1. Histology of The Liver and
Gall Bladder
By
Hanaa Said
Under Supervision of
Prof.Dr. Fadia Khalid

2. The Liver

3. Anatomy of the liver
The liver is the
second-largest organ
of the body and the
largest gland,
weighing about 1-1.5
kg.
It is situated in the
abdominal cavity
beneath the
diaphragm.

4. Anatomy of the liver
It is divided anatomically by deep
grooves into:
Two large lobes (the right and left
lobes)and
Two smaller lobes ( the quadrate
and caudate lobes).

5. Exocrine function
Endocrine function

6. • It produces most of the
circulating plasma proteins
(albumins,VLDL,glycoproteins,
• prothrombin and fibrinogen).
• It stores and converts several
vitamins(A,D and K) and iron.
• It degrades drugs and toxins by
oxidation then conjugation.

7. Liver Physiology
It secretes bile.
It modifies structure and function
of many hormones:
-Thyroxine
-Growth hormone.
-Insulin and glucagon.

8. Vascular Supply
•The liver has a dual blood supply,
receiving oxygenated blood from the
left hepatic artery and the right
hepatic artery (25%) and nutrientrich blood via the portal vein (75%).
Both vessels enter the liver at the
porta hepatis.

9. Vascular Supply
•Along the length of each slender
branch of the hepatic artery within
the portal area, fine branches,
known as distributing arterioles,
arise; like outstretched arms, they
reach toward their counterparts in
the neighboring portal areas.
Smaller vessels,

10. Vascular Supply
known as inlet arterioles, branch from
the distributing arterioles (or from the
parent vessel).
•In addition, the interlobular bile ducts
are vascularized by a peribiliary
capillary plexus.
•Venules are of two sizes: the larger
distributing veins and

11. Vascular Supply
the smaller inlet venules.
•The longitudinal axis of each classical
lobule is occupied by the central vein,
Hepatocytes radiate, from the central
vein, forming anastomosing, plates of
hepatocytes, separated from each other
by as hepatic sinusoids. Inlet
arterioles,

12. Vascular Supply
inlet venules, and branches from the
peribiliary capillary plexus pierce the
limiting plate to join the hepatic
sinusoids. As blood enters the
sinusoids, its flow slows considerably
and it slowly percolates into the central
vein.
•As the central vein leaves the lobule,

13. Vascular Supply
it terminates in the sublobular vein.
Numerous central veins deliver their
blood into a single sublobular vein;
• Sublobolar veins join each other to form
collecting veins, which in turn form the
right and left hepatic veins.

14. Vascular Supply
•Blood leaves the liver at the posterior
aspect of the organ through the
hepatic veins, which deliver their
contents into the inferior vena cava.

18. Portal area(Portal triad)

19. Histology of the liver
Histological
structure
of
the liver
Stroma
Connective
tissue
capsule
Trabeculae
Parenchyma
Reticular
network
Hepatocytes
Blood vessels
Bile ducts

20. Liver,
Silver impregnation

21. Liver lobules
The three types of liver lobules are the
classical lobules, portal lobules, and the
hepatic acinus (acinus of Rappaport).
I.Classical liver lobule:
In this concept, blood flows from the
periphery to the center of the lobule into
the central vein. Bile, manufactured by

22. Liver lobules
liver cells, enters into small intercellular
spaces, bile canaliculi, located
between hepatocytes, and flows to
the periphery of the lobule to the
interlobular bile ducts of the portal
areas.
II.Portal lobules

23. Liver lobules
all hepatocytes that deliver their bile to a
particular interlobular bile duct.
III.Hepatic acinus (acinus of
Rappaport) :
It is viewed as three poorly defined,
concentric regions of hepatic parenchyma
surrounding a distributing artery in the

24. Liver lobules
center. The outermost layer, zone 3,
extends as far as the central vein and is
the most oxygen-poor of the three zones.
The remaining region is divided into two
equal zones (1 and 2); zone 1 is the
richest in oxygen.

25. The Three Concepts of Liver
lobules

26. Hepatic Sinusoids and
Hepatocyte Plates
Anastomosing plates of hepatocytes, no
more than two cells thick prior to the age
of 7 years and one cell thick after that
age, radiate from the central vein toward
the periphery of the classical lobule.
The spaces between the plates of
hepatocytes are occupied by hepatic

27. Hepatic Sinusoids and
Hepatocyte Plates
sinusoids, and the blood flowing in these
wide vessels is prevented from coming
in contact with the hepatocytes by the
presence of an endothelial lining
composed of sinusoidal lining cells.
•sinusoidal lining cells have gaps of 0.5

28. Hepatic Sinusoids and
Hepatocyte Plates
µm between them and fenestrae that are
present in clusters,
known as sieve plates.

29. Fenenstrations in hepatic
blood sinusoids

30. Hepatic lobule, human

31. Perisinusoidal space (Space
of Disse´ )
•It lies between the basal surfaces of
hepatocytes and the basal surfaces of
endothelial cells and Kupffer cells.
•Small irregular microvilli project from the
basal surfaces of hepatocytes into this
space to increase surface area for
exchange of materials between
hepatocytes and plasma found in this
space.

32. Perisinusoidal space
(Space of Disse´ )
•This space contains also Ito cells
and reticular fibers supporting
endothelial capillaries.
•In the fetal liver, it contains islands
of blood-forming cells.

34. Kupffer cell
(Stellate macrophages)
•Member of the mononuclear phagocytic
system.
•They form part of the lining of the sinusoid.
•Processes of Kupffer cells often seem to
span the sinusoidal lumen and may partially
occlude it.
•Their cytoplasm contains red cell fragments
and ferritin.

35. Kupffer cell
(Stellate macrophages
Functions:
•They play a role in the final breakdown
of damaged or senile RBCs.
•Remove bacteria and debris that reach
the portal blood from gut and act as APC
in adaptive immunity .

36. Kupffer cells(H&E,
injected with India ink)

37. Kupffer cells and blood
sinusoids

38. Kupffer cell,TEM

39. Ito cells
(Hepatic stellate cells,Fat
storing cells)
- Have a mesenchymal origin.
-Found in the perisunsoidal space.
-They are the primary storage site for
hepaic vitamin A.
-They produce collagen III and growth
factors required by the liver for
proliferation
-In certain pathologic conditions, such as

40. Ito cells
(Hepatic stellate
cells,Fat storing cells)
cirrhosis, they lose their lipid and vitamin
A storage capability and differentiate into
cells with characteristics of
myofibroblasts.
- Ito cells play a role in remodelling the
extracellular matrix during recovery from
liver injury.

41. Ito cells
(Hepatic stellate cells,Fat
storing cells)

42. Hepatocyte,Ito cell and Kupffer
cell

43. Pit cells
(Hepatic NK cells or large
granular lymphocytes)
-They exist in the liver sinusoids and often
adhere to endothelial cells .
-Pseudopodia of pit cells can penetrate the
fenestrae of the endothelial cells, and
enter the space of Disse and can directly
contact the microvilli of hepatocytes.

44. Pit cells
(cont.)
-Most surface
antigens found
on rat pit cells
are similar to
that found on
spleen or
peripheral
blood NK cells.

45. Pit cell and Kupffer cell

46. Hepatocyte

47. Domains of Hepatocyte
Plasmalemma
The plasma membranes of hepatocytes
have two domains: lateral and sinusoidal .
1-lateral domains :
•responsible for the formation of bile
canaliculi.
• have isolated gap junctions

48. Bile canaliculus between
two hepatocytes

49. Bile canaliculus,
freeze fracture

50. Domains of Hepatocyte
Plasmalemma
2-Sinusoidal domains:
form microvilli that protrude into the
perisinusoidal space of Disse´.

51. Hepatocyte
•Forms about 80% of cell population of
the liver.
•Nucleus:
-Central, spherical.
-Most hepatocytes of adult liver are
binucleated .
-has one or 2 nucleoli

52. Hepatocyte
Cytoplasm:
•Generally acidophilic.
•Has basophilic area(RER and free
ribosomes).
•Numerous mitochondria demonstrated by
vital staining and enzyme histochemistry
•Numerous Golgi complexes can be
detected with silver staining.

53. Hepatocyte
•Many peroxisomes detected by
immunocytochemistry.
•Lipid droplets can be demonstrated with
Sudan black.
•Glycogen granules appear as foamy
areas in well preserved H&E sections.

54. Liver ,PAS staining

56. Hepatocyte

57. Hepatocyte
Hepatocytes are large, organelle-rich
cells that manufacture the exocrine
secretion bile as well as a large number
of endocrine secretions; in addition,
these cells can perform a large array of
metabolic functions.

58. Mitochondria
•Each cell contains as many as
2000 mitochondria.
•Cells near the central vein (zone 3
of the liver acinus) have nearly
twice as many, but considerably
smaller, mitochondria as
hepatocytes in the periportal area
(zone 1 of the liver acinus).

59. Mitochondria,TEM

60. Golgi apparatus
•As many as 50 Golgi units may be found
in hepatocyte.
•They are concentrated near the bile
canaliculus.
• Golgi cisternae and vesicles near the
sinusoidal surface contain electron dense
granules that are believed to be VLDL and
other lipoprotein precursors.

61. SER
•Cells in zone 3 of the liver acinus
have a much richer endowment of
SER than those in the periportal
area.
•the presence of certain drugs and
toxins in the blood induces an
increase in the SER content of
liver cells .

62. SER
•They contain enzymes involved in
degradation and conjugation of toxins and
drugs as well as enzymes responsible for
synthesizing cholesterol and the lipid
portion of lipoproteins.

63. SER,TEM

64. Peroxisomes
•Hepatocytes have as many as 200-300
peroxisomes.
•They are relatively large and vary in
diameter from 0.2 to 1.0µm.
•Peroxisomes play important role in the
process of detoxification and breakdown
of fatty acids as well as
gluconeogenesis and metabolism of
purines.

65. Peroxisomes,TEM

66. Lysosomes
In addition to normal lysosomal enzymes
, hepatocyte lysosomes also contain:
-Lipofuscin pigments.
-Partially digested cytoplasmic
organelles.
-Myelin figures.
They are the primary site for iron storage.
Increase in number in a wide variety of
pathologic conditions.

67. Glycogen deposits
•Present as accumulations of electrondense granules 20 to 30 nm in size,
known as β particles, in the vicinity of
the SER.
•Liver cells in the vicinity of the portal
area (zone 1 of liver acinus) display
large clumps of β particles surrounded
by SER.

68. Glycogen deposits
•On the other hand pericentral
hepatocytes (zone 3 of liver
acinus) exhibit diffuse glycogen
deposits.
•They are abundant subsequent
to eating and fewer after fasting.

69. Glycogen deposits,TEM

70. Lipid droplets
•They contain mainly VLDL.
•They increase in numder after fatty
meals.
•Hepatotoxic substances causes
increase of lipid droplets in cells of
zone 3.

71. Multilamellar bodies

72. Tight junctions
Macula adherens

73. Hepatic Ducts
•Bile canuliculi anastomose with one
another, forming labyrinthine tunnels
among the hepatocytes.
•As these bile canaliculi reach the
periphery of the classic lobules, they
merge with cholangioles, short tubules
composed of a combination of
hepatocytes and low cuboidal cells, and
occasional oval cells.

74. Hepatic Ducts
Bile from cholangioles enters the canals of
Hering, slender branches of the
interlobular bile ducts, that radiate
parallel to the inlet arterioles and inlet
venules.
Interlobular bile ducts merge to form
increasingly larger conduits, which
eventually unite to form the right hepatic
duct and the left hepatic duct.

76. Hering canal

77. Histological structure of
hepatic, cystic, and common
bile ducts
Mucosa:
Epithelial lining:
Simple columnar epithelium.
Lamina propria:
Thin.

78. Histological structure of
hepatic, cystic, and
common bile ducts
•Musculosa:
•
Thin layer of smooth muscles
that becomes thicker near the
duodenum and finally, in the
intramural portion, forms a sphincter
that regulates bile flow (sphincter of
Oddi).

79. Bile duct

80. Composition of bile
1. Water.
2. Phosphilipids(i.e.lecithin) and
cholesterol.
3. Bile salts (also called bile acids):
-Primary:cholic acid and
chenodeoxycholic acid.
-Secondary:deoxycholic acid and
lithocholic acid.

81. Composition of bile
4.Bile pigments, principally the
glucuronide of bilirubin produced in
the spleen , bone marrow, and liver
by the breakdown of hemoglobin.
5.Electrolytes:Na+,K+, Ca2+, Mg2+, Cl, and HCO3-.

82. Liver Regeneration
•The liver has a great ability to regenerate
after a hepatotoxic insult or even after a
portion of the liver is excised.
•The mechanism of regeneration is
controlled by
* Transforming growth factor-α
* Transforming growth factor-β

83. Liver Regeneration
* Epidermal growth factor.
* Interleukin-6.
* Hepatocyte growth factor.
•In most cases, the regeneration is due
to the replicative capability of the
remaining hepatocytes;

84. Liver Regeneration
•If the hepatotoxic insult is too
great, regeneration of the liver is due
to the mitotic activity of the oval cells
of cholangioles and canals of Hering.

85. Lymphatic drainage
•Plasma in perisinusoidal space drains
into space of Mall.
•Then it enters lymphatic capillaries.
•The lymph then moves in
progressively larger vessels in the
same direction of bile to the hilum of
the liver then finally into thr thoracic
duct.

86. Gall bladder

87. Anatomy
•Small, pear-shaped
organ situated on the
inferior aspect of the liver.
•10 cm in length and
4 cm in crosssection.

88. Histological Structure
Mucosa:
The mucosa of the empty gallbladder is
highly folded into tall, parallel ridges .
Epithelial lining:
simple columnar epithelium,
composed of two types of cells:
1.the more common clear cells
2. the infrequent brush cells

89. Histological Structure
L.M.:
nucleus:basal oval
Cytoplasm:
Supranuclear cytoplasm contains
occasional secretory granules.
E.M.:
their luminal surface displays short
microvilli coated by a thin layer of
glycocalyx.

90. Histological Structure
The basal region of the cytoplasm
is particularly rich in mitochondria.
Lamina propria:
composed of loose connective
tissue,rich in fenestrated capillaries
and small venules with no lymphatics.
It is rich in elastic and collagen fibers.

91. Histological Structure
In the neck of the gallbladder, the lamina
propria houses simple tubuloalveolar
glands, which produce a small amount of
mucus.
No Muscularis mucosa.
No Submucosa.
Musculosa:
thin, smooth muscle layer, composed

92. Histological Structure
mostly of obliquely oriented fibers,
whereas others are oriented
longitudinally.
Serosa or adventitia:
The hepatic surface is covered by
adventitia, while the remainder of gall
bladder surface is covered by serosa.

93. Gall bladder,H&E

95. Gall bladder,epithial lining

96. Gall bladder , SEM

97. Gall bladder , Colored
SEM

98. Function
•The main function of the gallbladder is to
store bile, concentrate it by absorbing its
water, and release it when necessary into
the digestive tract.
•This process depends on an active
sodium-transporting mechanism in the
gallbladder's epithelium. Water absorption
is an osmotic consequence of the sodium
pump.

99. Function
•Contraction of the smooth muscle
of the gallbladder is induced by
cholecystokinin, a hormone
produced by enteroendocrine cells
located in the epithelial lining of the
small intestine.
•Release of cholecystokinin is, in
turn, stimulated by the presence of
dietary fats in the small intestine.

100. Nerve supply
•Liver and gall bladder are innervated by
both sympathatic and parasympathetic
fibers .
•Nerves enter the liver through porta
hepatis and ramify through the liver in the
portal canals along with members of
portal triad.

101. Nerve supply
Sympathatic fibers innervate blood
vessels, while parasympathatic fibers
Large ducts and possibly blood vessels.