N P H insulin can be considerably shorter than 12
serum insulin concentration greater than 15 U/ml (refer hours, resulting in inadequate control of glycemia despite
ence range, 5 to 20 U/ml) in a newly diagnosed, untreated twice-daily administration (see Table 52-2). Although PZI is
diabetic cat supports the presence o f functional cells and a longer-acting insulin, the timing o f the glucose nadir is
partial destruction of the islets; however, l o w or undetectable variable and occurs within 9 hours of PZI administration in
serum insulin concentrations do not rule out partial cell the majority o f treated diabetic cats. In one study PZI sig
loss because o f the suppressive effects o f glucose toxicity o n nificantly improved control of glycemia i n newly diagnosed
circulating insulin concentrations. diabetic cats and poorly controlled diabetic cats previously
A thorough evaluation of the cat's overall health is recom treated with ultralente or N P H insulin (Nelson et a l , 2001).
mended once the diagnosis o f diabetes mellitus has been Comparison of efficacy between P Z I and lente insulin has
established, for reasons discussed o n p. 769. The m i n i m a l not been reported.
laboratory evaluation i n any diabetic cat should include a Insulin glargine is the longest-acting commercially avail
C B C , serum biochemical panel, serum thyroxine concentra able insulin for treatment of diabetes in humans and is cur
tion, and urinalysis with bacterial culture. If available, rently a popular initial choice by veterinarians for the
abdominal ultrasound should also be a routine part of the treatment o f diabetes in cats. A n unpublished study identi
diagnostic evaluation because o f the high prevalence of fied better glycemic control and a higher diabetes remission
chronic pancreatitis i n diabetic cats. Measurement o f base rate i n newly diagnosed diabetic cats treated with glargine
line serum insulin concentration or performance of an twice a day, compared with lente or P Z I administered twice
insulin secretory response test is not routinely done i n cats a day (Weaver and Rand, 2005). Another study found no
because o f problems encountered with glucose toxicity. difference i n glycemic control i n diabetic cats treated with
Additional tests may be warranted after obtaining the history, glargine once a day versus diabetic cats treated with lente
performing the physical examination, or identifying keto insulin twice a day, and a higher diabetes remission rate in
acidosis. See B o x 52-4 for a list of potential clinical patho diabetic cats treated with lente insulin (Weaver et al., 2006).
logic abnormalities. In m y experience, the duration of effect o f glargine is quite
variable, with the glucose nadir occurring as soon as 4 hours Cats are carnivores and, as such, have higher dietary
and as late as 20 hours after administration. Glargine works protein requirements than omnivores such as humans and
well when given once or twice a day in some diabetic cats dogs. Hepatic glucokinase and hexokinase activity is lower
and does not work very well i n others. Problems are usually i n cats, compared with that for carnivores with omnivorous
related to duration o f effect (i.e., too short or too long). eating habits, and suggests that diabetic cats may be predis
Currently, my personal preference for the initial treat posed to developing higher postprandial b l o o d glucose con
ment of newly diagnosed diabetes i n cats is P Z I at an initial centrations after consumption o f diets containing a high
dose of 1 U/cat. Because the majority o f diabetic cats require carbohydrate load, and vice versa. Dietary studies in diabetic
PZI insulin twice a day, I prefer to start with twice-daily cats have documented improved control o f glycemia with
insulin therapy while the insulin dose is l o w to prevent prob diets containing increased fiber content, increased protein
lems with hypoglycemia and the Somoygi response. I switch and decreased carbohydrate content, and increased fat and
to lente insulin given twice a day if problems with prolonged decreased carbohydrate content plus treatment with the
duration of P Z I effect develop and glycemic control cannot -glucosidase inhibitor acarbose. The central theme i n these
be maintained with once-daily P Z I , and I switch to glargine dietary studies has been restriction o f carbohydrate absorp
given twice a day i f problems with short duration o f P Z I tion by the gastrointestinal tract, either by inhibiting starch
effect develop. W h e n using glargine for the treatment o f digestion (acarbose), inhibiting intestinal glucose absorption
newly diagnosed diabetic cats, I use an initial dose o f 1 unit/ (fiber), or decreasing carbohydrate ingestion (low carbohy
cat administered once a day and switch to twice-daily therapy drate-containing diets). Intuitively, the most effective means
if subsequent blood glucose evaluations support a duration to m i n i m i z e gastrointestinal absorption o f carbohydrates i n
of effect of 12 hours or less. If P Z I insulin becomes unavail the diabetic cat is to feed diets that contain m i n i m a l amounts
able, I w o u l d use porcine lente insulin at an initial dose o f of carbohydrate. Current recommendations include diets
1 U/cat twice a day in the newly diagnosed diabetic cat. with high protein and l o w carbohydrate content and diets
containing increased fiber and moderate carbohydrate
DIET content (see B o x 52-6). W h i c h diet will be most beneficial i n
The general principles for dietary therapy are listed i n B o x improving control o f glycemia i n any given diabetic cat is
52-6. Obesity, feeding practices, and content o f the diet unpredictable. The initial diet o f choice is based o n personal
warrant discussion in diabetic cats. Obesity is c o m m o n i n preference. Currently, I initially use diets containing high
diabetic cats and results from excessive caloric intake typi protein and low carbohydrate content, and i f palatability,
cally caused by free-choice feeding o f dry cat food. Obesity problems with renal insufficiency, or adverse effects become
causes reversible insulin resistance that resolves as obesity is an issue or poor control o f glycemia persists despite adjust
corrected. C o n t r o l of glycemia often improves, and some ments i n insulin therapy, a switch to one o f the fiber-
diabetic cats may revert to a subclinical diabetic state after containing diets should be considered. Diets containing high
weight reduction. Correction of obesity is difficult i n cats fat and l o w carbohydrate content (e.g., growth diets) are not
because it requires restriction o f daily caloric intake without recommended because o f concerns related to the impact o f
a corresponding increase in caloric expenditure (i.e., exer high dietary fat content o n obesity, hepatic lipidosis, chronic
cise). Although there are several diets specifically formulated pancreatitis, and insulin resistancethe latter induced by
for weight reduction i n cats, diets containing increased increased circulating concentrations o f nonesterified fatty
amounts of fiber and diets containing increased protein and acids, -hydroxybutyric acid, and triglycerides.
decreased carbohydrate should be used i n the obese diabetic
cat for reasons discussed later. The reader is referred to IDENTIFICATION A N D CONTROL OF
Chapter 54 for more information on correction o f obesity CONCURRENT PROBLEMS
in cats. Identification and correction o f concurrent disorders that
The eating habits o f cats vary considerably, from those cause insulin resistance and interfere with the success o f
cats that eat everything at the time it is offered to those that insulin therapy is critical to the successful treatment o f dia
graze throughout the day and night. The primary goal o f betes i n cats. Examples include obesity; chronic pancreatitis
dietary therapy is to minimize the impact o f a meal o n post and other chronic inflammatory diseases; infection; and
prandial blood glucose concentrations. C o n s u m i n g the same insulin-resistant disease such as hyperthyroidism, hyperad
amount o f calories i n multiple small amounts throughout a renocorticism, and acromegaly. In diabetic cats with partial
12-hour period should have less impact than consuming the loss o f B cells correction o f insulin resistance may result
calories at a single large meal. H a l f o f the cat's total daily i n reversion from an insulin-dependent to a n o n - i n s u l i n -
caloric intake should be offered at the time o f each insulin dependent or subclinical diabetic state. A n evaluation o f the
injection and remain available to the cat to consume when diabetic cat for concurrent problems is indicated at the time
it wishes. Attempts to force a grazing cat to eat the entire diabetes is diagnosed and whenever control o f glycemia
meal at one time usually fail and are not warranted as long deteriorates i n a previously well-controlled cat and should
as the cat has access to the food during the ensuing 12 hours. include a thorough history, physical examination, C B C , serum
A similar approach is taken for diabetic dogs that are finicky biochemistry panel, serum thyroxine concentration, urinaly
eaters. sis with culture, and (if available) abdominal ultrasound.
O R A L HYPOGLYCEMIC D R U G S have severe N I D D M or the early stages of I D D M . Glipizide
In the U n i t e d States, five classes o f oral hypoglycemic drugs treatment has been found effective i n improving clinical
are approved for the treatment o f N I D D M i n h u m a n beings: signs and severity of hyperglycemia in approximately 20%
sulfonylureas, meglitinides, biguanides, thiazolidinediones, of diabetic cats.
and -glucosidase inhibitors. These drugs w o r k by stimulat N o consistent parameters have been identified that allow
ing pancreatic insulin secretion (sulfonylureas, meglitinides), the clinician to prospectively determine which cats will
enhancing tissue sensitivity to insulin (biguanides, thiazoli respond to glipizide or glyburide therapy. Identifying a high
dinediones), or slowing postprandial intestinal glucose preprandial serum insulin concentration or an increase in
absorption (-glucosidase inhibitors). A l t h o u g h controver serum insulin concentration during an insulin secretagogue
sial, c h r o m i u m and vanadium are trace minerals that may test supports the diagnosis of N I D D M , but failure to identify
also function as insulin sensitizers. Studies have documented these changes does not rule out the potential for a beneficial
the efficacy o f sulfonylureas for treating diabetes i n cats and response to glipizide or glyburide. Selection of diabetic cats
-glucosidase inhibitors for i m p r o v i n g glycemic control i n for treatment with glipizide must rely heavily on the veteri
diabetic dogs. Insulin sensitizers as the sole therapeutic agent narian's assessment o f the cat's health, severity of clinical
are of questionable benefit i n diabetic dogs and cats because signs, presence or absence o f ketoacidosis, other diabetic
they require the presence o f circulating insulin to be effec complications (e.g., peripheral neuropathy), and the client's
tive. M o s t diabetic cats subsequently shown to have N I D D M desires.
have l o w or nondetectable insulin concentrations at the Glipizide (Glucotrol, Pfizer; 2.5 mg/cat administered
time diabetes is diagnosed, i n part because o f the effects q l 2 h ) and glyburide (Micronase, Pharmacia and Upjohn
of concurrent glucose toxicity o n circulating insulin
Company; 0.625 mg/cat q l 2 h ) are initially administered in
concentrations.
conjunction with a meal to diabetic cats that are nonketotic
and relatively healthy on physical examination (Fig. 52-15).
Sulfonylureas Each cat is examined weekly during the first month of
Sulfonylurea drugs (e.g., glipizide, glyburide) are the most therapy. A history, complete physical examination, body
c o m m o n l y used oral hypoglycemic drugs for the treatment weight, urine glucose/ ketone measurement, and blood
of diabetes mellitus i n cats. Sulfonylureas stimulate insulin glucose concentration are evaluated at each examination. If
secretion by pancreatic cells. Some endogenous pancreatic adverse reactions (Table 52-4) have not occurred after 2
insulin secretory capacity must exist for sulfonylureas to be weeks o f treatment, the glipizide and glyburide dose is
effective. Clinical response to glipizide and glyburide treat increased to 5.0 m g and 1.25 mg, respectively, q12h. Therapy
ment i n diabetic cats has been variable, ranging from excel is continued as long as the cat is stable. If euglycemia or
lent (i.e., b l o o d glucose concentrations decreasing to less hypoglycemia develops, the dose may be tapered down or
than 200 mg/dl) to partial response (i.e., clinical improve discontinued and b l o o d glucose concentrations reevaluated
ment but failure to resolve hyperglycemia) to no response. 1 week later to assess the need for the drug. If hyperglycemia
Presumably, the population o f functioning cells varies recurs, the dose is increased or the sulfonylurea is reinitiated,
from none (severe I D D M ) to near n o r m a l (mild N I D D M ) with a reduction in dose i n those cats previously developing
i n treated cats, resulting i n a response range from none to hypoglycemia. Sulfonylurea treatment is discontinued and
excellent. Cats with a partial response to glipizide have some insulin therapy initiated i f clinical signs continue to worsen,
functioning cells but not enough to decrease the b l o o d the cat becomes i l l or develops ketoacidosis or peripheral
glucose concentration to less than 200 mg/dl. These cats may neuropathy, b l o o d glucose concentrations remain greater
TABLE 52-4
Vomiting within 1 hour of Vomiting usually subsides after 2 to 5 days of glipizide therapy; decrease dose or
administration frequency of administration if vomiting is severe; discontinue if vomiting persists >1 week
Increased serum hepatic Continue treatment and monitor enzymes every 1 to 2 weeks initially; discontinue glipizide
enzyme activities if cat becomes ill (lethargy, inappetence, vomiting) or the alanine transaminase activity
exceeds 5 0 0 IU/L
Icterus Discontinue glipizide treatment; reinstitute glipizide treatment at lower dose and frequency
of administration once icterus resolves (usually within 2 weeks); discontinue treatment
permanently if icterus recurs
Hypoglycemia Discontinue glipizide treatment; recheck blood glucose concentration in 1 week; reinstitute
glipizide therapy at lower dose or frequency of administration if hyperglycemia recurs
FIG 5 2 - 1 5
A l g o r i t h m for treating d i a b e t i c cats with the o r a l sulfonylurea d r u g , g l i p i z i d e . (From
Feldman E C , N e l s o n R W : Canine and feline endocrinology and reproduction, e d 3 , St
Louis, 2 0 0 4 , W B Saunders.)
than 300 mg/dl after 1 to 2 months of therapy, or the client cats, the drug is not c o m m o n l y used because of cost and
becomes dissatisfied with the treatment. In some cats sulfo adverse effects. Diarrhea and weight loss as a result of car
nylureas become ineffective weeks to months later, and exog bohydrate malassimilation occur i n approximately 35% of
enous insulin is ultimately required to control the diabetic treated dogs. Feeding carbohydrate-restricted diets is recom
state. Presumably, the progression to I D D M coincides with mended i n lieu of acarbose treatment in diabetic cats.
progressive loss of B cells, a loss that may be exacerbated by
sulfonylurea treatment. Regardless, the primary value of sul IDENTIFYING INITIAL INSULIN
fonylureas is an alternative palatable option (pills versus REQUIREMENTS
injections) for clients initially unwilling to consider insulin The approaches to identifying insulin requirements i n the
injections and contemplating euthanasia of their cat. D u r i n g newly diagnosed diabetic cat and dog are similar and dis
the ensuing weeks many of these clients become willing to cussed o n p. 773. M o s t clients of diabetic cats are happy with
try insulin injections i f sulfonylurea therapy fails. the response to insulin treatment i f the b l o o d glucose con
centrations range between 100 and 300 mg/dl throughout
Acarbose the day. Diabetic cats can have problems with hypoglycemia
Although the -glucosidase inhibitor acarbose has been and the Somogyi response (see p. 780) at relatively small
effective i n improving glycemic control i n diabetic dogs and doses of insulin (1 to 2 U/injection). A s such, the preference
is to have the client administer a fixed dose of insulin once the day o f the curve (typically, at the time of insulin admin
control o f glycemia is attained and discourage clients from istration and 3, 6, 9, and 12 hours later). Use of the ear prick
adjusting the insulin dose at home without first consulting technique i n cats has produced excellent results. Stress is
their veterinarian. often significantly reduced, and accuracy of the blood glucose
measurements improved. Problems with the marginal ear
Techniques for Monitoring Diabetic Control vein prick technique include overzealous clients who start
The techniques for m o n i t o r i n g diabetic control are discussed monitoring b l o o d glucose concentrations too frequently,
o n p. 774. One important factor that affects monitoring o f insulin overdosing and the Somogyi response caused by
diabetic cats is the propensity to develop stress-induced clients who interpret b l o o d glucose results and adjust the
hyperglycemia caused by frequent visits to the veterinary insulin dose independent o f input from the veterinarian,
hospital for b l o o d samplings. Once stress-induced hypergly difficulty obtaining b l o o d from the ear vein, and cats who
cemia develops, it is a perpetual problem and b l o o d glucose do not tolerate manipulation and pricking of the ear.
measurements can no longer be considered accurate. Veteri
narians must remain wary o f stress hyperglycemia i n dia Role of Serum Fructosamine in Stressed
betic cats and should take steps to prevent its development. Diabetic Cats
Micromanaging diabetic cats is not recommended, and serial The use o f serum fructosamine concentrations for assessing
b l o o d glucose curves should be done only when the clinician control of glycemia is discussed on p. 777. Serum fructos
perceives a need to change insulin therapy. The determina amine concentrations are not affected by acute transient
tion o f good versus poor control o f glycemia should be based increases i n b l o o d glucose concentration. Unlike blood
on the client's subjective o p i n i o n o f the presence and sever glucose measurements, evaluation o f serum fructosamine
ity o f clinical signs and the overall health o f the pet, ability concentration i n fractious or stressed diabetic cats provides
of the cat to j u m p , grooming behavior, findings on physical reliable objective information on the status of glycemic control
examination, and stability o f body weight. Generation o f a during the previous 2 to 3 weeks. In fractious or stressed cats
serial b l o o d glucose curve should be reserved for newly diag the clinician must make an educated guess as to where the
nosed and poorly controlled diabetic cats. problem lies (e.g., wrong type o f insulin, low insulin dose),
make an adjustment i n therapy, and rely on changes in serum
Protocol for Generating the Serial Blood fructosamine to assess the benefit o f the change in treatment.
Glucose Curve at Home Serum fructosamine concentrations can be measured before
A n alternative to hospital-generated b l o o d glucose curves is and 2 to 3 weeks after changing insulin therapy to assess the
to have the client generate the b l o o d glucose curve at home effectiveness o f the change. If changes i n insulin therapy are
using the marginal ear vein prick technique i n cats (the ear appropriate, a decrease i n serum fructosamine concentration
or lip prick technique i n dogs) and a portable home b l o o d should occur. If the serum fructosamine concentration is the
glucose monitoring device that allows the client to touch the same or has increased, the change was ineffective in improv
drop of blood on the ear with the end of the glucose test ing glycemic control, another change in therapy based on an
strip (Fig. 52-16). The marginal ear vein prick technique educated guess should be done, and the serum fructosamine
decreases the need for physical restraint during sample col measured again 2 to 3 weeks later.
lection, thereby m i n i m i z i n g the cat's discomfort and stress.
Accuracy o f blood glucose results are similar when b l o o d for INSULIN THERAPY DURING SURGERY
glucose determination is obtained by ear prick and veni The approaches to managing the diabetic cat and dog during
puncture. However, b l o o d glucose results obtained by por surgery are similar and are discussed on p. 778.
table b l o o d glucose m o n i t o r i n g devices may overestimate or,
more commonly, underestimate the actual b l o o d glucose COMPLICATIONS OF INSULIN THERAPY
values obtained with reference methods. This inherent error Complications of insulin therapy are similar for diabetic
must be considered when interpreting b l o o d glucose results dogs and cats and are discussed on p. 779. The most c o m m o n
obtained by a portable home b l o o d glucose monitoring complications of insulin therapy in the diabetic cat are recur
device. Several W e b sites explain i n detail the marginal ear ring hypoglycemia; insulin overdose, which causes the
vein prick technique i n layman's terms and provide informa Somogyi response; incorrect assessment of glycemic control
tion o n client experiences with the technique and with dif caused by stress-induced hyperglycemia; short duration of
ferent portable home b l o o d glucose meters. After diagnosing effect o f N P H ; lente and, less commonly, PZI and glargine
diabetes, the clinician should recommend a particular W e b insulin; prolonged duration o f effect o f P Z I and glargine
site and find out whether the client w o u l d be interested i n insulin; and insulin resistance caused by concurrent
monitoring b l o o d glucose concentrations at home. The cli inflammatory and hormonal disorders, most notably chronic
nician should allow for ample time to teach the technique to pancreatitis.
clients who are willing to give it a try and provide advice
regarding the proper way to perform a b l o o d glucose curve Stress Hyperglycemia
(ideally, no more frequently than 1 day every 4 weeks) and Transient hyperglycemia is a well-recognized problem in
how often to measure the b l o o d glucose concentration on fractious, scared, or otherwise stressed cats. Hyperglycemia
FIG 5 2 - 1 6
Ear prick technique for measuring b l o o d glucose concentration. A , A hot washcloth is a p p l i e d
to the p i n n a for 2 to 3 minutes to i n c r e a s e circulation to the e a r . B, A spot is identified o n
the p e r i p h e r y of the outer s i d e of the p i n n a , a small c o a t i n g of petrolatum jelly is a p p l i e d ,
a n d the spot is pricked with the lancet d e v i c e supplied with the portable b l o o d g l u c o s e meter.
G a u z e should b e p l a c e d b e t w e e n the p i n n a a n d the d i g i t h o l d i n g the p i n n a to prevent
pricking the finger if the b l a d e of the lancet a c c i d e n t a l l y passes through the p i n n a . Petrola
tum jelly is a p p l i e d to help the b l o o d form into a ball o n the p i n n a a s it s e e p s from the
site that is l a n c e d . C , Digital pressure is a p p l i e d in the a r e a of the l a n c e d skin to p r o m o t e
b l e e d i n g . The g l u c o s e test strip is t o u c h e d to the d r o p of c a p i l l a r y b l o o d that forms a n d is
r e m o v e d o n c e e n o u g h b l o o d h a s b e e n d r a w n into the test strip to activate the meter.
develops as a result of increased catecholamines and, i n therapy is invariably adjusted, often by increasing the insulin
struggling cats, lactate concentrations. B l o o d glucose con dose, and another b l o o d glucose curve recommended 1 to 2
centrations typically exceed 200 mg/dl i n affected cats, and weeks later. A vicious cycle ensues, which eventually c u l m i
values in excess o f 300 mg/dl are c o m m o n . Stress hypergly nates i n the Somogyi response, clinically apparent hypogly
cemia can significantly increase b l o o d glucose concentra cemia, or referral for evaluation of insulin resistance.
tions in diabetic cats despite the administration o f insulin, Failure to identify the presence o f stress hyperglycemia
an effect that seriously compromises the clinician's ability to and its impact on the interpretation o f b l o o d glucose mea
accurately judge the effectiveness o f the insulin injection. surements is one o f the most important reasons that the
Frequent hospitalizations and venipunctures for monitoring status o f glycemic control i n diabetic cats is misinterpreted.
blood glucose concentrations are the most c o m m o n cause o f Stress hyperglycemia should be suspected i f the cat is visibly
stress hyperglycemia. Blood glucose concentrations can upset or aggressive or struggles during restraint and the veni
remain greater than 400 mg/dl throughout the day despite puncture process. However, stress hyperglycemia can also be
administration of insulin. Failure to recognize the effect o f present i n diabetic cats that are easily removed from the cage
stress on blood glucose results may lead to the erroneous and do not resist the blood-sampling procedure. These cats
perception that the diabetic cat is poorly controlled. Insulin are scared, but rather than become aggressive, they remain
blood glucose measurements can no longer be considered
accurate. If stress hyperglycemia is suspected, reliance on
home monitoring of blood glucose or evaluation of sequen
tial serum fructosamine concentrations (see p. 792) should
be done, i n addition to the history and physical examination
findings.
Hypoglycemia
Hypoglycemia, a c o m m o n complication of insulin therapy,
is discussed o n p. 779. In diabetic cats symptomatic hypo
glycemia is most apt to occur after sudden large increases in
the insulin dose, after sudden improvement i n concurrent
insulin resistance, with excessive duration of insulin action
in cats receiving insulin twice a day, after prolonged inap
petence, and i n insulin-treated cats that have reverted to
a non-insulin-dependent state. In these situations severe
hypoglycemia may occur before glucose counterregulation
(i.e., secretion o f glucagon, Cortisol, epinephrine, growth
hormone) is able to compensate for and reverse low blood
glucose concentrations. The initial treatment approach for
hypoglycemia is to discontinue insulin until hyperglycemia
recurs and then reduce the ensuing insulin dose 25% to 50%.
If hypoglycemia remains a reoccurring problem despite
reductions i n the insulin dose, excessive duration of insulin
effect (see p. 781) or reversion to a noninsulin-dependent
diabetic state should be considered. Reversion to a n o n
insulin-dependent diabetic state should be suspected i f
hypoglycemia remains a persistent problem despite admin
FIG 5 2 - 1 7 istration of small doses of insulin (i.e., 1 U or less per injec
B l o o d g l u c o s e c o n c e n t r a t i o n curves in a 5 . 3 - k g m a l e c a t tion) a n d administration o f insulin once a day, i f blood
r e c e i v i n g 2 U o f r e c o m b i n a n t h u m a n ultralente insulin (pink glucose concentrations are consistently below 150 mg/dl
line) 2 w e e k s after the initiation of insulin therapy, 2 U of
before insulin administration, i f serum fructosamine con
r e c o m b i n a n t h u m a n ultralente insulin (blue line) 2 months
centration is less than 350 p m o l / L , or i f urine glucose test
later, a n d 6 U of r e c o m b i n a n t h u m a n ultralente insulin (red
line) 4 months later. The insulin d o s e h a d b e e n g r a d u a l l y strips are consistently negative. Insulin therapy should be
i n c r e a s e d o n the basis of the b l o o d g l u c o s e c o n c e n t r a t i o n discontinued a n d periodic urine glucose testing should be
curves. The client r e p o r t e d m i n i m a l c l i n i c a l signs r e g a r d l e s s performed i n the home environment to identify recurrence
of the insulin d o s e ; at the 4-month r e c h e c k the c a t h a d of glycosuria.
m a i n t a i n e d its b o d y w e i g h t a n d results of the p h y s i c a l
e x a n i n a t i o n w e r e n o r m a l . The c a t b e c a m e p r o g r e s s i v e l y Insulin Overdosing and the
more fractious d u r i n g e a c h h o s p i t a l i z a t i o n , s u p p o r t i n g the
existence of stress-induced h y p e r g l y c e m i a a s the r e a s o n for
Somogyi Response
the d i s c r e p a n c y b e t w e e n the b l o o d g l u c o s e v a l u e s a n d Insulin overdosing and the Somogyi response is discussed
other p a r a m e t e r s used to e v a l u a t e g l y c e m i c c o n t r o l . T, on p. 780. A similar phenomenon, characterized by wide
S u b c u t a n e o u s insulin injection a n d f o o d . (From F e l d m a n E C , fluctuations i n blood glucose concentration after which
N e l s o n R W : Canine and feline endocrinology and repro there are several days of persistent hyperglycemia, is recog
duction, e d 3 , St Louis, 2 0 0 4 , W B Saunders.)
nized clinically i n diabetic cats. However, the exact role of
the counterregulatory hormones remains to be clarified.
crouched i n the back of the cage, often have dilated pupils, Insulin overdose that induces the Somogyi response is one
and usually are flaccid when handled. Stress hyperglycemia of the most c o m m o n causes o f poor glycemic control i n
should also be suspected i f a disparity exists between assess diabetic cats. It can be induced with insulin doses of 1 to 2 U
ment o f glycemic control based o n results o f the history, per injection and can result i n cats receiving 10 to 15 U
physical examination, a n d stability o f body weight; assess of insulin per injection as veterinarians react to the persis
ment of glycemic control based o n results of b l o o d glucose tence o f clinical signs and increased blood glucose and
measurements; or when the initial b l o o d glucose concentra serum fructosamine concentrations. A cyclic history o f 1 or
tion measured i n the m o r n i n g is i n an acceptable range (i.e., 2 days of good glycemic control after which there are several
150 to 250 mg/dl) but subsequent b l o o d glucose concentra days of poor control should raise suspicion for insulin over
tions increase steadily throughout the day (Fig. 52-17). Once dosing and the Somogyi response. Arbitrarily decreasing the
stress hyperglycemia develops, it is a perpetual problem and insulin dose and evaluating the clinical response over the
ensuing 2 to 5 days is perhaps the best way to establish the c o m m o n i n diabetic cats treated with exogenous h u m a n
diagnosis. insulin, despite differences between h u m a n and feline insulin.
Studies identified an approximately equal frequency o f pos
Insulin Underdosing itive serum insulin antibody titers i n diabetic cats treated
Insulin underdosing is discussed on p. 780. C o n t r o l of gly with beef insulin and recombinant h u m a n insulin. In m y
cemia can be established in most diabetic cats using 1 U or experience, antiinsulin antibody titers are weakly positive i n
less of insulin/kg o f body weight administered twice each most cats that develop insulin antibodies, prevalence o f per
day. In general, insulin underdosing should be considered i f sistent titers is low, and presence o f serum insulin antibodies
the insulin dose is less than 1 U/kg/injection and the cat is do not appear to affect control of glycemia. Insulin resistance
receiving insulin twice a day. If insulin underdosing is sus caused by insulin antibody formation appears to be u n c o m
pected, the dose o f insulin should be gradually increased by m o n . Switching from recombinant h u m a n or porcine source
0.5 to 1 U/injection per week. The effectiveness of the change insulin to beef-/pork-source P Z I may improve control o f
in therapy should be evaluated by client perception o f clini glycemia i f insulin antibodies are the suspected cause for
cal response and measurement o f serum fructosamine or insulin ineffectiveness.
serial blood glucose concentrations. Other causes for poor
glycemic control should be ruled out before an increase in Concurrent Disorders Causing
the insulin dose above 1 U/kg/injection is considered. Insulin Resistance
Concurrent disorders causing insulin resistance is discussed
Short Duration of Insulin Effect on p. 783. The most c o m m o n concurrent disorders interfer
Short duration of insulin effect is discussed on p. 781. Short ing with insulin effectiveness i n cats include severe obesity,
duration of insulin effect is a c o m m o n problem i n diabetic chronic inflammation such as chronic pancreatitis and gin
cats despite twice-daily insulin administration. Short dura givitis, renal insufficiency, hyperthyroidism, acromegaly, and
tion of effect is most c o m m o n with N P H and lente insulin hyperadrenocorticism (see B o x 52-7). Obtaining a complete
(see Table 52-2). A diagnosis o f short duration o f insulin history and performing a thorough physical examination are
effect is made by demonstrating an initial b l o o d glucose the most important steps i n identifying these concurrent
concentration greater than 300 mg/dl combined with a disorders. If the history and physical examination are unre
glucose nadir above 80 mg/dl that occurs less than 8 hours markable, a C B C , serum biochemical analysis, serum thyrox
after insulin administration and recurrence o f hyperglycemia ine concentration, urinalysis with bacterial culture, and (if
(greater than 250 mg/dl) within 10 hours o f the insulin injec available) abdominal ultrasound should be obtained to
tion (see Fig. 52-7). Treatment involves changing to a longer- further screen for concurrent illness. A d d i t i o n a l tests will
acting insulin preparation (i.e., P Z I or glargine insulin). depend on the results o f the initial screening tests (see B o x
52-8).
Prolonged Duration of Insulin Effect
Prolonged duration o f insulin effect is discussed o n p. 781. CHRONIC COMPLICATIONS OF
In diabetic cats problems with prolonged duration o f insulin DIABETES MELLITUS
effect are most c o m m o n with twice-daily administration o f C h r o n i c complications o f diabetes mellitus are discussed o n
PZI and glargine insulin. p. 783. The most c o m m o n complications i n the diabetic cat
are hypoglycemia; chronic pancreatitis; weight loss; poor
Inadequate Insulin Absorption grooming behavior causing a dry, lusterless, and unkempt
Slow or inadequate absorption o f subcutaneously deposited haircoat; and peripheral neuropathy o f the h i n d limbs,
insulin was most commonly observed i n diabetic cats receiv causing weakness, inability to j u m p , a plantigrade stance,
ing ultralente insulin, a long-acting basal insulin that had a and ataxia (see B o x 52-5). Diabetic cats are also at risk for
slow onset and prolonged duration o f effect. In affected cats ketoacidosis.
the blood glucose concentration w o u l d decrease minimally,
if at all, despite insulin doses o f 8 to 12 U/cat. Ultralente Diabetic Neuropathy
insulin is no longer commercially available. A similar problem Diabetic neuropathy is one o f the most c o m m o n chronic
has not been reported for P Z I or glargine insulin. Impaired complications o f diabetes i n cats, with a prevalence o f
and erratic absorption o f insulin may occur as a result o f approximately 10%. Clinical signs o f a co-existent neuropa
thickening of the skin and inflammation o f the subcutane thy i n the diabetic cat include weakness, impaired ability to
ous tissues caused by chronic injection o f insulin i n the same j u m p , knuckling, a plantigrade posture with the cat's hocks
area of the body. Rotation o f the injection site helps prevent touching the ground when it walks (see Fig. 52-14), muscle
this problem. atrophy, depressed l i m b reflexes, and deficits i n postural
reaction testing. Clinical signs may progress to include the
Circulating Insulin-Binding Antibodies thoracic limbs (palmigrade posture; see Fig 52-14). A b n o r
Insulin-binding antibodies are discussed on p. 782. Feline malities o n electrophysiologic testing are consistent with
and beef insulin are similar, and feline, human, and porcine demyelination at all levels o f the motor and sensory periph
insulin differ. Fortunately, insulin antibody formation is not eral nerves and include decreased motor and sensory nerve
conduction velocities i n pelvic and thoracic limbs and lipolysis to increase, thus increasing the availability of FFAs
decreased muscle action potential amplitudes. Electromyo to the liver and i n turn promoting ketogenesis. As ketones
graphic abnormalities are usually absent and, when identi continue to accumulate i n the blood, the body's buffering
fied, are consistent with denervation. The most striking system becomes overwhelmed and metabolic acidosis devel
abnormality detected o n histologic examination o f nerve ops. As ketones accumulate i n the extracellular space, the
biopsies from affected cats is Schwann cell injury; axonal amount eventually surpasses the renal tubular threshold
degeneration is identified i n severely affected cats. The cause for complete resorption and they spill into the urine, con
of diabetic neuropathy is not k n o w n . Currently, there is no tributing to the osmotic diuresis caused by glycosuria and
specific therapy. Aggressive glucoregulation with insulin may enhancing the excretion o f solutes (e.g., sodium, potassium,
improve nerve conduction and reverse the posterior weak magnesium). Insulin deficiency per se also contributes to
ness and plantigrade posture (see Fig. 52-14). However, the the excessive renal losses of water and electrolytes. The result
response to therapy is variable, and the risks o f hypoglycemia is an excessive loss o f electrolytes and water, leading to
increase with aggressive insulin treatment. Generally, the volume contraction, an underperfusion of tissues, and the
longer the neuropathy has been present and the more severe development o f prerenal azotemia. The rise in the blood
the neuropathy, the less likely it is that i m p r o v i n g glycemic glucose concentration raises plasma osmolality, and the
control will reverse the clinical signs o f neuropathy. resulting osmotic diuresis further aggravates the rise in
plasma osmolality by causing water losses i n excess of salt
Prognosis loss. The increase i n plasma osmolality causes water to
Diabetic cats and dogs have a similar prognosis (see p. 785). shift out o f cells, leading to cellular dehydration. The meta
The mean survival time i n diabetic cats is approximately 3 bolic consequences o f D K A , which include severe acidosis,
years from time o f diagnosis. However, this survival time is hyperosmolality, obligatory osmotic diuresis, dehydration,
skewed because cats are usually 8 to 12 years o l d at the time and electrolyte derangements, eventually become life
of diagnosis, and a high mortality rate exists during the first threatening.
6 months because o f concurrent life-threatening or uncon
trollable disease (e.g., ketoacidosis, pancreatitis, renal failure). Clinical Features
Diabetic cats that survive the first 6 months can easily live D K A is a serious complication of diabetes mellitus that
longer than 5 years with the disease. occurs most c o m m o n l y i n dogs and cats with diabetes that
has gone undiagnosed. Less commonly, D K A develops i n an
insulin-treated diabetic dog or cat that is receiving an inad
DIABETIC KETOACIDOSIS equate dose of insulin, often occurring i n conjunction with
an infectious, inflammatory, or insulin-resistant hormonal
Etiology disorder. Because o f the close association between D K A and
The etiopathogenesis o f D K A is complex and usually affected newly diagnosed diabetes mellitus, the signalment of D K A
by concurrent clinical disorders. Virtually all dogs and cats i n dogs and cats is similar to that o f nonketotic diabetics.
with D K A have a relative or absolute deficiency o f insulin. The history and physical examination findings are vari
D K A develops in some diabetic dogs and cats even though able, i n part because of the progressive nature of the disorder
they receive daily injections o f insulin, and their circulating and the variable time between the onset of D K A and client
insulin concentrations may even be increased. The "relative" recognition o f a problem. Polyuria, polydipsia, polyphagia,
insulin deficiency i n these animals is created by concurrent and weight loss develop initially but are either unnoticed or
insulin resistance, w h i c h i n turn is created by concurrent considered insignificant by the client. Systemic signs of
disorders such as pancreatitis, infection, or renal insuffi illness (e.g., lethargy, anorexia, vomiting) ensue as ketonemia
ciency. Increased circulating concentrations o f diabetogenic and metabolic acidosis develop and worsen, with the severity
hormones, most notably glucagon, accentuate insulin of these signs directly related to the severity of the metabolic
deficiency by p r o m o t i n g insulin resistance; stimulate lipoly acidosis and the nature of concurrent disorders that are often
sis, leading to ketogenesis; and stimulate hepatic gluconeo present. The time interval from the onset of the initial clin
genesis, w h i c h worsens hyperglycemia. ical signs o f diabetes to the development of systemic signs of
Insulin deficiency and insulin resistance, together with D K A is unpredictable and ranges from a few days to longer
increased circulating concentrations o f diabetogenic hor than 6 months. Once ketoacidosis begins to develop, however,
mones, play a critical role i n the stimulation o f ketogenesis. severe illness usually becomes evident within 7 days.
For the synthesis o f ketone bodies (i.e., acetoacetic acid, C o m m o n physical examination findings include dehy
-hydroxybutyric acid, acetone) to be enhanced, there must dration, lethargy, weakness, tachypnea, vomiting, and some
be two major alterations i n intermediary metabolism: (1) times a strong odor of acetone on the breath. Slow, deep
enhanced mobilization o f free fatty acids (FFAs) from tri breathing may be observed in animals with severe metabolic
glycerides stored i n adipose tissue and (2) a shift i n hepatic acidosis. Gastrointestinal tract signs such as vomiting and
metabolism from fat synthesis to fat oxidation and ketogen abdominal pain are c o m m o n in animals with D K A , i n part
esis. Insulin is a powerful inhibitor o f lipolysis and F F A oxi because of the c o m m o n concurrent occurrence of pancre
dation. A relative or absolute deficiency o f insulin allows atitis. Other intraabdominal disorders should also be con-
sidered and diagnostic tests (e.g., abdominal ultrasound) ketoacidotic, diabetic pet are (1) to provide adequate
performed to help identify the cause of the gastrointestinal amounts o f insulin to suppress lipolysis, ketogenesis, and
signs. hepatic gluconeogenesis; (2) to restore water and electrolyte
losses; (3) to correct acidosis; (4) to identify the factors pre
Diagnosis cipitating the present illness; and (5) to provide a carbohy
The diagnosis of diabetes mellitus is based on appropriate drate substrate (i.e., dextrose) when necessary to allow
clinical signs, persistent fasting hyperglycemia, and glycos continued administration o f insulin without causing hypo
uria. Documenting ketonuria with reagent test strips that glycemia (Box 52-9). Proper therapy does not mean forcing
measure acetoacetic acid (KetoDiastix; Ames Division, Miles a return to a n o r m a l state as rapidly as possible. Because
Laboratories) establishes the diagnosis of diabetic ketosis osmotic and biochemical problems can arise as a result o f
(DK), and documenting metabolic acidosis establishes the overly aggressive therapy as well as from the disease itself,
diagnosis of D K A . If ketonuria is not present but D K A is rapid changes i n various vital parameters can be as harmful
suspected, serum or urine can be tested for acetone using as, or more harmful than, no change. If all abnormal param
Acetest tablets (Ames Division, Miles Laboratories), serum eters can be slowly returned toward n o r m a l over a period of
can be tested for the presence of [3-hydroxybutyrate using a 24 to 48 hours, therapy is more likely to be successful.
benchtop chemistry analyzer, and plasma from heparinized Critically important information for formulating the
hematocrit tubes can be used to test for the presence o f initial treatment protocol include hematocrit and total
acetoacetic acid using urine reagent strips used to document plasma protein concentration; serum glucose, albumin, cre
ketonuria. (3-hydroxybutyrate and acetone are derived from atinine, and urea nitrogen concentrations; serum electro
acetoacetic acid, and commonly used urine reagent strips do lytes; venous total C O or arterial acid-base evaluation; and
2
not detect (3-hydroxybutyrate and acetone. However, it is urine specific gravity. Abnormalities frequently associated
extremely u n c o m m o n for D K A to develop without an excess with D K A are listed i n B o x 52-10. Once treatment for D K A
of acetoacetic acid. is initiated, additional studies, such as a C B C , serum b i o
chemistry panel, urinalysis, thoracic radiographs, and
Treatment of "Healthy" Dogs or Cats with abdominal ultrasound, or diagnostic tests for pancreatitis,
Diabetic Ketosis or Diabetic Ketoacidosis diestrus i n the female dog, hyperthyroidism, and hyperadre
If systemic signs o f illness are absent or m i l d , serious abnor nocorticism are usually warranted to identify underlying
malities are not readily identifiable on physical examination, concurrent disorders (see B o x 52-8).
and metabolic acidosis is m i l d (i.e., total venous C O or arte
2
Hypotonic fluids (e.g., 0.45% saline) are rarely indicated i n fluid imbalance i n a slow but steady manner. As a general
dogs and cats with D K A , even when severe hyperosmolality rule o f thumb, a fluid rate o f 1.5 to 2 times maintenance
is present. H y p o t o n i c fluids do not provide adequate amounts (i.e., 60 to 100 ml/kg q24h) is typically chosen initially, with
of sodium to correct the sodium deficiency, restore normal subsequent adjustments based o n frequent assessment of
fluid balance, or stabilize b l o o d pressure. Rapid administra hydration status, urine output, severity of azotemia, and per
tion o f hypotonic fluids can also cause a rapid decrease i n sistence of vomiting and diarrhea.
the osmolality of extracellular fluid (ECF), which may result
in cerebral edema, deterioration i n mentation, and eventu Potassium Supplementation
ally coma. Hyperosmolality is best treated with isotonic Most dogs and cats with D K A initially have either normal or
fluids and the judicious administration o f insulin. F l u i d decreased serum potassium concentrations. D u r i n g therapy
administration should be directed at gradually replacing for D K A the serum potassium concentration decreases
hydration deficits over 24 hours while also supplying m a i n because of rehydration (dilution), insulin-mediated cellular
tenance fluid needs and matching ongoing losses. Rapid uptake of potassium (with glucose), continued urinary losses,
replacement of fluids is rarely indicated unless the dog or cat and correction of acidemia (translocation of potassium into
is in shock. Once the animal is out of this critical phase, fluid the intracellular fluid compartment; Fig. 52-18). Severe
replacement should be decreased i n an effort to correct the hypokalemia is the most c o m m o n complication that devel-
ops during the initial 24 to 36 hours of treatment of D K A . restored, urine production increases, and hyperkalemia is
Dogs and cats with hypokalemia require aggressive potas resolving.
sium replacement therapy to replace deficits and to prevent Ideally, the amount of potassium required should be
worsening, life-threatening hypokalemia after initiation of based on actual measurement of the serum potassium con
insulin therapy. The exception to potassium supplementa centration. If an accurate measurement of serum potassium
tion of fluids is hyperkalemia associated with oliguric renal is not available, 40 m E q of potassium should initially be
failure. Potassium supplementation should initially be with added to each liter of intravenous fluids. N o r m a l saline solu
held in these dogs and cats until glomerular filtration is tion does not contain potassium, and Ringer's solution con
tains 4 m E q of potassium per liter; thus these fluids should
be supplemented with 40 m E q and 36 m E q of potassium,
respectively. Subsequent adjustments i n potassium supple
BOX 52-10 mentation should be based on measurement of serum potas
sium, preferably every 6 to 8 hours until the dog or cat is
C o m m o n Clinicopathologic Abnormalities Identified i n
stable and serum electrolytes are i n the normal range.
Dogs and Cats with Diabetic Ketoacidosis
FIG 5 2 - 1 8
Redistribution of extracellular fluid (ECF) a n d intracellular fluid (ICF) h y d r o g e n , p o t a s s i u m ,
a n d p h o s p h a t e ions in r e s p o n s e to a d e c r e a s e in E C F p H (i.e., a c i d o s i s ) , a n i n c r e a s e in
E C F g l u c o s e a n d osmolality, a n d the t r a n s l o c a t i o n of w a t e r from the ICF to the E C F
c o m p a r t m e n t a n d subsequent c o r r e c t i o n of a c i d o s i s a n d the intracellular shift of g l u c o s e
+
a n d electrolytes with insulin treatment. A , N o r m a l E C F p H . B, E C F H c o n c e n t r a t i o n
+
increases d u r i n g a c i d o s i s , c a u s i n g H to m o v e into cells a n d d o w n its c o n c e n t r a t i o n
+
g r a d i e n t . Increase in E C F g l u c o s e a n d o s m o l a l i t y c a u s e s extracellular shift of w a t e r , K ,
+ 2 + +
a n d P O . C, E C F H c o n c e n t r a t i o n d e c r e a s e s d u r i n g c o r r e c t i o n of a c i d o s i s , c a u s i n g H
4
sium or 4 m E q o f sodium per milliliter. The recommended should be initiated. M a n y of these animals have severe
dosage for phosphate supplementation is 0.01 to 0.03 m m o l depression that may be a result o f concurrent severe central
of phosphate per kilogram o f body weight per hour, prefer nervous system acidosis. Metabolic acidosis should be
ably administered i n calcium-free I V fluids (e.g., 0.9% corrected slowly, thereby avoiding major alterations i n the
sodium chloride). In dogs and cats with severe hypophos p H o f the C S F . O n l y a portion o f the bicarbonate deficit
phatemia it may be necessary to increase the dosage to 0.03 is given initially over a 6-hour period. The bicarbonate
to 0.12 m m o l / k g / h o u r . Because the dose of phosphate neces deficit (i.e., the milliequivalents of bicarbonate initially
sary to replete an animal and the animal's response to therapy needed to correct acidosis to the critical level of 12 m E q / L
cannot be predicted, it is important to initially m o n i t o r the over a period o f 6 hours) is calculated by the following
serum phosphorus concentration every 8 to 12 hours and formula:
adjust the phosphate infusion accordingly. Adverse effects
mEq bicarbonate = body weight (kg) X 0.4 X (12 - animal's
from overzealous phosphate administration include iatro
bicarbonate) X 0.5
genic hypocalcemia and its associated neuromuscular signs,
hypernatremia, hypotension, and metastatic calcification. If the serum bicarbonate concentration is not known, the
Serum total or (preferably) ionized calcium concentration following formula should be used:
should be measured at the same time as serum phosphorus
mEq bicarbonate = body weight (kg) X 2
concentration and the rate o f phosphate infusion decreased
if hypocalcemia is identified. Phosphorus supplementation The difference between the animal's serum bicarbonate
is not indicated i n dogs and cats with hypercalcemia, hyper concentration and the critical value of 12 m E q / L represents
phosphatemia, oliguria, or suspected tissue necrosis. If renal the treatable base deficit i n D K A . If the animal's serum bicar
function is i n question, phosphorus supplementation should bonate concentration is not k n o w n , the number 10 should
not be done until the status o f renal function and serum be used for the treatable base deficit. The factor 0.4 corrects
phosphorus concentration are k n o w n . for the E C F space i n which bicarbonate is distributed (40%
of body weight). The factor 0.5 provides one half of the
Magnesium Supplementation required dose o f bicarbonate i n the I V infusion. This tech
Plasma total and ionized magnesium concentrations may be nique allows a conservative dose to be given over a 6-hour
within or below the reference range at the time D K A is diag period. Bicarbonate should never be given by bolus infusion.
nosed i n the dog or cat, often decrease during the initial After 6 hours o f therapy the acid-base status should be
treatment o f D K A , and typically normalize without treat reevaluated and a new dose calculated. Once the plasma
ment as the D K A resolves. Clinical signs o f hypomagnesemia bicarbonate level is greater than 12 m E q / L , further bicarbon
do not usually occur until the serum total and ionized mag ate supplementation is not indicated.
nesium concentration is less than 1.0 and 0.5 mg/dl, respec
tively, and even at these low levels many dogs and cats remain INSULIN THERAPY
asymptomatic. I do not routinely treat hypomagnesemia i n Insulin therapy is critical for the resolution of ketoacidosis.
dogs or cats with D K A unless problems with persistent leth However, overzealous insulin treatment can cause severe
argy, anorexia, weakness, or refractory hypokalemia or hypo hypokalemia, hypophosphatemia, and hypoglycemia during
calcemia are encountered after 24 to 48 hours o f fluid and the first 24 hours o f treatmentproblems that can be m i n
insulin therapy and another cause for the problem cannot imized by appropriate fluid therapy, frequent monitoring of
be identified (see p. 780). serum electrolytes and b l o o d glucose concentrations, and
modification of the initial insulin treatment protocol as indi
Bicarbonate Therapy cated. Initiating appropriate fluid therapy should always be
The clinical presentation o f the dog or cat, i n conjunction the first step i n the treatment o f D K A . Delaying insulin
with the plasma bicarbonate or total venous C O concentra
2 therapy for a m i n i m u m o f 1 to 2 hours is recommended to
tion, should be used to determine the need for bicarbonate allow the benefits o f fluid therapy to begin to be realized
therapy. Bicarbonate supplementation is not recommended before the glucose, potassium, and phosphorus-lowering
when plasma bicarbonate (or total venous C O ) is 12 m E q / L
2 effects o f insulin therapy commence. Additional delays and
or greater, especially i f the animal is alert. A n alert dog or cat decisions on the initial dosage o f insulin administered are
probably has a n o r m a l or near-normal p H i n the cerebrospi based on serum electrolyte results. If the serum potassium
nal fluid (CSF). The acidosis i n these animals is corrected concentration is within the normal range after 2 hours of
through insulin and fluid therapy. Improvement i n renal fluid therapy, insulin treatment should commence as
perfusion enhances urinary loss o f ketoacids, and insulin described i n the subsequent paragraphs. If hypokalemia per
therapy markedly diminishes the production o f ketoacids. sists, insulin therapy can be delayed an additional 1 to 2
Acetoacetate and [3-hydroxybutyrate are also metabolically hours to allow fluid therapy to replenish potassium, the
usable anions, and 1 m E q o f bicarbonate is generated from initial insulin dose can be reduced to dampen the intracel
each 1 m E q o f ketoacid metabolized. lular shift o f potassium and phosphorus, or both can be
done. However, insulin therapy should be started within 4 blood glucose concentration. If the b l o o d glucose concentra
hours of initiating fluid therapy. tion dips below 150 m g / d l or rises above 300 mg/dl, the
The amount of insulin needed by an individual animal is insulin dose can be lowered or raised accordingly. Dextrose
difficult to predict. Therefore an insulin preparation with a helps m i n i m i z e problems with hypoglycemia and allows
rapid onset of action and a brief duration of effect is ideal insulin to be administered on schedule. Delaying the a d m i n
for making rapid adjustments i n the dose and frequency of istration of insulin delays correction of the ketoacidotic
administration to meet the needs of that particular dog or state.
cat. Rapid-acting regular crystalline insulin meets these cri
teria and is recommended for the treatment of D K A . Constant Low-Dose Insulin
Insulin protocols for the treatment of D K A include the Infusion Technique
hourly intramuscular technique, the continuous low-dose I V Constant I V infusion of regular crystalline insulin is also
infusion technique, and the intermittent intramuscular then effective i n decreasing b l o o d glucose concentrations. T o
subcutaneous technique. A l l three routes (IV, intramuscular, prepare the infusion, regular crystalline insulin (2.2 U / k g for
subcutaneous) of insulin administration are effective i n dogs; 1.1 U / k g for cats) is added to 250 m l of 0.9% saline
decreasing blood glucose and ketone concentrations. Suc and initially administered at a rate of 10 m l / h o u r i n a line
cessful management of D K A is not dependent o n the route separate from that used for fluid therapy. This provides an
of insulin administration. Rather, it is dependent on proper insulin infusion of 0.05 (cat) and 0.1 (dog) U/kg/hour, an
treatment of each disorder associated with D K A . infusion rate that has been shown to produce plasma insulin
concentrations between 100 and 200 U/ml i n dogs. Because
Intermittent Intramuscular Regimen insulin adheres to glass and plastic surfaces, approximately
Dogs and cats with severe D K A should receive an initial 50 m l of the insulin-containing fluid should be r u n through
regular crystalline insulin loading dose of 0.2 U / k g followed the drip set before it is administered to the animal. The rate
by 0.1 U / k g every hour thereafter. The insulin dose can be of insulin infusion can be reduced for the initial 2 to 3 hours
reduced by 25% to 50% for the first 2 to 3 injections if hypo if hypokalemia is a concern. T w o separate catheters are rec
kalemia is a concern. The insulin should be administered ommended for treatment: a peripheral catheter for insulin
into the muscles of the rear legs to ensure that the injections administration and a central catheter for fluid a d m i n
are penetrating muscle rather than fat or subcutaneous istration and b l o o d sampling. A n infusion or syringe
tissue. Diluting regular insulin 1:10 with sterile saline and p u m p should be used to ensure a constant rate of insulin
using 0.3 m l U100 insulin syringes are helpful when small infusion.
doses of insulin are required. The blood glucose concentra Adjustments i n the infusion rate are based on hourly
tion should be measured every hour using a point-of-care measurements of b l o o d glucose concentration; an hourly
chemistry analyzer or portable blood glucose monitoring decline of 50 m g / d l i n the b l o o d glucose concentration is
device and the insulin dosage adjusted accordingly. The goal ideal. Once the b l o o d glucose concentration approaches
of initial insulin therapy is to slowly lower the b l o o d glucose 250 mg/dl, the insulin infusion can be discontinued and
concentration to the range of 200 to 250 mg/dl, preferably regular insulin given every 4 to 6 hours intramuscularly or
over a 6- to 10-hour period. A n hourly decline of 50 m g / d l every 6 to 8 hours subcutaneously, as discussed for the hourly
in the blood glucose concentration is ideal. This provides a intramuscular protocol. Alternatively, the insulin infusion
steady moderate decline, with no major shifts i n osmolality. can be continued (at a decreased rate to prevent hypoglyce
A declining blood glucose concentration also ensures that mia) until the insulin preparation is exchanged for a longer-
lipolysis and the supply of FFAs for ketone production have acting product. Dextrose should be added to the I V fluids
been effectively turned off. Glucose concentrations, however, once the b l o o d glucose concentration approaches 250 mg/dl,
decrease much more rapidly than do ketone levels. In general, as discussed i n the section on hourly intramuscular insulin
hyperglycemia is corrected within 12 hours, but ketosis may technique.
take 48 to 72 hours to resolve.
Once the initial hourly insulin therapy brings the b l o o d Intermittent Intramuscular/
glucose concentration near 250 mg/dl, hourly administra Subcutaneous Technique
tion of regular insulin should be discontinued and regular The intermittent intramuscular followed by intermittent
insulin given every 4 to 6 hours intramuscularly or, if hydra subcutaneous insulin technique is less labor intensive than
tion status is good, every 6 to 8 hours subcutaneously. The the other techniques for insulin administration, but the
initial dose is usually 0.1 to 0.3 U / k g , with subsequent adjust decrease i n b l o o d glucose can be rapid and the risk of hypo
ments based on blood glucose concentrations. In addition, glycemia is greater. The initial regular crystalline insulin dose
at this point the I V infusion solution should have enough is 0.25 U / k g , administered intramuscularly. Subsequent
50% dextrose added to create a 5% dextrose solution (100 m l intramuscular injections are repeated every 4 hours. Usually,
of 50% dextrose added to each liter of fluids). The b l o o d insulin is administered intramuscularly only once or twice.
glucose concentration should be maintained between 150 Once the animal is rehydrated, the insulin is administered
and 300 mg/dl until the animal is stable and eating. Usually, subcutaneously rather than intramuscularly every 6 to 8
a 5% dextrose solution is adequate i n maintaining the desired hours. Subcutaneous administration is not recommended
initially because o f problems with insulin absorption from and improve the chances o f a successful response to therapy,
subcutaneous sites o f deposition i n a dehydrated dog or cat. all abnormal parameters should be slowly returned toward
The dosage o f intramuscular or subcutaneous insulin is normal over a period of 24 to 48 hours, the physical and
adjusted according to b l o o d glucose concentrations, which mental status of the animal must be evaluated frequently (at
initially should be measured hourly beginning with the first least three to four times daily), and biochemical parameters
intramuscular injection. A n hourly decline o f 50 m g / d l i n (e.g., b l o o d glucose, serum electrolyte, blood gas values)
the b l o o d glucose concentration is ideal. Subsequent insulin must be evaluated i n a timely fashion. D u r i n g the initial 24
dosages should be decreased by 25% to 50% i f this goal is hours the b l o o d glucose concentration should be measured
exceeded. Dextrose should be added to the I V fluids once the every 1 to 2 hours and serum electrolyte and b l o o d gas values
blood glucose concentration approaches 250 mg/dl, as measured every 6 to 8 hours, with modifications i n fluid,
discussed i n the section on hourly intramuscular insulin insulin, and bicarbonate therapy made accordingly.
technique.
Prognosis
Initiating Longer-Acting Insulin D K A remains one o f the most difficult metabolic therapeu
Longer-acting insulin (e.g., N P H , lente, PZI) should not tic challenges i n veterinary medicine. Despite all precautions
be administered until the dog or cat is stable; eating; and diligent therapy, a fatal outcome is sometimes inevitable.
maintaining fluid balance without any I V infusions; and no Approximately 30% of cats and dogs with severe D K A die or
longer acidotic, azotemic, or electrolyte-deficient. The initial are euthanized during the initial hospitalization. Death is
dose o f the longer-acting insulin is similar to the regular usually the result o f a severe underlying illness (e.g., oliguric
insulin dose being used just before switching to the longer- renal failure, necrotizing pancreatitis), severe metabolic aci
acting insulin. Subsequent adjustments i n the longer-acting dosis (i.e., arterial b l o o d p H less than 7), or complications
insulin dose should be based on clinical response and mea that develop during therapy (e.g., cerebral edema, hypokale
surement o f b l o o d glucose concentrations, as described mia). Nevertheless, i f logical therapy is implemented and
o n p. 775. animals are monitored carefully, a positive outcome is
attainable.
CONCURRENT ILLNESS
Therapy for D K A frequently involves the management o f
concurrent, often serious illness. C o m m o n concurrent i l l INSULIN-SECRETING
nesses i n dogs and cats with D K A include bacterial infection; BETA-CELL NEOPLASIA
pancreatitis; congestive heart failure; renal failure; cholan
giohepatitis; and insulin-antagonistic disorders, most notably Etiology
hyperadrenocorticism, hyperthyroidism, and diestrus. It Functional tumors arising from the cells of the pancreatic
may be necessary i n such animals to modify the therapy for islets are malignant tumors that secrete insulin independent
D K A (e.g., fluid therapy i n animals with concurrent heart of the typically suppressive effects o f hypoglycemia, cell
failure) or implement additional therapy (e.g., antibiotics), tumors, however, are not completely autonomous and
depending o n the nature o f the concurrent illness. Insulin respond to provocative stimuli such as an increase in blood
therapy, however, should never be delayed or discontinued. glucose by secreting insulin, often i n excessive amounts.
Resolution o f ketoacidosis can be achieved only through Immunohistochemical analysis o f cell tumors has revealed
insulin therapy. If nothing is to be given per os, insulin therapy a high incidence o f m u l t i h o r m o n a l production, including
should be continued and the b l o o d glucose concentration pancreatic polypeptide, somatostatin, glucagon, serotonin,
maintained with I V dextrose infusions. If a concurrent and gastrin. However, insulin has been identified as the most
insulin-antagonistic disease is present, it may be necessary to c o m m o n product demonstrated within the neoplastic cells,
eliminate the disease while the animal is still ill to improve and clinical signs are primarily those that result from insulin-
insulin effectiveness and resolve the ketoacidosis. induced hypoglycemia.
Insulin-secreting cell tumors are u n c o m m o n i n dogs
COMPLICATIONS O F THERAPY FOR and rare i n cats. Virtually all cell tumors in dogs are malig
DIABETIC KETOACIDOSIS nant, and most dogs have microscopic or grossly visible
Complications caused by therapy for D K A are c o m m o n and metastatic lesions at the time o f surgery. The most common
include hypoglycemia, central nervous system signs second metastatic sites are the regional lymphatics and l y m p h nodes,
ary to cerebral edema, severe hypokalemia, severe hyperna liver, and peripancreatic mesentery. Pulmonary metastasis is
tremia and hyperchloremia, and hemolytic anemia resulting u n c o m m o n and occurs late i n the disease. In most dogs
from hypophosphatemia. Complications usually result from hypoglycemia recurs weeks to months after surgical excision
overly aggressive treatment, inadequate m o n i t o r i n g o f the of the tumor. The high prevalence o f metastatic lesions at
animal's condition, and failure to reevaluate biochemical the time afflicted dogs are initially examined results, in part,
parameters i n a timely manner. D K A is a complex disorder from the typically protracted time it takes for clinical signs
that is associated with a high mortality rate i f improperly to develop and the interval between the time a client initially
managed. T o m i n i m i z e the risk of therapeutic complications observes signs and seeks assistance from a veterinarian. Most
PHYSICAL E X A M I N A T I O N
BOX 52-1 1
Physical examination findings i n animals with cell tumors
Clinical Signs Associated with Insulin-Secreting Tumors are surprisingly unremarkable; dogs are usually free of visible
in Dogs or palpable abnormalities. Weakness and lethargy are the
most c o m m o n findings and are identified i n approximately
Seizures*
40% and 20% o f our cases, respectively. Collapsing episodes
Weakness*
and seizures may occur during the examination but are
Collapse
u n c o m m o n . Weight gain is evident i n some dogs and is
Ataxia
probably a result o f the potent anabolic effects o f insulin.
Polyphagia
Weight gain
Muscle fasciculations
Peripheral Neuropathy
Posterior weakness (neuropathy) Peripheral neuropathies have been observed i n dogs with p
Lethargy cell tumors and may cause paraparesis to tetraparesis; facial
Nervousness paresis to paralysis; hyporeflexia to areflexia; hypotonia; and
Bizarre behavior muscle atrophy o f the appendicular, masticatory, and/or
facial muscles. Sensory nerves may also be affected. Onset o f
* Common clinical signs.
clinical signs may be acute (i.e., days) or insidious (i.e., weeks
to months). The pathogenesis o f the polyneuropathy is not
k n o w n . Proposed theories include metabolic derangements
dogs are symptomatic for 1 to 6 months before being brought of the nerves induced by chronic and severe hypoglycemia
to a veterinarian. or some other tumor-induced metabolic deficiency, an
immune-mediated paraneoplastic syndrome resulting from
Clinical Features shared antigens between t u m o r and nerves, or toxic factors
produced by the t u m o r that deleteriously affect the nerves.
SIGNALMENT OF TREATMENT Treatment is aimed at surgical removal o f the cell tumor.
cell tumors typically occur i n middle-aged or older dogs. Prednisone therapy (initially 1 mg/kg q24h) may also
The median age at the time of diagnosis o f a cell t u m o r i n improve clinical signs.
97 dogs i n our series was 10 years with an age range o f 3 to
14 years. N o sex-related predilection is seen, cell tumors CLINICAL P A T H O L O G Y
are most commonly diagnosed i n large breeds o f dogs such Results o f the C B C and urinalysis are usually n o r m a l . The
as the German Shepherd D o g , Labrador Retriever, and only consistent abnormality identified i n serum biochemis
Golden Retriever, cell tumors have been reported i n try profiles is hypoglycemia. The median initial b l o o d glucose
Siamese and mixed-breed cats older than 10 years o f age. concentration i n 97 o f our dogs with a cell t u m o r was
38 mg/dl, with a range o f 15 to 78 mg/dl. N i n e t y percent o f
CLINICAL SIGNS the dogs had a r a n d o m b l o o d glucose concentration less
Clinical signs are caused by hypoglycemia and an increase i n than 60 mg/dl. Dogs with cell tumors occasionally have a
circulating catecholamine concentrations and include sei blood glucose concentration of 60 to 80 mg/dl. Such a finding
zures, weakness, collapse, ataxia, muscle fasciculations, and does not rule out hypoglycemia as a cause o f episodic weak
bizarre behavior (Box 52-11). The severity o f clinical signs ness or seizure activity. Fasting with hourly evaluations o f
depends on the duration and severity of hypoglycemia. Dogs the b l o o d glucose concentration should be carried out i n
with chronic hypoglycemia or with recurring episodes appear dogs with suspected hypoglycemia. The time required to
to tolerate low blood glucose concentrations (20 to 30 m g / induce hypoglycemia with fasting i n dogs with a cell t u m o r
dl) for prolonged periods without clinical signs, and only depends i n part on the extent o f disease at the time the dog
small additional changes i n the b l o o d glucose concentration is examined and ranges from a few hours to longer than 24
are then required to produce symptomatic episodes. Fasting, hours. The remainder o f the serum biochemistry profile is
excitement, exercise, and eating may trigger the development usually normal. H y p o a l b u m i n e m i a , hypophosphatemia,
of clinical signs. Because of the compensatory counterregu hypokalemia, and increased alkaline phosphatase and alanine
latory mechanisms that are designed to increase the b l o o d aminotransferase activities may occur, but these findings
glucose concentration when hypoglycemia develops, clinical are considered nonspecific and not helpful i n arriving at
signs tend to be episodic and are generally observed for only a definite diagnosis. A correlation between increased liver
a few seconds to minutes. If these counterregulatory mecha enzyme activities and metastasis o f cell tumors to the liver
nisms are inadequate, seizures occur as the b l o o d glucose has not been established.
concentration continues to decrease. Seizures are often self-
limiting, lasting from 30 seconds to 5 minutes, and may Diagnosis
stimulate further catecholamine secretion and the activation The diagnosis o f a cell tumor requires initial confirmation
of other counterregulatory mechanisms that increase the of hypoglycemia, followed by documentation o f inappropri
blood glucose concentration above critical levels. ate insulin secretion and identification o f a pancreatic mass
secretion i n normal animals, with the degree of suppression
directly related to its severity. Hypoglycemia fails to have this
same suppressive effect on insulin secretion i f the insulin is
synthesized and secreted from autonomous neoplastic cells
because tumor cells that produce and secrete insulin are less
responsive to hypoglycemia than are normal B cells. Invari
ably, the dog with a B cell tumor will have an inappropriate
excess of insulin relative to that needed for a particular blood
glucose concentration. Confidence i n identifying an inap
propriate excess of insulin depends on the severity of the
hypoglycemia; the lower the blood glucose concentration,
the more confident the clinician can be i n identifying inap
propriate hyperinsulinemia, especially when the serum
insulin concentration falls i n the normal range. If the blood
glucose concentration is l o w and the insulin concentration
is i n the upper half of the normal range or increased, the
animal has a relative or absolute excess of insulin that can
best be explained by the presence of an insulin-secreting B
cell tumor.
M o s t dogs with B cell neoplasia are persistently hypogly
cemic. If the blood glucose concentration is less than 60 mg/
dl (preferably less than 50 mg/dl), serum should be submit
ted to a commercial veterinary endocrine laboratory for
determination of glucose and insulin concentrations. If the
blood glucose concentration is greater than 60 mg/dl, fasting
may be necessary to induce hypoglycemia. Blood glucose
FIG 5 2 - 1 9 concentrations should be evaluated hourly during the fast
Ultrasonogram of the pancreas showing an islet -cell tumor and b l o o d obtained for glucose and insulin determination
(arrow) (A) and an enlarged hepatic lymph node (arrows) when the blood glucose concentration decreases to less than
(B) resulting from metastasis of the -cell tumor to the liver in 50 mg/dl. It is important to remember that blood glucose
a 9-year-old Cocker Spaniel.
results obtained from portable home blood glucose-
monitoring devices are often lower than results obtained
using benchtop methodologies. A blood sample for submis
using ultrasonography or laparotomy. Considering the sion to a commercial laboratory for glucose and insulin
potential differential diagnoses for hypoglycemia (see B o x determinations should not be obtained until the blood
52-2), a tentative diagnosis of a B cell tumor can often be glucose measured on these devices is less than 40 mg/dl.
made on the basis of the history, physical examination Once hypoglycemia has been induced, the dog can be fed
findings, and an absence of abnormalities other than hypo several small meals over the next 1 to 3 hours to prevent a
glycemia shown by routine b l o o d tests. A b d o m i n a l ultraso marked increase i n the blood glucose concentration and a
nography can be used to identify a mass i n the region of the potential postprandial reactive hypoglycemia.
pancreas and to look for evidence of potential metastatic Serum insulin concentrations must be evaluated simulta
disease i n the liver and surrounding structures (Fig. 52-19). neously i n relation to the blood glucose concentration. The
Because of the small size of most B cell tumors, abdominal serum insulin and glucose concentrations i n the healthy
ultrasonographic findings are often interpreted as normal, fasted dog are usually between 5 and 20 U/ml and 70 and
although a pancreatic mass or metastatic lesion can be found 110 mg/dl, respectively. Fnding a serum insulin concentra
at surgery. A normal abdominal ultrasonographic finding tion greater than 20 U/ml in a dog with a corresponding
does not rule out the diagnosis of a B cell tumor. A l t h o u g h blood glucose concentration less than 60 mg/dl (preferably
computed tomographic imaging was better than ultrasonog less than 50 mg/dl) i n combination with appropriate clinical
raphy or somatostatin receptor scintigraphy at identifying signs and clinicopathologic findings strongly supports the
primary tumors, false-positive identification of metastatic diagnosis of a B cell tumor. A B cell tumor is also possible
sites was unacceptably high i n one study (Robben et al., if the serum insulin concentration is i n the high-normal
2005). Thoracic radiographs are of m i n i m a l value i n docu range (10 to 20 U/ml). Insulin values i n the low-normal
menting metastatic disease, primarily because identifiable range (5 to 10 U/ml) may be found i n animals with other
metastatic nodules i n the lung occur late i n the disease. causes of hypoglycemia as well as a B cell tumor. Carefully
The diagnosis of a cell tumor is established by evaluat reviewing the history, physical examination findings, and
ing the serum insulin concentration at a time when hypo diagnostic tests results and, i f necessary, repeating serum
glycemia is present. Hypoglycemia suppresses insulin glucose and insulin measurements when hypoglycemia is
more severe will usually identify the cause of the hypoglyce
mia. A n y serum insulin concentration that is below the
normal range (typically less than 5 (U/ml) is consistent with Long-term M e d i c a l Therapy for Dogs with
insulinopenia and does not indicate the presence o f a [3 cell -Cell Neoplasia
tumor. Similar guidelines are used for cats with a suspected
cell tumor. Standard Treatments
1. Dietary therapy
Treatment a. Feed canned or dry food in three to six small meals
daily
OVERVIEW OF TREATMENT b. Avoid foods containing monosaccharides, disaccha
Treatment options for a p cell tumor include surgical explo rides, propylene glycol and corn syrup
ration, medical treatment for chronic hypoglycemia, or both. 2. Limit exercise
3. Glucocorticoid therapy
Surgery offers a chance to cure dogs with a resectable solitary
a. Prednisone, 0.5 m g / k g divided into two doses
mass. In dogs with nonresectable tumors or w i t h obvious
initially
metastatic lesions, removal of as m u c h abnormal tissue as
b. Gradually increase dose and frequency of adminis
possible frequently results in remission, or at least allevia tration, as needed
tion, of clinical signs and an improved response to medical c. G o a l is to control clinical signs, not to reestablish
therapy. Survival time is longer in dogs undergoing surgical euglycemia
exploration and tumor debulking followed by medical d. Consider alternative treatments if signs of iatrogenic
therapy, compared with dogs that receive only medical treat hypercortisolism become severe or glucocorticoids
ment. Despite these benefits, surgery remains a relatively become ineffective
aggressive mode of treatment, in part because o f the high
Additional Treatments
prevalence of metastatic disease, the older age o f many dogs
1. Diazoxide therapy
at the time cell neoplasia is diagnosed, and the potential
a. Continue standard treatment; reduce glucocorticoid
for postoperative pancreatitis. As a general rule, I am less
dose to minimize adverse signs
inclined to recommend surgery i n aged dogs (i.e., 12 years
b. Diazoxide, 5 m g / k g q12h initially
and older), dogs with metastatic disease identified by ultra c. Gradually increase dose as needed, not to exceed
sonography, and dogs with significant concurrent disease. 60 mg/kg/day
(See Suggested Readings for detailed information on surgical d. G o a l is to control clinical signs, not to reestablish
techniques.) euglycemia
2. Somatostatin therapy
PERIOPERATIVE M A N A G E M E N T O F a. Continue standard treatment; reduce glucocorticoid
DOGS U N D E R G O I N G SURGERY dose to minimize adverse signs
U n t i l surgery is performed, the dog or cat with a cell tumor b. Octreotide (Novartis Pharmaceuticals), 10 to 4 0 g/
dog administered subcutaneously q12h to q8h
must be protected from episodes o f severe hypoglycemia.
3. Streptozotocin therapy
This can usually be accomplished through the frequent
a. Continue standard treatment; reduce glucocorticoid
feeding of small meals and administration o f glucocorticoids dose to minimize adverse signs
(Box 52-12). The I V administration of a balanced electrolyte b. 0.9% saline diuresis for 3 hours, then streptozotocin,
solution containing 2.5% to 5% dextrose is important during 2
5 0 0 m g / m , in 0.9% saline and administered intra
the perioperative period. The goal o f the dextrose infusion venously over 2 hours, then 0.9% saline diuresis for
is to prevent clinical signs of hypoglycemia and maintain the 2 additional hours
blood glucose concentration at greater than 35 mg/dl, not to c. Administer antiemetics immediately after streptozoto
reestablish a normal blood glucose concentration. cin administration to minimize vomiting
If the dextrose infusion is ineffective i n preventing severe d. Repeat treatment every 3 weeks until hypoglycemia
hypoglycemia, a constant rate infusion o f glucagon should resolves or adverse reactions develop (e.g., pancre
atitis, renal failure)
be considered. Glucagon is a potent stimulant o f hepatic
gluconeogenesis and is effective in maintaining normal
blood glucose concentrations in dogs with cell neoplasia
when administered by constant-rate infusion. Lyophilized
glucagon U S P (1 mg) is reconstituted with the diluent pro POSTOPERATIVE COMPLICATIONS
vided by the manufacturer (Eli Lilly), and the solution is The most c o m m o n postoperative complications are pancre
added to 1 L o f 0.9% saline, making a 1 g/ml solution that atitis, hyperglycemia, and hypoglycemia. The development
can be administered by syringe p u m p . The initial dose is 5 of these complications is directly related to the expertise o f
to 10 ng/kg of body weight/minute. The dose is adjusted, as the surgeon, the location of the tumor in the pancreas (i.e.,
needed, to maintain the blood glucose concentration within peripheral lobe versus central region; Fig. 52-20), the pres
the normal range. W h e n discontinuing glucagon, the dose ence or absence o f functional metastatic lesions, and the
should be gradually decreased over 1 to 2 days. adequacy o f fluid therapy during the perioperative period.
Rarely, a dog will remain diabetic for more than a year. Client
evaluation of the pet's urine glucose level is helpful in iden
tifying when insulin therapy is no longer needed. Failure to
identify glucose i n the urine i n conjunction with the disap
pearance of polyuria and polydipsia is an indication to dis
continue insulin therapy. If hyperglycemia and glycosuria
recur, insulin therapy can be reinstituted but at a lower
dose.
Dogs that remain hypoglycemic after surgical removal of
a cell tumor have functional metastatic lesions. The dex
trose and/or glucagon infusion should be continued postop
eratively until pancreatitis has resolved (if present); the dog
is stable, eating, and drinking; and medical treatment for
chronic hypoglycemia can be initiated (see Box 52-12).
pain, and shock i f b l o o d loss is severe or ulcers have perfo proton p u m p inhibitors). Baseline serum gastrin concentra
rated. Potential abnormalities identified o n a C B C include a tions may vary, with occasional values i n the reference range
regenerative anemia, hypoproteinemia, and neutrophilic i n animals with gastrinoma. Provocative testing (e.g., secre
leukocytosis. Abnormalities i n the serum biochemistry panel tin stimulation test, calcium challenge test) may be consid
include hypoproteinemia, hypoalbuminemia, hypocalcemia, ered i n dogs strongly suspected of having gastrinoma but
and m i l d increases i n serum alanine aminotransferase and with normal baseline serum gastrin concentrations. Explor
alkaline phosphatase activities. Hyponatremia, hypochlore atory laparotomy should also be considered. (See Suggested
mia, hypokalemia, and metabolic alkalosis may develop i n Readings for more information o n provocative testing).
dogs and cats that vomit frequently. Hyperglycemia and
hypoglycemia have been noted i n a few cases. The urinalysis Treatment
is usually unremarkable. Treatment should be directed at surgical excision of the
A b d o m i n a l radiographs are usually normal. If an ulcer tumor and control of gastric acid hypersecretion. Gastroin
has perforated through the serosal surface, radiographic testinal tract ulceration can usually be managed by reducing
signs consistent with peritonitis may be present. Contrast- gastric hyperacidity through the administration of H -recep
2
enhanced radiographic studies may show gastric or duode tor antagonists (e.g., ranitidine, famotidine), proton pump
nal ulcers; thickening of the gastric rugal folds, pyloric inhibitors (e.g., omeprazole), gastrointestinal tract protec
antrum, or intestine; and the rapid intestinal transit of tants (e.g., sucralfate), or prostaglandin E1 analogs (e.g.,
barium. In an animal with concurrent severe esophagitis, misoprostol). (See Chapter 30 for more information on these
secondary megaesophagus or aberrant, nonperistaltic esoph gastrointestinal tract drugs.) Surgical resection of an ulcer
ageal motility may be identified fluoroscopically. Ultrasono may be required, especially i f the ulcer has perforated the
graphic evaluation of the abdomen may identify a pancreatic bowel. Surgical resection of the tumor is necessary to obtain
mass or its metastasis. However, gastrinomas vary tremen a cure, although metastasis to the liver, regional lymph nodes,
dously i n size and may not be detected with ultrasound. and mesentery is c o m m o n . Even i f metastatic disease is
Gastroduodenoscopy may reveal severe esophagitis and present, tumor debulking may enhance the success of medical
ulceration, especially near the cardia. Gastric rugal folds may therapy.
be thickened. Gastric and duodenal hyperemia, erosions, or
ulcerations are often visible. Histologic evaluation of esoph Prognosis
ageal, gastric, and duodenal biopsy specimens may be normal The long-term prognosis for gastrinoma is guarded to poor.
or may reveal variable degrees of inflammation consisting of Evidence of metastasis was present i n 76% of reported dogs
infiltrates of lymphocytes, plasma cells and neutrophils, and cats at the time a gastrinoma was diagnosed. Reported
gastric mucosal hypertrophy, fibrosis, and loss of the mucosal survival time i n dogs and cats treated surgically, medically,
barrier. or both ranged from 1 week to 18 months (mean, 4.8
months). However, the short-term prognosis has improved
Diagnosis with the advent of drugs that can reduce gastric hyperacidity
Gastrinoma should be included among the differential diag (e.g., ranitidine, famotidine) and protect and promote
noses for any dog or cat with melena or hematemesis or in healing of the ulcers (e.g., sucralfate, misoprostol).
which severe gastric and duodenal ulceration is identified.
Unless a pancreatic mass is identified by ultrasonography,
Suggested Readings
most dogs and cats with gastrinoma will inadvertently be
Feldman EC, Nelson RW: Canine and feline endocrinology and
diagnosed with severe inflammatory bowel disease, gastro
reproduction, ed 3, St Louis, 2004, WB Saunders.
duodenal erosions, and ulcers, and they will be treated with
Fossum TW: Small animal surgery, ed 3, St Louis, 2007, Mosby.
inhibitors of gastric acid secretion, mucosal protectants, Slatter D: Textbook ofsmall animal surgery, ed 3, Philadelphia, 2003,
antibiotics, and changes i n diet. The probability of a gastri WB Saunders.
n o m a increases if ultrasonography reveals a pancreatic mass,
the dog or cat does not respond to medical therapy directed DIABETES MELLITUS
at nonspecific inflammation and ulceration of the gastroin Alt N et al: Day-to-day variability of blood glucose concentration
curves generated at home in cats with diabetes mellitus, ] Am Vet
testinal tract, or clinical signs and gastrointestinal tract
Med Assoc 230:1011, 2007.
ulceration recur after antiulcer therapy is discontinued. A
Beam S et al: A retrospective-cohort study on the development of
definitive diagnosis of gastrinoma requires histologic and cataracts in dogs with diabetes mellitus: 200 cases, Vet Ophthal
immunocytochemical evaluation of a pancreatic mass mol 2:169, 1999.
excised at surgery. Finding increased baseline serum gastrin Bennett N et al: Comparison of a low carbohydrate-low fiber diet
concentrations from b l o o d obtained after an overnight fast and a moderate carbohydrate-high fiber diet in the management
increases the suspicion of gastrinoma. Additional differential of feline diabetes mellitus, / Fel Med Surg 8:73, 2006.
Briggs C et al: Reliability of history and physical examination Weaver K E et al: Use of glargine and lente insulins in cats with
findings for assessing control of glycemia in dogs with diabetes diabetes mellitus, / Vet Intern Med 20:234, 2006.
mellitus: 53 cases (1995-1998), J Am Vet Med Assoc 217:48, 2000. Wess G et al: Assessment of five portable blood glucose meters for
Casella M et al: Home-monitoring of blood glucose in cats with use in cats, Am / Vet Res 61:1587, 2000.
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Surg 7:163, 2004. cats and use of portable meters to measure glucose concentra
Cohn LA et al: Assessment of five portable blood glucose meters, a tion, / Small Anim Pract 41:60, 2000.
point-of-care analyzer, and color test strips for measuring blood
glucose concentration in dogs, / Am Vet Med Assoc 216:198, DIABETIC KETOACIDOSIS
2000. Brady M A et al: Evaluating the use of plasma hematocrit
Davison LJ et al: Anti-insulin antibodies in dogs with naturally samples to detect ketones utilizing urine dipstick colorimetric
occurring diabetes mellitus, Vet Immunol Immunopath 91:53, methodology in diabetic dogs and cats, / Vet Emerg Crit Care
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Feldman EC et al: Intensive 50-week evaluation of glipizide admin Bruskiewicz K A et al: Diabetic ketosis and ketoacidosis in cats: 42
istration in 50 cats with previously untreated diabetes mellitus, cases (1980-1995), J Am Vet Med Assoc 211:188, 1997.
J Am Vet Med Assoc 210:772, 1997. Duarte R et al: Accuracy of serum (3-hydroxybutyrate measure
Frank G et al: Use of a high-protein diet in the management of ments for the diagnosis of diabetic ketoacidosis in 116 dogs, / Vet
feline diabetes mellitus, Vet Therap 2:238, 2001. Intern Med 16:411, 2002.
Goossens M et al: Response to insulin treatment and survival in Fincham SC et al: Evaluation of plasma-ionized magnesium con
diabetic cats: 104 cases (1985-1995), / Vet Intern Med 12:1, 1998. centration in 122 dogs with diabetes mellitus: A retrospective
Graham PA et al: Influence of a high fibre diet on glycaemic control study, / Vet Intern Med 18:612, 2004.
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Pract 43:67, 2003. cases (1993-2003), / Vet Intern Med 20:547, 2006.
Guptill L et al: Is canine diabetes on the increase? In Recent advances Norris CR et al: Serum total and ionized magnesium concentra
in clinical management of diabetes mellitus, Dayton, Ohio, 1999, tions and urinary fractional excretion of magnesium in cats with
lams Co, p 24. diabetes mellitus and diabetic ketoacidosis, I Am Vet Med Assoc
Hess RS et al: Effect of insulin dosage on glycemic response in dogs 215:1455, 1999.
with diabetes mellitus: 221 cases (1993-1998), J Am VetMed Assoc
216:217, 2000. INSULIN-SECRETING ISLET CELL NEOPLASIA
Hess RS et al: Breed distribution of dogs with diabetes mellitus Fischer JR et al: Glucagon constant-rate infusion: a novel strategy
admitted to a tertiary care facility, J Am Vet Med Assoc 216:1414, for the management of hyperinsulinemic-hypoglycemic crisis in
2000. the dog, / Am Anim Hosp Assoc 36:27, 2000.
Monroe W E et al: Efficacy and safety of a purified porcine insulin Moore AS et al: A diuresis protocol for administration of strepto-
zinc suspension for managing diabetes mellitus in dogs, / Vet zotocin to dogs with pancreatic islet cell tumors, / Am Vet Med
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Vet Med Assoc 212:380, 1998. Robben JH et al: Comparison of ultrasonography, computed
Nelson RW et al: Transient clinical diabetes mellitus in cats: 10 cases tomography, and single-photon emission computed tomography
(1989-1991), / Vet Intern Med 13:28, 1998. for the detection and localization of canine insulinoma, / Vet
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Struble A L et al: Systemic hypertension and proteinuria in dogs GASTRINOMA
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CHAPTER 53
Disorders of the
Adrenal Gland
FIG 53-2
The pituitary-adrenocortical a x i s in d o g s with a functioning a d r e n o c o r t i c a l tumor (AT; left)
a n d in d o g s with pituitary-dependent h y p e r a d r e n o c o r t i c i s m ( P D H ; right). Excess Cortisol
secretion from a n AT c a u s e s pituitary s u p p r e s s i o n , d e c r e a s e d p l a s m a a d r e n o c o r t i c o t r o p i c
h o r m o n e ( A C T H ) c o n c e n t r a t i o n , a n d a t r o p h y of the contralateral a d r e n a l g l a n d . D o g s with
P D H h a v e excess A C T H secretion, usually from a functional pituitary a d e n o m a , w h i c h
causes bilateral a d r e n o m e g a l y a n d e x c e s s p l a s m a Cortisol c o n c e n t r a t i o n s .
Adrenocortical adenoma and carcinoma occur with equal Bilateral A T s can occur in dogs but are rare. A nonfunc
frequency. There are no consistent clinical or biochemical tional A T or an A T causing hyperadrenocorticism and a
features that help distinguish dogs with functional adrenal pheochromocytoma i n the contralateral gland is a more
adenomas from those with adrenal carcinomas, although c o m m o n cause of bilateral adrenal masses i n dogs. Mac
carcinomas tend to be larger than adenomas on abdominal ronodular hyperplasia of the adrenals has also been identified
ultrasound. Adrenocortical carcinomas may invade adjacent in dogs. The adrenals i n such animals are usually grossly
structures (e.g., phrenicoabdominal vein, caudal vena cava, enlarged, with multiple nodules of varying sizes within the
kidney) or metastasize to the liver and lung. adrenal cortex. The exact pathogenesis of this latter syn-
drome is unclear, although most cases i n dogs are presumed pecia, m i l d muscle weakness, and lethargy (Fig. 53-3; Table
to represent an anatomic variant o f P D H . Increased plasma 53-1). M o s t dogs exhibit several, but not all, of these clinical
17-OH-progesterone concentrations have also been docu signs. The more signs evident i n the history, the greater the
mented i n dogs with an adrenal mass and clinical manifesta index o f suspicion for hyperadrenocorticism. Additional
tions o f hyperadrenocorticism but n o r m a l plasma Cortisol findings on physical examination (see Table 53-1) help
concentrations after administration o f A C T H or dexameth establish the diagnosis.
asone (see the section on atypical Cushing's syndrome, Dogs are occasionally seen because of isolated polyuria
p. 830). and polydipsia, bilaterally symmetric endocrine alopecia, or
Adrenocortical tumors causing hyperadrenocorticism panting. There may be no other historic or physical exami
( A T H s ) are autonomous and functional and randomly nation findings consistent with hyperadrenocorticism. The
secrete excessive amounts o f Cortisol independent o f p i t u diagnosis of hyperadrenocorticism is not readily apparent
itary control. The Cortisol produced by these tumors sup in these dogs. Fortunately, hyperadrenocorticism is a dif
presses circulating plasma A C T H concentrations, causing ferential diagnosis for polyuria and polydipsia, endocrine
cortical atrophy o f the uninvolved adrenal and atrophy o f all alopecia, and panting and will be identified as the clinician
normal cells i n the involved adrenal (see Fig. 53-2). This works through the differentials for these problems. Similarly,
atrophy creates asymmetry i n the size o f the adrenal glands, hyperadrenocorticism causes insulin resistance and can
w h i c h can be identified by abdominal ultrasonography. lead to the development of diabetes mellitus. Clinical signs
Most, i f not all, of these tumors appear to retain A C T H (other than polyuria and polydipsia) and physical examina
receptors and respond to administration o f exogenous tion findings suggestive o f hyperadrenocorticism are often
A C T H . A T H s are typically unresponsive to manipulation o f missing i n diabetic dogs with concurrent hyperadrenocorti
the hypothalamic-pituitary axis with glucocorticoids such as cism. A clinical suspicion for hyperadrenocorticism develops
dexamethasone. after critical evaluation o f routine blood test results (e.g.,
increased serum alkaline phosphatase [ALP] activity, isos
IATROGENIC HYPERADRENOCORTICISM thenuric urine) or after resistance to insulin treatment is
Iatrogenic hyperadrenocorticism typically results from the identified.
excessive administration of glucocorticoids to control aller
gic or immune-mediated disorders. It can also develop as a
result of the administration o f eye, ear, or skin medications
containing glucocorticoids, especially i n small dogs (weight
less than 10 kg) receiving them long term. Because the hypo TABLE 53-1
thalamic-pituitary-adrenocortical axis is normal, the pro
longed excessive administration of glucocorticoids suppresses Clinical Signs and Physical Examination Findings in Dogs
circulating plasma A C T H concentrations, causing bilateral with Hyperadrenocorticism
adrenocortical atrophy. In these animals A C T H stimulation PHYSICAL EXAMINATION
test results are consistent with spontaneous hypoadrenocor CLINICAL SIGNS FINDINGS
ticism despite clinical signs o f hyperadrenocorticism.
Polyuria, polydipsia* Endocrine alopecia*
Clinical Features Polyphagia* Epidermal atrophy*
Panting* Comedones*
SIGNALMENT Abdominal enlargement* Cutaneous
FIG 5 3 - 5
A , Lateral r a d i o g r a p h from a d o g with a d r e n a l - d e p e n d e n t h y p e r a d r e n o c o r t i c i s m s h o w i n g
a c a l c i f i e d a d r e n a l mass c r a n i a l to the k i d n e y (arrow). B, V e n t r o d o r s a l r a d i o g r a p h from a
d o g with a d r e n a l - d e p e n d e n t h y p e r a d r e n o c o r t i c i s m s h o w i n g a c a l c i f i e d a d r e n a l mass
c r a n i o m e d i a l to the k i d n e y a n d lateral to the s p i n e (arrow). C o m p r e s s i o n of the a b d o m e n
in the r e g i o n of the a d r e n a l g l a n d with a p a d d l e has e n h a n c e d r a d i o g r a p h i c contrast,
a l l o w i n g better v i s u a l i z a t i o n of the a d r e n a l mass.
adrenal mass (Fig. 53-7). Size is quite variable, ranging from invasion into adjacent blood vessels and organs may occur
1.5 to greater than 8 c m i n m a x i m u m width. Small adrenal (Fig. 53-8). These changes suggest adrenocortical carcinoma.
masses (i.e., less than 3 c m i n m a x i m u m width) often main Identification of calcification within the mass does not dif
tain a smooth contour and may distort only a portion of the ferentiate adenoma from carcinoma. Generally, the larger the
adrenal gland; one or both poles of the adrenal gland may mass, the more likely it is carcinoma. Asymmetry i n the size
still appear normal. W i t h large adrenal masses (typically of the adrenal glands is evident (see Fig. 53-2). Ideally, the
greater than 3 c m i n m a x i m u m width), the adrenal gland contralateral unaffected adrenal should be small or unde
usually becomes distorted and unrecognizable, the contour tectable (maximum width typically less than 0.3 cm) as a
of the gland becomes irregular, and compression and/or result of A T - i n d u c e d adrenocortical atrophy (see Fig. 53-7),
FIG 53-6
Ultrasound i m a g e s of the a d r e n a l g l a n d in three d o g s with pituitary-dependent h y p e r a d r e
nocorticism (PDH) illustrating the differences in s i z e a n d s h a p e of the a d r e n a l g l a n d that
c a n o c c u r with P D H . A , The a d r e n a l g l a n d in this d o g has m a i n t a i n e d the t y p i c a l kidney-
b e a n s h a p e often identified in n o r m a l d o g s . H o w e v e r , the m a x i m u m d i a m e t e r of the g l a n d
w a s e n l a r g e d at 0 . 8 5 c m . The c o n t r a l a t e r a l a d r e n a l g l a n d w a s similar in s i z e a n d s h a p e .
B, The a d r e n a l g l a n d in this d o g is uniformly t h i c k e n e d a n d a p p e a r s p l u m p rather than
k i d n e y - b e a n s h a p e d . The m a x i m u m d i a m e t e r of the g l a n d w a s 1.2 c m . The c o n t r a l a t e r a l
a d r e n a l g l a n d w a s similar in s i z e a n d s h a p e . C, A l t h o u g h the a d r e n a l g l a n d has m a i n
t a i n e d s o m e s e m b l a n c e of a k i d n e y - b e a n s h a p e in this d o g , the g l a n d has u n d e r g o n e
m a r k e d e n l a r g e m e n t , with a m a x i m u m d i a m e t e r of 2 . 4 c m . The contralateral a d r e n a l
g l a n d w a s similar in s i z e a n d s h a p e .
although a normal-size contralateral adrenal gland does not of macronodular hyperplasia (Fig. 53-10). Bilateral adrenal
rule out hyperadrenocorticism caused by A T . Identification macronodular hyperplasia is believed to represent an ana
of an adrenal mass and a normal-to-large contralateral tomic variant of P D H . Failure to identify either adrenal is
adrenal gland i n a dog with clinical signs supportive of considered an inconclusive finding, and ultrasonography
hyperadrenocorticism suggests the possibility of P D H and a should be repeated at a later time.
concurrent adrenal mass that may be a pheochromocytoma, C T and M R I can be used to evaluate the pituitary gland
a functional adrenocortical tumor, or a nonfunctional A T for a macroadenoma and assess the size and symmetry of
(Fig. 53-9). Finding normal-size adrenal glands i n a dog with the adrenal glands. Contrast enhancement using an iodin
confirmed hyperadrenocorticism is most consistent with a ated contrast agent (CT) or gadolinium ( M R I ) given by con
diagnosis of P D H . Finding bilateral adrenomegaly with the tinuous intravenous (IV) infusion during the imaging
appearance of multiple nodules of varying size is suggestive procedure aids i n the identification of a pituitary macroad-
FIG 5 3 - 7
U l t r a s o u n d i m a g e s of the a d r e n a l g l a n d s in a n 11-year-old male castrated G o l d e n
Retriever with a d r e n a l - d e p e n d e n t h y p e r a d r e n o c o r t i c i s m . A , Cortisol-secreting tumor
affecting the right a d r e n a l g l a n d [arrows). The m a x i m u m d i a m e t e r of the a d r e n a l mass
w a s 1.6 c m . B, The left a d r e n a l g l a n d has u n d e r g o n e m a r k e d a t r o p h y (arrows a n d
crosses) a s a result of s u p p r e s s i o n of pituitary a d r e n o c o r t i c o t r o p i c h o r m o n e secretion after
n e g a t i v e f e e d b a c k inhibition c a u s e d b y the a d r e n o c o r t i c a l tumor. The m a x i m u m d i a m e t e r
of the left a d r e n a l g l a n d w a s less than 0 . 2 c m .
FIG 5 3 - 1 0
Ultrasound i m a g e s of the a d r e n a l g l a n d s (arrows) in a n 11-year-old f e m a l e s p a y e d S h i h
T z u . The right a d r e n a l g l a n d (A) m e a s u r e d 1.8 c m in m a x i m u m d i a m e t e r a n d h a d a
n o d u l a r e c h o g e n i c pattern. In contrast, the left a d r e n a l g l a n d (B) h a d a l a r g e n o d u l e
l o c a t e d in e a c h p o l e of the g l a n d ; e a c h m e a s u r e d a p p r o x i m a t e l y 1.4 c m in m a x i m u m
diameter. Tests of the pituitary-adrenocortical a x i s w e r e d i a g n o s t i c for pituitary-dependent
h y p e r a d r e n o c o r t i c i s m ; this f i n d i n g , in conjunction with the findings o n ultrasound, suggests
m a c r o n o d u l a r h y p e r p l a s i a of the a d r e n a l g l a n d s .
False-positive and false-negative test results occur with all results o f diagnostic tests. If there is doubt or uncertainty
of the diagnostic tests for hyperadrenocorticism. W h e n the about the diagnosis, therapy for hyperadrenocorticism
results are unexpected or questionable, another diagnostic should be withheld and the dog reevaluated several months
test can be performed or the same diagnostic test repeated, later.
preferably after waiting several months. Occasionally,
results of different diagnostic tests performed i n the same Urine Cortisol : Creatinine Ratio
dog are contradictory. The decision to perform discrimina The U C C R is an excellent initial screening test for hyper
tory tests or to initiate therapy should depend o n the clini adrenocorticism in dogs. Ideally, the U C C R should be deter
cian's index of suspicion for the disease formulated from a mined from free-catch urine samples obtained by the client
review of the history, findings o n physical examination, and in the nonstressful home environment. The stress associated
TABLE 53-2
Diagnostic Tests to Assess the Pituitary-Adrenocortical Axis in Dogs with Suspected Hyperadrenocorticism
Urine Cortisol: Rule out Cushing's Urine collected at home Normal Not supportive of
creatinine ratio syndrome Cushing's
syndrome
Increased Additional tests for
Cushing's indicated
4-hr post-dexamethasone: 8-hr post-dexamethasone:
Low-dose Diagnose Cushing's 0.01 mg dexamethasone/kg IV; < 1.5 g/dl Normal
dexamethasone syndrome and serum pre- and 4- a n d 8-hr post- <1.5 g / d l > 1.5 g/dl PDH
suppression test differentiate PDH dexamethasone <50% of pre-value > 1.5 g/dl PDH
from ATH >1.5 g / d l and <50% PDH
of pre-value
>1.5 g / d l and >50% of > 1.5 g/dl PDH or ATH
pre-value
A C T H stimulation Diagnose Cushing's 2.2 IU A C T H g e l * / k g IM; serum pre- Post-ACTH Cortisol concentration: Strongly suggestive
syndrome and 2-hr post-ACTH >24 g/dl Suggestive
or 19-24 g/dl Normal
0.25 mg of synthetic A C T H * / d o g IM; 8-18 g/dl Iatrogenic Cushing's
serum pre- and 1 -hr post-ACTH <8 g/dl syndrome
High-dose Differentiate PDH 0.1 mg of dexamethasone/kg IV; Post-dexamethasone Cortisol concentration: PDH
dexamethasone from ATH serum pre- and 8-hr post- <50% of pre-value PDH
suppression test dexamethasone < 1.5 g/dl PDH or ATH
>50% of pre-value
O r a l dexamethasone Differentiate PDH Urine sample for U C C R on 2 Post-dexamethasone UCCR value: PDH
suppression test from ATH consecutive mornings, then 0.1 mg <50% of baseline v a l u e * * PDH or ATH
of dexamethasone/kg per os q 8 h 50% of baseline value
for 3 treatments, then urine sample
for U C C R the following morning
Endogenous A C T H Differentiate PDH Plasma sample obtained between 8- <2 pmol/L ATH
from ATH 10 A.M. 2-10 pmol/L Nondiagnostic
Special handling required >10 pmol/L PDH
PDH, Pituitary-dependent hyperadrenocorticism; ATH, adrenocortical tumor-dependent hyperadrenocorticism; IV, intravenous; ACTH, adrenocorticotropic hormone; IM, intramuscular; UCCR,
urine Cortisol : creatinine ratio.
* A C T H gel: Acthar Gel, Questcor Pharmaceuticals; synthetic ACTH: Cortrosyn, Amphastar Pharmaceuticals.
* * Baseline value is the mean of two UCCR values obtained before dexamethasone administration,
Strongly suggestive of hyperadrenocorticism.
Suggestive of hyperadrenocorticism.
FIG 53-1 1
Urinary corticoid : creatinine (C: C) ratio measured in 12 pet dogs before and after a visit
to a referral clinic for orthopedic examination (A) and in 9 healthy pet dogs before, during,
and after a 1.5-day hospitalization at a referral clinic (B). The arrows indicate time of visit
to the referral clinic. Note the increase in the urinary C : C ratio in a few dogs affiliated
with a visit to a veterinary practice. (From van Vonderen IK et al: Influence of veterinary
care on the urinary corticoid: creatinine ratio in dogs, J Vet Intern Med 12:431, 1998.)
Low-Dose Dexamethasone
Suppression Test
In the normal dog relatively small doses of dexamethasone
given intravenously can inhibit pituitary secretion of A C T H ,
causing a prolonged decline i n the serum Cortisol concentra
tion (Fig. 53-13). Dexamethasone is used because it does not FIG 5 3 - 1 2
Box plots of the urine Cortisol : creatinine ratios found in
interfere with the radioimmunoassays used to measure Cor
normal dogs, dogs with hyperadrenocorticism (HAC), dogs
tisol. The abnormal pituitary i n dogs with P D H is somewhat in which hyperadrenocorticism was initially suspected but
resistant to the negative feedback action of dexamethasone, that did not have the disease (suspect H A C ) , and dogs with
and the metabolic clearance o f dexamethasone may be a variety of severe, nonadrenal diseases. For each box plot,
abnormally accelerated as well. The administration o f a T-bars represent the main body of data, which in most
small dose of dexamethasone to a dog with P D H causes the instances are equal to the range. Each box represents an
interquartile range (twenty-fifth to seventy-fifth percentile).
serum Cortisol concentration to be variably suppressed;
The horizontal bar in each box is the median. Open circles
however, it is no longer suppressed b y 8 hours after dexa
represent outlying data points. Numbers in parentheses
methasone administration, compared with the response seen indicate the numbers of dogs in each group. (From Smiley
in normal dogs. A T H function independently o f A C T H LE et al: Evaluation of a urine Cortisol : creatinine ratio as a
control, and dexamethasone does not affect the serum Cor screening test for hyperadrenocorticism in dogs, J Vet Intern
tisol concentration, regardless of the dose or time of blood Med 7:163, 1993.)
anticonvulsant drugs, stress, excitement, exogenous gluco
corticoids, and nonadrenal disease; the more severe the non-
adrenal disease, the more likely the L D D S test result will be
falsely positive. W h e n performing the L D D S test, the clini
cian must ensure that all stressors are kept to a m i n i m u m ;
other procedures should not be performed until the test is
completed, and the effect of concurrent clinical problems
should be considered when interpreting results.
The protocol for the L D D S test and interpretation of
results are described in Table 53-2. The clinician may use
either dexamethasone sodium phosphate or dexamethasone
in polyethylene glycol. The 8-hour postdexamethasone
serum Cortisol concentration is used to confirm hyperadre
nocorticism. N o r m a l dogs typically have serum Cortisol
values less than 1.0 g/dl, whereas dogs with P D H and A T
have serum Cortisol concentrations greater than 1.5 g/dl 8
hours after dexamethasone administration. In general, the
higher the 8-hour postdexamethasone serum Cortisol con
centration is above 1.5 g/dl, the more supportive the test
result is for hyperadrenocorticism. Cortisol concentrations
between 1.0 and 1.5 g/dl are nondiagnostic. If results are in
the nondiagnostic range, the clinician must rely on other
information, including other tests of the pituitary-adreno
cortical axis, to determine i f hyperadrenocorticism is the
correct diagnosis.
If the 8-hour postdexamethasone serum Cortisol value
supports a diagnosis of hyperadrenocorticism, the 4-hour
serum Cortisol value may then be of value in identifying
P D H . L o w doses of dexamethasone suppress pituitary A C T H
secretion and serum Cortisol concentrations i n approxi
FIG 5 3 - 1 3 mately 60% of dogs with P D H . Suppression does not occur
Effects of d e x a m e t h a s o n e a d m i n i s t r a t i o n o n the pituitary- in dogs with A T , nor does it occur in approximately 40% of
a d r e n o c o r t i c a l a x i s in healthy d o g s or cats a n d in d o g s o r dogs with P D H . Suppression is defined as a 4-hour postdexa
cats with either pituitary-dependent h y p e r a d r e n o c o r t i c i s m
methasone serum Cortisol concentration of less than 1.5 g/
(PDH) o r a d r e n o c o r t i c a l n e o p l a s i a . In P D H d e x a m e t h a s o n e
dl, a 4-hour postdexamethasone serum Cortisol concentra
m a y initially suppress pituitary a d r e n o c o r t i c o t r o p i c h o r m o n e
( A C T H ) s e c r e t i o n , but the s u p p r e s s i o n is short-lived. The tion less than 50% of the baseline concentration, or an 8-
p l a s m a Cortisol c o n c e n t r a t i o n s initially d e c l i n e but i n c r e a s e hour postdexamethasone serum Cortisol concentration less
a b o v e n o r m a l w i t h i n 2 to 6 hours of d e x a m e t h a s o n e than 50% of the baseline concentration. A n y dog with hyper
a d m i n i s t r a t i o n . In a d r e n o c o r t i c a l n e o p l a s i a pituitary A C T H adrenocorticism that meets one or more of these criteria
secretion is a l r e a d y s u p p r e s s e d ; thus d e x a m e t h a s o n e has no
most likely has P D H . If none of these criteria is met, then
effect.
results of the L D D S test are consistent with lack of suppres
sion but not informative i n terms of whether it is pituitary
or adrenal i n origin. Differentiation between P D H and A T
sampling because pituitary corticotrophs are already sup must rely on results of abdominal ultrasound, the H D D S
pressed and blood A C T H concentration is undetectable. test, or plasma endogenous A C T H concentration.
The L D D S test is a reliable diagnostic test for differentiat
ing n o r m a l dogs from those with hyperadrenocorticism and Oral Dexamethasone Suppression Test
may identify P D H . Sensitivity and specificity are approxi A n alternative at-home oral dexamethasone suppression test
mately 90%. The L D D S does not identify iatrogenic hyper has been used for years at the University of Utrecht, The
adrenocorticism, nor is it used to assess a dog's response to Netherlands. This test relies entirely on results of U C C R s to
mitotane (lysodren) or trilostane therapy. A n o r m a l or establish the diagnosis of hyperadrenocorticism and to iden
inconclusive L D D S test result does not by itself rule out tify P D H . The client is instructed to collect two urine samples
hyperadrenocorticism. If hyperadrenocorticism is suspected, from the dog on 2 consecutive mornings and store them in
additional tests of the pituitary-adrenocortical axis should the refrigerator. After collection of the second urine sample,
be performed. Similarly, an abnormal L D D S test result does the client should administer 3 doses of dexamethasone
not by itself confirm hyperadrenocorticism. Results of the (0.1 mg/kg/dose) to the dog orally at 8-hour intervals. Urine
L D D S test may be affected by concurrently administered is collected on the m o r n i n g of the third day, and all three
samples are delivered to the veterinarian for measurement
of U C C R s . The first two urine samples are the screening test
to diagnose hyperadrenocorticism. A b n o r m a l values support
hyperadrenocorticism; normal values rule out the disease. If
both values are abnormal, then the average of the two values
is used as the baseline value and compared with the third
value obtained after dexamethasone administration. The
dog is described as having responded to dexamethasone
(suppressed) if the U C C R result from the third urine sample
is less than 50% o f the baseline value. Dogs meeting this
criteria have results consistent with P D H , whereas those failing
to demonstrate suppression could have either A T or P D H .
Adrenocorticotropic Hormone
Stimulation Test
The A C T H stimulation test is used to establish the diagnosis
of hyperadrenocorticism and hypoadrenocorticism, identify
iatrogenic hyperadrenocorticism, identify atypical hyper
adrenocorticism (see p. 830), and monitor mitotane and
trilostane treatment. A C T H stimulation test results do not
distinguish between P D H and A T . In our experience A C T H
stimulation test results are clearly abnormal i n approximately
30%, in the borderline range i n another 30% and within the
reference range i n approximately 40% of dogs with P D H .
Identification of A C T H stimulation test results i n the bor FIG 5 3 - 1 4
derline range is c o m m o n , and clearly abnormal test results Interpretation of the a d r e n o c o r t i c o t r o p i c h o r m o n e (ACTH)
occur i n dogs that do not have hyperadrenocorticism. stimulation test in d o g s . Ideally, d o g s with C u s h i n g ' s
Because of problems with sensitivity and specificity c o m syndrome have a n increased post-ACTH administration
Cortisol c o n c e n t r a t i o n (line a). P o s t - A C T H Cortisol values that
bined with the high cost of A C T H , I do not routinely use the
fall into the " g r a y z o n e " (line b) c o u l d b e consistent with
A C T H stimulation test when evaluating dogs for hyperadre
C u s h i n g ' s s y n d r o m e o r result from the effects of concurrent
nocorticism. illness o r c h r o n i c stress. P o s t - A C T H Cortisol values m a y a l s o
The protocol for the A C T H stimulation test is given i n fall into the n o r m a l r a n g e in d o g s with C u s h i n g ' s s y n d r o m e .
Table 53-2. W h e n synthetic A C T H is being used, a lower dose The a b s e n c e of a response to A C T H stimulation is sugges
(5 g/kg, administered intravenously or intramuscularly) is tive of a d r e n o c o r t i c a l n e o p l a s i a [lines c a n d d] o r i a t r o g e n i c
h y p e r a d r e n o c o r t i c i s m (lines d a n d e). History a n d p h y s i c a l
also effective and the unused reconstituted A C T H can be
e x a m i n a t i o n f i n d i n g s should differentiate b e t w e e n these
stored frozen at 20C i n plastic syringes for 6 months with
possibilities.
no adverse effects o n bioactivity o f the A C T H . Four ranges
of values are used i n the interpretation of the A C T H stimu
lation test (Fig. 53-14). P o s t - A C T H serum Cortisol values
between 6 and 18 g/dl are within the n o r m a l reference clinical presentation o f the dog can help differentiate iatro
range, values o f 5 g/dl and below are suggestive o f iatro genic hyperadrenocorticism from spontaneous hypoadreno
genic hyperadrenocorticism or hypoadrenocorticism, values corticism. In rare instances a dog with A T will have a m i n i m a l
between 18 and 24 g/dl are considered borderline for Cortisol response to A C T H ; however, its p r e - A C T H and post-
hyperadrenocorticism, and values greater than 24 g/dl are A C T H administration serum Cortisol concentrations are
supportive of hyperadrenocorticism, assuming the clinical within or above the reference range.
findings and clinicopathologic data are consistent with the
disease. A n increased p o s t - A C T H serum Cortisol value, espe High-Dose Dexamethasone
cially one between 18 and 24 g/dl, does not by itself confirm Suppression Test
a diagnosis of hyperadrenocorticism, especially i f the clinical ATs function independently o f pituitary A C T H ; therefore,
features and clinicopathologic data are not consistent with regardless of the dose, dexamethasone should never suppress
the diagnosis. the serum Cortisol concentration i f the source of the Cortisol
P o s t - A C T H serum Cortisol concentrations that do not is an A T . In contrast, dexamethasone-induced suppression of
increase above the preadministration value suggest iatro A C T H secretion from a pituitary tumor is variable and may
genic hyperadrenocorticism or spontaneous hypoadreno depend o n the dexamethasone dose. The administration o f
corticism, especially i f the Cortisol values are below the increased amounts of dexamethasone should eventually sup
normal baseline range (i.e., less than 5 g/dl; see Fig. 53-14). press pituitary A C T H secretion i n most dogs with P D H . The
A history of recent glucocorticoid administration and the protocol for the high-dose dexamethasone suppression
( H D D S ) test is similar to that for the L D D S test protocol, Adrenocortical tumors and iatrogenic hyperadrenocorticism
except that a higher dose (i.e., 0.1 mg/kg o f body weight) o f should suppress A C T H secretion, and P D H is the result of
dexamethasone is used i n an attempt to suppress pituitary excessive A C T H secretion (see Fig. 53-2). Approximately
A C T H secretion (see Table 53-2). Obtaining a 4-hour post 60% of dogs with A T H have undetectable plasma A C T H
dexamethasone b l o o d sample is optional; in our experience, concentrations, whereas 85% to 90% of dogs with P D H have
this has been informative i n only 2% o f dogs tested with both plasma A C T H concentrations greater than 10 pmol/L and
the L D D S and H D D S tests. Suppression is defined as a 4- 35% have A C T H concentrations greater than 25 pmol/L.
hour or 8-hour postdexamethasone serum Cortisol concen Plasma A C T H concentrations of 2 to 10 p m o l / L are nondi
tration less than 1.5 g/dl and a 4-hour or 8-hour agnostic. Several commercial veterinary endocrine laborato
postdexamethasone serum Cortisol concentration less than ries perform endogenous A C T H assays for dogs. The
50% o f the baseline concentration. A n y dog with hyper laboratory should be consulted for information on sample
adrenocorticism that meets one or more o f these criteria collection and handling; results should be interpreted on the
most likely has P D H . If a dog does not meet any o f these basis o f the reference range established for the laboratory
criteria, this is consistent with lack o f suppression. A p p r o x i being used.
mately 25% o f dogs with P D H and essentially 100% o f dogs
with A T H do not show suppression w i t h the H D D S test. Medical Treatment
Higher doses o f dexamethasone (e.g., 1.0 mg/kg) could be Medical options for treating hyperadrenocorticism are listed
administered in an attempt to suppress pituitary A C T H in Table 53-3. The most viable treatment options for dogs
secretion i n dogs with dexamethasone-resistant P D H . are mitotane and trilostane.
However, the percentage o f dogs with P D H that show sup
pression at higher doses o f dexamethasone is similar to that MITOTANE
observed for the 0.1 mg/kg protocol. Chemotherapy using mitotane ( o , o ' D D D ; Lysodren; Bristol
Myers Oncology) is the most c o m m o n l y used treatment for
Endogenous Adrenocorticotropic P D H and is a viable alternative to adrenalectomy for treat
Hormone Concentration ment o f A T s causing hyperadrenocorticisim. There are two
I do not routinely measure plasma A C T H concentrations treatment protocols: the traditional approach, the goal of
because the L D D S test and abdominal ultrasound are very which is to control the hyperadrenal state without causing
effective i n differentiating between P D H and A T . I use plasma clinical signs o f hypoadrenocorticism, and medical adrenal
A C T H concentrations to provide clarity i n confusing cases ectomy, the goal of which is to destroy the adrenal cortex and
in which test results for hyperadrenocorticism and findings create hypoadrenocorticism. I prefer the traditional approach
on abdominal ultrasound conflict (e.g., a dog with an adrenal initially and consider medical adrenalectomy in dogs that fail
mass but suppression o n the L D D S test or a dog with an to respond to the traditional approach or that become non-
adrenal mass, enlargement of the contralateral adrenal gland, responsive to mitotane after months or years of maintenance
and lack o f suppression o n the L D D S test). Determination therapy.
of a baseline plasma A C T H concentration is not used to
diagnose hyperadrenocorticism because many o f the con Traditional Approach to
centrations in dogs with hyperadrenocorticism are within Mitotane Treatment
the reference range (2 to 25 p m o l / L ) . However, determina For the traditional approach, there are two phases of mito
tion o f a single baseline plasma A C T H concentration may tane therapy: an initial induction phase designed to gain
aid i n distinguishing dogs with A T H from those with P D H control o f the disorder, and a lifelong maintenance phase
once the diagnosis of hyperadrenocorticism is established. designed to prevent recurrence of the signs of the disease.
TABLE 53-3
Mitotane Lysis of adrenal cortex PDH, ATH 5 0 m g / k g divided q12h with food >80%
Trilostane Inhibition of Cortisol biosynthesis PDH, ATH 0.5 to 1.0 m g / k g q12h ~80%
Ketoconazole Inhibition of Cortisol biosynthesis PDH, ATH 5 m g / k g q12h <75%
Deprenyl Inhibition of dopamine metabolism* PDH 1 m g / k g q24h <20%
Cyproheptadine Serotonin antagonist PDH <10%
Bromocriptine Dopamine agonist PDH <10%
FIG 5 3 - 1 5 ADRENALECTOMY
Steroid biosynthetic pathways in the adrenal cortex. The Adrenalectomy is the treatment o f choice for an A T unless
branching pathways for glucocorticoids, mineralocorticoids,
metastatic lesions or invasion of surrounding organs or
and adrenal androgens are shown. The site of blockade in
b l o o d vessels is identified during the preoperative evalua
the steroid biosynthetic pathways by the enzyme inhibitors
trilostane (T), ketoconazole (K), metyrapone (M), and tion; the dog is considered a poor anesthetic risk because it
aminoglutethimide (A) are also shown. has a concurrent disease (e.g., heart failure) or is debilitated
as a result o f its hyperadrenal state; or the probability of
perioperative thromboembolism is considered high because
of systemic hypertension, an increased urine protein : cre
of trilostane administration should be increased to twice a atinine ratio, or a decreased serum antithrombin III concen
day. Serum electrolytes are monitored for changes consistent tration. The probability o f successful adrenalectomy is lower
with the onset o f hypoaldosteronism. Once control o f the and the likelihood o f perioperative complications is greater
hyperadrenal state is attained, an A C T H stimulation test, the larger the adrenal mass. Removal of an adrenal mass that
serum electrolytes, and U C C R should be evaluated every 3 has a diameter i n excess o f 6 c m can be difficult even when
to 4 months. the surgery is performed by an experienced surgeon. The
Adverse effects o f trilostane include lethargy, vomiting, larger the adrenal mass, the greater the probability that the
and electrolyte shifts compatible with hypoadrenocorticism. adrenal mass is a carcinoma and that metastasis has occurred,
Permanent hypoadrenocorticism has been reported i n a regardless o f findings during the preoperative evaluation.
small number o f dogs. Histopathologic examination o f the Treatment with mitotane or trilostane offers a viable alterna
adrenal gland i n dogs treated with trilostane has revealed tive to adrenalectomy, especially for aged dogs or dogs at
adrenocortical necrosis o f variable severity i n some dogs increased risk for anesthetic, surgical, or postsurgical prob
findings that, i f severe, could explain persistent hypoadreno lems. (See Suggested Readings for detailed information on
corticism i n affected dogs. Acute death has been reported i n surgical techniques.)
a small number o f dogs shortly after the initiation o f trilo The most worrisome complication o f adrenalectomy is
stane treatment. thromboembolism, which typically develops during or
w i t h i n 72 hours of surgery and carries a high mortality rate
KETOCONAZOLE (see p. 814). Several steps help m i n i m i z e this complication.
Ketoconazole reversibly inhibits adrenal steroidogenesis (see Trilostane treatment for 3 to 4 weeks before surgery can
Fig. 53-15). The initial dosage o f ketoconazole is 5 mg/kg reverse the metabolic derangements o f hyperadrenocorti
q l 2 h , and subsequent increases i n the dosage are based o n cism and m i n i m i z e many o f the complications associated
results o f an A C T H stimulation test performed 10 to 14 days with adrenalectomy. Plasma is a source o f antithrombin III
later and while the dog is still receiving ketoconazole. The and should be administered during surgery. Heparin or
goals o f therapy are similar to those discussed for trilostane. other anticoagulant therapy should be administered during
Approximately 20% to 25% o f dogs do not respond to the and for several days after adrenalectomy (see Chapter 12).
drug as a result o f poor intestinal absorption. Adverse reac Dogs should go for frequent short walks within hours of the
tions are primarily a result o f hypocortisolism and include surgery to promote b l o o d flow and minimize clot formation.
lethargy, inappetence, vomiting, and diarrhea. Unfortunately, Anesthetic drugs and pain medications should be adminis
it is difficult to control the clinical signs o f hyperadrenocor tered at dosages that allow the dog to be ambulatory within
ticism without creating problems with hypocortisolism. 4 hours of the surgery. Despite these measures, thromboem
bolism remains a c o m m o n perioperative complication that
L-DEPRENYL should be thoroughly discussed with clients who are consid
L-Deprenyl (Anipryl, Deprenyl A n i m a l Health) inhibits ering adrenalectomy.
dopamine metabolism and increases hypothalamic and pitu Glucocorticoid therapy is not indicated before adrenalec
itary concentrations o f dopamine, w h i c h i n turn inhibits tomy because it may worsen hypertension, cause overhydra
corticotropin-releasing hormone ( C R H ) and A C T H secre tion, and increase the risk o f thromboembolic episodes.
tion. The current dosage recommendation for L-Deprenyl is Beginning with anesthesia, I V fluids should be administered
1 mg/kg once daily initially, with an increase to 2 mg/kg once at a surgical maintenance rate. Acute hypocortisolism uni
daily i f there is no response after 2 months. The efficacy o f formly occurs after adrenalectomy. After the surgeon identi-
fies the adrenal tumor, dexamethasone (0.05 to 0.1 mg/kg)
should be placed in the I V infusion bottle. This dose should
be given over a 6-hour period. A tapering dose (e.g., decreas
ing the dose by 0.02 mg/kg/24 h) of dexamethasone should
continue to be administered intravenously at 12-hour inter
vals until the dog can safely be given oral medication without
the danger of vomiting (typically 24 to 72 hours postopera
tively). A t that point, the glucocorticoid supplement should
be switched to oral prednisone (0.25 to 0.5 mg/kg q l 2 h ) .
Once the dog is eating and drinking on its own, the fre
quency of prednisone administration should be decreased to
once a day and given i n the morning. The prednisone dosage
is then gradually reduced during the ensuing 3 to 4 months.
If a unilateral adrenalectomy has been performed, predni
sone supplementation can eventually be discontinued once
the contralateral normal adrenocortical tissue becomes
functional. Lifelong prednisone at a dosage of 0.1 to 0.2 mg/
kg administered once or twice daily is usually required for
dogs that undergo bilateral adrenalectomy.
Serum electrolyte concentrations should be closely m o n
itored postoperatively. Development of m i l d hyponatremia
and hyperkalemia is c o m m o n within 72 hours of surgery
and usually resolves i n a day or two as exogenous glucocor
ticoid doses are reduced and the dog begins to eat. Miner
alocortioid treatment is recommended i f the serum sodium
concentration decreases to less than 135 m E q / L or serum
potassium concentration increases to greater than 6.5 m E q /
L. A n injection of desoxycorticosterone pivalate ( D O C P ;
Percorten-V; Novartis Pharmaceuticals) is recommended,
with measurement of serum electrolytes performed 25 days
after the injection (see p. 840). If the dog is healthy and
serum electrolytes are normal on day 25, the dog should be
reevaluated 7 days later. If serum electrolytes are still normal,
additional D O C P treatment is not needed. If hyponatremia
or hyperkalemia is identified on day 25, another injection of
D O C P should be administered but with the dosage reduced
by 50% and serum electrolytes evaluated 25 days later.
RADIATION THERAPY
FIG 5 3 - 1 6
Approximately 50% of dogs have a pituitary mass identified
A , C o m p u t e d t o m o g r a p h y (CT) i m a g e of the pituitary r e g i o n
on C T or M R I at the time P D H is diagnosed. In approxi
of a 9 - y e a r - o l d , f e m a l e s p a y e d C o c k e r S p a n i e l with
mately 50% of these dogs, the pituitary mass grows over the pituitary-dependent h y p e r a d r e n o c o r t i c i s m (PDH). The P D H
ensuing 1 to 2 years, eventually causing pituitary macrotu h a d b e e n treated with mitotane for 2 y e a r s , at w h i c h time
mor syndrome (see p. 814). Pituitary macroadenoma is ten the d o g d e v e l o p e d lethargy, i n a p p e t e n c e , a n d w e i g h t loss.
tatively diagnosed by ruling out other causes of the neurologic A l a r g e mass m e a s u r i n g a p p r o x i m a t e l y 2 . 0 c m in d i a m e t e r
is evident in the h y p o t h a l a m i c - p i t u i t a r y r e g i o n (arrow).
disturbances and is confirmed by C T or M R I findings (see
B, C T i m a g e of the pituitary r e g i o n 1 8 months after
Fig. 53-4). Development of neurologic signs from a pituitary
c o m p l e t i o n of r a d i a t i o n therapy. The v o l u m e of the mass
macrotumor is a c o m m o n reason for clients to request d e c r e a s e d b y a p p r o x i m a t e l y 75%, c o m p a r e d with the
euthanasia of dogs with P D H . Irradiation has successfully v o l u m e b e f o r e treatment. C l i n i c a l signs related to the
reduced the tumor size and lessened or eliminated neuro pituitary m a c r o t u m o r r e s o l v e d , a n d mitotane treatment w a s
logic signs i n dogs with pituitary macrotumor syndrome d i s c o n t i n u e d after r a d i a t i o n treatment.
(Fig. 53-16). The primary mode of radiation treatment is
cobalt 60 photon irradiation or linear accelerator photon cally administered to hyperadrenal dogs with pituitary mac
irradiation. Treatment usually involves the delivery of a pre roadenoma at our hospital.
determined total dose of radiation given i n fractions over a Prognostic factors that affect survival time after radiation
period of several weeks. Currently a total dose of 48 Gy, given therapy include the severity of neurologic signs and the
in 4 G y doses 3 to 5 days per week for 3 to 4 weeks, is typi relative size of the tumor. Generally, dogs with subtle or m i l d
neurologic clinical signs and the smallest tumors show the secreting A T s . In contrast, dogs with atypical Cushing's syn
best response to treatment. T h e o n et al. (1998) found a mean drome have normal or inconclusive serum Cortisol
survival time after radiation of 25 months i n dogs with m i l d concentrations and an increase i n one or more adrenocorti
neurologic signs, 17 months i n dogs with severe neurologic cal steroid hormone intermediates, most notably 17-hydroxy-
signs, and only 5 months i n untreated dogs w i t h neurologic progesterone.
signs. Because o f the high prevalence o f a pituitary mass at Adrenal tumors that secrete progesterone and 17-hydroxy-
the time P D H is diagnosed and the potential for future progesterone cause a clinical syndrome that mimics hyper
growth and development o f neurologic signs, examination adrenocorticism i n dogs and cats. Clinical signs presumably
of the pituitary gland using C T or M R I and radiation therapy result from intrinsic glucocorticoid activity of progestins,
if a mass is identified should be discussed with the client at progestin-induced displacement o f Cortisol from cortisol-
the time P D H is diagnosed. The goal o f radiation therapy is binding protein i n the circulation, or both. A n atypical form
to shrink the mass and prevent development o f macrotumor of P D H has also been described i n which clinical features
syndrome; mitotane or trilostane therapy may still be needed m i m i c hyperadrenocorticism, abdominal ultrasound reveals
to control clinical signs o f hyperadrenocorticism. adrenal glands that are n o r m a l or mildly increased i n size,
tests o f the pituitary-adrenocortical axis are normal or
Prognosis inconclusive, pre- and p o s t - A C T H serum 17-hydroxypro-
The average life expectancy i n dogs with adrenal-dependent gesterone concentrations are increased, and clinical signs
hyperadrenocorticism that survive the initial postadrenalec improve with mitotane treatment. Diagnosis requires evalu
tomy m o n t h is approximately 36 months. Dogs with adre ation o f serum and plasma adrenocortical steroid hormone
nocortical adenoma and adrenocortical carcinoma that has intermediates and sex hormones before and 1 hour after the
not metastasized (uncommon) have a good prognosis, I V administration o f 5 g/kg o f synthetic A C T H (Cosyntro
whereas dogs with metastatic adrenocortical carcinoma pin). The most c o m m o n abnormality is an increase i n serum
(common) have a poor prognosis, with these dogs typically 17-hydroxyprogesterone concentration. Currently, the only
succumbing to the disease w i t h i n a year o f diagnosis. laboratory with established normal values for precursor and
Although clinical signs can be controlled with trilostane and sex steroids is the Endocrinology Laboratory at the Univer
mitotane, death ultimately results from the debilitating sity of Tennessee, College of Veterinary Medicine, Knoxville,
effects o f the tumor, complications o f hyperadrenocorticism T N 37901-1071. Treatment recommendations have included
(e.g., pulmonary thromboembolism), or other geriatric dis low dosages of mitotane (10 mg/kg/day initially) and trilo
orders (e.g., renal insufficiency, congestive heart failure). stane, although Sieber-Ruckstuhl et al. (2006) failed to doc
The prognosis for dogs with P D H depends i n part o n the ument a decrease i n 17-hydroxyprogesterone concentrations
age and overall health o f the dog and on the client's c o m m i t i n dogs with P D H treated with trilostane.
ment to therapy. The mean life span o f affected dogs after I do not routinely measure serum adrenocortical steroid
diagnosis of P D H is approximately 30 months. Younger dogs hormone intermediates or sex hormones when initially eval
may live considerably longer (i.e., 5 years or longer). M a n y uating dogs for hyperadrenocorticism. I reserve measure
dogs ultimately die or are euthanized because o f complica ment o f these hormones for those dogs with clinical features
tions related to hyperadrenocorticism (e.g., pituitary macro suggestive o f hyperadrenocorticism but persistently normal
t u m o r syndrome) or other geriatric disorders. or equivocal test results for hyperadrenocorticism.
reference range for the U C C R performed o n urine collected non and the fragile state o f many diabetic hyperadrenal cats,
-5
at home is less than 3.6 x 10 (often listed as less than 36); I typically use only one dexamethasone suppression test pro
this value may vary among laboratories. I use the U C C R as tocol (0.1 mg/kg dexamethasone administered intravenously;
the initial screening test for hyperadrenocorticism i n cats. A b l o o d obtained before and 4 and 8 hours after dexametha
n o r m a l U C C R is a strong finding against the diagnosis; an sone administration) when evaluating the pituitary-adreno
increased ratio does not establish the diagnosis by itself but cortical axis i n cats. A n 8-hour postdexamethasone serum
supports performing the dexamethasone suppression test. Cortisol concentration less than 1.0 g/dl is suggestive of a
n o r m a l pituitary-adrenocortical axis, values between 1.0 and
Dexamethasone Suppression Test 1.4 g/dl are inconclusive, and values greater than 1.4 g/dl
The duration o f the suppressive effects o f intravenously are supportive o f the diagnosis o f hyperadrenocorticism.
administered dexamethasone o n serum Cortisol concentra The higher the 8-hour post-dexamethsone serum Cortisol
tions is more variable i n cats than dogs. Approximately 20% concentration above 1.4 g/dl, the more supportive the test
of healthy cats do not experience the suppressive effects of is for the diagnosis o f hyperadrenocorticism. Similarly, a
dexamethasone, and their serum Cortisol concentrations are serum Cortisol concentration greater than 1.4 g/dl at the
greater than 1.4 g/dl 8 hours after dexamethasone a d m i n 4-hour postdexamethasone blood sampling time adds
istration. This "escape phenomenon" is more likely to occur further support for the diagnosis of hyperadrenocorticism
i n cats receiving lower doses o f dexamethasone. Because of (Fig. 53-19). Whenever the 4-hour post-dexamethasone Cor
potential misinterpretation caused by the escape phenome tisol value is less than 1.4 g/dl (especially less than 1.0 g/
FIG 53-18
A , A 15-year-old cat with pituitary-dependent h y p e r a d r e n o c o r t i c i s m (PDH), insulin-resistant
d i a b e t e s mellitus, a n d feline fragile skin s y n d r o m e . N o t e the torn skin o v e r the b a c k of the
neck that o c c u r r e d w h i l e the cat w a s b e i n g restrained d u r i n g a p h y s i c a l e x a m i n a t i o n .
B, A 1 2-year-old cat with h y p e r a d r e n o c o r t i c i s m a n d severe insulin-resistant d i a b e t e s mellitus.
This cat w e i g h e d 2 . 2 kg a n d w a s r e c e i v i n g 2 5 units of regular insulin three times a d a y
with no g l u c o s e - l o w e r i n g effect. N o t e the e m a c i a t e d a p p e a r a n c e , p r e s u m a b l y resulting
from protracted p o o r g l y c e m i c c o n t r o l , a l o p e c i a , severe d e r m a l a n d e p i d e r m a l atrophy,
a n d lesions resulting from e a s i l y torn skin (arrow). C, A 17-year-old cat with P D H a n d
insulin-resistant d i a b e t e s mellitus. N o t e the e m a c i a t e d a p p e a r a n c e of the cat, the e n l a r g e d
a b d o m e n (pot-belly a p p e a r a n c e ) , a n d a b s e n c e of hair g r o w t h on the ventral a b d o m e n ,
w h i c h h a d b e e n s h a v e d for a n a b d o m i n a l ultrasound 1 0 months b e f o r e p r e s e n t a t i o n .
dl), the test results should be considered consistent with, but after the administration of synthetic or porcine A C T H ,
not definitively diagnostic of, hyperadrenocorticism and the respectively. Whenever porcine A C T H gel is used, blood
clinician must rely on the clinical signs, physical examination samples for Cortisol determination should be obtained 1 and
findings, and results of other diagnostic tests to help estab 2 hours after its administration. Whenever synthetic A C T H
lish the diagnosis. Results of the dexamethasone suppression is used, blood samples should be obtained 30 minutes and 1
test should never constitute the sole evidence for hyperadre hour after its administration. The reference range for peak
nocorticism in cats. p o s t - A C T H serum Cortisol concentration is 5 to 15 g/dl.
P o s t - A C T H serum Cortisol concentrations greater than
Adrenocorticotropic Hormone 15 g/dl are suggestive of hyperadrenocorticism. The sensi
Stimulation Test tivity of the A C T H stimulation test i n identifying hyperad
The peak increase in the p o s t - A C T H serum Cortisol concen renocorticism is low i n cats. Fewer than 50% of cats with
tration occurs earlier i n cats than in dogs, and serum Cortisol hyperadrenocorticism confirmed at necropsy have abnormal
concentrations can approach baseline values by 1 or 2 hours A C T H stimulation test results consistent with the disease.
TABLE 53-4
Diagnostic Tests to Assess the Pituitary-Adrenocortical Axis in Cats with Suspected Hyperadrenocorticism
Urine Cortisol: Rule out Cushing's Urine collected at home Normal Not supportive of
creatinine ratio syndrome Cushing's syndrome
Increased Additional tests for
Cushing's indicated
8-hr post-dexamethasone:
Dexamethasone Diagnose Cushing's 0.1 mg dexamethasone/kg IV; < 1.0 g/dl Normal
suppression test syndrome serum pre- and 4 and 8 hr 1.0-1.5 g/dl Nondiagnostic
post-dexamethasone >1.5 g/dl and Suggestive
4 h r < 1.5 g/dl Strongly
>1.5 g/dl and suggestive
4 h r > 1.5 g/dl
Post-ACTH Cortisol concentration:
A C T H stimulation Diagnose Cushing's 2.2 IU of A C T H g e l * / k g IM; >20 g / d l Strongly suggestive
syndrome serum pre- and 1 and 2 hrs 15-20 g/dl Suggestive
post-ACTH or 0 . 1 2 5 mg of 5-15 g / d l Normal
synthetic A C T H * / c a t IM; <5 g/dl Iatrogenic Cushing's
serum pre- and 3 0 and syndrome
60 min post-ACTH
Endogenous A C T H Differentiate Plasma sample obtained <2 pmol/L ATH
PDH from ATH between 8 and 10 AM 2-10 pmol/L Nondiagnostic
Special handling required >10 pmol/L PDH
ACTH, Adrenocorticotropic hormone; IM, intramuscular; PDH, pituitary-dependent hyperadrenocorticism; ATH, adrenal tumor causing
hyperadrenocorticism.
* A C T H gel: Acthar Gel, Questcor Pharmaceuticals; Synthetic ACTH: Cortrosyn, Amphastar Pharmaceuticals.
Suggestive of hyperadrenocorticism.
$ Strongly suggestive of hyperadrenocorticism.
Diagnosis
FIG 5 3 - 1 9
Hyperadrenocorticism is diagnosed o n the basis of history;
Dexamethasone suppression test results in seven cats with
findings o n physical examination; results of routine blood
histologically confirmed hyperadrenocorticism. Blood for the
Cortisol determination was drawn before and 4, 6, and 8 and urine tests, abdominal ultrasonography, and tests of the
hours after the intravenous administration of 0.1 mg of pituitary-adrenocortical axis; and the clinician's index of
dexamethasone/kg body weight. In most cats the plasma suspicion for the disease. Ideally, all diagnostic tests per
Cortisol concentration remained more than 1.4 g/dl formed i n the assessment o f a cat with suspected hyperad
throughout the testresults that are very consistent with a renocorticism should be abnormal. Discordant test results
diagnosis of hyperadrenocorticism.
raise doubt regarding the diagnosis. False-positive and false-
negative results occur w i t h all o f the diagnostic tests used to
assess the pituitary-adrenocortical axis. Although normal
UCCR and dexamethasone suppression test results are
inconsistent with a diagnosis of hyperadrenocorticism,
abnormal results o f these tests do not by themselves confirm i n cats that remain symptomatic at the starting dose given
the diagnosis. If there is doubt or uncertainty about the once daily. In one study by Neiger et al. (2004), three cats
diagnosis, therapy for hyperadrenocorticism should be with with P D H were still alive 6, 11, and 20 months after starting
held and the cat reevaluated 1 to 2 months later. trilostane therapy at 30 mg/cat once a day.
Aminoglutethimide (Cytadren, 30 mg/cat, administered
Treatment orally q l 2 h ; Ciba-Geigy Pharmaceuticals) inhibits the con
Treatment o f hyperadrenocorticism is problematic i n cats, version o f cholesterol to pregnenolone, thereby reducing
primarily because a reliable medical treatment for P D H has Cortisol hypersecretion. Aminoglutethimide has been used
not been identified. Trilostane is the current treatment o f successfully i n controlling clinical signs o f hyperadrenocorti
choice because other treatments, such as mitotane, ketocon cism and hyperprogesteronemia i n cats with progesterone-
azole, and the enzyme inhibitor metyrapone, are ineffective secreting tumors (Fig. 53-20) and appears to maintain its
or only transiently effective. The trilostane treatment and efficacy for a relatively prolonged period o f time (i.e.,
monitoring protocols are similar for dogs and cats (see months). Cobalt irradiation may be tried i n cats with pitu
p. 827). The initial dose is 1 to 2 mg/kg of body weight once itary macrotumor, although clinical signs o f hypercorti
daily. Adjustments i n the dose and frequency o f administra solemia may persist despite shrinkage o f the tumor.
tion are based on clinical response and results o f the A C T H Adrenalectomy is the treatment of choice for A T H , and
stimulation test, U C C R , and serum electrolyte concentra bilateral adrenolectomy is also an effective treatment for
tions. In general, twice-daily dosing provides better control P D H . Medical treatment with trilostane is usually necessary
than once-daily dosing and should be the initial adjustment for 4 to 6 weeks before adrenalectomy to reverse the catabolic
FI6 5 3 - 2 0
A , A 9-year-old male castrated d o m e s t i c l o n g - h a i r e d c a t with a 2 - y e a r history of p o o r l y
controlled d i a b e t e s mellitus, failure of hair to r e g r o w after c l i p p i n g 1 y e a r b e f o r e presenta
tion, a n d recent d e v e l o p m e n t of feline fragile skin s y n d r o m e . D i a g n o s t i c e v a l u a t i o n
r e v e a l e d a n a d r e n o c o r t i c a l tumor, i n c r e a s e d serum p r o g e s t e r o n e c o n c e n t r a t i o n , a n d
suppression of the p i t u i t a r y - a d r e n o c o r t i c a l a x i s o n a d r e n o c o r t i c o t r o p i c h o r m o n e stimulation
a n d d e x a m e t h a s o n e s u p p r e s s i o n testing. A progesterone-secreting a d r e n o c o r t i c a l tumor
w a s s u s p e c t e d . B, Five w e e k s after initiating treatment with a m i n o g l u t e t h e m i d e . Feline
fragile skin s y n d r o m e w a s r e s o l v i n g , hair w a s g r o w i n g , a n d g y n e c o m a s t i a h a d devel
o p e d . The serum p r o g e s t e r o n e c o n c e n t r a t i o n h a d d e c r e a s e d from a pretreatment v a l u e of
4 . 7 n g / m l to less than 1 n g / m l . C , Four months after a d r e n a l e c t o m y . Insulin-requiring
d i a b e t e s mellitus h a d r e s o l v e d .
state of the cat, improve skin fragility and w o u n d healing, adrenal cortex by neoplasia (e.g., lymphoma), granuloma
and decrease the potential for perioperative complications. tous disease, hemorrhagic infarction, arterial thrombosis, or
The surgical approach and medical management during and drugs such as mitotane and trilostane can also cause primary
after surgery are similar to those used i n dogs (see p. 828). adrenocortical insufficiency. For clinical signs to develop, it
Treatment for hypoadrenocorticism should begin i m m e d i is believed that at least 90% of the adrenal cortices must be
ately after bilateral adrenalectomy and include injectable destroyed. The zones of the adrenal cortices are usually
desoxycorticosterone pivalate ( D O C P , 2.2 mg/kg, adminis damaged at about the same rate, with aldosterone and glu
tered subcutaneously every 25 days initially, Percoten-V; cocorticoid deficiency typically occurring in tandem.
Novartis Pharmaceuticals) or fludrocortisone acetate (Flori Destruction is progressive, ultimately leading to complete
nef, 0.05 mg/cat, administered orally q l 2 h initially; E R loss of adrenocortical function. Dogs and cats typically have
Squibb & Sons) and prednisolone (1.0 to 2.5 m g once complete loss of adrenocortical function at the time hypo
daily). Subsequent adjustments in the dose of D O C P or adrenocorticism is diagnosed. A partial deficiency syndrome
fludrocortisone acetate should be based o n periodically mea characterized by inadequate adrenal reserve may occur ini
sured serum electrolyte concentrations (see p. 840). Insulin tially, with clinical signs manifested only during times of
therapy can be discontinued i n approximately 50% of cats stress such as boarding, travel, and surgery. As destruction
once hyperadrenocorticism is eliminated, and diabetes is of the adrenal cortex progresses, hormone secretion becomes
easier to control using less insulin i n the remaining cats. inadequate even under nonstressful conditions and a true
metabolic crisis occurs without any obvious inciting event.
Prognosis Mineralocorticoids (i.e., aldosterone) control sodium,
The prognosis is guarded to poor. Untreated hyperadrenal potassium, and water homeostasis. In the setting of primary
cats die within months after the diagnosis has been estab adrenocortical insufficiency, a loss of aldosterone secretion
lished because o f the deleterious effects o f chronic hypercor results i n impaired renal conservation of sodium and chlo
tisolism and insulin-resistant diabetes mellitus on skin ride and the excretion of potassium, leading to the develop
integrity and on i m m u n e and cardiovascular function and ment of hyponatremia, hypochloremia, and hyperkalemia.
as a result of progressive weight loss leading to severe The inability to retain sodium and chloride reduces extracel
cachexia. The effectiveness of trilostane remains to be deter lular fluid volume, leading to progressive development of
mined. Unilateral ( A T H ) or bilateral ( P D H ) adrenalectomy hypovolemia, hypotension, a reduced cardiac output, and
has the potential for excellent success; however, success decreased perfusion of the kidneys and other tissues. Hyper
depends, i n part, on correction of the debilitated state and kalemia has a deleterious effect on cardiac function, causing
skin fragility with medical treatment before surgery, involve decreased myocardial excitability, an increased myocardial
ment of a surgeon with expertise i n adrenal surgery, avoid refractory period, and slowed conduction. A concurrent glu
ance of perioperative complications, and the client's cocorticoid deficiency typically results in gastrointestinal
commitment to managing the iatrogenic adrenal insufficiency tract signs (e.g., anorexia, vomiting, diarrhea, weight loss)
after bilateral adrenalectomy. Periodic evaluation of serum and changes i n mental status (e.g., lethargy). One of the
electrolytes and review of the treatment protocol are i m p o r hallmark signs of hypocortisolism is impaired tolerance to
tant. A n addisonian crisis occurred months after surgery i n stress, and clinical signs often become more pronounced
several cats treated in our clinic and was believed to be when the animal is placed i n stressful situations.
responsible for the death of some. Some dogs and cats with hypoadrenocorticism present to
the veterinarian with clinical signs of glucocorticoid defi
ciency but serum electrolyte concentrations that are within
HYPOADRENOCORTICISM the reference range at initial presentation. A deficiency in
glucocorticoid but not mineralocorticoid secretion is referred
Etiology to as atypical hypoadrenocorticism and is discussed on p. 841.
Hypoadrenocorticism is a deficiency of mineralocorticoids, Glucocorticoid deficiency resulting from pituitary dysfunc
glucocorticoids, orboth. Primary adrenocortical insufficiency tion is also called secondary hypoadrenocorticism. Destructive
(Addison's disease) involving a deficiency of both mineralo lesions i n the pituitary gland or hypothalamus, the long-
corticoid and glucocorticoid secretion is the most c o m m o n . term administration of exogenous glucocorticoids, and idio
The etiology of primary hypoadrenocorticism is usually pathic loss of function are the most c o m m o n causes of
classified as idiopathic because the cause of the disease is not secondary adrenal insufficiency. Naturally occurring, iso
obvious and necropsies are usually done years after the diag lated hypoaldosteronism is rare i n dogs and cats.
nosis is established, at which time idiopathic atrophy of all
layers of the adrenal cortex is the most frequent histopatho Clinical Features
logic finding. Immune-mediated destruction of the adrenal
cortices is believed to occur i n most dogs and cats with idio SIGNALMENT
pathic adrenal insufficiency; lymphocytes, plasma cells, and Hypoadrenocorticism is typically a disease of young to
fibrosis are c o m m o n findings i n animals that undergo nec middle-aged female dogs, with a median age of 4 to 6 years
ropsy near the time of diagnosis. Bilateral destruction of the and a range of 2 months to 12 years. Dogs with glucocorti-
coid-deficient hypoadrenocorticism tend to be older at the lemia. Bradycardia by itself, however, is not pathognomonic
time of diagnosis than dogs with mineralocorticoid and glu for hypoadrenocorticism, especially i n an otherwise healthy
cocorticoid deficient hypoadrenocorticism. Breeds reported dog. Similarly, dogs with hypoadrenocorticism can have
to be at increased risk for hypoadrenocorticism are listed i n normal heart rates. Polyuria and polydipsia are rarely pre
Box 53-6. Hypoadrenocorticism is rare in cats. There is no senting signs, although they may surface during the taking
apparent sex-related predisposition i n cats, although it tends of a complete history.
to occur in young to middle-aged cats (average age 6 years). Clinical signs are often vague and easily ascribed to more
Hypoadrenocorticism can, however, occur i n aged dogs and c o m m o n disorders involving the gastrointestinal and urinary
cats as well. tracts. Observant clients may occasionally describe an illness
with a waxing-waning or episodic course; however, this bit
CLINICAL SIGNS A N D PHYSICAL of historic information is the exception rather than the rule.
EXAMINATION FINDINGS M o s t dogs with hypoadrenocorticism are first seen because
Clinical signs and physical examination findings are listed i n of progressive problems that vary i n severity, depending o n
Box 53-7. The most c o m m o n clinical manifestations are the degree of stress and the adrenocortical reserve.
related to alterations i n the gastrointestinal tract and mental If hyponatremia and hyperkalemia become severe, the
status and include lethargy, anorexia, vomiting, and weight resultant hypovolemia, prerenal azotemia, and cardiac
loss. Weakness is also a c o m m o n client complaint. Additional arrhythmias may result i n an addisonian crisis. The clinical
physical examination findings may include dehydration, bra manifestations are as previously described; the only differ
dycardia, weak femoral pulses, and abdominal pain. Hyper ence is i n the severity of signs. In severe cases the animal may
kalemia and hypoadrenocorticism should be suspected i n an be presented i n shock and be m o r i b u n d . A n addisonian crisis
animal with bradycardia and signs consistent with hypovo- must be differentiated from other life-threatening disorders,
such as diabetic ketoacidosis, necrotizing pancreatitis, acute
hepatitis, septic peritonitis, and acute renal failure.
corticoid or mineralocorticoid or both). M a n y dogs and cats <12 mmol/L or animal is severely ill. mEq H C O = body
3
with primary adrenal insufficiency are presented i n varying weight (kg) x 0.5 x base deficit (mEq/L); if base deficit
stages of an acute addisonian crisis, requiring immediate, unknown, use 10 mEq/L. A d d one quarter of calculated
aggressive therapy. In contrast, dogs and cats with isolated H C O dose to IV fluids and administer over 6 hours.
3
glucocorticoid deficiency often have a chronic course that Repeat only if plasma H C O remains <12 mEq/L.
3
TABLE 53-7
TESTS TO ESTABLISH
HORMONE SECRETED SPECIES CLINICAL SYNDROME DIAGNOSIS
RECOMMENDED DOSE
GENERIC NAME (TRADE
NAME) PURPOSE DOG CAT
Continued
Drugs Used in Endocrine Disorderscont'd
RECOMMENDED DOSE
GENERIC NAME (TRADE
NAME) PURPOSE DOG CAT
PO, By mouth; IM, intramuscular; SC, subcutaneous; BSA, body surface area; GH, growth hormone; IV, intravenous.
PART SEVEN METABOLIC AND ELECTROLYTE
DISORDERS
R i c h a r d W . N e l s o n , S e a n J . D e l a n e y a n d D e n i s e A . Elliott
C H A P T E R 54
Disorders of Metabolism
FIG 54-1
A , Length of the lower leg (LIM) from the middle of the patella. B , Measurement of the rib
cage circumference.
FIG 5 4 - 2
Feline body mass index (FBMI).
The patient's current body weight should be recorded and Given the large variation i n energy requirement that can
a BCS assigned. The BCS can be used to determine the per be seen i n cats and dogs, the best method to determine the
centage of body weight that must be lost. Remembering that amount o f calories to feed a patient to induce weight loss is
each point above a 5 on a 9-point scale represents an addi the use o f an accurate diet history. Typically, the weight of
tional 10% to 15% o f weight over ideal, the clinician can overweight and obese patients is relatively stable at presenta
calculate the percentage of weight that should be lost. For tion; therefore feeding 80% o f the patient's current caloric
example, a patient that has a B C S o f 8 out o f 9 is 30% to intake based on an accurate diet history results i n weight loss
45% overweight. For reasons that will be discussed later, of 0.5% to 2 % o f body weight loss per week. In patients i n
patients should not lose more than 2% o f their body weight which an accurate diet history cannot be determined or that
per week. Therefore it should be expected that most over are not roughly weight stable, the client may feed 80% of
weight and obese patients w i l l take at least several months R E R for cats and R E R for dogs. Regardless o f the method
to lose enough adipose tissue to attain their ideal body used to determine the number o f calories to feed to initiate
weight. Given the necessary length o f time, it is imperative weight loss, clients should be told to expect to adjust the
to break down the ultimate goal of an ideal body weight into amount o f food on the basis o f frequent weigh-ins. Initially,
smaller goals that can be achieved i n shorter periods o f time. it can be expected that some patients will gain weight on the
Therefore the clinician may recommend that the patient lose new weight loss plan, some may stay weight stable, some may
2% to 4% o f body weight every 2 weeks; later, monthly goals lose the desired amount, and some may even lose weight too
of 4% to 8% may be set. These shorter-term goals are typi quickly.
cally more manageable and provide more opportunities for After determining the daily amount o f calories to feed the
adjustment o f a weight loss plan i f needed and for praise i f patient, the clinician should consider the most suitable type
the plan is proving effective. of food. There are essentially two m a i n dietary options:
A rate of weight loss o f 1% to 2% of current body weight either feed a reduced amount o f the regular maintenance
per week is typically recommended for several reasons. First, food or feed a food that has been specifically formulated for
greater rates o f weight loss will require that the patient weight reduction. It is not advisable to feed less of the regular
receive a very small allowance of food, which is most likely food because this most likely was the food that resulted i n
to encourage begging behavior and garbage scavenging. the problem i n the first place. M o r e important, feeding a
These undesirable behaviors, along with the small volume o f maintenance food decreases compliance and increases the
food to be provided, can jeopardize client compliance. risk o f nutrient deficiency and unhealthy weight loss. M o s t
Second, weight loss greater than 2 % of body weight per week foods designed for weight reduction are one-half to two-
is considered unhealthy and has been associated with a thirds less energy dense than typical maintenance foods.
greater loss of lean body mass compared with fat mass. Therefore clients w i l l not visually perceive as m u c h o f a
Third, rapid weight loss is most likely to result i n a rebound decrease i n "bowl fill" when feeding a food designed for
weight gain effect after cessation o f the program. weight reduction. Decreased energy density is achieved by
decreasing the fat content o f the food, air-puffing kibble, portion of fat loss while preserving or, indeed, increasing the
increasing the moisture content of canned or pouched foods, lean body mass. The lean body mass is the most metabolically
and/or by adding fiber. There does appear to be some satiety active portion o f the body and includes skeletal muscle
effect by increasing "bowel fill". M o r e significantly, canine tissues. Preservation o f lean body mass i n humans has been
and feline maintenance foods are formulated according to shown to facilitate successful long-term maintenance of the
energy intake. This means that i f a dog or cat eats its daily ideal body weight once weight loss has been achieved. Lower
energy requirement, it w i l l automatically consume the ing the percentage o f calories from fat i n foods helps reduce
required amounts o f additional essential nutrients, such as the energy density of the food because fat provides almost 2.5
amino acids, essential fatty acids, minerals, and vitamins. B y times the amount o f calories per gram as protein or carbohy
feeding less o f the maintenance food, the client is reducing drate does. Lower-carbohydrate foods specifically designed
not only the amount of energy but also the amount of amino for weight reduction have become available. According to
acids, fatty acids, minerals, and vitamins, thereby risking initial reports, these foods result i n greater fat mass loss with
malnutrition, especially given the length of time that is often the same amount of caloric restriction compared with higher-
needed to achieve an ideal body condition. Conversely, foods carbohydrate foods. The proposed mechanism for this differ
that have been specifically formulated for weight reduction ence relates to shifting metabolism from a lypogenic state to
contain more essential nutrients relative to the energy a lypolytic state, especially i n the cat. One drawback of some
content o f the food. This means that the patient w i l l receive lower-carbohydrate foods designed for weight reduction is
the required amounts o f essential nutrients even though it their potential to be more energy dense and thus have a
is ingesting fewer calories. decreased bowl- and bowel-filling effect.
Foods formulated specifically for weight reduction typi Carnitine is an amino acid derivative that is vital for
cally vary according to energy density, fiber content, and energy metabolism. Carnitine facilitates the movement of
caloric distribution (Tables 54-2 and 54-3). M o s t foods long-chain fatty acids across the mitochondrial membrane,
designed for weight reduction are less energy dense than where they are used for energy production. Carnitine sup
maintenance foods. This enables a greater filling o f both the plementation is believed to facilitate weight loss by increas
b o w l and the bowel, w h i c h should lead to increased c o m p l i ing the efficiency o f "burning" fat as an energy source.
ance and satiety. Traditionally, higher-fiber foods are initially However, a study evaluating the effect o f carnitine supple
suggested for weight loss. Fiber is used as a bulking agent mentation o n body weight loss failed to demonstrate any
to decrease energy density and provide a satiating effect. benefits (Center et al., 2000). Cats that received carnitine
However, there is conflicting research as to whether fiber supplementation lost the same percentage of body weight i n
increases satiety. Because some patients may not respond well the same period o f time as cats that d i d not receive carnitine
to higher-fiber foods, some manufacturers do not use this supplementation. In addition, neither group of cats devel
nutritional strategy. Caloric distribution refers to the percent oped hepatic lipidosis.
age o f calories provided from protein, fat, and carbohydrate. As this chapter was being completed, a new drug (dirlo
Higher-protein foods have been reported to increase the pro tapide) has become available that helps reduce the appetites
TABLE 54-2
Level of Key Nutrients in Selected Therapeutic Commercial Foods Suitable for Weight Loss in Dogs*