Target organs and systemic toxicology: Liver

Target organs and systemic toxicology: Liver
Numerous industrial compounds and therapeutic agents have been found to injure the liver and it can consider as a target site of specific toxins. Ingested toxins are absorbed from the gastrointestinal tract in a lipid-soluble state and are transported directly to the liver through the portal system, exposing the liver to the highest concentrations of these agents. In addition, because of its central role in the detoxification of xenobiotics, the liver is especially susceptible to toxic injury by metabolites of the toxin. Reactive metabolites produced by the process of detoxification often cause hepatocellular injury at the site of their formation.
The major functions of the liver can be altered harmfully by acute or chronic exposure to toxicants. In acute exposure, toxicants can inhibit or delay hepatic transport and synthetic processes without appreciable cell damage. Chronic exposure can kill an appreciable number of cells and replace them by nonfunctional scar tissue.

Structural Organization
Hepatocytes are the main structural unit of the liver. While the acinus is the functional unit of the liver. It consists of a hepatic arteriole, a portal venule, and a bile ductule. The acinus has three zones:
Zone 1: it is closest to the entry of blood, rich in O2 and nutrients, also contains large amount of enzymes responsible for gluconeogenesis and fatty acid oxidation, protein synthesis, amino acids catabolism, bile acid secretion and it is GSH- rich region.
Zone 2: is intermediate where regeneration occurs from cells located in this region.
Zone 3: it is adjacent to the terminal hepatic vein, it has less O2 and nutrients, it contains large amounts of smooth endoplasmic reticulum, NADPH, Cyt P450. Lipid synthesis occurs in this region and it is the most affected by toxicants.