Exocrine pancreatic insufficiency
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Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack of digestive enzymes made by the pancreas. EPI is found in humans afflicted with cystic fibrosis and Shwachman–Diamond syndrome, and is common in dogs. EPI is caused by a progressive loss of the pancreatic cells that make digestive enzymes; loss of digestive enzymes leads to maldigestion and malabsorption of nutrients from normal digestive processes.
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Chronic pancreatitis is the most common cause of EPI in humans and cats. In dogs, the most common cause is pancreatic acinar atrophy, arising as a result of genetic conditions, a blocked pancreatic duct, or prior infection.
The exocrine pancreas is a portion of this organ that contains clusters of ducts (acini) producing bicarbonate anion, a mild alkali, as well as an array of digestive enzymes that together empty by way of the interlobular and main pancreatic ducts into the duodenum (upper small intestine). The hormones cholecystokinin and secretin secreted by the stomach and duodenum in response to distension and the presence of food in turn stimulate the production of digestive enzymes by the exocrine pancreas. The alkalization of the duodenum neutralizes the acidic chyme produced by the stomach that is passing into it; the digestive enzymes serve to catalyze the breakdown of complex foodstuffs into smaller molecules for absorption and integration into metabolic pathways. The enzymes include proteases (trypsinogen and chymotrypsinogen), hydrolytic enzymes that cleave lipids (the lipases phospholipase A2 and lysophospholipase, and cholesterol esterase), and amylase to digest starches. EPI results from progressive failure in the exocrine function of the pancreas to provide its digestive enzymes, often in response to a genetic condition or other disease state, resulting in the inability of the animal involved to properly digest food.
Signs and symptomsEdit
Loss of pancreatic enzymes leads to maldigestion and malabsorption, which may in turn lead to:
- anemia (Vitamin B12, iron, folate deficiency)
- bleeding disorders (Vitamin K malabsorption)
- edema (hypoalbuminemia)
- flatulence and abdominal distention (bacterial fermentation of unabsorbed food)
- metabolic bone disease (Vitamin D deficiency)
- neurologic manifestation
- weight loss
Causes and pathogenesisEdit
In humans, the most common causes of EPI are chronic pancreatitis and cystic fibrosis, the former a longstanding inflammation of the pancreas altering the organ's normal structure and function that can arise as a result of malnutrition, heredity, or (in the Western world especially), behaviour (alcohol use, smoking), and the latter a recessive hereditary disease most common in Europeans and Ashkenazi Jews where the molecular culprit is an altered, CFTR-encoded chloride channel. According to WebMD, "Crohn's disease and celiac disease can also lead to EPI in some people". In children, another common cause is Shwachman-Bodian-Diamond syndrome, a rare autosomal recessive genetic disorder resulting from mutation in the SBDS gene.
The three main tests used in considering a diagnosis of EPI are: fecal elastase test, fecal fat test, and a direct pancreatic function test.  The latter is a limitedly used test that assesses exocrine function in the pancreas by inserting a tube into the small intestine to collect pancreatic secretions.
EPI is often treated with pancreatic enzyme replacement products (PERPs) such as pancrelipase, that are used to break down fats (via a lipase), proteins (via a protease), and carbohydrates (via amylase) into units that can be digested. Pancrelipase is typically porcine derived and requires large doses.
Causes and pathogenesisEdit
Chronic pancreatitis is the most common cause of EPI in cats. In dogs, where the condition has been deemed common, the usual cause is by pancreatic acinar atrophy, arising as a result of genetic conditions, a blocked pancreatic duct, or prior infection.
In dogs, EPI is most common in young German Shepherds, and in Finland Rough Collies, and is inherited. In German Shepherds, the method of inheritance is through an autosomal recessive gene. In these two breeds, at least, the cause appears to be immune-mediated as a sequela to lymphocytic pancreatitis. The German Shepherd makes up about two-thirds of cases seen with EPI. Other breeds reported to be predisposed to EPI include terrier breeds, Cavalier King Charles Spaniels, Chow Chows, and Picardy Shepherds.
In animals, signs of EPI are not present until 85 to 90 percent of the pancreas is unable to secrete its enzymes. In dogs, symptoms include weight loss, poor hair coat, flatulence, increased appetite, coprophagia, and diarrhea. Feces are often yellow-gray in color with an oily texture. There are many concurrent diseases that mimic EPI, and severe pancreatitis is one that if allowed to continue unabated can lead to EPI.
Diagnosis and treatmentEdit
In dogs, the best treatment is to supplement the animals' food with dried pancreatic extracts. There are commercial preparations available, but chopped bovine pancreas from the butcher can also be used. (Pork pancreas should not be used because of the rare transmission of pseudorabies). Symptoms usually improve within a few days, but lifelong treatment is required to manage the condition. A rare side-effect of use of dried pancreatic extracts is oral ulceration and bleeding.
Because of malabsorption, serum levels of cyanocobalamin (vitamin B12) and tocopherol (vitamin E) may be low. These may be supplemented, although since cyanocobalamin contains the toxic chemical cyanide, dogs that have serious cobalamin issues should instead be treated with hydroxocobalamin or methylcobalamin.
Cyanocobalamin deficiency is very common in cats with EPI because about 99 percent of intrinsic factor (which is required for cyanocobalamin absorption from the intestine) is secreted by the pancreas. In dogs, this figure is about 90 percent, and only about 50 percent of dogs have this deficiency.
In dogs failing to gain weight or continuing to show symptoms, modifying the diet to make it low-fiber and highly digestible may help. Despite previous belief that low-fat diets are beneficial in dogs with EPI, more recent studies have shown that a high-fat diet may increase absorption of nutrients and better manage the disease. However, it has been shown that different dogs respond to different dietary modifications, so the best diet must be determined on a case-by-case basis.
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