The biochemical pathology of liver cell necrosis.
Cell death and necrosis are important reactions of liver cells to injury that play a role in a wide variety of human liver diseases. A review is given of the important facets known about the biochemical basis of toxic liver cell death. Liver cells can withstand a great many specific biochemical and morphologic changes without loss of viability. Disturbances in RNA and protein synthesis, mitochondrial function, or release of lysosomal enzymes do not play a primary causative role in cell death. Many previous studies have tended to implicate the plasma membrane and its presumed role in maintaining the proper Ca2+ balance as the primary site of the development of irreversible hepatocyte damage. These studies have generally faced a major difficulty in determining if the observed changes are the cause or an effect of cell death. Galactosamine-induced liver cell injury seems to offer a potentially analyzable model for the experimental analysis of liver cell necrosis. Our studies on the role of plasma membrane injury and associated increases in total cellular calcium are reviewed, and a tentative working hypothesis for the pathogenesis of galactosamine-induced liver cell necrosis is presented.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D005688:Galactosamine; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009336:Necrosis; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D014529:Uridine / Q000494:pharmacology
D012313:RNA; D005688:Galactosamine; D002118:Calcium; D014529:Uridine