Pathophysiology of acute pancreatitis

Recent experiments in different animal models of acute pancreatitis have improved our understanding of the pathophysiology of this disease. The present review discusses the individual steps and mechanisms and puts them into a pathophysiologic concept for the two most important forms of acute pancreatitis (alcoholic and biliary form). In biliary acute pancreatitis a temporary occlusion of the common channel by impacted stones may be followed by a reflux into the pancreatic duct. This reflux results in an increase of ductal permeability and extravasation of cytotoxic agents into the surrounding tissue. As consequences, disturbances of compartimentation and faulty activation of enzymes occur in pancreatic cells. Long-term cellular damage, obstruction of pancreatic ducts and increase of ductal permeability with leakage of noxious agents play a substantial role in pathophysiology of alcoholic pancreatitis. Sustained abuse of alcohol usually leads to chronic pancreatitis. Additional, as yet unknown factors are necessary to induce acute alcoholic pancreatitis. Following its initiation by different etiological sources, pathophysiology of acute pancreatitis may take a similar course. Digestive enzymes are activated and set free into intracellular, intraductal and interstitial spaces. Trypsin as the trigger-enzyme of activation cascade is thought to play a major role. In addition, lipolytic enzymes may be involved in the pathophysiologic process. Phospholipase A is known to release lysolecithin which causes membrane damage. Recent studies indicate that the release of fatty acids by lipase causes acinar cell necrosis. New insights into the pathophysiology may lead to a rational and more successful therapy of acute pancreatitis.