Primary Chemical Driver of Breathing: Arterial PCO₂

The most potent stimulus for increasing respiratory rate and depth is a rise in arterial partial pressure of carbon dioxide (PaCO₂).

Central chemoreceptors in the medulla respond to CO₂-induced pH changes in cerebrospinal fluid. Peripheral chemoreceptors (carotid/aortic bodies) also respond to low PaO₂ and low pH, but CO₂ is the dominant daily regulator.

Clinical relevance: CO₂ retention (e.g., COPD) blunts this drive; O₂ therapy can worsen hypercapnia in some patients.