Liver

The liver is one of the largest internal organs of the human body.

The liver is an organ in vertebrates, including humans. It plays a major role in metabolism and has a number of functions in the body including drug detoxification, glycogen storage, and plasma protein synthesis. It also produces bile, which is important for digestion. Medical terms related to the liver often start in hepato- or hepatic from the Greek word for liver, hepar.

Anatomy

View from below

Ventral view of perfused rat liver

The adult human liver normally weighs between 1.0 - 2.5 kilograms, and is a soft, pinkish-brown "boomerang shaped" organ. It is the second largest organ (the largest organ being the skin) Its anatomical postion in the body is : immediately under the diaphragm on the right side of the upper abdomen. The liver lies on the right of the stomach and makes a kind of bed for the gallbladder (which stores bile).

The liver is supplied by two major blood vessels: the hepatic artery and the portal vein. The hepatic artery normally comes off the celiac trunk. The portal vein brings venous blood from the spleen, pancreas, and small intestines, so that the liver can process the nutrients and byproducts of food digestion. The hepatic veins drain directly into the inferior vena cava.

The bile produced in the liver is collected in bile canaliculi, which merge to form bile ducts. These eventually drain into the right and left hepatic ducts, which in turn 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 duodenum together at the ampulla of Vater. The branchings of the bile ducts resemble those of a tree, and indeed the term "biliary tree" is commonly used in this setting.

The liver is one of the only internal human organs capable of natural regeneration of lost tissue; as little as 25% of remaining liver can regenerate into a whole liver again. This is predominantly due to the hepatocytes acting as unipotential stem cells. There is also some evidence of bipotential stem cells, called oval cells, which can differentiate into either hepatocytes or cholangiocytes (cells that line the bile ducts).

Surface anatomy

Apart from a patch where it connects to the diaphragm, 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. Traditional gross anatomy divided the liver into four lobes 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 is 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.

Functional anatomy

For purposes such as advanced liver surgery, it is crucial to understand the organization of liver based on blood supply and biliary drainage. The central area where the common bile duct, portal vein, and hepatic artery enter the liver 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 a plane joining the gallbladder fossa to the inferior vena cava. In the widely used Couinaud or "French" system, the functional lobes are further divided into a total of eight segments based on secondary and tertiary branching of the blood supply. The segments corresponding to the surface anatomical lobes are as follows:

Physiology

The various functions of the liver are carried out by the liver cells or hepatocytes.

• The liver produces and excretes bile required for food digestion. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.
• The liver performs several roles in carbohydrate metabolism:
  • Gluconeogenesis (the formation of glucose from certain amino acids, lactate or glycerol)
  • Glycogenolysis (the formation of glucose from glycogen)
  • Glycogenesis (the formation of glycogen from glucose)
  • The breakdown of insulin and other hormones
• The liver also performs several roles in lipid metabolism:
  • Cholesterol synthesis
  • The production of triglycerides (fats).
• The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, and XI, as well as protein C, protein S and antithrombin.
• The liver breaks down hemoglobin (bile pigments are its metabolites), toxic substances and most medicinal products. This sometimes results in toxication, when the metabolite is more toxic than its precursor.
• The liver converts ammonia to urea.
• The liver stores a multitude of substances, including glucose in the form of glycogen, vitamin B12, iron, and copper.
• In the first trimester fetus, the liver is the main site of red blood cell production. By the 42nd week of gestation, the bone marrow has almost completely taken over that task.

Producing an artificial organ or device capable of emulating all functions of the liver is outside the reach of science in the foreseeable future. Some functions can be emulated by liver dialysis, an experimental treatment for liver failure.

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 hemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.

• Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons, autoimmunity or hereditary conditions.
• Cirrhosis is the formation of fibrous tissue in the liver, replacing dead liver cells. The death of the liver cells can for example be caused by viral hepatitis, alcoholism or contact with other liver-toxic chemicals
• Hemochromatosis, a hereditary disease causing the accumulation of iron in the body, eventually leading to liver damage
• Cancer of the liver (primary hepatocellular carcinoma or cholangiocarcinoma and metastatic cancers, usually from other parts of the gastrointestinal tract)
• Wilson's disease, a hereditary disease which causes the body to retain copper
• Primary sclerosing cholangitis, an inflammatory disease of the bile duct, autoimmune in nature.
• Primary biliary cirrhosis, autoimmune disease of small bile ducts
• Budd-Chiari syndrome, obstruction of the hepatic vein.

A number of liver function tests are available to test the proper function of the liver. These are enzymes that are most abundant in liver tissue, metabolites or products.

Liver transplantation

Liver transplantation is an 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 two donor deaths out of the first several hundred cases.

Development

The liver develops as an endodermal outpocketing of the foregut called the hepatic diverticulum. Its initial blood supply is primarily from the vitelline veins that drain blood from the yolk sac. The superior part of the hepatic diverticulum gives rise to the hepatocytes and bile ducts, while the inferior part becomes the gallbladder and its associated cystic duct.

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 thence to the inferior vena cava, allowing placental blood to bypass the liver.

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.

Analogous organs

Arthropods have a digestive gland that functions like a combination of the liver and the pancreas. In insects this organ is known as the fat body.

Liver as food

Mammal and bird livers are commonly eaten as food: products include liver paté, Leberwurst, Braunschweiger, foie gras, chopped liver and liver sashimi.

Both animal and fish livers are rich in Vitamin A, cod liver oil being commonly used as a supplement. Vitamin A levels can be toxic, particularly in polar animals; the Antarctic explorers Douglas Mawson and Xavier Mertz were both poisoned, the latter fatally, from eating husky liver.

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, Ethon) would peck out his liver, which would grow again overnight. Curiously, the liver is the only human internal organ that actually can regenerate itself to a certain extent, a characteristic which may have already been known to the Greeks.

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

References

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 0781730074
• Sheila Sherlock, James Dooley. Diseases of the liver and biliary system, 11th ed. Oxford, UK ; Malden, MA : Blackwell Science. 2002. ISBN 0632055820
• David Zakim, Thomas D. Boyer. eds. Hepatology : a textbook of liver disease, 4th ed. Philadelphia: Saunders. 2003. ISBN 0721690513
• Sanjiv Chopra. The Liver Book: A Comprehensive Guide to Diagnosis, Treatment, and Recovery, Atria, 2002, ISBN 0743405854
• 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 1583331883. her webpage.
• Howard J. Worman. The Liver Disorders Sourcebook, McGraw-Hill, 1999, ISBN 0737300906. his Columbia U web site, Diseases of the liver

See also

• Liver function tests

External links

• American Association for the Study of Liver Diseases AASLD
• American Liver Society ALS
• WikiLiver: A Wiki dedicated to the liver