Medical Physiology, 3rd Edition

Overview of Liver Physiology

After the skin, the liver and the brain are the largest organs in the human body. The liver weighs between 1200 and 1500 g, representing 2% to 5% of body weight in the adult and ~4% to 5% in the newborn. The liver is strategically situated in the circulatory system to receive the portal blood that drains the stomach, small intestine, large intestine, pancreas, and spleen (see Fig. 24-7A). In this position, the liver plays a key role in handling foodstuffs assimilated by the small intestine. However, the liver's role is far more diverse; it serves as a chemical factory, an excretory system, an exocrine gland, and an endocrine gland.

The liver biotransforms and degrades substances taken up from blood and either returns them to the circulation or excretes them into bile

A major function of the liver is to metabolize, detoxify, and inactivate both endogenous compounds (e.g., steroids and other hormones) and exogenous substances (e.g., drugs and toxins). In addition, by virtue of its large vascular capacity and abundance of phagocytes (Kupffer cells), the liver provides an important filtering mechanism for the circulation by removing foreign particulate matter, including bacteria, endotoxins, parasites, and aging red blood cells. Kupffer cells constitute 80% to 90% of the fixed macrophages of the reticuloendothelial system.

The liver has the capacity to convert important hormones and vitamins into a more active form. Examples include the initial hydroxylation of vitamin D and the deiodination of the thyroid hormone thyroxine (T₄) to triiodothyronine (T₃). Moreover, numerous enzymes in the liver process lipophilic chemicals into more polar, water-soluble metabolites, which are more readily excreted into bile.

Bile is a complex secretory product produced by the liver. Biliary secretion has two principal functions: (1) elimination from the body of many endogenous and exogenous waste products, such as bilirubin and cholesterol; and (2) promotion of digestion and absorption of lipids from the intestine. The composition of bile is modified significantly as a result of the absorptive and secretory properties of epithelial cells that line the intrahepatic and extrahepatic bile ducts. Moreover, bile solutes are further concentrated as bile is stored in the gallbladder.

The liver stores carbohydrates, lipids, vitamins, and minerals; it synthesizes carbohydrates, protein, and intermediary metabolites

The products of digested food, including carbohydrates, peptides, vitamins, and some lipids, are avidly extracted from portal blood by the liver. Depending on the metabolic requirements of the body, these substrates may be stored by the hepatocytes or released into the bloodstream either unbound (e.g., glucose) or associated with a carrier molecule (e.g., a triacylglycerol molecule complexed to a lipoprotein).

The liver also synthesizes—in a highly regulated fashion—many substances that are essential to the metabolic demands of the body. These substances include albumin, coagulation factors, and other plasma proteins; glucose; cholesterol; fatty acids for triacylglycerol biosynthesis; and phospholipids. The liver must provide a supply of substrates as fuels for other organs, particularly in the fasted state. For example, the liver produces ketone bodies, which can be used by the central nervous system during periods of fasting; this use of ketone bodies as fuel spares ~50% of the amount of glucose that would otherwise be used by this tissue. Thus, the liver has a critical and unique role in the energy metabolism of all nonhepatic organs.