[Etiology, pathogenesis and pathophysiology of acute pancreatitis].
The etiology of acute pancreatitis is based on several causes, among which idiopathic nature (< 30%) is second to biliary stone disease (60-70%). It is still under debate whether alcohol as the main cause of chronic pancreatitic disease can cause acute pancreatitis. Based on Opie's "obstruction theory" of 1901 and experimental data, it is now widely accepted that the gallstone passage into or through the terminal biliopancreatic ductal system triggers acute (necrotizing) pancreatitis by causing pancreatic ductal obstruction. However, the sequential intracellular mechanisms in the pathogenesis of acute pancreatitis remain unclear. A co-localization hypothesis has been proposed to explain the premature intracellular activation of trypsinogen to trypsin: due to a yet unknown defect in the intracellular protein transport and sorting system within the acinar cell, lysosomal hydrolases (i.e. cathepsin B) and secretory proteins (i.e. trypsinogen) co-localize in a fragile postgolgi vacuole where activation can occur. In addition, alterations of exo- and endocytosis at the apical pole exist (i.e. secretion block). The pathophysiological events are characterized by local and systemic hypovolemia and (micro)circulatory failure aggravating necrosis, followed by ARDS, renal failure and several other severe complications (i.e. sepsis and DIC). The systemic overflow of proteolytic enzymes (i.e. PLA-2) and kinins plays a major role as mediating factor in severe cases, resulting in multiorgan failure.
Rünzi
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Abteilung für Gastroenterologie, Universitätsklinikum Essen.
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D042882:Gallstones / Q000150:complications / Q000503:physiopathology; D006801:Humans; D007705:Kinins / Q000502:physiology; D009102:Multiple Organ Failure / Q000209:etiology / Q000503:physiopathology; D019283:Pancreatitis, Acute Necrotizing / Q000209:etiology* / Q000503:physiopathology; D019512:Pancreatitis, Alcoholic / Q000150:complications / Q000503:physiopathology; D010447:Peptide Hydrolases / Q000502:physiology
D007705:Kinins; D010447:Peptide Hydrolases