A patient is brought in with bright cherry-red lividity, nausea, headache and a blood carboxyhaemoglobin (COHb) level of 40%. Which intracellular mechanism MOST directly explains the cellular hypoxia in CO poisoning beyond simple displacement of O2 from haemoglobin?
- A CO competitively inhibits carbonic anhydrase, reducing CO2 transport
- B CO triggers massive norepinephrine release causing vasoconstriction
- C CO increases 2,3-DPG levels, shifting the oxygen dissociation curve rightward
- D CO binds cytochrome c oxidase (Complex IV), directly inhibiting mitochondrial electron transport ✓
Explanation
Beyond displacing O2 from haemoglobin (left-shift of ODC), CO binds to haem-containing intracellular proteins—most critically cytochrome c oxidase (Complex IV of the mitochondrial electron transport chain)—directly inhibiting oxidative phosphorylation and causing histotoxic hypoxia independent of the haemoglobin effect. This explains why cellular damage can exceed that predicted by COHb levels alone. CO does not inhibit carbonic anhydrase, nor does it cause sympathomimetic vasoconstriction; it actually decreases 2,3-DPG-mediated oxygen offloading by the left-shifting effect.
Reference: The Essentials of Forensic Medicine and Toxicology (Narayan Reddy), 34th ed.
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Written and medically reviewed by the StethoPrep medical team.