The liver cells are about 100 billion; make up 80% of the cell population of the
liver; they have a multifaceted appearance, with six or more faces, variable in
shape and size, with an average diameter of 20-30 microns and a volume of about
5,000 microncubes. They are organized in single-celled laminae with each other
anastomosed and interposed to the course of the sinusoids, and form the hepatic
lobule - at the lobule periphery level, at the level of the portobiliary space
and below the Glisson capsule - a limiting lamina that deals with the connective
tissue surrounding. The shape and volume of hepatocytes varies depending on age,
location in the lobule and regenerative activity; in relation to the intake of
solutes the transmembrane movement of water can increase the cell volume by 5%.
The hepatocyte has a triple polarity consisting of three different domains,
located on the various faces that the cell presents: the sinusoidal one, or
vascular pole, facing the sinusoids and the subendothelial space (space of
Disse); the canalicular one, or biliary pole, which delimits the thin canalicles
(secretion capillaries) bent dug between two adjacent hepatocytes; the lateral
one, where intercellular spaces are not interfaced with the biliary canaliculi.
The sinusoidal domain, or vascular pole, constitutes from 37% to 70% of the cell
surface. In these areas, the cell surface is covered by 25-50 microvilli per
micron / square, up to 0.5 μ long and 0.1 μ in diameter. The numerous microvilli
are projected in the subendothelial space (perisinusoidal space of Disse)
towards the fenestrations of endothelial cells.
The vascular pole also has numerous small vesicles of pinocytosis, invaginations and bulbous protrusions, characteristic of exocytosis, as well as of selective endocytosis. Ultrastructural studies under scanning electron microscopy have shown that Disse's spaces are not limited to the subendothelial region, but extend between adjacent hepatocytes, forming narrow and irregular recesses (perisinusoidal recesses). In all these spaces, both perisinusoidal and subendothelial, the surfaces of the hepatocytes are rich in microvilli. An extensive microlabyrinthine system of perivascular and intercellular spaces is thus created, where blood plasma circulates freely, thus making intense and direct exchanges between the blood and the vascular pole of the hepatocytes possible. The liquid resulting from such exchanges with high metabolic activity, on one side falls within the circulatory stream, on the other, flowing inside the spaces of Disse, is conveyed towards the periphery of the lobule where it is poured into a space circumscribed by numerous fibers collagen at the level of the periphery of the portal spaces (Mail space). The liquids contained in the spaces of Disse and Mail are not lymph in the strict sense, but must be considered as interstitial fluids that contribute to the formation of the actual lymph, which is formed at the level of lymphatic vessels provided with their own wall, located, in close contact with the Mail spaces in the Portobiliare region.
The canalicular domain; or biliary pole, constitutes 13-15% of the cell surface. The cell surfaces that serve to delimit the biliary capillaries are flat and tightly packed, except for a small area where the surface appears to be sunken in a shower. This, juxtaposing itself to a similar depression present on the wall of the adjacent cell, delimits the wall of the biliary canaliculus. The diameter of the canaliculi varies from 0.5 microns in the pericentral area to 2.5 microns in the periportal area. The surfaces of the hepatocyte that delimit the biliary canaliculus are provided with numerous short microvilluses protruding into the lumen and are separated from the adjacent intercellular spaces by jointing complexes (occludent areas). The cytoplamic channels that form the bile canaliculi; they can be considered as true intracellular roots of the bile canaliculi.
The lateral domain extends between the margin of the canaliculi to the vascular one, from which it is separated from junctional complexes, constituting the remaining 15-50% of the surface with the role of connection and communication between the hepatocytes. Under normal conditions, no communication is possible between the bile pole closed by the junction complexes and the vascular pole of the hepatic cell. Therefore, adjacent surfaces of the same hepatocyte can simultaneously be engaged in highly differentiated absorption and secretion functions. On the whole, the cellular surfaces aimed at the perivascular spaces are much wider than those that delimit the bile canaliculi; this is in accordance with the greater metabolic commitment that the hepatocyte develops at the level of the sinusoidal domain (absorption and increase in the circulatory stream) compared to the biliary one (secretion).
In the cytosol of hepatocytes there is a dynamic three-monthly network of
cytoskeleton elements; the microfilaments, positive for the actin reaction, are
mainly located around the biliary capillaries involved in the motility of the
canaliculi; as regards intermediate filaments, it is important to note that K18
is the most expressed cytokeratin in hepatocytes: a K18 mutation is associated
with cryptogenic hepatic cirrhosis; microtubules, essential for the maintenance
of the cellular form as well as for vesicular transport and for mitosis, are
positive for tubulin. It should be noted that the expression of K19, present in
many simple epithelial tissues including the bile ducts, is not present in adult
hepatocytes and therefore characterizes the cells of the biliary tract. The
nucleus of hepatocytes is usually very voluminous and spherical, contains one or
more obvious nucleoli and constitutes 5-10% of cell volume. 20% of hepatocytes
are binucleated, and about 15% have a tetraploid kit. Under normal conditions,
adult liver cells rarely enter mitosis; in regenerative processes, however,
mitosis can be numerous.
Cellular organelles have a rather precise cytoplasmic location, linked to
specific cellular functions. The endoplasmic reticulum (REL) is presented in its
two forms, smooth and wrinkled, while free ribosomes (polyribosomes) are also
abundantly distributed in the cytoplasm. The number and extent of the canaliculi
and cisterns of the endoplasmic reticulum of the hepatocyte are subject to
continuous variations that reflect the different dynamic functional engagement
of the organ. The endoplasmic reticulum constitutes 15% of the cell volume, with
a surface 35 times greater than that of the plasma membrane. The rough
endoplasmic reticulum (RER) predominantly dominates the smooth reticulum (REL);
the relationship between the two types varies according to the physiological
state and the position of the hepatocytes in the grape: the surface of the
smooth reticulum is double in zone 3 compared to zone 1 of the berry.
Parenchymal cells of the ligand are grouped in concentric areas in the center of
the portal space, zone 1 is the nearest, while zones 2 and 3 are located more
distally than the afferent blood vessels; the oxygen tension and the level of
the nutrients of the blood are reduced from zone 1 to that 3; the hepatocytes of
zone 1 are, therefore, the first to receive oxygenated blood and the last to be
affected by necrosis; zones 2 and 3 receive blood with oxygen and nutrient
content very vulnerable to the action of liver toxins and to hypoxic lesions (see
hepatic circulation).
A precise topographic relationship was observed between included glycogen and
smooth endoplasmic reticulum membranes; such membranes with their enzymatic kit
(glucose-6-phosphatase) can contribute to the process of glycogenolysis followed
by the introduction of glucose into the blood. In addition, the lipids absorbed
by the blood through the vascular pole of the hepatocyte are conveyed into the
smooth endoplasmic reticulum to whose membranes is linked part of the enzymes
responsible for the synthesis of cholesterol and the degradation of many
liposoluble drugs (such as barbiturates). The granular endoplasmic reticulum and
free ribosomes are responsible for the synthesis of plasma proteins produced by
the liver and circulated through the vascular pole of the hepatocytes (albumin,
fibrinogen). The endoplasmic reticulum of hepatocytes also plays an important
role in the assembly of lipoprotein molecules: in the vascular pole, the
hepatocytes free, in the space of Disse, particles called VLDL (very low density
lipoprotein) that appear already inside the tubules of the smooth endoplasmic
reticulum, close to the vascular pole.
index topics of gastroenterology