The liver plays an essential role in metabolic homeostasis. Hepatic functions include the synthesis, storage, and breakdown of glycogen. In addition, the liver is important in the metabolism of lipids; the synthesis of albumin, clotting factors, and other important proteins; the synthesis of the bile acids necessary for absorption of lipids and lipid soluble vitamins; and the metabolism of cholesterol.64,159 Hepatocytes facilitate the excretion of metals, most importantly iron, copper, zinc, manganese, mercury, and aluminum, as well as the detoxification of products of metabolism, such as bilirubin and ammonia.32,74 Generalized disruption of these important functions results in manifestations of liver failure: hyperbilirubinemia, coagulopathy, hypoalbuminemia, hyperammonemia, and hypoglycemia.86,89,137 Disturbances of more specific functions result in accumulation of lipids, metals, and bilirubin, and the development of lipid-soluble vitamin deficiencies.64,159
The liver is also the primary site of biotransformation and detoxification of xenobiotics. Its interposition between the gut and systemic circulation makes it the first-pass recipient of xenobiotics absorbed from the gastrointestinal tract. The liver receives blood from the systemic circulation and participates in the detoxification and elimination of xenobiotics that reach the bloodstream through other routes, such as inhalation or cutaneous absorption.142,159,160
Many xenobiotics are lipophilic and inert and require chemical modification followed by conjugation to make them sufficiently water-soluble to be eliminated. The liver contains the highest concentration of enzymes involved in phase I oxidation-reduction reactions, the first stage of detoxification for many lipophilic xenobiotics. Conjugation of the reactive products of phase I biotransformation with molecules such as glucuronide facilitates excretion (Chap. 13). Although many xenobiotics that are detoxified in the liver are subsequently excreted in the urine, the biliary tract provides a second essential route for the elimination of detoxified xenobiotics and products of metabolism.32,56,160 Although phase I activation of xenobiotics is usually followed by phase II conjugation that results in detoxification, it can also lead to the production of xenobiotics with increased toxicity, which may cause injury to hepatocytes at the site of their synthesis.142,160
MORPHOLOGY AND FUNCTION OF THE LIVER
Two pathologic concepts are used to describe the appearance and function of the liver: a structural one represented by the hepatic lobule and a functional one represented by the acinus. The basic structural unit of the liver as characterized by light microscopy is the hepatic lobule, a hexagon with the central hepatic vein at the center and the portal triads at the angles. The portal triad consists of the portal vein, the common bile duct, and the hepatic artery. Cords of hepatocytes are oriented radially around the central hepatic vein, forming sinusoids. In contrast, the acinus, or “metabolic lobule” is the functional unit of the liver. Located between two central hepatic veins, it is bisected by terminal branches ...