SpecificOrgan/System Toxicity: the Liver

Mammalian liver consists of at least fourteen different types of cells. Hepatocytes, the most common site of toxic action, account for between 60 per cent (rat) and 85 per cent (man) of the total number of cells in the liver, or 90-95 per cent of the total weight of the liver. The reticuloendothelial cells (also called Kupffer, littoral or sinusoidal cells) only constitute 5-10 per cent of liver by weight but they can comprise up to 35 per cent of the total cell population. Other cells include fat storing and pit cells. Despite their morphological similarity, hepatocytes are not a homogeneous population. For example, those from the centrilobular region contain significantly higher levels of cytochrome P-450 (and are much more responsive to induction by phenobarbitone) than those derived from the mid-zonal or periportal regions. Cells of the periportal area tend to be more metabolically active than those of mid-zonal and centrilobular regions, probably because they are more richly endowed with blood and consequently with nutrients and oxygen. The liver has a wide range of important physiological functions and is the site of a wide range of intermediary metabolite reactions. These functions include: