Hepatocytes: Function & Diseases

Hepatocytes are the actual liver cells that make up more than 80 percent of the liver. They are responsible for most metabolic processes such as synthesis of proteins and drugs, breakdown of metabolites, and detoxification reactions. Disturbances in hepatocyte function can lead to central metabolic diseases and symptoms of intoxication.

What are hepatocytes?

Hepatocytes make up the majority of liver cells (over 80 percent) and form what is known as the liver parenchyma. The liver parenchyma is associated with the most important functions of the liver. Hepatocytes are very large cells with a diameter of 30-40 micrometers. They also have a large nucleus and sometimes they contain two nuclei. Their chromosome set is usually diploid. However, hepatocytes can also have a polyploid chromosome set. Very intense metabolic processes occur within hepatocytes, controlled by a large number of cell organelles. They divide very rarely. Their formation occurs mainly from pluripotent stem cells in the transition area of liver tissue and the outgoing bile ducts. There, stem cells transform into both hepatocytes and cholangiocytes. Hepatocytes are also in direct contact with blood plasma via basolateral membranes.

Anatomy and structure

Hepatocytes are very large cells with large nuclei and numerous cell organelles that provide very intense metabolic activity. In this context, the hepatocyte has a highly polarized structure and function. Thus, basolateral (sinusoidal) and apical (canalicular) membranes are present. At the same time, the basal lamina is absent. The apical membranes are responsible for the secretion of bile through the numerous microvilli. The basolateral membranes are adjacent to a sinusoid through microvilli so that substances can be exchanged between blood and hepatocyte. To carry out their numerous metabolic functions, hepatocytes possess a number of cell organelles. First, they contain large diploid or polyploid nuclei. Furthermore, many mitochondria, peroxisomes and lysosomes are present. Individual lipid droplets and glycogen fields are located in the hepatocytes as storage substances. The concentration of glycogen depends on the nutritional status and changes several times during the day. A strongly developed endoplasmic reticulum and a strong Golgi apparatus testify to the high metabolic activity of liver cells. Certain active substances are secreted via numerous secretory vesicles. Finally, a well-developed cytoskeleton maintains the shape of hepatocytes.

Function and tasks

Hepatocytes play a central role in the body’s metabolic processes. For example, they are responsible for providing transport proteins for hormones, lipids, vitamins, or foreign substances. As transport proteins they provide albumins and for energy production amino acids, fats and glucose. The degradation of metabolic products also takes place via the hepatocytes. The same applies to the detoxification of foreign substances and the excretion of their degradation products via kidneys and bile. Another important function of hepatocytes is the formation of bile. With the help of bile, cholesterol, bile acids, bilirubin and the degradation products of toxic foreign substances can be excreted. The acid-base balance is also regulated by the hepatocytes. Most metabolic functions are controlled in the cell organelles. For example, the storage, synthesis and degradation of glucogen take place in the cytosol. Furthermore, glucose is also produced there from amino acids by the process known as gluconeogenesis. Likewise, part of heme synthesis also takes place in the cytosol of hepatocytes. Furthermore, part of heme synthesis, gluconeogenesis and part of the urea cycle and urea synthesis takes place in the mitochondria of hepatocytes. In addition, toxic substances including drugs are degraded there via the cytochrome P450 system. In the smooth endoplasmic reticulum and the Golgi apparatus of the hepatocytes, the synthesis of bile acids and cholesterol takes place. In addition, heme is degraded into bilirubin there. In the rough endoplasmic reticulum, the synthesis of albumin, transport proteins, coagulation factors and apoliproteins occurs. The same reactions do not take place in all hepatocytes.The intensity of the individual metabolic processes depends on the position of the corresponding liver cell in relation to the vascular system. Thus, metabolic functions within the liver parenchyma are divided into three zones. Zone 1 represents the area where portal blood enters the liver tissue. Zone 3 is where blood collects from the liver tissue to the central veins leading away. Zone 2 lies in between.

Diseases

There are liver diseases that mainly involve the hepatocytes. In other liver disorders, they are not involved at all. Liver diseases with exclusive involvement of hepatocytes include liver inflammation (hepatitis), fatty liver, toxic damage to the liver, allergic-hyperergic mechanisms, or congenital storage diseases. Liver inflammation can have a variety of causes. For example, several viral hepatidis forms are known. Autoimmunologic liver inflammations also occur. Liver inflammations result in the death of liver parenchyma. Since liver tissue is very capable of regeneration, the hepatocytes are replaced once the disease is overcome. However, in a chronic course, liver tissue may scar with the development of liver cirrhosis. The detoxification capacity of the liver decreases more and more. In the final stage, general organ failure occurs due to poisoning of the body. However, severe acute and chronic poisoning can also lead to the breakdown of liver tissue with the formation of liver cirrhosis. For example, a typical acute poisoning is caused by eating the green button mushroom. If the patient survives, cirrhosis of the liver develops. Chronic poisoning is caused, among other things, by regular alcohol consumption and drug abuse. Here, too, the detoxification capacity of the hepatocytes is overtaxed in the long term, so that severe liver damage develops.