zone 1

The liver acinus is divided into three functional zones based on blood flow from the portal triad to the central vein: Zone 1 (periportal), Zone 2 (intermediate), and Zone 3 (pericentral/centrilobular). Zone 1 hepatocytes are closest to the terminal branches of the hepatic artery and portal vein, giving them the highest oxygen and nutrient supply.

Clinical significance: Zone 1 is preferentially affected by direct-acting hepatotoxins such as yellow phosphorus and ingested toxins delivered via the portal circulation (e.g., certain phosphorus compounds), because these substances enter first through the portal vein. Zone 1 is also the first area affected in viral hepatitis (periportal inflammation) and in conditions of impaired bile flow (cholestasis) since it's closest to bile ductules.

In contrast to Zone 3 (which is most susceptible to ischemic injury, hypoxia, and metabolic toxins like acetaminophen and CCl4 due to lowest oxygen tension and high concentration of CYP450 enzymes), Zone 1 is more resistant to hypoxic damage but more susceptible to viral hepatitis and toxins absorbed directly from the portal blood.

Zone 1 hepatocytes are also the primary site of gluconeogenesis, beta-oxidation of fatty acids, and cholesterol synthesis, given their oxygen-rich environment favoring oxidative metabolism. This is in contrast to Zone 3, which is more involved in glycolysis, lipogenesis, and drug/xenobiotic metabolism via cytochrome P450 enzymes.

Understanding zonal hepatic anatomy is essential for interpreting patterns of liver injury on biopsy and for predicting which zone will be affected by specific toxins, ischemia, or infections.