Gastroenterology

Pathogenesis

Pathology

Medicine

Pancreatitis

Premature activation of digestive enzymes in the pancreas has been linked to development of pancreatitis for more than a century. Recent development of novel models to study the role of pathologic enzyme activation has led to advances in our understanding of the mechanisms of pancreatic injury. Colocalization of zymogen and lysosomal fraction occurs early after pancreatitis-causing stimulus. Cathepsin B activates trypsinogen in these colocalized organelles. Active trypsin increases permeability of these organelles resulting in leakage of cathepsin B into the cytosol leading to acinar cell death. Although trypsin-mediated cell death leads to pancreatic injury in early stages of pancreatitis, multiple parallel mechanisms, including activation of inflammatory cascades, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction in the acinar cells are now recognized to be important in driving the profound systemic inflammatory response and extensive pancreatic injury seen in acute pancreatitis. Chymot...

Early Intra-Acinar Events in Pathogenesis of Pancreatitis