Exocrine pancreatic insufficiency (EPI) is a syndrome caused by insufficient synthesis and secretion of digestive enzymes by the exocrine portion of the pancreas.
EPI is less common than pancreatitis in both dogs and cats; however, it is the second most common exocrine pancreatic disorder in both species.
Etiology and Pathophysiology of Exocrine Pancreatic Insufficiency in Dogs and Cats
Pancreatic acinar atrophy is the most common cause of exocrine pancreatic insufficiency in German Shepherd Dogs, "rough" Collies, and Eurasiers (Eurasians), whereas chronic pancreatitis is the most common cause in dogs of other breeds and in cats.
Rare causes of EPI in dogs and cats are pancreatic and extrapancreatic masses that lead to obstruction of the pancreatic duct.
Pathogenesis of Exocrine Pancreatic Insufficiency in Dogs and Cats
The exocrine pancreas has a remarkable functional reserve, approximately 90% or more of which must be lost before clinical signs of EPI develop.
Pancreatic acinar enzymes play an integral role in the assimilation of all major macronutrients, and a lack of pancreatic digestive enzymes leads primarily to maldigestion. However, animals with EPI also show evidence of malabsorption, the pathogenetic basis of which is less well understood. The nutrients remaining in the intestinal lumen lead to loose, voluminous feces and steatorrhea.
The lack of absorption of nutrients also causes weight loss and can lead to vitamin deficiencies.
In animals with EPI caused by chronic pancreatitis, destruction of pancreatic tissue may not be limited to the acinar cells, and concurrent diabetes mellitus may develop.
Cobalamin absorption depends on adequate synthesis and secretion of intrinsic factor. In both dogs and cats, most intrinsic factor is synthesized and secreted by the exocrine pancreas, and most dogs and almost all cats with EPI are cobalamin deficient. Also, in a study of dogs with EPI, cobalamin deficiency was the only independent risk factor for poor outcome (1).
Pearls & Pitfalls
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Other hypovitaminoses have also been reported in animals with EPI (2). For example, vitamin K deficiency leading to a coagulopathy has been reported in a few cats with EPI (3).
Epidemiology of Exocrine Pancreatic Insufficiency in Dogs and Cats
Exocrine pancreatic insufficiency due to pancreatic acinar atrophy is most frequent in young adult German Shepherd Dogs but has also been described in rough Collies and Eurasiers.
Dogs with EPI due to other causes and cats can be of any age and breed.
Clinical Findings of Exocrine Pancreatic Insufficiency in Dogs and Cats
Clinical signs of EPI most commonly reported are weight loss and loose stools; in addition, dogs also commonly have polyphagia.
Vomiting and anorexia are observed in some patients and may be a sign of concurrent conditions rather than of EPI itself.
Feces are most commonly pale, loose, and voluminous and may be malodorous. In rare cases, watery diarrhea can be observed.
In a small portion of cats with EPI, the high fat content of the feces can lead to a greasy appearance of the coat, especially in the perianal and tail region.
Diagnosis of Exocrine Pancreatic Insufficiency in Dogs and Cats
Measurement of serum trypsin-like immunoreactivity
Measurement of serum cobalamin and folate concentrations
A low serum trypsin-like immunoreactivity (TLI) concentration (≤ 5.5 mcg/L in dogs or ≤ 8.0 mcg/L in cats) is diagnostic for exocrine pancreatic insufficiency.
Because digestion of a macronutrient can often be accomplished by more than one enzyme, lack of exocrine pancreatic secretions does not necessarily lead to clinical signs. For example, subclinical EPI has been reported in several German Shepherd Dogs. These dogs had severely decreased serum TLI concentrations and a lack of exocrine pancreatic tissue but no or only intermittent clinical signs of EPI.
An assay that measures fecal elastase in dogs has been validated. Unfortunately, some healthy dogs or dogs with chronic small intestinal disease may have a severely decreased fecal elastase concentration, making this test much less reliable than serum TLI concentration.
Serum cobalamin and folate concentrations should be routinely evaluated in small animals with suspected EPI.
Treatment of Exocrine Pancreatic Insufficiency in Dogs and Cats
Pancreatic enzyme replacement therapy (PERT)
Cobalamin supplementation
Dietary change
Most dogs and cats with exocrine pancreatic insufficiency can be successfully managed by PERT.
Various enzyme formulations for PERT are available. Powders are more effective than tablets, capsules, and especially enteric-coated products.
Initially, for dogs, 1 teaspoon/10 kg body weight should be given in food with each meal, and for cats, 1 teaspoon/cat in food with each meal.
Fresh pancreatic tissue may be a viable alternative to the use of powder; 30–90 g (1–3 ounces) of raw chopped pancreas can replace 1 teaspoon of pancreatic extract. Raw pancreas can be kept frozen for several months without loss of enzymatic activity.
Preincubation of the food with pancreatic enzymes or supplementation with bile salts is not necessary.
Once clinical signs have completely resolved, the dose can be slowly decreased until the lowest effective dose has been reached. However, the lowest effective dose can vary between enzyme batches. In one study, oral bleeding was reported in 3 of 25 dogs with EPI treated with pancreatic enzyme supplements; bleeding stopped in all three dogs after the dose was decreased (4). Moistening the food and pancreatic powder mix may also decrease the frequency of this adverse effect.
Even though PERT decreases clinical signs in almost all animals, nutrient absorption, especially that of fats, is not normalized. Feeding low-fat diets to accommodate impaired fat digestion has been suggested; however, this may further decrease fat assimilation and lead to deficiencies of fat-soluble vitamins and/or essential fatty acids and is thus not recommended.
Some types of dietary fiber interfere with pancreatic enzyme activity, and a diet low in insoluble or nonfermentable fiber should be fed. In contrast, fermentable fiber (eg, fructooligosaccharides, beet pulp, or similar) can be given.
Enzyme supplementation alone may not lead to complete resolution of clinical signs; cobalamin deficiency should be considered as a possible cause.
Dogs and cats with cobalamin deficiency, suggested by a severely decreased serum cobalamin concentration, should be supplemented with cobalamin, either parenterally (dogs: 25 mcg/kg, SC, once weekly; cats: 250 mcg/cat, SC, once weekly) or orally (dogs: 25 mcg/kg, PO, every 24 hours; cats: 250 mcg/cat, PO, every 24 hours).
Some animals may not respond to enzyme supplementation and cobalamin therapy and likely have concurrent small intestinal disease. Animals with EPI commonly have concurrent small intestinal dysbiosis and may benefit from antimicrobial therapy (eg, tylosin) or fecal microbiota transplantation (FMT). Chronic inflammatory enteropathy (often referred to as inflammatory bowel disease) also occurs in some animals with EPI.
Although antacid therapy is unnecessary in most cases of EPI, in patients that do not respond to PERT, administration of a proton pump inhibitor (eg, omeprazole, 0.7–1.0 mg/kg, every 12 hours) can be tried to prevent inactivation of pancreatic enzymes during transit to the small intestine.
Prognosis of Exocrine Pancreatic Insufficiency in Dogs and Cats
Exocrine pancreatic insufficiency results from an irreversible loss of pancreatic acinar tissue in most cases, and recovery is rare. However, with appropriate management and monitoring, affected animals usually gain weight quickly, pass normal feces, and can live a normal life for a normal lifespan.
Key Points
Exocrine pancreatic insufficiency is diagnosed by measurement of serum trypsin-like immunoreactivity concentration.
Treatment of dogs and cats with EPI includes pancreatic enzyme replacement therapy and cobalamin supplementation.
For More Information
Serum trypsin-like immunoreactivity (TLI). Texas A&M University Gastrointestinal Laboratory.
Serum cobalamin (vitamin B12 and folate). Texas A&M University Gastrointestinal Laboratory.
Also see pet owner content regarding disorders of the pancreas in cats and dogs.
References
Batchelor DJ, Noble PJ, Taylor RH, Cripps PJ, German AJ. Prognostic factors in canine exocrine pancreatic insufficiency: prolonged survival is likely if clinical remission is achieved. J Vet Intern Med. 2007;21(1):54-60. doi:10.1111/j.1939-1676.2007.tb02928.x
Barko PC, Williams DA. Serum concentrations of lipid-soluble vitamins in dogs with exocrine pancreatic insufficiency treated with pancreatic enzymes. J Vet Intern Med. 2018;32(5):1600-1608. doi:10.1111/jvim.15292
Perry LA, Williams DA, Pidgeon G, Boosinger TR. Exocrine pancreatic insufficiency with associated coagulopathy in a cat. J Am Anim Hosp Assoc. 1991;27(1):109-114.
Rutz GM, Steiner JM, Williams DA. Oral bleeding due to pancreatic enzyme supplementation in three dogs with exocrine pancreatic insufficiency (EPI). J Am Vet Med Assoc. 2002;221(12):1714-1716. doi:10.2460/javma.2002.221.1716
