The Hepatic Microvascular System in Health and Its Response to Toxicants

This review briefly summarizes what is known about the dynamic morphology of the hepatic microvascular system that includes all vessels in the liver with a diameter less than 300 microm and various morphological sites within these vessels that regulate the distribution of blood flow. The latter include the various segments of the afferent portal venules and hepatic arterioles, the sinusoids, and central and hepatic venules. Sinusoids are unique exchange vessels lined by fenestrated endothelial cells which have important endocytotic functions and phagocytic Kupffer cells which are important for host defense. These are encircled by extraluminal stellate cells that are specialized pericytes containing fat droplets that store vitamin A. The principle sites for regulating blood flow are in the sinusoidal network with stellate and endothelial cells playing a major role in regulating the diameters of sinusoids and the distribution of blood flow in individual sinusoids, lobules, or segments of lobules. The sinusoidal endothelial cells are a sensitive and early target for several toxicants. For example, as early as 30 minutes after the administration of acetaminophen, the endothelial cells become swollen and begin to lose the ability to endocytose ligands. Within 2 hr, gaps through the cytoplasm appear formed by the destruction and/or coalescence of fenestrae which permit red blood cells to penetrate into the space of Disse. Subsequently, the sinusoid may collapse or disintegrate reducing blood flow.