Expansion
Carbon dioxide is the dominant drive, sensed centrally through cerebrospinal fluid pH
Expansion
Central chemoreceptors in the ventral medulla account for about 80 per cent of the response.
The mechanism turns on membrane permeability:
- Carbon dioxide crosses the blood-brain barrier freely
- Hydrogen ions and bicarbonate do not
- Within cerebrospinal fluid, carbon dioxide is hydrated to carbonic acid, lowering pH and stimulating the receptors
Because cerebrospinal fluid has little protein buffering, its pH changes more sharply than blood pH for a given change in carbon dioxide, making the system very sensitive. Ventilation increases by roughly 2 to 3 litres per minute for each 1 mmHg rise in arterial carbon dioxide.
Two important consequences:
- In chronic hypercapnia, bicarbonate is actively transported into cerebrospinal fluid over 1 to 2 days, normalising its pH and blunting the response; ventilation then depends more on hypoxic drive
- The response is depressed by opioids, benzodiazepines, volatile anaesthetics and sleep, which is the basis of opioid-induced respiratory depression