The liver's functional unit is the lobule: a hexagonal arrangement of hepatocyte cords radiating from six peripheral portal triads (portal vein + hepatic artery + bile duct) inward to a central vein. Blood flows centripetally through sinusoids — portal triad → central vein — while bile flows the opposite way.
dHealth/dt = regen·(1−H) − injury(zone)·H
injury(zone) ∝ toxin · susceptibility(zone), zone 3 (pericentral) > zone 1 (periportal)
dFibrosis/dt = k1·toxin − k2·regen, staged F0 → F4 (cirrhosis)
- Fat load — drives lipid droplet accumulation inside hepatocytes (macrovesicular steatosis, the hallmark of NAFLD).
- Toxin / alcohol exposure — injures hepatocytes preferentially in zone 3 (pericentral), the most hypoxic, CYP450-rich, and vulnerable zone — the classic pattern in alcoholic and drug-induced liver injury.
- Regeneration capacity — hepatocyte turnover rate that restores lost tissue and resists fibrosis; chronic injury outpaces it, allowing collagen septa to bridge portal tracts.
- Blood flow rate — sets the speed of red cells through the sinusoids; normal hepatic blood flow is roughly 25% of resting cardiac output (~1.2–1.5 L/min).
- Scenario presets — healthy liver, fatty liver (NAFLD), steatohepatitis (NASH, fat + inflammation), and cirrhosis (bridging fibrosis, nodules, shunted flow).
Real-world relevance: liver biopsies are staged with this same F0–F4 fibrosis scale (METAVIR/Ishak), and roughly a quarter of adults worldwide now have some degree of NAFLD.