HEPATOCYTES: FUNCTIONS, STRUCTURE, HISTOLOGY, LIFE SPAN - BIOLOGY - 2025

The hepatocytes are one of the four basic cell types that make up the liver. They come to represent up to 80% of the total cells of this 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 outside the human body, these cells lose their functionality within hours and it is very difficult to keep them alive in cell culture.

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

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

The establishment of the gut 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

Hepatocytes live for approximately one year and although they renew at a relatively slow rate, they show 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 renewal rate is slow, a small imbalance between the production rates and cell death can lead to serious damage to the organ.

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

Structure

The shape of hepatocytes is polyhedral or polygonal. They measure 20 to 30 micrometers in diameter and have a volume of around 3,000 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 duplicate genetic material are tetraploid and those that contain material duplicated up to twice are octaploid. They have more than one well-defined nucleolus and the state of the cytoplasm depends on the presence of fat or glycogen stores; if glycogen stores are abundant, the smooth endoplasmic reticulum is also abundant. In addition, they have abundant peroxisomes, lizosomes, and mitochondria.

Histology

Like other epithelial cells, hepatocytes are polarized cells, that is, they present distinctive regions such as the basement, lateral and apical membranes. Each of these membrane types present characteristic molecules, specifically delivered 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 unions between hepatocytes or molecular regionalization, leads to disorganization in the tissue and causes diseases.

The basement and lateral membranes are attached to a low-density extracellular matrix that facilitates the transport of molecules. The apical membrane is one that is in contact with another hepatocyte and where the bile canaliculi responsible for transporting bile and metabolic waste products are formed.

Hepatocytes are arranged in 1 cell thick layers, separated by vascular channels (sinusoids). They are not anchored to a basal layer, but are arranged in spongy clusters in three dimensions. This structural arrangement facilitates the main functions of the liver.

Features

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 to and from 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

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

Bile production

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

Urea secretion

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 of fats -processing and facilitating their transport.

Body detoxification

Likewise, the detoxification of the body is carried out by the 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 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 uptake of iron essential for their survival or by assisting in phagocytosis, where cells of the immune system literally eat pathogens.

Thanks to these functions, processes such as coagulation, cell communication, the transport of molecules in the blood, processing of drugs, pollutants and molecules are ensured, 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 In 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, MJ, Gao, B. Hepatocytes: a key cell type for innate immunity. Cellular & Molecular Immunology. 2016. pp. 301-315.