histology of normal liver

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

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Compilation on normal liver histology

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Page 1: Histology of normal liver

LIVERNormal Histology

Rifat Mannan,MDMount Sinai St.-Luke’s Roosevelt Hospital Center, New York

Page 2: Histology of normal liver

Anatomy • Second-largest

organ of the body and the largest gland, weighing about 1-1.5 kg.

• Comprises 2% of body weight.

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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

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Ligaments of the liver

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PORTA HEPATIS

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Blood Supply

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

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Lobes of the liver How many?

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Two large lobes

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Two smaller lobes

CAUDATE LOBE

QUADRATE LOBE

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Riedel’s lobe

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Couinaud segments

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

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Cantlie’s line

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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.

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Histologicalstructure

of the liver

Stroma Parenchyma

Connective tissue capsule

TrabeculaeReticular network

Hepatocytes Blood vessels Bile ducts

Hepatic microarchitecture

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CONCEPT of ‘HEPATIC LOBULES’

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c

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Sublobular vein

Central vein

Portal triad

CLASSIC HEPATIC LOBULE

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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

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Classic lobule

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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.

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Liver lobule (contd..)

• The blood flows from periphery to centre.

• Bile flows from centre to periphery.

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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.

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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.

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Zone 1: close to the blood vessels Zone 2: intermediat zoneZone 3: adjacent to central vein

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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.

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Hepatocytes and bile canaliculi

The hepatocytes are arranged in one- cell layer thick plates separated by sinusoids

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Reticulin stain, normal liver

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HEPATOCYTES

• Polyhedral cells having one or two spherical nuclei with well developed nucleoli.

• Constitutes 80% of liver volume.

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centrally located, round, and contains one or more nucleoli

Hepatocyte nucleus

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Regeneration

Neonatal hepatitis

Multinucleated hepatocytes

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CYTOPLASM

• Abundant eosinophilic • Contains fine basophilic granules representing

RER • Cytoplasmic glycogen is present

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MITOCHONDRIA

GLYCOGEN GRANULES

CYTOPLASM

- SER, RER, many mitochondria, lysosomes and well-developed Golgi apparatus, - features indicating a high metabolic activity. - Glycogen granules and lipidvacuoles are usually prominent.

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PAS PAS with diastase

CYTOPLASMIC CONTENTS……???

GLYCOGEN

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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.

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Iron pigment

In periportal hepaticytes

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Copper

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Bile pigment

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Apoptotic cellaka Councilman body

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GROUND GLASS HEPATOCYTE

HBsAg +ve

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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.

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• Bile canaliculi form a chicken wire like network in the center of the hepatic plates

• Can be demonstrated polyclonal CEA /CD10

Bile canaliculus

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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.

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Sinusoidal lining cells

• Sinusoids are slit like spaces separating cords of hepatocytes

• Lined by endothelial cells, Kupffer cells and reticulin fibers

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sinusoids

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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

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Space of Disse

Kupffer cell

Space of disse

Space between hepatocytes and sinusoidal lining cellsZone of intercellular exchangecontains plasma, scanty connective tissue , and perisinusoidal cells such as hepatic stellate cells (Ito cells, interstitial fat-storing cells, or hepatic lipocytes) and pit cells.

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Prominent in autopsy liver

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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

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

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Prominent Ito cell in hypervitaminosis A

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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 .

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Pit cells

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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.

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• 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

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Fibrosis in pericapsular region; normal

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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,

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Normal

Primary Sclerosing Cholangitis

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• 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

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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 .

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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)

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Piecemeal necrosis in Chronic hepatitis

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Special stains in liver biopsy

• Masson’s trichrome:- To demonstrate fibrous tissue

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Orcein/ Victoria blue

• (HBsAg), elastic fibers, and copper-binding protein

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D-PAS

• glycoproteins, including alpha-1-antitrypsin inclusions , ceroid in macrophages

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Reticulin

Normal

HCC

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Iron

PRUSSIAN BLUE

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Hep Par-1

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CK18 CAM5.2

CKAE1/AE3

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CK7/CK19

Other negative stains:EMA, vimentin, AFP

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CK 7 positivity in transformed hepatocytes

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Bile canaliculi

pCEA/CD10

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CD34

HCCNormal liver

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Glutamine synthetase

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