Hepatocytes: functions, structure, histology, life time

The hepatocytes They are one of the four basic cell types that make up the liver. They reach to represent up to 80% of the total of cells of said organ and given their abundance and the importance of their functions, they are recognized as the main liver cells.

Hepatocytes are epithelial cells that make up the functional or essential tissue of the organ called parenchyma. When they are outside the human body, these cells lose their functionality in a matter of hours and it is very difficult to keep them alive in cell cultures.

Hepatocytes in a chronic hepatitis B infection with a high viral load. Hepatic biopsy. H & E staining

In the liver, they are accompanied by other cells at all times, such as ITO or stellate cells, which provide them with support functions such as storage.

In humans, the complete maturation of hepatocytes takes up to two years after birth and is promoted by several factors. Oxygen levels and nutrition change drastically at birth, with this new systems are activated in different organs and substances involved with the liver come to promote maturation.

The establishment of the intestinal microbiome in the first week after birth is related to a reorganization in the immature liver that promotes the maturation or functional specialization of hepatocytes through vitamins and precursors derived from the microbiome.

Time of life

The hepatocytes live for about a year and although they are renewed at a relatively slow rate, they have a great capacity for proliferation and regeneration when the tissue is affected.

In a healthy liver, they are renewed around every five months, so it is not common to find them in stages of cell division. However, even when the rate of renewal is slow, a small imbalance between production rates and cell death can lead to severely affecting the organ.

On the other hand, if the liver suffers some acute damage, the liver tissue responds by increasing the processes of cell regeneration.

Structure

The shape of the hepatocytes is polyhedral or polygonal. They measure from 20 to 30 micrometers in diameter and have a volume around 3000 cubic micrometers. These dimensions place them in the group of cells considered large.

They have nuclei of variable size centered in the cellular space. Some contain two nuclei (binucleate) and many are polyploid, that is, they contain more than two sets of chromosomes (between 20% to 30% in humans and up to 85% in mice).

Those that contain the duplicated genetic material are tetraploids and those that contain duplicate material up to twice are octaploids. They have more than one well-defined nucleolus and the state of the cytoplasm it depends on the presence of stores of fat or glycogen; If the glycogen stores are abundant, the endoplasmic reticulum is also abundant. In addition, they have abundant peroxisomes, lymphosomes and mitochondria .

Histology

Like other epithelial cells, hepatocytes are polarized cells, that is, they have distinctive regions such as the basal, lateral and apical membranes. Each of these membrane types have characteristic molecules, delivered specifically to their destination by the Golgi apparatus and the cytoskeleton.

The polarity of the membranes is established during embryonic development and is essential for many functions. Its loss, by breaking the bonds between hepatocytes or molecular regionalization, leads to disorganization in the tissue and causes diseases.

The basal and lateral membranes are linked to an extracellular matrix of low density that facilitates the transport of molecules. The apical membrane is that which is in contact with another hepatocyte and where the bile canaliculi are formed responsible for transporting the bile and metabolic products of waste.

The hepatocytes are arranged in layers of one cell of thickness, separated by vascular channels (sinusoids). They are not anchored to a basal layer, but arranged in spongy clusters in three dimensions. This structural arrangement facilitates the main functions of the liver.

Functions

The hepatocytes carry out many cellular functions that involve processes of synthesis, degradation and storage of numerous substances, in addition to enabling the exchange of metabolites from and to the blood.

Metabolize the products of digestion

Its main function is to metabolize the products of digestion to make them available to other cells in the body, that is, they have direct communication with the intestine through the bile canaliculi and with the blood flow through the sinusoids.

Metabolic functions

Among its metabolic functions, the synthesis of bile salts (necessary for the digestion of fats), lipoproteins (necessary for the transport of lipids in blood), phospholipids, and some plasma proteins such as fibrinogen, albumin, α and β globulins and prototrombin.

Bile production

Other well-known functions are the production of bile and its release into the digestive tract to aid in the digestive process, and the synthesis and regulation of cholesterol.

Urea discharge

On the other hand, they secrete urea as a product of protein metabolism and most of the plasma proteins found in the blood.

In addition, they play an important role in the metabolism of carbohydrates -transforming and storing them as glycogen- and fats -processing them and facilitating their transport.

Detoxification of the organism

Likewise, detoxification of the organism is carried out by hepatocytes since they not only receive substances produced by the digestion of food, but also receive substances such as alcohol and drugs that are processed in the peroxisomes and endoplasmic reticulum, respectively.

Additionally, they are responsible for the excretion of processed substances that become toxic metabolites such as bilirubin or steroid hormones.

Storage of vitamins, proteins and minerals

On the other hand, they carry out the storage of vitamins (A, B12, folic acid, heparin), minerals (iron) and proteins in cytosolic deposits since the free versions of some of these molecules can be toxic .

Likewise, they contain the molecular systems to process and transport these molecules to the rest of the body when it is required. They also present a hormonal function releasing hepcidicin which regulates the systemic concentration of iron.

Activate the immune system

Furthermore, hepatocytes activate the innate immune system by synthesizing and secreting proteins that help defend against bacterial infections. These proteins can kill bacteria through processes such as iron uptake essential for the survival of these or assist in phagocytosis, where cells of the immune system literally eat pathogens.

Thanks to these functions, processes such as coagulation, cellular communication, the transport of molecules in blood, processing of drug , contaminants and molecules, as well as the elimination of waste, which ultimately contributes to maintaining metabolic homeostasis.

References

1. Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter. Chapter 22 Histology the lives and deaths of cells in tissues. In Molecular Biology of the Cell, Fourth Edition. Garland Science, 2002. Pp. 1259-1312.
2. Chen C, Soto-Gutierrez A, Baptista PM, Spee B, Biotechnology Challenges to Vitro Maturation of Hepatic Stem Cells, Gastroenterology (2018), doi: 10.1053 / j.gastro.2018.01.066.
3. Gissen P, Arias IM. 2015. Structural and functional hepatocyte polarity and liver disease. Journal of hepatholoty. 63: 1023-1037.
4. Syeda H. Afroze, Kendal Jensen, Kinan Rahal, Fanyin Meng, Gianfranco Alpini, Shannon S. Glaser. Chapter 26 Liver Regeneration: The Stem Cell Approach. In Regenerative Medicine Applications in Organ Transplantation. Edited by: Giuseppe Orlando. pp. 375-390. 2014. ISBN: 978-0-12-398523-1.
5. Zhou, Z., Xu, M.J., Gao, B. Hepatocytes: a key cell type for innate immunity. Cellular & Molecular Immunology. 2016. pp. 301-315.