The Compendium May 1996
PERSPECTIVES IN VETERINARY MEDICINE
Feline Trypsinlike Immunoreactivity
in Feline Exocrine Pancreatic Disease
Jörg M. Steiner,
MedVet, DrMedVet
David A. Williams,
MA, VetMB, PhD, MRCVS
Diplomate, ACVIM
Gastrointestinal Laboratory
Department of Veterinary
Clinical Sciences
School of Veterinary Medicine
Purdue University
West Lafayette, Indiana
D
iseases of the exo-
crine pancreas have
always been consid-
ered to be much less common
in cats than in humans or dogs.
However, one recent retrospec-
tive study reported significant
pathologic lesions in 1.3% of
6504 feline pancreata and in
1.7% of 9342 canine pancreata
at postmortem examination.1
Nevertheless, diseases of the
exocrine pancreas in feline pa-
tients are infrequently diag-
nosed, possibly because of the
vague clinical signs of pancre-
atic disease in cats. A low index
of suspicion for pancreatic dis-
orders in cats may also con-
tribute, but the lack of a sensi-
tive and specific marker for
pancreatic disease in cats may
be the most important reason
for the infrequent diagnosis. A
newly developed assay for fe-
line trypsinlike immunoreactivi-
ty (fTLI) shows promise for the
Spring Feline Focus
diagnosis of exocrine pancreat-
ic insufficiency as well as pan-
creatitis in cats.
Feline Pancreatitis
Pancreatitis is an inflamma-
tory condition and is the most
common disorder of the feline
exocrine pancreas. Pancreatitis
is classified as acute or chronic;
in chronic cases, fibrosis is
found during histopathologic
evaluation. Acute or chronic
pancreatitis can be mild or se-
vere, depending on whether
systemic complications are pres-
ent. The causes of most cases
of pancreatitis in cats are un-
known. Some cases have been
associated with severe abdomi-
nal trauma (high-rise syndrome
or automobile accidents), infec-
tion (herpesvirus 1, feline infec-
tious peritonitis virus, Toxo-
plasma gondii, or Amphimerus
pseudofelineus), cholangitis,
cholangiohepatitis, or organo-
phosphate or drug toxicity.2
Whatever the cause, pancre-
atic zymogens are activated
within acinar cells, thus initiat-
ing a pathophysiologic cascade
in the pancreas as well as in
distant organs. As mentioned,
the clinical presentation is
vague3 (Table One). Vomiting
and abdominal pain are the
most consistent clinical signs in
dogs and humans suffering
from pancreatitis.4 In contrast,
vomiting and signs of abdomi-
V
nal pain are found only occa-
sionally in affected cats. Hema-
tologic abnormalities are un-
common and nonspecific.
Serum biochemical abnormali-
ties can include mild elevations
of alanine transaminase, serum
alkaline phosphatase, and
bilirubin—probably reflecting
secondary hepatic changes.5
Azotemia is also common and
is usually attributable to dehy-
dration. Abnormal urinalysis
findings are unusual and if pre-
sent are nonspecific.
Radiographic abnormalities
can be present but are often
■ Tests for trypsinlike immunoreactivity are
species specific.
KEY POINTS
■ An assay for feline trypsinlike immunoreactivity
is available.
■ The feline assay is useful for the diagnosis of
pancreatitis and exocrine pancreatic insufficien-
cy in cats.
subtle, and their interpretation
is subjective. Decreased con-
trast in the cranial abdomen, di-
lated and gas-filled small in-
testines, and transposition of
the duodenum, stomach, and
transverse colon are commonly
reported.3,6 The only ultrasono-
graphic abnormality in the ab-
domen that is reported with
some frequency is a mass ef-
fect in the cranial abdomen.3
The measurement of serum
Small Animal
lipase and amylase activities is
not useful in the diagnosis of
pancreatitis in cats. Even
though serum lipase was re-
portedly increased and serum
amylase decreased in six cases
of experimentally induced pan-
creatitis in cats, this finding has
not been confirmed in sponta-
neous cases of pancreatitis.7 In
a recent study of 12 cats with
severe pancreatitis, serum li-
pase as well as serum amylase
concentrations in all of the ani-
mals were within the reference
range.8
Exocrine Pancreatic
Insufficiency
Exocrine pancreatic insuffi-
ciency results from inadequate
secretion of digestive enzymes
by the pancreas. Most of the fe-
line cases result from loss of
acinar cells because of chronic
pancreatitis.9 Other causes of
exocrine pancreatic insufficien-
cy in cats are rarely reported
but include Eurytrema procyo-
nis infection and obstruction of
Small Animal
the pancreatic duct by a pan-
creatic or other abdominal
mass.
Clinical signs probably do
not occur before more than
90% of the pancreatic exocrine
function is lost. The most com-
monly reported clinical signs in
affected cats are polyphagia,
weight loss, diarrhea, and
steatorrhea.2,9 Greasy soiling of
the haircoat secondary to steat-
orrhea may be observed (Figure
1). Vitamin K–responsive coag-
ulopathy has been reported as a
complication of severe fat mal-
absorption secondary to exo-
crine pancreatic insufficiency in
cats. Emaciation is often the
only abnormal finding on physi-
cal examination. Diagnostic
imaging offers little help.
The complete blood count is
usually unremarkable. The
serum chemistry profile may
show a mild increase in alanine
transaminase or serum alkaline
phosphatase, as well as a mild
decrease in serum cholesterol
or triglyceride concentrations.
Neither the increase in liver en-
zymes nor the decrease in
serum lipids is consistent or
specific. Serum cobalamin con-
Figure 1A
Figure 1—A cat with diagnosed exocrine pancreatic insufficiency. (A) The cat was presented be-
cause of weight loss and diarrhea. Note the greasy soiling of the haircoat at presentation. (B) The
same patient after enzyme supplementation.
centration is severely subnor-
mal in most cases.10
Several tests have been pro-
posed for the estimation of exo-
crine pancreatic function. The
bentiromide test and the plas-
ma turbidity test have been
suggested. Feces have been
evaluated microscopically for
undigested fat, starch, or mus-
cle fibers; fecal proteolytic ac-
tivity has been assayed. Most of
these tests, however, are either
impractical or unreliable.
The most reliable of these
tests is the assay of fecal proteo-
lytic activity; an azoprotein or
radial enzyme diffusion method
is used. Analysis of three con-
secutive fecal samples is neces-
sary to achieve reasonable
specificity. Fecal proteolytic
activity is labile, and samples
must therefore be frozen imme-
diately and shipped overnight to
avoid falsely low readings.
Feline Trypsinlike
Immunoreactivity
Assays for trypsinlike im-
munoreactivity in serum are
well established for the diagno-
sis of exocrine pancreatic dis-
ease in humans and dogs. Early
Figure 1B
The Compendium May 1996
TABLE ONE
Clinical Signs in 40 Cats with
Pancreatitis Confirmed at Necropsya
Clinical Sign Percentage of Cats Affected
Lethargy 100
Anorexia 97
Dehydration 92
Hypothermia 68
Vomiting 35
Abdominal pain 25
Palpable abdominal mass 23
Dyspnea 20
Ataxia 15
Diarrhea 15
a
Data from Hill RC, Van Winkle TJ: Acute necrotizing pancreatitis and
acute suppurative pancreatitis in the cat: A retrospective study of 40 cas-
es (1976–1989). J Vet Intern Med 7:25–33, 1993.
attempts to develop catalytic proteolytic enzymes into the
assays to estimate the proteo- bloodstream. The immuno-
lytic activity from the pancreas assays, however, are species
were disappointing. Subse- specific; assays developed for
quently, immunoassays proved dogs or humans cannot be
reliable in detecting leakage of used for cats.
Recently, a radioimmuno-
assay for the determination of
feline trypsinlike immunoreac-
tivity (see the box) has been es-
tablished and validated.10 The
control range of this assay is 17
to 49 µg/L.10
The normal pancreas leaks a
small amount of trypsinogen
into the vascular space. The as-
say for trypsinlike immunoreac-
tivity measures trypsinogen
plus trypsin because of their
structural similarity.
In cases of pancreatitis, cap-
illary permeability is greatly in-
creased and large amounts of
inappropriately activated en-
zymes leak into the blood-
Small Animal
ASSAY FOR FELINE
TRYPSINLIKE
IMMUNOREACTIVITY
The assay for feline
trypsinlike
immunoreactivity is
currently available only
through the
Gastrointestinal
Laboratory at Purdue
University School of
Veterinary Medicine.
For information on
sample submission,
call 317-494-0331;
fax 317-496-1796.
stream. Even though some of
the trypsin is immediately
bound to plasma protease in-
hibitors present in serum,
trypsinlike immunoreactivity in-
creases significantly. This in-
crease has been found in hu-
mans and in dogs.
A recent report has shown
similar findings in cats suffering
from severe pancreatitis.8 The
feline serum trypsinlike im-
munoreactivity of 12 cats suf-
fering from severe pancreatitis
ranged from 14.8 to 540.0
µg/L, with a mean of 100.1
µg/L.8 Figure 2 shows the pan-
creas of one of the cats from
this report. Feline trypsinlike
immunoreactivity was signifi-
cantly higher in the 12 cats with
pancreatitis than in control cats
or cats with nonpancreatic dis-
ease.8
In cases of exocrine pancre-
atic insufficiency, when the
pancreas is secreting insuffi-
cient amounts of digestive en-
zymes into the duodenum, the
The Compendium May 1996
amount of trypsinogen leaking
into the vascular space also de-
creases dramatically. This de-
crease is the basis for the use
of serum trypsinlike immuno-
reactivity for the diagnosis of
exocrine pancreatic insufficien-
cy.11 A recent report suggests
that feline trypsinlike im-
munoreactivity is also useful for
diagnosis of exocrine pancreat-
ic insufficiency in cats.10
From 500 samples of pa-
tients’ serum evaluated at the
Gastrointestinal Laboratory at
Purdue University, 11 samples
had significantly decreased fe-
line trypsinlike immunoreactivi-
ty (≤8 µg/L). The medical
records of these 11 cats were
evaluated retrospectively. All 11
had clinical signs compatible
with exocrine pancreatic insuffi-
ciency (e.g., weight loss; soft,
voluminous stool; or greasy
soiling of the haircoat). Fecal
proteolytic activity was as-
sessed for five of the cats and
found to be negligible for all five.
Histopathologic examination
of biopsy samples from the Figure 2—This pancreas was taken from a cat with severe pan-
pancreas of three of the ani- creatitis. Note the areas of necrosis in the pancreas and in the
peripancreatic fat. The feline trypsinlike immunoreactivity of
mals was performed. In all
this cat was 75.2 µg/L. (Courtesy of T. Van Winkle, VMD,
three cases, pancreatic acinar University of Pennsylvania, Philadelphia, PA)
tissue was markedly decreased.
Nine of the 11 cats showed a
favorable response to therapy.
The other two died shortly after
diagnosis. Because pancreatic
biopsy had been performed for
both of these cats, however, the
diagnosis of exocrine pancreat-
ic insufficiency was confirmed
for all 11 cats.
Figure 3 shows the serum fe-
line trypsinlike immunoreactivi-
ty of these 11 cats. These re-
sults suggest that the test is
highly specific for the diagnosis
of feline exocrine pancreatic in-
Figure 3—The serum feline trypsinlike immunoreactivity
sufficiency. However, further (fTLI) of the 21 normal cats used to establish the control range
clinical research is needed to as well as the results for the 11 cats with a presumptive diagno-
determine its sensitivity. Never- sis of feline exocrine pancreatic insufficiency (EPI).
The Compendium May 1996
theless, the newly developed assay for feline trypsinlike immunore-
activity appears to be useful for the diagnosis of pancreatitis in cats
and highly specific for the diagnosis of feline exocrine pancreatic in-
sufficiency.
References
1. Hänichen T, Minkus G: Retrospektive Studie zur Pathologie der
Erkrankungen des exokrinen Pankreas bei Hund und Katze. Tierärztl
Umschau 45:363–368, 1990.
2. Dill-Macky E: Pancreatic diseases of cats. Compend Contin Educ Pract
Vet 15(4):589–598, 1993.
3. Hill RC, Van Winkle TJ: Acute necrotizing pancreatitis and acute sup-
purative pancreatitis in the cat: A retrospective study of 40 cases
(1976–1989). J Vet Intern Med 7:25–33, 1993.
4. Williams DA: Exocrine pancreatic disease, in Ettinger SJ, Feldman EC
(eds): Textbook of Veterinary Internal Medicine, ed 4. Philadelphia, WB
Saunders Co, 1994, pp 1372–1392.
5. Akol KG, Washabau RJ, Saunders HM, Hendrick MJ: Acute pancreati-
Small Animal
tis in cats with hepatic lipidosis. J Vet Intern Med 7:205–209, 1993.
6. Garvey MS, Zawie DA: Feline pancreatic disease. Vet Clin North Am
Small Anim Pract 14:1231–1246, 1984.
7. Kitchell BE, Strombeck DR, Cullen J, Harrold D: Clinical and pathologic
changes in experimentally induced acute pancreatitis in cats. Am J Vet
Res 47:1170–1173, 1986.
8. Parent C, Washabau RJ, Williams DA, et al: Serum trypsin-like im-
munoreactivity, amylase and lipase in the diagnosis of feline acute
pancreatitis (abstract). J Vet Intern Med 9:194, 1995.
9. Williams DA: Feline exocrine pancreatic insufficiency, in Kirk RW,
Bonagura JD (eds): Current Veterinary Therapy. XII. Philadelphia, WB
Saunders Co, 1995, pp 732–735.
10. Steiner JM, Williams DA: Validation of a radioimmunoassay for feline
trypsin-like immunoreactivity (fTLI) and serum cobalamin and folate
concentrations in cats with exocrine pancreatic insufficiency (EPI) (ab-
stract). J Vet Intern Med 9:193, 1995.
11. Williams DA, Batt RM: Sensitivity and specificity of radioimmunoassay
of serum trypsin-like immunoreactivity for the diagnosis of canine en-
docrine pancreatic insufficiency. JAVMA 192:195–201, 1988.