Liver Histology

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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

Hepatic (classic) lobule

The classic lobule is the traditional description and the one that you have most likely heard of the most.
It consists of hexagonal plates of hepatocytes stacked on top of each other. Within each plate, the
hepatocytes radiate outwards from a central vein. As they extend towards the periphery, the
hepatocytes are arranged into strips, similar to the spokes of a cartwheel. Hepatic sinusoids travel
between the strips of hepatocytes, draining into the central vein.
One portal canal is located at each corner of the hexagonal classic lobule, making a total of six for each
lobule. These portal canals are composed of the portal triads, which are surrounded by loose stromal
connective tissue. A periportal space (space of Mall), where lymph is produced, is sandwiched between
the connective tissue of the portal canals and the hepatocytes.

While connective tissue is present around the portal canals, the interlobular quantity is very small in
humans. This can make routine histological visualizations of the classic lobule difficult.

Portal lobule

While the classic lobule view focuses on the blood supply and hepatic mass arrangement, the portal
lobule view underlines the exocrine function of the liver i.e. bile secretion. In this case, each functional
unit is a triangle, having a central axis through a portal field and the imaginary vertices through the three
different but closest portal canals surrounding it. The area covered by the triangle represents the
hepatic regions that secrete bile into the same bile duct.
Liver acinus

The focus of this description is the perfusion, metabolism and pathology of hepatocytes, providing a
more accurate description of the physiology of the liver. A liver acinus functional unit is in the shape of
an oval. The short axis is represented by a shared border between two adjacent lobules together with
the portal canals. The long axis is an imaginary line between two adjacent central veins.

Each half of the liver acinus can be divided into three zones:

Zone 1 – It is the one closest to the short axis, hence to the portal canals and supply of arterial blood.
The hepatocytes in zone 1 receive the highest amount of oxygen.

Zone 2 – It is the one located between zones 1 and 3.


Zone 3 – It is the one furthest from the short axis but closest to the central vein, hence the hepatocytes
receive the least amount of oxygen.
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.

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