Pancreatitis in Dogs and Cats

The fundamental mechanism of disease in pancreatitis is autodigestion of pancreatic tissue by digestive enzymes that are prematurely activated within the pancreatic acinar cells. Normally, pancreatic digestive enzymes are released from the pancreas as inactive precursor zymogen granules. Trypsinogen within these granules is proteolytically cleaved and activated when it reaches the duodenal lumen by an enzyme called enteropeptidase (previously named enterokinase). The newly-formed trypsin is then able to activate other zymogens in the duodenal lumen by proteolytically cleaving from each of them a small amino terminal peptide called the ‘activation peptide’. In acinar cells, the developing granules are normally kept strictly separated from lysosomes, where they might inadvertently get activated. In many experimental models of acute pancreatitis, zymogen granules fuse abnormally with lysosomes inside acinar cells leading to inappropriate intra-pancreatic activation of the zymogens. Lysosomes contain proteases that, at low pH, are capable of activating the zymogens. For protection, the pancreas contains trypsin inhibitors. Also, trypsin can auto-catalyse its own degradation, further enhancing safety. However, the inhibitor present in zymogen granules is not active at the low pH present in lysosomes. If the zymogen activation process proceeds too vigorously, pancreatitis can result.