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Liver and intrahepatic bile ducts-nontumor

Normal histology

Reviewers: Komal Arora, M.D. (see Reviewers page)
Revised: 27 June 2012, last major update April 2012
Copyright: (c) 2004-2012, PathologyOutlines.com, Inc.

General
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● Size of structures varies according to closeness to hepatic hilum

Acini

General
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● Hemodynamic model of hepatic microanatomy that explains centrilobular necrosis
● A concept, not an identifiable microscopic structure; triangular (spherical) area
● Base is terminal twigs of hepatic artery and portal vein

Diagram
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Acini

Bile canaliculi

General
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● Drain bile from hepatocytes to portal space
● 1-2 micron wide areas between neighboring hepatocytes, formed by grooves in plasma membranes and separated from vascular space by tight junctions
● Intracellular actin and myosin filaments surrounding the canaliculi, propel secreted biliary fluid along canaliculi into canals of Hering, the terminal tributaries of the bile duct system (low cuboidal epithelium), to interlobular bile ducts (more robust cuboidal epithelium)
● Connected to bile ducts by cholangioles (bile ductules), usually not visible unless distended by bile
● Highlighted by CEA which stains biliary glycoprotein I in canalicular membrane (cross reacting substance)

Micro images
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Bile canaliculi between hepatocytes


Silver stain shows network of canaliculi radiating away from central vein of lobule

Electron microscopy images
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Bile canaliculi (BC), MV=microvilli

Bile ducts (intrahepatic)

General
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● Develop from primitive hepatocytes of periportal limiting plate

Micro description
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● Cuboidal cells with mildly basophilic cytoplasm and single nuclei

Micro images
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Normal bile ducts

Positive stains
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● CK7, CK 8/18, CK 19

Bile ductules

General
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● Also called ductular cells, cholangioles
● Converge from hepatic lobule onto portal tract and connect bile canaliculi to the interlobular bile ducts
● Represent the most proximal portion of the bile drainage pathway with a cholangiocyte lining
● Usually not seen in normal liver
● Proliferate in pathologic conditions, and can differentiate into hepatocytes to repopulate a destroyed liver

General
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● Small ovoid cells lying singly at periphery of portal tract or as strings within the lobule; not accompanied by artery

Micro images
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Bile ductules due to chronic hepatitis C

           
Bile ductules due to focal nodular hyperplasia (H&E, CK7)


Bile ductules (CK7+) due to sarcoidosis

Positive stains
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● CK7, CK8, CK18, CK19, HLA-DR

Central veins

General
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● Also called terminal hepatic venules (NOT terminal hepatic vein)
● Found at center of hepatic lobule
● Smallest component of venous outflow tract, merge to form hepatic veins, then empty into inferior vena cava

Micro images
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Single vein at center of lobule

Hepatocytes

General
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● Polygonal cells 25-30 microns, arranged in three dimensional plates that radiate away from central vein towards portal tracts
● Two cells thick in children ages 0-5 years; one cell thick at age 5 years or more
● Lined by sinusoids on two sides in which blood flows from portal space to central vein
● Also have biliary and lateral surfaces (for attachment to adjacent hepatocytes)
● Cells are uniform with abundant granular and eosinophilic cytoplasm with scattered fat vacuoles, glycogen and lipofuscin (prominent in centrilobular hepatocytes, increases with age); have central round to oval nuclei, but nuclei may be pleomorphic and multiple (all mononuclear at birth, 10% binuclear at 8 years, 15% at 15 years, 25% in adults)
● Hepatocytes are continuously renewed with proliferation near portal space and death near central vein at 50-300 days
● Mitotic figures are rare

Micro images
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Hepatocytes

Positive stains
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● CK 8/18, CAM 5.2, HepPar1

EM image
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Various images

Kupffer cells

General
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● Attached to endothelium in space of Disse
● Phagocytic cells that are part of reticuloendothelial system; triangular or star shaped with bean-shaped nuclei and clear to granular cytoplasm
● Proliferate and enlarge in response to hepatocyte damage
● Degrade hemoglobin to unconjugated bilirubin
● Contain ceroid pigment, PAS+ diastase resistant granules that represent degraded cellular debris

Micro images
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Kupffer cells


PAS diastase

Positive stains
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● Macrophage markers (lysozyme, CD68)

Limiting plate

General
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● Encircling ring around portal tracts formed by lamina propria of hepatocytes immediately abutting the portal tract
● Disrupted by inflammation with hepatocellular death (piecemeal necrosis)

Micro images
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Normal portal tract with bile duct, hepatic arteriole, portal venule, and clearly defined limiting plate (arrows)


Chronic hepatitis shows destruction of limiting plate by inflammatory cells extending from portal tract into periportal parenchyma with necrosis/apoptosis of hepatocytes

Lobules

General
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● Traditional model of hepatic microanatomy
● 1-2 mm hexagonal area with a central terminal hepatic venule (also called central vein) and 3-6 portal tracts at periphery
● Centrilobular zone surrounds central vein and periportal zone adjoins portal tract
● Zone 1 is closest to vascular supply/portal tract, zone 3 is closest to central vein, is called centrilobular area, is furthest from arterial blood and most prone to vascular insults

Micro images
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Diagrams

   
Lobule with central vein


Portal vein dye injection highlights lobule and blood flow towards not visible central vein

Portal triad / portal tract

General
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● Contains intrahepatic bile ducts, branches of hepatic artery, branches of portal vein
● 70-80% of arteries are normally accompanied by bile ducts
● Normally contains small numbers of lymphocytes and macrophages and occasional mast cells and eosinophils
● No neutrophils or plasma cells normally
● Row of hepatocytes around portal tract is ductal plate (limiting plate), contains stem cells responsible for bile duct growth and development
● Bile ducts are lined by cuboidal epithelium
● Portal tracts are more fibrotic in subcapsular zone

Micro image
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Diagrams


Portal tract

Reticulum

General
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● Collagen fibers in space of Disse, stain black with silver impregnation, produced by Ito cells
● Forms supporting framework of hepatocytes
● If present, even necrotic liver can regenerate
● If damaged, liver heals with fibrosis and possibly cirrhosis

Micro image
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Reticulin stain

Sinusoids

General
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● Interposed between hepatic plates, carry arterial/venous blood to terminal hepatic vein, lined by fenestrated and discontinuous endothelial cells and Kupffer cells, which demarcate an extrasinusoidal space of Disse into which hepatocyte microvilli protrude
● Endothelial cells lack a basement membrane and lack the endothelial markers of larger vessels

Micro images
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Sinusoids


Endothelial cells of sinusoid (PAS diastase)

Negative stains
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● von Willebrand Factor, CD34, Ulex europaeus

Electron microscopy images
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Sinusoids

Stellate cells

General
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● Also called Ito cells
● Fat containing hepatic stellate cells of mesenchymal origin in space of Disse
● Not normally seen on routine H&E sections
● Activated after injury and transformed into myofibroblasts with liver fibrosis and inflammation
● Store and metabolize Vitamin A
● May become laden with fat in hypervitaminosis A

Micro image
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Fat stain


Stellate cell (Ito cell) lipidosis

Positive stains
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● Smooth muscle actin, desmin

End of Liver and intrahepatic bile ducts-nontumor > Normal histology

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