The liver’s strategic location between intestinal tract and the rest of the body facilitates its maintenance of metabolic homeostasis in the body.
The liver extracts ingested nutrients, vitamins, metals, drugs, environmental toxicants, and waste products of bacteria from the blood for catabolism, storage, and/or excretion into bile.
Formation of bile is essential for uptake of lipid nutrients from the small intestine, protection of the small intestine from oxidative insults, and excretion of endogenous and xenobiotic compounds.
Cholestasis is either a decrease in the volume of bile formed or an impaired secretion of specific solutes into bile, which results in elevated serum levels of bile salts and bilirubin.
Hepatocytes have phase I enzymes that often convert xenobiotics to reactive electrophilic metabolites and phase II enzymes that add a polar group to a molecule and thereby enhance its removal from the body. The balance between phase I and phase II reactions determines whether a reactive metabolite will initiate liver cell injury or be safely detoxified.
The liver performs many critical life functions, including processing of foods and other substances absorbed from the intestinal tract and subsequent delivery of processed nutrients to other organs in the body. The liver also contributes to immunity that protects mammals from harmful pathogens. It is the main organ where exogenous chemicals are metabolized for eventual excretion into bile and urine.
Knowledge of liver physiology and anatomy lends insight as to how the liver functions and provides underpinnings for understanding how toxicants cause liver dysfunction. Chemical-induced liver injury is typically initiated by one or more critical events, such as formation of a toxic metabolite, which trigger intracellular responses that can progress to dysfunction or death of hepatic parenchymal cells (i.e., HPCs, hepatocytes). These intrahepatocellular events can in turn prompt secondary events involving activation of nonparenchymal cells that magnify or attenuate the initial injury.
LIVER ANATOMY AND PHYSIOLOGY
Hepatic Functional Anatomy
The liver has a dual blood supply (Fig. 13–1). The hepatic artery supplies a minority of blood entering the liver. The hepatic portal vein, which comprises venous drainage from the stomach and intestine, is the major supplier of blood that contains food-borne xenobiotic agents absorbed into the blood from the gastrointestinal (GI) tract, and that is poorly oxygenated.
Liver circulation and lobular organization. (A) Physiologically based model of the body; the liver is unusual among organs in having a dual blood supply, one from arterial blood and the other from blood that drains the gastrointestinal tract. (Reprinted with permission from Kuo I, Akpa BS. Validity of the lipid sink as a mechanism for the reversal of local anesthetic systemic toxicity: a physiologically based pharmacokinetic model study. Anesthesiology. 2013;118(6):1350–1361.) (B) Blood enters the liver from the hepatic artery and from the portal vein, which arises from gastrointestinal and ...