1

Fourth year
Fourth year
Second term
Second term
2
II. General medicine lectures for
dentistry students.
Second term
Cardiology
1- Rheumatic fever:
An acute inflammatory complication of group A streptococcal
infection, with a possiility of residual heart disease as a result of
carditis. It occurs most often in children !streptococcal sore throat is
common" , the pea# age-related incidence is etween $ and 1$ years.
%he disease is more common among population with low social and
economic standards, due to overcrowding.
&athogenesis:
Rheumatic fever follows acute eta-hemolytic streptococcal infection
!group A" of the pharyn'.
%he mechanism of development of rheumatic fever after infection is
still un#nown.
%he hypothesis of (antigenic mimicry( etween heart valves and
myocardial cells with acterial antigens was suggested, anormal
immune response y the human host to these antigens, will result in
damage to the cardiac tissue. Genetic predisposition may e
involved.
)iagnosis of rheumatic fever
*linical diagnosis is the main method of diagnosis supported y
laoratory evidence of streptococcal infection. laoratory tests may
help in the diagnosis of R+ ut all of them are non-specific.
*riteria of diagnosis: ! Updated Jones criteria"
,a-or criteria: $ criteria
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1. *arditis.
.. ,igratory polyarthritis.
/. Sydenham0s chorea !Rheumatic chorea".
1. Sucutaneous nodules.
$. 2rythema marginatum.
,inor criteria:
1. +ever.
.. Arthralgia.
/. 2levated acute phase reactants ! c- reactive proteins".
1. &rolonged &-R interval in 2*G.
$. 2vidence of a recent streptococcal infection !AS3%, %hroat
culture".
At least 456 of patients with acute R+ have an elevated anti-
streptolysin-3 titer at presentation.
%o diagnose Rheumatic fever: According to 7ones criteria. 2ither:
. ma-or criteria.
one ma-or 8 two minor criteria.
&lus evidence of an recent streptococcal infection for oth.
1- *arditis:
&ancarditis involving the pericardium, myocardium, and
endocardium. *linical manifestations includes: Sinus tachycardia,
the murmur of mitral regurgitation, an S/ gallop, a pericardial
friction ru, and cardiomegaly, and may e evidence of heart
failure. 2*G may show prolonged &-R interval.
3utcome of rheumatic carditis:
9ealing of the rheumatic valvulitis may cause firous thic#ening
and adhesion, resulting in the most serious complication of
rheumatic fever, valvular stenosis and:or regurgitation of the valve.
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%he mitral valve is involved most fre;uently, followed y the aortic
valve.
)iseased valve is susceptile to acterial endocarditis.
.- ,igratory polyarthritis:
+ound in <$ percent of cases. ,ost often affecting large -oints li#e
an#les, wrists, #nees, and elows over a period of days. It does not
affect small -oints of the hands or feet
and seldom involves the hip -oints.
It is e'tremely painful, leaving one -oint to start inflammation in the
other -oint !migratory", causing pain and swelling.
/. Sydenham=s chorea !Rheumatic chorea":
3ccurs in less than 15 6 of patients with rheumatic fever.
%he latent period etween the onset of the initiating streptococcal
infection and the onset of Sydenham=s chorea may e as long as
several months.
*linically the patient shows involuntary rapid, -er#y, irregular
movements that tends to occur in the lims or the face, these
movements may cause falling of things from the patient=s hand.
1- Sucutaneous nodules:
&resent in less than 15 6 of cases. %hey are found over e'tensor
surfaces of the -oints, most often in patients with long-standing
rheumatic heart disease.
$. 2rythema marginatum:
An uncommon manifestation. It is an evanescent macular eruption
with rounded orders, usually concentrated on the trun#.
%reatment of rheumatic fever:
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1. Antiiotics %herapy immediately: a complete 15-day
course in adults of :
3ral penicillin > !$55 mg twice daily".
2rythromycin !.$5 mg four times daily" for those with penicillin
allergy.
?en@athine penicillin G !a single intramuscular in-ection of 1..
million units" may e used to prevent coloni@ation in the throat.
.. Salicylates for rheumatic arthritis: Given in increasing doses
up to . g four times daily. +or 1 to A wee#s and gradually tapered
to prevent reound.
/. &rednisone ! *orticosteroids" for rheumatic carditis in doses
up to /5 mg four times daily in severe cases, as the patient
improves, salicylates can e added during the tapering of the
steroid doseB this may re;uire 1 to A wee#s.
Secondary prophyla'is:
!According to American 9eart Association and of the Corld 9ealth 3rgani@ation."
%o prevent suse;uent coloni@ation of the upper respiratory tract
with group A streptococci, and prevent recurrence of rheumatic fever.
?en@athine penicillin G !Intramuscular", 1.. million units every 1
wee#s.
&enicillin > !.$5 mg twice daily" orally.
Sulfadia@ine !1.5 g daily" orally.
)uration of prophylactic treatment:
Should e individuali@ed ut at least for $ years.
9igh ris# group may e for life !patients with rheumatic heart
disease".
3utcome of Rheumatic fever:
*omplete healing.
Residual damage to the heart valves.
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%he heart may escape the first attac# of rheumatic fever
without residual damage, ut rarely escape the second
attac#, so prophylactic treatment is mandatory after the first
attac#.

..>alvular heart diseases:
,itral stenosis !,S":
2tiology:
%wo-thirds of all patients with mitral stenosis !,S" are females. It is
generally rheumatic in origin !post-rheumatic fever". It is rarely
congenital. &ure or predominant ,S occurs in appro'imately 15 6 of
all patients with rheumatic heart disease.
&athology:
%he valve leaflets are thic#ened y firous tissue, the mitral
commissures fuse, the chordae tendineae fuse and shorten, the
valvular cusps ecome rigid, leading to narrowing at the ape' of the
funnel-shaped valve, sometimes calcific deposits occur in the valve.
*linical picture:
Chen the mitral valve is stenosed more than /56, a significant rise
of the intra-atrial pressure occurs trying to force the lood into the
left ventricle to maintain the cardiac output.
%his rise in pressure eventually will e reflected on the pulmonary
circulation and on the right side of the heart leading to symptoms.
1.2'ertional dyspnea:
%he first symptom to appear. %he more tight the valve, the lesser the
e'ertion needed to cause dyspnea.
Dormally during e'ertion, lood flow from the left atrium to the left
ventricle increases, ut in ,S, lood accumulates in the left atrium
and pulmonary veins leading to pulmonary congestion and dyspnea.
..&aro'ysmal nocturnal dyspnea:
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)yspnea occurring at night, due to recumet position, the effect of
gravity on the venous return to the right side of the heart is
aolished, venous lood flow increase to the pulmonary circulation,
,S hinders lood flow to the left ventricle , pulmonary congestion
and dyspnea will result.
%he attac# typically awa#en patient from sleep, few minutes later it is
releived y sitting in ed.
/. 9emoptysis:
*oughing of lood due to pulmonary congestion especially during
effort, it occurs due to e'travasation of lood from the alveoli due to
sudden rise of pulmonary pressure.
In advanced cases massive hemoptysis may occur due to the
development of ronchial varices.
1. Recurrent pulmonary infection
%he patient is liale to recurrent chest infections! ronchitis",
ecause the lung is devitalised due to pulmonary congestion.
*omplications of mitral stenosis:
1. &ulmonary edema:
&rogressive stenosis may lead to this serious condition, causing severe
and sudden rise of pulmonary pressure, e'cess fluid e'travasation
occurs into the alveoli, the chest ecomes uling, the patient is
cyanosed and sweating, mortality rate is high, %he patient drowns in his
own secretions.
.. Right sided heart failure:
&rolonged pulmonary congestion results in pulmonary
hypertension, which is reflected on the right ventricle and right
atrium, resulting in right ventricular hypertrophy and dilation, then
right sided failure.
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Symptoms include edema in the lower lims, right sided adominal
pain due to hepatic congestion, and dyspepsia due to splanchnic
congestion.
/. Atrial firillation:
A very common complication to ,>), normal heart eats are
replaced y irregular rapid eats due to anormal atrial rhythm.
Asence of normal atrial contraction causes stagnation of lood and
increases the liaility to thromus formation, which may lead to
emolism, cereral or peripheral.
&hysical signs of ,S:
*ardiac auscultation shows the presence of a mid diastolic rumling
murmur on the mitral area.
Irregular rapid pulse in patients with atrial firillation.
)iagnosis of ,S:
9istory E e'amination.
F-ray chest.
2chocardiography.
*ardiac catheteri@ation.
%reatment of mitral stenosis
Asymptomatic patients:
&reventive therapy of further rheumatic activity, or infective
endocarditis.
Symptomatic patients:
Improvement usually occurs with restriction of sodium inta#e and
maintenance doses of oral diuretics.
Anticoagulants should e administered for at least 1 year in patients
with ,S who have suffered systemic and:or pulmonary emoli@ation.
Atrial firillation:
9
)igitalis glycosides may help patients with A+ to slow the ventricular
rate. ?eta loc#ers may help.
*ontinuous anticoagulants for prolonged cases to prevent emolism.
Surgery: +or severe cases, either valvotomy or valve replacement.
,itral regurgitation:
2tiology:
1. Gsually rheumatic, ,R is more common in males contrary to ,S.
.. ,itral valve prolapse.
/. *ongenital.
1. &apillary muscle rupture post acute myocardial infarction.
$. *hest trauma, due to spontaneous rupture of chorda tendineae.
A. Acute ,R: In acute infective endocarditis.
Symptoms and signs of ,R :
Dormally the mitral valve closes during ventricular systole to prevent
regurgitation of lood into the left atrium, and allow the lood to flow
only in the aorta.
In ,R, the valve is defective allow the lood to flow ac# into the left
atrium causing ac# pressure on the pulmonary circulation and
pulmonary congestion.
1. &alpitation: awareness of heart eats due to e'cess ventricular
filling due to regurgitant lood from the left atrium.
.. )yspnea: due to pulmonary congestion.
/. 2molism is possile with atrial firillation.
*ardiac e'amination: &an-systolic murmur on the mitral area
radiating to the a'illa.
)iagnosisE treatment:
)iagnosis: same as ,S.
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%reatment of ,R:
1. ,edical therapy for cases with restricting physical activities
that regularly produce dyspnea and e'cessive fatigue,
reducing sodium inta#e, and enhancing sodium e'cretion
with the appropriate use of diuretics.
.. >asodilators and digitalis increase ventricular filling
angiotensin-converting en@yme inhiitors !A*2" are useful
in chronic ,R.
/. &rophyla'is against I2, rheumatic activity, and emolism.
1. Surgery for refractory cases: >alve replacement.
Aortic stenosis:
2tiology:
45 6 of adult patients with symptomatic valvular AS are males.
Rheumatic fever.
*ongenital stenosis.
*alcific AS !senile".
Symptoms and signs.
Symptoms occur only if stenotic valve is /$6 of its original si@e.
How cardiac output:
1. Syncopal attac#s ! )ecreased cereral flow".
.. Anginal pains ! )ecreased coronary perfusion".
/. 2asy fatigaility ! )ecreased muscle perfusion"
2'ertional dyspnea due to late left sided failure.
*ardiac e'amination:
1. 2-ection systolic murmur over first aortic area, radiating to the
nec#.
.. How volume pulse.
)iagnosis of AS:
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9istory E e'amination.
F-ray chest: may e normal until heart failure occur.
2*G: Heft ventricular hypertrophy.
2chocardiography.
*ardiac catheteri@ation.
%reatment of AS
1. &rophyla'is against I2, rheumatic activity.
.. In patients with severe AS, strenuous physical activity
should e avoided even in the asymptomatic stage.
/. )igitalis glycosides, sodium restriction, and the cautious
administration of diuretics are indicated in the treatment of
congestive heart failure.
1. Surgery is preferred to avoid sudden death : >alve
replacement.
Aortic regurgitation:
2tiology:
&ure or predominant AR are males, females predominate among
patients with AR who have associated mitral valve disease.
,ost cases are rheumatic in origin.
Acute AR also may result from infective endocarditis, which can
develop on a valve previously affected y rheumatic disease.
*ongenital stenosis.
&athogenesis:
Dormally the aortic valve closes at the end of ventricular systole
to avoid regurgitation of lood ac# to the left ventricle to
maintain perfusion to the different tissues.
?ut in AR the valve does not close allowing lood to flow ac# to
the left ventricle together with lood coming normally from the left
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atrium, volume overload occur and ventricular dilatation occur.
%he left ventricle have to pump e'tra-volume of lood it receives
resulting in hyperdynamic circulation and ig volume pulse, and
many other peripheral signs.
Symptoms:
&atients with severe AR may remain asymptomatic for 15 to 1$ years.
&alpitation !awarness of heart eats", may persist for years efore
dyspnea occur.
2'ersional dyspnea.
3rthopnea, paro'ysmal nocturnal dyspnea, and chest pain.
Signs:
9igh pulse volume.
9yper#inetic cardiac ape'.
2arly diastolic murmur on the second aortic area.
)iagnosis and treatment of AR:
Same as AS.
Infective endocarditis !I2"
A serious complication to valvular heart disease either rheumatic or
congenital. %he most common organism causing I2 is streptococcus
viridans, S. fecalis. Chich are normal commensals in the oral cavity.
,inor procedures ! dental e'traction " may result in actremia,
settling on the valve and cause endocarditis.
Symptoms:
Symptoms of I2 include prolonged fever usually I /J degrees,
mar#ed to'emia !anaemia, anore'ia, and weight loss".
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&eripheral emolisation in different organs !#idneys causing
hematuria, s#in, eyes".
Splenomegaly.
%reatment of I2:
+or streptococcus viridans:
&enicillin G 23 million units IV / 4h for 1 wee#s.
3R:
&enicillin G .3 million units IV / 4h + gentamicin 1 mg/kg
IM or IV / 8h, both for 2 Weeks.
&rophyla'is of I2:
Should e given for any patient with rheumatic or congenital
valvular lesions efore any surgical procedure especially in the
mouth.
+or oral cavity, respiratory tract, or esophageal procedures:
1. Standard regimen:
Amo'icillin . g orally 1 hour efore procedure.
.. Inaility to ta#e oral medication:
Ampicillin . g I> or I, within /5 min of procedure.
/. &enicillin allergy:
larithrom!cin "## mg orall! 1 h before
$roce%ure.
e$hale&in or cefa%ro&il 2.# g orall! 1 h before
$roce%ure.
1. &enicillin allergy 8 Inaility to ta#e oral medication:
*efa@olin 1 g I> or I, /5 min efore procedure.
Ischemic heart disease
)efinition:
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Ischemia is lac# of o'ygen due to inade;uate perfusion, which
results from an imalance etween o'ygen supply and demand.
%he most common cause of myocardial ischemia is
atherosclerotic disease of coronary arteries.
*auses of myocardial ischemia:
1. Atherosclerosis of coronary arteries.
.. Arterial thromosis.
/. *oronary spasm.
1. Severe ventricular hypertrophy !hypertension or aortic stenosis"
due to relative increase in o'ygen demands. 3r decreased o'ygen
in lood as in severe anemia.
$. *oronary emolism !Rare".
D.?: A comination of . causes is possile.
*oronary atherosclerosis:
Ris# factors: Anormal lood lipids, cigarette smo#ing,
hypertension, and diaetes mellitus.
%hese factors leads to suintimal collections of anormal fat,
cells, and deris !atherosclerotic pla;ues", leading to narrowing
of coronary lumen
Symptoms:
1. Angina pectoris:
$5- to A5-year-old man or A$- to <$-year-old woman.
,ales are mostly affected y myocardial ischemia!<56".
Angina is s;uee@ing, central, retrosternal pain, lasting 1 - $ min. It
can radiate to the left shoulder and to oth arms and especially to
the ulnar surfaces of the left forearm and hand, ac#, nec#, -aw,
teeth, and epigastrium.
Anginal pains are provo#ed y:
2'ertion !e'ercise, hurrying, or se'ual activity".
2motions !stress, anger, fright, frustration".
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*igarette smo#ing.
2'posure to cold.
9eavy meals.
Anginal pains are relieved y rest.
Angina occurring at rest is called unstale angina.
)iagnosis:
%he typical history of pain is diagnostic.
2*G: %ypical changes during pain.
Stress test: Recording 2*G changes during e'ercise.
Stress myocardial perfusion: imaging after the intravenous
administration of a radioisotope such as thallium .51 or
technetium JJm.
%wo-dimensional echocardiography of the left ventricle to
assess wall motion anormalities due to myocardial infarction or
persistent ischemia.
*oronary Arteriography: %o map out the coronary
circulation especially efore surgery.
Haoratory and F-ray investigations:
?lood sugar to e'clude diaetes mellitus.
Serum creatinine for renal disease, since ), and renal failure may
accelerate atherosclerosis.
?lood lipids !cholesterol, low density, and high density".
F-ray chest: Aortic calcification, cardiac si@e.
%reatment:
1. Explanation and reassurance.
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.. Identification and treatment of aggravating conditions and risk
factors:
3esity, hypertension, hyperthyroidism, anormal lipids, cigarette
smo#ing, ),.
/. Adaptation of activity: %ry to adapt his activity to prevent the pain,
avoid anger, fre;uent meals.
D.?: *igarette smo#ing accelerates coronary atherosclerosis in oth
se'es and at all ages and increases the ris# of myocardial infarction
and death. ?y increasing myocardial o'ygen needs and reducing
o'ygen supply it aggravates angina.
1. )rug therapy:
Ditrates: It causes systemic venodilation, therey reducing
myocardial wall tension and o'ygen re;uirements, and dilating the
coronary vessels and increasing lood flow in collateral vessels.
%here are short acting SH nitrates and long acting talets.
?eta-loc#ers: &ropranolol, reduce myocardial o'ygen demand
!inhiiting the increases in heart rate and myocardial contractility".
*alcium antagonists: Difedipine, and verapamil.
%hey reduce cardiac o'ygen demand, dilate coronary arteries.
Aspirin:
Anti-platelet aggregator, protect against ischemia especially post
infarction.
Acute ,yocardial infarction
,I occurs if sudden decrease in coronary lood flow following a
thromotic occlusion of a coronary artery previously narrowed y
atherosclerosis.
*linical presentation:
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In aout $56 of patients there is a precipitating factor as vigorous
physical e'ercise, emotional stress, or a medical or surgical
illness.
1. Severe chest pain descried as heavy, s;uee@ing, and crushing is
the most common symptom.
Site is central chest and:or the epigastrium, sometimes it radiates
to the arms.
Hess common sites of radiation include the adomen, ac#, lower
-aw, and nec#.
Gsually accompanied y wea#ness, sweating, nausea, vomiting,
an'iety, and a sense of impending death.
2'amination:
&atients are an'ious and restless, trying to relieve the pain y
moving aout in ed, altering their position, and stretching.
&allor is associated with perspiration and coolness of the
e'tremities.
,ay e changes in lood pressure, and pulse.
Investigations:
1. 2*G: %ypical changes in S% segment and KRS comple'.
.. Serum cardiac mar#ers:
*reatine phospho#inase !*L": rises within 1 to 4 h and generally
returns to normal y 14 to <. h. !*L,?: specific for myocardial
muscle".
*ardiac-specific troponins: &roteins found in cardiac muscle,
normally undetectale ut rises over .5 times in ,I.
3ther non-specific mar#ers: Raised white cell count, 2SR, SG3%,
H)9.
/. %wo-dimensional echocardiography: Anormal wall motion.
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1. ,yocardial perfusion imaging with thallium .51 or technetium
JJm: Reveal a cold spot.
%reatment:
1. &re-hospital care: rapid transfer to the hospital with a trained
team capale of resuscitative maneuvers, including defirillation.
.. 9ospital management:
Emergency treatment: Aspirin, o'ygen inhalation, SH nitrates,
Intravenous eta loc#ers and morphine to control pain.
Decrease infarct size:
%hrompolysis: Gsing tissue plasminogen activator !t&A", or
strepto#inase intravenously.
&ercutaneous %ransluminal *oronary Angioplasty !&%*A": *an
also decrease infarcted area.
Drug therapy:
9eparin: anticoagulant.
?eta-loc#ers.
%reatment of complications:
Arrhythmia.
*ardiogenic shoc#.
9ypertension
1. Arterial hypertension:
2levation of systolic and:or diastolic lood pressure, either
primary or secondary.
Chen hypertension is suspected, lood pressure should e measured at
least twice during two separate e'aminations after the initial screening.
*lassification of lood pressure in adults:
(Nollenberg NK, summary of the joint national committee and WHO and international society of
hypertension 1995!
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Dormal lood pressure:
Systolic I 1/5
)iastolic I 4$ mmhg.
9igh normal lood pressure:
Systolic 1/5 M 1/J mm hg
)iastolic 4$ M 4J mm hg
,ild hypertension: stage 1
Systolic 115 M 1$J mm hg
)iastolic J5 M JJ mm hg
,oderate hypertension: stage .
Systolic 1A5 M 1<J mm hg
)iastolic 155 M 15J mm hg
Severe hypertension: stage /
Systolic 145 M .5J mm hg
)iastolic 115 M 11J mm hg
>ery severe hypertension: stage 1
Systolic N .15
)iastolic N 1.5.
orderline isolated systolic hypertension: )iastolic ?& is I J5 mm9g,
systolic ?& etween 115 and 1$J.
Isolated systolic hypertension: )iastolic ?& is I J5 mm9g, Systolic ?&
is N 1A5 mm9g.
Haile hypertension:
&atients who are sometimes, ut not always, have arterial pressures in
the hypertensive range. %hey are considered to have orderline ?&.
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,alignant hypertension: lood pressure aove .55:115, the condition is
defined y the presence of papilledema, usually accompanied y retinal
hemorrhages and e'udates, rather than y the asolute pressure level.
&atient evaluation:
9istory, physical e'amination.
Symptoms: ,ost patients with hypertension have no specific
symptoms, identified only in the course of a physical e'amination. Chen
symptoms occur, it may e related to:
1- %he elevated pressure itself , headache only in severe hypertension in
the occipital region , present in the morning susides spontaneously
after several hours.
3ther complaints that may e di@@iness, palpitations, easy
fatigaility, and impotence.
.- %he hypertensive vascular disease, epista'is, hematuria, lurring of
vision owing to retinal changes, episodes of wea#ness or di@@iness
due to transient cereral ischemia, angina pectoris, and dyspnea
due to cardiac failure. &ain due to dissection of the aorta or to a
lea#ing aneurysm is an occasional presenting symptom.
/- %he underlying disease, in the case of secondary hypertension.
2'amination of the patient: ,ainly to reveal secondary causes of
hypertension, as endocrinal causes, renovascular occlusion.
Haoratory tests:
?asic initial evaluation: Grine analysis, lood sugar, serum creatinine,
lood lipids, and 2*G.
Screening for secondary hypertension: +or renovascular hypertension,
*ushing=s syndrome, and pheochromocytoma
A. &rimary or essential hypertension !29"
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&atients with arterial hypertension with no definale cause are
said to have primary, essential, or idiopathic hypertension.
It is the most common cause of hypertension.
%here is a familial tendency for hypertension.
Invironmental factors involved in the disease:
salt inta#e, oesity, occupation, alcohol inta#e, family si@e, and
crowding. %hese factors have all een assumed to e important in the
increase in lood pressure with age.
1. +A*%3RS %9A% ,3)I+O %92 *3GRS2 3+ 29:
Age, race, se', smo#ing, alcohol inta#e, serum cholesterol, glucose
intolerance, and weight may all alter the prognosis of this disease.
Age: the younger the patient when hypertension is first noted, the
greater is the reduction in life e'pectancy if he is untreated.
Race: in GSA uran lac#s have aout twice the prevalence of
hypertension as whites, and 1 times mortality.
Se': At all ages, oth white and nonwhite populations, females with
hypertension are etter than males.
+actors: as elevated serum cholesterol, glucose intolerance, and
cigarette smo#ing, significantly enhance the effect of hypertension on
mortality rate regardless of age, se', or race.
Ceight: A gain in weight is associated with an increased fre;uency of
hypertension in su-ects with normal ?&, weight loss in oese su-ects
with hypertension lowers their ?&.
2ffects of hypertension:
Shortening of life y 15 to .5 years, usually related to an acceleration of
the atherosclerotic process , mild disease without evidence of end
organ damage, that is left untreated for < to 15 years have a high ris# of
developing significant complications. Dearly /5 percent will e'hiit
atherosclerotic complications, and more than $5 percent will have end
organ damage related to the hypertension itself, such as cardiomegaly,
congestive heart failure, retinopathy, a cererovascular accident and:or
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renal insufficiency. %hus, even in its mild forms, hypertension is a
progressive and lethal disease if left untreated.
%he heart: 9ypertrophy, enlargement and finally heart failure.
%he retina: retinal changes include narrowing of the arterioles, as well
as the appearance of hemorrhages, e'udates, and papilledema resulting
in scotomata, lurred vision, and even lindness, if the changes are in
the macular area.
%he *DS: Include vascular occlusion causing cereral infarction is
secondary to the increased atherosclerosisB cereral hemorrhage is the
result of oth the elevated arterial pressure and the development of
cereral vascular microaneurysms.
%he #idney:
*hanges in the glomerular capillaries, causing proteinuria, hematuria
and lastly renal failure.
%reatment:
General measures:
!1" relief of stress.
!." dietary management: Reduce sodium, calory , and saturated fats.
!/" regular aeroic e'ercise.
!1" weight reduction !if needed".
!$" control of other ris# factors contriuting to the development of
arteriosclerosis.
)rug therapy:
1- )iuretics: Acts through depletion of plasma volume
! %hia@ides, spironolactone".
.- Antiadrenergic agents: alpha-receptor agonists. Stimulation of
alpha
.
receptors in the vasomotor centers of the rain reduces
sympathetic outflow agents !clonidine, methyldopa".
/- Alpha-Adrenergic Receptor ?loc#ers: loc#ing sympathetic
receptors P1 and P. in the *DS! pra@ocin".
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1- ?eta-Adrenergic Receptor ?loc#ers: loc# sympathetic effects
on the heart , reducing cardiac output, lowering arterial
pressure when there is increased cardiac sympathetic nerve
activity !cardioselective ?1 loc#er:atenolol ", ! &ropranolol:
non-selective".
$- >asodilators: Arteriolar vasodilators: Reduce peripheral
resistance !9ydrala@ine".
A- A*2 inhiitors: &revent production of angiotensin . !potent
vaso-constrictor", preserve rady#inin !vaso-dilator",
!*aptopril".
<- *alcium channel antagonists: modify *a intry into the cells,
cause peripheral vasodilation !nifedipine".
9ow to start treatment Q:
Start with low dose A*2I, eta-loc#ers, or *a channel loc#ersR..If the
&? is not controlledR. )oule the doseRthen add low dose thia@ide
diureticsRthen assess any secondary causeR.. If no Ruse drug
comination.
%he goal of treatment is to achieve normal ?& with minimal side effects,
and good ;uality of life for the patients.
9eart failure
)efinition: +ailure of the heart to pump lood at a rate suitale for
of the metaolism of the ody tissues.
*auses of heart failure:
1. ,yocardial failure: a primary anormality in heart muscle, as occurs
in the cardiomyopathies and in viral myocarditis.
.. *oronary atherosclerosis which leads to myocardial ischemia and
infarction.
24
/. Anormalities of the heart valves in which the heart muscle is
damaged y the long-standing e'cessive hemodynamic urden
imposed y the valvular anormality, and rheumatic process.
1. 9ypertension: causing left ventricular overload.
&recipitating causes of heart failure:
1. infection: &atients with pulmonary vascular congestion are also more
susceptile to pulmonary infections, any infection in a predisposed
patient may lead to heart failure.
.. Anemia: defective o'ygenation is compensated y increase in the
cardiac output, which can e maintained y a normal heart, ut not a
diseased heart.
/. %hyroto'icosis and pregnancy: as in anaemia, oth conditions lead
to increased cardiac output.
1. Arrhythmias. In patients with compensated heart disease,
tachyarrhythmia reduce ventricular filling. In patients with ischemic
heart disease, it also cause ischemic myocardial dysfunction.
$. Rheumatic and other forms of myocarditis.
A. Infective endocarditis.
<. &hysical, dietary, fluid, environmental, and emotional e'cesses.
4. Systemic hypertension. Rapid elevation of arterial pressure, may
result in cardiac decompensation.
J. ,yocardial infarction in a patient with compensated heart may cause
heart failure.
15. &ulmonary emolism: result in further elevation of pulmonary arterial
pressure, and increase cardiac decompensation.
+orms of heart failure:
1. Systolic failure: Inaility to contract normally and e'pel sufficient
lood.
.. )iastolic failure: Inaility to rela' and fill normally.
/. How output failure: &atients with low *3&, it is mostly due to
ischemic heart disease, hypertension, dilated cardiomyopathy, and
valvular and pericardial disease.
25
1. 9igh output failure: *3& is increased as in thyroto'icosis, and
anemia.
$. Heft sided failure: when the left ventricle cannot pump lood, it
accumulates ehind in the pulmonary circulation resulting in
dyspnea and orthopnea as a result of pulmonary congestion.
A. Right sided failure: when the right ventricle is affected as in
pulmonary hypertension, symptoms are usually those of systemic
venous congestion: lower lim edema, congestive hepatomegaly.
S?iventricular failure: Chen oth ventricles fail. Giving rise to symptoms
of oth sides, it occurrs due to a myocardial disease affecting oth
ventricles simultaneously, or left sided failure followed later y right
sided failure due to pulmonary hypertension. As in aortic valve disease.
Symptoms of heart failure:
1. )yspnea "
Respiratory distress that occurs as the result of increased effort in
reathing is the most common symptom of heart failure.
.. 3rthopnea: )yspnea in the recument position is usually a late
manifestation of heart failure.
/. &aro'ysmal !nocturnal" )yspnea: Severe shortness of reath and
coughing that generally occur at night, usually awa#en the patient
from sleep, relieved y sitting in ed.
1. +atigue, Cea#ness, And Adominal Symptoms: Anore'ia and
nausea associated with adominal pain and fullness are fre;uent
complaints and may e related to the congested liver and portal
venous system.
&hysical e'amination:
1. Sinus tachycardia, cardiac enlargement.
.. *yanosis of the lips and nail eds, the patient may insist on sitting
upright !3rthopnea".
26
/. Systemic venous congestion in right sided failure: edema in lower
lims, enlarged pulsating tender liver, congested nec# viens,
hydrothora' and ascites, and -aundice.
1. &ulmonary Rales: ,oist, inspiratory, crepitant rales in the lung ase.
%reatment of heart failure:
!1" Removal of the precipitating cause.
!." *orrection of the underlying cause. 2.g mitral valve replacement in
mitral valve disease.
!/" *ontrol of the congestive heart failure state:
Reduction of cardiac wor# load, including oth the preload and the
afterload, reducing physical activity, reducing the sodium inta#e,
diuretics, vasodilators to reduce afterload, A*2 inhiitors,
pra@osin, and sodium nitroprusside are some of the drugs used.
*ontrol of e'cessive retention of salt and water !diet control,
diuretics".
2nhancement of myocardial contractility: )igo'in, improve cardiac
contractility.
*ardiac transplantation is advised if patients are refractory to treatment.
Shoc#
Is the state in which failure of the circulatory system to maintain
ade;uate cellular perfusion results in widespread reduction in delivery
of o'ygen and other nutrients to tissues. *irculatory insufficiency
causes cellular and then organ dysfunction, which may ecome
irreversile unless corrected promptly.
*auses of shoc#:
1" *ardiogenic:
i" ,yopathic:
!a" Acute myocardial infarction.
27
!" )ilated cardiomyopathy.
!c" ,yocardial depression in septic shoc#.
ii" ,echanical:
!a" ,itral regurgitation.
!" >entricular septal defect.
." 2'tracardiac ostructive shoc#:
i" *ardiac tamponade.
ii" ,assive pulmonary emolism.
/" 9ypovolemic shoc#:
i" 9emorrhage.
ii" +luid depletion.
1" )istriutive shoc#:
i" Septic shoc#.
ii" )rug overdose.
iii" Anaphylactic.
iv" Deurogenic.
v" 2ndocrinological.
9ypovolemic shoc#:
Reduction in circulating lood volume, which decreases preload and
leads to inade;uate ventricular filling, the result is decreased stro#e
volume and inade;uate cardiac output. 9ypovolemic shoc# may result
from hemorrhage or from fluid depletion due to vomiting, diarrhea,
urns, or dehydration. 9ypovolemic shoc# is the most common type
seen clinically.
Hoss of 156 of total lood volume is corrected y compensatory
mechanisms that improve ventricular filling and *3&, and
maintain ?&:
28
1. Sympathetic discharge and adrenal release of catecholamines, leads
to arterial vasoconstriction, augmented venous return, and
tachycardia.
.. Reduction of hydrostatic pressure in the peripheral capillaries favors
transudation of fluid from the e'tracellular space into the vessels.
/. Intravascular volume contraction leads to activation of the renin-
angiotensin system, increased release of antidiuretic hormone
!A)9", and elevated levels of A*%9 and aldosterone.
Chen .5 to .$ 6 of the lood volume is lost rapidly, the
compensatory mechanisms egin to fail and the clinical shoc#
syndrome occurs. *ardiac output declines, and there is
hypotension despite generali@ed vasoconstriction, followed y
end organ damage.
*ardiogenic shoc#:
Severe depression of cardiac performance. 9emodynamically, it is
characteri@ed y a systolic lood pressure I45 mm9g. %he most
common cause is myocardial infarction with loss of 15 6 or more of the
left ventricular mass.
2'tracardiac ostructive shoc#:
*ardiac tamponade: *auses increased pericardial pressure which
impairs ventricular diastolic filling, decrease preload, stro#e volume,
and cardiac output.
,assive pulmonary emolism: Also results in right sided failure, and
decreased left ventricular filling.
)istriutive shoc#:
*aused y peripheral vasodilatationB although cardiac output may e
normal or high, organ and tissue perfusion pressures are inade;uate.
29
Septic shoc# is an e'ample of this type of shoc#B other causes include
anaphyla'is, neurogenic and adrenal insufficiency.
Septic shoc#:
*aused y severe acterial infection, acteria circulating in the lood
releases acterial to'ins, which is a potent stimulator of cyto#ines and
mediators release such as histamine and #inines and others , causing
peripheral vasodilatation which causes hypotension, and myocardial
depression leading to reduction in cardiac output, organ system failure
occur then death follows if not corrected.
,ortality in untreated cases is aout $56.
Anaphyla'is:
Hife-threatening anaphylactic response of a sensiti@ed human after
e'posure to a specific antigen, and is manifested y respiratory distress
often followed y vascular collapse or y shoc#, cutaneous
manifestations include prurites and urticaria, with or without
angioedema are characteristic of such systemic anaphylactic reactions.
Gastrointestinal manifestations include nausea, vomiting, crampy
adominal pain, and diarrhea.
,aterials causing this reaction are numerous:
)rugs !insulin, penicillin, cephalosporins, amphotericin ?,
nitrofurantoin", insect ites, food !eggs, seafoods, nuts, grains and
eans", local anesthetics !procaine and lidocaine".
*linically: Symptoms appear seconds to minutes after introduction of
the antigen, generally y in-ection or less commonly y ingestion. %here
may e upper or lower airway ostruction or oth. Haryngeal edema may
e e'perienced as a (lump( in the throat, hoarseness, or stridor, chest
tightness and ronchial spasm, urticarial eruptions are intensely pruritic
and may e locali@ed or disseminated. %hey may coalesce to form giant
hives.
A locali@ed, nonpitting, deeper edematous cutaneous process,
angioedema may occur.
30
&atients may die of vascular collapse due to peripheral vasodilatation,
and critical reduction of lood volume.
*linical picture of shoc#:
Shoc# is characterised y hypotension, which in adults generally refers
to a mean arterial pressure elow A5 mm9g.
3ther signs and symptoms include tachycardia, oliguria, a clouded
sensorium, and cool, mottled e'tremities indicative of reduced lood
flow to the s#in. ,etaolic acidosis, often due to elevated lood lactate
levels, reflects prolonged inade;uate lood flow to tissues.
3ther clinical manifestations are specific to the type of shoc#. &atients
with hypovolemic shoc# fre;uently have a history of gastrointestinal
leeding, hemorrhage from another site, or clear evidence of large
volume losses via diarrhea and:or vomiting.
&atients with cardiogenic shoc# usually have symptoms and signs of
heart disease, mechanical causes of cardiogenic shoc# fre;uently cause
heart murmurs, such as those of mitral regurgitation, aortic stenosis, or
ventricular septal defect. &atients with septic shoc# there may e
evidence of locali@ed infection as well as fever and chills.
%reatment:
1. Shoc# is an emergency situationB the patient should e managed in
intensive care unit. *ontinuous electrocardiographic monitoring
should e performed for detection of rhythm disturances.
.. +re;uent measurements of arterial lood gases, serum electrolytes,
complete lood counts, and coagulation parameters should e done
to follow the patient=s progress and to monitor the effects of therapy.
/. %he main goal of treatment is to maintain mean arterial pressure, and
to ensure ade;uate perfusion and delivery of o'ygen and other
nutrients to the vital organs.
1. 9ypovolemic shoc#: infusion of fluid is the fundamental treatment of
acute hypovolemia, infusion of crystalloid solutions !saline" or
31
colloid solutions !alumin", or lood transfusion in hemorrhagic
shoc#.
$. *ardiogenic shoc#: If due to myocardial infarction, attention should
e directed to reducing myocardial ischemia, y supplemental
o'ygen, and administration of intravenous nitroglycerin if ?& allows,
up to even emergency coronary angioplasty. )opamine and
analogues may e useful as enotropic agents.
A. Septic shoc#: %reat infection y surgical drainage and:or antiiotic
therapy, o'ygen inhalation, lood and fluid transfusion to
maintenance tissue o'ygen delivery.
<. Anaphyla'is: 2arly recognition is important since death occurs
within minutes to hours after the first symptoms.
,ild symptoms such as pruritus and urticaria can e controlled y
administration of 5.. to 5.$ mH of 1:1555 epinephrine S.*, a material
in-ected into e'tremities apply a tourni;uet to reduce the rate of
asorption, administration of 5.. mH of 1:1555 epinephrine into the
site of in-ection.
volume e'panders such as normal saline to replace intravascular
volume, and vasopressor agents such as dopamine if intractale
hypotension occurs. 2pinephrine causes vascular vasoconstriction,
ronchodilation. ?-loc#ers are contraindicated in patients with
anaphyla'is.
3ther treatments include antihistaminics, o'ygen inhalation.
*orticosteroids may e used to prevent late recurrence of
symptoms.
D.?: Steroid use in shoc# was a routine procedure ecause it is
supposed to improve microcirculation, and support capillaries, ut
studies showed that it has no effect on moridity or mortality.
)iaetes mellitus
32
), is the most common endocrine disease worldwideB it is
characteri@ed y metaolic anormalities and y long-term
complications involving the eyes, #idneys, nerves, and lood vessels.
*haracteri@ed y hyperglycemia, either due to reduced insulin secretion,
decreased glucose usage, and increased glucose production.
Action of insulin:
Insulin is the most important regulator of the alance etween hepatic
glucose production and peripheral glucose upta#e and utili@ation.
In the fasting state, low insulin levels promote hepatic gluconeogenesis
and glycogenolysis to prevent hypoglycemia. How insulin levels
decrease glycogen synthesis, reduce glucose upta#e in insulin-
sensitive tissues, and promote moili@ation of stored precursors. %hese
processes are of critical importance to ensure an ade;uate glucose
supply for the rain.
&ostprandially, a large glucose load elicits a rise in insulin and fall in
glucagon, leading to a reversal of these processes. %he ma-or portion of
postprandial glucose is utili@ed y s#eletal muscle.
*lassification of ),:
I. &rimary:
1. %ype 1: Insulin dependent ),: ? cell destruction !A-immune
mediated E ?- Idiopathic".
.. %ype .: Don-insuline dependent: Insuline rTsistant diaetes
mellitus.

33
II. Secondary:
1 !ancreatic disease
" #ormonal a$normalities
% Chemical induced dia$etes
& 'nsulin receptor a$normalities
( Dia$etes )ith genetic syndromes
&athogenesis of type 1A ! I)),": Immune mediated type 1:
Autoimmune destruction of the eta cells of the pancreas, triggered y
an environmental factor !viral infection", which is followed y
autoimmune inflammation and gradual destruction of the eta cells with
time, insuline levels drop until it is not enough to control lood sugar,
then clinical disease appears.
%he stage in which the patient is not symptomati@ing during active
inflammation is termed prediaetes.
%he role of inheretance in this type of diaetes is still unclear.
&revention of %ype 1A ),:
%heoretical adminstration of immunosuppressive drugs to reduce ? cell
destruction at an early stage, may prevent the disease.
&athogenesis of type . ),:
%ype . ), has a strong genetic component, there is a strong familial
predisposition, this type is characteri@ed y impaired insulin secretion,
peripheral insulin resistance, and e'cessive hepatic glucose production.
3esity, particularly visceral or central, is very common in type . ),.

&revention of type . ),: Hife-style modifications have een
suggested to prevent or delay its onset. Individuals with a strong family
history or those at high ris# for developing ), should e strongly
encouraged to maintain a normal ody mass inde' and to engage in
regular physical activity.
34
*linical picture of ),:
Symptoms of hyperglycemia include polyuria, polydipsia, weight loss,
fatigue, wea#ness, lurry vision, fre;uent superficial infections
!vaginitis, fungal s#in infections", and slow healing of s#in lesions after
minor trauma. ,etaolic derangements relate mostly to hyperglycemia
!osmotic diuresis, reduced glucose entry into muscle" and to the
cataolic state of the patient !urinary loss of glucose and calories,
muscle rea#down due to protein degradation and decreased protein
synthesis". ?lurred vision results from changes in the water content of
the lens and resolves as the hyperglycemia is controlled.
&hysical e'amination:
+ull e'amination with special attention to weight or ody mass inde',
retinal e'amination, orthostatic lood pressure, foot e'amination,
peripheral pulses, and insulin in-ection sites.
*areful e'amination of the lower e'tremities should see# evidence of
peripheral neuropathy, calluses, and superficial fungal infections. Dail
disease, and foot deformities in order to identify sites of potential s#in
ulceration.
>iratory sensation, and the aility to sense touch, is useful to detect
moderately advanced diaetic neuropathy.
Since dental disease is more fre;uent in ),, the teeth and gums should
also e e'amined.
&atients with type 1 ), tend to have the following characteristics:
!1" 3nset of disease efore the age of /5 years.
!." Hean ody.
!/" Re;uirement of insulin as the initial therapy.
!1" Hiaility to develop #etoacidosis.
!$" An increased ris# of other autoimmune disorders such as
autoimmune thyroid disease, adrenal insufficiency, pernicious anemia,
and vitiligo.

35
In contrast, &atients with type . ), often have the following features:
!1" )evelop diaetes after the age of /5.
!." Are usually oese !456 are oese, ut elderly individuals may e
lean".
!/" ,ay not re;uire insulin therapy initially.
!1" ,ay have associated conditions such as insulin resistance,
hypertension, cardiovascular disease, dyslipidemia, or polycystic ovary
syndrome.
In type . ),, insulin resistance is often associated with adominal
oesity !as opposed to hip and thigh oesity" and hypertriglyceridemia.
Haoratory assessment:
*riteria of diagnosis of ), are:
1. +asting !overnight": >enous plasma glucose concentration 1.A
mg:dH on at least two separate occasions.
.. %wo-hour plasma glucose concentration .55 mg:dH during oral
glucose tolerance test.
/. Random lood sugar .55 mg:dH 8 symptoms of diaetes
!polyuria, polydipsia, and weight loss"
D.?: If the . hours reading is one .55 mg:dH, and the other is
etween 115 and .55 mg:dH, the diagnosis is impaired glucose
tolerance.
%he patient should e screened for ),-associated conditions !e.g.,
microaluminuria, dyslipidemia, thyroid dysfunction". Individuals
at high ris# for cardiovascular disease should e screened for
asymptomatic coronary artery disease y appropriate cardiac
stress testing, when indicated.
%reatment of ),:
%he goals of therapy for type 1 or type . ), are to:
!1" 2liminate symptoms related to hyperglycemia.
36
!." Reduce or eliminate the long-term microvascular and
macrovascular complications of ),.
!/" Allow the patient to achieve as normal a life-style as possile.
%o achieve this goal we need:
&atient education aout ),:
Self-monitoring of lood glucose, using plasma glucose
assessment and glycated hemogloin or !9A1c".
Grine #etone monitoring !type 1),"B
Insulin administrationB
Guidelines for diaetes management during illnessesB
,anagement of hypoglycemiaB
+oot and s#in careB
)iaetes management efore, during, and after e'erciseB
Ris# factor-modifying activities.
Dutrition:
,edical nutrition therapy !,D%" is a term used y the American
)iaetes Association !A)A" to descrie the optimal coordination of
caloric inta#e with other aspects of diaetes therapy !insulin, e'ercise,
weight loss". 9istorically, nutrition has imposed restrictive, complicated
regimens on the patient. *urrent practices have greatly changed,
though many patients and health care providers still view the diaetic
diet as monolithic and static. +or e'ample, modern ,D% now includes
foods with sucrose and see#s to modify other ris# factors such as
hyperlipidemia and hypertension rather than focusing e'clusively on
weight loss in individuals with type . ),.
%he ma-ority of type . ), individuals are oese, and weight loss is still
strongly encouraged and should remain an important goal. ,edical
treatment of oesity is a rapidly evolving area.
2'ercise
2'ercise is an integral component of diaetes care that can have
multiple positive enefits !cardiovascular enefits, reduced lood
37
pressure, maintenance of muscle mass, reduction in ody fat, weight
loss, etc.". +or individuals with type 1 or type . ),, e'ercise is also
useful for lowering plasma glucose !during and following e'ercise" and
increasing insulin sensitivity.
%ype 1 )iaetes ,ellitus "
%he goal is to design and implement insulin regimens that mimic
physiologic insulin secretion. ?ecause individuals with type 1 ), lac#
endogenous insulin production, administration of asal, e'ogenous
insulin is essential for regulating glycogen rea#down,
gluconeogenesis, lipolysis, and #etogenesis. Hi#ewise, postprandial
insulin replacement should e appropriate for the carohydrate inta#e
and promote normal glucose utili@ation and storage.
Insulin preparations:
Short acting insulin: Regular insulin.
Intermediate acting: D&9.
Hong acting: Glargin, ultralente.
*ominations: ,i'ed <5:/5. !D&98regular".
Insulin regimens:
%wice in-ection of mi'ed insulin morning and evening is a very
common regemin.
Hong acting insulin at night, and multiple short acting insulin efore
meals.
*ontinuous sucutaneous insulin infusion !*SII" is another
multiple-component insulin regimen. Sophisticated insulin infusion
devices are now availale that can accurately deliver small doses of
insulin !microliters per hour". %he prolem is occurance of local
infection, hyperglycemia if the system is interrupted.
%ype . )iaetes ,ellitus "
%he goals of therapy for type . ), are similar to those in type 1:
improved glycemic control with near normali@ation of the 9A1c. %he
38
care of individuals with type . ), must also include attention to the
treatment of conditions associated with type . ), !oesity,
hypertension, dyslipidemia, cardiovascular disease" and detection E
management of ),-related complications. ),-specific complications
may e present in up to .5 to $56 of individuals with newly diagnosed
type . ),.
?egin with diet therapy for one month, if glycemic control is not
reached drug therapy is to e started.
3ral glucose lowering drugs are to e used in type . diaetes
only, they are ineffective in type 1 ),.
3ral drugs:
%hose increasing insulin secretion: Sulphonylurea,
glyenclamide !daonil", glipi@ide !diamicron", glimepride
!amaryl". Side effects: hypoglycemia, weight gain.
?iguanides: Increase glucose utili@ation, decraese hepatic
glucose production, promote weight loss !metformine U
glucophage".
Alpha glucosidase inhiitors: &revent glucose asorption
!acarose U glucoay".
%hia@olidinediones: Dew group reduce insulin resistance,
increase glucose utili@ation !rosiglita@one U avandia". Side
effects: weight gain.
Insulin therapy in type. ),:
Insulin should e considered as the initial therapy in type . ),,
particularly in lean individuals or those with severe weight loss,
in individuals with underlying renal or hepatic disease that
precludes oral glucose-lowering agents, or in individuals who
are hospitali@ed or acutely ill.
&regnancy, patients with transplanted #idney.
39
Insulin therapy is ultimately re;uired y a sustantial numer of
individuals with type . ), ecause of the progressive nature of
the disorder and the relative insulin deficiency that develops in
patients with long-standing diaetes.
%reatment is started as single dose of S.* intermediate acting
insulin at edtimeB it can e comined with oral drugs.
Dew treatment:
&ancreatic transplantation.
&ancreatic islet cell transplantation.
*omplications of ),
1- Acute complications:
a- )iaetic #etoacidosis.
- Don-#etotic hyperosmolar state.
c- 9ypoglycemia.
)IA?2%I* L2%3A*I)3SIS !)LA"
It is seen mainly in type 1 ), more than type . ),.
It is potentially associated with serious complications if not treated
promptly.
Symptoms:
Dausea and vomiting are often present, thirst and polyuria due to
hyperglycemia and glucosuria leading to dehydration, tachycardia and
hypotension, adominal pain, altered mental state, rapid acidotic
reathing.
&hysical signs:
40
%achycardia, reduced s#in elasticity, dry mucous memranes,
dehydration, hypotension, tachypnea, Lussmaul respirations and
an acetone odor on the patient=s reath !oth secondary to
metaolic acidosis" are classic signs of the disorder, adominal
tenderness, fever, Hethargy and central nervous system depression
may evolve into coma with severe )LA. *ereral edema, an
e'tremely serious complication of )LA, is seen most fre;uently in
children.
&recipitating factors:
Inade;uate insulin inta#e, infection, infarction !coronary, cereral,
peripheral", and drugs.
&athophysiology:
%his condition results from insulin deficiency comined with
counterregulatory hormone e'cess !glucagon, catecholamines, cortisol,
and growth hormone". ?oth insulin deficiency and glucagon e'cess, in
particular, are necessary for )LA to develop.
%his results in increased gluconeogenesis, glycogenolysis, and #etone
ody formation in the liver, as well as increasing sustrate delivery from
fat and muscle !free fatty acids, amino acids" to the liver.
*etosis results from a mar#ed increase in free fatty acid release from
adipocytes, with a resulting shift toward #etone ody synthesis in the
liver.
In normal &9, #etone odies e'ist as #etoacids, which are neutrali@ed y
icaronate. As icaronate stores are depleted, metaolic acidosis
ensues.
Haoratory alterations:
)LA is characteri@ed y hyperglycemia, #etosis, and metaolic acidosis,
Serum icaronates are reduced, ody stores of electrolytes are
reduced !sodium, chloride, phosphorous, and magnesium".
%reatment:
41
*onfirm diagnosis !hyperglycemia, metaolic acidosis, and #etone
odies".
9ospital admission, etter intensive care.
*ontinue laoratory assessment for electrolytes, acid ase and
#idney function.
Replace fluids, y normal saline 1-. liters in the first few hours,
then half normal saline, then $6 de'trose plus half normal saline if
the R?S reach .$5 mg6.
Regular insulin I, or I> 15-.5 units, then $-15 units:hour y I>
infusion.
%reat precipitating factors: Infection, infarction, drugs !*ociane".
*orrect electrolytes, especially L which is depleted due to L entry
into the cell with glucose, hypo#alemia is fatal if not treated.
*ontinue treatment until the patient is stale, acidosis disappear,
lood sugar etween 1$5-.$5 mg 6.
Chen the patient start to eat, shift to long acting or comined
insulin.
*omplications of )LA:
%he ma-or nonmetaolic complication of )LA therapy is cereral edema,
which most often develops in children as )LA is resolving.
>enous thromosis and adult respiratory distress syndrome
occasionally complicate )LA.
D3DL2%3%I* 9O&2R3S,3HAR S%A%2:
&athophysiology:
Insulin deficiency is less severe than )LA, hyperglycemia induces
osmotic diuresis that leads to profound intravascular volume depletion,
which is e'acerated y inade;uate fluid replacement, there is no or
little #etosis ! insulin : glucagon does not favor #etosis ", mar#ed
hyperglycemia !V1555 mg6".
*linical +eatures:
42
It is most commonly seen in elderly individuals with type .),. Its most
prominent features include polyuriaB orthostatic hypotensionB and a
variety of neurologic symptoms that include altered mental status,
lethargy, sei@ure, and possily coma.
%reatment:
%he patient with DL9S is usually older, more li#ely to have mental
status changes, and thus more li#ely to have a life-threatening
precipitating event with accompanying complications. 2ven with proper
treatment, DL9S has a higher mortality than )LA up to $56.
9ypotonic saline infusion !5.1$6 saline" should e used. After
hemodynamic staility is reached, correct the free water deficit using
hypotonic fluids !5.1$6 saline initially then $6 de'trose in water". %he
calculated free water deficit !which averages J to 15 H" should e
reversed over the ne't 1 to . days. &otassium repletion is usually
necessary.
+luid therapy lowers glucose initiallyB insulin therapy is less re;uired
than )LA, insulin $ to 15 units first followed y intravenous constant
infusion rate !/ to < units:h".
9ypoglycemia:
%he most serious complication of diaetes mellitus therapy.
Symptoms:
?ehavioral changes, confusion, fatigue, sei@ure, loss of consciousness,
and, if hypoglycemia is severe and prolonged, death.
9ypoglycemia-induced autonomic responses include palpitations,
tremor, and an'iety as well as cholinergic symptoms such as sweating,
hunger, and paresthesia.
%reatment:
3ral treatment with glucose talets or glucose-containing fluids, candy,
or food. A reasonale initial dose is .5 g of glucose. &arenteral therapy
43
is necessary. Intravenous glucose !.$ g" should e given using a $56
solution followed y a constant infusion of $ or 156 de'trose.
*9R3DI* *3,&HI*A%I3DS of ),
>ascular complications:
1- ,icrovascular:
a- 2ye complications: retinopathy, cataract, glaucoma.
- Deuropathy: Sensory, motor, autonomic.
c- Dephropathy.
.- ,acrovascular:
a- *oronary artery disease.
- &eripheral vascular disease.
c- *ererovascular disease.
Don-vascular complications:
a- Gastrointestinal !gastroparesis, diarrhea".
- Genitourinary !Se'ual dysfunction".
c- )ermatologic.
,echanisms of chronic complications:
%hese complications result from chronic hyperglycemia in type 1), and
type .),.
%here are theories e'plaining the possiility of complications to e due
to either:
&roduction of intracellular sustances that accelerate
atherosclerosis, promote glomerular dysfunction, reduce nitric
o'ide synthesis, induce endothelial dysfunction, and alter
e'tracellular matri' composition and structure.
9yperglycemia increases glucose metaolism via a pathway that
produces sustances !Soritol E diacylglycerol" causing cellular
dysfunction, and promote complications.
44
D.?: Studies showed that improvement of glycemic control reduced nonproliferative
and proliferative retinopathy !1<6 reduction", microaluminuria !/J6 reduction",
clinical nephropathy !$16 reduction", and neuropathy !A56 reduction".
Improved glycemic control also slowed the progression of early diaetic
complications. *ontrol of hypertension also reduce complications.
3&9%9AH,3H3GI* *3,&HI*A%I3DS 3+ )IA?2%2S ,2HHI%GS:
), is the leading cause of lindness etween the ages of .5 and <1 in
the Gnited States. Individuals with ), are .$ times more li#ely to
ecome lind than individuals without ),.
)uration of ), and degree of glycemic control are the est predictors of
the development of retinopathy. Donproliferative retinopathy is found in
almost all individuals who have had ), for V.5 years.
Don-proliferative diaetic retinopathy: Appears etween the first
and second decade. *hanges include retinal vascular
microaneurysms, lot hemorrhages, and cotton wool spots, leading
at the end in retinal ischemia.
&roliferative diaetic retinopathy : %he appearance of
neovasculari@ation in response to retinal hypo'ia is the hallmar# of
this type, rupture of these vessels leads to vitreous hemorrhage,
firosis, and ultimately retinal detachment. Dot every patient with
nonproliferative retinopathy develop proliferative retinopathy.
%reatment:
%he most effective therapy for diaetic retinopathy is prevention.
Intensive glycemic control will greatly delay the development or slow
the progression of retinopathy in individuals with either type 1 or type .
),.
Haser photocoagulation is very successful in preserving vision.
&roliferative retinopathy is usually treated with panretinal laser
photocoagulation.
45
R2DAH *3,&HI*A%I3DS 3+ )IA?2%2S ,2HHI%GS "
)iaetic nephropathy is the leading cause of end stage renal failure
in the Gnited States. &roteinuria in individuals with ), is
associated with mar#edly reduced survival and increased ris# of
cardiovascular disease. Individuals with diaetic nephropathy
almost always have diaetic retinopathy also.
%he cause is due to chronic hyperglycemia that causes
hemodynamic alterations in the renal microcirculation !glomerular
hyperfiltration, increased glomerular capillary pressure", and
structural changes in the glomerulus, Smo#ing accelerates the
decline in renal function.
$ to 15 years of type 1 ), 156 of individuals egin to e'crete small
amounts of alumin in the urine: microaluminuria which is defined
as /5 to /55 mg:d in a .1-h collection. %he appearance of
microaluminuria !incipient nephropathy" in type 1 ), is a very
important predictor of progression to overt proteinuria !V/55 mg:d",
which once present a steady decline in G+R !Glomerular filtration
rate" occur, and $56 of individuals reach 2SR) in < to 15 years.
D.?: &atients with ), are predisposed to radiocontrast-induced nephroto'icity.
%reatment of diaetic nephropathy:
&revention is the optimal therapy, strict glycemic control, control of
lood pressure, and A*2I treatment which slows the progression to
overt nephropathy if given in the microaluminuria stage.
If the patient develops renal failure, dialysis then renal transplantation is
considered.
Deuropathy:
46
)iaetic neuropathy occurs in appro'imately $56 of individuals with
long-standing type 1 and type . ),, the development of neuropathy
correlates with the duration of diaetes and glycemic control.
&olyneuropathy :
%he most common form of diaetic neuropathy is distal symmetrical
polyneuropathy. presents with distal sensory loss. 9yperesthesia,
parathesia, and pain may also occur.
&hysical e'amination reveals sensory loss, loss of an#le refle'es, and
anormal position sense. &arethesia is characteristically perceived as a
sensation of numness, tingling, sharpness, or urning that egins in
the feet and spreads pro'imally.
Deuropathic pain develops in some of these individuals, occasionally
preceded y improvement in their glycemic control.
&ain typically involves the lower e'tremities, is usually present at rest,
and worsens at night.
,ononeuropathy, polyradiculopathy, and autonomic neuropathy:
,ononeuropathy is pain and motor wea#ness in the distriution of a
single nerve, most commonly cranial nerves, the third cranial nerve is
the most commonly affected and starts y diplopia. &hysical
e'amination reveals ptosis and opthalmoplegia with normal papillary
constriction to light.
)iaetic polyradiculopathy:
Is a syndrome characteri@ed y severe disaling pain in the distriution
of one or more nerve roots. It may e accompanied y motor wea#ness.
Intercostal or truncal radiculopathy causes pain over the thora' or
adomen. Involvement of the lumar ple'us or femoral nerve may cause
pain in the thigh or hip and may e associated with muscle wea#ness in
the hip fle'ors or e'tensors. It is a self limiting condition within a year.
47
Autonomic neuropathies:
Affection of the autonomic nervous system, symptoms vary according
to the system affected.
*ardiovascular system causes resting tachycardia and orthostatic
hypotension. Reports of sudden death have also een attriuted to
autonomic neuropathy.
Gastroparesis and ladder-emptying anormalities are also li#ely
related to the autonomic neuropathy seen in ),.
9yperhidrosis of the upper e'tremities and anhidrosis of the lower
e'tremities result from sympathetic nervous system dysfunction!
%he patient may not feel symptoms of hypoglycemia.
%reatment of diaetic neuropathy:
%reatment is not satisfactory, control of lood sugar may improve a little
the nerve function ut not the symptoms.
Avoidance of neuroto'ins !alcohol", supplementation with vitamins for
possile deficiencies !?
1.
, ?
A
, folate".
Symptomatic treatment with analgesics !DSAI)S", antidepressants,
gaapentin, and carama@epine.
Gastrointestinal complications:
Hongstanding ), may affect the motility and function of the gut,
through autonomic neuropathy. Gastroparesis may present with
symptoms of anore'ia, nausea, vomiting, early satiety, and adominal
distension. Docturnal diarrhea, alternating with constipation, is a
common feature of ),-related GI autonomic neuropathy.
Genitourinary complications:
*ystopathy egin with an inaility to sense a full ladder and a failure to
void completely. As ladder contractility worsens, ladder capacity and
the postvoid residual increase, leading to symptoms of urinary
48
hesitancy, decreased voiding fre;uency, incontinence, and recurrent
urinary tract infections.
2rectile dysfunction and female se'ual dysfunction !reduced se'ual
desire, dyspareunia, reduced vaginal lurication".
2rectile dysfunction and retrograde e-aculation are very common in ),
and may e one of the earliest signs of diaetic neuropathy.
%reatment:
Glycemic control, and symptomatic treatment for nausea and vomiting
as metoclopramid, and domperidone. Symptomatic treatment for
impotence, and cystopathy.
Hower lims complications:
)iaetes is the leading cause of nontraumatic lower e'tremity
amputation in the Gnited States. +oot ulcers and infections are also a
ma-or source of moridity in individuals with ),.
,any factors are involved in the pathogenesis of these complications,
neuropathy interferes with normal protective mechanisms and allows
the patient to sustain repeated trauma to the foot, peripheral vascular
disease leading to poor wound healing.
Autonomic neuropathy results in anhidrosis promoting drying of the
s#in, fissure formation, and hence s#in ulceration.
Ris# factors for foot ulcers or amputation include: male se', diaetes
V15 years= duration, peripheral neuropathy, anormal structure of foot
!ony anormalities, callus, and thic#ened nails", peripheral vascular
disease, smo#ing, and history of previous ulcer or amputation.
%reatment:
%he optimal therapy for foot ulcers and amputations is prevention, y
patient education especially high ris# patients:
1. *areful selection of footwear.
49
.. )aily inspection of the feet to detect early signs of poor-
fitting footwear or minor trauma.
/. )aily foot hygiene to #eep the s#in clean and moist.
1. Avoidance of self-treatment of foot anormalities and high-
ris# ehavior !e.g. wal#ing arefoot".
$. *onsultation if an anormality arises.
*orrect other ris# factors for vascular disease !smo#ing, dyslipidemia,
and hypertension" and improve glycemic control.
*areful surgical and medical therapy for patients with infected foot
ulceration is mandatory.
Hiaility to infection in ),:
&atients with ), show greater fre;uency and severity of infection,
which may e due to anormalities in cell-mediated immunity and
phagocyte function associated with hyperglycemia, as well as
diminished vasculari@ation secondary to long-standing diaetes.
9yperglycemia li#ely aids the coloni@ation and growth of a variety of
organisms !Candida and other fungal species".
&neumonia, urinary tract infections, and s#in and soft tissue infections
are all more common in the diaetic population.
Gram-negative organisms, + aureus, and ,ycoacterium tuerculosis
are more fre;uent pathogens.
)iaetic s#in complications:
1. %he most common s#in complication is protracted wound healing,
and s#in ulceration.
.. )iaetic dermopathy, sometimes termed pigmented pretiial papules,
or (diaetic s#in spots,( egins as an erythematous area then ends
in a circular hyperpigmentation. Sometimes pretiial ullae. %his
lesion results from minor mechanical trauma in the pretiial region
and are more common in elderly men with ),.
50
/. Decroiosis lipoidica diaeticorum, a rare lesion affects young
women with type 1 ),, it starts as erythematous pla;ue or papules
that gradually enlarge, dar#en, and develop irregular margins, with
atrophic centers and central ulceration.
1. Acanthosis nigricans !sometimes a feature of severe insulin
resistance", hyperpigmented velvety pla;ues seen on the nec# or
e'tensor surfaces.
$. 3ther manifestations as lipoatrophy occuring at insulin in-ection
sites, scleredema !areas of s#in thic#ening on the ac# or nec# at the
site of previous superficial infections" are more common in the
diaetic population. and granuloma annulare !erythematous pla;ues
on the e'tremities or trun#".
Anemia
)efinition:
A pathological deficiency in the o'ygen-carrying component of the
lood, measured in unit volume concentrations of hemogloin, red
lood cell volume, or red lood cell numer.
3r anemia is a condition in which there is reduction of of R?*s count
and: or hemogloin content due to either lood loss, decreased
production, or increased destruction of R?*s.
Regulation of R?*s production:
Red cell production occur in the one marrow, erythropoeitin hormone
is released from the #idney and regulates day to day production of
R?*s. 2rythropoeitin secretion occur if there is impaired 3
.
delivery to
the #idney e.g: decreased red cell mass !anemia", impaired 3
.
loading
of the hemogloin molecule !hypo'emia", or, rarely, impaired lood flow
to the #idney !renal artery stenosis".
51
Dormal life span of R?*s is 1.5 days, so 1:1.5 of the total cell mass
must e replaced daily, these young cells are called reticulocytes , they
represent one marrow activity.
*lassification of anemias:
1. Anemia due to lood loss: Acute or chronic.
.. Anemia due to decreased red cell production.
a- 9ypochromic microcytic: ! reduced ,*> and ,*9"
i- Iron deficiency anemia.
ii- Anemia of chronic disease.
- Dormochromic normocytic:! Dormal ,*> and ,*9"
i- 9ypoproliferative ! Renal disease, endocrine disease".
ii- Aplastic anemia.
c- ,egaloplastic anemia: ! Incraesed ,*> ":
i- Anemia due to ?1., folic acid, or copper
deficiency.
/- Anemia due to e'cessive red cell destruction: ! 9emolytic anemia"
*linical picture of anemia:
1. ,ild anemia may e discovered accidentally during routine
laoratory tests, it may not give rise to symptoms. Symptoms
depend upon the severity and duration of anemia.
.. Symptoms associated with moderate or severe anemia include
fatigue, wea#ness, loss of energy, reathlessness, di@@iness,
headache, spots on vision, irritaility, amenorrhea and tachycardia
!particularly with physical e'ertion". 9owever, ecause of the
intrinsic compensatory mechanisms !changes in the cardiac output
and regional lood flow", the gradual onset of anemia particularly in
young patients may not e associated with signs or symptoms until
the anemia is severe: Whemogloin I < to 4 g:dHX.
/. Symptoms and signs associated with specific types of anemia:
a- Iron deficiency anemia: Associated with smooth tongue, spoon
nails, low serum iron, microcytic hypochromic anemia.
52
- ?1. deficiency: GI% involvement, *DS involvement, low ?1.
level, megalolastic anemia.
c- Aplastic anemia: &atient may give history of e'posure to
to'ines, hypoplastic one marrow.
d- 9emolytic anemia: Acute hemolysis is associated with
increased indirect iliruin, e'cess uroilinogen in urine and stools,
increased reticulocytic count, hyperplastic one marrow.
Haoratory evaluation:
%o diagnose anemia, routine investigations include:
1. *?*U complete lood picture including:
9emogloin: !normal 9: 1/-14 gm:dl for males, and 1.-1A
gm:dl for females".
R?*s count: 1,1$5 555 - 1, J55 555: mmY.
9ematocrite value: &ac#ed cell volume:
- ,ales: 1.-$.6.
- +emales: /<-146.
Red lood cell indices:
- ,*9: ,ean corpuscular hemogloin! .4-// pg".
- ,*>: ,ean corpuscular volume! 4A-J4 ugY".
Reticulocytic count ! normally 1-.6".
.. Iron supply studies: Serum iron, total iron inding capacity.
/. ?one marrow e'amination y aspiration or iopsy.
*riteria for diagnosis of anemia are:
,ales:
R?*s count I 1.1$ million: mmY.
9emogloin I 1/ gm:dl.
9ematocrite I 1.6.
+emales:
R?*s count I 1.1$ million: mmY.
9emogloin I 1. gm:dl.
53
9ematocrite I /<6.
Iron deficiency anemia
Stages:
Iron deficiency anemia passes into a stage of negative iron alance !Iron
loss e'ceeds gain", then one marrow iron stores ecome e'hausted,
microcytic cells start to appear in lood, then lastly iron deficiency
anemia.
*auses of Iron deficiency anemia:
1. Increased iron demand: &regnancy, and rapid growth in infants.
.. Increased iron loss: ,enses, piles, lood donation.
/. )ecreased iron inta#e !inade;uate diet", or asorption
!malasorption".
*linical picture of Iron ) A:
In addition to the usual signs and symptoms of anemia: pallor,
wea#nessR *heilosis !fissures at the corners of the mouth", glossitis
and #oilonychia !spooning of the fingernails" are signs of advanced
tissue iron deficiency.
%he diagnosis of iron deficiency is typically ased on laoratory results.
Haoratory diagnosis:
Reduced serum iron: Dormally iron circulates in plasma ound to
a protein !transferring", reduction of iron increases inding
capacity of the protein !%I?*".
,icrocytic hypochromic anemia in peripheral lood.
Reduced serum ferritin: Iron is stored in the tissues ound to a
protein as ferritin, which reflects tissue iron stores.
?one marrow aspiration: showing changes in erythroid :
granulocyte ratio.
54
%reatment of Iron deficiency anemia:
1. 3ral iron therapy:
+errous sulphate.
+errous fumarate.
D.?: Iron preparations may cause gastric upsets, vomiting,
constipation, and adominal pain.
.. &arenteral iron therapy: Is used for patients who cannot tolerate
oral iron, or need more iron supply.
/. Red cell transfusion: pac#ed R?*s transfusion is used in patients
with severe anemia, unstale cardiovascular system, cells are
given as iron stores to e reused.
Aplastic anemia
Aplastic anemia is pancytopenia with one marrow hypocellularity. A
common occurrence of marrow hypocellularity after intensive cytoto'ic
chemotherapy for cancer.
2tiology:
Radiation: Duclear accidents.
*hemicals: ?en@ene causes aplastic anemia, acute leu#emia, and
lood and marrow anormalities.
)rugs: *ytoto'ic drugs, chloramphenicol, insecticides, DSAI)S,
antiiotics, sulphonamides.
Infections: 9epatitis is the most common preceding infection,
patients are usually young men who have recovered from a mild
out of liver inflammation 1 to . months earlierB the suse;uent
pancytopenia is very severe.
*ongenital or inherited disease.
*linical features:
55
?leeding is the most common early symptomB a complaint of
days to wee#s of easy ruising, oo@ing from the gums, nose
leeds, heavy menstrual flow, and sometimes petechiae will have
een noticed.
Cith thromocytopenia, massive hemorrhage is unusual, ut
small amounts of leeding in the central nervous system can
result in catastrophic intracranial or retinal hemorrhage.
Symptoms of anemia are also fre;uent, including lassitude,
wea#ness, shortness of reath, and a pounding sensation in the
ears.
Infection is an unusual first symptom in aplastic anemia !unli#e in
agranulocytosis, where pharyngitis, anorectal infection, or fran#
sepsis occur early".
&atients often feel and loo# remar#aly well despite drastically
reduced lood counts.
Systemic complaints and weight loss should point to other
etiologies of pancytopenia.
9istory of drug use, chemical e'posure, and preceding viral
illnesses is usually found.
&hysical 2'amination: &etechiae and ecchymoses are often
present, and retinal hemorrhages may e present. &allor of the
s#in and mucous memranes is common.
Haoratory study:
&ancytopenia in peripheral lood.
9ypocellular one marrow.
%reatment:
)iscontinue drugs that may e responsile for one marrow
depression.
?one marrow transplantation: the est therapy in young adults.
Immunosuppressive drugs may induce recovery, may e
comined with transplantation.
56
Supportive treatment: %reatment of infection, R?*s and platelet
transfusion to maintain their count.
9emolytic anemia
)efinition:
Dormal life span of R?*s is 1.5 days, when they age they are destroyed
y the Reticuloendothelial system mainly in the spleen, the main feature
of hemolysis is shortened R?*s life span, hemolytic anemia results
when one marrow cannot compensate for R?*s destruction.
*auses:
a- 9emolysis due to an e'trinsic cause:
i- 9ypersplenism.
ii- Autoimmune hemolytic anemia.
- 9emolysis due to a defect in the R?*s:
i- ,emrane defect !&orphyria"
ii- 2n@yme defect ! GA&) deficiency".
iii- 9emogloin defect: !%halassemia, sic#le cell anemia"
*linical and laoratory features:
Acute hemolysis !hemolytic crisis" is uncommon, may e
accompanied y chills, fever, ac# pain, and adominal pain,
shoc#.
Increased R?*s destruction is associated with -aundice !indirect
type", and splenomegaly.
Increased reticulocytic count ! due to active one marrow".
9yperactive one marrow.
7aundice is associated with dar# stools!uroilinogen", and normal
colored urine.
&igment stones may form in the gall ladder in chronic hemolysis.
%reatment according to the cause of hemolysis.
57
&urpura E coagulation defects
&urpura: Small !/ mm" red lesions in the s#in, due to
e'travasation of red lood cells into the dermis, the lesions do not
lanch with pressure. It may e palpale !raised over the surface",
or non-palpale.
&etechiae: Smaller lesions ! . mm ".
*auses of purpura:
1. &rimary s#in disease: trauma, solar, steroids.
.. Systemic disease:
Don-palpale:
&latelet defect: %hromocytopenia, anormal
platelet function.
*lotting factor defect.
>ascular fragility: Amyloidosis, scurvy.
%hromi: %hromotic thromocytopenic purpura
!%%&", )I*.
2molic: +at emolism.
&alpale:
>asculitis: &olyarteritis nodosa, allergic vasculitis
!9enoch-Schonlein purpura".
2molic: Acute meningococcemia.
%hromocytopenia:
58
Reduction of the platelet numer, which may e due to failure of
production as in cases of marrow aplasia, firosis, or infiltration with
malignant cells, increased destruction as in idiopathic
thromocytopenic purpura !I%&", or increased splenic se;uestration,
when the spleen enlarges, the fraction of se;uestered platelets
increases, lowering the platelet count. %he most common cause of
splenomegaly is portal hypertension secondary to liver disease.
)rug induced thromocytopenia
)rugs causing reduction of platelets are antiiotics li#e sulpha drugs,
penicillin, cephalosporins, thia@ide diuretics, heparin or cytoto'ic drugs.
%he mechanism is either depression of mega#aryocyte production !e.g
cytoto'ic drugs", or through an immune response !most drugs".
,ost patients recover after drug withdrawal <-15 days.
Symptoms and signs of thromocytopenia:
?leeding into the s#in !petechiae, ecchymoses, and purpura".
?leeding from mucous memranes !epista'is, GI tract, genitourinary
and vaginal leeding".
*DS leeding is uncommonB leeding into the -oints is rare.

Idiopathic thromocytopenic purpura:
Acute I%& is common in children and accounts for J56 of the pediatric
cases of immunologic thromocytopenia. It is usually self limiting.
*hronic I%&: Comen age .5 to 15 are afflicted most commonly and
outnumer men y a ratio of /:1. %hey may present with an arupt fall in
platelet count and leeding similar to patients with acute I%&.
59
%hese patients have an autoimmune disorder with antiodies directed
against target antigens in the platelets.
?one marrow e'amination shows aundant mega#aryocytes.
%reatment: *orticosteroids, splenectomy.
)rug induced platelet dysfunction:
DSAI)s, antihistaminics, antidepressants, inhiit platelet aggregation,
causing prolongation of leeding time.
So aspirin is used as a prophylactic treatment of ischemic heart disease
to prevent platelet aggregation and thromus formation.
9enoch-Schonlein purpura : !Anaphylactoid purpura"
It is a systemic vasculitis syndrome that is characteri@ed y palpale
purpura !most commonly distriuted over the uttoc#s and lower
e'tremities", arthralgias, gastrointestinal signs and symptoms, and
glomerulonephritis. It is a small vessel vasculitis.
2tiology:
%he disease is usually seen in childrenB most patients range in age from
1 to < yearsB however, the disease may also e seen in infants and
adults, it is an immune comple' disease triggered y upper respiratory
tract infection, drugs, or immunisations.
Symptoms:
%he typical palpale purpura is seen in virtually all patientsB most
patients develop polyarthralgias in the asence of fran# arthritis.
Gastrointestinal involvement, which is seen in almost <56 of pediatric
patients, is characteri@ed y colic#y adominal pain usually associated
with nausea, vomiting, diarrhea, or constipation and is fre;uently
accompanied y the passage of lood and mucus per rectum. %he renal
involvement is usually characteri@ed y mild glomerulonephritis leading
60
to proteinuria and microscopic hematuria, renal failure is the most
common cause of death which rarely occurs in those patients.
%reatment:
,ost patients recover without treatment, corticosteroids may e
needed.
*oagulation defects
Inherited plasma coagulation disorders are due to defects in
single coagulation proteins, with the two F-lin#ed disorders,
factors 4 and J deficiency.
Ac;uired coagulation disorders:
- disseminated intravascular coagulation !)I*".
- %he hemorrhagic diathesis of liver disease.
- >itamin L deficiency and complications of anticoagulants.
9ereditary coagulation disorders
%he hemophilias:
?leeding disorder due to inherited deficiencies of coagulation factors,
most commonly is factor 4 or factor J.
9emophilia is inherited as '- lin#ed trait, male patients only develop the
disease, while females carriers transmitt the anormal gene.
Symptoms:
Start in early childhood, persist through life, leeding develop from
trivial in-ury causing pathognomonic leeding manifestations
!9emarthrosis, hematomas, hematuria".
61
)iagnosis: )efective factor 4 or J, prolonged &%%.
%reatment:
+actor 4 transfusion.
Ac;uired coagulation disorders
1- )eficiency of the vitamine L dependent coagulation
factors:
%here is comined dficiency of factors <,J, 15 and prothromin,
which are synthesi@ed in the liver y a process that re;uires
vitamine L.
*auses:
*hronic liver diseases !*holestatic -aundice".
3ral anticoagulant drugs as warfarin and dicumarol which
compete for vitamin L.
Antiiotics causing gut sterilsation !normal source of vitamin L".
*linical picture:
?leeding in the s#in ecchymosis, ruises.
9ematemesis and melena.

Haoratory:
&rolonged &%%!partial thromoplastin time" and prothromin time.
%reatment:
%reat the underlying cause.
>itamin L orally, I>, or I, is effective for overdose of oral
anticoagulants and vitamin L deficiency.
+resh fro@en plasma is a rapid treatment to control leeding until
vitamin L ta#es effect.
62
.- )isseminated intravascular coagulopathy !)I*":
A coagulation disorder resulting from widespread activation of the
clotting mechanism.
2tiology:
Activation of the clotting mechanism y tissue or acterial products
introduced in the lood stream, results in e'tensive firin deposition on
the arterial surfaces, depleting firinogen, prothromin, factor $ and <
and platelets, hence the name consumption coagulopathy.
Cith the formation of firinogen degradation products.
Sustances causing this condition:
%issue products from missed aortion, carcinoma, ischemic
tissue following acute in-ury, urns, or shoc#.
?acterial endoto'in in gram negative sepsis.
Hipid sustances from hemolysed R?*s in hemolytic anemia.

*linical picture:
,ucosal leeding and generali@ed ecchymoses leading to shoc#.
Renal necrosis from vascular thromi, resulting in oliguria or
renal shutdown.
>enous thromposis may develop.
Haoratory findings:
)ecreased levels of factor $, 4, and firinogen.
&rolonged &% and &%%.
)ecreased platelet count.
Increased +)&! firin degradation products".
)iagnosis:
)I* is suspected if leeding occurs in a case of postoperative
infection, complicated pregnancy, cancer patients.
%reatment:
63
%reatment of the underlying cause.
Supportive treatment: platelet transfusion, plasma transfusion.
Renal thromposis can e treated with heparin anticoagulation
!after control of leeding".