Foundations · Year 1 · from Foundations
Case 1: Cyanide Poisoning (Electron Transport Chain Inhibition)
Clinical Image
Source: Wikipedia - Cyanide poisoning - CC BY-SA 4.0
Case Presentation
A 45-year-old firefighter is brought to the emergency department after being rescued from a structure fire involving burning synthetic materials. He was found unresponsive inside the building. On arrival, he is obtunded with GCS 8, has cherry-red skin coloration, and is in respiratory distress. Vital signs show heart rate 130, blood pressure 85/50, respiratory rate 28, and oxygen saturation 98% on high-flow oxygen (paradoxically high despite clinical distress). Arterial blood gas reveals severe metabolic acidosis (pH 7.05, lactate 18 mmol/L) with a narrowed arteriovenous oxygen difference. The elevated venous oxygen saturation indicates that tissues cannot extract oxygen despite adequate delivery, a hallmark of histotoxic hypoxia. Cyanide poisoning from smoke inhalation is suspected. He is immediately treated with hydroxocobalamin (Cyanokit), which binds cyanide to form cyanocobalamin (vitamin B12). His mental status rapidly improves, and lactate normalizes over several hours. The mechanism of toxicity is explained: cyanide binds to the ferric (Fe3+) iron in cytochrome c oxidase (complex IV), blocking electron flow to oxygen and halting oxidative phosphorylation throughout the body.
Key Learning Points
- Cyanide irreversibly inhibits cytochrome c oxidase (complex IV) by binding to the heme iron, preventing the final transfer of electrons to oxygen and halting ATP production via oxidative phosphorylation
- Tissues cannot utilize oxygen even though it is abundant, creating histotoxic hypoxia characterized by elevated venous oxygen saturation and severe lactic acidosis
- Hydroxocobalamin is the preferred antidote as it directly binds cyanide; alternatively, nitrites can be used to generate methemoglobin (which binds cyanide), followed by thiosulfate to convert cyanide to thiocyanate for renal excretion