The perplexing pancreas: Pathophysiology of pancreatic disease (Proceedings)


The perplexing pancreas: Pathophysiology of pancreatic disease (Proceedings)

Aug 01, 2009

Pancreatitis, either acute or chronic, is a significant clinical problem in both dogs and cats. It can be a difficult disease to diagnose initially and subsequently characterize adequately. Ironically, with the advent of the SNAP PLI test, it may soon become a disease that is over-diagnosed; the clinical presentation and laboratory changes are similar to a number of gastrointestinal diseases and ending the diagnostic work-up with a positive SNAP PLI result may lead to the potentially erroneous conclusion that the only, or even the most important disease process in a particular patient is an inflammation of the pancreas.

Pancreatic enzymes are normally inactive "zymogens" until released into the lumen of the GI tract where specific enzymes convert these zymogens into powerful digestive enzymes. Premature activation, or the breakdown of the normal protective packaging within lysosomes can result in local, autodigestion of surrounding cells and tissue. This results in acute, local inflammation, the "itis" of acute pancreatitis. The body is equipped with a variety of protective mechanisms and molecules designed to deal with these inappropriately activated enzymes, but if those mechanisms fail there is a rapid amplification of local enzymes as well as systemic mediators - local acute pancreatitis rapidly progresses to life-threatening systemic disease. Critical care specialists have coined a variety of acronyms to describe this systemic insult – SIRS, MODS, ARDS, DIC – that are beyond the scope of this review. Suffice it to say, none of them sound good, and no organ, tissue or system is safe. Local complications can include the formation of a pancreatic pseudocyst, abscess, necrosis and infection, and fat saponification. These patients are at risk for the development of coagulopathies and thromboembolism, suppurative cholangiohepatitis, extrahepatic biliary obstruction, acute renal failure, peritonitis, as well as significant respiratory, cardiac, and neurologic abnormalities. In humans, chronic pancreatitis frequently results in diabetes mellitus or exocrine pancreatic insufficiency, explaining why insulin and pancreatic enzymes are listed as treatments for this disease in that species.

Table 1. Risk Factors for Pancreatitis
The clinical presentation of pancreatitis appears to be somewhat different in dogs and cats. Dogs are more "classic" with vomiting and abdominal pain being prominent complaints, whereas cats are more subtle (or more difficult to evaluate) and simply stop eating and get lethargic. Dogs may become febrile whereas cats may become hypothermic. Both species may end up collapsed and in shock. Chronic, "smoldering", or recurrent pancreatitis can be even more of a clinically challenging diagnosis with signs that are vague and intermittent.

Although a minimum database (CBC, biochemical profile, urinalysis) is important in the diagnostic work-up of any patient presenting for gastrointestinal signs, none of the potential abnormalities are specific for pancreatitis, including elevations in serum amylase or lipase. One study did show that a low ionized calcium is a poor prognostic indicator, and a clear understanding of electrolyte and acid-base abnormalities is important for planning supportive care. The blood test that currently appears to be the most sensitive and specific for pancreatic inflammation is the species-specific pancreatic lipase immunoreactivity, or PLI. As with any test, it is important to remember what a positive result actually represents – in this case, an abnormal release of pancreas-specific enzymes into circulation. A positive PLI is consistent with the presence of some degree of pancreatic inflammation, making it very likely that the pancreas is, to some degree, responsible for the clinical presentation. A positive test result does not mean the pancreas is the sole source, the primary source, or even necessarily the most important source of the patient's problems.

Imaging studies are an important part of the diagnostic work-up in cases of GI disease. There are a number of reports with an even greater number of claims regarding the sensitivity and/or specificity of abdominal radiographs and ultrasound. The take-home message appears to be that the skill of the person interpreting the results is crucial and a "negative" result should not take pancreatitis off the list of differentials if clinical acumen put it there in the first place.

Table 2. Treatment Considerations and Controversies
At Colorado State University we completed a retrospective study that highlighted the important role that laparoscopic visualization and biopsy of the pancreas can play in the diagnosis of pancreatic disease. Laparoscopy is a minimally invasive and diagnostically powerful technique that requires a relatively modest investment of time, money and training before it is a very viable practice tool.