Which organ is most at risk of injury from acetaminophen overdose?

Which organ is most at risk of injury from acetaminophen overdose?

• A. Heart
• B. Liver
• C. Lung
• D. Brain

Answer: (B)

The main concept here is that acetaminophen overdose primarily damages the liver. The liver is where most of the drug is metabolized and detoxified. At therapeutic doses, acetaminophen is safely processed through conjugation pathways, but when overdose occurs, those pathways become saturated and more drug is shunted toward the cytochrome P450 system, generating a toxic metabolite called NAPQI. NAPQI is normally neutralized by glutathione, but in an overdose, glutathione stores are depleted. With insufficient glutathione, NAPQI binds to cellular proteins and disrupts cellular function, especially in liver cells. This causes oxidative stress and mitochondrial damage, leading to hepatocellular injury and necrosis. The centrilobular zone of the liver (where those detoxifying enzymes are most active) is particularly affected, which is why liver injury can be severe and lead to acute liver failure if not treated promptly. Clinically, you’d see signs of liver injury such as elevated liver enzymes and potential coagulopathy or jaundice. While acetaminophen overdose primarily targets the liver, other organs are not the primary sites of injury from this toxin. Treatments like N-acetylcysteine help by replenishing glutathione stores and reducing damage if given early.

The main concept here is that acetaminophen overdose primarily damages the liver. The liver is where most of the drug is metabolized and detoxified. At therapeutic doses, acetaminophen is safely processed through conjugation pathways, but when overdose occurs, those pathways become saturated and more drug is shunted toward the cytochrome P450 system, generating a toxic metabolite called NAPQI.

NAPQI is normally neutralized by glutathione, but in an overdose, glutathione stores are depleted. With insufficient glutathione, NAPQI binds to cellular proteins and disrupts cellular function, especially in liver cells. This causes oxidative stress and mitochondrial damage, leading to hepatocellular injury and necrosis. The centrilobular zone of the liver (where those detoxifying enzymes are most active) is particularly affected, which is why liver injury can be severe and lead to acute liver failure if not treated promptly.

Clinically, you’d see signs of liver injury such as elevated liver enzymes and potential coagulopathy or jaundice. While acetaminophen overdose primarily targets the liver, other organs are not the primary sites of injury from this toxin. Treatments like N-acetylcysteine help by replenishing glutathione stores and reducing damage if given early.