A hepatocyte is a cell of the main

parenchyma upright=1.6, Lung parenchyma showing damage due to large subpleural bullae. Parenchyma () is the bulk of functional substance in an animal organ such as the brain or lungs, or a structure such as a tumour. In zoology, it is the tissue that ...

l tissue of the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

. Hepatocytes make up 80% of the liver's mass. These cells are involved in: *

Protein synthesis Protein biosynthesis, or protein synthesis, is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critica ...

* Protein storage * Transformation of

carbohydrate A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...

s * Synthesis of

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

bile salts Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...

and

phospholipid Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

s * Detoxification, modification, and excretion of exogenous and endogenous substances * Initiation of formation and secretion of

bile Bile (from Latin ''bilis''), also known as gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, is pro ...

Structure

The typical hepatocyte is cubical with sides of 20-30

μm The micrometre (Commonwealth English as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer (American English), also commonly known by the non-SI term micron, is a unit of length in the International System ...

, (in comparison, a

human hair Hair is a protein filament that grows from follicles found in the dermis. Hair is one of the defining characteristics of mammals. The human body, apart from areas of glabrous skin, is covered in follicles which produce thick terminal and f ...

has a diameter of 17 to 180 μm).The

diameter In geometry, a diameter of a circle is any straight line segment that passes through the centre of the circle and whose endpoints lie on the circle. It can also be defined as the longest Chord (geometry), chord of the circle. Both definitions a ...

of human hair ranges from 17 to 181 μm. The typical volume of a hepatocyte is 3.4 x 10⁻⁹ cm³. Smooth

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

is abundant in hepatocytes, in contrast to most other cell types.

Microanatomy

Hepatocytes display an

eosinophilic Eosinophilic (Greek suffix '' -phil'', meaning ''eosin-loving'') describes the staining of tissues, cells, or organelles after they have been washed with eosin, a dye commonly used in histological staining. Eosin is an acidic dye for stainin ...

cytoplasm, reflecting numerous

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

, and

basophilic Basophilic is a technical term used by pathologists. It describes the appearance of cells, tissues and cellular structures as seen through the microscope after a histological section has been stained with a basic dye. The most common such dye ...

stippling due to large amounts of

rough endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for "little n ...

and free

ribosomes Ribosomes () are macromolecular machines, found within all cells, that perform biological protein synthesis (messenger RNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA molecules to fo ...

. Brown

lipofuscin Lipofuscin is the name given to fine yellow-brown pigment Granule (cell biology), granules composed of lipid-containing residues of Lysosome, lysosomal digestion. It is considered to be one of the aging or "wear-and-tear" pigments, found in the l ...

granules are also observed (with increasing age) together with irregular unstained areas of cytoplasm; these correspond to cytoplasmic

glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. It is the main storage form of glucose in the human body. Glycogen functions as one of three regularly used forms ...

and

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

stores removed during histological preparation. The average life span of the hepatocyte is 5 months; they are able to regenerate. Hepatocyte nuclei are round with dispersed

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...

and prominent

nucleoli The nucleolus (; : nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis. The nucleolus also participates in the formation of signal recognition particles and plays a ro ...

. Anisokaryosis (or variation in the size of the nuclei) is common and often reflects tetraploidy and other degrees of

polyploidy Polyploidy is a condition in which the cells of an organism have more than two paired sets of ( homologous) chromosomes. Most species whose cells have nuclei (eukaryotes) are diploid, meaning they have two complete sets of chromosomes, one fro ...

, a normal feature of 30-40% of hepatocytes in the adult human liver. Binucleate cells are also common. Hepatocytes are organised into plates separated by vascular channels (

sinusoids A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the inn ...

), an arrangement supported by a

reticulin Reticular fibers, reticular fibres or reticulin is a type of fiber in connective tissue composed of type III collagen secreted by reticular cells. They are mainly composed of reticulin protein and form a network or mesh. Reticular fibers cros ...

(

collagen type III Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

) network. The hepatocyte plates are one cell thick in mammals and two cells thick in the chicken. Sinusoids display a discontinuous, fenestrated

endothelial The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...

cell lining. The endothelial cells have no

basement membrane The basement membrane, also known as base membrane, is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tis ...

and are separated from the hepatocytes by the

space of Disse The perisinusoidal space (or space of Disse) is a space between a hepatocyte, and a sinusoid in the liver. It contains the blood plasma. Microvilli of hepatocytes extend into this space, allowing proteins and other plasma components from the s ...

, which drains

lymph Lymph () 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 to be recirculated. At the ori ...

into the portal tract

lymphatics The lymphatic vessels (or lymph vessels or lymphatics) are thin-walled vessels (tubes), structured like blood vessels, that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vessel ...

Kupffer cell 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 ...

s are scattered between endothelial cells; they are part of the

reticuloendothelial system In anatomy the term reticuloendothelial system (abbreviated RES), often associated nowadays with the mononuclear phagocyte system (MPS), was employed by the beginning of the 20th century to denote a system of specialised cells that effectively cl ...

and phagocytose spent

erythrocytes Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

. Stellate (Ito) cells store

vitamin A Vitamin A is a fat-soluble vitamin that is an essential nutrient. The term "vitamin A" encompasses a group of chemically related organic compounds that includes retinol, retinyl esters, and several provitamin (precursor) carotenoids, most not ...

and produce

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

and

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

; they are also distributed amongst endothelial cells but are difficult to visualise by light microscopy.

Function

Protein synthesis

The hepatocyte is a

cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

in the

body Body may refer to: In science * Physical body, an object in physics that represents a large amount, has mass or takes up space * Body (biology), the physical material of an organism * Body plan, the physical features shared by a group of anim ...

that manufactures

serum albumin Serum albumin, often referred to simply as blood albumin, is an albumin (a type of globular protein) found in vertebrate blood. Human serum albumin is encoded by the ''ALB'' gene. Other mammalian forms, such as bovine serum albumin, are chem ...

fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...

, and the

prothrombin Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin. Thrombin (Factor IIa) (, fibrose, thrombase, throm ...

group of clotting factors (except for Factors 3 and 4). It is the main site for the synthesis of

lipoprotein A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, sur ...

ceruloplasmin Ceruloplasmin (or caeruloplasmin) is a ferroxidase enzyme that in humans is encoded by the ''CP'' gene. Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in ...

transferrin Transferrins are glycoproteins found in vertebrates which bind and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Iron(III), Fe3+ ions. Human transferrin is ...

complement Complement may refer to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-class collections into complementary sets * Complementary color, in the visu ...

, and

glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) 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 a ...

s. Hepatocytes manufacture their own structural proteins and intracellular

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s. Synthesis of proteins is by the

(RER), and both the rough and smooth endoplasmic reticulum (SER) are involved in secretion of the proteins formed. The

(ER) is involved in conjugation of proteins to lipid and carbohydrate moieties synthesized by, or modified within, the hepatocytes. Proteins produced by hepatocytes that function as hormones are known as

hepatokine Hepatokines (Greek ''heapto-'', liver; and ''-kinos'', movement) are proteins produced by liver cells (hepatocytes) that are Secretion, secreted into the Circulatory system, circulation and function as hormones across the organism. Research is most ...

Carbohydrate metabolism

The

forms fatty acids from

s and synthesizes triglycerides from fatty acids and glycerol. Hepatocytes also synthesize apoproteins with which they then assemble and export lipoproteins (

VLDL Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins (chylomicrons, VLDL, intermediate-density lipoprotein, LDL, low-density ...

, HDL). The liver is also the main site in the body for

gluconeogenesis Gluconeogenesis (GNG) is a metabolic pathway that results in the biosynthesis of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In verte ...

, the formation of carbohydrates from precursors such as

alanine Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group sid ...

glycerol Glycerol () is a simple triol compound. It is a colorless, odorless, sweet-tasting, viscous liquid. The glycerol backbone is found in lipids known as glycerides. It is also widely used as a sweetener in the food industry and as a humectant in pha ...

, and

oxaloacetate Oxaloacetic acid (also known as oxalacetic acid or OAA) is a crystalline organic compound with the chemical formula HO2CC(O)CH2CO2H. Oxaloacetic acid, in the form of its conjugate base oxaloacetate, is a metabolic intermediate in many processes ...

Lipid metabolism

The liver receives many

s from the systemic circulation and metabolizes

chylomicron Chylomicrons (from the Greek χυλός, chylos, meaning ''juice'' (of plants or animals), and micron, meaning ''small''), also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85–92%), ...

remnants. It also synthesizes

from

acetate An acetate is a salt formed by the combination of acetic acid with a base (e.g. alkaline, earthy, metallic, nonmetallic, or radical base). "Acetate" also describes the conjugate base or ion (specifically, the negatively charged ion called ...

and further synthesizes

bile salt Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...

s. The liver is the sole site of bile salts formation.

Detoxification

Hepatocytes have the ability to metabolize, detoxify, and inactivate exogenous compounds such as

drugs A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via inhalation, injection, smoking, ingestio ...

(see

drug metabolism Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set o ...

insecticide Insecticides are pesticides used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. The major use of insecticides is in agriculture, but they are also used in home and garden settings, i ...

s, and endogenous compounds such as

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

s. The drainage of the

intestinal 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 tract is the largest of the body's systems, after the cardiovascular system. T ...

venous Veins () are blood vessels in the circulatory system of humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are those of the pulmonary and fetal c ...

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

into the

requires efficient detoxification of miscellaneous absorbed substances to maintain

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

and protect the body against ingested toxins. One of the detoxifying functions of hepatocytes is to modify ammonia into

urea Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...

for excretion. The most abundant organelle in liver cells is the smooth endoplasmic reticulum.

Aging

As mammalian liver cells age, damages in their DNA increase in prevalence. A review of the literature indicated that in mouse liver cells DNA damages (single-strand breaks, oxidized bases and

7-methylguanine 7-Methylguanine is a modified purine nucleobase. It is a methylated version of guanine. The 7-methylguanine nucleoside is called 7-methylguanosine. However, the free 7-methylguanine base is not involved in the synthesis of nucleotides and not inc ...

) increase with age. Also, in rat liver, DNA single- and double-strand breaks, oxidized bases, and methylated bases increase with age; and in rabbit liver, cross-linked bases increase with age. Liver cells depend on

DNA repair DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...

pathways that specifically protect the transcribed compartment of the

genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...

to promote sustained functionality and cell preservation with age.

Society and culture

Use in research

Primary hepatocytes are commonly used in cell biological and biopharmaceutical research. In vitro model systems based on hepatocytes have been of great help to better understand the role of hepatocytes in (patho)physiological processes of the liver. In addition, pharmaceutical industry has heavily relied on the use of hepatocytes in suspension or culture to explore mechanisms of drug metabolism and even predict in vivo drug metabolism. For these purposes, hepatocytes are usually isolated from animal or human whole liver or liver tissue by collagenase digestion, which is a two-step process. In the first step, the liver is placed in an isotonic solution, in which calcium is removed to disrupt cell-cell

tight junctions Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes between epithelial cells, sealing and preventing leakage of solutes and water. They also play a ...

by the use of a calcium

chelating agent Chelation () is a type of bonding of ions and their molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These l ...

. Next, a solution containing collagenase is added to separate the hepatocytes from the liver stroma. This process creates a suspension of hepatocytes, which can be seeded in multi-well plates and cultured for many days or even weeks. For optimal results, culture plates should first be coated with an extracellular matrix (e.g. collagen, Matrigel) to promote hepatocyte attachment (typically within 1-3 hr after seeding) and maintenance of the hepatic phenotype. In addition, and overlay with an additional layer of extracellular matrix is often performed to establish a sandwich culture of hepatocytes. The application of a sandwich configuration supports prolonged maintenance of hepatocytes in culture. Freshly-isolated hepatocytes that are not used immediately can be cryopreserved and stored. They do not proliferate in culture. Hepatocytes are intensely sensitive to damage during the cycles of cryopreservation including freezing and thawing. Even after the addition of classical

cryoprotectant A cryoprotectant is a substance used to protect biological tissue from freezing damage (i.e. that due to ice formation). Arctic and Antarctic insects, fish and amphibians create cryoprotectants ( antifreeze compounds and antifreeze proteins) in th ...

s there is still damage done while being cryopreserved. Nevertheless, recent cryopreservation and resuscitation protocols support application of cryopreserved hepatocytes for most biopharmaceutical applications.

Additional images

File:Hepato-biliary.jpg, Schematic diagram of biliary system File:Hepatocyte Culture.tif, Hepatocytes in cell culture File:Membrane proteins of the polarized hepatocytes.jpg, Schematic of hepatocyte

polarization Polarization or polarisation may refer to: Mathematics *Polarization of an Abelian variety, in the mathematics of complex manifolds *Polarization of an algebraic form, a technique for expressing a homogeneous polynomial in a simpler fashion by ...

, showing proteins localized to the basolateral and apical surfaces of the hepatocyte, referred to as the sinusoidal and canalicular membranes, respectively

References

External links

* - "Ultrastructure of the Cell: hepatocytes and sinusoids"
Hepatic Histology: Hepatocytes (Colorado State University
{{Authority control Liver anatomy Animal cells Human cells

Structure

Microanatomy

Function

Protein synthesis

Carbohydrate metabolism

Lipid metabolism

Detoxification

Aging

Society and culture

Use in research

Additional images

See also

References

External links