Feline pancreatitis (Proceedings)

Pancreatitis is being diagnosed more and more frequently in cats. Cats typically have chronic pancreatitis whereas dogs usually suffer acute disease. The difference in presentation between the species as well as a lack of appropriate diagnostic tools led to pancreatitis in cats being widely underdiagnosed. As we have learned to recognize the more subtle presentation in cats as well as having developed better tests, veterinarians have come to realize that pancreatitis is not uncommon in cats.

Etiology

Pancreatitis is the end-result of autodigestion of the pancreas by the activation of digestive enzymes within the pancreas. A variety of different mechanisms can start this process which then results in pancreatic autodigestion. Following an insult, there is initially a decrease in the secretion of pancreatic enzymes. This results in the formation of abnormal cytoplasmic vacuoles. Inside these vacuoles, the contents of the lysozomes and zymogen granules colocalize, leading to intracellular activation of trypsin. The activation of trypsin leads to activation of other zymogens, including proteases and phospholipases. The activated digestive enzymes can cause both local and systemic effects. Local effects include pancreatic inflammation, hemorrhage, cellular necrosis, and peripancreatic fat necrosis. Systemic effects may arise from release of the activated digestive enzymes into the bloodstream. Potential systemic effects may include hypotension from vasodilation, pulmonary edema, pleural effusion, disseminated intravascular coagulation, renal failure, and multi-organ failure.

In most cases of feline pancreatitis, the underlying cause is unknown. There are a few infectious agents that have been associated with pancreatitis in cats. Toxoplasma gondii infection has been shown to cause pancreatitis as has the hepatic fluke Amphimerus pseudofelineus. Close to 1/5 of cats with pancreatitis have antibodies against Bartonella sp. Some viral agents such as panleukopenia and feline infectious peritonitis have also been implicated. Blunt abdominal trauma can lead to pancreatitis, most likely secondary to ischemia. Unlike the situation in humans where drugs are commonly implicated as the cause of pancreatitis, drugs have very rarely been shown to have a cause-and-effect relationship with feline pancreatitis. Organophosphate intoxication has been documented to cause pancreatitis in cats. While still not fully understood, there is a suspected relationship between pancreatitis in cats and inflammation in neighbouring organs including the liver and/or gastrointestinal tract. Whether "triaditis" (concurrent pancreatitis, hepatitis, and inflammatory bowel disease) is a true clinical entity is hotly debated; however, definite associations between pancreatitis and inflammatory bowel disease are frequently seen. Pancreatitis is also seen in conjunction with hepatic disease.

Diagnosis

Clinical presentation

The history and presenting complaints for cats with pancreatitis varies tremendously. Examination of the literature does not suggest any strong age, breed or sex predilection. While pancreatitis has been diagnosed in cats as young as five weeks of age, there is some suggestion that pancreatitis is more likely to be seen in middle-aged and older cats. Cats typically present with chronic pancreatitis. Studies of pancreatitis in cats suggest that a more chronic form is seen in 65-89% of all cases of pancreatitis. The clinical signs most often reported are very non-specific and include lethargy, anorexia and weight loss. Less commonly seen are the "classic" signs of pancreatitis such as vomiting and abdominal pain. A small percentage of cats will present as the typical acute pancreatitic with a very brief history of extreme lethargy and vomiting. Perhaps the most classic aspect of pancreatitis in cats is in illustrating the fact that cats aren't small dogs!

Physical examination findings in cats with pancreatitis are non-specific as well. Dehydration and depression are frequently seen. Mucous membranes may be pale or icteric. Abdominal pain or palpable abdominal masses are infrequently noted. Changes in respiration including tachypnea and dyspnea have been reported.

Clinical Pathology

A minimum database consisting of a CBC, chemistry profile and urinalysis should be obtained in all cats suspected of having pancreatitis. While changes on the minimum database are non-specific for pancreatitis, the results are useful in ruling out other causes of the non-specific clinical signs as well as for evaluating for concurrent disease. In mild cases of pancreatitis, there may not be any changes in the minimum data base. Possible CBC changes include leukocytosis which is seen in approximately ½ of pancreatitic cats and less commonly leukopenia. A mild anemia, typically nonregenerative is seen in up to ¼ of cats. Hemoconcentration reflecting the dehydrated state may also be found. Thrombocytopenia is rarely noted but should prompt the concern for possible disseminated intravascular coagulopathy.

Chemistry profile changes are also mild and non-specific. Elevations in liver enzymes including alanine aminotransferase (ALT), alkaline phosphatase (SAP) and bilirubin are seen in about half of the cats. These elevations often reflect concurrent cholangiohepatitis or secondary hepatic lipidosis. Azotemia is also commonly seen, and may be due to either dehydration or a concurrent nephritis. The specific gravity of the urine prior to fluid therapy is essential in determining whether the azotemia is pre-renal in nature. Other biochemical changes reported for cats with pancreatitis include hypoalbuminemia, hypercholesterolemia, and hyperglycemia. Electrolyte changes, reported in half of the cats, include hypokalemia and hypocalcemia. Hypophosphatemia has also been reported. Low cobalamin and folate levels have been documented in cats with pancreatitis.

Pancreatic Enzyme

Serum amylase and lipase activities have been proven to be of no value in diagnosing pancreatitis in cats. Feline trypsin-like immunoreactivity (fTLI) which measures both trypsinogen and trypsin in serum has been evaluated for its usefulness in diagnosing pancreatitis in cats. Unfortunately both the sensitivity and specificity of this assay for determining pancreatitis appear inadequate. More recently, an assay for feline pancreatic lipase immunoreactivity (fPLI) has been developed. Feline pancreatic lipase immunoreactivity only measures lipase of pancreatic origin whereas previous catalytic assays for lipase indiscriminately measured all lipases including those of gastric and duodenal origins. Studies in cats with both experimentally-induced and spontaneous pancreatitis have shown fPLI to have the highest sensitivity of any assay for diagnosing pancreatitis (one study found the sensitivity to be 100% in cats with spontaneous moderate-to-severe pancreatitis). Serum fPLI concentration is also more specific than fTLI or abdominal ultrasound. The measurement of fPLI is available through the GI lab at Texas A&M (http://www.cvm.tamu.edu/gilab/). Recently the GI lab at Texas A&M collaborated with IDEXX to develop a spec fPL. They report this assay to have the same clinical utility as the fPLI but with a faster turn-around time.

Diagnostic imaging

Abdominal radiographs have little usefulness in diagnosing pancreatitis but may be helpful in ruling out other diseases that present similarly. Radiographs have the advantages of being relatively inexpensive and widely available. Changes that may be seen in pancreatitis include decreased detail "ground glass appearance" in the cranial abdomen consistent with a localized peritonitis, widening of the angle between the pylorus and proximal duodenum, static gas pattern within the duodenum, dilation of the small intestine, hepatomegaly and a cranial abdominal mass. Abdominal radiography has been shown to have low sensitivity and specificity for diagnosing pancreatitis. Ultrasound has been found to highly specific for diagnosing pancreatitis. However, the sensitivity is fairly low and is extremely operator-dependent. Even in the hands of boarded radiologists, ultrasound abnormalities may be seen in only one-third of cases! Ultrasonographic changes seen in pancreatitis include a hypoechoic pancreas with surrounding peripancreatic hyperechoic mesentery. Ascites may also be noted. Studies examining the useful of computed tomography (CT) in detecting pancreatitis have also revealed a disappointingly low sensitivity. Endosonography has recently been examined as a diagnostic tool (Schweighauser et al, J Fel Med Surg 2009). Endosonography is performed using an endoscope that is equipped with an ultrasound transducer at its tip. After the endoscope is positioned in the stomach, the liver, pancreas and surrounding structures can be examined ultrasonographically. The preliminary study had too few animals to draw any statistical conclusions but the authors comment endosonography provided better visualization of the normal pancreas and of pancreatic margins in sick patients.

Histopathology

While rarely performed, histopathology is considered the "gold standard" in establishing a definitive diagnosis of pancreatitis in the cat. Both exploratory laparotomy and laparoscopy allow direct visualization of the pancreas as well as an opportunity to obtain samples for histopathological examination. Gross findings consistent with a diagnosis of pancreatitis include pancreatic hemorrhage or swelling, a dull, granular capsular surface and peripancreatic fat necrosis. There are many limitations regarding the usefulness of pancreatic biopsy as a means for establishing a diagnosis. While pancreatic biopsy itself is a safe procedure, its practicality is limited by the expense involved and potential contra-indications for general anesthesia. Additionally, the inflammatory lesions of pancreatitis are often quite localized and may be missed. A 2007 study found histopathologic lesions of pancreatitis in 45% of apparently healthy cats, suggesting that either subclinical pancreatitis is exceedingly common or that histopathology is not very specific.

Treatment

Supportive care is the mainstay in the treatment of pancreatitis. Cats with moderate-to-severe pancreatitis usually present dehydrated. Correcting dehydration is crucial to maintain pancreatic perfusion. Electrolyte and acid-base disturbances need to be identified and appropriately treated. Low cobalamine levels should also be addressed. Fresh frozen plasma is often recommended for severe pancreatitis. Plasma contains albumin and α-macroglobulins and provides oncotic support. α-macroglobulins are a scavenger protein for activated proteases in serum. There has been debate over whether plasma contains enough α-macroglobulins to make a significant difference. Anecdotal reports suggest that plasma is very beneficial for veterinary patients with pancreatitis.

Analgesia

Due to the stoic nature of cats, abdominal pain in pancreatitis is most likely under-reported. Pain may very well contribute to anorexia and should be a consideration in formatting a therapeutic plan. Injectable opiates such as buprenorphine are useful in immediately ameliorating pain. Fentanyl patches are easy to apply and can provide substantial pain relief.

Antiemetic therapy

Antiemetics should be used in any cat with persistent vomiting due to pancreatitis. Even in cats not vomiting, antiemetics should be considered to treat nausea.

Nutrition

Recent studies suggest the dogma of "resting the pancreas" by not feeding patients is not beneficial for cats. While concern exists for feeding vomiting patients, cats with pancreatitis rarely vomit. Cats are particularly susceptible to negative consequences of withholding food due to their propensity to develop hepatic lipidosis. Early nutritional support appears beneficial in the management of pancreatitis in both humans and dogs. Ideally nutrition would be achieved using a jejunostomy tube in order to bypass the pancreas. However j-tubes are not practical in most situations. In cats that will not eat on their own, a variety of feeding tubes including nasoesophageal and nasogastric tubes can be used. In cats where there is an expectation that anorexia may be prolonged, an esophagostomy tube should be considered. A 2009 study by Klaus et al. found that nasogastric tube feeding was well tolerated in cats with pancreatitis and associated with few complications. Enteral nutrition is preferred to TPN or PPN because it is beneficial for enterocyte health. The composition of the diet fed (ie fat content) does not seem to be of importance in feline pancreatitis (either in generation of disease or in treatment).

Antibiotic therapy

There is no evidence supporting that bacteria plays a role in the generation of feline pancreatitis. Antibiotic therapy should be used in cases with concurrent diseases such as neutrophilic cholangitis or with suspected infectious complications such as pancreatic abscess. The role of antibiotics in the treatment of uncomplicated pancreatitis is controversial.

Other therapies

A plethora of other therapeutic strategies have been recommended in the treatment of pancreatitis, both in humans and in veterinary patients. Few of these have been critically evaluated in cats. Dopamine infusion was shown to have beneficial effects if administered within twelve hours of experimentally inducing feline pancreatitis, but not to be beneficial if administered later in the course of disease. Dopamine is therefore not recommended for routine use. Surgery has been anecdotally recommended for patients with pancreatic abscesses and pseudocyts as well as for cats with complete biliary obstruction; surgery also allows placement of jejunostomy tubes. There has not been any rigorous scientific study of the role of surgery in treating feline pancreatitis.

Prognosis

Pancreatitis in cats varies tremendously in terms of severity and prognosis. Cats with single episodes of mild pancreatitis have an excellent prognosis. Some cats suffer from repeated bouts of severe pancreatitis and have a much more guarded prognosis. There is no currently known treatment or dietary strategy to prevent future episodes of pancreatitis in cats. Aggressive fluid therapy and nutritional support are recommended in the treatment of feline pancreatitis. Identification and appropriate treatment of concurrent disorders is essential.