Pancreatitis: Clinical signs depend on severity of disease

Pancreatitis: Clinical signs depend on severity of disease

Q: Could you review pancreatitis and its diagnosis indogs and cats?

A: Pancreatitis is a common gastrointestinal disorder in bothdogs and cats. The following article describes the current diagnosis ofcanine and feline pancreatitis ­ Steiner JM, Williams DA: Diagnosisof canine and feline pancreatitis. Proc 20th Annual Forum ACVIM 20:562-564,2002.

Clinical findings

Clinical signs in dogs with pancreatitis depend on the severity of thedisease. Mild cases may remain subclinical. More severe cases may presentwith anorexia, vomiting, weakness, abdominal pain and diarrhea. Cats, evenwith severe pancreatitis, present with even less specific clinical signsthan dogs do. Cats with severe pancreatitis may show the clinical signsof lethargy, anorexia, vomiting, abdominal pain, a palpable abdominal massand diarrhea.

Why clinical signs

Clinical signs in animals with pancreatitis are from pancreatic inflammationor from the systemic effects of the pancreatic inflammation. Recent dataindicate the exocrine pancreas responds to several different noxious stimuliby a decrease in secretion of pancreatic enzymes. This is followed by theformation of giant cytoplasmic vacuoles in acinar cells. Biochemical studieshave shown that these vacuoles are the product of co-localization of zymogensof digestive enzymes and lysosomal enzymes, which are normally strictlysegregated. The ensuing decrease in pH and/or the presence of the lysosomalenzymes such as cathepsin B lead to premature activation of trypsinogen.Trypsin in turn activates other zymogens, leading to local effects suchas inflammation, pancreatic edema and hemorrhage, pancreatic necrosis, andparapancreatic fat necrosis (saponified fat). These local effects are associatedwith clinical signs such as lethargy, vomiting, and abdominal pain.

Recent data also indicate other systemic sequelae are a consequence ofthe release of inflammatory mediators released into the vascular space inresponse to pancreatic inflammation. A systemic inflammatory response, consistingof release of neutrophils from the bone marrow, chemotaxis of leucocytes,and degranulation of mast cells, basophils, and eosinophils, and plateletaggregation, occur commonly in animals with severe forms of pancreatitis.Other systemic effects seen in animals with severe pancreatitis are systemicvasodilation leading to hypotension and sometimes acute renal failure, pulmonaryedema leading to respiratory failure, disseminated intravascular coagulation,and in some cases multi-organ failure. A few animals also develop systemiclipodystrophy, also known as pancreatitis associated panniculitis. Neurologicsigns such as disorientation have been seen in animals with severe pancreatitisand are referred to as pancreatic encephalopathy.

Laboratory findings

In dogs with severe pancreatitis, CBC findings may include neutrophilia(and possibly with a left shift), thrombocytopenia and anemia. In cats withsevere pancreatitis, CBC findings may include anemia, hemoconcentration,leukocytosis and leukopenia. The serum chemistry profile may show mild elevationsof hepatic enzymes. Azotemia may be seen and may be from dehydration ormay be an indicator of renal failure secondary to pancreatitis. Urinalysisoften reveals an elevated urine specific gravity secondary to dehydration.However, in the most severe cases renal failure may ensue and urine specificgravity may drop and casts may be seen in the sediment. None of the findingson CBC, serum chemistry profile, or urinalysis are specific. They more importantlyserve to rule out disorders of other organs and to assess the overall healthstatus of the animal.

Minimally invasive diagnostic tests

Many minimally invasive diagnostic tests for canine pancreatitis havebeen described; however, few tests have been found to be clinically useful.Serum canine trypsin-like immunoreactivity (TLI) has a specificity of 65.4percent and a sensitivity of only 33.3 percent. Serum amylase activity showsa specificity of 57.1 percent and a sensitivity of 62.1 percent. Serum lipaseactivity showed a specificity of only 55.2 percent and a sensitivity of73.3 percent.

One cannot depend on using serum lipase activity in diagnosing pancreatitis.Serum lipase activity has been used for the diagnosis of canine pancreatitisfor several decades.

Considerable serum lipase activity remains in dogs after pancreatectomyindicating that lipase activity in serum originates not only from the exocrinepancreas. Similarly, in dogs with exocrine pancreatic insufficiency serumlipase 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, hepatocellularcarcinoma, bile duct carcinoma, and lymphosarcoma, or other lesions suchas hemangiosarcoma of the heart, intestinal adenocarcinoma, GI lymphoma,or amyloidosis of multiple organs are all associated with an increase inserum lipase activity. Also, heat stress and administration of prednisoneor dexamethasone can cause an increase in serum lipase activity in dogs.While some dogs with pancreatitis have elevated serum lipase activity, othersdisplay no or only mild elevations of serum lipase activity. This all saysthat an elevation of serum lipase activity should only be used as a screeningtest and the diagnosis should be confirmed by other diagnostic modalities.

In cats, serum lipase activity has been shown to be of no clinical usefulnessfor the diagnosis of pancreatitis. Also, serum amylase activity has beenshown to be of no clinical usefulness in the diagnosis of pancreatitis incats.

Serum TLI concentration has been shown to be specific for exocrine pancreaticfunction in both dogs and cats. Serum TLI concentrations are significantlydecreased in dogs and cats with exocrine pancreatic insufficiency. Dogsand cats with experimental pancreatitis have increased serum TLI concentrations.Also, some dogs and cats with spontaneous pancreatitis have elevations ofserum TLI concentrations. However, less than 40 percent of dogs with spontaneouspancreatitis and 30-60 percent of cats with spontaneous pancreatitis havean elevated serum TLI concentration.

Preferred diagnostic test

Recently, new assays for the measurement of serum pancreatic lipase indogs (cPLI) and cats (fPLI) have been developed and validated. The referencerange for serum cPLI, as measured by ELISA, is 2.2 to 102.1 ug/L ­ withabove 200 ug/L being diagnostic for pancreatitis in dogs. Serum cPLI concentrationis significantly decreased in dogs with exocrine pancreatic insufficiencythat indicate serum cPLI is specific for exocrine pancreatic function. Ina recent study of dogs with biopsy-proven pancreatitis, the sensitivityof serum cPLI for pancreatitis was above 80 percent. Therefore, serum cPLIis not only a specific marker for exocrine pancreatic function but is alsohighly sensitive for the diagnosis of canine pancreatitis. Preliminary resultswould suggest that, as in dogs, measurement of serum fPLI concentrationis more sensitive than any other diagnostic tool for the diagnosis of felinepancreatitis.

Summary

Serum amylase and lipase activities are useful as a quick screening testfor pancreatitis in the dog only. Furthermore, the diagnosis of pancreatitisshould be confirmed by other diagnostic modalities and normal test resultsdo not eliminate the possibility of pancreatitis. Abdominal ultrasound ishighly specific for pancreatitis in both dogs and cats but is not very sensitive,especially in cats. Serum cPLI concentration is highly specific for exocrinepancreatic function and is also highly sensitive for pancreatitis. The measurementof serum fPLI appears to be clinically useful in cats suspected as havingpancreatitis.