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.