Liver Function

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Liver function

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. The liver's highly specialized tissues regulate a wide variety of high-volume biochemical reactions, 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 (ἡπαρ )


Anatom
The liver is a reddish brown organ with four lobes of unequal size and shape. A 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. It 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 nutrients from the small intestine and the descending colon. These blood vessels subdivide into capillaries which then lead to a lobule. Each lobule is made up of millions of hepatic cells which are the basic metabolic cells.


Blood flow
The liver receives a dual blood supply from 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.


Billiard flow
The term billiard 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 extra hepatic (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 ampullae’s of Vaster


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 aciform ligament and the right and left triangular ligaments.
These "lets" 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 aciform ligament, which attaches the liver to the posterior portion of the anterior body wall.


Lobes
Traditional gross anatomy divided the liver into four lobes based on surface features. The aciform 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 ligament venous and ligament tares (anything left of these is the left lobe), the transverse fissure (or portal hepatics) divides the caudate from the quadrate lobe, and the right societal fossil, 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
* or lobe in the case of the caudate lobe.


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


The central area where the common bile duct, hepatic portal vein, and hepatic artery proper enter is the haulm or "portal hepatics". 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 fosses 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 ligament terse also separates the medial and lateral segments. The medial segment is also called the quadrate lobe. In the widely used Coquina (or "French") system, the functional lobes are further divided into a total of eight sub segments 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
Further information: Proteins produced and secreted by the liver


* A large part of amino acid synthesis


* The liver performs several roles in carbohydrate metabolism:


o Gluconeogenesis (the synthesis of glucose from certain amino acids, lactate or glycerol). Note that humans and some other mammals cannot synthesize glucose from glycerol.


o Glycogenolysis (the breakdown of glycogen into glucose)


o Glycogen sis (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


Lip genesis, 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 ant thrombin.


* 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 yellowish 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.


* 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 (e.g., methylamine) and most medicinal products in a process called drug metabolism. This sometimes results in oxidations, when the metabolite is more toxic than its precursor. Preferably, the toxins are conjugated to avail excretion in bile or urine.

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 (1-3 years' supply), iron, and copper.


* The liver is responsible for immunological effects- the reticuloendothelial system of the liver contains many immunologic ally active cells, acting as a 'sieve' for antigens carried to it via the portal system.


* The liver produces albumin, the major similar component of blood serum.


* The liver synthesizes angiotensinogen, a hormone that is responsible for raising the blood pressure when activated by rennin, an enzyme that is released when the kidney senses low blood pressure.


Diseases of the liver Main article: Liver disease Left lobe liver tumor


The liver supports almost every organ in the body and is vital for survival. Because of its strategic location and multidimensional functions, the liver is also prone to many diseases.

The most common include: Infections such as hepatitis A, B, C, E, alcohol damage, fatty liver, cirrhosis, cancer, drug damage (especially acetaminophen, cancer drugs)


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.


There are also many pediatric liver diseases including billiard Artesia, alpha-1 antitypic deficiency, flagella syndrome, progressive familial intrahepatic homeostasis, and Lange Hans cell histiocytosis, to name but a few.


Diseases that interfere with liver function will lead to derangement of these processes. However, the liver has a great capacity to regenerate and has a large reserve capacity. In most cases, the liver only produces symptoms after extensive damage.


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


Disease signs The classic signs of liver damage include the following:


* Pale stools occur when Stercobilin, a brown pigment, is absent from the stool. Stercobilin is derived from bilirubin metabolites produced in the liver.


* Dark urine occurs when bilirubin mixes with urine


* Bilirubin when it deposits in skin, causes an intense itch. Itching is the most common complaint by people who have liver failure. Often this itch cannot be relieved by drugs.


* Swelling of the abdomen, ankles and feet occurs because the liver fails to make albumin.


* Excessive fatigue occurs from a generalized loss of nutrients, minerals and vitamins.


* Bruising and easy bleeding are other features of liver disease. The liver makes substances which help prevent bleeding. When liver damage occurs, these substances are no longer present and severe bleeding can occur.

Diagnosis


The diagnosis of liver function is made by blood tests. Liver function tests can readily pinpoint the extent of liver damage. If infection is suspected, then other serological tests are done. Sometimes one may require an ultrasound or a CT scan to image the liver.


Physical exam of the liver is not accurate in determining the extent of liver damage. Physical exam can only reveal presence of tenderness or size of liver but in all cases some type of radiological study is required to look at the liver.


Biopsy
The ideal way to look at damage to the liver is with a biopsy. A biopsy is not required in all cases but may be necessary when the cause is unknown. The procedure is done at the bedside and only requires local anesthetic. A small thin needle is inserted into the skin just below the rib cage and a biopsy is obtained. The tissue is sent to the laboratory where it is analyzed under a microscope. Sometimes the radiologist may perform a liver biopsy under ultrasound guidance if only a small area is involved.


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.


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 velocities or hepatic oval cells, which are thought to reside in the canals of Haring. These cells can differentiate into either hepatocytes or cholangiocytes, the latter being the cells that line the bile ducts.


The capability for the liver to regenerate itself has been known since at least the times of the ancient Greeks, whose mythology includes a story about Prometheus being chained to a rock in the Caucasus Mountain and his liver being partially eaten during the day by an eagle only to "regenerate" in the night. The story, however, embellishes the speed with which this occurs.


Liver transplantation
Human liver transplants were first performed by Thomas Startle in the United States and Roy Carlen in Cambridge, England in 1963 and 1965, respectively.


After resection of left lobe liver tumor
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 fulminates hepatic failure, in which liver failure occurs over days to weeks.


Liver allograft for transplant usually comes 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 (Coquina 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 operations than that in 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 volume try. MRI is used for billiard tree anatomy. Donors with very unusual vascular anatomy, which makes them unsuitable for donation, could be screened out to avoid unnecessary operations.

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