Normal Liver Physiology
The liver, weighing roughly 1.2-1.6 kg, performs many of the functions necessary for staying healthy. It is located in the right side of the body under the lower ribs and is divided into four lobes of unequal size. Two large vessels carry blood to the liver. The hepatic artery comes from the heart and carries blood rich in oxygen. The portal vein brings the liver blood rich in nutrients absorbed from the small intestine. These vessels divide into smaller and smaller vessels, ending in capillaries. These capillaries end in the thousands of lobules of the liver. Each lobule is composed of hepatocytes, and as blood passes through, they are able to monitor, add, and remove substances from it. The blood then leaves the liver via the hepatic vein, returns to the heart, and is ready to be pumped to the rest of the body.
Among the most important liver functions are:
· Removing and excreting body wastes and hormones as well as drugs and other foreign substances These substances have entered the blood supply either through production by metabolism within the body or from the outside in the form of drugs or other foreign compounds. Enzymes in the liver alter some toxins so they can be more easily excreted in urine.
· Synthesizing plasma proteins, including those necessary for blood clotting Most of the 12 clotting factors are plasma proteins produced by the liver. If the liver is damaged or diseased, it can take longer for the body to form clots. Other plasma proteins produced by the liver include albumin which binds many water-insoluble substances and contributes to osmotic pressure, fibrogen which is key to the clotting process, and certain globulins which transport substances such as cholesterol and iron.
· Producing immune factors and removing bacteria, helping the body fight infection The phagocytes in the liver produce acute-phase proteins in response to microbes. These proteins are associated with the inflammation process, tissue repair, and immune cell activities.
Other important but less immediate functions include:
· Producing bile to aid in digestion Bile salts aid in fat digestion and absorption. Bile is continuously secreted by the liver and stored in the gallbladder until a meal, when bile enters the beginning of the small intestine. Bile production ranges from 250 mL to 1 L per day depending of amount of food eaten.
· Excretion of bilirubin Bilirubin is one of the few waste products excreted in bile. Macrophages in the liver remove worn out red blood cells from the blood. Bilirubin then results from the breakdown of the hemoglobin in the red blood cells and is excreted into bile by hepatocytes. Jaundice results when bilirubin cannot be removed from the blood quickly enough due to gallstones, liver disease, or the excessive breakdown of red blood cells.
· Storing certain vitamins, minerals, and sugars The liver stores enough glucose in the form of glycogen to provide about a day's worth of energy. The liver also stores fats, iron, copper, and many vitamins including vitamins A, D, K, and B12.
· Processing nutrients absorbed from digestive tract The liver converts glucose into glycogen, its storage form. This glycogen can then be transformed back into glucose if the body needs energy. The fatty acids produced by the digestion of lipids are used to synthesize cholesterol and other substances. The liver also has the ability to convert certain amino acids into others.
Despite the wide variety of functions performed by the liver, there is very little specialization among hepatocytes (liver cells). Aside from the macrophages called Kupffer cells in the liver, hepatocytes all seem to be able to perform the same wide variety of tasks.One of the liver's most interesting abilities is self-repair and the regeneration of damaged tissues. In clearing the body of toxins, the liver is damaged by exposure to harmful substances, demonstrating why this capability is important. It also gives hope that if a failing liver can be supported for a certain period of time, it might regenerate and allow the patient to survive and regain a normal life.
|fat and cholesterol|
|vitamins, in particular fat-soluble ones (A, D, E, K)|
|Synthesis||proteins including the clotting factors (~50g/day)|
|bile acids (important in fat digestion)|
|somatomedins (homones that promote growth in bone, soft tissues)|
|acute phase proteins|
|Excretion||cholesterol, bile acids, phospholipids|
|poisons including heavy metals|
|nutrients including amino acids, sugars, and fats|
|bilirubin, bile acids|
|dead or damaged cells in circulatory system|
|Immune||excretes IgA into digestive tract|
|Kupffer cells (macrophages) filter out antigens|
Tzanakakis et al. "Liver Assist Devices." Annual Review of Biomedical Engineering, 2000, 02:p.607-632.
Liver, a Vital Organ. 24 Apr 2002. http://www.liverfoundation.org/html_filz/livheal.dir/lh_ldd_dox.dir/_lhf001.htm
Sherwood, Lauralee. Human Physiology: From Cells to Systems. 3rd ed. Boston: Wadsworth, 1997
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