The pancreas has two separate functions within the body, often referred to as the exocrine and endocrine pancreata. The endocrine pancreas secretes hormones, including insulin and glucagon, which regulate blood glucose metabolism. The exocrine pancreas secretes zymogens and active enzymes that, ultimately, aid in digestion. Exocrine pancreatic insufficiency (EPI) is a condition of maldigestion and usually doe not involve the endocrine pancreas. In this article, we review the etiologic factors, diagnostic tools, and management recommendations for dogs with EPI.
NORMAL EXOCRINE PANCREATIC FUNCTION
The exocrine pancreas secretes many different zymogens for digesting carbohydrates, fats, and proteins (Figure 1). Protein digestion is catalyzed by the enzymes trypsin, chymotrypsin, and carboxypeptidase. These proteolytic digestive enzymes are initially released from the pancreas as the zymogens trypsinogen, chymotrypsinogen, and procarboxypeptidase, respectively, and are activated once they reach the small intestine. In the presence of chyme, enterocytes release enteropeptidase, which activates some of the trypsinogen. Additionally, the newly formed trypsin assists in activating all three zymogens. This delayed activation prevents autodigestion of pancreatic proteins. Once activated, trypsin and chymotrypsin break down proteins into smaller peptides, while carboxypeptidase further processes some of these peptides into amino acids.
Carbohydrate digestion is facilitated by pancreatic amylase secretion, which hydrolyzes most carbohydrates into disaccharides and some trisaccharides. Finally, the exocrine pancreas facilitates fat digestion by releasing the enzymes pancreatic lipase, cholesterol esterase, and phospholipase and the zymogen procolipase, which is activated by trypsin to form colipase.
Figure 1. Normal exocrine pancreatic function in animals.
Exocrine pancreatic secretions contain digestive enzymes and sodium bicarbonate in an aqueous solution. Acetylcholine and cholecystokinin stimulate the release of digestive enzymes, while secretin stimulates the release of large quantities of bicarbonate and water. The digestive enzymes are produced and secreted by the pancreatic acinar cells, while epithelial cells of the pancreatic ductules secrete bicarbonate. Once within the duodenum, sodium bicarbonate neutralizes gastric secretions.1
EXOCRINE PANCREATIC INSUFFICIENCY
In patients with EPI, inadequate production of digestive enzymes by the pancreatic acinar cells leads to maldigestion and malabsorption of nutrients. The persistence of undigested food within the small intestine often results in bacterial overgrowth, further compromising intestinal function. Fortunately, the pancreas has a high reserve capacity, so signs of maldigestion do not occur until 90% of the exocrine pancreatic function is lost.2 In rare cases of EPI in people, there is selective deficiency of individual pancreatic enzymes. Isolated lipase deficiency has been described in a single dog.3
CAUSES OF EPI
Causes of EPI include pancreatic acinar atrophy, chronic pancreatitis, pancreatic hypoplasia, and neoplasia.
Pancreatic acinar atrophy
The most common cause of EPI in dogs is pancreatic acinar atrophy. The severity of this condition ranges from subclinical disease to a complete absence of secretory capacity.2 Pancreatic acinar atrophy is thought to be an immune-mediated condition that begins with lymphocytic pancreatitis.4 Selective destruction of acinar cells with replacement by atypical parenchyma, ductal structures, and adipose tissue is seen in the late stages of the disease.
Immunohistochemical analysis of pancreatic biopsy samples from dogs with subclinical EPI reveals a predominance of intra-acinar CD4+ and CD8+ T lymphocytes, supporting an immune-mediated cause.5 Other histologic characteristics include piecemeal tissue destruction, large groups of lymphocytes that resemble lymphoid follicle germinal centers, and necrotic and apoptotic acinar cell death.4