Pathogenesis of Chronic Pancreatitis with Special Emphasis on Genes

The pathogenesis of alcohol-induced chronic pancreatitis is still not completely understood. One discusses alcohol-induced fatty degeneration of pancreatic acinar cells, disturbances in ethanol detoxification, reduced synthesis of lithostathines, changes in duct permeability, a pressure increase of the papilla of Vater, generation of free radicals, etc. Hereditary chronic pancreatitis (HCP) is a rare form of early-onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features, and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2), the serine protease inhibitor, Kazal type 1 (SPINK1), and the cystic fibrosis transmembrane conductance regulator (CFTR) have been found to be associated with chronic pancreatitis (idiopathic and hereditary) as well. The findings in HCP highlight that the protease trypsin seems to play a major role in pathogenesis of chronic pancreatitis.