Why does pancreatic overstimulation cause pancreatitis?

Annu Rev Physiol. 2007;69:249-69. doi: 10.1146/annurev.physiol.69.031905.161253.

Abstract

Many animal models are available to investigate the pathogenesis of pancreatitis, an inflammatory disorder of the pancreas. However, the secretagogue hyperstimulation model of pancreatitis is the most commonly used. Animals infused with high doses of cholecystokinin (CCK) exhibit hyperamylasemia, pancreatic edema, and acinar cell injury, which closely mimic pancreatitis in humans. Intra-acinar zymogen activation is an essential early event in the pathogenesis of secretagogue-induced pancreatitis. Early in the course of pancreatitis, lysosomal hydrolases colocalize with digestive zymogens and activate them. These activated zymogens then cause acinar cell injury and necrosis, a characteristic of pancreatitis. Besides being the site of initiation of injury in pancreatitis, acinar cells also synthesize and release cytokines and chemokines very early in the course of pancreatitis, which then attract and activate inflammatory cells and initiate the disease's systemic phase.

Publication types

  • Review

MeSH terms

  • Animals
  • Cholecystokinin / physiology
  • Ethanol / pharmacology
  • Extracellular Space / physiology
  • Humans
  • Pancreas / physiopathology*
  • Pancreatitis / physiopathology*
  • Solvents / pharmacology

Substances

  • Solvents
  • Ethanol
  • Cholecystokinin