Exocrine Pancreatic Insufficiency

Introduction: Exocrine pancreatic insufficiency is characterized by the failure of the pancreas to secrete digestive pancreatic enzymes. Causes of EPI include pancreatic acinar atrophy (PAA), chronic pancreatitis, and pancreatic neoplasia (rare). In cats, pancreatitis is thought to be the most common cause of EPI, while in dogs acinar atrophy is most common cause. EPI results in clinical signs of maldigestion diarrhea and extreme weight loss, often despite a ravenous appetite. Diabetes mellitus may also be a clinical feature if significant damage to islet cells occurs, as may happen as a sequela to pancreatitis or pancreatic neoplasia.

Pathophysiology: The functional reserve of the pancreas is extensive. Thus, signs of pancreatic insufficiency are not seen until greater than 80-85% of the pancreatic acinar cell tissue is lost.

Failure of intraluminal digestion	Lack of pancreatic digestive enzymes causes failure of intraluminal digestion and leads to a reduction in degradation of exposed brush border proteins. The abnormal accumulation of these and other proteins may interfere with the normal absorption process. Thus, the absence of pancreatic enzymes contributes in many ways to the inability of undigested nutrients to cross the GI mucosa (maldigestion and secondary malabsorption). This build-up of undigested nutrients results in weight loss and osmotic diarrhea.
Altered function of mucosal enzymes	Mucosal enzyme pathology is not well understood. However, multiple features of EPI may contribute to the altered function of mucosal enzymes, thus altering digestion and absorption. Abnormal activity of mucosal enzymes, as well as abnormal transport of carbohydrates, amino acids, and fatty acids, leads to a failure of intraluminal digestion. Pancreatic enzymes and other hormones also normally have a trophic effect on the GI mucosa. Lack of pancreatic enzymes, insulinopenia, and hormonal changes occurring with protein cachexia and malnutrition may all contribute to changes in mucosal enzymes resulting in decreased absorption of nutrients.
Bacterial overgrowth	Small intestinal bacterial overgrowth (SIBO) is common in EPI. Pancreatic enzymes normally keep bacterial populations in check due to their antibacterial properties. The lack of these enzymes, or abnormalities of intestinal immunity or motility, cause changes in the intestinal microflora to occur. Different types of bacteria can be involved in the overgrowth. If obligate anaerobes are involved, these bacteria produce enzymes which destroy exposed brush border enzymes. This decrease in enzyme activity can cause partial villous atrophy in some cases. Regardless of which microflora are involved in the overgrowth, the abnormal numbers of bacteria may impair absorption indirectly by competing for nutrients and/or changing intraluminal biochemistry (i.e. changing conjugated bile salts). Another factor contributing to SIBO is protein malnutrition. Protein malnutrition in EPI can impair the immune response that helps regulate bacterial numbers. Thus, the pathological numbers of bacteria and their actions contribute to the clinical signs of diarrhea and weight loss. For more information on mechanisms by which SIBO causes diarrhea, click here.

Pancreas: In cases of EPI caused by PAA, the pancreas is small due to severe atrophy of acinar tissue. In cases caused by chronic pancreatitis, the pancreas is smaller than normal and nodular. Fibrous adhesions to adjacent organs may be present. Generally, no gross lesions seen in the intestine.

Pancreatic acinar atrophy (PAA) in a dog. The black arrowhead points to residual pancreatic tissue in the mesoduodenum. However, the vast majority of the pancreas is gone due to severe atrophy.

Pancreas: Histopathology will vary depending on the etiology. With PAA atrophy of acinar tissue with healthy islands of islet cells and patent exocrine ducts is present. In cases of EPI caused by chronic pancreatitis, lobules of atrophied pancreatic parenchyma are surrounded by fibrous connective tissue. Usually, no lesions are present in the GI tract. Partial villous atrophy may be seen which can occur secondarily to bacterial overgrowth.

Pancreatic atrophy and fibrosis in a cat. Small rounded lobules are surrounded by connective tissue. Image copyright Cornell College of Veterinary Medicine,

Diagnosis: A diagnosis of exocrine pancreatic insufficiency is usually made by combining the history and physical exam findings with appropriate clinical pathology findings.