Exocrine Pancreatic Insufficiency (EPI)

EPI occurs when the pancreas produces insufficient digestive enzymes. The disease is far more common in dogs than cats.

The most common cause is idiopathic pancreatic acinar atrophy, which according to recent studies is immune-mediated, and may be hereditary in some breeds. It is typical of young dogs under two years of age, particularly German Shepherds and Wire-Haired Collies. In middle-aged and older animals, EPI can be caused by chronic pancreatitis (the most common form in cats) or recurrent acute pancreatitis. In some cases, EPI can be secondary to diseases that interfere with pancreatic enzyme secretion (inflammation- or tumour-induced obstruction of the pancreatic duct) or with the activation of enzymes in the intestinal lumen (duodenal hyperacidity, lack of cholecystokinin, duodenal enterokinase or bile acids).

Inhibition of enzymatic activity impairs digestion and prevents nutrients from being absorbed in the small intestine. The result is an accumulation of carbohydrates and fats in the intestinal lumen with the corresponding bacterial fermentation, hydroxylation of fatty acids and precipitation of bile acids, acidification of the medium, and bacterial overgrowth.

Symptoms

The most characteristic symptom is frequent defecation (3-8 times a day) of soft, sometimes bloody, voluminous, foul-smelling stools, with steatorrhea and amylorrhea, often associated with coprophagia. Affected animals are often active, and show significant weight loss despite their voracious appetite (polyphagia).

Distended intestinal loops with semi-liquid content and borborygmi may be observed on physical examination. The severity of the symptoms will depend on the diet, the adaptive capacity of the animal’s intestines, and the extension of the disease.

Interpretation of laboratory tests

General Tests

• Complete blood count, protein profile, blood biochemistry: These tests are important to assess the animal’s overall status. Although significant alterations are rare, mild anormochromic-normocytic anaemia, hypocholesterolaemia and hypoproteinaemia can be detected.
• Coprological examination: This is a qualitative assessment of maldigestion. A series of fresh stool samples should be analysed. The test can detect the presence of fat (Sudan III staining), muscle fibres and undigested starch granules in the stool.

Specific tests

• TLI is a radioimmunoassay that is the diagnostic test of choice for EPI (an ELISA analysis technique has recently been developed) and must be species-specific.Trypsin-like immunoreactivity (TLI)
• The assay measures the trypsinogen and trypsin released by the pancreas into the intravascular space, thus giving an indirect assessment of the function of the exocrine pancreas without interference from other intestinal alterations. It is therefore a highly specific test.
  • In dogs, values less than 2.5 ng/mL are diagnostic of EPI.
    Values between 2.5 and 5 ng/mL are considered inconclusive. The test must be repeated after 5-6 days.
  • In cats, values of up to 8 ng/mL are diagnostic of EPI.

Other factors may elevate TLI values, such as kidney failure or treatment with corticosteroids in the days prior to sample extraction; however, they are not likely to interfere with the diagnosis of EPI.

• Faecal elastase-1 assay: A novel monoclonal antibody ELISA test that quantifies levels of elastase-1. It has the advantage of being a non-invasive technique that also appears to be highly sensitive.
• Fat absorption (triglycerides): Lipaemia is measured before oral administration of vegetable oil and then re-measured every hour for 3 hours. If there is no evidence of lipaemia, the test is repeated after incubating the oil with a pancreatic enzyme supplement for 30-60 minutes. The presence of lipaemia confirms maldigestion; no lipaemia indicates malabsorption.
• Vitamin A absorption: The animal is given 200,000 IU of vitamin A orally and a blood sample is collected immediately afterwards and again 6-8 hours later. Vitamin A levels are measured in both samples. Absorption of less than three times the baseline vitamin A is a sign of malabsorption or maldigestion (the test is not specific for either).

Complementary tests

Serum cobalamin (vitamin B12) and folate: This determination is used to confirm or rule out bacterial overgrowth in the small intestine, which is frequently associated with EPI in dogs. Low serum cobalamin and elevated folate levels indicate bacterial overgrowth.

* Tests such as faecal protease activity, the bentiromide test, and faecal trypsin that were widely used a few years ago have now been superseded. Some of these techniques, such as faecal protease activity, have been updated using radial enzyme diffusion (RED) techniques, and would be useful in rare cases where TLI may give false negatives (EPI associated with acute pancreatitis or recurrent chronic pancreatitis, kidney failure without uraemia, pancreatic duct obstruction, dogs with extreme malnutrition or animals treated with corticosteroids).

Bibliography

• WILLIAMS, D.A. (2000) : Exocrine pancreatic disease. in: Ettinger-Feldman (Ed.) Textbook of Veterinary Internal Medicine. (5ª ed.) Saunders, pg. 1345-1367
• SODIKOFF, C.H. (2002) : Pruebas diagnósticas y de laboratorio en pequeños animales. (3ª ed.) Harcourt Ed., pg. 63-71
• VONDRAKOVA, K.; KLIMES, J. (2002) : Acta Vet. Brno 71, pg. 223-228
• MOELLER, E.M.; STEINER, J.M.; CLARK, L.A. et al. (2002) : Am. J. Vet. Res. 63 (10), pg. 1429-1434
• LUCENA, R.; GINEL, P.J.; NOVALES, M.; MOLLEDA, J.M. (1999) : Am. J. Vet. Res. 60 (11) pg.1357-1359
• RALLIS, T.; ADAMAMAMORAITOU, K.K.; SOUBASIS, N. (1999) : Canine Practice 24 (6) pg. 12-15
• RUTZ, G.M.; STEINER, J.M.; WILLIAMS, D.A. (2001) : Compendium on Continuing Education for the Practicing Veterinarian 23 (4) pg. 347-355
• STEINER, J.M.; WILLIAMS, D.A. (1997) : Compendium on Continuing Education for the Practicing Veterinarian 19 (7) pg, 836-848
• STEINER, J.M.; WILLIAMS, D.A. (1999) : Vet. Clin. North. Am. Small Anim. Pract. 29 (2) pg. 551-575
• STEINER, J.M.; WILLIAMS, D.A. (2000): J. Vet. Intern. Med. 14 (6) pg. 627-629
• SPILLMANN, T.; WITTKER, A.; TEIGELKAMP, S., et al. (2001) : J. Vet. Diagn. Invest. 13 (6) pg. 468-474
• WARITANI, T.; OKUNO, Y.; ASHIDA, Y. et al. (2002): Vet. Immunol. Immunopathol. 87 (1-2) pg. 41-49
• WIBERG, M.E.; NURMI, A.K.; WESTERMARCK, E. (1999) : J. Vet. Intern. Med. 13 (5) pg. 426-432
• WIBERG, M.E.; SAARI, S.A.; WESTERMARCK, E. (1999): Vet. Pathol. 36 (6) pg. 530-41
• WIBERG, M.E.; SAARI, S.A.; WESTERMARCK, E.; MERI, S. (2000): Vet. Immunol. Immunopathol. 76 (1-2) pg.103-115
• WIBERG, M.E.; WESTERMARCK, E. (2002) J. Am. Vet. Med. Assoc. 15: 220 (8) pg. 1183-1187