Possible mechanisms of acute pancreatitis induced by ethanol.
We investigated the effect of intravenous and intragastric ethanol on pancreatic duct pressure, duct permeability to dextran molecules (20,000 molecular weight), and on the development of acute pancreatitis in an experimental model of the disease. Intragastric ethanol caused a small increase in pancreatic duct pressure (6 to 7 mm Hg) and an increase in duct permeability to dextran. Intravenous ethanol with exclusion of the sphincter of Oddi did not increase pancreatic duct pressure or permeability. Intravenous ethanol and intragastric normal saline solution altered neither pressure nor permeability. Artificial elevation of pancreatic duct pressure alone with no ethanol had no effect on duct permeability. However, when intravenous ethanol was given to produce similar systemic concentrations as achieved in the intragastric experiments (250 mg/dl) and duct pressure was artificially raised, duct permeability was increased. Ethanol concentrations similar to those found in peripheral blood were detected in secretin-stimulated pancreatic juice. Perfusion of the pancreatic duct with activated pancreatic enzymes after intragastric but not intravenous ethanol (that is, only in animals with increased duct permeability) caused acute edematous pancreatitis. Our results confirmed that increased duct permeability was necessary to produce acute pancreatitis in this model, and that this increase in permeability resulted from both a small increase in duct pressure and probably from the toxic metabolic effects of ethanol.
Harvey
M H
MH
Department of Surgery, University of Missouri Health Sciences Center.
Cates
M C
MC
Reber
H A
HA
D000208:Acute Disease; D000818:Animals; D002415:Cats; D000431:Ethanol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D007262:Infusions, Intravenous; D010183:Pancreatic Ducts / Q000503:physiopathology; D010189:Pancreatic Juice / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000503:physiopathology*; D010539:Permeability; D011312:Pressure; D009803:Sphincter of Oddi / Q000503:physiopathology; D013270:Stomach
D000431:Ethanol