The liver, which is part of the digestive system, performs more than 500 different functions, all of which are essential to life. Its essential functions include helping the body to digest fats, storing reserves of nutrients, filtering poisons and wastes from the blood, synthesizing a variety of proteins, and regulating the levels of many chemicals found in the bloodstream. The liver is unique among the body’s vital organs in that it can regenerate, or grow back, cells that have been destroyed by some short-term injury or disease. But if the liver is damaged repeatedly over a long period of time, it may undergo irreversible changes that permanently interfere with function.
 

Despite its many complex functions, the liver is relatively simple in structure. It consists of two main lobes, left and right, which overlap slightly. The right lobe has two smaller lobes attached to it, called the quadrate and caudate lobes.

Each lobe contains many thousands of units called lobules that are the building blocks of the liver. Lobules are six-sided structures each about 1 mm (0.04 in) across. A tiny vein runs through the center of each lobule and eventually drains into the hepatic vein, which carries blood out of the liver. Hundreds of cubed-shaped liver cells, called hepatocytes, are arranged around the lobule's central vein in a radiating pattern. On the outside surface of each lobule are small veins, ducts, and arteries that carry fluids to and from the lobules. As the liver does its work, nutrients are collected, wastes are removed, and chemical substances are released into the body through these vessels.

Unlike most organs, which have a single blood supply, the liver receives blood from two sources. The hepatic artery delivers oxygen-rich blood from the heart, supplying about 25 percent of the liver's blood. The liver also receives oxygen-depleted blood from the hepatic portal vein. This vein, which is the source of 75 percent of the liver's blood supply, carries blood to the liver that has traveled from the digestive tract, where it collects nutrients as food is digested. These nutrients are delivered to the liver for further processing or storage.

Tiny blood vessel branches of the hepatic artery and the hepatic portal vein are found around each liver lobule. This network of blood vessels is responsible for the vast amount of blood that flows through the liver—about 1.4 l (about 3 pt) every minute. Blood exits the liver through the hepatic vein, which eventually drains into the heart.

Understanding function and dysfunction of the liver, more than most other organs, depends on understanding its structure. The major aspects of hepatic structure that require detailed attention include:

The hepatic vascular system, which has several unique characteristics relative to other organs
The biliary tree, which is a system of ducts that transports bile out of the liver into the small intestine
The three dimensional arrangements of the liver cells, or hepatocytes and their association with the vascular and biliary systems.

The circulatory system of the liver is unlike that seen in any other organ. Of great importance is the fact that a majority of the liver's blood supply is venous blood! The pattern of blood flow in the liver can be summarized as follows:

Roughly 75% of the blood entering the liver is venous blood from the portal vein. Importantly, all of the venous blood returning from the small intestine, stomach, pancreas and spleen converges into the portal vein. One consequence of this is that the liver gets "first pickings" of everything absorbed in the small intestine, which, as we will see, is where virtually all nutrients are absorbed.

The remaining 25% of the blood supply to the liver is arterial blood from the hepatic artery.

Terminal branches of the hepatic portal vein and hepatic artery empty together and mix as they enter sinusoids in the liver. Sinusoids are distensible vascular channels lined with highly fenestrated or "holey" endothelial cells and bounded circumferentially by hepatocytes. As blood flows through the sinusoids, a considerable amount of plasma is filtered into the space between endothelium and hepatocytes (the "space of Disse"), providing a major fraction of the body's lymph.

Blood flows through the sinusoids and empties into the central vein of each lobule

Hepatic Blood Volume and Reservoir Function
The liver receives approximately 30% of resting cardiac output and is therefore a very vascular organ. The hepatic vascular system is dynamic, meaning that it has considerable ability to both store and release blood - it functions as a reservoir within the general circulation.
In the normal situation

Formation of Lymph in the Liver
Approximately half of the lymph formed in the body is formed in the liver. Due to the large pores or fenestrations in sinusoidal endothelial cells, fluid and proteins in blood flow freely into the space between the endothelium and hepatocytes (the "space of Disse"), forming lymph

The Hepatic Phagocytic System
The liver is host to a very important part of the phagocytic system. Lurking in the sinusoids are large numbers of a type of tissue macrophage known as the Kupffer cell.   Kuppfer cells are actively phagocytic and represent the main cellular system for removal of particulate materials and microbes from the circulation. Their location just downstream from the portal vein allows Kupffer cells to efficiently scavenge bacteria that get into portal venous blood through breaks in the intestinal epithelium, thus preventing invasion of the systemic circulation.

Another crucial function of the liver is the production of bile, a yellowish-brown liquid containing salts necessary for the digestion of lipids, or fats. These salts are produced within the lobules. Bile leaves the liver through a network of ducts and is transported to the gallbladder, which concentrates the bile and releases it into the small intestine.

Vitamins are also stored in the liver. Drawing on the nutrient-rich blood in the hepatic portal vein, the liver collects and stores supplies of vitamins A, D, E, and K. The B vitamins are also stored here, including a two- to four-year supply of Vitamin B12.

The liver also functions as the body’s chemical factory. Several important proteins found in the blood are produced in the liver. One of these proteins, albumin, helps retain calcium and other important substances in the bloodstream. Albumin also helps regulate the movement of water from the bloodstream into the body’s tissues. The liver also produces globin, one of the two components that form hemoglobin—the oxygen-carrying substance in red blood cells. Certain globulins, a group of proteins that includes antibodies, are produced in the liver, as are the proteins that make up the complement system, a part of the immune system that combines with antibodies to fight invading microorganisms.

Many other chemicals are produced by the liver. These include fibrinogen and prothrombin, which help wounds to heal by enabling blood to form clots, and cholesterol, a key component of cell membranes that transports fats in the bloodstream to body tissues.

In addition to manufacturing chemicals, the liver helps clear toxic substances, such as drugs and alcohol, from the bloodstream. It does this by absorbing the harmful substances, chemically altering them, and then excreting them in the bile.

Diseases of the liver range from mild infection to life-threatening liver failure. For many of these ailments, the first sign of a problem is a condition called jaundice, characterized by a yellowish coloring of the skin and the whites of the eye. It develops when liver cells lose their ability to process bilirubin, the yellowish-brown pigment found in bile.

The liver can be harmed whenever injury or disease affects the rest of the body. For example, cancer may spread from the stomach or intestines to the liver, and diabetes, if not properly treated, may result in damage to the liver. Some diseases caused by parasites, including amebiasis and schistosomiasis, can damage the liver. Drug use, including long-term use of some prescription medications as well as illegal drugs, can also cause liver damage. Poisons can easily damage liver cells and even cause complete liver failure, especially the poisons found in certain mushrooms.

One of the most common liver diseases is hepatitis, an inflammation of the liver. Hepatitis may be caused by exposure to certain chemicals, by autoimmune diseases, or by bacterial infections. But hepatitis is most often caused by one of several viruses. The hepatitis A virus (HAV) can produce flulike symptoms and jaundice, but many people who contract it have no symptoms. The disease tends to resolve on its own. Because HAV lives in feces in the intestinal tract, hepatitis A is prevalent in areas where drinking water is contaminated with raw sewage. Good hygiene practices and a hepatitis A vaccination are effective measures of prevention.

Hepatitis B is a more serious ailment. Unlike HAV, hepatitis B virus (HBV) may remain active in the body for many years after the time of infection, sometimes permanently damaging the liver. HBV is found in blood and other body fluids—tears, saliva, and semen—and is spread through unprotected sexual intercourse and the sharing of infected needles or other sharp objects that puncture the skin.

In developed countries, alcohol-induced liver diseases far outnumber hepatitis and all other liver disorders. Heavy alcohol use causes fat deposits to build up in the liver, possibly leading to chronic hepatitis, which causes scarring and destruction of liver cells. Over many years, scarring in the liver can progress to cirrhosis, a disease characterized by diminished blood flow through this important organ. When this occurs, toxins are not adequately removed from the blood, blood pressure increases in the hepatic portal vein, and substances produced by the liver, such as blood proteins, are not adequately regulated. Cirrhosis cannot be reversed, but liver function can significantly improve in people who stop consuming alcohol during the early stages of this condition. Beyond abstinence from alcohol, treatments for cirrhosis may include drug therapy or surgery to redirect blood flow.

For people with severe liver disease or impending liver failure, organ transplantation may be an option. Unlike some organ transplants, such as kidney transplants, liver transplants are complex procedures that have not had high long-term success rates. Fortunately, new techniques and drugs are improving the outcome of liver transplants. Current success rates range between 60 and 80 percent, with more than half of recent transplant recipients surviving more than five years. Most of these people have an excellent prognosis for leading healthy, normal lives.