Hepatocyte

Hepatocytes are polygonal cells about 10 to 30 µm in size, which take up about 80% of the liver volume. They originate from the entoderm of the intestinal tract, are metabolically highly active and contain numerous highly specialized cell organelles. The hepatocytes lie close to the blood-filled sinusoids and form single-layered, radially tapered liver cell plates from the portal fields towards the central vein.

The hepatocyte, like all epithelial cells, has a polarized structure and function. It has a basolateral (sinusoidal) and an apical (canalicular) membrane. The narrow apical bile pole carries numerous microvilli and secretes bile. The broad basolateral blood pole has direct contact with the blood plasma because the basal membrane around the small communicating sinusoids is missing. Furthermore, the endothelial cells contain small windows through which larger molecules can pass. Laterally, one hepatocyte borders on its neighbouring hepatocyte, from which it is separated by a submicroscopically narrow gap. On the apical surface, the bile ducts are located between the hepatocytes. While the lateral paracellular space is not separated from the dissecting space, there are tight junctions around the bile capillaries, the "tight junctions", so that bile cannot escape from the bile tubules into the intercellular spaces. If there is a congestion in the draining bile ducts, the bile is secreted into the bloodstream of the liver sinusoids.

The fetal liver contains hematopoietic colony-forming CD34- and CD117-positive pluripotent cells with high proliferation potential.

Hepatocyte functions

Hepatocytes serve the body for central metabolic functions. These include in particular:

synthesis, storage and degradation of glycogen, gluconeogenesis (synthesis of glucose from pyruvate, lactate and amino acids), hem synthesis

Detoxification of toxic substances including drugs via cytochrome P450 enzymes, part of the urea cycle, urea synthesis.

Synthesis of bile acids (their production is specific to the liver), cholesterol, bilirubin, protein (e.g. albumin, coagulation factors, transport proteins, apolipoproteins), degradation of haem.

Synthesis and degradation of amino acids: The liver is a major site of amino acid conversion due to a variety of anabolic and catabolic processes. The amino acids for hepatic protein synthesis come from food, from the body's own proteins (especially muscle protein), and from direct synthesis in the liver. The breakdown of amino acids in the liver consists essentially of 2 reactions: transamination and oxidative deamination. In transamination, the amino group of an amino acid is transferred to a keto acid. This process is catalysed by aminotransferases. The best studied is the glutamate-oxalate transferase, which is used in different types of amino acids. Liver cracks are measured in increased amounts. During oxidative deamination, amino acids are converted into keto acids and ammonia.

Serum proteins: Liver cells synthesize most serum proteins: nalpha, beta globulins (often increase in chronic liver disease when the reticulo-endothelial system is damaged or bypassed by portal venous shunts), but not gamma globulins (produced and secreted by plasma cells), albumin and clotting factors. In addition, specific proteins such as alpha1-antitrypsin, coeruloplasmin (reduced in Wilson's disease), transferrin and ferritin (belong to the acute phase proteins). Serum albumin is the main responsible for the colloid osmotic pressure of the plasma, furthermore albumins transport a variety of substances.

The liver cells in the various The liver cells in the various sections of a liver lobule (acinar) behave metabolically heterogeneously in carrying out their complex functions. For example, glucogenesis takes place mainly in zone 1 (cells in the area of the glisson triangle), glycolysis mainly in zone 3 (cells in the area of the central veins).

Regeneration ability of the hepatocytes

Hepatocytes are constantly being regenerated; old cells are replaced; there are different specifications in the literature for their average life span, ranging from 1 to 8 months. The liver probably regenerates completely several times within one year. Growth is supported by endocrine factors such as growth hormones, insulin, noradrenalin, serotonin and T3/T4. Replacement by new cells is synchronized.

Substances such as the "hepatocyte growth factor" (HGF) are involved in controlling hepatic regeneration. HGF is not produced by hepatocytes, but by mesenchymal cells in the liver. Other growth factors also appear to be involved in regeneration (e.g. interleukin-6, EGF, TGF).

Storage function of hepatocytes

Depending on the situation, the liver can store carbohydrates (postprandial: glycogen formation) or provide them when needed (glycogenolysis, gluconeogenesis). Hepatocytes thus constitute an important metabolic buffer in their entirety. The liver cells also store vitamins (all fat-soluble, many water-soluble vitamins), as well as trace elements (iron, zinc, copper, etc.).

Copper: 60-90% of the copper resorbed in the intestine is absorbed by liver cells and bound to metalloproteins ("copper chaperones" - chaperones are proteins that accelerate the correct folding of newly formed proteins without becoming part of the structure themselves). These are able to transfer copper to certain enzymes whose function is linked to the incorporation of the metal (such as superoxide dismutase, cytochrome C oxidase). Excess copper is bound with the bile mainly to large protein molecules and is thus excreted in an unabsorbable way (≈80% of the daily amount absorbed in the intestine per day). If this mechanism is inhibited, copper storage diseases (e.g. Wilson's disease) occur.

Function of non-parenchymatous cells

Many of the functions of hepatocytes are influenced or regulated by nonparenchymatous cells of the liver. These include endothelial cells, Kupffer cells and HS cells (hepatic stellate cells also known as Ito cells or fat storing cells), but also lymphocytes and pit cells (large-grain lymphocytes/natural killer cells). Depending on the condition, endothelial cells secrete cytokines, prostaglandins, leukotrienes, endothelin-1 and nitric oxide (NO), Kupffer cells (stationary macrophages of the liver) inflammatory mediators such as TNF-alpha, prostaglandins and interleukins. These mediator substances influence the function of liver cells. Kupffer cells promote glucose formation in neighbouring liver cells via prostaglandins by stimulating glycogen degradation. They also cooperate with hepatocytes in the synthesis of leukotriene LTC4: Kupffer cells synthesize their precursor and hepatocytes complete the formation.

HSC (hepatic stellate cells, Ito cells): these are pericytes located in the dissecting space of the liver tissue. These cells make up about 1% of the hepatic cells and store most of the vitamin A ingested with food. HSC are able to promote or inhibit the cell turnover of hepatocytes by producing HGF (hepatocyte growth factor) or TGF-beta. They can differentiate into myofibroblasts and then synthesize type 3 collagen.

Special cells

Underlying hepatocytes: Smaller eosinophilic cells with a pynotic nucleus are occasionally found in liver tissue; these are undergoing apoptosis. Physiologically, they are most likely to be found in the lobule centre; cell replenishment is from the portal field boundaries of the liver lobule.

Ground glass hepatocytes: This cell type is found in hepatitis B. Milk glass hepatocytes are large hepatocytes with homogeneous light-eosinophilic cytoplasm under the light microscope. They have a particularly high content of HBsAg.

Special (pathological) intracellular structures

Depending on the size of the fat droplets, fat droplets (lipid droplets) cause large and medium-droplet or fine-droplet microvesicular fat deposition (steatosis). In most cases, large and medium droplet deposition predominates (predominant in metabolic syndrome, diabetes mellitus, obesity). Microvesicular steatosis is rare, such as in Reye's syndrome and drug toxicity (e.g. tetracyclines).

Glycogen (storage form of glucose) can be detected in hepatocytes depending on the nutritional status. In diabetes mellitus, glycogen deposits are also found in the nuclei of liver cells ("glycogen nuclei"). In glycogen storage diseases, hepatocytes are fully loaded with glycogen.

Sphingomyelins are accumulated intracellularly in Niemann-Pick's disease.

Lipofuscin (also known as "age pigment") is a lysosomal oxidation product of unsaturated fatty acids.

Mallory corpuscles are eosinophilic hyaline inclusions in the cytoplasm of hepatocytes, which can be detected in over 50% of cases of alcohol abuse, but also occur in other liver diseases (e.g. Wilson's disease).