Pancreatic pathophysiology – Acute pancreatic necrosis (APN)
The initiating event of acute pancreatitis is the premature activation of digestive zymogens within the acinar cell. Premature
activation of digestive zymogen results in acinar cell necrosis and pancreatic autodigestion. In acute pancreatic necrosis,
protein synthesis and intracellular transport to the Golgi complex appear to be normal, but digestive zymogens then become
co-localized along with lysosomal hydrolases in large vacuoles. Cell biology studies have revealed that lysosomal and zymogen
granule fractions become co-localized through a process known as crinophagy, a process used by many cells to degrade accumulated
secretory products when the need for secretion is no longer present. Although this process takes place in other cells without
adverse consequences, it can be lethal in pancreatic acinar cells because of the peculiarity of their secretion products (digestive
zymogens). Lysosomal hydrolases, such as cathepsin B and N-acetyl glucosaminidase, activate trypsinogen to the active trypsin
form, and the enhanced fragility of these large vacuoles permits release of active enzyme into the cell cytoplasm. Trypsin
acts auto-catalytically to activate other trypsinogen molecules and other zymogens, each inducing a unique chemical pathology
in pancreatic and extra-pancreatic cells. A variety of inflammatory mediators and cytokines (tumor necrosis factor-α, interferon-α,
interferon-γ, platelet-activating factor), interleukins (IL-1, IL-2, IL-6, IL-8, IL-10), nitric oxide, and free radicals are
involved in the further evolution of pancreatic acinar cell necrosis and inflammation.
New findings in canine acute pancreatitis
Canine acute pancreatitis (AP) is a common disorder which may result in death if not diagnosed in a timely fashion. This frequently
encountered disease remains difficult to diagnose because the clinical signs, physical examination findings, and clinicopathologic
changes are often non-specific. Therefore, knowledge of risk factors of canine AP and recognition of the clinical manifestations
of this disorder are important.
The risk factors discussed in this manuscript were identified in a group of dogs in which all dogs had histopathologic confirmation
of AP. The control group included dogs in which histopathologic examination excluded the possibility of AP. Clinicopathologic,
radiographic, and ultrasonographic findings also pertain to dogs in which a diagnosis of AP was confirmed by histopathologic
examination of the pancreas.
Risk factors for canine acute pancreatitis
Yorkshire terriers are at increased risk of developing AP, whereas miniature poodles and Labrador retrievers are at decreased
risk for AP. Breed predisposition may suggest that there is a hereditary component to AP. Hereditary pancreatitis in humans
can occur in association with a genetic defect of lipoprotein lipase, in individuals with hypertriglyceridemia and diabetes
mellitus, or as an autosomal dominant trait, of unknown etiology, with a chronic recurrent presentation, and an early onset
(usually in childhood). Further investigation is needed to determine if familial lipid metabolism disorders, or other genetic
defects, predispose Yorkshire terriers to AP.
The mean age of dogs with AP is 8 years. Dogs with AP may be middle to older age dogs because several of the risk factors
for AP (diabetes mellitus, hyperadrenocorticism, and hypothyroidism) develop in middle to older aged dogs. Obesity, which
is another risk factor for AP may also be a problem of middle-aged dogs. Additionally, the increased age of dogs with AP could
be a reflection of a degenerative pancreatic or extrapancreatic process, or a result of accumulating metabolic disorders that
increase the risk of AP.
Males and neutered females are at increased risk compared to intact female dogs. This finding may indicate that sex hormones
or other gender specific factors are involved in the pathophysiology of AP.