Overview

Share of liver volume≈80%

Diameter≈20–30 µm

Hepatocytes measure about 20–30 µm and are often binucleate or polyploid. Their organelles reflect their range of work: abundant rough ER for plasma proteins, smooth ER for drug metabolism, lipid and steroid synthesis and glucuronidation, numerous mitochondria, peroxisomes, a large Golgi, and stores of glycogen and lipid.

They are polarised in three directions. The sinusoidal (basolateral) surface faces the space of Disse, carries microvilli, takes up solutes and secretes proteins and lipoproteins into the blood. The lateral surfaces join neighbouring cells through junctions. The canalicular (apical) surface forms the bile canaliculi, sealed by tight junctions. Here ATP-dependent pumps export bile components: BSEP for bile salts, MRP2 for conjugated bilirubin and other organic anions, MDR3 for phosphatidylcholine, and ABCG5/8 for cholesterol.

Hepatocytes live for months and rarely divide. After injury or resection, however, they rapidly re-enter the cell cycle, which is the basis of liver regeneration.

Anatomy

Histology: Polygonal eosinophilic cells with central round nuclei, prominent nucleoli and granular cytoplasm, arranged in plates. They stain PAS-positive for glycogen.

Function

Synthesises plasma proteins (albumin, clotting factors, transport and acute-phase proteins) and lipoproteins.
Glucose homeostasis (glycogen, gluconeogenesis); fatty-acid oxidation and ketogenesis.
Ammonia detoxification by the urea cycle.
Bile acid synthesis and bile secretion; bilirubin conjugation (UGT1A1).
Biotransformation of drugs, hormones and toxins (CYP450, conjugation).
Stores glycogen, iron, copper, vitamin B12 and fat-soluble vitamins.

Clinical significance

Liver enzymes

Hepatocellular injury releases ALT (more liver-specific) and AST. An AST:ALT ratio above 2 suggests alcohol. ALP and GGT rise mainly in cholestasis. Albumin and prothrombin time reflect synthetic function.

Inherited bilirubin disorders

Gilbert syndrome is mildly reduced UGT1A1 activity, causing mild unconjugated jaundice with fasting or illness; it is benign. Crigler–Najjar syndrome is absent (type I) or severely reduced (type II) UGT1A1, with a risk of kernicterus. Dubin–Johnson syndrome is an MRP2 defect causing conjugated hyperbilirubinaemia and a black liver.

Steatotic liver disease

Triglyceride accumulates in hepatocytes when lipid input exceeds oxidation and VLDL export (metabolic syndrome, alcohol). It can progress to steatohepatitis, fibrosis and cirrhosis.

Test yourself

In paracetamol overdose, hepatocyte necrosis is concentrated in which zone of the hepatic acinus?

Zone 1 (periportal)
Zone 2 (intermediate)
Zone 3 (centrilobular)
Equally in all zones

Answer: Zone 3 (centrilobular)

Zone 3 has the most CYP2E1, which makes the toxic metabolite NAPQI, and the least oxygen. It is therefore hit first by paracetamol, ischaemia and venous congestion ("nutmeg liver").