Table of Contents
Definition / general | Essential features | Terminology | Physiology | Diagrams / tables | Clinical features | Laboratory | Gross description | Gross images | Frozen section description | Frozen section images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Electron microscopy description | Electron microscopy images | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Leonard N, Evason KJ. Histology. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/livernormalhistology.html. Accessed May 29th, 2023.
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
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
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
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
- Hepatocytes
- 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
- Periportal zone / zone 1
Microscopic (histologic) images
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
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
Additional references
Board review style question #1
Board review style answer #1
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