Anatomy

The adult human liver normally weighs between 1.3 - 3.0 kilograms, and is a soft, pinkish-brown "boomerang shaped" organ. It is the second largest organ (the largest organ being the skin) and the largest gland within the human body. Its anatomical position 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 main blood vessels on its right lobe: 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 branching of the bile ducts resemble those of a tree, and indeed the term "biliary tree" is commonly used in this setting.

The liver is among the few 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 (i.e. a single hepatocyte can divide into two hepatocyte daughter 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).

Physiology

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

• The liver produces and excretes bile required for dissolving fats. 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 is responsible for the mainstay of protein metabolism.
• 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, creating metabolites that are added to bile as pigment.
• The liver breaks down toxic substances and most medicinal products in a process called drug metabolism. 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 32nd week of gestation, the bone marrow has almost completely taken over that task.
• 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.

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.

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.
• Gilbert's syndrome, a genetic disorder of bilirubin metabolism, found in about 5% of the population.

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

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

Liver function tests

Liver function tests (LFTs or LFs), which include liver enzymes, are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. Most liver diseases cause only mild symptoms initially, while it is vital that these diseases be detected early. Hepatic involvement in some diseases can be of crucial importance.

Total Protein (TP)

The liver produces most of the plasma proteins in the body making a measure of the amount of protein in the blood useful. Reference range (60-80 g/L).

Albumin (Alb)

Albumin is a protein made specifically by the liver, and can be measured cheaply and easily. It is the main constituent of total protein; the remaining fraction is called globulin (including e.g. the immunoglobulins). Albumin levels are decreased in chronic liver disease, such as cirrhosis. It is also decreased in nephrotic syndrome, where it is lost through the urine. Poor nutrition or states of protein catabolism may also lead to hypoalbuminaemia. The half-life of albumin is approximately 20 days. Albumin is not considered to be an especially useful marker of liver synthetic function, coagulation factors (see below) are much more sensitive. The reference range is 30-50 g/L. (3.0-5.0 mg/dL)

Alanine transaminase (ALT)

Alanine transaminase (ALT), also called Serum Glutamic Pyruvic Transaminase (SGPT) or Alanine aminotransferrase (ALAT) is an enzyme present in hepatocytes (liver cells). When a cell is damaged, it leaks this enzyme into the blood, where it is measured. ALT rises dramatically in acute liver damage, such as viral hepatitis or paracetamol (acetaminophen) overdose. Elevations are often measured in multiples of the upper limit of normal (ULN). The reference range is 15-45 U/L in most laboratories.

Aspartate transaminase (AST)

Aspartate transaminase (AST) also called Serum Glutamic Oxaloacetic Transaminase (SGOT) or aspartate aminotransferase (ASAT) is similar to ALT in that it is another enzyme associated with liver parenchymal cells. It is raised in acute liver damage. It is also present in red cells, and cardiac and skeletal muscle. The ratio of AST:ALT is useful in differentiating between causes of acute hepatitis.

Alkaline phosphatase (ALP)

Alkaline phosphatase (ALP) is an enzyme in the cells lining the biliary ducts of the liver. ALP levels in plasma will rise with large bile duct obstruction, intrahepatic cholestasis or infiltrative diseases of the liver. ALP is also present in bone and placental tissue, so it is higher in growing children (as their bones are being remodelled). The reference range is usually 30-120 U/L.

Total bilirubin (TBIL)

Bilirubin is a breakdown product of heme (a part of hemoglobin in red blood cells). The liver is responsible for clearing this, excreting it out through bile into the intestine. Problems with the liver or blockage of the drainage of bile will cause increased levels of bilirubin, as will increased haemolysis of red cells.

Direct bilirubin, or conjugated bilirubin is often measured in tandem, especially if the total bilirubin level is elevated. Bilirubin is unconjugated before the liver modifies it for excretion. It is dangerous in babies, as it can pass the blood-brain barrier causing kernicterus.

Other tests commonly requested alongside LFTs:

Gamma glutamyl transpeptidase (GGT)

Although reasonably specific to the liver and a more sensitive marker for cholestatic damage than ALP, Gamma glutamyl transpeptidase (GGT) may be elevated with even minor, sub-clinical levels of liver dysfunction. It can also be helpful in identifying the cause of an isolated elevation in ALP. GGT is raised in alcohol toxicity (acute and chronic).