zone 3
Summary
Zone 3 refers to the perivenous/centrilobular region of the hepatic lobule, located closest to the central vein and farthest from the portal triad's oxygenated blood supply. It is the most metabolically active zone (rich in cytochrome P450 enzymes) and thus most susceptible to ischemic injury, toxin-mediated damage, and drug-induced hepatotoxicity.
Detail
The liver is functionally divided into three zones based on the rappaport (or acinar) model of blood flow from the portal triad to the central vein. Zone 1 (periportal) receives oxygen-rich blood first and is involved in oxidative metabolism, gluconeogenesis, and is most resistant to ischemia but most susceptible to viral hepatitis and ascending cholangitis. Zone 2 (midzonal) is intermediate. Zone 3 (centrilobular/perivenous) is farthest from the blood supply, receiving the least oxygenated blood, making it the most vulnerable to hypoxia/ischemia (e.g., in shock, right heart failure causing centrilobular congestion and 'nutmeg liver'). Zone 3 contains the highest concentration of cytochrome P450 enzymes, making it the primary site of drug and toxin metabolism—and consequently the most susceptible to toxin/drug-induced injury, such as acetaminophen overdose, carbon tetrachloride toxicity, and halothane hepatitis. It is also the first area affected in alcoholic hepatitis and the site of fatty change progression in steatohepatitis. Yellow fever characteristically causes midzonal necrosis, an exception to typical zonal patterns. Understanding zonal hepatic pathology is high-yield for correlating clinical scenarios (ischemia vs. toxin exposure vs. infection) with the pattern of liver injury seen on histology.
Sources
- Robbins and Cotran Pathologic Basis of Disease
- Goljan Rapid Review Pathology
- First Aid for the USMLE Step 1
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