title: Acute pancreatitis in man. A clinical and biochemical study of pathophysiology and treatment.
abstract: The correlation between clinical course, protease inhibitors, complement and kinin activation was studied in vivo in 27 attacks of acute pancreatitis and also in vitro. The value of peritoneal lavage was retrospectively analyzed in 73 pancreatitis attacks. The effect of aprotinin was studied in vitro. Complement and kinin activation occurred in vitro when alpha-macroglobulin (alpha 2-M) concentration was below 35%, in spite of 90% free and reactive alpha 1-protease inhibitor. These low alpha 2-M levels were found in the general circulation in severe attacks. Functional alpha 2-M levels were lower than electroimmunoassay values during the acute disease. Complement and kinin activation was present both in blood and in peritoneal fluid. The extent of activation was closely correlated to the severity of the pancreatitis attack. Classical as well as alternative complement activation occurred. Kinin activation was caused by plasma kallikrein as well as by other kininogenases. Functional kallikrein inhibition was lower than electroimmunoassay values for the C1 inactivator. High levels of activated trypsin was found in complex with alpha 1-protease inhibitor in severe attacks. These findings together with the low functional alpha 2-M and a possible functional deficiency also of the C1 inactivator make trypsin-induced activation of the complement as well as the kinin system possible in acute pancreatitis. Changes in proteases and protease inhibitors were most pronounced in the peritoneal fluid, functional alpha 2-M and C1 inactivator being zero, indicating that the primary event occurs locally in and around the pancreas. Peritoneal lavage thus ought to be beneficial. The good results achieved with peritoneal lavage in the retrospective analysis of the 73 clinically severe attacks seem to verify this conclusion. The biochemical changes seen in vivo indicate alpha 2-M and C1 inactivator to be most important against proteolytic activation of the complement and kinin systems. Treatment with purified protease inhibitors might be beneficial. This also seems to be true of aprotinin, according to the in vitro results, provided very high doses are used. All antiprotease therapy seems to be most important intraperitoneally.
mesh_terms: D000208:Acute Disease; D000818:Animals; D007611:Aprotinin / Q000627:therapeutic use; D003165:Complement System Proteins / Q000276:immunology; D004285:Dogs; D006801:Humans; D007610:Kallikreins / Q000097:blood; D007705:Kinins / Q000097:blood; D010195:Pancreatitis / Q000201:enzymology / Q000503:physiopathology* / Q000628:therapy; D010537:Peritoneum; D011379:Prognosis; D011480:Protease Inhibitors / Q000097:blood / Q000276:immunology; D013045:Species Specificity; D007507:Therapeutic Irrigation; D014357:Trypsin / Q000378:metabolism
chemical_list: D007705:Kinins; D011480:Protease Inhibitors; D003165:Complement System Proteins; D007611:Aprotinin; D007610:Kallikreins; D014357:Trypsin