Hypoxic hepatocellular injury.

Low flow hypoxia to the isolated, perfused rat liver produced stable, circumscribed zones of virtual anoxia which were confined to centrilobular regions of the liver lobule. As a result, centrilobular hepatocytes were injured while periportal tissue was spared. In hypoxic areas, blebs of hepatocyte plasma membrane cytoplasm protruded into sinusoids through fenestrations of the endothelium, evidently as a result of disruption of the cytoskeleton. Upon resumption of normal flow rates (reoxygenation), blebs disappeared and hepatocytes decreased markedly in volume. Concomitantly, sinusoids widened, endothelial fenestrations dilated, and lactate dehydrogenase activity appeared in the effluent. Filtration of perfusates following resumption of flow yielded cytoplasmic fragments, and it was concluded that blebs were released into the circulation. This shedding of cytoplasmic fragments may represent the cellular basis for the appearance of hepatic enzymes in the sera of patients with liver disease.