[dwerten]

New Concepts in Canine Pancreatitis

Jörg M. Steiner, med.vet., Dr.med.vet., PhD, Dipl. ACVIM, Dipl. ECVIM-CA
Associate Professor and Director Gastrointestinal Laboratory Department of Small Animal Medicine and
Surgery Texas A&M University, College Station, TX


Introduction

The incidence of exocrine pancreatic disorders in dogs is quite large. In a large retrospective study of
necropsy findings, 1.5% of 9,342 canine pancreata showed significant pathological lesions.
Approximately 50% of all canine patients with exocrine pancreatic disorders have pancreatitis and
approximately 2/3 of dogs with pancreatitis have acute disease. According to the current classification
system of human pancreatitis, acute pancreatitis is an inflammatory condition of the pancreas that is
completely reversible after removal of the inciting cause.1 Chronic pancreatitis is characterized by
irreversible histopathologic changes (i.e., fibrosis and/or atrophy) of exocrine pancreatic tissue. Both
forms can be mild or severe. Mild forms of pancreatitis are associated with no or little pancreatic
necrosis and systemic complications and often allow recuperation of the patient. In contrast, severe
forms of pancreatitis are associated with extensive pancreatic necrosis, multiple organ involvement,
and often a poor prognosis.

Etiology and Pathogenesis

According to a generally accepted pathogenic model, pancreatic acinar cells ultimately respond in a
common fashion to a variety of harmful stimuli, leading to inappropriate intracellular activation of
trypsin and subsequently activation of other digestive zymogens.2 The activated digestive enzymes
cause local changes, such as inflammation, hemorrhage, acinar cell necrosis, and peripancreatic fat
necrosis. Digestive enzymes released into the blood stream may cause systemic changes, including
systemic inflammatory changes, systemic vasodilatation leading to hypotension, pulmonary edema,
disseminated intravascular coagulation, central neurologic deficits, respiratory failure, renal failure, and
multiorgan failure. However, more recently, cytokines are believed to play a more important role in the
progression of pancreatitis and the development of systemic effects.3

Several diseases and risk factors have been associated with pancreatitis.4 Hyperlipidemia and dietary
indiscretion have been implicated in causing pancreatitis in dogs but experimental evidence supporting
this implication are sparse. Traumatic pancreatitis (due to road traffic accidents) has been reported as a
cause of pancreatitis. Surgical trauma can cause pancreatitis but many human patients that undergo
surgery of organs distant from the pancreas have also been shown to be at an increased risk for
pancreatitis suggesting that hypoperfusion of the exocrine pancreas during anesthesia may be of
bigger concern than surgical handling of the organ itself. Infectious agents, such as Toxoplasma gondii
or hepatic fluke infestation have been shown to cause rare cases of pancreatitis in cats, but not in dogs.
Many pharmaceutical compounds have been implicated in causing pancreatitis in human beings and
dogs. Finally, more than 90% of all cases of canine pancreatitis are idiopathic.

Clinical picture

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 (91%; data from a study of 70 dogs with fatal
pancreatitis), vomiting (90%), weakness (79%), abdominal pain (58%), dehydration (46%), and diarrhea
(33%).5 Severe cases can present with systemic clinical signs, such as fever or even cardiovascular
shock. Clinical signs in patients with pancreatitis are due to pancreatic inflammation or systemic effects
to the pancreatic inflammation. Recent data suggest that 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, visible only by electron microscopy. Biochemical
studies have shown that these vacuoles are the product of co-localization of zymogens of digestive 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 commonly 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. 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 patients with severe forms of pancreatitis and
can lead to fever. Other systemic effects seen in patients 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 patients also develop systemic lipodystrophy, also known as pancreatitis associated panniculitis or
Weber-Christian syndrome. Neurologic signs, such as disorientation have been seen in human and
canine patients with severe pancreatitis and are sometimes referred to as pancreatic encephalopathy.
While clinical signs are not specific for pancreatitis, vomiting and cranial abdominal pain are key clinical
signs in dogs with pancreatitis and a dog presenting with both of these signs should be carefully
evaluated for the presence of pancreatitis.