THE NATURE AND SIGNIFICANCE OF LIVER-CELL VACUOLATION FOLLOWING HEPATOCELLULAR INJURY - AN ANALYSIS BASED ON OBSERVATIONS ON RATS RENDERED TOLERANT TO HEPATOTOXIC DAMAGE

Swelling with nonlipid cytoplasmic vacuolation of diffusely distribute d hepatocytes is seen consistently after mild acute and subacute liver injury. Several lines of evidence point to the possibility that this change may reflect a cellular adaptation beneficial to the host, rathe r than a degenerative change. The nature and significance of this morp hological manifestation were rested in batches of albino rats given sm all doses of a variety of hepatotoxins, some of which were subsequentl y challenged with a large highly necrogenic dose of carbon tetrachlori de (CCl4). Morphological and biochemical investigations showed that cy toplasmic vacuolation of liver cells following low doses of toxins was due to excess accumulation of glycogen, predominantly of the monopart iculate form. These cells lacked features of degeneration or regenerat ion and were much less susceptible to injury by the large dose CCl4, a s assessed by structural and serum enzyme analyses. This tolerance to toxic damage seemed to be associated with excess accumulation of intra cellular glycogen. We conclude from these and other observations on an imal and human livers that many of the vacuolated hepatocytes seen in liver injury are cells adaptively altered to resist further insult rat her than cells undergoing hydropic degeneration, as is commonly believ ed.