PATHOLOGY OF THE EXOCRINE PANCREAS

The exocrine pancreas is a typical exocrine gland with acini and a duct system. The pancreatic duct enters the duodenum in close association with the bile duct. An accessory pancreatic duct enters the duodenum a short distance more distally in the duodenum. Acinar cells contain so-called zymogen granules: inactive digestive enzymes (lipase, protease, amylase) which are activated upon secretion. The pancreas is a lobulated pink to grey leaf-like gland found in the mesoduodenum Pathology of the exocrine pancreas is not especially common, but is often spectacular and certainly will be encountered in small animal practice. It is also very straight forward. Dysfunction of the exocrine pancreas either results in site-inappropriate digestive enzymatic activity or a deficiency of digestive enzymatic activity. While all the normal pathological processes may occur in the pancreas, a summary of the most important conditions follows. Of course, the pancreas also has an endocrine component intimately associated with the exocrine part (the Islets of Langerhans or Pancreatic Islets); the pathology of which will be discussed in the section on Pathology of the Endocrine System.

Consequences of Disease of the Exocrine Pancreas Like the liver, the exocrine pancreas has a large functional reserve, therefore it is only disease that disrupts a large proportion of the pancreatic mass that will have an effect on function. Exocrine pancreatic insufficiency (EPI) occurs most frequently in the dog (chronic pancreatitis) but can also occur in cats and cattle (calves with pancreatic hypoplasia). It is manifested by maldigestion which results in the clinical signs of steatorrhoea (fatty stool), diarrhoea and weight loss or failure to thrive despite a ravenous appetite.

Hypoplasia Hypoplasia of the exocrine pancreas occurs occasionally in dogs. Grossly, the pancreas is much reduced in size, giving it a feathery outline and making the ducts prominent. In extremely severe cases, the hypoplasia may be to such a degree that only the ducts can easily be detected grossly. Clinical signs will only occur when the degree of hypoplasia is severe since the organ has a large functional reserve. Affected dogs produce insufficient quantities of enzymes to digest complex fats, proteins and carbohydrates and as a result have a tendency to render their neighbour's footpath with a pale, voluminous, rancid diarrhoea; they also fail to gain weight despite a ravenous appetite. Importantly, pancreatic hypoplasia does not affect islet cells so these dogs do not suffer diabetes mellitus.

Acute Pancreatitis Also referred to as acute pancreatic necrosis, this condition involves an idiopathic activation of enzymes prior to normal secretion with the result that the pancreas begins to digest itself; this indiscriminate attack can extend to surrounding stuctures and results in extreme abdominal pain. The gross appearance is dominated by hyperaemia and haemorrhage of affected serosal surfaces and nodular, pale omental fat as it is digested. A severe acute inflammatory response may be detected systemically, however, the main finding histologically is necrosis. The inflammatory response, in most cases is likely secondary to the tissue destruction at the site of self-digestion.

Sequelae of acute pancreatitis can include shock, peritoneal adhesions, bile duct obstruction, chronic pancreatitis, abscessation, extensive scarring of the pancreas and diabetes mellitus. How do you think these complications come about, and what effect might they have?

Nodular changes 1. Nodular hyperplasia. This is a common change in old dogs and cats with no clinical significance. Grossly, there are few to numerous pale, raised lobule-shaped foci which may have a slightly altered colour compared to surrounding pancreatic lobules. The importance of this condition is that it may be confused with the next 2 conditions on gross examination, if one is careless.

2. Neoplasia. Carcinoma (adeno- or duct) is the only significant neoplasm of the exocrine pancreas; it is an aggressive neoplasm which has usually metastasised to local lymph nodes and often the liver by the time clinical signs appear. Often the first clinical sign is jaundice - why? 3. Chronic pancreatitis. This is relatively common in cats as an idiopathic event, possibly representing the end-point of a heterogeneous group of conditions. These cats usually have not had detectable episodes of acute pancreatitis. Thin bands of scar tissue spreading through the interstitium combined with limited regeneration, cause the pancreas to become markedly nodular and shrunken (like a Chokito bar); the islets are usually preserved. It is not usually associated with detectable clinical signs in cats. In dogs chronic pancreatitis is the result of multiple acute pancreatic necrosis events and the inevitable progressive destruction of pancreatic tissue. A poor regenerative response combined with fibrosis and atrophy of existing pancreatic tissue (probably due to disruption to ducts) may lead to EPI and possibly even diabetes mellitus (pancreatic endocrine insufficiency).

Pancreatic Lithiasis Calcium carbonate calculi may form in the pancreas and pancreatic ducts. This can be found especially in feedlot cattle usually as an incidental finding, however, is rare in other species.

Post mortem changes Oedema and interlobular haemorrhage are very common effects of barbiturate euthanasia and should never be confused with pancreatitis. Ever. Remember, also, that the pancreas undergoes autolysis very rapidly following death, due to the release and activation of pancreatic enzymes and migration of gut bacteria the short distance up the pancreatic and accessory pancreatic ducts. This leads to a colour change from light pink to dark red.

Useful Clinical Pathology Findings in Exocrine Pancreatic Disease Pancreatic Necrosis / Acute pancreatitis - The two enzymes that are measured most frequently in an attempt to detect pancreatic disease are the enzymes amylase and lipase, the theory being that if these enzymes spill over into the serum compartment then cell damage is likely occurring. Unfortunately, neither of these enzymes is particularly reliable with regards to detecting pancreatic necrosis. Both can be elevated in the absence of pancreatic disease and may not be elevated in cases of pancreatic disease, however, in
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conjunction with appropriate clinical signs large elevations (especially lipase) are in practicality usually regarded as confirmatory of pancreatic necrosis. Confusing matters, amylase can be found in several tissues including liver, intestine and pancreas and is normally excreted in the urine. Therefore, renal function will have an effect on amylase levels in serum as do small intestinal obstruction and liver disease. Amylase levels >3x the upper range of normal may be considered significant. Serum amylase is of no diagnostic value in the cat. Serum lipase is considered more reliable, however, is also present in the stomach and therefore chronic gastric disease may also elevate serum lipase. Again lipase is degraded by the kidneys, therefore renal function has an impact on lipase levels. Lipase levels >3x normal can be considered diagnostic of pancreatitis, however, the severity of disease cannot be gauged by the severity of lipase increase. It may be that excessively high TLI might also be supportive of a diagnosis of acute pancreatic necrosis but only early in the course of the disease. Exocrine Pancreatic Insufficiency (EPI) Serum Trypsin-Like Immunoreactivity (TLI) is the definitive diagnostic test for EPI in dogs (and now cats also although currently only one lab in the U.S. performs this test). This measures the presence of trypsin in serum, the idea being that trypsin is not only necessary for digestion of proteins but is also present to activate the other digestive enzymes including amylase and lipase. Therefore, there will be a normal level of spillage of trypsin into the serum but that if very low or no levels are detected then it is likely that the animal has significantly decreased pancreatic mass and/or activity, and if extremely high levels are detected then increased activitation of digestive enzymes is occurring and likely auto-digestion of pancreatic acini.

QUIZ 1. 2. 3. 4. 5. What is the exocrine function of the pancreas? What is exocrine pancreatic insufficiency (EPI)? Where is the pancreas? What are some of the implications of the anatomical position of the pancreas? How does the pancreas avoid self-digestion? What is the most common pathological process affecting the exocrine pancreas of the dog (and cat)? a. Neoplasia b. Hyperplasia c. Hypoplasia d. Circulatory disturbances e. Inflammation f. Cell Injury
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