The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion. The liver is necessary for survival; there is currently no way to compensate for the absence of liver function.

This organ plays a major role in metabolism and has a number of functions in the body, including glycogen storage, decomposition of red blood cells, plasma protein synthesis, hormone production, and detoxification. It lies below the diaphragm in the thoracic region of the abdomen. It produces bile, an alkaline compound which aids in digestion, via the emulsification of lipids. It also performs and regulates a wide variety of high-volume biochemical reactions requiring highly specialized tissues, including the synthesis and breakdown of small and complex molecules, many of which are necessary for normal vital functions.

Medical terms related to the liver often start in hepato- or hepatic from the Greek word for liver, hēpar (ήπαρ).

Basic info on Structure

The liver is the largest glandular organ with a weight of about 1.5 kg/3 lb. It is reddish brown organ with four lobes of unequal size and shape. The liver is on the right side of the abdominal cavity just below the diaphragm and is connected to two large blood vessels, one called the hepatic artery and one called the portal vein. The hepatic artery carries blood from the aorta whereas the portal vein carries blood containing digested food from the small intestine. These blood vessels subdivide into capillaries which then lead to a lobule. Each lobule is made up of thousands of hepatic cells which are the basic metabolic cells.

Anatomy

An adult human liver normally weighs between 1.4-1.6 kg (3.1-3.5 lb), and is a soft, pinkish-brown, triangular organ. It is both the largest internal organ (the skin being the largest organ overall) and the largest gland in the human body.

It is located in the right upper quadrant of the abdominal cavity, resting just below the diaphragm. The liver lies to the right of the stomach and overlies the gallbladder.

Blood flow

The liver receives a dual blood supply consisting of the hepatic portal vein and hepatic arteries. Supplying approximately 75% of the liver's blood supply, the hepatic portal vein carries venous blood drained from the spleen, gastrointestinal tract, and its associated organs. The hepatic arteries supply arterial blood to the liver, accounting for the remainder of its blood flow. Oxygen is provided from both sources; approximately half of the liver's oxygen demand is met by the hepatic portal vein, and half is met by the hepatic arteries.


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

The central veins coalesce into hepatic veins, which leave the liver and empty into the inferior vena cava.

Biliary flow

The term biliary tree is derived from the arboreal branches of the bile ducts. The bile produced in the liver is collected in bile canaliculi, which merge to form bile ducts. Within the liver, these ducts are called intrahepatic (within the liver) bile ducts, and once they exit the liver they are considered extrahepatic (outside the liver). The intrahepatic ducts eventually drain into the right and left hepatic ducts, which merge to form the common hepatic duct. The cystic duct from the gallbladder joins with the common hepatic duct to form the common bile duct.

Bile can either drain directly into the duodenum via the common bile duct or be temporarily stored in the gallbladder via the cystic duct. The common bile duct and the pancreatic duct enter the second part of the duodenum together at the ampulla of Vater.

Surface anatomy

Peritoneal ligaments

Apart from a patch where it connects to the diaphragm (the so-called "bare area"), the liver is covered entirely by visceral peritoneum, a thin, double-layered membrane that reduces friction against other organs. The peritoneum folds back on itself to form the falciform ligament and the right and left triangular ligaments.

These "ligaments" are in no way related to the true anatomic ligaments in joints, and have essentially no functional importance, but they are easily recognizable surface landmarks. An exception to this is the falciform ligament, which attaches the liver to the posterior portion of the anterior body wall.

Lobes

Traditional gross anatomy divided the liver into four lobe based on surface features.The falciform ligament is visible on the front (anterior side) of the liver. This divides the liver into a left anatomical lobe, and a right anatomical lobe.

If the liver flipped over, to look at it from behind (the visceral surface), there are two additional lobes between the right and left. These are the caudate lobe (the more superior), and below this the quadrate lobe.

From behind, the lobes are divided up by the ligamentum venosum and ligamentum teres (anything left of these is the left lobe), the transverse fissure (or porta hepatis) divides the caudate from the quadrate lobe, and the right sagittal fossa, which the inferior vena cava runs over, separates these two lobes from the right lobe.

Each of the lobes is made up of lobules; a vein goes from the centre of each lobule which then joins to the hepatic vein to carry blood out from the liver.

On the surface of the lobules there are ducts, veins and arteries that carry fluids to and from them.

Functional anatomy

Correspondence between anatomic lobes and Couinaud segments

Segment*	Couinaud segments
Caudate	1
Lateral	2, 3
Medial	4a, 4b
Right	5, 6, 7, 8
* or lobe in the case of the caudate lobe. Each number in the list corresponds to one in the table. Caudate Superior subsegment of the lateral segment Inferior subsegment of the lateral segment Superior subsegment of the medial segment Inferior subsegment of the medial segment Inferior subsegment of the anterior segment Inferior subsegment of the posterior segment Superior subsegment of the posterior segment Superior subsegment of the anterior segment

The central area where the common bile duct, hepatic portal vein, and hepatic artery proper enter is the hilum or "porta hepatis". The duct, vein, and artery divide into left and right branches, and the portions of the liver supplied by these branches constitute the functional left and right lobes.

The functional lobes are separated by an imaginary plane joining the gallbladder fossa to the inferior vena cava. The plane separates the liver into the true right and left lobes. The middle hepatic vein also demarcates the true right and left lobes. The right lobe is further divided into an anterior and posterior segment by the right hepatic vein. The left lobe is divided into the medial and lateral segments by the left hepatic vein. The fissure for the ligamentum teres also separates the medial and lateral segments. The medial segment is also called the quadrate lobe. In the widely used Couinaud (or "French") system, the functional lobes are further divided into a total of eight subsegments based on a transverse plane through the bifurcation of the main portal vein. The caudate lobe is a separate structure which receives blood flow from both the right- and left-sided vascular branches.

In other animals

The liver is found in all vertebrates, and is typically the largest visceral organ. Its form varies considerably in different species, and is largely determined by the shape and arrangement of the surrounding organs. Nonetheless, in most species it is divided into right and left lobes; exceptions to this general rule include snakes, where the shape of the body necessitates a simple cigar-like form. The internal structure of the liver is broadly similar in all vertebrates.

An organ sometimes referred to as a liver is found associated with the digestive tract of the primitive chordate Amphioxus. However, this is an enzyme secreting gland, not a metabolic organ, and it is unclear how truly homologous it is to the vertebrate liver.

Physiology

The various functions of the liver are carried out by the liver cells or hepatocytes. Currently, there is no artificial organ or device capable of emulating all the functions of the liver. Some functions can be emulated by liver dialysis, an experimental treatment for liver failure.

Synthesis

• A large part of amino acid synthesis
• The liver performs several roles in carbohydrate metabolism:
  • Gluconeogenesis (the synthesis of glucose from certain amino acids, lactate or glycerol)
  • Glycogenolysis (the breakdown of glycogen into glucose)
  • Glycogenesis (the formation of glycogen from glucose)(muscle tissues can also do this)
• The liver is responsible for the mainstay of protein metabolism, synthesis as well as degradation
• The liver also performs several roles in lipid metabolism:
  • Cholesterol synthesis
  • Lipogenesis, the production of triglycerides (fats).
• The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, X and XI, as well as protein C, protein S and antithrombin.
• In the first trimester fetus, the liver is the main site of red blood cell production. By the 32nd week of gestation, the bone marrow has almost completely taken over that task.
• The liver produces and excretes bile (a greenish liquid) required for emulsifying fats. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.
• The liver also produces insulin-like growth factor 1 (IGF-1), a polypeptide protein hormone that plays an important role in childhood growth and continues to have anabolic effects in adults.
• The liver is a major site of thrombopoietin production. Thrombopoietin is a glycoprotein hormone that regulates the production of platelets by the bone marrow.

Breakdown

• The breakdown of insulin and other hormones
• The liver breaks down hemoglobin, creating metabolites that are added to bile as pigment (bilirubin and biliverdin).
• The liver breaks down or modifies toxic substances (eg. methylation) and most medicinal products in a process called drug metabolism. This sometimes results in toxication, when the metabolite is more toxic than its precursor. Preferably, the toxins are conjugated to avail excretion in bile or urine.
• The liver converts ammonia to urea.

Other functions

• The liver stores a multitude of substances, including glucose (in the form of glycogen), vitamin A (1–2 years' supply), vitamin D (1–4 months' supply), vitamin B12, iron, and copper.
• The liver is responsible for immunological effects- the reticuloendothelial system of the liver contains many immunologically active cells, acting as a 'sieve' for antigens carried to it via the portal system.
• The liver produces albumin, the major osmolar component of blood serum.
• The liver synthesizes angiotensinogen, a hormone that is responsible for raising the blood pressure when activated by renin, a kidney enzyme that is released when the juxtaglomerular apparatus senses low blood pressure.

Diseases of the liver

Many diseases of the liver are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakup of the haemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.

There are also many pediatric liver diseases, including biliary atresia, alpha-1 antitrypsin deficiency, alagille syndrome, progressive familial intrahepatic cholestasis, and Langerhans cell histiocytosis to name but a few.

Liver diseases may be diagnosed by liver function tests, for example, by production of acute phase proteins.

Regeneration

The liver is the only internal human organ capable of natural regeneration of lost tissue; as little as 25% of a liver can regenerate into a whole liver. A human liver is known to grow back in no less than 8 years, due to hyptochronatin cells in the remaining liver.

This is predominantly due to the hepatocytes re-entering the cell cycle. That is, the hepatocytes go from the quiescent G0 phase to the G1 phase and undergo mitosis. This process is activated by the p75 receptors. There is also some evidence of bipotential stem cells, called ovalocytes or hepatic oval cells, which are thought to reside in the canals of Hering. These cells can differentiate into either hepatocytes or cholangiocytes, the latter being the cells that line the bile ducts.

Liver transplantation

Human liver transplants were first performed by Thomas Starzl in the United States and Roy Calne in Cambridge, England in 1963 and 1965 respectively. Liver transplantation is the only option for those with irreversible liver failure. Most transplants are done for chronic liver diseases leading to cirrhosis, such as chronic hepatitis C, alcoholism, autoimmune hepatitis, and many others. Less commonly, liver transplantation is done for fulminant hepatic failure, in which liver failure occurs over days to weeks.

Liver allografts for transplant usually come from non-living donors who have died from fatal brain injury. Living donor liver transplantation is a technique in which a portion of a living person's liver is removed and used to replace the entire liver of the recipient. This was first performed in 1989 for pediatric liver transplantation. Only 20% of an adult's liver (Couinaud segments 2 and 3) is needed to serve as a liver allograft for an infant or small child.

More recently, adult-to-adult liver transplantation has been done using the donor's right hepatic lobe which amounts to 60% of the liver. Due to the ability of the liver to regenerate, both the donor and recipient end up with normal liver function if all goes well. This procedure is more controversial as it entails performing a much larger operation on the donor, and indeed there have been at least 2 donor deaths out of the first several hundred cases. A recent publication has addressed the problem of donor mortality, and at least 14 cases have been found. The risk of postoperative complications (and death) is far greater in right sided hepatectomy than left sided operations.

With the recent advances of non-invasive imaging, living liver donors usually have to undergo imaging examinations for liver anatomy to decide if the anatomy is feasible for donation. The evaluation is usually performed by multi-detector row computed tomography (MDCT) and magnetic resonance imaging (MRI). MDCT is good in vascular anatomy and volumetry. MRI is used for biliary tree anatomy. Donors with very unusual vascular anatomy, which makes them unsuitable for donation, could be screened out to avoid unnecessary operations.Image:LDLTA.jpg|MDCT image. Arterial anatomy contraindicated for liver donation.Image:LDLTP.jpg|MDCT image. Portal venous anatomy contraindicated for liver donation.Image:LDLT volume measure.jpg|MDCT image. 3D image created by MDCT can clearly visualize the liver, measure the liver volume, and plan the dissection plane to facilitate the liver transplantation procedure.

Development

Fetal blood supply

In the growing fetus, a major source of blood to the liver is the umbilical vein which supplies nutrients to the growing fetus. The umbilical vein enters the abdomen at the umbilicus, and passes upward along the free margin of the falciform ligament of the liver to the inferior surface of the liver. There it joins with the left branch of the portal vein. The ductus venosus carries blood from the left portal vein to the left hepatic vein and then to the inferior vena cava, allowing placental blood to bypass the liver.

In the fetus, the liver develops throughout normal gestation, and does not perform the normal filtration of the infant liver. The liver does not perform digestive processes because the fetus does not consume meals directly, but receives nourishment from the mother via the placenta. The fetal liver releases some blood stem cells that migrate to the fetal thymus, so initially the lymphocytes, called T-cells, are created from fetal liver stem cells. Once the fetus is delivered, the formation of blood stem cells in infants shifts to the red bone marrow.

After birth, the umbilical vein and ductus venosus are completely obliterated two to five days postpartum; the former becomes the ligamentum teres and the latter becomes the ligamentum venosum. In the disease state of cirrhosis and portal hypertension, the umbilical vein can open up again.

As food

Mammal, bird and fish livers are commonly eaten as food by humans. Livers from calf, chicken, and goose are widely available in supermarkets.

Liver can be baked, boiled, broiled, fried, stir-fried, or eaten raw (liver sashimi). The most widespread liver dish is liver and onions. In many preparations pieces of liver are combined with pieces of meat or kidneys, like in mixed grill or in Meurav Yerushalmi. Liver is also often made into spreads; well-known examples include liver pâté, foie gras, chopped liver, and leverpostej. Liver sausages such as Braunschweiger and liverwurst are also a valued meal; liver sausages may also be used as spreads.

Animal livers are rich in iron and Vitamin A, and cod liver oil is commonly used as a dietary supplement. Traditionally some fish livers were valued as food, especially the stingray liver. It was used to prepare delicacies such as "poached skate liver on toast" in England, as well as the "beignets de foie de raie" and "foie de raie en croute" in French cuisine.

Poisoning

Very high doses of Vitamin A have the potential to be toxic and can cause hypervitaminosis A, a dangerous disorder. Russian sailor Alexander Konrad, who accompanied explorer Valerian Albanov in a tragic ordeal over the Arctic ice in 1912 wrote about the awful effects of consuming polar bear liver. Also, in 1913, Antarctic explorers Douglas Mawson and Xavier Mertz were both poisoned, the latter fatally, from eating husky liver.

Poisoning will less likely result from consuming oil-based vitamin A products and liver than from consuming water-based and solid preparations.

Inuit will not eat the liver of polar bears (a polar bear's liver contains so much Vitamin A as to be poisonous to humans), or seal.

Cultural allusions

In Greek mythology, Prometheus was punished by the gods for revealing fire to humans, by being chained to a rock where a vulture (or an eagle) would peck out his liver, which would regenerate overnight. (The liver is the only human internal organ that actually can regenerate itself to a significant extent.)

Many ancient peoples of the Near East and Mediterranean areas practised a type of divination called haruspicy, whereby they tried to obtain information from examining the livers of sheep and other animals.

The Talmud (tractate Berakhot 61b) refers to the liver as the seat of anger, with the gallbladder counteracting this.

In the Persian, Urdu, and Hindi languages, the liver (جگر or जिगर or jigar) refer to the liver in figurative speech to refer to courage and strong feelings, or "their best," e.g. "This Mecca has thrown to you the pieces of its liver!" . The term jan e jigar literally "the strength (power) of my liver" is a term of endearment in Urdu. In Persian slang, jigar is used as an adjective for any object which is desirable, especially women.

The legend of Liver-Eating Johnson says that he would cut out and eat the liver of each man killed after dinner.

In the motion picture The Message, Hind bint Utbah is implied or portrayed eating the liver of Hamza ibn ‘Abd al-Muttalib during the Battle of Uhud.

See also

• Artificial liver
• Bile
• Bile canaliculus
• Hepatocyte
• Liver function tests
• Liver shot

References

1. The Greek word "ήπαρ" was derived from hēpaomai ( ηπάομαι): to mend, to repair, hence hēpar actually means "repairable", indicating that this organ can regenerate itself spontaneously in the case of lesion.
2. Calvin W. Schwabe Unmentionable Cuisine
3. Valerian Albanov. In the Land of White Death. Appendix; A. Konrad's notes.
4. A. Aggrawal, Death by Vitamin A
5. Myhre et al., "Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations", Am. J. Clinical Nutrition, 78, 1152 (2003)
6. Man's best friend? - Student BMJ
7. THE GREAT BATTLE OF BADAR (Yaum-e-Furqan)

Further reading

The following are standard medical textbooks:

• Eugene R. Schiff, Michael F. Sorrell, Willis C. Maddrey, eds. Schiff's diseases of the liver, 9th ed. Philadelphia : Lippincott, Williams & Wilkins, 2003. ISBN 0-7817-3007-4
• Sheila Sherlock, James Dooley. Diseases of the liver and biliary system, 11th ed. Oxford, UK ; Malden, MA : Blackwell Science. 2002. ISBN 0-632-05582-0
• David Zakim, Thomas D. Boyer. eds. Hepatology: a textbook of liver disease, 4th ed. Philadelphia: Saunders. 2003. ISBN 0-7216-9051-3

These are for the lay reader or patient:

• Sanjiv Chopra. The Liver Book: A Comprehensive Guide to Diagnosis, Treatment, and Recovery, Atria, 2002, ISBN 0-7434-0585-4
• Melissa Palmer. Dr. Melissa Palmer's Guide to Hepatitis and Liver Disease: What You Need to Know, Avery Publishing Group; Revised edition May 24, 2004, ISBN 1-58333-188-3. her webpage.
• Howard J. Worman. The Liver Disorders Sourcebook, McGraw-Hill, 1999, ISBN 0-7373-0090-6. his Columbia University web site, "Diseases of the liver"

External links

• Liver at the Open Directory Project.
• VIRTUAL Liver - online learning resource