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Exocrine Pancreatic Insufficiency
World Small Animal Veterinary Association World Congress Proceedings, 2003
Edward J. Hall, MA, VetMB, PhD, DECVIM-CA, MRCVS
University of Bristol, Dept. Clinical Veterinary Science
Langford, Bristol, England

Exocrine pancreatic insufficiency (EPI) is a syndrome of maldigestion and malabsorption resulting from the failure of secretion of the pancreatic enzymes necessary for the normal digestion of food. It is a relatively common problem in dogs, especially in the German shepherd breed, but is quite rare in cats. There are several potential causes of EPI, of which pancreatic acinar atrophy is the most common in dogs.

Pancreatic acinar atrophy (PAA)

This is an acquired condition, although there is likely to be a genetic predisposition in most cases; heritability has already been demonstrated in German shepherd dogs and Rough collies. Unknown factors trigger atrophy of the pancreatic acinar tissue: the endocrine tissue is largely spared, but there can be complete loss of acini and, consequently, enzyme secretion. Recent work has suggested that acinar atrophy is preceded by a lymphocytic pancreatitis. Curiously, sequential biopsy studies of lymphocytic pancreatitis have shown that some dogs progress to PAA, some resolve spontaneously, and others remain in a state of subclinical EPI. As stated above, PAA is the most common cause of EPI in dogs; it is very rare in cats. The condition usually manifests between 6 months and 6 years of age, and there is no sex predisposition. It can affect any breed of dog and even mixbreeds, but is most commonly seen in German shepherds. In several studies German shepherds comprise two-thirds of the cases identified, and affected mixbreed dogs are often of shepherd origin. Other breeds reportedly over-represented are collies, especially Rough collies, terrier breeds, Cavalier King Charles spaniels, and Chow Chows.

Pancreatic hypoplasia

Hypoplasia is a rare, congenital condition, with signs of maldigestion / malabsorption occurring before six months of age.

Chronic pancreatitis

Repeated bouts of acute pancreatitis may eventually destroy enough pancreatic functional reserve that EPI occurs. As stated, EPI is very rare in cats and when it occurs, it is usually the result of chronic pancreatitis.

Pathophysiology of malabsorption

The lack of pancreatic amylase, lipase and proteases results in maldigestion and hence malabsorption. The effect on fat digestion is the most profound as the majority of lipase is derived from the pancreas whereas there are brush border peptidases and saccharidases. The faeces are often voluminous and putty-like as the osmotic effect of undigested food is not high. The occurrence of watery diarrhoea suggests secondary bacterial overgrowth. A lack of enzymes and enriched environment allow bacterial proliferation, resulting in bile salt deconjugation and fatty acid hydroxylation, both causing colonic secretion. In addition, there may be concurrent inflammatory bowel disease.

Clinical signs

The clinical signs of EPI are related maldigestion & malabsorption. Typically there is a large volume of foul smelling, greasy, steatorrhoeic faeces. They range in consistency from putty-like to watery. As a consequence of the malabsorption there is weight loss and emaciation; stunting occurs if EPI commences before the animal is skeletally mature. And in response to the malabsorption, the patient typically is ravenously hungry: it exhibits polyphagia and coprophagia. It may vomit, probably because it scavenges. It often develops a dry, scurfy coat. As not all cases of EPI present with overt diarrhoea, a test for EPI should be performed in all cases of weight loss and suspected malabsorption before other diagnostic tests.

Sequelae

Failure to treat EPI results in progressive weight loss and emaciation. Serum protein concentrations are surprisingly well maintained, but anaemia will develop. Complications of EPI that have been reported are the development of gastric dilatation & volvulus and mesenteric torsion.

Diagnosis

The diagnosis of EPI cannot be made on clinical signs alone. Signs are typical of any cause of malabsorption (polyphagia, diarrhoea & weight loss). For example, small intestinal bacterial overgrowth and inflammatory bowel diseases can produce identical signs, and both occur more frequently in German shepherd dogs than EPI.

The definitive diagnosis of PAA can only be made by pancreatic biopsy. However, indirect tests are used to obviate the need for surgery. Historically a number of tests have been used:

 faecal proteolytic activity ("faecal trypsin")

 benzoyl-tyrosyl para-amino benzoic acid (BT-PABA) test

 oral fat tolerance test

 24 hour fat balance study

All these test are now considered obsolete because of the high rate of spurious results and the development of better tests.

Measurement of serum trypsin-like immunoreactivity (TLI) is a sensitive and specific test of pancreatic acinar atrophy and, if available, is the only test needed by practitioners to diagnose EPI. The normal pancreas leaks (or secretes?) some trypsinogen into blood; this is absent in EPI. Serum trypsinogen concentration is measured by radioimmunoassay, and the fasting TLI concentration is an indirect measure of functional exocrine tissue mass. The reference range for canine TLI is >5 to 35 µg/l. In EPI, values are typically <2.5µg/l.

Values between 2.5 to 5.0 µg/l are indicative of a dog developing EPI, or one that has subclinical EPI because of lymphocytic pancreatitis or chronic pancreatitis. It has been suggested that a TLI stimulation test, measuring cTLI after stimulation by eating, or injection of secretin or caeruletide (a cholecystokinin analogue) can be helpful in discriminating equivocal results. The original TLI test is species-specific for dogs (cTLI). This means that it is not affected by the patient being on enzyme replacement, but also that it cannot be used to diagnose EPI in cats. A TLI for cats (fTLI) is available from the USA. A fTLI <8.5 µg/l is indicative of feline EPI.

Faecal elastase, as a marker of pancreatic function can be measured using a simple ELISA assay. Elastase has good faecal stability and since the assay is canine-specific there is no cross-reaction even if the dog is on replacement therapy. It has been shown to be quite sensitive and specific, and represents the best screening test if TLI cannot be measured.

Treatment

The treatment of EPI is expensive and lifelong, and the commitment of the owner to treatment should be discussed at the outset. One study showed that the major cause of death in EPI was euthanasia because of treatment costs.

Oral pancreatic extract

The mainstay of treatment of EPI is replacement of pancreatic enzymes by oral enzyme extracts. Fresh (frozen) pancreas is an excellent source of enzymes but there is often limited availability. Approximately 100-150 g of fresh bovine or porcine pancreas is fed per meal. Of the commercial enzyme preparations available, uncoated powders have been shown to work best. Enteric-coated preparations may not dissolve because the duodenal pH is not sufficiently alkaline to dissolve the coating. However, the uncoated powders are unpleasant to handle, and may cause dermatitis of the lips as well as give the patient an unpleasant odour. The powder should be mixed with food, but pre-incubation before feeding is unnecessary.

Diet

A highly digestible food that is high in non-complex carbohydrate and protein is ideal. Historically, a fat restricted diet has been recommended. However, studies have shown that this is of no benefit, and indeed may prevent the patient gaining weight. For there is experimental evidence to show that the percentage fat absorption increases the higher the percentage of fat that is fed. Therefore, current recommendations are merely to give a good quality food. Frequent small meals are also often recommended. However, as enzyme must be given with each, it becomes counter-productive to feed more than three meals per day. In order to gain weight the patient should be fed up to 150% of the maintenance requirements of its ideal body weight in three divided meals. The third meal is dropped when the target weight is reached.

Antibiotics

Even with adequate enzyme replacement, fat absorption never normalizes, and the fat can act as a substrate for secondary bacterial overgrowth. It is therefore helpful, especially in the early stages of treatment, to give a broad-spectrum antibiotic such as oxytetracycline (10 mg/kg PO q8h). Often this treatment can be reduced or even withdrawn once the signs are controlled.

Vitamins

Dogs with EPI are often deficient in vitamin B12 (cobalamin) and vitamin E. These should be supplemented for optimum treatment, but vitamin B12 requires parenteral administration.

Failure of treatment

Assuming the correct diagnosis, treatment failure often reflects poor owner compliance. Most commonly, the owner tries to save money by giving inadequate amounts of enzyme. It should be explained that this is a false economy, especially in the early stages of treatment, but that ultimately the dosage may be reduced with continuing clinical efficacy. Secondary bacterial overgrowth must also be addressed. Finally, concurrent inflammatory bowel disease may prevent treatment success, but as immunosuppression more commonly causes the signs of EPI to worsen, it is prudent to obtain histological proof before commencing glucocorticoids.

Speaker Information
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Edward J. Hall, MA, VetMB, PhD, DECVIM-CA, MRCVS
University of Bristol, Dept. Clinical Veterinary Science
Langford, Bristol, England


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Copyright 1991- World Small Animal Veterinary Association World Congress Proceedings, 2003