Overview

The exocrine pancreas is responsible for the synthesis of digestive enzymes which are released in response to several stimuli. In response to secretin and an acidic pH in the duodenum, a large volume of bicarbonate-rich fluid is released from the epithelial duct system of the exocrine pancreas. The presence of food in the duodenum induces pancreozymin to stimulate pancreatic acinar cells to release a low volume, enzyme rich fluid, containing amylase, lipase, and proteolytic enzymes. Amylase and lipase are released in an active form, but the proteolytic enzymes must be activated. Trypsin, which is derived from the action of enterokinase on trypsinogen, is the most powerful of the proteolytic enzymes as it can activate most of the others in a positive feedback mechanism. The potential for severe tissue damage (autodigestion) is great if these enzymes are released directly into pancreatic tissue rather than into the duodenum.

Exocrine pancreatic diseases

Exocrine pancreatic diseases are broadly divided into inflammatory and noninflammatory subtypes. Inflammatory pancreatic diseases include acute pancreatitis and chronic recurrent pancreatitis, while the noninflammatory diseases include exocrine pancreatic insufficiency (EPI) and pancreatic neoplasia. Pancreatitis is seen predominantly in dogs and cats. Animals with mild or subclinical disease are not always presented to the veterinary clinic or may be treated symptomatically without diagnostic testing. Therefore, many cases of pancreatitis may remain undiagnosed or unconfirmed.

Acute pancreatitis in dogs

Middle-aged, overweight, sedentary female dogs are particularly predisposed to acute pancreatitis. The disease may be precipitated by a large fatty meal or dietary indiscretion (garbage-eating). Affected dogs may present with abdominal pain and vomiting.

Hematology

Pancreatitis in dogs is usually associated with an inflammatory leukogram, although the changes vary with the severity and stage of the disease. Leukocytosis characterized by neutrophilia with a left shift and monocytosis is often seen. Occasionally a degenerative left shift occurs, particularly with acute severe pancreatitis or necrotizing pancreatitis leading to peritonitis. The stress of illness and subsequent increased corticosteroid release leads to lymphopenia. Vomiting and diarrhea, which usually accompany pancreatitis in the dog, lead to fluid loss which can be detected by elevations in hematocrit and total protein. Hemorrhagic pancreatitis is associated with significant blood loss into the peripancreatic region of the abdomen, and when this occurs, the hematocrit and total protein may be low rather than reflecting hemoconcentration.

Biochemical panel

With injury of pancreatic acinar cells, digestive enzymes leak into the interstitial tissues of the pancreas and are absorbed into the lymphatics and blood, resulting in increases in serum amylase and lipase activities. Although the increased serum amylase activity detected with pancreatitis is of pancreatic origin, the intestinal mucosa and liver also synthesize amylase and should be considered as possible sources when unexplained amylase increases occur. Primary or secondary renal dysfunction, particularly with oliguria or anuria, is often associated with hyperamylasemia in dogs. The mechanism of increased amylase activity under these circumstances is not clear, but may relate to decreased renal excretion or inactivation of the enzyme. Corticosteroids have been reported to both increase and decrease serum amylase activity.

In addition to pancreatitis, elevated serum lipase activity has been associated with renal disease, gastrointestinal disease, corticosteroid therapy, and pancreatic and hepatic neoplasms. Although both serum amylase and lipase activities can be elevated due to nonpancreatic causes in dogs, and may not be elevated, particularly at all timepoints, in dogs with pancreatitis, measuring both and interpreting changes relative to history, clinical findings, and other diagnostic findings is useful in diagnosing pancreatitis in this species. Monitoring changes in serum amylase and lipase activities over several days may also be useful in the dog. Early in the course of pancreatitis, activities of one or both enzymes may not be elevated, but dramatic changes can occur in a short period of time. Measuring amylase and lipase activities in peritoneal fluid may also be useful when pancreatitis is suspected, but serum activities are not increased.

Other tests have been developed to help diagnose pancreatitis, with limited success. Measurement of serum canine pancreatic lipase immunoreactivity (cPLI) can be useful in diagnosing canine pancreatitis since nonpancreatic sources of lipase (e.g. hepatic, gastric) are not detected by this test. Serum trypsinogen and trypsin can be measured by an assay which detects both without distinguishing the two and is, therefore, called trypsin-like immunoreactivity (TLI). This test is particularly useful for diagnosing EPI (discussed below), but lacks sensitivity for the diagnosis of pancreatitis in dogs and is not recommended for this purpose. Also, trypsinogen is filtered by the kidneys so renal dysfunction, for whatever reason, can increase TLI.

There may be numerous other biochemical changes occurring with pancreatitis. Dogs with pancreatitis frequently vomit, and fluid volume contraction often leads to prerenal azotemia with increased urea and creatinine and concentrated urine. If azotemia is present but the USG is isosthenuric, renal disease is likely; amylase and lipase may be elevated due to lack of renal excretion/inactivation of these enzymes. Dogs with pancreatitis often have hypercholesterolemia and hypertriglyceridemia. The increased serum triglycerides cause the plasma and serum to appear lipemic. The mechanism of elevated lipids is not clear and, in some cases, may predispose to, rather than result from, pancreatitis. Cholestasis, perihepatitis, and ascending cholangiohepatitis often accompany pancreatitis in the dog. These changes can result in hypercholesterolemia, hyperbilirubinemia, and increased serum activities of ALP, GGT, and ALT. Also, the stress of illness may contribute to elevations in hepatic enzyme activities.

Electrolyte and acid-base disturbances may result from vomiting, diarrhea, anorexia, and adipsia. Hypocalcemia is sometimes seen and the pathogenesis is unclear but may relate to calcium deposition in saponified abdominal fat.

Dogs with pancreatitis are often hyperglycemic, which can be transient or due to diabetes mellitus. Stress, glucagon release, and transient impairment of insulin production/release can result in hyperglycemia that is resolved when the pancreatitis subsides. Permanent damage to islet cells from chronic pancreatitis or repeated episodes of acute pancreatitis may result in diabetes mellitus, requiring insulin therapy. Differentiation between transient hyperglycemia and diabetes mellitus may be difficult while the pancreatitis is ongoing. The presence of ketonuria supports pre-existing diabetes mellitus. Careful history-taking may help determine if classical signs of diabetes mellitus were present before the animal developed pancreatitis. In some cases, it may be necessary to assess the endocrine pancreas after the animal has recovered from pancreatitis, to determine if insulin therapy will be required.

Abdominocentesis

Abdominocentesis may reveal a serosanguinous fluid with a high nucleated cell count and high protein concentration consistent with an exudate. The exudate may be septic if the bowel is sufficiently damaged or devitalized.

Chronic recurrent pancreatitis in dogs

The clinical signs with chronic recurrent pancreatitis are generally more subtle than with acute pancreatitis, and the disease is more difficult to diagnose. In addition to diabetes mellitus, progressive destruction of the pancreas may culminate in pancreatic exocrine insufficiency. Typically with chronic pancreatitis, serum enzyme activities of amylase and lipase are not elevated to the same degree as with acute pancreatitis, and other laboratory changes are also milder or nonexistent.

Pancreatitis in cats

Pancreatitis is more clinically subdued in cats compared to dogs and confirming the diagnosis is often more difficult. Cats with pancreatitis are often presented with nonspecific signs such as lethargy, anorexia, lack of grooming, and dehydration rather than the vomiting and abdominal pain that are more consistently seen in dogs with pancreatitis. Pancreatitis in cats is more often a chronic disease compared to dogs where it is usually acute. Most cases in cats are considered idiopathic, although certain risk factors have been determined.

Hematologic evidence of inflammation is usually milder in cats as compared to dogs and the CBC may be normal in cats with chronic pancreatitis. Measuring serum amylase and lipase activities in cats is not useful and almost never aids in diagnosing pancreatitis in this species. Although these enzymes are not released into the blood in large amounts, local release into the abdominal cavity and tissues surrounding the pancreas may occur. Thus, pancreatitis in cats is often associated with concurrent inflammation of the liver and intestinal tract, and measurement of peritoneal fluid amylase and lipase activities may be useful. Mild to moderate hyperbilirubinemia and mild hypocalcemia may be seen in cats with pancreatitis, especially the acute form.

A feline test for serum pancreatic lipase immunoreactivity (fPLI) has been developed and can be useful for the detection of moderate to severe pancreatitis, but is less sensitive for detecting mild pancreatitis. TLI lacks sensitivity for the diagnosis of pancreatitis in cats, similar to dogs. Ultrasound imaging, particularly when performed by an experienced ultrasonographer may be useful in detecting pancreatitis in cats. In some cases, clinicians may make the diagnosis without additional laboratory testing. Histopathology of pancreatic tissue facilitates the definitive diagnosis of pancreatitis in cats and other species. However, if lesions are localized and not readily visualized, histopathology can be inconclusive.

Exocrine pancreatic insufficiency

EPI may be due to either pancreatic atrophy from repeated damage to the pancreas (usually from pancreatitis), or inherited pancreatic acinar atrophy, seen most commonly in young dogs especially of the German Shepherd breed. A familial predisposition has also been found in the Rough Collie breed. Lack of pancreatic secretions leads to maldigestion of food, weight loss, voluminous stools, and often a ravenous appetite. Cats with EPI may not have a ravenous appetite and may vomit and have an unkempt haircoat. EPI has not been recognized in horses and cattle. Chronic maldigestion can lead to malabsorption due to secondary intestinal abnormalities including bacterial overgrowth. In the past, several blood and fecal tests were done to try to differentiate maldigestion and malabsorption; however, now maldigestion is usually readily diagnosed in dogs and cats by measuring TLI in the serum. TLI measures trypsinogen predominantly, but also trypsin, including trypsin bound to proteinase inhibitors. Measurement of TLI is species specific and assays are available for dogs and cats. Normally, a small amount of trypsinogen, but no trypsin, is present in the serum. With EPI, serum TLI is decreased.

Pancreatic neoplasia

Carcinomas of the exocrine pancreas occur in cats and dogs, and less commonly in other species. Cats with this neoplasm are usually geriatric; dogs are more variable in age. Weight loss, inappetence, abdominal pain, and abdominal effusion are common clinical signs. Laboratory changes are highly variable and somewhat dependent on whether other organs are involved, such as the liver. Dogs with pancreatic neoplasms may have elevations in serum activities of amylase and lipase. Extreme hyperlipasemia has been seen occasionally. Many cats with pancreatic adenocarcinoma have an abdominal effusion, usually a modified transudate, without other laboratory changes. Cytology of abdominal fluid or ultrasound-guided aspirate of the pancreas will often reveal a population of malignant epithelial cells that may display features consistent with secretory/glandular tissue.

Beta cell (insulin-secreting) tumors of the pancreas are discussed in Chapter 10: Endocrine System. Non-beta cell islet neoplasms are rare and signs relate to the specific hormone(s) being produced. Hypersecretion of gastrin, as with gastrinoma, results in gastric and duodenal ulceration, intestinal hemorrhage, vomiting, and acid-base disturbances (as discussed under acid-base disturbances associated with intestinal diseases later in this chapter).