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Liver & intrahepatic bile ducts

General

Anatomy & histology

Authors: Nicole Leonard, M.D., Kimberley J. Evason, M.D., Ph.D.

Editorial Board Member: Raul S. Gonzalez, M.D.

Deputy Editor-in-Chief: Catherine E. Hagen, M.D.

Last author update: 11 May 2021

Last staff update: 19 September 2024

Copyright: 2002-2024, PathologyOutlines.com, Inc.

PubMed Search: Liver anatomy & histology

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Table of Contents

Cite this page: Leonard N, Evason KJ. Anatomy & histology. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livernormalhistology.html. Accessed December 2nd, 2024.

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

Embryology

Arises at embryonic junction (septum transversum): where ectoderm of amnion meets endoderm of yolk sac (externally) and where foregut meets midgut (internally); mesenchymal structure of transverse septum provides support so blood vessels and liver can form in underlying splanchnic mesoderm (UNSW Embryology: Gastrointestinal Tract - Liver Development [Accessed 23 October 2017])
Hepatic diverticulum buds from ventral foregut at end of third week, grows into primitive septum transversum
Liver forms from endodermal cells of diverticulum, termed hepatoblasts and mesenchyme
Blood supply primarily from umbilical vein; also portal vein and hepatic artery
Placenta clears wastes in bile and absorbs nutrients
- Umbilical vein blood bypasses liver via ductus venosus
All elements of the biliary tree are recognizable by week 5, although bile duct system is not complete until after birth
- Derived from endoderm (large ducts) and embryonic ductal plate (smaller intrahepatic ducts) (Dig Surg 2010;27:87)
Hematopoietic cells are present in embryonic / fetal liver but absent at term

Physiology

Drug metabolism
- Phase 1 reactions increase polarity and water solubility of compounds via oxidation, reduction and hydrolysis through the cytochrome p450 system
- Phase 2 reactions create fewer 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, 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

Anatomy

See also Gross description
Divided into right and left lobes by Cantlie line projecting between the gallbladder fossa and vena cava and defined by the middle hepatic vein
Right lobe is divided into anterior and posterior segments by right hepatic vein
Left lobe is divided into medial and lateral segments by left hepatic vein
Intrahepatic biliary tree: classified into intrahepatic large bile ducts (grossly visible with fibrous ductal wall and peribiliary glands) and small bile ducts
Regional lymph nodes: hilar, hepatoduodenal ligament, caval

Accessory lobe

May appear clinically as hepatic mass
Anterior abdominal wall defects are frequently associated with accessory hepatic lobes
Can present with torsion (Surg Radiol Anat 2011;33:819)

Diagrams / tables

Images hosted on other servers:

Lobule and portal triad

Anatomy and functional segments

Embryonic hepatic bud formation

Anterior and posterior views

Blood supply

Intrahepatic biliary tree

Anatomy of abdomen

Location of liver

Superior view of liver

Inferior view of liver

Impressions of liver

Cells, ducts, blood vessels

Microscopic anatomy

Types of capillaries

Parts of liver

Hilum of liver

Couinaud segments

Liver and veins

Liver, lobule, portal tract

Biliary tract

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 and exits via the left and right hepatic veins to inferior vena cava
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

Images hosted on other servers:

Liver at autopsy

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.

Portal tract

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 ducts and ductules
  - 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
  - Normal portal tracts will not 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

Trichrome

Portal tract

PASD

Trichrome large portal tract

Hepatocytes and sinusoids

Central vein

Canaliculi

Reticulin

Kupffer cells

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, Pap

Positive stains

Hepatocytes: HepPar1, CAM5.2, CD10 (bile canaliculi), polyclonal CEA (bile canaliculi) (Manual of Surgical Pathology 2006;71)
Cholangiocytes: CK7, CK19, AE1 / AE3
Kupffer cells: CD68
Routine stains:
- Trichrome: highlights collagen fibers to assess and stage fibrosis
- Reticulin: highlights reticulin fibers to assess hepatic plates for expansion or collapse
- Periodic acid-Schiff (PAS): highlights glycogen
- Periodic acid-Schiff with diastase (PASD):
  - Highlights the basement membrane of bile ducts and ductules
  - Stains abnormal alpha-1 antitrypsin globules in hepatocytes in the setting of alpha-1 antitrypsin deficiency
- Iron: aids in evaluating iron deposits in hepatocytes and Kupffer cells

Negative stains

Hepatocytes: CK7, CK19
Cholangiocytes: HepPar1 (J Hepatobiliary Pancreat Sci 2012;19:289)

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

Videos

Development of foregut related to the peritoneum

Liver anatomy (function, topography, external structures, ligaments)

Anatomy of the abdominal viscera: liver, bile ducts and gallbladder

Anatomy dissection of liver

Additional references

Arch Intern Med 1983;143:2291, Arch Pathol Lab Med 2013;137:270, World J Surg Oncol 2004;2:5

Board review style question #1

What is the pigment seen in the image above?

Bile
Hemosiderin
Lipofuscin
Melanin

Board review style answer #1

C. Lipofuscin. Lipofuscin is a finely granular, yellow-brown pigment that is present within hepatocytes. Typically lipofuscin is most prominent in central zones, as seen here. Answer A is incorrect because bile is typically chunkier, has a greener hue and is located within hepatocytes and distending canaliculi. Answer B is incorrect because hemosiderin typically has a darker brown-black hue. Hemosiderin may be seen within hepatocytes or Kupffer cells. When hemosiderin is present within hepatocytes, it is typically most prominent around portal areas, not central zones. Answer D is incorrect because melanin is typically seen in melanocytes / melanoma cells and is not stored or produced by hepatocytes.

Comment Here

Reference: Liver - Anatomy & histology

Board review style question #2

Which of the following tests can be used to evaluate synthetic function of the liver?

Albumin
Alkaline phosphatase
Aspartate transaminase
Bilirubin

Board review style answer #2

A. Albumin. Albumin, coagulation factors, prothrombin time (PT) and partial thromboplastin time (PTT) can be utilized to evaluate synthetic function. Answer C is incorrect because aspartate transaminase (AST), as well as alanine transaminase (ALT) are used to evaluate potential hepatocyte damage. Answers B and D are incorrect because alkaline phosphatase and bilirubin are used to evaluate the biliary system and excretion.

Comment Here

Reference: Liver - Anatomy & histology

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