Pancreatitis: Clinical signs depend on severity of disease
Q: Could you review pancreatitis and its diagnosis in dogs and cats?
A: Pancreatitis is a common gastrointestinal disorder in both dogs and cats. The following article describes the current diagnosis of canine and feline pancreatitis Steiner JM, Williams DA: Diagnosis of canine and feline pancreatitis. Proc 20th Annual Forum ACVIM 20:562-564, 2002.
Clinical signs in dogs with pancreatitis depend on the severity of the disease. Mild cases may remain subclinical. More severe cases may present with anorexia, vomiting, weakness, abdominal pain and diarrhea. Cats, even with severe pancreatitis, present with even less specific clinical signs than dogs do. Cats with severe pancreatitis may show the clinical signs of lethargy, anorexia, vomiting, abdominal pain, a palpable abdominal mass and diarrhea.
Why clinical signs
Clinical signs in animals with pancreatitis are from pancreatic inflammation or from the systemic effects of the pancreatic inflammation. Recent data indicate the exocrine pancreas responds to several different noxious stimuli by a decrease in secretion of pancreatic enzymes. This is followed by the formation of giant cytoplasmic vacuoles in acinar cells. Biochemical studies have shown that these vacuoles are the product of co-localization of zymogens of digestive enzymes and lysosomal enzymes, which are normally strictly segregated. The ensuing decrease in pH and/or the presence of the lysosomal enzymes such as cathepsin B lead to premature activation of trypsinogen. Trypsin in turn activates other zymogens, leading to local effects such as inflammation, pancreatic edema and hemorrhage, pancreatic necrosis, and parapancreatic fat necrosis (saponified fat). These local effects are associated with clinical signs such as lethargy, vomiting, and abdominal pain.
Recent data also indicate other systemic sequelae are a consequence of the release of inflammatory mediators released into the vascular space in response to pancreatic inflammation. A systemic inflammatory response, consisting of release of neutrophils from the bone marrow, chemotaxis of leucocytes, and degranulation of mast cells, basophils, and eosinophils, and platelet aggregation, occur commonly in animals with severe forms of pancreatitis. Other systemic effects seen in animals with severe pancreatitis are systemic vasodilation leading to hypotension and sometimes acute renal failure, pulmonary edema leading to respiratory failure, disseminated intravascular coagulation, and in some cases multi-organ failure. A few animals also develop systemic lipodystrophy, also known as pancreatitis associated panniculitis. Neurologic signs such as disorientation have been seen in animals with severe pancreatitis and are referred to as pancreatic encephalopathy.
In dogs with severe pancreatitis, CBC findings may include neutrophilia (and possibly with a left shift), thrombocytopenia and anemia. In cats with severe pancreatitis, CBC findings may include anemia, hemoconcentration, leukocytosis and leukopenia. The serum chemistry profile may show mild elevations of hepatic enzymes. Azotemia may be seen and may be from dehydration or may be an indicator of renal failure secondary to pancreatitis. Urinalysis often reveals an elevated urine specific gravity secondary to dehydration. However, in the most severe cases renal failure may ensue and urine specific gravity may drop and casts may be seen in the sediment. None of the findings on CBC, serum chemistry profile, or urinalysis are specific. They more importantly serve to rule out disorders of other organs and to assess the overall health status of the animal.
Minimally invasive diagnostic tests
Many minimally invasive diagnostic tests for canine pancreatitis have been described; however, few tests have been found to be clinically useful. Serum canine trypsin-like immunoreactivity (TLI) has a specificity of 65.4 percent and a sensitivity of only 33.3 percent. Serum amylase activity shows a specificity of 57.1 percent and a sensitivity of 62.1 percent. Serum lipase activity showed a specificity of only 55.2 percent and a sensitivity of 73.3 percent.
One cannot depend on using serum lipase activity in diagnosing pancreatitis. Serum lipase activity has been used for the diagnosis of canine pancreatitis for several decades.
Considerable serum lipase activity remains in dogs after pancreatectomy indicating that lipase activity in serum originates not only from the exocrine pancreas. Similarly, in dogs with exocrine pancreatic insufficiency serum lipase activity is not significantly different from clinically healthy dogs. Additionally, many conditions such as renal failure, glomerular disease, hepatic lesions such as hepatic necrosis, hepatic fatty degeneration, hepatocellular carcinoma, bile duct carcinoma, and lymphosarcoma, or other lesions such as hemangiosarcoma of the heart, intestinal adenocarcinoma, GI lymphoma, or amyloidosis of multiple organs are all associated with an increase in serum lipase activity. Also, heat stress and administration of prednisone or dexamethasone can cause an increase in serum lipase activity in dogs. While some dogs with pancreatitis have elevated serum lipase activity, others display no or only mild elevations of serum lipase activity. This all says that an elevation of serum lipase activity should only be used as a screening test and the diagnosis should be confirmed by other diagnostic modalities.
In cats, serum lipase activity has been shown to be of no clinical usefulness for the diagnosis of pancreatitis. Also, serum amylase activity has been shown to be of no clinical usefulness in the diagnosis of pancreatitis in cats.
Serum TLI concentration has been shown to be specific for exocrine pancreatic function in both dogs and cats. Serum TLI concentrations are significantly decreased in dogs and cats with exocrine pancreatic insufficiency. Dogs and cats with experimental pancreatitis have increased serum TLI concentrations. Also, some dogs and cats with spontaneous pancreatitis have elevations of serum TLI concentrations. However, less than 40 percent of dogs with spontaneous pancreatitis and 30-60 percent of cats with spontaneous pancreatitis have an elevated serum TLI concentration.
Preferred diagnostic test
Recently, new assays for the measurement of serum pancreatic lipase in dogs (cPLI) and cats (fPLI) have been developed and validated. The reference range for serum cPLI, as measured by ELISA, is 2.2 to 102.1 ug/L with above 200 ug/L being diagnostic for pancreatitis in dogs. Serum cPLI concentration is significantly decreased in dogs with exocrine pancreatic insufficiency that indicate serum cPLI is specific for exocrine pancreatic function. In a recent study of dogs with biopsy-proven pancreatitis, the sensitivity of serum cPLI for pancreatitis was above 80 percent. Therefore, serum cPLI is not only a specific marker for exocrine pancreatic function but is also highly sensitive for the diagnosis of canine pancreatitis. Preliminary results would suggest that, as in dogs, measurement of serum fPLI concentration is more sensitive than any other diagnostic tool for the diagnosis of feline pancreatitis.
Serum amylase and lipase activities are useful as a quick screening test for pancreatitis in the dog only. Furthermore, the diagnosis of pancreatitis should be confirmed by other diagnostic modalities and normal test results do not eliminate the possibility of pancreatitis. Abdominal ultrasound is highly specific for pancreatitis in both dogs and cats but is not very sensitive, especially in cats. Serum cPLI concentration is highly specific for exocrine pancreatic function and is also highly sensitive for pancreatitis. The measurement of serum fPLI appears to be clinically useful in cats suspected as having pancreatitis.