Which organ is most at risk after acetaminophen overdose?

Which organ is most at risk after acetaminophen overdose?

• A. Liver
• B. Kidney
• C. Brain
• D. Stomach

Answer: (A)

Understanding how acetaminophen is processed in the body explains why the liver is at greatest risk with an overdose. Most of the drug is safely metabolized, but a portion is converted by liver enzymes into a toxic compound called NAPQI. Normally, NAPQI is quickly neutralized by glutathione. In an overdose, glutathione stores are overwhelmed and depleted, so NAPQI accumulates and damages liver cells by binding to cellular proteins and causing oxidative injury. The liver is especially vulnerable because it handles most of the drug’s metabolism and contains high activity of the enzymes that produce NAPQI, with the most injury often in the central portion of the liver lobule (where metabolism is high and oxygen is limited). This can lead to hepatocellular necrosis and, if not treated, liver failure. The kidneys can also be affected, but they are not the primary organ damaged in acetaminophen overdose, while brain and stomach injuries are not typical targets.

Understanding how acetaminophen is processed in the body explains why the liver is at greatest risk with an overdose. Most of the drug is safely metabolized, but a portion is converted by liver enzymes into a toxic compound called NAPQI. Normally, NAPQI is quickly neutralized by glutathione. In an overdose, glutathione stores are overwhelmed and depleted, so NAPQI accumulates and damages liver cells by binding to cellular proteins and causing oxidative injury. The liver is especially vulnerable because it handles most of the drug’s metabolism and contains high activity of the enzymes that produce NAPQI, with the most injury often in the central portion of the liver lobule (where metabolism is high and oxygen is limited). This can lead to hepatocellular necrosis and, if not treated, liver failure. The kidneys can also be affected, but they are not the primary organ damaged in acetaminophen overdose, while brain and stomach injuries are not typical targets.