Liver

Definition

The liver is the largest gland and largest internal organ in the human body (the skin is the largest organ overall).

Description

Weighing 3-3.5 lb (1.4-1.6 kg), the liver is a dark red, wedge-shaped gland approximately eight and a half inches long (roughly the size of a football). It is located in the right side of the abdominal area just below the diaphragm and above the stomach.

Approximately 1.5 qt (1.5 L) of blood flow through the liver each minute. The liver holds about 13% of the body's blood supply. It is furnished with blood from two large vessels, the portal vein and the hepatic artery (hepatic means liver). Blood that has circulated through the stomach, spleen, and intestine enters the liver through the portal vein as part of the portal circulation system. The liver extracts nutrients and toxins from this blood, which is then returned through the hepatic vein to the right side of the heart. The hepatic artery supplies oxygenated blood directly from the heart to the liver.

Function

Some of the liver's many important functions include:

• Production of bile which is stored in the gall bladder and used to digest fats. If the excretion of bile is blocked, the stools become pale and retain fat. As a result, fat-soluble vitamins (vitamins A, D, E, and K) are not properly absorbed and levels of bilirubin, the main component of bile, rises in the blood. Once bilirubin levels reach a certain level, jaundice or yellowing of the skin and eyes occurs.
• Synthesis of proteins, including albumin. Albumin is the predominant protein in blood plasma and helps to retain fluid within the blood vessels. The loss of albumin results in fluid shifting from blood vessels to the surrounding tissue. The result is swelling of tissue, a condition called edema.
• Production of blood-clotting factors that control bleeding. Loss of clotting factors leads to increased chance of hemorrhage.
• Metabolism of hormones and medications, such as estrogen and acetominophen (Tylenol). When the liver is damaged, its ability to metabolize hormones decreases. This can result in changes to estrogen and testosterone levels in the body. Symptoms of these changes include loss of pubic hair and the development of spider angiomas, small clusters of red blood vessels on the skin of the upper body, in both males and females. Men sometimes experience a decrease of testicular size and development of breast tissue (a condition called gynecomastia). A decline in the body's ability to metabolize medications means that normal doses can turn into toxic levels. Therefore, doses of medicines are often reduced for people who have liver disease.
• Regulation of glucose levels. Loss of liver cells leads to poorly controlled glucose levels. Glucose levels may soar after eating (hyperglycemia) or fall dangerously low between meals (hypoglycemia). This poor regulation of blood sugar is due to a different mechanism than the mechanisms that lead to diabetes types I and II.
• Conversion of ammonia, a by-product of metabolism, into a less toxic form called urea. Inability to convert ammonia to urea results in elevated ammonia levels in the blood. This can result in a condition called hepatic encephalopathy, which is a neurological syndrome characterized by alterations in mental status and behavior. Although acute episodes can be reversible, severe cases of hepatic encephalopathy can lead to coma and death.

Role in human health

A healthy liver enables the human body to:

• produce energy when needed
• manufacture new proteins
• store certain vitamins, minerals, and sugars
• regulate transport of fat stores
• regulate blood clotting
• facilitate the digestive process by producing bile
• control the production and excretion of cholesterol
• neutralize and destroy toxic substances
• metabolize alcohol
• monitor proper chemical and drug blood levels
• cleanse the blood and discharging waste products into the bile
• maintain hormone balance
• serve as the main fetal blood forming organ
• resist infection
• regenerate its damaged tissue
• store iron

Common diseases and disorders

Symptoms and signs of liver disease:

• jaundice, or abnormal yellowing of the skin and eyes (often the first, and may be the only, sign of liver disease)
• dark urine
• gray, yellow, or light colored stools
• nausea, vomiting, and/or loss of appetite
• intestinal bleeding due to liver diseases obstructing blood flow (Bleeding may result in vomiting of blood, and bloody or black stools.)
• abdominal swelling (Liver disease may cause ascites, an accumulation of fluid in the abdominal cavity.)
• prolonged generalized itching
• an increase or decrease of more than 5% body weight in two months
• abdominal pain
• sleep disturbances, mental confusion, and coma that may result from an accumulation of toxic substances that impairs brain function
• fatigue or loss of stamina
• loss of sexual drive or diminished performance

The most common liver diseases are as follows:

Viral hepatitis

• Hepatitis A spreads through contaminated water and food.
• Hepatitis B may be transmitted through transfusions, cuts, kissing, tooth brushing, ear piercing, tattooing, dental work, or during sexual contact.
• Hepatitis C primarily spreads through infected blood.

The liver often becomes tender and enlarged, and the patient usually experiences fever, weakness, nausea, vomiting, jaundice, and aversion to food. The virus may be present in the bloodstream, intestines, feces, saliva, and other body secretions. Hepatitis is common in the United States and some forms of it can be extremely infectious. Most people recover from viral forms of the disease without treatment, but some die and others may develop a chronic, disabling illness. In the United States there are more than four million hepatitis carriers.

Alcohol-related liver disorders

Liver disorders related to alcohol include fatty liver, alcoholic hepatitis, and alcoholic cirrhosis.

Fatty liver, the most common alcohol-related liver disorder, causes liver enlargement and abdominal discomfort. Swollen livers are often tender or painful, and may cause jaundice and liver function abnormalities.

Alcoholic hepatitis often results in nausea, vomiting, abdominal pain, fever, jaundice, liver enlargement and tenderness, and white blood cell count elevation. At times alcoholic hepatitis may be asymptomatic.

Cirrhosis

Over 25,000 Americans die from cirrhosis each year. It is the seventh leading cause of death. Among those 25-44, it is the fourth disease-related cause of death. Cirrhosis of the liver occurs when damaged liver cells are replaced by scar tissue causing diminished blood flow, which causes additional liver cell death. Loss of liver function results in gastrointestinal disturbances, emaciation, liver and spleen enlargement, jaundice, fluid accumulation in the abdomen and other tissues. Obstructed circulation often causes massive vomiting of blood.

Any severe liver injury may cause cirrhosis. Over half of the deaths from cirrhosis result from alcohol abuse, hepatitis, and other viruses. Toxins, chemicals, excessive iron or copper, severe drug reactions, and bile duct obstruction may also cause cirrhosis.

Gallstones

Gallstones form when cholesterol and/or pigment in bile crystallize into gall stones. Gall stones vary in size from small pebbles to golf balls. Occasionally gallstones become lodged in the bile ducts leading from the gallbladder to the duodenum (first part of the small intestine ). This may cause extreme abdominal pain. When gall stones block bile ducts, bile cannot flow into the intestines, and backs up into the bloodstream causing jaundice.

Gallstones are more common in people over 40, especially among women and the obese. Each year in the United States, 400-500,000 gallbladders are surgically removed.

Children's liver disorders

Tens of thousands of American children contract liver diseases causing hundreds of deaths each year. The most common of these diseases are:

Biliary atresia is caused by the lack, or inadequate size, of bile ducts connecting the liver to the intestine. Unable to excrete bile, death results from cirrhosis and bleeding by two years of age.

Chronic active hepatitis destroys liver cells replacing them with scar tissue. It is caused by an unknown process that resembles an allergy to the child's own liver tissue.

Galactosemia, an inherited disease, is caused by the lack of an enzyme needed to digest milk sugar. As a result, milk sugar accumulates in the liver and other organs, leading to cirrhosis of the liver, cataracts, and brain damage.

Wilson's disease occurs when copper accumulates in the liver due to an inherited abnormality, causing cirrhosis and brain damage.

Reyes syndrome is a fatal disorder in which fat accumulates in the liver.

Cirrhosis may result from extensive liver injury.

Liver cancer

Most liver cancer results from the spread of cancer from other organs to the liver (metastasis).

KEY TERMS

Ascites— Accumulation of fluid in the abdominal cavity.

Bile— Yellowish substance released by the liver into the intestines to digest fats.

Resources

BOOKS

Cotran, Ramzi, S. Robbins Pathologic Basis of Disease. 6th ed. Philadelphia: W.B. Saunders Company, 1999.

Guyton, Arthur C. Textbook of Medical Physiology. 10th ed. Philadelphia: W.B. Saunders Company, 2000.

PERIODICALS

Smales, Caroline. "Hepatitis: Symptoms, Treatments, and Prevention." Nursing Times (4 November 1998): 58-60.

ORGANIZATIONS

American Liver Foundation. 75 Maiden Lane, Suite 603, New York, NY 10038. 1-800-GOLIVER (1-800) 465-4837) 〈http://www.liverfoundation.org/〉.

liver The concept that certain organs, such as the liver, brain, and heart, enjoyed a higher status than others was first proposed and accepted in the earliest days of medical thought. Indeed, the Babylonians considered the liver to be the seat and mirror of the soul and, as a consequence, this organ became the focus of divination ceremonies, in which the livers of sacrificial animals were carefully inspected by priests for signs of damage prior to being offered as gifts to the gods. The observed condition of the excised organ was taken to portend the future and, especially, to predict whether or not conditions were favourable for battle. Prayers at these solemn ceremonies were even inscribed on tablets shaped like livers, many of which were subsequently recovered from countries bordering the Mediterranean, far beyond the limits of Babylon.

It was the Greeks who first abandoned superstition in favour of an approach to the understanding of the body based on anatomy and physiology, and it is in the writings of Aristotle where the first attempts to describe animals' livers based on dissection are to be found. However, because of his great influence, Aristotle also helped to perpetuate the notion that human emotions were controlled by four cardinal ‘humours’, two of which — yellow bile and black bile — emanated from the liver. These liver-derived humours were held to be responsible for choleric and melancholic moods, respectively. The coming of the Renaissance age and the scientific revolution put paid to the notion that body organs exist under a hierarchical structure, and the fallacy of the four humour theory was exposed. Rather than denigrate the importance of the liver, however, advances in anatomy and physiology over the years have instead highlighted how important the liver is for normal bodily function.

Anatomy

The liver — the largest internal organ of the body — weighs approximately 1200–1500 g or, on average, one fiftieth of the total adult body weight. It is relatively larger in the infant, comprising approximately one twentieth of the birth weight. Situated in the upper abdomen, beneath the right rib cage and separated from the chest cavity by the diaphragm, the upper border of the liver lies approximately at the level of the nipples. Largely composed of cells known as hepatocytes, which are involved in a multiplicity of synthetic, metabolic, and biotransformatory processes, the liver is unusual in that it is perfused with a dual blood supply. The portal vein carries blood from the spleen and intestines and accounts for approximately 75% of the liver's blood supply, whilst the hepatic artery, which arises indirectly from the aorta, delivers the remaining 25%. Owing to the higher oxygen content of arterial blood, oxygen delivery to the liver is about equally derived from the portal vein and hepatic artery. There is continuous exchange between hepatocytes and the perfusing blood, as various chemicals delivered to the liver from elsewhere in the body by the bloodstream are taken up for degradation and further metabolism, whilst others produced by the liver are, conversely, exported from it. An alternative pathway for dispersal of substances produced in the liver is through secretion into an extensive system of minute canals which eventually form the bile ducts draining into the intestine.

Functions

A multitude of functions of the liver have already been well described, and there are many more of which relatively little is currently known. One of the most important — and easily recognizable when deranged — is the metabolism of the pigment, bilirubin, a chemical predominantly derived from products released during the normal destruction of senescent red blood cells. Yellow discolouration of the eyes and the skin (jaundice) ensues when overproduction of bilirubin exceeds the liver's metabolic capability or when hepatic metabolism of bilirubin is impaired.

Another important function of the liver is the synthesis of bile acids, which are then transported via the bile ducts into the intestine to aid in the digestion of fatty foods and the absorption of certain fat-soluble vitamins, particularly vitamins A, D, E, and K. These vitamins are important for night vision, building strong bones and maintaining normal skin integrity and nerve function, as well as for ensuring normal clotting of the blood. Cholesterol and phospholipids — each of which are important constituents of all cell membranes — and triglycerides — which contain a variety of fatty acids and act as an important storage form of energy — are also synthesized in the liver.

The liver is the main site for the metabolism of a vast range of chemical substances produced as a result of the digestion of food in the intestine. For example, ammonia, produced by digestive processes and by the action of intestinal bacteria on dietary protein, is absorbed into the bloodstream. Ammonia in high quantities interferes with normal brain function — an eventuality prevented by its conversion in the liver to the non-toxic compound, urea. Many other amino acids — the building blocks for protein synthesis — which are derived from the diet and from tissue degradation, are also carried by the bloodstream to the liver. Once there they are metabolized to various proteins with a wide range of important functions, including the prevention of fluid accumulation within the tissues and the binding of potentially toxic compounds, such as copper and iron. The liver has a remarkable capacity for such tasks. Under experimental conditions, at least 85% of the liver must be removed or damaged before protein synthesis is substantially impaired.

The liver also plays a key role in carbohydrate metabolism, resulting in the synthesis of glucose for energy and the generation of body heat. Excess quantities are stored as glycogen, which can subsequently be mobilized as required. There is also a complex system of enzymes which function to convert a myriad of drugs and other toxins, including alcohol, to non-toxic metabolites. The activity of these enzyme systems may be modified by various factors. For example, the capacity of the liver to metabolize alcohol is increased by a steady high level of drinking but markedly impaired by alcohol binges.

Another important function of the liver is performed by so-called ‘phagocytic’ Kupffer cells, which line the vascular networks. These cells play an important role in the prevention of systemic infection and inflammation, by extracting and destroying particulate matter, such as pro-inflammatory bacterial cell walls, as it passes through the liver via the bloodstream.

Advancing age has various effects on the liver. Liver weight and blood supply are each reduced in the healthy elderly subject, but most functions of the liver are well maintained. However, the metabolism of certain drugs may be impaired and this may be at least partly responsible for the increased sensitivity to drugs and possibly also for the high prevalence of adverse drug reactions in this group, especially when multiple drugs are ingested.

Disorders

Any or all of the various liver functions outlined above may be disturbed to varying extents in acute liver disorders, such as acute viral hepatitis. Most such episodes resolve spontaneously without sequelae, owing to the great capacity of liver cells to regenerate. Chronic liver disorders, such as cirrhosis, in which fibrosis and nodule formation occur as the common end result of many disorders causing destruction of hepatocytes, may have more serious consequences. Over the past thirty-five years, liver transplantation has grown from a largely experimental procedure to become a well-established treatment option, not only for that subgroup of patients who have advanced cirrhosis and an otherwise poor prognosis, but also for those patients with the less commonly encountered acute liver failure or liver-based metabolic disorders. Over 650 liver transplantations are performed annually in the UK alone, with over 70% of recipients making a full recovery.

It is clear that, even though ancient cultures were mistaken as to the functions of the liver, they were certainly correct in attaching so much importance to it. Indeed, the maxim that ‘life depends on the liver’ is as pertinent today as ever before.

Stephen M. Riordan, and Roger Williams

See alimentary system.See also bile; gall bladder; jaundice.

liver, largest glandular organ of the body, weighing about 3 lb (1.36 kg). It is reddish brown in color and is divided into four lobes of unequal size and shape. The liver lies on the right side of the abdominal cavity beneath the diaphragm. Blood is carried to the liver via two large vessels: the hepatic artery carries oxygen-rich blood from the aorta, and the portal vein carries blood containing digested food from the small intestine. These blood vessels subdivide in the liver repeatedly, terminating in minute capillaries. Each capillary leads to a lobule. Liver tissue is composed of thousands of lobules, and each lobule is made up of hepatic cells, the basic metabolic cells of the liver. One of the liver's major functions is the manufacture and secretion of bile, which is stored in the gall bladder and released in the small intestine. Bile salts emulsify fats, a process that prepares the latter for digestion by the intestinal enzymes (see digestive system). The hepatic cells assimilate carbohydrates, fats, and proteins. They convert glucose to its stored form, glycogen, which is reconverted into glucose as the body requires it for energy. The ability of the liver to maintain the proper level of glucose in the blood is called its glucose buffer function. The end products of fat digestion, fatty acids, are used to synthesize cholesterol and other substances needed by the body. Excess carbohydrates and protein are also converted into fat by the liver. Digested proteins in the form of amino acids are broken down further in the liver by deamination. Part of the amino acid molecule is converted into glycogen and other compounds. Urea, a waste product of protein breakdown, is produced by the liver, a process which removes poisonous ammonia from the body fluids. The liver is also capable of synthesizing certain amino acids (the so-called nonessential amino acids) from other amino acids in a process called transamination. Some essential components of blood are manufactured by the liver, including about 95% of the plasma proteins and the blood-clotting substances (fibrinogen, prothrombin, and other coagulation factors). The liver also filters harmful substances from the blood. Phagocytic cells in the liver, called Kupffer cells, remove large amounts of debris and bacteria. In addition, the liver stores important vitamins and minerals, including vitamins A, D, K, and B₁₂. Several diseases states can affect the liver, such as hepatitis (an inflammation of the liver) and cirrhosis (a chronic inflammation that progresses ultimately to organ failure). Alcohol alters the metabolism of the liver, which can have overall detrimental effects over long periods of abuse. In 1994, a bioartificial liver, part machine, part cloned living liver cells, was used for the first time. Functioning somewhat like a kidney dialysis machine, the bioartificial liver can support patients with acute liver failure until their own livers regenerate, or it can be used by patients while waiting for a liver transplant.

Liver

The liver is the largest organ in the abdominal cavity and is located under the right and central portions of the diaphragm. It performs over two hundred functions including digestive, metabolic, storage, and other functions. This reddish-brown organ consists of two major lobes, the right lobe and the left lobe, and two smaller lobes, the caudate lobe and the quadrate lobe.

Lying under the right lobe is the gallbladder, a muscular sac that is anatomically and physiologically associated with the liver. Emerging from the gallbladder is the cystic duct.

The lobes contain liver cells (hepatocytes), which secrete bile, an alkaline , yellow-green liquid that is composed of water, bile salts, and several other substances. Bile is delivered to the duodenum, the first portion of the small intestine, where the bile salts emulsify lipids ; that is, break down large lipid globules into small droplets, in order to increase the efficiency of lipid digestion and absorption by the small intestine.

The hepatocytes secrete bile into numerous tiny ducts, which merge to form progressively wider ducts. These ducts ultimately merge to form the common hepatic duct, which descends from the liver. This duct merges with the gallbladder's cystic duct to form the bile duct, which opens into the duodenum. The opening is guarded by a sphincter , a circular muscle that is usually closed. Since the sphincter is usually closed, bile flowing down from the liver is prevented from entering the duodenum and, consequently, backs up via the cystic duct into the gallbladder.

Within the gallbladder, bile is stored and concentrated until it is expelled, when needed, via the cystic and bile ducts into the duodenum. Expulsion of bile occurs due to the simultaneous contraction of the gallbladder walls and relaxation of the sphincter guarding the entrance to the duodenum.

In addition to producing bile for the emulsification of dietary lipids, the liver also plays an important role in the maintenance of normal blood glucose concentration, inactivation of toxins, synthesis of plasma proteins , and the metabolism of carbohydrates , fats, and proteins.

see also Blood Sugar Regulation; Digestion; Digestive System; Poisons

Izak Paul

Bibliography

Saladin, Kenneth S. Anatomy & Physiology: The Unity of Form and Function, 2nd ed. New York: McGraw-Hill, 2001.

liver A large lobed organ in the abdomen of vertebrates that plays an essential role in many metabolic processes by regulating the composition and concentration of nutrients and toxic materials in the blood. It is made up of units called lobules, each of which is a roughly hexagonal structure consisting largely of hepatocytes arranged around a central vein. The liver receives the products of digestion dissolved in the blood via the hepatic portal vein and its most important functions are to convert excess glucose to the storage product glycogen, which serves as a food reserve; to break down excess amino acids to ammonia, which is converted to urea or uric acid and excreted via the kidneys; and to store and break down fats (see lipolysis). Other functions of the liver are (1) the production of bile; (2) the breakdown (detoxification) of poisonous substances in the blood; (3) the removal of damaged red blood cells; (4) the synthesis of vitamin A and the blood-clotting substances prothrombin and fibrinogen; and (5) the storage of iron (see ferritin).

Liver •aquiver, downriver, forgiver, giver, quiver, river, shiver, sliver, upriver •silver • mitzvah • lawgiver • Oliver •miniver, Nineveh •quicksilver •conniver, contriver, diver, driver, fiver, Godiva, Ivor, jiver, Liver, reviver, saliva, skiver, striver, survivor, viva •skydiver • slave-driver • piledriver •screwdriver •bovver, hover •Moskva •revolver, solver •windhover •Canova, Casanova, clover, Dover, drover, Grsbover, Jehovah, left-over, Markova, Moldova, moreover, Navrátilová, nova, ova, over, Pavlova, rover, trover, up-and-over •layover • flyover • handover •changeover •makeover, takeover •walkover • spillover • pullover •Hanover • turnover • hangover •wingover • sleepover • slipover •popover, stopover •Passover • crossover • once-over •pushover • leftover

liv·er¹ / ˈlivər/ • n. a large lobed glandular organ in the abdomen of vertebrates, involved in many metabolic processes. ∎  a similar organ in other animals. ∎  the flesh of an animal's liver as food: slices of calf's liver [as adj.] liver pâté chicken livers. ∎  (also liver color) a dark reddish brown. liv·er² • n. [with adj.] a person who lives in a specified way: a clean liver high livers.

liver Large organ located in the upper right abdomen of vertebrates. Weighing up to 4.5lbs (2kg) in an adult human, it divides into four lobes and has many functions. It is extremely important in the control of the body's internal environment (homeostasis). It receives nutrients from the intestine, and is a site of the metabolism of proteins, carbohydrates, and fats. It synthesizes bile and some vitamins, regulates the blood-glucose level, produces blood-clotting factors, breaks down worn-out erythrocytes (red blood cells), and removes toxins from the blood. The many metabolic reactions that occur in the liver are the body's main source of heat, which is distributed around the body by the blood. See also insulin

liver Usually from calf, pig, ox, lamb, or poultry; a 150‐g portion (fried or stewed) is an exceptionally rich source of iron and vitamins A, D, B₂, B₆, and B₁₂; a rich source of protein, zinc, copper, selenium, niacin, and vitamin B₁; also, unusually for meat, a good source of vitamin C; contains 10 g of fat, of which one‐third is saturated; supplies 300–380 kcal (1250–1600 kJ). The vitamin A content of liver is high enough for it to pose a possible hazard to unborn children, and pregnant women have been advised not to eat liver. See vitamin A toxicity. Fish liver is a particularly rich source of vitamins A and D, and fish liver oils (especially cod and halibut) are used as sources of these vitamins as nutritional supplements.