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The liver is a major
organ Organ may refer to: Biology * Organ (biology), a part of an organism Musical instruments * Organ (music), a family of keyboard musical instruments characterized by sustained tone ** Electronic organ, an electronic keyboard instrument ** Hammond ...
only found in vertebrates which performs many essential biological functions such as
detoxification Detoxification or detoxication (detox for short) is the physiological or medicinal removal of toxic substances from a living organism, including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of ...
of the organism, and the synthesis of proteins and biochemicals necessary for
digestion Digestion is the breakdown of large insoluble food molecules into small water-soluble food molecules so that they can be absorbed into the watery blood plasma. In certain organisms, these smaller substances are absorbed through the small intest ...
and growth. In humans, it is located in the right upper quadrant of the
abdomen The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the to ...
, below the
diaphragm Diaphragm may refer to: Anatomy * Thoracic diaphragm, a thin sheet of muscle between the thorax and the abdomen * Pelvic diaphragm or pelvic floor, a pelvic structure * Urogenital diaphragm or triangular ligament, a pelvic structure Other * Diap ...
. Its other roles in
metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...
include the regulation of glycogen storage, decomposition of
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "hol ...
s, and the production of
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s. The liver is an accessory digestive organ that produces
bile Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bi ...
, an
alkaline In chemistry, an alkali (; from ar, القلوي, al-qaly, lit=ashes of the saltwort) is a basic, ionic salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as a base that dissolves in water. A solution of a ...
fluid containing
cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell memb ...
and
bile acid Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primar ...
s, which helps the breakdown of fat. The
gallbladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although ...
, a small pouch that sits just under the liver, stores bile produced by the liver which is later moved to the small intestine to complete digestion. The liver's highly specialized tissue, consisting mostly of
hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...
s, regulates 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. Estimates regarding the organ's total number of functions vary, but is generally cited as being around 500. It is not known how to compensate for the absence of liver function in the long term, although
liver dialysis A liver support system or diachysis is a type of therapeutic device to assist in performing the functions of the liver. Such systems focus either on removing the accumulating toxins (liver dialysis), or providing additional replacement of the met ...
techniques can be used in the short term. Artificial livers have not been developed to promote long-term replacement in the absence of the liver. ,
liver transplantation Liver transplantation or hepatic transplantation is the replacement of a Liver disease, diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for Cirrhosis, end-stage liver disease and ...
is the only option for complete liver failure.


Structure

The liver is a reddish-brown, wedge-shaped
organ Organ may refer to: Biology * Organ (biology), a part of an organism Musical instruments * Organ (music), a family of keyboard musical instruments characterized by sustained tone ** Electronic organ, an electronic keyboard instrument ** Hammond ...
with two lobes of unequal size and shape. A human liver normally weighs approximately and has a width of about . There is considerable size variation between individuals, with the standard reference range for men being and for women . It is both the heaviest internal organ and the largest
gland In animals, a gland is a group of cells in an animal's body that synthesizes substances (such as hormones) for release into the bloodstream (endocrine gland) or into cavities inside the body or its outer surface (exocrine gland). Structure De ...
in the human body. Located in the right upper quadrant of the
abdominal cavity The abdominal cavity is a large body cavity in humans and many other animals that contains many organs. It is a part of the abdominopelvic cavity. It is located below the thoracic cavity, and above the pelvic cavity. Its dome-shaped roof is th ...
, it rests just below the diaphragm, to the right of the stomach, and overlies the
gallbladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although ...
. The liver is connected to two large
blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide awa ...
s: the hepatic artery and the
portal vein The portal vein or hepatic portal vein (HPV) is a blood vessel that carries blood from the gastrointestinal tract, gallbladder, pancreas and spleen to the liver. This blood contains nutrients and toxins extracted from digested contents. Approx ...
. The hepatic artery carries oxygen-rich blood from the aorta via the
celiac trunk The celiac () artery (also spelled ''coeliac''), also known as the celiac trunk or truncus coeliacus, is the first major branch of the abdominal aorta. It is about 1.25 cm in length. Branching from the aorta at thoracic vertebra 12 (T12) in ...
, whereas the portal vein carries blood rich in digested nutrients from the entire
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
and also from the
spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
and
pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an ...
. These blood vessels subdivide into small capillaries known as liver sinusoids, which then lead to
lobules In anatomy, a lobe is a clear anatomical division or extension of an organ (as seen for example in the brain, lung, liver, or kidney) that can be determined without the use of a microscope at the gross anatomy level. This is in contrast to t ...
. Lobules are the functional units of the liver. Each lobule is made up of millions of hepatic cells (hepatocytes), which are the basic metabolic cells. The lobules are held together by a fine, dense, irregular
fibroelastic
connective tissue layer extending from the fibrous capsule covering the entire liver known as
Glisson's capsule The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it is ...
. This extends into the structure of the liver by accompanying the blood vessels, ducts, and nerves at the hepatic hilum. The whole surface of the liver, except for the bare area, is covered in a
serous In physiology, serous fluid or serosal fluid (originating from the Medieval Latin word ''serosus'', from Latin ''serum'') is any of various body fluids resembling serum, that are typically pale yellow or transparent and of a benign nature. The fl ...
coat derived from the
peritoneum The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mes ...
, and this firmly adheres to the inner
Glisson's capsule The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it is ...
.


Gross anatomy

Terminology related to the liver often starts in ''hepat-'' from ἡπατο-, from the
Greek Greek may refer to: Greece Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group. *Greek language, a branch of the Indo-European language family. **Proto-Greek language, the assumed last common ancestor ...
word for liver.


Lobes

The liver is grossly divided into two parts when viewed from above – a right and a left lobe - and four parts when viewed from below (left, right, caudate, and quadrate lobes). The falciform ligament makes a superficial division of the liver into a left and right lobe. From below, the two additional lobes are located between the right and left lobes, one in front of the other. A line can be imagined running from the left of the
vena cava In anatomy, the venae cavae (; singular: vena cava ; ) are two large veins (great vessels) that return deoxygenated blood from the body into the heart. In humans they are the superior vena cava and the inferior vena cava, and both empty into th ...
and all the way forward to divide the liver and gallbladder into two halves. This line is called Cantlie's line. Other anatomical landmarks include the ligamentum venosum and the
round ligament of the liver The round ligament of the liver (or ligamentum teres, or ligamentum teres hepatis) is a ligament that forms part of the free edge of the falciform ligament of the liver. It connects the liver to the umbilicus. It is the remnant of the left umbi ...
, which further divide the left side of the liver in two sections. An important anatomical landmark, the porta hepatis, divides this left portion into four segments, which can be numbered starting at the caudate lobe as I in an anticlockwise manner. From this parietal view, seven segments can be seen, because the eighth segment is only visible in the
visceral In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a f ...
view.


Surfaces

On the diaphragmatic surface, apart from a triangular bare area where it connects to the diaphragm, the liver is covered by a thin, double-layered membrane, the
peritoneum The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mes ...
, that helps to reduce friction against other organs. This surface covers the convex shape of the two lobes where it accommodates the shape of the diaphragm. The peritoneum folds back on itself to form the falciform ligament and the
right Rights are legal, social, or ethical principles of freedom or entitlement; that is, rights are the fundamental normative rules about what is allowed of people or owed to people according to some legal system, social convention, or ethical ...
and
left triangular ligament The left triangular ligament is a large peritoneal fold. It connects the posterior part of the upper surface of the left lobe of the liver to the thoracic diaphragm. Structure The left triangular ligament connects the posterior part of the up ...
s. These peritoneal ligaments are not related to the anatomic ligaments in joints, and the right and left triangular ligaments have no known functional importance, though they serve as surface landmarks. The falciform ligament functions to attach the liver to the posterior portion of the
anterior Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek language, Greek roots, describe something in its standard anatomical position. Th ...
body wall. The visceral surface or inferior surface is uneven and concave. It is covered in peritoneum apart from where it attaches the gallbladder and the porta hepatis. The fossa of gallbladder lies to the right of the quadrate lobe, occupied by the gallbladder with its cystic duct close to the right end of porta hepatis.


Impressions

Several impressions on the surface of the liver accommodate the various adjacent structures and organs. Underneath the right lobe and to the right of the gallbladder fossa are two impressions, one behind the other and separated by a ridge. The one in front is a shallow colic impression, formed by the hepatic flexure and the one behind is a deeper renal impression accommodating part of the right kidney and part of the
suprarenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...
. The suprarenal impression is a small, triangular, depressed area on the liver. It is located close to the right of the fossa, between the bare area and the caudate lobe, and immediately above the renal impression. The greater part of the suprarenal impression is devoid of peritoneum and it lodges the right suprarenal gland. Medial to the renal impression is a third and slightly marked impression, lying between it and the neck of the gall bladder. This is caused by the descending portion of the duodenum, and is known as the duodenal impression. The inferior surface of the left lobe of the liver presents behind and to the left of the gastric impression. This is moulded over the upper front surface of the stomach, and to the right of this is a rounded eminence, the tuber omentale, which fits into the concavity of the lesser curvature of the stomach and lies in front of the anterior layer of the
lesser omentum The lesser omentum (small omentum or gastrohepatic omentum) is the double layer of peritoneum that extends from the liver to the lesser curvature of the stomach, and to the first part of the duodenum. The lesser omentum is usually divided into th ...
.


Microscopic anatomy

Microscopically, each liver lobe is seen to be made up of hepatic lobules. The lobules are roughly hexagonal, and consist of plates of hepatocytes, and sinusoids radiating from a central vein towards an imaginary perimeter of interlobular portal triads. The central vein joins to the hepatic vein to carry blood out from the liver. A distinctive component of a lobule is the
portal triad In histology (microscopic anatomy), the lobules of liver, or hepatic lobules, are small divisions of the liver defined at the microscopic scale. The hepatic lobule is a building block of the liver tissue, consisting of a portal triad, hepatocy ...
, which can be found running along each of the lobule's corners. The portal triad consists of the hepatic artery, the portal vein, and the common bile duct. The triad may be seen on a liver ultrasound, as a Mickey Mouse sign with the portal vein as the head, and the hepatic artery, and the common bile duct as the ears.
Histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures v ...
, the study of microscopic anatomy, shows two major types of liver cell:
parenchymal cells Parenchyma () is the bulk of functional substance in an animal organ or structure such as a tumour. In zoology it is the name for the tissue that fills the interior of flatworms. Etymology The term ''parenchyma'' is New Latin from the word π ...
and nonparenchymal cells. About 70–85% of the liver volume is occupied by parenchymal hepatocytes. Nonparenchymal cells constitute 40% of the total number of liver cells but only 6.5% of its volume. The liver sinusoids are lined with two types of cell,
sinusoidal endothelial cells A liver sinusoid is a type of capillary known as a sinusoidal capillary, discontinuous capillary or sinusoid, that is similar to a fenestrated capillary, having discontinuous endothelium that serves as a location for mixing of the oxygen-rich blo ...
, and phagocytic
Kupffer cells Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. K ...
. Hepatic stellate cells are nonparenchymal cells found in the
perisinusoidal space The perisinusoidal space (or space of Disse) is a location in the liver between a hepatocyte and a sinusoid. It contains the blood plasma. Microvilli of hepatocytes extend into this space, allowing proteins and other plasma components from the si ...
, between a sinusoid and a hepatocyte. Additionally, intrahepatic
lymphocytes A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ada ...
are often present in the sinusoidal lumen. 2423 Microscopic Anatomy of Liver.jpg, Microscopic anatomy of the liver 2104 Three Major Capillary Types.jpg, Types of capillaries–sinusoid on right 3D Medical Animation liver parts.jpg, alt=3D Medical Animation Still Shot Depicting parts of liver, 3D Medical Animation Still Shot Depicting parts of liver


Functional anatomy

The central area or hepatic hilum, includes the opening known as the porta hepatis which carries the
common bile duct The common bile duct, sometimes abbreviated as CBD, is a duct in the gastrointestinal tract of organisms that have a gallbladder. It is formed by the confluence of the common hepatic duct and cystic duct and terminates by uniting with pancrea ...
and
common hepatic artery The common hepatic artery is a short blood vessel that supplies oxygenated blood to the liver, pylorus of the stomach, duodenum, pancreas, and gallbladder. It arises from the celiac artery and has the following branches: Additional images ...
, and the opening for the portal vein. The duct, vein, and artery divide into left and right branches, and the areas of the liver supplied by these branches constitute the functional left and right lobes. The functional lobes are separated by the imaginary plane, Cantlie's line, 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 Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek language, Greek roots, describe something in its standard anatomical position. Th ...
and posterior segment by the right hepatic vein. The left lobe is divided into the medial and
lateral Lateral is a geometric term of location which may refer to: Healthcare *Lateral (anatomy), an anatomical direction * Lateral cricoarytenoid muscle * Lateral release (surgery), a surgical procedure on the side of a kneecap Phonetics *Lateral co ...
segments by the left hepatic vein. The hilum of the liver is described in terms of three ''plates'' that contain the
bile duct A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. ...
s and blood vessels. The contents of the whole plate system are surrounded by a sheath. The three plates are the ''hilar plate'', the ''cystic plate'' and the ''umbilical plate'' and the plate system is the site of the many anatomical variations to be found in the liver.


Couinaud classification system

In the widely used
Couinaud Claude Couinaud (12 February 1922, in Neuilly-sur-Seine – 4 May 2008, in Paris) was a French surgeon and anatomist who made significant contributions in the field of Hepatobiliary system, hepatobiliary surgery. He is best known for his detailed ...
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 that receives blood flow from both the right- and left-sided vascular branches. The Couinaud classification divides the liver into eight functionally independent liver segments. Each segment has its own vascular inflow, outflow and biliary drainage. In the centre of each segment are branches of the portal vein, hepatic artery, and bile duct. In the periphery of each segment is vascular outflow through the hepatic veins. The classification system uses the vascular supply in the liver to separate the functional units (numbered I to VIII) with unit 1, the caudate lobe, receiving its supply from both the right and the left branches of the portal vein. It contains one or more hepatic veins which drain directly into the inferior vena cava. The remainder of the units (II to VIII) are numbered in a clockwise fashion:


Gene and protein expression

About 20,000 protein coding genes are expressed in human cells and 60% of these genes are expressed in a normal, adult liver. Over 400 genes are more specifically expressed in the liver, with some 150 genes highly specific for liver tissue. A large fraction of the corresponding liver-specific proteins are mainly expressed in hepatocytes and secreted into the blood and constitute plasma proteins and
hepatokines Hepatokines (Greek ''heapto-'', liver; and ''-kinos'', movement) are proteins produced by liver cells (hepatocytes) that are secreted into the circulation and function as hormones across the organism. Research is mostly focused on hepatokines that ...
. Other liver-specific proteins are certain liver enzymes such as HAO1 and RDH16, proteins involved in bile synthesis such as BAAT and
SLC27A5 Bile acyl-CoA synthetase is an enzyme that in humans is encoded by the ''SLC27A5'' gene. The protein encoded by this gene is an isozyme of very long-chain acyl-CoA synthetase ( VLCS). It is capable of activating very long-chain fatty-acids conta ...
, and transporter proteins involved in the metabolism of drugs, such as
ABCB11 ATP-binding cassette, sub-family B member 11 also known as ABCB11 is a protein which in humans is encoded by the gene. Function The product of the ''ABCB11'' gene is an ABC transporter named BSEP (bile salt export pump), or sPgp (sister of ...
and SLC2A2. Examples of highly liver-specific proteins include apolipoprotein A II, coagulation factors F2 and F9, complement factor related proteins, and the
fibrinogen beta chain Fibrinogen beta chain, also known as FGB, is a gene found in humans and most other vertebrates with a similar system of blood coagulation. The protein encoded by this gene is the beta component of fibrinogen, a blood-borne glycoprotein composed ...
protein.


Development

Organogenesis, the development of the organs, takes place from the third to the eighth week during
embryogenesis An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
. The origins of the liver lie in both the ventral portion of the
foregut The foregut is the anterior part of the alimentary canal, from the mouth to the duodenum at the entrance of the bile duct. Beyond the stomach, the foregut is attached to the abdominal walls by mesentery. The foregut arises from the endoderm, devel ...
endoderm Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gast ...
(endoderm being one of the three embryonic
germ layer A germ layer is a primary layer of cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans (animals that are sister taxa to the sponges) produce two or three p ...
s) and the constituents of the adjacent septum transversum
mesenchyme Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every ...
. In the human
embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...
, the
hepatic diverticulum The hepatic diverticulum (or liver bud) is a primordial cellular extension of the embryonic foregut endoderm that gives rise to the parenchyma of the liver and the bile duct. It typically differentiates from the endoderm in the third or fourth we ...
is the tube of endoderm that extends out from the foregut into the surrounding mesenchyme. The mesenchyme of septum transversum induces this endoderm to proliferate, to branch, and to form the glandular epithelium of the liver. A portion of the hepatic diverticulum (that region closest to the digestive tube) continues to function as the drainage duct of the liver, and a branch from this duct produces the gallbladder. Besides signals from the septum transversum mesenchyme, fibroblast growth factor from the developing heart also contributes to hepatic competence, along with retinoic acid emanating from the lateral plate mesoderm. The hepatic endodermal cells undergo a morphological transition from columnar to pseudostratified resulting in thickening into the early liver bud. Their expansion forms a population of the bipotential hepatoblasts. Hepatic stellate cells are derived from mesenchyme. After migration of hepatoblasts into the septum transversum mesenchyme, the hepatic architecture begins to be established, with liver sinusoids and bile canaliculi appearing. The liver bud separates into the lobes. The left umbilical vein becomes the ductus venosus and the right vitelline vein becomes the portal vein. The expanding liver bud is colonized by
hematopoietic cells Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells ...
. The bipotential hepatoblasts begin differentiating into biliary epithelial cells and hepatocytes. The biliary epithelial cells differentiate from hepatoblasts around portal veins, first producing a monolayer, and then a bilayer of cuboidal cells. In ductal plate, focal dilations emerge at points in the bilayer, become surrounded by portal mesenchyme, and undergo tubulogenesis into intrahepatic bile ducts. Hepatoblasts not adjacent to portal veins instead differentiate into hepatocytes and arrange into cords lined by sinusoidal epithelial cells and bile canaliculi. Once hepatoblasts are specified into hepatocytes and undergo further expansion, they begin acquiring the functions of a mature hepatocyte, and eventually mature hepatocytes appear as highly polarized epithelial cells with abundant glycogen accumulation. In the adult liver, hepatocytes are not equivalent, with position along the portocentrovenular axis within a liver lobule dictating expression of metabolic genes involved in drug metabolism, carbohydrate metabolism, ammonia detoxification, and bile production and secretion. WNT/β-catenin has now been identified to be playing a key role in this phenomenon. At birth, the liver comprises roughly 4% of body weight and weighs on average about . Over the course of further development, it will increase to but will only take up 2.5–3.5% of body weight.


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 does not perform the normal digestive processes and filtration of the infant liver because nutrients are received directly from the mother via the
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mate ...
. The fetal liver releases some blood stem cells that migrate to the fetal
thymus The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or '' T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders ...
, creating the
T-cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
or T-lymphocytes. After birth, the formation of blood stem cells shifts to the red
bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
. After 2–5 days, the umbilical vein and ductus venosus are obliterated; the former becomes the round ligament of liver and the latter becomes the ligamentum venosum. In the disorders of
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...
and
portal hypertension Portal hypertension is abnormally increased portal venous pressure – blood pressure in the portal vein and its branches, that drain from most of the intestine to the liver. Portal hypertension is defined as a hepatic venous pressure gradient ...
, the umbilical vein can open up again.


Functions

The various functions of the liver are carried out by the liver cells or hepatocytes. The liver is thought to be responsible for up to 500 separate functions, usually in combination with other systems and organs. Currently, no artificial organ or device is capable of reproducing all the functions of the liver. Some functions can be carried out by
liver dialysis A liver support system or diachysis is a type of therapeutic device to assist in performing the functions of the liver. Such systems focus either on removing the accumulating toxins (liver dialysis), or providing additional replacement of the met ...
, an experimental treatment for liver failure. The liver also accounts for about 20% of resting total body oxygen consumption.


Blood supply

The liver receives a dual blood supply from the hepatic portal vein and hepatic arteries. The hepatic portal vein delivers around 75% of the liver's blood supply and 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 remaining quarter of its blood flow. Oxygen is provided from both sources; about half of the liver's oxygen demand is met by the hepatic portal vein, and half is met by the hepatic arteries. The hepatic artery also has both alpha- and beta-adrenergic receptors; therefore, flow through the artery is controlled, in part, by the splanchnic nerves of the autonomic nervous system. Blood flows through the liver sinusoids and empties into the central vein of each lobule. The central veins coalesce into hepatic veins, which leave the liver and drain into the inferior vena cava. Liver veins.jpg, left, Liver veins– Liver vascular anatomy.svg, Diagram of liver, lobule, and portal tract and their inter-relations


Biliary flow

The
biliary tract The biliary tract, (biliary tree or biliary system) refers to the liver, gallbladder and bile ducts, and how they work together to make, store and secrete bile. Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids and ...
is derived from the branches of the bile ducts. The biliary tract, also known as the biliary tree, is the path by which bile is secreted by the liver then transported to the first part of the small intestine, the
duodenum The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine m ...
. The bile produced in the liver is collected in
bile canaliculi Bile canaliculus (plural:bile canaliculi; also called bile capillaries) is a thin tube that collects bile secreted by hepatocytes. The bile canaliculi empty into a series of progressively larger bile ductules and ducts, which eventually become comm ...
, small grooves between the faces of adjacent hepatocytes. The canaliculi radiate to the edge of the liver lobule, where they merge to form bile ducts. Within the liver, these ducts are termed intrahepatic bile ducts, and once they exit the liver, they are considered extrahepatic. The intrahepatic ducts eventually drain into the right and left hepatic ducts, which exit the liver at the transverse fissure, and 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. The biliary system and connective tissue is supplied by the hepatic artery alone. Bile either drains directly into the duodenum via the common bile duct, or is 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 hepatopancreatic ampulla, also known as the
ampulla of Vater The ampulla of Vater, also known as the or the hepatopancreatic duct, is formed by the union of the pancreatic duct and the common bile duct. The ampulla is specifically located at the major duodenal papilla. The ampulla of Vater is an imp ...
.


Metabolism

The liver plays a major role in carbohydrate, protein, amino acid, and lipid metabolism.


Carbohydrate metabolism

The liver performs several roles in carbohydrate metabolism: * The liver synthesizes and stores around 100g of glycogen via
glycogenesis Glycogenesis is the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage. This process is activated during rest periods following the Cori cycle, in the liver, and also activated by insulin in ...
, the formation of glycogen from
glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
. * When needed, the liver releases glucose into the blood by performing
glycogenolysis Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase. Mechanism T ...
, the breakdown of glycogen into glucose. * The liver is also responsible for
gluconeogenesis Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non- carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In verteb ...
, which is the synthesis of glucose from certain
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
s,
lactate Lactate may refer to: * Lactation, the secretion of milk from the mammary glands * Lactate, the conjugate base of lactic acid Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with w ...
, or
glycerol Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...
. Adipose and liver cells produce glycerol by breakdown of fat, which the liver uses for gluconeogenesis. * Liver also does glyconeogenesis which is synthesis of
glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one of ...
from
lactic acid Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as nat ...
.


Protein metabolism

The liver is responsible for the mainstay of protein
metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...
, synthesis as well as degradation. All
plasma proteins Blood-proteins, also termed plasma proteins, are proteins present in blood plasma. They serve many different functions, including transport of lipids, hormones, vitamins and minerals in activity and functioning of the immune system. Other blood p ...
except Gamma-globulins are synthesised in the liver. It is also responsible for a large part of
amino acid synthesis Amino acid synthesis is the set of biochemical processes (metabolic pathways) by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to sy ...
. The liver plays a role in the production of clotting factors, as well as red blood cell production. Some of the proteins synthesized by the liver include coagulation factors I (fibrinogen), II (prothrombin), V,
VII VII or vii may refer to: the Roman numeral 7 Art and entertainment * The Vii, a video game console * vii, leading-tone triad, see diminished triad * ''VII'' (Blitzen Trapper album) * ''VII'' (Just-Ice album) * ''VII'' (Teyana Taylor album) * ...
, VIII, IX, X, XI, XII, XIII, as well as
protein C Protein C, also known as autoprothrombin IIA and blood coagulation factor XIX, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and cell death and maintainin ...
, protein S and antithrombin. The liver is a major site of production for thrombopoietin, a
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glyco ...
hormone that regulates the production of
platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...
s by the bone marrow.


Lipid metabolism

The liver plays several roles in
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids in ...
metabolism: it performs
cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell memb ...
synthesis,
lipogenesis In biochemistry, lipogenesis is the conversion of fatty acids and glycerol into fats, or a metabolic process through which acetyl-CoA is converted to triglyceride for storage in fat. Lipogenesis encompasses both fatty acid and triglyceride s ...
, and the production of
triglyceride A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other vertebrates, as ...
s, and a bulk of the body's lipoproteins are synthesized in the liver. The liver plays a key role in digestion, as it produces and excretes
bile Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bi ...
(a yellowish liquid) required for emulsifying fats and help the absorption of vitamin K from the diet. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder. The liver produces
insulin-like growth factor 1 Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults. IGF-1 is a protein that in humans ...
, a
polypeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
hormone that plays an important role in childhood growth and continues to have anabolic effects in adults.


Breakdown

The liver is responsible for the breakdown of
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism ...
and other
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
s. The liver breaks down
bilirubin Bilirubin (BR) ( Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from t ...
via
glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gl ...
, facilitating its excretion into bile. The liver is responsible for the breakdown and excretion of many waste products. It plays a key role in breaking down or modifying toxic substances (e.g.,
methylation In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These ...
) 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 Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous ...
into
urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important ...
as part of the ornithine cycle or the urea cycle, and the urea is excreted in the urine.


Blood reservoir

Because the liver is an expandable organ, large quantities of blood can be stored in its blood vessels. Its normal blood volume, including both that in the hepatic veins and that in the hepatic sinuses, is about 450 milliliters, or almost 10 percent of the body's total blood volume. When high pressure in the right atrium causes backpressure in the liver, the liver expands, and 0.5 to 1 liter of extra blood is occasionally stored in the hepatic veins and sinuses. This occurs especially in cardiac failure with peripheral congestion. Thus, in effect, the liver is a large, expandable, venous organ capable of acting as a valuable blood reservoir in times of excess blood volume and capable of supplying extra blood in times of diminished blood volume.


Lymph production

Because the pores in the hepatic sinusoids are very permeable and allow ready passage of both fluid and proteins into the
perisinusoidal space The perisinusoidal space (or space of Disse) is a location in the liver between a hepatocyte and a sinusoid. It contains the blood plasma. Microvilli of hepatocytes extend into this space, allowing proteins and other plasma components from the si ...
, the
lymph Lymph (from Latin, , meaning "water") is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues ...
draining from the liver usually has a protein concentration of about 6 g/dl, which is only slightly less than the protein concentration of plasma. Also, the high permeability of the liver sinusoid epithelium allows large quantities of lymph to form. Therefore, about half of all the lymph formed in the body under resting conditions arises in the liver.


Other

* The liver stores a multitude of substances, including
vitamin A Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably ...
(1–2 years' supply),
vitamin D Vitamin D is a group of Lipophilicity, fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group ar ...
(1–4 months' supply), vitamin B12 (3–5 years' supply),
vitamin K Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation ...
,
vitamin E Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vi ...
,
iron Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in ...
,
copper Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pink ...
,
zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
,
cobalt Cobalt is a chemical element with the symbol Co and atomic number 27. As with nickel, cobalt is found in the Earth's crust only in a chemically combined form, save for small deposits found in alloys of natural meteoric iron. The free element, p ...
,
molybdenum Molybdenum is a chemical element with the symbol Mo and atomic number 42 which is located in period 5 and group 6. The name is from Neo-Latin ''molybdaenum'', which is based on Ancient Greek ', meaning lead, since its ores were confused with lead ...
, etc. * Haemopoiesis - The formation of blood cells is called haemopoiesis. In embryonic stage RBC and WBC are formed by liver. In the first trimester fetus, the liver is the main site of
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "hol ...
production. By the 32nd week of
gestation Gestation is the period of development during the carrying of an embryo, and later fetus, inside viviparous animals (the embryo develops within the parent). It is typical for mammals, but also occurs for some non-mammals. Mammals during pr ...
, the
bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
has almost completely taken over that task. *Liver helps in purification of blood. The Kupffer cells of liver are phagocytic cells, helps in phagocytosis of dead blood cells and bacteria from the blood. * The liver is responsible for immunological effects – the mononuclear phagocyte system of the liver contains many immunologically active cells, acting as a 'sieve' for antigens carried to it via the
portal system In the circulatory system of animals, a portal venous system occurs when a capillary bed pools into another capillary bed through veins, without first going through the heart. Both capillary beds and the blood vessels that connect them are c ...
. * The liver produces
albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Album ...
, the most abundant protein in
blood serum Serum () is the fluid and solute component of blood which does not play a role in clotting. It may be defined as blood plasma without the clotting factors, or as blood with all cells and clotting factors removed. Serum includes all proteins not ...
. It is essential in the maintenance of oncotic pressure, and acts as a transport for
fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...
s and steroid hormones. * The liver synthesizes
angiotensinogen Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adre ...
, a hormone that is responsible for raising the
blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure ...
when activated by
renin Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the ...
, an enzyme that is released when the
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
senses low blood pressure. * The liver produces the enzyme
catalase Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting t ...
to break down
hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3 ...
, a toxic oxidising agent, into water and oxygen.


With aging

The oxidative capacity of the liver decreases with aging, and therefore any medications that require oxidation (for instance,
benzodiazepines Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...
) are more likely to accumulate to toxic levels. However, medications with shorter
half-lives Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...
, such as
lorazepam Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety disorders, trouble sleeping, severe agitation, active seizures including status epilepticus, alcohol withdrawal, and che ...
and oxazepam, are preferred in most cases when benzodiazepines are required in regard to geriatric medicine.


Clinical significance


Disease

The liver is a vital organ and supports almost every other organ in the body. Because of its strategic location and multidimensional functions, the liver is prone to many diseases. The bare area of the liver is a site that is vulnerable to the passing of infection from the abdominal cavity to the thoracic cavity. Liver diseases may be diagnosed by
liver function tests Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...
–blood tests that can identify various markers. For example, acute-phase reactants are produced by the liver in response to injury or inflammation.
Hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ( jaundice), poor appetite, vomiting, tiredness, abdominal ...
is a common condition of inflammation of the liver. The most usual cause of this is viral, and the most common of these infections are
hepatitis A Hepatitis A is an infectious disease of the liver caused by ''Hepatovirus A'' (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop the ...
, B, C, D, and E. Some of these infections are
sexually transmitted Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs) and the older term venereal diseases, are infections that are spread by sexual activity, especially vaginal intercourse, anal sex, and oral ...
. Inflammation can also be caused by other viruses in the family
Herpesviridae ''Herpesviridae'' is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ''ἕρπει� ...
such as the ''
herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names '' Human alphaherpesvirus 1'' and ''Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral in ...
''. Chronic (rather than acute) infection with hepatitis B virus or hepatitis C virus is the main cause of
liver cancer Liver cancer (also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy) is cancer that starts in the liver. Liver cancer can be primary (starts in liver) or secondary (meaning cancer which has spread from elsewhere to th ...
. Globally, about 248 million individuals are chronically infected with hepatitis B (with 843,724 in the U.S.), and 142 million are chronically infected with hepatitis C (with 2.7 million in the U.S.). Globally there are about 114 million and 20 million cases of hepatitis A and hepatitis E respectively, but these generally resolve and do not become chronic. Hepatitis D virus is a "satellite" of hepatitis B virus (it can only infect in the presence of hepatitis B), and co-infects nearly 20 million people with hepatitis B, globally.
Hepatic encephalopathy Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stage ...
is caused by an accumulation of toxins in the bloodstream that are normally removed by the liver. This condition can result in coma and can prove fatal.
Budd–Chiari syndrome Budd–Chiari syndrome is a very rare condition, affecting one in a million adults. The condition is caused by occlusion of the hepatic veins that drain the liver. It presents with the classical triad of abdominal pain, ascites, and liver enlar ...
is a condition caused by
blockage ''Blockage'' (Persian: سد معبر, romanized: Sade Ma'bar) is a 2017 Iranian drama film directed by Mohsen Gharaie and written by Saeed Roustayi. The film screened for the first time at the 35th Fajr Film Festival and received 4 nominations. I ...
of the hepatic veins (including
thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (th ...
) that drain the liver. It presents with the classical triad of abdominal pain, ascites and liver enlargement. Many diseases of the liver are accompanied by
jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
caused by increased levels of
bilirubin Bilirubin (BR) ( Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from t ...
in the system. The bilirubin results from the breakup of the
hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythroc ...
of dead
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "hol ...
s; normally, the liver removes bilirubin from the blood and excretes it through bile. Other disorders caused by excessive alcohol consumption are grouped under
alcoholic liver disease Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibros ...
s and these include
alcoholic hepatitis Alcoholic hepatitis is hepatitis (inflammation of the liver) due to excessive intake of alcohol. Patients typically have a history of at least 10 years of heavy alcohol intake, typically 8-10 drinks per day. It is usually found in association with ...
,
fatty liver Fatty liver disease (FLD), also known as hepatic steatosis, is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complica ...
, and
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...
. Factors contributing to the development of alcoholic liver diseases are not only the quantity and frequency of alcohol consumption, but can also include gender, genetics, and liver insult. Liver damage can also be caused by drugs, particularly
paracetamol Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferio ...
and drugs used to treat cancer. A rupture of the liver can be caused by a liver shot used in combat sports. Primary biliary cholangitis is an
autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
of the liver. It is marked by slow progressive destruction of the small
bile duct A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. ...
s of the liver, with the intralobular ducts (
Canals of Hering The canals of Hering, or intrahepatic bile ductules, are part of the outflow system of exocrine bile product from the liver. Liver stem cells are located in the canals of Hering. Structure They are found between the bile canaliculi and interlob ...
) affected early in the disease. When these ducts are damaged,
bile Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bi ...
and other toxins build up in the liver ( cholestasis) and over time damages the liver tissue in combination with ongoing immune related damage. This can lead to scarring (
fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...
) and
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...
. Cirrhosis increases the resistance to blood flow in the liver, and can result in
portal hypertension Portal hypertension is abnormally increased portal venous pressure – blood pressure in the portal vein and its branches, that drain from most of the intestine to the liver. Portal hypertension is defined as a hepatic venous pressure gradient ...
. Congested anastomoses between the
portal venous system In the circulatory system of animals, a portal venous system occurs when a capillary bed pools into another capillary bed through veins, without first going through the heart. Both capillary beds and the blood vessels that connect them are con ...
and the systemic circulation, can be a subsequent condition. There are also many pediatric liver diseases, including
biliary atresia Biliary atresia, also known as extrahepatic ductopenia and progressive obliterative cholangiopathy, is a childhood disease of the liver in which one or more bile ducts are abnormally narrow, blocked, or absent. It can be congenital or acquired. I ...
,
alpha-1 antitrypsin deficiency Alpha-1 antitrypsin deficiency (A1AD or AATD) is a genetic disorder that may result in lung disease or liver disease. Onset of lung problems is typically between 20 and 50 years of age. This may result in shortness of breath, wheezing, or an inc ...
,
alagille syndrome Alagille syndrome is a genetic disorder that affects primarily the liver and the heart. Problems associated with the disorder generally become evident in infancy or early childhood. The disorder is inherited in an autosomal dominant pattern, and ...
,
progressive familial intrahepatic cholestasis Progressive familial intrahepatic cholestasis (PFIC) is a group of familial cholestatic conditions caused by defects in biliary epithelial transporters. The clinical presentation usually occurs first in childhood with progressive cholestasis. Thi ...
, Langerhans cell histiocytosis and hepatic hemangioma a
benign tumour A benign tumor is a mass of cells ( tumor) that does not invade neighboring tissue or metastasize (spread throughout the body). Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have re ...
the most common type of liver tumour, thought to be congenital. A genetic disorder causing multiple cysts to form in the liver tissue, usually in later life, and usually asymptomatic, is polycystic liver disease. 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.
Hepatomegaly Hepatomegaly is the condition of having an enlarged liver. It is a non-specific medical sign having many causes, which can broadly be broken down into infection, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdo ...
refers to an enlarged liver and can be due to many causes. It can be palpated in a
liver span The liver span is a measurement performed during physical examination to determine the size of the liver and identify possible hepatomegaly. It is the distance between the lower border of the liver in the mid-clavicular line obtained by palpation, ...
measurement.


Symptoms

The classic symptoms 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 * Jaundice (yellow skin and/or whites of the eyes) This is where
bilirubin Bilirubin (BR) ( Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from t ...
deposits in skin, causing an intense
itch Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...
. Itching is the most common complaint by people who have liver failure. Often this itch cannot be relieved by drugs. * Swelling of the abdomen, and swelling of the ankles and feet occurs because the liver fails to make albumin. * Excessive fatigue occurs from a generalized loss of nutrients,
minerals In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid chemical compound with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed ...
and vitamins. *
Bruising A bruise, also known as a contusion, is a type of hematoma of tissue, the most common cause being capillaries damaged by trauma, causing localized bleeding that extravasates into the surrounding interstitial tissues. Most bruises occur close ...
and easy bleeding are other features of liver disease. The liver makes clotting factors, substances which help prevent bleeding. When liver damage occurs, these factors are no longer present and severe bleeding can occur. * Pain in the upper right quadrant can result from the stretching of Glisson's capsule in conditions of
hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ( jaundice), poor appetite, vomiting, tiredness, abdominal ...
and
pre-eclampsia Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease ...
.


Diagnosis

The diagnosis of liver disease is made by
liver function tests Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...
, groups of
blood test A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose test or a choles ...
s, that can readily show the extent of liver damage. If
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
is suspected, then other
serological Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mic ...
tests will be carried out. A physical examination of the liver can only reveal its size and any tenderness, and some form of imaging such as an
ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies ...
or CT scan may also be needed. Sometimes a liver biopsy will be necessary, and a tissue sample is taken through a needle inserted into the skin just below the rib cage. This procedure may be helped by a sonographer providing ultrasound guidance to an interventional radiologist. File:Axial CT anomalous hepatic veins.jpg, Axial CT image showing anomalous hepatic veins coursing on the subcapsular anterior surface of the liver. File:Anterior MIP image of anomalous hepatic veins.jpg, Maximum intensity projection (MIP) CT image as viewed anteriorly showing the anomalous hepatic veins coursing on the anterior surface of the liver File:Lateral MIP CT of anomalous surface hepatic veins.jpg, Lateral MIP view in the same patient File:CTscanofmyLiver.jpg, A CT scan in which the liver and portal vein are shown.


Liver regeneration

The liver is the only human internal organ capable of natural regeneration of lost tissue; as little as 25% of a liver can regenerate into a whole liver. This is, however, not true regeneration but rather
compensatory growth Compensatory growth, known as catch-up growth and compensatory gain, is an accelerated growth of an organism following a period of slowed development, particularly as a result of nutrient deprivation. The growth may be with respect to weight or ...
in mammals. The lobes that are removed do not regrow and the growth of the liver is a restoration of function, not original form. This contrasts with true regeneration where both original function and form are restored. In some other species, such as zebrafish, the liver undergoes true regeneration by restoring both shape and size of the organ. In the liver, large areas of the tissues are formed but for the formation of new cells there must be sufficient amount of material so the circulation of the blood becomes more active. This is predominantly due to the
hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...
s re-entering the
cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and sub ...
. That is, the hepatocytes go from the quiescent
G0 phase The G0 phase describes a cellular state outside of the replicative cell cycle. Classically, cells were thought to enter G0 primarily due to environmental factors, like nutrient deprivation, that limited the resources necessary for proliferation ...
to the
G1 phase The G1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell division. In this part of interphase, the cell synthesizes mRNA and proteins in preparation for subsequent steps ...
and undergo mitosis. This process is activated by the p75 receptors. There is also some evidence of
bipotential Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta. According to Latin terms, Pluripotentia means the ability for many thin ...
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of ...
s, called hepatic oval cells or ovalocytes (not to be confused with oval red blood cells of ovalocytosis), which are thought to reside in the
canals of Hering The canals of Hering, or intrahepatic bile ductules, are part of the outflow system of exocrine bile product from the liver. Liver stem cells are located in the canals of Hering. Structure They are found between the bile canaliculi and interlob ...
. These cells can differentiate into either
hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...
s or cholangiocytes. Cholangiocytes are the epithelial lining cells of the
bile duct A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. ...
s. They are cuboidal epithelium in the small interlobular bile ducts, but become columnar and mucus secreting in larger bile ducts approaching the porta hepatis and the extrahepatic ducts. Research is being carried out on the use of stem cells for the generation of an artificial liver. Scientific and medical works about liver regeneration often refer to the Greek
Titan Titan most often refers to: * Titan (moon), the largest moon of Saturn * Titans, a race of deities in Greek mythology Titan or Titans may also refer to: Arts and entertainment Fictional entities Fictional locations * Titan in fiction, fictiona ...
Prometheus In Greek mythology, Prometheus (; , , possibly meaning " forethought")Smith"Prometheus". is a Titan god of fire. Prometheus is best known for defying the gods by stealing fire from them and giving it to humanity in the form of technology, kn ...
who was chained to a rock in the
Caucasus The Caucasus () or Caucasia (), is a region between the Black Sea and the Caspian Sea, mainly comprising Armenia, Azerbaijan, Georgia, and parts of Southern Russia. The Caucasus Mountains, including the Greater Caucasus range, have historica ...
where, each day, his liver was devoured by an eagle, only to grow back each night. The myth suggests the
ancient Greeks Ancient Greece ( el, Ἑλλάς, Hellás) was a northeastern Mediterranean civilization, existing from the Greek Dark Ages of the 12th–9th centuries BC to the end of classical antiquity ( AD 600), that comprised a loose collection of cult ...
may have known about the liver's remarkable capacity for self-repair.


Liver transplantation

Human liver transplants were first performed by
Thomas Starzl Thomas Earl Starzl (March 11, 1926 – March 4, 2017) was an American physician, researcher, and expert on organ transplants. He performed the first human liver transplants, and has often been referred to as "the father of modern transplantatio ...
in the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...
and
Roy Calne Sir Roy Yorke Calne, FRCP, FRCS, FRS (born 30 December 1930) is a British surgeon and pioneer in organ transplantation. Career His most notable achievements are the world's first liver, heart, and lung transplant together with John Wallwork ...
in
Cambridge Cambridge ( ) is a university city and the county town in Cambridgeshire, England. It is located on the River Cam approximately north of London. As of the 2021 United Kingdom census, the population of Cambridge was 145,700. Cambridge bec ...
,
England England is a country that is part of the United Kingdom. It shares land borders with Wales to its west and Scotland to its north. The Irish Sea lies northwest and the Celtic Sea to the southwest. It is separated from continental Europe ...
in 1963 and 1967, respectively.
Liver transplantation Liver transplantation or hepatic transplantation is the replacement of a Liver disease, diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for Cirrhosis, end-stage liver disease and ...
is the only option for those with irreversible liver failure. Most transplants are done for chronic liver diseases leading to
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...
, such as chronic
hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, ...
,
alcoholism Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomi ...
, and autoimmune hepatitis. Less commonly, liver transplantation is done for
fulminant hepatic failure Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complicati ...
, in which liver failure occurs rapidly over a period of days or weeks. Liver allografts for transplant usually come from 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 (
hepatectomy Hepatectomy is the surgical resection (removal of all or part) of the liver. While the term is often employed for the removal of the liver from a liver transplant donor, this article will focus on partial resections of hepatic tissue and hepato ...
) and used to replace the entire liver of the recipient. This was first performed in 1989 for pediatric liver transplantation. Only 20 percent 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 percent 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 were at least two donor deaths out of the first several hundred cases. A 2006 publication addressed the problem of donor mortality and found at least fourteen cases. 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 noninvasive 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 multidetector row computed tomography (MDCT) and
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
(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. File:LDLTA.jpg, MDCT image. Arterial anatomy contraindicated for liver donation File:LDLTP.jpg, MDCT image. Portal venous anatomy contraindicated for liver donation File: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. File:R vs L Liver by CT.PNG, Phase contrast CT image. Contrast is perfusing the right liver but not the left due to a left portal vein thrombus.


Society and culture

Some cultures regard the liver as the seat of the
soul In many religious and philosophical traditions, there is a belief that a soul is "the immaterial aspect or essence of a human being". Etymology The Modern English noun '' soul'' is derived from Old English ''sāwol, sāwel''. The earliest att ...
. In
Greek mythology A major branch of classical mythology, Greek mythology is the body of myths originally told by the ancient Greeks, and a genre of Ancient Greek folklore. These stories concern the origin and nature of the world, the lives and activities o ...
, the gods punished
Prometheus In Greek mythology, Prometheus (; , , possibly meaning " forethought")Smith"Prometheus". is a Titan god of fire. Prometheus is best known for defying the gods by stealing fire from them and giving it to humanity in the form of technology, kn ...
for revealing fire to humans by chaining him to a rock where a
vulture A vulture is a bird of prey that scavenges on carrion. There are 23 extant species of vulture (including Condors). Old World vultures include 16 living species native to Europe, Africa, and Asia; New World vultures are restricted to North and ...
(or an
eagle Eagle is the common name for many large birds of prey of the family Accipitridae. Eagles belong to several groups of genera, some of which are closely related. Most of the 68 species of eagle are from Eurasia and Africa. Outside this area, j ...
) 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 practiced a type of
divination Divination (from Latin ''divinare'', 'to foresee, to foretell, to predict, to prophesy') is the attempt to gain insight into a question or situation by way of an occultic, standardized process or ritual. Used in various forms throughout history ...
called
haruspicy In the religion of ancient Rome, a haruspex (plural haruspices; also called aruspex) was a person trained to practise a form of divination called haruspicy (''haruspicina''), the inspection of the entrails (''exta''—hence also extispicy ( ...
or hepatomancy, where they tried to obtain information by examining the livers of sheep and other animals. In Plato, and in later physiology, the liver was thought to be the seat of the darkest emotions (specifically wrath, jealousy and greed) which drive men to action. The
Talmud The Talmud (; he, , Talmūḏ) is the central text of Rabbinic Judaism and the primary source of Jewish religious law ('' halakha'') and Jewish theology. Until the advent of modernity, in nearly all Jewish communities, the Talmud was the ce ...
(tractate ''Berakhot 61b'') refers to the liver as the seat of
anger Anger, also known as wrath or rage, is an intense emotional state involving a strong uncomfortable and non-cooperative response to a perceived provocation, hurt or threat. A person experiencing anger will often experience physical effects, su ...
, with the
gallbladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although ...
counteracting this. The Persian,
Urdu Urdu (;"Urdu"
'' Hindi Hindi (Devanāgarī: or , ), or more precisely Modern Standard Hindi (Devanagari: ), is an Indo-Aryan language spoken chiefly in the Hindi Belt region encompassing parts of northern, central, eastern, and western India. Hindi has been ...
languages ( or or ) refer to the liver in figurative speech to indicate courage and strong feelings, or "their best"; e.g., "This
Mecca Mecca (; officially Makkah al-Mukarramah, commonly shortened to Makkah ()) is a city and administrative center of the Mecca Province of Saudi Arabia, and the holiest city in Islam. It is inland from Jeddah on the Red Sea, in a narrow v ...
has thrown to you the pieces of its liver!". The term , literally "the strength (power) of my liver", is a term of endearment in Urdu. In Persian slang, is used as an adjective for any object which is desirable, especially women. In the
Zulu language Zulu (), or isiZulu as an endonym, is a Southern Bantu language of the Nguni branch spoken in Southern Africa. It is the language of the Zulu people, with about 12 million native speakers, who primarily inhabit the province of KwaZulu-Nata ...
, the word for liver () is the same as the word for courage. In English the term 'lily-livered' is used to indicate cowardice from the medieval belief that the liver was the seat of courage. Spanish also means "courage". However the secondary meaning of Basque is "indolence". In biblical Hebrew, the word for liver, (, stemmed or , similar to Arabic ), also means heavy and is used to describe the rich ("heavy" with possessions) and honor (presumably for the same reason). In the Book of Lamentations (2:11) it is used to describe the physiological responses to sadness by "my liver spilled to earth" along with the flow of tears and the overturning in bitterness of the intestines. On several occasions in the
book of Psalms The Book of Psalms ( or ; he, תְּהִלִּים, , lit. "praises"), also known as the Psalms, or the Psalter, is the first book of the ("Writings"), the third section of the Tanakh, and a book of the Old Testament. The title is derived ...
(most notably 16:9), the word is used to describe happiness in the liver, along with the heart (which beats rapidly) and the flesh (which appears red under the skin). Further usage as the self (similar to "your honor") is widely available throughout the old testament, sometimes compared to the breathing soul (Genesis 49:6, Psalms 7:6, etc.). An honorable hat was also referred to with this word (Job 19:9, etc.) and under that definition appears many times along with - grandeur. These four meanings were used in preceding ancient
Afro-Asiatic languages The Afroasiatic languages (or Afro-Asiatic), also known as Hamito-Semitic, or Semito-Hamitic, and sometimes also as Afrasian, Erythraean or Lisramic, are a language family of about 300 languages that are spoken predominantly in the geographic s ...
such as
Akkadian Akkadian or Accadian may refer to: * Akkadians, inhabitants of the Akkadian Empire * Akkadian language, an extinct Eastern Semitic language * Akkadian literature, literature in this language * Akkadian cuneiform Cuneiform is a logo-syllabic ...
and Ancient Egyptian preserved in classical Ethiopic Ge'ez language.


Food

Humans commonly eat the livers of mammals, fowl, and fish as food. Domestic pig, ox, lamb, calf, chicken, and goose livers are widely available from butchers and supermarkets. In the
Romance languages The Romance languages, sometimes referred to as Latin languages or Neo-Latin languages, are the various modern languages that evolved from Vulgar Latin. They are the only extant subgroup of the Italic languages in the Indo-European language ...
, the anatomical word for "liver" (
French French (french: français(e), link=no) may refer to: * Something of, from, or related to France ** French language, which originated in France, and its various dialects and accents ** French people, a nation and ethnic group identified with Franc ...
''foie'', Spanish ''hígado'', etc.) derives not from the
Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through ...
anatomical term, ''jecur'', but from the culinary term ''ficatum'', literally "stuffed with figs," referring to the livers of geese that had been fattened on figs. Animal livers are rich in iron,
vitamin A Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably ...
and vitamin B12; and
cod liver oil Cod liver oil is a dietary supplement derived from liver of cod fish (Gadidae). As with most fish oils, it contains the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and also vitamin A and vitamin D. Histori ...
is commonly used as a
dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
. Liver can be baked, boiled, broiled, fried, stir-fried, or eaten raw (''asbeh nayeh'' or ''sawda naye'' in
Lebanese cuisine Lebanese cuisine is the culinary traditions and practices originating from Lebanon. It includes an abundance of whole grains, fruits, vegetables, fresh fish and seafood. Poultry is eaten more often than red meat, and when red meat is eaten, it ...
, or liver
sashimi is a Japanese delicacy consisting of fresh raw fish or meat sliced into thin pieces and often eaten with soy sauce. Origin The word ''sashimi'' means "pierced body", i.e. " 刺身" = ''sashimi'', where 刺 し = ''sashi'' (pierced, stu ...
in
Japanese cuisine Japanese cuisine encompasses the regional and traditional foods of Japan, which have developed through centuries of political, economic, and social changes. The traditional cuisine of Japan ( Japanese: ) is based on rice with miso soup and oth ...
). In many preparations, pieces of liver are combined with pieces of meat or kidneys, as in the various forms of Middle Eastern mixed grill (e.g. ''
meurav Yerushalmi Jerusalem mixed grill ( he, מעורב ירושלמי) (''me'orav Yerushalmi'') is a grilled meat dish considered a specialty of Jerusalem. It consists of chicken hearts, spleens and liver mixed with bits of lamb cooked on a flat grill, seasoned ...
''). Well-known examples include liver pâté,
foie gras Foie gras (, ; ) is a specialty food product made of the liver of a duck or goose. According to French law, foie gras is defined as the liver of a duck or goose fattened by gavage (force feeding). Foie gras is a popular and well-known delica ...
, chopped liver, and leverpastej. Liver
sausage A sausage is a type of meat product usually made from ground meat—often pork, beef, or poultry—along with salt, spices and other flavourings. Other ingredients, such as grains or breadcrumbs may be included as fillers or extenders. ...
s, such as Braunschweiger and liverwurst, are also a valued meal. Liver sausages may also be used as spreads. A traditional
South Africa South Africa, officially the Republic of South Africa (RSA), is the southernmost country in Africa. It is bounded to the south by of coastline that stretch along the South Atlantic and Indian Oceans; to the north by the neighbouring coun ...
n delicacy, skilpadjies, is made of minced lamb's liver wrapped in ''netvet'' (caul fat), and grilled over an open fire. Traditionally, some fish livers were valued as food, especially the
stingray Stingrays are a group of sea rays, which are cartilaginous fish related to sharks. They are classified in the suborder Myliobatoidei of the order Myliobatiformes and consist of eight families: Hexatrygonidae (sixgill stingray), Plesiobatidae ...
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 French cuisine () is the cooking traditions and practices from France. It has been influenced over the centuries by the many surrounding cultures of Spain, Italy, Switzerland, Germany and Belgium, in addition to the food traditions of the re ...
.


Giraffe liver

The Humr are one of the tribes in the Baggara ethnic group, native to southwestern Kordofan in
Sudan Sudan ( or ; ar, السودان, as-Sūdān, officially the Republic of the Sudan ( ar, جمهورية السودان, link=no, Jumhūriyyat as-Sūdān), is a country in Northeast Africa. It shares borders with the Central African Republic t ...
who speak ''Shuwa'' ( Chadian Arabic), make a non-alcoholic drink from the liver and
bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
of the
giraffe The giraffe is a large African hoofed mammal belonging to the genus ''Giraffa''. It is the tallest living terrestrial animal and the largest ruminant on Earth. Traditionally, giraffes were thought to be one species, '' Giraffa camelopardal ...
, which they call ''umm nyolokh''. They claim it is intoxicating (Arabic سكران ''sakran''), causing dreams and even waking
hallucination A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...
s. Anthropologist Ian Cunnison accompanied the Humr on one of their giraffe-hunting expeditions in the late 1950s, and noted that: :It is said that a person, once he has drunk ''umm nyolokh'', will return to giraffe again and again. Humr, being Mahdists, are strict abstainers rom alcoholand a Humrawi is never drunk (''sakran'') on
liquor Liquor (or a spirit) is an alcoholic drink produced by distillation of grains, fruits, vegetables, or sugar, that have already gone through alcoholic fermentation. Other terms for liquor include: spirit drink, distilled beverage or h ...
or beer. But he uses this word to describe the effects which ''umm nyolokh'' has upon him. Cunnison's remarkable account of an apparently psychoactive mammal found its way from a somewhat obscure scientific paper into more mainstream literature through a conversation between W. James of the Institute of Social and Cultural
Anthropology Anthropology is the scientific study of humanity, concerned with human behavior, human biology, cultures, societies, and linguistics, in both the present and past, including past human species. Social anthropology studies patterns of be ...
at the
University of Oxford , mottoeng = The Lord is my light , established = , endowment = £6.1 billion (including colleges) (2019) , budget = £2.145 billion (2019–20) , chancellor ...
and specialist on the use of
hallucinogen Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorize ...
s and intoxicants in society, and R. Rudgley, who discussed it in a book on psychoactive drugs for general readers. He speculated that a hallucinogenic compound
N,N-Dimethyltryptamine ''N'',''N''-Dimethyltryptamine (DMT or ''N'',''N''-DMT, SPL026) is a substituted tryptamine that occurs in many plants and animals, including human beings, and which is both a derivative and a structural analog of tryptamine. It is used as ...
in the giraffe liver might account for the intoxicating properties claimed for ''umm nyolokh''. Cunnison, on the other hand, writing in 1958 found it hard to believe in the literal truth of the Humr's assertion that the drink was intoxicating: :I can only assume that there is no intoxicating substance in the drink, and that the effect it produces is simply a matter of convention, although it may be brought about subconsciously. The study of
entheogen Entheogens are psychoactive substances that induce alterations in perception, mood, consciousness, cognition, or behavior for the purposes of engendering spiritual development or otherwiseRätsch, Christian, ''The Encyclopedia of Psychoac ...
s in general – including entheogens of animal origin (e.g. hallucinogenic fish and
toad venom Bufotoxins are a family of toxic steroid lactones or substituted tryptamines of which some may or may not be toxic. They occur in the parotoid glands, skin, and poison of many toads (genus '' Bufo'') and other amphibians, and in some plants and mu ...
) – has, however, made considerable progress in the sixty-odd years since Cunnison's report; the idea that some intoxicating substance might reside in giraffe livers may no longer be as far-fetched as it seemed to Cunnison. However, to date, proof (or disproof) still waits on detailed analyses of the organ and the beverage made from it.


Arrow/bullet poison

Certain
Tungusic peoples Tungusic peoples are an ethno-linguistic group formed by the speakers of Tungusic languages (or Manchu–Tungus languages). They are native to Siberia and Northeast Asia. The Tungusic phylum is divided into two main branches, northern (Evenic ...
of northeast Asia formerly prepared a type of
arrow poison Arrow poisons are used to poison arrow heads or darts for the purposes of hunting and warfare. They have been used by indigenous peoples worldwide and are still in use in areas of South America, Africa and Asia. Notable examples are the poisons se ...
from rotting animal livers, which was, in later times, also applied to
bullet A bullet is a kinetic projectile, a component of firearm ammunition that is shot from a gun barrel. Bullets are made of a variety of materials, such as copper, lead, steel, polymer, rubber and even wax. Bullets are made in various shapes and co ...
s. Russian anthropologist S. M. Shirokogoroff wrote that: :Formerly the using of poisoned arrows was common. For instance, among the Kumarčen, Oroqen.html" ;"title="Oroqen_people.html" ;"title=" subgroup of the Oroqen people">Oroqen">Oroqen_people.html" ;"title=" subgroup of the Oroqen people">Oroqeneven in recent times, a poison was used which was prepared from decaying liver. :[Note] This has been confirmed by the Kumarčen. I am not competent to judge as to the chemical conditions of production of poison which is not destroyed by the heat of explosion. However, the Tungus themselves compare this method f poisoning ammunitionwith the poisoning of arrows.


Other animals

The liver is found in all
vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with ...
s and is typically the largest internal
organ Organ may refer to: Biology * Organ (biology), a part of an organism Musical instruments * Organ (music), a family of keyboard musical instruments characterized by sustained tone ** Electronic organ, an electronic keyboard instrument ** Hammond ...
. The internal structure of the liver is broadly similar in all vertebrates, though 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
snake Snakes are elongated, limbless, carnivorous reptiles of the suborder Serpentes . Like all other squamates, snakes are ectothermic, amniote vertebrates covered in overlapping scales. Many species of snakes have skulls with several more ...
s, where the shape of the body necessitates a simple cigar-like form. An organ sometimes referred to as a liver is found associated with the digestive tract of the primitive chordate '' Amphioxus''. Although it performs many functions of a liver, it is not considered a "true" liver but rather a ''homolog'' of the vertebrate liver. The amphioxus hepatic caecum produces the liver-specific proteins vitellogenin, antithrombin,
plasmin Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encode ...
ogen, alanine aminotransferase, and
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism ...
/
Insulin-like growth factor The insulin-like growth factors (IGFs) are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system (often referred to as the IGF " ...
(IGF)


See also

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Porphyria Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. The types that affect the nervous system are also known as acute porphyria, as symptoms are ...
*
Johann Joseph Dömling Johann Joseph Dömling (13 January 1771 – 7 March 1803) was a German physician and professor of physiology at the University of Würzburg. Early life and education Dömling, whose last name is also spelled Doemling, was born in Merkershause ...
(published ''Is the liver a purifying organ'' in 1798)


References


Works cited

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External links


Liver at the Human Protein Atlas

VIRTUAL Liver – online learning resource

Liver enzymes
* with several diagrams. * Beaver tail liver {{Authority control Organs (anatomy)