histology of normal liver
DESCRIPTION
Compilation on normal liver histologyTRANSCRIPT
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