Liver
Liver of a sheep: (1) right lobe, (2) left lobe, (3) caudate lobe, (4) quadrate lobe, (5) hepatic artery and portal vein, (6) hepatic lymph nodes, (7) gall bladder.
Gray's	subject #250 1188
Artery	hepatic artery
Vein	hepatic vein, portal vein
Nerve	celiac ganglia, vagus[1]
Precursor	foregut
MeSH	Liver

The liver is an organ in some animals, including mammals (and therefore humans), birds, and reptiles. It plays a major role in metabolism and has a number of functions in the body including glycogen storage, plasma protein synthesis, and drug detoxification. This organ also is the largest gland in the human body. It produces bile, which is important in digestion. It performs and regulates a wide variety of high-volume biochemical reactions requiring specialized tissues. Medical terms related to the liver often start in hepato- or hepatic from the Greek word for liver, hepar.

Contents [hide] 1 Anatomy 1.1 Flow of blood 1.2 Flow of bile 1.3 Regeneration 1.4 Traditional (Surface) anatomy 1.4.1 Peritoneal ligaments 1.4.2 Lobes 1.5 Modern (Functional) anatomy 2 Physiology 3 Diseases of the liver 4 Liver transplantation 5 Development 5.1 Fetal blood supply 6 Liver as food 7 Cultural allusions 8 Further reading 9 See also 10 References 11 Additional images 12 External links

  Anatomy

The adult human liver normally weighs between 1.3 - 3.0 kilograms, and it 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.

It is located on the right side of the upper abdomen body diaphragm. The liver lies on the right of the stomach and makes a kind of bed for the gallbladder (which stores bile).

  Flow of blood

The splenic vein, joining with the superior mesenteric vein to form the portal vein, brings venous blood from the spleen, pancreas, small intestine, and large intestine, so that the liver can process the nutrients and byproducts of food digestion.

The hepatic veins drain directly into the inferior vena cava.

The hepatic artery is generally a branch from the celiac trunk, although occasionally some or all of the blood can be from other branches such as the superior mesenteric artery.

Approximately ⅔ of the blood flow to the liver is from the portal venous system, and ⅓ is from the hepatic artery.

  Flow of bile

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.

  Regeneration

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).

  Peritoneal ligaments

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.

  Lobes

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.

  Modern (Functional) anatomy

For purposes such as advanced liver surgery, it is crucial to understand the fundamental importance of the liver on the blood supply and biliary drainage system. 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. This 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 (the ligamentum teres becomes the falciform ligament) also separates the medial and lateral segmants. The medial segment is what used to be 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.^[2][3] The subsegments corresponding to the anatomical lobes are as follows:

Segment*	Couinaud segments
Caudate	1
Lateral	2, 3
Medial	4a, 4b
Right	5, 6, 7, 8

• or lobe in the Caudate's case.

Each number in the list corresponds to one in the table.

1. Caudate
2. Superior subsegment of the lateral segment
3. Inferior subsegment of the lateral segment
4.  
   1. Superior subsegment of the medial segment
   2. Inferior subsegment of the medial segment
5. Inferior subsegment of the anterior segment
6. Inferior subsegment of the posterior segment
7. Superior subsegment of the posterior segment
8. Superior subsegment of the anterior segment

  Physiology

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

• The liver produces and excretes bile required for emulsifying 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 synthesis of glucose from certain amino acids, lactate or glycerol)
  • Glycogenolysis (the breakdown of glycogen into glucose) (muscle tissues can also do this)
  • 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, X 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 (bilirubin and biliverdin).
• 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.
• Glycogen storage disease type II,The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system.

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 transplantation

Main article: Liver transplantation

Human liver transplant was first performed by Thomas Starzl in USA and Roy Calne in 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.^[4] The risk of postoperative complications (and death) is far greater in right sided hepatectomy than left sided operations

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.

In the fetus, the liver is developing 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.

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. This testing is performed by a Medical technologist on a patient's serum or plasma which is collected by a phlebotomist.

Contents [hide] 1 Standard liver panel 1.1 Total Protein (TP) 1.2 Albumin (Alb) 1.3 Alanine transaminase (ALT) 1.4 Aspartate transaminase (AST) 1.5 Alkaline phosphatase (ALP) 1.6 Total bilirubin (TBIL) 2 Other tests commonly requested alongside LFTs: 2.1 Gamma glutamyl transpeptidase (GGT) 2.2 5' nucleotidase (5'NTD) 2.3 Coagulation tests (e.g. INR) 2.4 Serum glucose (BG, Glu)

  Standard liver panel

  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 g/dL)

  Alanine transaminase (ALT)

Alanine transaminase (ALT), also called Serum Glutamic Pyruvic Transaminase (SGPT) or Alanine aminotransferase (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, but is also present in red cells, and cardiac and skeletal muscle and is therefore not specific to the liver. The ratio of AST to ALT is sometimes useful in differentiating between causes of liver damage:

• ALT>AST: acute viral hepatitis, drug-induced hepatitis or Non-alcoholic fatty liver disease
• ALT<AST: Alcoholic liver disease

In resource-poor settings, the AST is more frequently available than the ALT, because it is a cheaper assay.

  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 haemoglobin in red blood cells). The liver is responsible for clearing the blood of bilirubin. It does this by the following mechanism: bilirubin is taken up into hepatocytes, conjugated (modified to make it water-soluble), and secreted into the bile, which is excreted into the intestine.

Liver function tests typically measure Total bilirubin (TBIL) and Direct bilirubin (a.k.a. conjugated bilirubin, CB). Indirect bilirubin (a.k.a. unconjugated bilirubin, UCB) is obtained by subtracting direct bilirubin from total bilirubin.

Increased total bilirubin causes jaundice, and can signal a number of problems:

1. Increased bilirubin production. This can be due to a number of causes, including hemolytic anemias and internal hemorrhage.

2. Problems with the liver, which are reflected as deficiencies in bilirubin metabolism (e.g. reduced hepatocyte uptake, impaired conjugation of bilirubin, and reduced hepatocyte secretion of bilirubin). Some examples would be cirrhosis and viral hepatitis.

3. Obstruction of the bile ducts, reflected as deficiencies in bilirubin excretion. (Obstruction can be located either within the liver or outside the liver.)

The diagnosis is narrowed down further by looking at the levels of direct bilirubin. If direct (i.e. conjugated) bilirubin is normal, then the problem is an excess of unconjugated bilirubin, and the location of the problem is upstream of bilirubin excretion. Anemia, viral hepatitis, or cirrhosis can be suspected. If direct bilirubin is elevated, then the liver is conjugating bilirubin normally, but is not able to excrete it. Bile duct obstruction by gallstones or cancer should be suspected.

  :

 

  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).

  5' nucleotidase (5'NTD)

5'NTD is another test specific for cholestasis or damage to the intra or extrahepatic biliary system, and in some laboratories, is used as a substitute for GGT for ascertaining whether an elevated ALP is of biliary or extra-biliary origin.

  Coagulation tests (e.g. INR)

The liver is responsible for the production of coagulation factors. The international normalized ratio (INR) measures the speed of a particular pathway of coagulation, comparing it to normal. If the INR is increased, it means it is taking longer than usual for blood to clot. The INR will only be increased if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired: it is not a sensitive measure of liver function.

It is very important to normalize the INR before operating on people with liver problems (usually by transfusion with blood plasma containing the deficient factors) as they could bleed excessively.

  Serum glucose (BG, Glu)

The liver's ability to produce glucose (gluconeogenesis) is usually the last function to be lost in the setting of fulminant liver failure.

From Wikipedia, the free encyclopedia

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. This testing is performed by a Medical technologist on a patient's serum or plasma which is collected by a phlebotomist.

Contents [hide] 1 Standard liver panel 1.1 Total Protein (TP) 1.2 Albumin (Alb) 1.3 Alanine transaminase (ALT) 1.4 Aspartate transaminase (AST) 1.5 Alkaline phosphatase (ALP) 1.6 Total bilirubin (TBIL) 2 Other tests commonly requested alongside LFTs: 2.1 Gamma glutamyl transpeptidase (GGT) 2.2 5' nucleotidase (5'NTD) 2.3 Coagulation tests (e.g. INR) 2.4 Serum glucose (BG, Glu)

  Standard liver panel

 

  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 g/dL)

 

  Alanine transaminase (ALT)

Alanine transaminase (ALT), also called Serum Glutamic Pyruvic Transaminase (SGPT) or Alanine aminotransferase (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, but is also present in red cells, and cardiac and skeletal muscle and is therefore not specific to the liver. The ratio of AST to ALT is sometimes useful in differentiating between causes of liver damage:

• ALT>AST: acute viral hepatitis, drug-induced hepatitis or Non-alcoholic fatty liver disease
• ALT<AST: Alcoholic liver disease

In resource-poor settings, the AST is more frequently available than the ALT, because it is a cheaper assay.

 

  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 haemoglobin in red blood cells). The liver is responsible for clearing the blood of bilirubin. It does this by the following mechanism: bilirubin is taken up into hepatocytes, conjugated (modified to make it water-soluble), and secreted into the bile, which is excreted into the intestine.

Liver function tests typically measure Total bilirubin (TBIL) and Direct bilirubin (a.k.a. conjugated bilirubin, CB). Indirect bilirubin (a.k.a. unconjugated bilirubin, UCB) is obtained by subtracting direct bilirubin from total bilirubin.

Increased total bilirubin causes jaundice, and can signal a number of problems:

1. Increased bilirubin production. This can be due to a number of causes, including hemolytic anemias and internal hemorrhage.

2. Problems with the liver, which are reflected as deficiencies in bilirubin metabolism (e.g. reduced hepatocyte uptake, impaired conjugation of bilirubin, and reduced hepatocyte secretion of bilirubin). Some examples would be cirrhosis and viral hepatitis.

3. Obstruction of the bile ducts, reflected as deficiencies in bilirubin excretion. (Obstruction can be located either within the liver or outside the liver.)

The diagnosis is narrowed down further by looking at the levels of direct bilirubin. If direct (i.e. conjugated) bilirubin is normal, then the problem is an excess of unconjugated bilirubin, and the location of the problem is upstream of bilirubin excretion. Anemia, viral hepatitis, or cirrhosis can be suspected. If direct bilirubin is elevated, then the liver is conjugating bilirubin normally, but is not able to excrete it. Bile duct obstruction by gallstones or cancer should be suspected.

 

  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).

 

  5' nucleotidase (5'NTD)

5'NTD is another test specific for cholestasis or damage to the intra or extrahepatic biliary system, and in some laboratories, is used as a substitute for GGT for ascertaining whether an elevated ALP is of biliary or extra-biliary origin.

 

  Coagulation tests (e.g. INR)

The liver is responsible for the production of coagulation factors. The international normalized ratio (INR) measures the speed of a particular pathway of coagulation, comparing it to normal. If the INR is increased, it means it is taking longer than usual for blood to clot. The INR will only be increased if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired: it is not a sensitive measure of liver function.

It is very important to normalize the INR before operating on people with liver problems (usually by transfusion with blood plasma containing the deficient factors) as they could bleed excessively.

 

  Serum glucose (BG, Glu)

The liver's ability to produce glucose (gluconeogenesis) is usually the last function to be lost in the setting of fulminant liver failure.