Liver & intrahepatic bile ducts

General

Histology


Editorial Board Member: Raul S. Gonzalez, M.D.
Deputy Editor-in-Chief: Catherine E. Hagen, M.D.
Nicole Leonard, M.D.
Kimberley J. Evason, M.D., Ph.D.

Topic Completed: 11 May 2021

Minor changes: 11 May 2021

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: Liver histology[TI] normal [TIAB]


Nicole Leonard, M.D.
Kimberley J. Evason, M.D., Ph.D.
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Cite this page: Leonard N, Evason KJ. Histology. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livernormalhistology.html. Accessed December 3rd, 2021.
Definition / general
  • Liver is the largest solid organ and is located in the right upper quadrant of the abdomen
Essential features
  • Functional unit is the hepatic lobule, composed of hepatocyte plates surrounding a central vein with portal tracts at the periphery
  • Main cell type is the hepatocyte, which is critical for producing bile and for metabolizing drugs, proteins, fats, carbohydrates and vitamins
  • Biliary epithelial cells (cholangiocytes) line bile ducts, which transport and modify bile
  • Hepatic stellate cells, located in the space of Disse, store vitamin A and become activated and fibrogenic in response to injury
  • Dual blood flow from hepatic artery and portal vein passes through sinusoids and exits the liver via hepatic vein branches
Terminology
  • Hepatic: of or relating to the liver
Physiology
  • Drug metabolism
    • Phase 1 reactions increase polarity and water solubility of compounds through oxidation, reduction and hydrolysis through the cytochrome p450 system
    • Phase 2 reactions create less toxic byproducts through transferase reactions and conjugations
  • Lipid metabolism
    • During prolonged fasting states, free fatty acids (FFAs) produced by lipolysis in adipose tissue are transported to the liver
    • FFAs are beta-oxidized in liver to release ketone bodies to fuel the brain or formed into triglycerides for storage or transportation
  • Carbohydrate metabolism
    • In the fed state, carbohydrates are stored as glycogen in the liver
    • In the fasting state, this glycogen can be broken down for systemic use (glycogenolysis)
    • Lactate, amino acids and glycerol can be converted into glucose (gluconeogenesis)
  • Protein metabolism
    • Ingested proteins are broken down into amino acids to be used throughout the body
    • Excess amino acids are oxidized for energy or converted into glucose, ketone bodies or fat
    • Nitrogen waste products are converted to urea to be excreted in the urine
    • Various proteins are synthesized, including albumin, coagulation factors and fibrinolytic components
  • Bile production (Compr Physiol 2013;3:1035)
    • Bile salts are produced by hepatocytes from cholesterol and conjugated with glycine or taurine, secreted into canaliculi, modified by cholangiocytes and stored and further concentrated in the gallbladder
    • Bile salts returning from the GI tract via the portal vein are actively transported into hepatocytes to be recycled
    • Free bilirubin is taken up by hepatocytes, conjugated to glucuronic acid and secreted with bile
  • Vitamin metabolism
    • Vitamin A storage (hepatic stellate cells)
    • Vitamin D 25-hydroxylation
    • Vitamins A, D, E and K absorption from intestine, which requires bile salts
    • B vitamin uptake, storage and metabolism / conversion
Diagrams / tables

Images hosted on other servers:

Lobule and portal triad

Anatomy and functional segments

Clinical features
  • Metabolic differences among the zones of hepatic lobules influence hepatocytes’ susceptibility to viral infection, drug injury, nonalcoholic fatty liver disease and other insults (Exp Biol Med (Maywood) 2017;242:1605)
Laboratory
  • Aspartate transaminase (AST) and alanine transaminase (ALT) to evaluate potential hepatocyte damage
  • Albumin, coagulation factors, prothrombin time (PT) and partial thromboplastin time (PTT) to evaluate synthetic function
  • Alkaline phosphatase and bilirubin to evaluate the biliary system and excretion
  • Reference: CMAJ 2005;172:367
Gross description
  • Normal weight in adults is 1,400 - 1,600 grams (Am J Surg Pathol 1987;11:709)
  • Can be divided into 4 lobes: right, left, caudate and quadrate
  • Gallbladder (if present) is located on posterior surface of right lobe
  • Dual blood supply (hepatic artery and portal vein) enters at the hilum / porta hepatis on the inferior aspect
  • Peritoneum covers the superior, anterior and lateral surfaces
  • External surface is smooth and red-brown
  • Cut surface is firm and red-brown, with branches of portal vein, hepatic artery, bile ducts and hepatic vein seen throughout
Gross images

Contributed by Michelle Wilkinson, B.S., P.A. (ASCP)
Red-brown cut surface

Red-brown cut surface

Frozen section description
  • Frozen section may be done to evaluate potential donor livers
    • Assess for large and small droplet steatosis, fibrosis and inflammation
    • Sinusoids may appear prominent and mimic steatosis
    • Submitting tissue sample in saline may introduce water artifact mimicking steatosis
  • Reference: J Clin Med Res 2011;3:191
Frozen section images

Contributed by Kimberley J. Evason, M.D., Ph.D.
Frozen section portal tract

Frozen section portal tract

Frozen section central zone

Frozen section central zone

Microscopic (histologic) description
  • Main liver cell types
    • Hepatocytes
      • Arranged in plates 1 - 2 cells thick
      • Polygonal cells with round, centrally located nuclei and abundant eosinophilic cytoplasm with fine basophilic granules; can be pleomorphic and multinucleated
      • May contain fat vacuoles, glycogen or lipofuscin pigment
    • Cholangiocytes (bile duct epithelial cells)
      • Line bile ductules and bile ducts
      • Cuboidal epithelial cells with round, centrally located nuclei
    • Kupffer cells
      • Located in the sinusoids
      • Mononuclear, phagocytic cells (macrophages) that respond to cell injury
      • Bean shaped nucleus with abundant cytoplasm and star shaped cytoplasmic extensions
    • Stellate cells
      • Located in the space of Disse (not normally seen on H&E)
      • Become activated in response to cell injury and differentiate into myofibroblasts
      • Store fat and vitamin A (Physiol Rev 2008;88:125)
    • Endothelial cells
      • Line sinusoids as well as blood vessels
      • Indistinct cytoplasm and small, elongated nuclei
  • Important microscopic features
    • Limiting plate: formed by hepatocytes joining together to form a distinct row around portal tracts
    • Bile canaliculi: intercellular space formed by adjacent hepatocytes (often not well visualized in normal liver unless distended)
    • Sinusoids
      • These separate cords of hepatocytes
      • Lined by endothelial cells and Kupffer cells
    • Space of Disse: space between endothelial cells and hepatocytes (not well visualized on H&E)
    • Central hepatic veins: lined by endothelium; lack valves
    • Portal triad / portal tract:
      • Hepatic artery: lined by endothelium and a thin muscular layer, approximately the same diameter as a bile duct
      • Portal vein: lined by endothelium
      • Bile duct: lined by cuboidal epithelium, approximately the same diameter as a hepatic artery
      • Not every normal portal tract will always show an artery, vein and bile duct; some will show multiple artery or duct faces (Hepatology 1998;28:323)
      • Lymphatics: not normally seen on H&E
      • May contain few lymphocytes, macrophages, mast cells and eosinophils
      • Tend to be more fibrotic in subcapsular zone
  • 2 concepts for describing microscopic architecture
    • Acinus: functional unit centered around portal triad to include surrounding central veins
    • Lobule: functional unit centered around central vein to include surrounding portal triads
      • Periportal zone / zone 1
        • Higher content of oxygen and nutrients
        • Highest metabolic activity
        • Least susceptible to ischemia and toxic injury
      • Midlobular zone / zone 2
      • Centrilobular zone / zone 3
        • Most susceptible to ischemia and toxic injury
Microscopic (histologic) images

Contributed by Kimberley J. Evason, M.D., Ph.D.
Lobule

Lobule

Trichrome

Trichrome

Portal tract

Portal tract

PASD

PASD

Trichrome large portal tract

Trichrome large portal tract

Hepatocytes and sinusoids

Hepatocytes and sinusoids


Central vein

Central vein

Canaliculi

Canaliculi

Reticulin

Reticulin

Kupffer cells

Kupffer cells

Iron

Iron

Cytology description
  • Hepatocytes
    • Polygonal to round cells with abundant dense granular to vacuolated cytoplasm and round, centrally located nuclei with prominent nucleoli
    • Arranged singly in 2 dimensional clusters or trabeculae 2 - 3 cell layers thick
  • Cholangiocytes (bile duct epithelial cells)
    • Cuboidal to columnar cells with scant pale cytoplasm and small, round nuclei with inconspicuous nucleoli
    • Arranged in picket fences with nuclear palisading or monolayered honeycomb sheets
  • Endothelial cells: rarely seen
  • Kupffer cells: rarely seen
  • Reference: Cytojournal 2005;2:7
Cytology images

Contributed by Kimberley J. Evason, M.D., Ph.D.
Benign hepatocytes, Diff-Quik

Benign hepatocytes, Diff-Quik

Benign hepatocytes, Pap

Benign hepatocytes, Pap

Positive stains
Negative stains
Electron microscopy description
  • Kupffer cells, endothelial cells, hepatic stellate cells, sinusoids, bile canaliculi, the space of Disse and intracellular components like mitochondria may be visualized with electron microscopy
  • Limited use diagnostically except in the evaluation of some metabolic disorders
  • References: World J Gastroenterol 2010;16:2851, Compr Physiol 2013;3:1035
Electron microscopy images

Images hosted on other servers:

Endothelium, tangential cut

Bile canaliculus

Board review style question #1

What is the name of the pigment seen in the above image?

  1. Bile
  2. Hemosiderin
  3. Lipofuscin
  4. Melanin
Board review style answer #1
C. Lipofuscin

Comment Here

Reference: Liver normal histology
Board review style question #2
Which of the following tests can be used to evaluate synthetic function of the liver?

  1. Albumin
  2. Alkaline phosphatase
  3. Aspartate transaminase
  4. Bilirubin
Board review style answer #2
A. Albumin

Comment Here

Reference: Liver normal histology
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