Liver histology

Functions and physiology

The liver performs several important functions in the human body, such as given below:

• Plasma protein synthesis - albumins, lipoproteins, glycoproteins, prothrombin, fibrinogen
• Vitamin storage and modification - vitamins A, D, and K
• Iron storage and metabolism - transferrin, haptoglobin, hemopexin, ferritin
• Drugs and toxins degradation
• Bile production
• Carbohydrate metabolism

Histological components

The liver consists of the following major histological components:

• Parenchyma, which is represented by hepatocytes
• Stroma, which is a continuation of the surrounding capsule of Glisson. It consists of connective tissue and contains the vessels. The capsule is also covered by a layer of mesothelium, arising from the peritoneum covering the liver. The connective tissue of the stroma is type III collagen (reticulin), which forms a meshwork that provides integrity for the hepatocytes and sinusoids.

• Sinusoids, which are capillaries travelling between hepatocytes
• Spaces of Disse (perisinusoidal spaces), which are located between the hepatocytes and the sinusoids.

Structure

In histological terms, the liver consists of a large number of microscopic functional units that work in unison to ensure the overall, proper activity of the entire organ. There are three possible ways of describing one such unit, as given below:

• Hepatic (classic) lobule
• Portal lobule
• Liver acinus

Hepatocytes

These large and polyhedral (six surfaces) cells make up 80% of the total cells of the liver. They can contain between two and four nuclei, which are large and spherical, occupying the centre of the cells. Each nucleus has at least two nucleoli. The typical lifespan of a hepatocyte is five months. The adjacent hepatocytes leave a very small space between them known as bile canaliculi which are almost 1.0-2.0 μm in diameter. The cell membranes near these canaliculi are joined by tight junctions.

The cytoplasm is acidophilic in routine H&E staining, dotted with basophilic regions represented by rough endoplasmic reticulum (rER) and ribosomes. In addition, hepatocytes contain the following organelles:

• Smooth endoplasmic reticulum (sER), which is essential in toxin degradation and conjugation, as well as cholesterol synthesis.
• Mitochondria (up to 1000/cell)
• Golgi network, which is composed of approximately 50 small Golgi units. They contain granules with very low density lipoprotein and bile precursors.
• Peroxisomes, which contain oxidases and catalases. These enzymes are responsible for detoxification reactions taking place in the liver, for example, that of alcohol.
• Glycogen deposits, which are lost in during H&E preparations, leaving irregular stained areas.
• Lipid droplets
• Lysosomes, which are responsible for iron storage under the form of ferritin.

Perisinusoidal space (space of Disse)

This space is situated between the layers of hepatocytes and the sinusoidal endothelial cells. The hepatocytes extend villi into the perisinusoidal space, increasing the extent and rate of material exchange, together with the microvilli.

The perisinusoidal space contains a specific type of cell called Ito, or hepatic stellate, cells. Their role is the storage of hepatic vitamin A inside lipid droplets, which is subsequently released as retinol. However, Ito cells are also responsible for hepatic fibrosis, since they are the ones secreting large amounts of collagen during liver injury.

Vasculature

Biliary tree

This is a system consisting of channels that carries bile from the source, this being the hepatocytes, all the way to the gallbladder and intestines. The epithelial cells lining this system are called cholangiocytes. They range in shape from cuboidal in small ductules, to columnar in large ductules. Cholangiocytes have several histological features, such as:

• Few organelles
• Presence of tight junctions between the cells
• Microvilli on their apical domains
• Primary cillium

The hepatocytes secrete bile into the bile canaliculi, which are the smallest channels of the biliary tree. The secretion into these canaliculi is an active process. They partially loop around the hepatocytes and become the canals of Hering close to the portal canal.

These canals are lined by both hepatocytes and cuboidal cholangiocytes. The flow of bile is opposite to that of the blood and the canals of Hering are capable of contracting and assisting this flow towards the portal canal. The canals of Hering also posses hepatic stem cells, which represent the source of hepatocytes and cholangiocytes.

The canals of Hering flow into intrahepatic bile ductules in the periportal space (of Mall), which are completely lined by cholangiocytes. In turn, the intrahepatic bile ductules flow into interlobular bile ducts, which are lined by cuboidal to columnar cholangiocytes and form part of the portal triad. As these ducts travel towards the porta hepatis, they increase in diameter and become invested inside dense connective tissue composed of elastic fibers. Finally, these interlobular ducts join to form the right and left hepatic ducts, which in turn merge to form the common hepatic duct. This duct is lined by columnar epithelial cells. The cystic duct branches from the common hepatic duct, carrying bile to and from the gallbladder.

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