Pancreatitis Information

Introduction

Pancreatitis, an inflammatory condition of the exocrine pancreas, occurs frequently in both dogs and cats. While the true prevalence of pancreatitis in dogs and cats is unknown, recent studies would suggest that pancreatitis is a rather common and underdiagnosed condition in both dogs and cats. In a large retrospective study of necropsy findings 1.5% of 9,342 canine and 1.3% of 6,504 feline pancreata showed important pathological lesions. Pancreatitis can be difficult to diagnose. This may be due to the non-specific clinical signs commonly displayed by pancreatitis patients. However, there also has been a lack of diagnostic tests for pancreatitis that are both sensitive and specific for pancreatitis.

Clinical picture

Clinical signs of dogs and cats with pancreatitis depend on the severity of the disease. Mild cases may remain subclinical while more severe cases may present with a wide variety of clinical signs. In a recent retrospective study of 70 dogs with fatal pancreatitis the following clinical signs were reported: anorexia in 91% of the cases, vomiting in 90%, weakness in 79%, abdominal pain in 58%, dehydration in 46%, and diarrhea in 33%. These findings are somewhat surprising as abdominal pain is the key clinical sign of pancreatitis in human patients. Thus, the question arises whether dogs with pancreatitis have abdominal pain less frequently than humans, or more likely, whether we fail to correctly identify abdominal pain. It also should be recognized that retrospective studies could underestimate the true prevalence of abdominal pain due to lack of reporting, difference in investigator, or other factors. Classically, diarrhea has not been described as a typical clinical sign of pancreatitis. However, with 33% of dogs with pancreatitis in this study having diarrhea it would seem prudent to assess any dog presenting with diarrhea for potential pancreatitis during a systematic work-up.

Cats, even with severe pancreatitis, present with less specific clinical signs than do dogs. In a recent review of a large number of cats with pancreatitis the following clinical signs were reported: anorexia in 87%, lethargy in 81%, dehydration in 54%, weight loss in 47%, vomiting and hypothermia in 46%, icterus in 37%, fever in 25%, abdominal pain in 19%, diarrhea in 12%, and a palpable abdominal mass in 11%. Especially remarkable in this report is the low incidence of vomiting and abdominal pain in cats with pancreatitis.

Clinical signs in patients with pancreatitis are either due to activity of prematurely activated pancreatic enzymes or to systemic effects of the inflammatory response to pancreatic autodigestion. Recent data suggest that the exocrine pancreas responds to many different noxious stimuli in a similar fashion. The first common change reported is a decrease in secretion of pancreatic enzymes. This is followed by the formation of giant cytoplasmic vacuoles in acinar cells, visible only by electron microscopy. 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. These local effects are associated with clinical signs such as vomiting and abdominal pain.

Until recently it was believed that systemic signs seen in pancreatitis patients, like local effects, are a direct result of circulating pancreatic enzymes. While there is little doubt that some of these systemic effects, such as systemic lipodystrophy, are caused by circulating pancreatic enzymes, recent data would suggest that other systemic sequelae are a consequence of the release of inflammatory mediators in response to pancreatic inflammation. Systemic effects seen in patients with severe pancreatitis include fever, 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 patients also develop systemic lipodystrophy. Neurologic signs such as disorientation have been seen in human, canine, and feline patients with severe pancreatitis and are sometimes referred to as pancreatic encephalopathy. While clinical signs are not specific for pancreatitis, vomiting, anorexia, and cranial abdominal pain are key clinical signs in dogs with pancreatitis. Cats display these key clinical signs less frequently and a conclusive diagnosis of pancreatitis in this species is much more difficult to arrive at.

General clinical pathology

Complete blood count and serum chemistry profile often show mild and nonspecific changes. While these findings maybe useful in the overall assessment of the health status of the patient, they are not useful for arriving at a specific diagnosis of pancreatitis in either dogs or cats.

Diagnostic imaging

Changes seen on abdominal radiographs may include a decreased contrast in the cranial abdomen and displacement of abdominal organs. However, these changes are rather subjective and abdominal radiography is non-specific for canine or feline pancreatitis. However, abdominal radiographs are crucial in ruling out other differential causes of acute-onset vomiting and anorexia, such as an obstruction due to a foreign body.

Abdominal ultrasound was first described as a diagnostic tool for pancreatitis in the mid-80ties. Since then both the technology and expertise of veterinary radiologists in this area have markedly increased. While this development has led to a significant increase in sensitivity of this diagnostic modality for pancreatitis it has also led to a decrease in specificity. The sensitivity of abdominal ultrasonography for pancreatitis when performed by a veterinary radiologist has been reported to be up to 68% in dogs and up to 35% in cats. Changes identified include pancreatic enlargement, changes in echogenicity of the pancreas (hypoechogenicity is generally believed to be an indication of pancreatic necrosis and hyperechogenicity that of pancreatic fibrosis) and of peripancreatic fat (hyperechogenicity of the peripancreatic fat is generally believed to indicate peripancreatic fat necrosis), fluid accumulation around the pancreas, a mass effect in the area of the pancreas, a dilated pancreatic duct, and a swollen major duodenal papilla. When stringent criteria are applied abdominal ultrasonography is useful for the diagnosis of pancreatitis in both dogs and cats.

Abdominal computed tomography is a routine procedure used in humans suspected of having pancreatitis, but appears to be very insensitive for the diagnosis of pancreatitis in the cat and data in dogs are extremely limited.

Minimally-invasive diagnostic tests

Many minimally invasive diagnostic tests for canine and feline pancreatitis have been described, but few have been found to be clinically useful.

Serum lipase activity

Serum lipase activity has been used for the diagnosis of human and canine pancreatitis for several decades. However, it has long been recognized that serum lipase activity is neither very sensitive nor very specific for pancreatitis in either species.

Serum lipase activity has been reported to decrease in dogs after pancreatectomy, indicating that some of the lipase activity present in the serum does originate from the exocrine pancreas. However, considerable serum lipase activity is still present in these dogs after pancreatectomy, indicating that lipase activity must originate from additional sources. It should be noted that there are many cell types that synthesize and secrete lipases. These lipases of different cellular origins share a common function and thus can not be differentiated by use of a catalytic assay such as the ones that are being used to determine lipase activity in serum. To further illustrate this phenomenon serum lipase activity was measured in dogs with exocrine pancreatic insufficiency (EPI). These dogs have no significant pancreatic functional reserve yet in this group of 25 dogs with EPI mean serum lipase activity did not differ significantly from that in 74 healthy dogs and only one dog with EPI had a decreased serum lipase activity below the lower limit of the reference range.

In addition, many non-pancreatic conditions are associated with a significant increase in serum lipase activity, leading to false-positive results. In summary, serum lipase activity is neither very sensitive nor very specific for diagnosing pancreatitis in dogs and should thus only be used if an in-house assay is available and until the diagnosis can be confirmed by another, more specific, diagnostic modality. Finally, if serum lipase activity is analyzed it should be interpreted cautiously and only elevations of 3-5 times the upper limit of the reference range should be considered suggestive of pancreatitis.

In one study not a single cat with pancreatitis had a serum lipase activity above the upper limit of the reference range. These data would suggest that serum lipase activity is of no clinical usefulness for the diagnosis of pancreatitis in cats.

Serum amylase activity

The diagnostic utility of serum amylase activity for canine and feline pancreatitis is very similar to that of serum lipase activity. Some dogs with spontaneous pancreatitis have an elevated serum amylase activity, but others have serum amylase activities in the normal range. Furthermore, dogs with non-pancreatic conditions can have elevations of serum amylase activities. In contrast to its effect on serum lipase activity, the administration of prednisone and dexamethasone to clinically healthy dogs led to a decrease in serum amylase activity. These data would suggest that, as for serum lipase activity, serum amylase activity should only be used for the diagnosis of pancreatitis if an in-house assay is available and until the diagnosis can be confirmed by more accurate diagnostic modalities.

In a study serum amylase activity was not significantly different between cats with spontaneous pancreatitis, clinically healthy cats, and cats with non-pancreatic diseases. This would suggest that serum amylase activity has no clinical usefulness in the diagnosis of pancreatitis in cats.

Serum trypsin-like immunoreactivity (TLI)

Serum trypsin-like immunoreactivity (TLI) is an assay that mainly measures trypsinogen in serum, but will also detect trypsin and some trypsin molecules bound to proteinase inhibitors. During health a small amount of trypsinogen is secreted into the vascular space but very little or no trypsin is present in serum during health. Serum TLI has been shown to originate from the exocrine pancreas almost exclusively. Similar studies are not available for cats, but as in dogs no evidence is available that would suggest that serum TLI concentration can originate from cells other than pancreatic acinar cells.

Only 30-60% of dogs and cats with spontaneous pancreatitis have an elevated serum TLI concentration. This is most likely due to the sort half-life of serum TLI concentration.

Pancreatic lipase immunoreactivity (PLI)

Recently, assays for measurement of pancreatic lipase immunoreactivity in dogs and cats (cPLI and fPLI, respectively) have been developed and validated. As mentioned previously, many different cell types in the body synthesize and secrete lipases. In contrast to catalytic assays for the measurement of lipase activity, use of immunoassays does allow for the specific measurement of lipase originated from the exocrine pancreas.

Serum cPLI was measured in a group of dogs with exocrine pancreatic insufficiency and the median serum cPLI concentration was significantly decreased compared to clinically healthy dogs. In addition, serum cPLI concentration was non-detectable in most of the dogs, indicating that serum cPLI concentration mostly, if not exclusively, originates from the exocrine pancreas. The sensitivity of different minimally-invasive diagnostic tests was compared in dogs with biopsy-proven pancreatitis. The sensitivity of serum TLI concentration was below 35% and that of serum lipase activity was less than 55%. In contrast, the sensitivity for serum cPLI concentration for pancreatitis was above 80%.

In another study of cats with spontaneous pancreatitis serum fPLI concentration was more sensitive and more specific than serum fTLI concentration or abdominal ultrasonography.

These initial data would suggest that serum PLI concentration is highly sensitive and specific for the diagnosis of pancreatitis in dogs and cats. Commercial assays for measurement of cPLI (Spec cPL™) and fPLI (Spec fPL™) are based on the original cPLI and fPLI technology and are available through the GI Lab.

Pancreatic biopsy

Traditionally, a pancreatic biopsy has been viewed as the most definitive diagnostic tool for pancreatitis. The presence of pancreatitis can sometimes be easily determined by gross appearance of the pancreas. However, the absence of pancreatitis can be difficult to prove. In a recent study histopathological findings in dogs with pancreatitis were highly localized, suggesting that even if multiple biopsies are being collected, pancreatic inflammation, especially in cases of chronic pancreatitis, may be easily missed. It should also be noted that while a pancreatic biopsy in itself is not associated with many complications many patients with pancreatitis are poor anesthetic risks. In some patients pancreatic biopsy may be useful for the differentiation of pancreatitis and exocrine pancreatic neoplasia.

Dr. Jörg M. Steiner

References

  1. Newman SJ, Steiner JM, Woosley K, et al. Localization of histologic pancreatitis lesions in dogs. J Vet Int Med 2004; 18:488-493.
  2. Forman MA, Marks SL, De Cock HEV, et al. Evaluation of serum feline pancreatic lipase immunoreactivity and helical computed tomography versus conventional testing for the diagnosis of feline pancreatitis. J Vet Int Med 2004; 18:807-815.
  3. Steiner JM, Gumminger SR, Rutz GM, et al. Serum canine pancreatic lipase immunoreactivity (cPLI) concentrations in dogs with exocrine pancreatic insufficiency. J Vet Int Med 2001;15:274 (abstract).
  4. Steiner JM, Broussard J, Mansfield CS, et al. Serum canine pancreatic lipase immunoreactivity (cPLI) concentrations in dogs with spontaneous pancreatitis. J Vet Int Med 2001;15:274 (abstract).