Alcohol-induced pancreatic injury (Part I). Unexplained features and ductular theories of pathogenesis.
The pathogenesis of alcoholic pancreatitis continues to be a puzzle. Classical theories of pathogenesis tend to overlook the dual nature of the disease, i.e., symptomatic acute attacks and chronic progressive parenchymal destruction. Furthermore, it is unknown why only a small minority of alcoholics develop clinical pancreatic injury. In addition, there is a lack of basic data concerning the natural history of the condition after cessation of alcohol consumption. The most widely accepted theory of pathogenesis postulates the deposition of protein plugs in peripheral pancreatic ducts as the initial lesion. However, it has not been established that these plugs are the cause rather than a result of pancreatic injury. The so-called "Big Duct" theories of pathogenesis (biliary-pancreatic reflux, duodeno-pancreatic reflux, and obstruction-hypersecretion) are confounded by a lack of agreement concerning the effect of alcohol on the sphincter of Oddi. Nutritional factors and heredity may be responsible for the selectivity of alcohol in this condition; in this regard, a number of dietary and HLA studies have been performed, but these have generally been inadequately controlled. Subcellular pancreatic injury (fat droplets, autophagic vacuoles, and mitochondrial lesions) has been observed in alcoholics without pancreatitis and in animals fed alcohol. In addition, ethanol feeding in animals has been shown to affect pancreatic cholesterol, phospholipid, and fatty acid metabolism as well as pancreatic content of digestive enzymes. Research is hampered by the lack of a suitable animal model of the disease.
Wilson
J S
JS
Gastroenterology Section, VA Medical Center, Bronx, NY 10468.
Korsten
M A
MA
Pirola
R C
RC
D000428:Alcohol Drinking; D001646:Bile / Q000502:physiology; D001652:Bile Ducts / Q000502:physiology; D001655:Bile Reflux / Q000150:complications; D004032:Diet / Q000009:adverse effects; D004198:Disease Susceptibility; D000431:Ethanol / Q000009:adverse effects*; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications; D008962:Models, Theoretical; D010179:Pancreas / Q000502:physiology; D010195:Pancreatitis / Q000139:chemically induced* / Q000209:etiology / Q000235:genetics; D011312:Pressure; D009803:Sphincter of Oddi / Q000187:drug effects / Q000502:physiology
D000431:Ethanol