Histology of the liver-Maha Hammady.pptx

LIVER HISTOLOGY
PART 2
By/ Maha Hammady Hemdan
MBBCh- MMSc - Faculty of Medicine, Alexandria University. 2015

BLOOD VESSELS OF
THE PARENCHYMA

BLOOD VESSELS OF THE PARENCHYMA
4
Blood flow trough the classical hepatic lobule
• The larger interlobular vessels branch into distributing vessels that are located at the periphery of
the lobule. These distributing vessels send inlet vessels to the sinusoids
• the blood flows centripetally toward the central vein (CV), also termed “terminal hepatic
venule”
• CV empties into a sublobular vein.
• Several sublobular veins converge to form larger hepatic veins that empty into the inferior vena
cava.
Eroschenko VP. Atlas of histology with functional correlations.
13th ed. Philadelphia: Lippincott Williams & Wilkins; 2017
Pawlina W, Ross MH. Histology: A text and atlas, international edition: With
correlated cell and molecular biology: Wolters Kluwer Law & Business; 2019

6
The Portal Tract
Standring S. Gray'sanatomy: The anatomical
basis of clinical practice. 42th ed. Philadelphia:
Elsevier; 2020
• The portal tract is a small area found at the periphery of a liver lobule. Covered by connective
tissue sleeve which is continuous with the connective tissue of the porta hepatis.

7
The Portal Tract
• It typically consists of three main structures:
1-Branch of the portal vein: The lumen is much larger than that of the artery associated with it.
2-Branch of the hepatic artery: Th e structure of the hepatic artery is like that of other arteries (i.e.,
it has a thick muscular wall).
3-branch of the bile duct: lined by simple cuboidal epithelium.
• The term "portal triad" is commonly used in anatomy to refer to a specific arrangement of structures in the
liver. In reality, the hepatic portal triad is not always comprised of just three structures. It often
includes additional components such as lymphatic vessels, nerves, and small branches of other blood
vessels. Therefore, the term "portal triad" fails to capture the full extent of the structures present in this
region.
Eroschenko VP. Atlas of histology with functional correlations. 13th ed. Philadelphia: Lippincott Williams & Wilkins; 2017

8
The Portal Tract
Young B, O'Dowd G, Woodford P. Wheater's functional histology. 7th edition ed. New York: Elsevier; 2022

9
The Portal Tract
Ovalle WK, Nahirney PC. Netter’s essential histology. 3rd ed. Philadelphia: Elsevier; 2020

10
The Portal Tract
Misdraji J. Embryology, anatomy, histology, and developmental anomalies of the liver. Sleisenger and
fordtran's gastrointestinal and liver disease. 11th ed: Elsevier; 2020. p. 1201-6. e1.

THE HEPATIC SINUSOIDS
12
The Hepatic sinusoids
• sinusoidal capillaries (sinusoids), are vascular channels between the plates of hepatocytes.
• The blood vessels of the portal triads send distributing branches along the sides of the lobule, and these
branches open into the hepatic sinusoids.
Pawlina W, Ross MH. Histology: A text and atlas, international edition: With correlated cell and molecular biology: Wolters
Kluwer Law & Business; 2019

13
• The hepatic sinusoids are characterized by a thin and discontinuous endothelium,
with a basal lamina that is also discontinuous, particularly in larger areas where it
is absent.
• One distinctive feature of hepatic sinusoids is the presence of stellate sinusoidal
macrophages, known as Kupffer cells, which are a regular component of the vessel
lining. These Kupffer cells are part of the mononuclear phagocytic system and
originate from monocytes.
• Through scanning electron microscopy (SEM) and transmission electron
microscopy (TEM), it is evident that Kupffer cells contribute to the lining of the
sinusoid, contrary to earlier beliefs that they resided solely on the luminal surface
of endothelial cells.
• Although the processes of Kupffer cells may overlap with endothelial cells, they
do not form junctions with them.
• Furthermore, these Kupffer cell processes often extend across the sinusoidal lumen
and can even partially obstruct it.
Fig. 2. Scanning microscopy of a Kupffer cell
in the sinusoid. The cell
extends several microvilli or pseudopodia on
its surface. 3000
Naito, M., Hasegawa, G., Ebe, Y. et
al. Differentiation and function of Kupffer
cells. Med Electron Microsc 37, 16–28 (2004).
https://doi.org/10.1007/s00795-003-0228-x

14
Carl von Kupffer and a scanning electron micrograph demonstrating a Kupffer cell (KC) from rat liver. Because activated cells
appear ruffled (K), Carl von Kupffer called them sternzellen (‘star cells’) but everyone since then has called them Kupffer
cells. S, sinusoid; h, hepatocyte. Images obtained from the Clending History of Medicine Library (http://clendening.kumc.edu)
and from Lemasters et al., Ann Rev Pharmacol Toxicol 1997; 37: 327–38.
Bilzer, M., Roggel, F. and Gerbes, A.L. (2006), Role of Kupffer cells in host defense and liver disease. Liver International, 26:
1175-1186. https://doi.org/10.1111/j.1478-3231.2006.01342.x

15

16
Gartner L. Cell biology and histology. 8th ed. New York: Wolters
Kluwer; 2019

17
Fig. 1. Kupffer cell in rat liver. The cell adheres to the surface of endothelial cells and possesses several lysosomes and an ingested
erythrocyte(R) in the cytoplasm. Perfusion fixation. 10 000
Naito, M., Hasegawa, G., Ebe, Y. et al. Differentiation and function of Kupffer cells. Med Electron Microsc 37, 16–28 (2004).
https://doi.org/10.1007/s00795-003-0228-x

18
Gartner L. Cell biology and histology. 8th ed. New York: Wolters Kluwer; 2019

19

21
The Space of Disse (perisinusoidal space)
• This space lies between the
endothelial lining of the hepatic
sinusoids and the hepatocytes,
forming a crucial interface within
the liver lobule. It contains plasma,
and the microvilli of the
hepatocytes are projecting into it.
• It is also filled with a loose network
of reticular fibers, or collagen
fibrils. These elements provide
structural support.
• Ito cells (hepatic stellate cells)
reside within the perisinusoidal
space and play pivotal roles in liver
function and pathology. They store
vitamin A in lipid droplets and are
involved in extracellular matrix
remodeling and fibrosis in response
to liver injury.
Pawlina W, Ross MH. Histology: A text and atlas, international edition: With
correlated cell and molecular biology: Wolters Kluwer Law & Business; 2019

22

23

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Localization of Kupffer cells within the hepatic sinusoid in healthy and diseased liver. The Kupffer cell is located to the hepatic
sinusoid and is therefore in close proximity to other cells in the sinusoid, including natural killer (NK) and natural killer T cells
(NKT), as well as the liver sinusoidal endothelial cells (LSEC). Despite the barrier of the LSEC, Kupffer cell products, such as
cytokines, chemokines, reactive nitrogen, and oxygen species, influence the activity of both stellate cells and hepatocytes.
Dixon LJ, Barnes M, Tang H, Pritchard MT, Nagy LE. Kupffer cells in the liver. Compr Physiol. 2013;3(2):785-97.

25

26
Color atlas of cytology, histology, and microscopic anatomy by Wolfgang Kuehnel

LYMPHATIC PATHWAY
28
Lymphatic pathway
Lymphatic drainage from the liver begins in the perisinusoidal space. Plasma remaining in this space flows into the
periportal connective tissue, where a small cavity known as the periportal space (or space of Mall) exists between
the portal canal stroma and the outermost hepatocytes (the limiting plate).
From here, the fluid enters lymphatic capillaries that accompany the components of the portal triad. The lymph
then proceeds through progressively larger vessels, moving in the same direction as bile—away from the
hepatocytes, toward the portal canals, and ultimately reaching the liver hilum.
It is suggested that 80 % or more of hepatic lymph drains into portal lymphatic vessels, while the remainder drains
through sublobular and capsular lymphatic vessels.
Ohtani O, Ohtani Y. Lymph circulation in the liver. Anat Rec (Hoboken). 2008;291(6):643-52.
Tanaka M, Iwakiri Y.
The hepatic lymphatic
vascular system:
Structure, function,
markers, and
lymphangiogenesis.
Cell Mol
Gastroenterol
Hepatol.
2016;2(6):733-49.

LYMPHATIC PATHWAY
29
Lymphatic pathway
“There are spaces or channels which penetrate through the portal limiting plate with collagen fibers, independent
of the blood vessels. In line with early studies by Mall (1901) and Viragh et al. (1978)., these findings indicate that
fluids in the space of Disse pass through the space between limiting plate hepatocytes to enter the space of Mall as
well as through the space around the initial segment of the hepatic sinusoids (or inlet venules). “
“We have examined the ultrastructure of the periportal limiting plate by the KOH-maceration/SEM method
(Ushiki and Ide,1988). KOH-maceration at 60°C for 10 min followed by microdissection under a binocular
microscope exposes the surface of the limiting plate (Ohtani et al.,2003). SEM of the samples shows many
openings of channels extending through the limiting plate (Fig. 5). These openings are generally located in the
areas where three hepatocytes meet. The density of the openings is approximately 1.3 × 103/mm. Undigested
collagen fibers can sometimes be observed to emerge from the channels between limiting plate hepatocytes.
Accidentally fractured limiting plates also show channels containing undigested collagen fibers, which pass
through the limiting plate to connect the space of Disse with the interstitial space of the portal tract (Ohtani et
al.,2003). Thus, it is evident that the space of Disse is in continuity with the interstitial space of the portal tract or
space of Mall through the channels traversing the periportal limiting plate as well as the space along the inlet
venules.”

LYMPHATIC PATHWAY
30
Lymphatic pathway
Scanning electron micrograph
of the rat liver treated with the
KOH-maceration technique,
showing surface view of the
portal tract side of limiting
plate. There are many
openings (arrowheads) of
channels between limiting
plate hepatocytes.

LYMPHATIC PATHWAY
31
Lymphatic pathway
A schematic representation of pathways of fluid and migrating cells such as dendritic cells (Dc) extending from the sinusoids (S)
through the space of Disse, channels in the limiting plate, and interstitial space of the portal tract to portal lymphatic vessels (L).
Arrows indicate the presumable flow direction. C, collagen fibers; iA, interlobular artery; iV, interlobular vein; iB, interlobular bile
duct; F, fibroblast; I, Ito cell (or stellate cell); K, Kupffer cell; N, nerve; PbP, peribiliary capillary plexus; a, afferent vessel of PbP; e,
efferent vessel of PbP.

LYMPHATIC PATHWAY
32
Lymphatic pathway
Fig. 5. Terminal lymphatics of the periportal
area. The thick arrows indicate the possible
lymph flow, coming from the space of Disse
and entering a terminal lymphatic. The
continuity between the space of Disse and
the periportal area is represented by collagen
fibers. I, blood capillary entering the
liver parenchyma; 2, terminal lymph vessel;
3, sinusoid; 4, periportal hepatocyte;
5, space of Disse; 6, space of Mall; 7, collagen
fibers entering the limiting plate; 8, network
of periportal collagen fibers;
9, anchoring filaments
Trutmann M, Sasse D. The lymphatics of the
liver. Anat Embryol (Berl). 1994;190(3):201-9.
.

LYMPHATIC PATHWAY
33
Lymphatic pathway
Scanning electron micrograph of the lymphatic corrosion cast of the rabbit liver. The lymphatic network in the portal tract extends
as far as terminal portal tract. Arrows indicate partially filled sinusoids in the vicinity of the portal tract.

LYMPHATIC PATHWAY
34
Lymphatic pathway
Jeong J, Tanaka M, Iwakiri Y. Hepatic lymphatic vascular system in health and disease. J Hepatol. 2022;77(1):206-18.

THE HEPATOCYTE
36
The Hepatocyte
• Hepatocytes comprise approximately
80% of the liver's cellular population.
• These cells are typically large and
polygonal.
• surfaces face the perisinusoidal space
called the sinusoidal domains.
• others face neighboring hepatocytes and
bile canaliculi called the lateral domain
• Their nuclei, which are often spherical
and large, are situated centrally within
the cell. Many hepatocytes in adult liver
tissue contain two nuclei, while most are
tetraploid.
• Each nucleus contains two or more well-
defined nucleoli.
• Hepatocytes are relatively long-lived
cells compared to those found in other
parts of the digestive system, with an
average lifespan of about 5 months.
• Moreover, they exhibit remarkable
regenerative capacity.
• The cytoplasm of hepatocytes typically
stains acidophilic. Gartner L. Cell biology and histology. 8th ed. New York: Wolters Kluwer; 2019

THE HEPATOCYTE
37
The Hepatocyte
Specific components within the cytoplasm can be
distinguished:
• Many rER and free ribosomes.
• Many sER. Cells in zone 3 have a much richer
sER than those in zone 1.
• numerous mitochondria, ranging from 800 to
1,000 per cell. Cells in zone 3 have nearly twice
as many, but considerably smaller, mitochondria
as hepatocytes in zone 1 of the liver acinus.
• multiple small Golgi complexes. There are as
many as 50 Golgi units and they are
concentrated near the bile canaliculus. they are
believed to be associated with the exocrine
secretion of bile.
• abundant peroxisomes. Hepatocytes have as
many as 200 to 300 peroxisomes per cell.
• deposits of glycogen, which stain positively
with PAS. Liver cells in zone 1display large
clumps of β particles surrounded by sER,
whereas hepatocytes in zone 3 exhibit diffuse
glycogen deposits.
• Lipid droplets of various sizes.
• Lysosomes containing lipofuscin pigment,
partially digested organelles, or myelin figures.
Mescher A. Junqueira’s basic histology text and atlas. 15th ed. new
york: McGraw-Hill Education; 2018

THE HEPATOCYTE
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The Hepatocyte
Eroschenko VP. Atlas of histology with functional correlations. 13th ed. Philadelphia: Lippincott
Williams & Wilkins; 2017

THE HEPATOCYTE
39
The Hepatocyte
Young B, O'Dowd G, Woodford P. Wheater's functional histology. 7th edition ed. New York: Elsevier; 2022

THE HEPATOCYTE
40
The Hepatocyte

THE HEPATOCYTE
41
The Hepatocyte

THE HEPATOCYTE
42
The Hepatocyte
Pawlina W, Ross MH. Histology: A text and atlas, international edition: With correlated cell and molecular
biology: Wolters Kluwer Law & Business; 2019

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