Compilation on normal liver histology

1. LIVER
Normal Histology
Rifat Mannan,MD
Mount Sinai St.-Luke’s Roosevelt Hospital Center, New York

2. Anatomy
• Second-largest
organ of the body
and the largest
gland, weighing
about 1-1.5 kg.
• Comprises 2% of
body weight.

4. Structure
• Liver is completely invested by a fibrous
capsule called
• Glisson’s capsule is thickened at the porta hepatis
and sends trabeculae into the interior dividing the
parenchyma into incomplete lobules.
GLISSON’S CAPSULE

5. Ligaments of the liver

6. PORTA HEPATIS

7. Blood Supply
• Dual blood supply:
Portal vein: 3/4
Hepatic artery:1/4
• Venous outflow:
Hepatic veins: left, right and middle
Drains into IVC

8. Lobes of the liver
How many?

9. Two large lobes

10. Two smaller lobes
CAUDATE LOBE
QUADRATE LOBE

11. Riedel’s lobe

12. Couinaud segments
• 8 ‘functional segments’
• According to vascular supply.
• Each has its own vascular inflow, outflow
and biliary/ lymphatic drainage.

13. Cantlie’s line

15. Clinical significance
• Each segment can be resected without damaging
those remaining.
• For the liver to remain viable, resections must proceed
along the vessels that define the peripheries of these
segments.
• Liver resections [anatomic resections]are done
according to this vascular segments
• The liver has the unique capacity of regeneration, and
will regrow to its original size some 6-12 months after
resection.
• As much as 80% of the liver mass can be removed
safely.

16. Histological
structure
of
the liver
Stroma Parenchyma
Connective
tissue
capsule
Trabeculae
Reticular
network
Hepatocytes Blood vessels Bile ducts
Hepatic microarchitecture

17. CONCEPT of ‘HEPATIC LOBULES’

18. c

20. Sublobular vein
Central vein
Portal triad
CLASSIC HEPATIC LOBULE

21. Classic lobule
• It forms the structural
and functional unit of
the organ
• Hexagonal in shape
• It has a vein at the
centre, the central vein
• Portal tracts in the
periphery

22. Classic lobule

24. Liver lobule (contd..)
• Hepatocytes are
arranged in one call
thick plates radiating
from the central vein
towards the periphery
of the lobule.
• The irregular spaces
between the hepatic
plates are occupied by
liver sinusoids lined
by fenestrated
endothelial cells.

25. Liver lobule (contd..)
• The blood flows from
periphery to centre.
• Bile flows from
centre to periphery.

26. The sinusoids are irrigated by mixed arterial
blood from hepatic artery and venous blood
from portal vein. The blood then flows
towards central vein — sublobar vein —
hepatic vein — IVC.

27. Hepatic acinus
(acinus of Rappaport)
• Another functional unit of liver
• Three poorly defined, concentric regions of
hepatic parenchyma surrounding a
distributing artery in the center.

28. Zone 1: close to the blood vessels
Zone 2: intermediat zone
Zone 3: adjacent to central vein

32. PORTAL LOBULE
- It is defined as the part of the liver parenchyma that drains bile
into the hepatic ductule present at the portal triad.
-It is triangular in shape and can be visualised by drawing imaginary
lines connecting the central veins of three adjacent liver lobules with
portal triad at the centre.

33. Hepatocytes and bile canaliculi
The hepatocytes are arranged in one- cell
layer thick plates separated by sinusoids

34. Reticulin stain, normal liver

35. HEPATOCYTES
• Polyhedral cells having one
or two spherical nuclei with
well developed nucleoli.
• Constitutes 80% of liver
volume.

36. centrally located, round, and contains one or more nucleoli
Hepatocyte nucleus

37. Regeneration
Neonatal hepatitis
Multinucleated hepatocytes

38. CYTOPLASM
• Abundant eosinophilic
• Contains fine basophilic granules representing
RER
• Cytoplasmic glycogen is present

39. MITOCHONDRIA
GLYCOGEN GRANULES
CYTOPLASM
- SER, RER, many mitochondria,
lysosomes and well-developed
Golgi apparatus,
- features indicating
a high metabolic activity.
- Glycogen granules and lipid
vacuoles are usually prominent.

40. PAS PAS with diastase
CYTOPLASMIC CONTENTS……???
GLYCOGEN

41. Lipofuscin
[lipochrome]
- The wear and tear pigment,
- PAS-positive diastase-resistant,
- In zone 3, particularly at the canalicular pole
-Progressive increase of its amount and in the
number of cells involved in older individuals.

42. Iron pigment
In periportal hepaticytes

43. Copper

44. Bile pigment

45. Apoptotic cell
aka Councilman body

46. GROUND GLASS HEPATOCYTE
HBsAg +ve

47. Bile canaliculus
• An intercellular space with a diameter of
approximately 1µm,
• Formed by the apposition of the edges of
gutterlike hemicanals on adjacent surfaces of
two or three neighboring hepatocytes.

48. • Bile canaliculi form a chicken wire like
network in the center of the hepatic plates
• Can be demonstrated polyclonal CEA /CD10
Bile canaliculus

50. Canals of Hering
• Connect the bile canaliculi to the bile ductules
• Minute bile canaliculi form nets with polygonal meshes in
the hepatic plates.
• Hepatic plates thus enclose a network of canaliculi which
pass to the lobular periphery, where they join to form
narrow intralobular ductules (terminal ductules or the
canals of Hering)
• These enter bile ductules in the portal canals
• The flow of bile is thus towards the periphery of lobules, in
the opposite direction to the blood flow, which is
centripetal.

52. Sinusoidal lining cells
• Sinusoids are slit like spaces separating cords of
hepatocytes
• Lined by endothelial cells, Kupffer cells and
reticulin fibers

53. sinusoids

54. Kupffer cells
• Hepatic macrophages derived from blood monocytes.
• Lie within sinusoidal lumen, attached to endothelial
surface.
• They have a bean-shaped nucleus and plump
cytoplasm with star-shaped extensions . They are more
numerous near the portal tracts.
• These cells respond actively to many types of injury by
proliferation and enlargement.
• They contain vacuoles and, particularly in the diseased
liver, many diastase-resistant PAS (PAS-D) positive
lysosomes and phagosomes, as well as aggregates of
ceroid pigment

56. Space of Disse
Kupffer cell
Space of disse
Space between hepatocytes and sinusoidal lining cells
Zone of intercellular exchange
contains plasma, scanty connective tissue , and perisinusoidal cells
such as hepatic stellate cells (Ito cells, interstitial fat-storing cells, or hepatic lipocytes)
and pit cells.

57. Prominent in autopsy liver

58. Hepatic stellate cells
• Ito cells, perisinusoidal lipocytes
• They are irregular ;lie within the hepatic
plates, between the bases of hepatocytes.
• Difficult to differentiate from sinusoidal lining
cells
• Modified resting fibroblasts that can store fat
and vitamin A

60. Produce hepatocyte growth factor and collagen.
They play a significant role in hepatic fibrogenesis.

61. Prominent Ito cell in hypervitaminosis A

62. Pit cells
• Have not been characterized by light
microscopy.
• Under the electron microscope, they have
neurosecretory-like electron-dense granules
and rod-cored vesicles.
• Recent evidence indicates that pit cells are
not endocrine cells but correspond to the
large granular lymphocytes and have natural
killer cell activity .

63. Pit cells

64. Portal tract
• Each portal tract contains a bile duct and
several bile ductules, a hepatic artery branch,
a portal vein branch, and lymphatic channels
embedded in connective tissue .
• They normally contain a few lymphocytes,
macrophages, and mast cells
• but no polymorphonuclear leukocytes or
plasma cells.

65. • The connective tissue consists mainly of
collagen type I, which is seen as thick, deep
blue fibers on the trichrome stain
• In the subcapsular region of the liver, the
portal tracts contain more and denser
connective tissue.
• must not be interpreted as cirrhosis in wedge
or superficial biopsy specimens of subcapsular
parenchyma

69. Fibrosis in pericapsular region; normal

70. Bile ducts
• The larger intrahepatic or septal bile ducts are
lined by tall columnar epithelial cells
• located in the central part of the portal tracts
and have more periductal fibrous tissue than
the smaller ones.
• The collagen fibers are arranged in an
irregular and circumferential but not
‘concentric”manner,

71. Normal
Primary Sclerosing Cholangitis

72. • The smaller or interlobular bile ducts are lined by cuboidal or low
columnar epithelium.
• They have a basement membrane and a small amount of periductal
connective tissue.
• One or more interlobular ducts may be present in a portal tract.
Interlobular bile ducts

73. Bile ductules
• Located in the peripheral zone of the portal
tracts and are smaller (lumen of less than 20
µm) than the interlobular bile ducts .

74. Limiting plate
• The hepatocytes bordering the portal tracts
are joined together and form a distinct row
called the limiting plate .
• Destruction of this limiting plate by
necroinflammation and/or apoptosis is a
hallmark of chronic hepatitis (piecemeal
necrosis/interface hepatitis)

75. Piecemeal necrosis in
Chronic hepatitis

76. Special stains in liver biopsy
• Masson’s trichrome:
- To demonstrate fibrous tissue

77. Orcein/ Victoria blue
• (HBsAg), elastic fibers, and copper-binding
protein

78. D-PAS
• glycoproteins, including alpha-1-antitrypsin
inclusions , ceroid in macrophages

79. Reticulin
Normal
HCC

80. Iron
PRUSSIAN BLUE

81. Hep Par-1

82. CK18
CAM5.2
CKAE1/AE3

83. CK7/CK19
Other negative stains:
EMA, vimentin, AFP

84. CK 7 positivity in transformed hepatocytes

85. Bile canaliculi
pCEA/CD10

86. CD34
HCC
Normal liver

87. Glutamine synthetase