histology of normal liver

LIVERNormal Histology

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

Anatomy • Second-largest

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

• Comprises 2% of body weight.

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

Ligaments of the liver

PORTA HEPATIS

Blood Supply

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

Lobes of the liver How many?

Two large lobes

Two smaller lobes

CAUDATE LOBE

QUADRATE LOBE

Riedel’s lobe

Couinaud segments

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

Cantlie’s line

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.

Histologicalstructure

of the liver

Stroma Parenchyma

Connective tissue capsule

TrabeculaeReticular network

Hepatocytes Blood vessels Bile ducts

Hepatic microarchitecture

CONCEPT of ‘HEPATIC LOBULES’

c

Sublobular vein

Central vein

Portal triad

CLASSIC HEPATIC LOBULE

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

Classic lobule

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.

Liver lobule (contd..)

• The blood flows from periphery to centre.

• Bile flows from centre to periphery.

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.

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.

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

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.

Hepatocytes and bile canaliculi

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

Reticulin stain, normal liver

HEPATOCYTES

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

• Constitutes 80% of liver volume.

centrally located, round, and contains one or more nucleoli

Hepatocyte nucleus

Regeneration

Neonatal hepatitis

Multinucleated hepatocytes

CYTOPLASM

• Abundant eosinophilic • Contains fine basophilic granules representing

RER • Cytoplasmic glycogen is present

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.

PAS PAS with diastase

CYTOPLASMIC CONTENTS……???

GLYCOGEN

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.

Iron pigment

In periportal hepaticytes

Copper

Bile pigment

Apoptotic cellaka Councilman body

GROUND GLASS HEPATOCYTE

HBsAg +ve

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.

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

• Can be demonstrated polyclonal CEA /CD10

Bile canaliculus

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.

Sinusoidal lining cells

• Sinusoids are slit like spaces separating cords of hepatocytes

• Lined by endothelial cells, Kupffer cells and reticulin fibers

sinusoids

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

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.

Prominent in autopsy liver

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

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

Prominent Ito cell in hypervitaminosis A

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 .

Pit cells

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.

• 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

Fibrosis in pericapsular region; normal

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,

Normal

Primary Sclerosing Cholangitis

• 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

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 .

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)

Piecemeal necrosis in Chronic hepatitis

Special stains in liver biopsy

• Masson’s trichrome:- To demonstrate fibrous tissue

Orcein/ Victoria blue

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

D-PAS

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

Reticulin

Normal

HCC

Iron

PRUSSIAN BLUE

Hep Par-1

CK18 CAM5.2

CKAE1/AE3

CK7/CK19

Other negative stains:EMA, vimentin, AFP

CK 7 positivity in transformed hepatocytes

Bile canaliculi

pCEA/CD10

CD34

HCCNormal liver

Glutamine synthetase