Acetaminophen poisoning

Epidemiology

Leading cause of acute liver failure

Exhaustion of hepatic metabolic pathways causes accumulation of a toxic metabolite of acetaminophen, N-acetyl-p-benzoquinoneimine (NAPQI).
- Glutathione initially inactivates NAPQI, but its reserves are eventually depleted, leading to NAPQI accumulation.
- NAPQI → irreversible oxidative hepatocyte injury → liver cell necrosis
APAP-induced hepatotoxicity
- Defined as peak AST or ALT > 1000 IU/L
- Most commonly caused by APAP overdose
- Occurs rarely at therapeutic doses in patients with:
  - Alcohol consumption
  - Prolonged fasting
  - Chronic liver disease

Feature	Salicylate (ASA) Poisoning	Acetaminophen (APAP) Poisoning	Reye Syndrome
Classic Hx	Overdose (intentional/accidental)	Intentional OD; chronic EtOH use	Child after viral illness + ASA use
Pathophysiology	Uncouples ox-phos; Resp center stim; Direct ototoxicity	Glutathione depletion -> toxic metabolite (NAPQI) -> liver necrosis	Mitochondrial dysfunction -> fatty liver & encephalopathy
Presentation	Tinnitus, fever, hyperventilation, AMS	Asymptomatic initially -> RUQ pain -> fulminant liver failure	Profuse vomiting, delirium/coma, NO jaundice
Key Lab Finding	Mixed resp. alkalosis + metabolic acidosis	Massive AST/ALT elevation (>1000s)	Hyperammonemia, elevated LFTs, hypoglycemia
Antidote / Tx	IV Sodium Bicarbonate, Hemodialysis	N-acetylcysteine (NAC)	Supportive care (manage ICP, hypoglycemia)
Buzzword	"Mixed acid-base disorder"	"Rumack-Matthew nomogram"	"Child + virus + aspirin"

Antidote: PO or IV N-acetylcysteine (NAC) is used to treat and prevent APAP-induced hepatoxicity.
- NAC regenerates glutathione