Etiology and Pathogenesis
Exocrine pancreatic insufficiency (EPI) is a syndrome, which is caused by insufficient synthesis and secretion of digestive
enzymes by the exocrine portion of the pancreas, leading to insufficient activity of digestive enzymes in the lumen of the
small intestine. Pancreatic acinar atrophy is the most common cause of EPI in the dog, followed by chronic pancreatitis. In
contrast, chronic pancreatitis is the most common cause of EPI in cats and humans. Other, less common causes of EPI in dogs
and cats are pancreatic or extrapancreatic masses that lead to an obstruction of the pancreatic duct. Congenital pancreatic
hypo- or aplasia, as well as deficiencies of individual pancreatic digestive enzymes or of enteropeptidase have not been reported
in dogs and cats, but likely do occur sporadically.
In human beings it has been shown that the exocrine pancreas has a remarkable functional reserve. Ninety percent of its functional
reserve must be lost before clinical signs of EPI develop. Digestive enzymes of pancreatic acinar origin play an integral
role in the assimilation of all major components of food stuff and a lack of pancreatic digestive enzymes leads to malassimilation
in two ways. First and foremost, the digestive tract is inefficient in breaking down macromolecules when pancreatic digestive
enzymes are lacking. In addition, intestinal mucosal transport mechanisms for mono- and disaccharides, amino acids, and fatty
acids are also disturbed. The cause of this malabsorption is unknown, but it is speculated by some to be due to a lack of
trophic factors, normally secreted by the exocrine pancreas. The nutrients remaining in the intestinal lumen lead to loose
voluminous stools and steatorrhea. At the same time, a lack of nutrients causes weight loss and may lead to vitamin deficiencies
in some cases. Serum cobalamin (vitamin B12) concentrations are undetectable or markedly decreased in almost all cats and a more than 80% of dogs with EPI. Serum folate
concentrations in dogs with EPI are often increased suggesting the presence of complicating small intestinal bacterial overgrowth.
In contrast, serum folate concentrations in cats with EPI are often decreased, indicating concurrent small intestinal disease.
Secondary vitamin K responsive coagulopathy is rare in dogs and cats with EPI but has been reported and should be tested for
if a bleeding tendency is present.
In patients with EPI caused by chronic pancreatitis, destruction of pancreatic tissue may not be limited to the acinar cells
and concurrent diabetes mellitus (DM) may be observed. In most human patients with chronic pancreatitis, both exocrine and
endocrine functional reserve are ultimately lost. However, overt DM usually appears later in the disease process than does
malassimilation. At this point it is unknown whether dogs and cats with chronic pancreatitis follow the same pattern of progression,
but it is intriguing to speculate whether EPI may be common, but often undiagnosed in those dogs and cats with DM that are
difficult to regulate.
Clinical Picture and Diagnosis
Dogs with EPI due to PAA are most often young adult German Shepherd dogs, but dogs and cats with EPI due to other causes are
usually middle-aged to older and can be of any breed. Clinical signs most commonly reported in dogs and cats with EPI are
polyphagia, weight loss, and loose stools or diarrhea. Vomiting and anorexia are observed in some patients with EPI and may
indicate the presence of a concurrent condition, such as inflammatory bowel disease, rather than a primary clinical sign of
EPI. All of the clinical signs observed in patients with EPI are non-specific and are also seen in other disorders more commonly
seen in middle aged to older dogs and cats. Some common conditions causing polyphagia in middle-aged to older small animals
are hyperthyroidism in cats, corticosteroid treatment in both dogs and cats, and diabetes mellitus also in both dogs and cats.
Common differential diagnoses for dogs and cats presenting with weight loss are hyperthyroidism in cats and dental disorders,
chronic renal failure, heart failure, neoplasia, and chronic intestinal disorders, such as inflammatory bowel disease in both
dogs and cats. Finally, the most common disorders causing diarrhea in middle aged to older dogs and cats are chronic intestinal
disease, such as inflammatory bowel disease and chronic renal failure.
The feces from small animal patients with EPI are most commonly pale, loose, voluminous, and may be quite malodorous. In rare
instances these patients may also develop watery diarrhea. The high fat content of the feces can lead to a greasy appearance
of the hair coat, especially in the perianal and tail region of cats.
Results from routine blood tests are within the normal range in most cases. In a few cases lymphopenia, lymphocytosis, neutrophilia,
eosinophilia, and elevations of hepatic enzymes have been reported. Also, abdominal radiography or ultrasonography do not
show any specific changes in these patients. Several tests have been recommended to estimate exocrine pancreatic function
in dogs and cats. The bentiromide absorption test, commonly known as PABA test, plasma turbidity test, microscopic examination
of feces for undigested fat, starch, or muscle fibers, and fecal proteolytic activity (FPA), all have been recommended for
the diagnosis of EPI. With the exception of FPA, all of these tests are rather unreliable or impractical and are therefore
not recommended. Fecal proteolytic activity can be determined by either azocasein- or azoalbumin- based methods, or by a radial
enzyme diffusion method, but at least three stool samples from consecutive days should be evaluated and feces should be frozen
immediately and shipped on ice in order to prevent loss of FPA in the samples, making this test not very practical. Currently,
evaluation of FPA is only recommended in species for which a serum TLI assay is not available.
Immunoassays for the measurement of serum trypsin-like immunoreactivity (TLI) in dogs and cats have been developed and validated.
These tests are highly specific for EPI in both dogs and cats. Dogs with a serum cTLI of ≤ 2.5 µg/L and cats with a serum
fTLI ≤ 8.0 µg/L can be diagnosed with EPI, respectively. A recent report has shown that some German Shepherd dogs have subclinical
EPI with severely decreased serum cTLI concentrations. These dogs have a lack of exocrine pancreatic tissue at biopsy, but
no or only intermittent clinical signs of EPI. This highlights the remarkable functional reserve of the exocrine pancreas
and the entire gastrointestinal tract in dogs.
Recently, a new assay for measurement of fecal elastase in dogs has been developed and validated. Unfortunately, some normal
dogs or dogs with chronic small intestinal disease may have a decreased fecal elastase concentration. Because of the low incidence
of dogs with EPI a few false positive results of the assay lead to an overall large number of false positive dogs (low positive
predictive value) making this test unreliable.
Another new diagnostic test for the assessment of exocrine pancreatic function, pancreatic lipase immunoreactivity has been
developed and validated for use in dogs and cats. While serum PLI concentration is highly specific for exocrine pancreatic
function there is some minimal degree of overlap of serum cPLI concentrations between healthy dogs and dogs with EPI. Therefore,
serum cTLI and fTLI concentrations remain the diagnostic tests of choice for dogs and cats with exocrine pancreatic insufficiency,
respectively.
