Alcohol-induced hepatomegaly: pathogenesis and role in the production of portal hypertension.
Hepatomegaly after chronic alcohol consumption results from an increase in cell size and not in cell number. About 50--60% of the increase in liver weight is accounted for by an increase in intracellular water, while extracellular water remains constant. Therefore, a substantial reduction in the ratio of extracellular to intracellular water occurs. Intracellular potassium can osmotically account for 40--50% of the excess water retained in the hepatocytes. It is proposed that an increase in hepatocyte size after chronic alcohol consumption compresses vascular-sinusoidal pathways. This results, after a threshold in cell size is exceeded, in increased intrahepatic and portal pressure. Possible factors responsible for the threshold are proposed. By applying the concept that animal cells act as osmometers, a new in vitro model has been developed to study the relationship between cell enlargement and portal pressure. In this model, the existence of a threshold and the generation of portal hypertension associated with hepatocyte enlargement have been demonstrated. In humans with alcoholic liver disease, a threshold in hepatocyte size enlargement (1600--1700 micrometer 2) before pressures were increased was also observed. In these patients, a strong correlation was also found between hepatocyte size and intrahepatic pressure. The same correlation occurs regardless of the presence or absence of cirrhosis, therefore suggesting that a major determinant of portal hypertension in cirrhosis is cell size and not the existence of nodules of fibrous septa. The higher portal pressures found in cirrhotics may be explained by the fact that these patients have larger hepatocytes.
D000818:Animals; D004247:DNA / Q000032:analysis; D005260:Female; D006529:Hepatomegaly / Q000139:chemically induced*; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology*; D006984:Hypertrophy; D066298:In Vitro Techniques; D008099:Liver / Q000032:analysis; D008102:Liver Circulation; D008104:Liver Cirrhosis, Alcoholic / Q000503:physiopathology; D008108:Liver Diseases, Alcoholic / Q000150:complications*; D008297:Male; D008954:Models, Biological; D009929:Organ Size; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D011188:Potassium / Q000378:metabolism; D051381:Rats; D014882:Water-Electrolyte Balance / Q000187:drug effects
D004247:DNA; D011188:Potassium