When you hold your breath, which of the following stimulus would first lead to the urge to breathe? 

A chemo-sensitive area is situated adjacent to the rhythm centre as well as the chemoreceptors associated with aortic arch and carotid artery are highly sensitive to CO₂ and H⁺. Increase in CO₂ and H⁺ signal the rhythm centre to make necessary adjustments in the respiratory process by which these substances can be eliminated.