Chemical factors such as changing CO2, O2, and H+ levels in arterial blood play a critical role in influencing respiration depth and rates. These variations are detected by chemoreceptors—specialized sensors located in two primary body areas. Central chemoreceptors are found throughout the brain stem, including the ventrolateral medulla, while peripheral chemoreceptors are located in the aortic arch and carotid arteries.
CO2 has a potent influence on respiration and is strictly regulated. Under normal conditions, the arterial pCO2 is maintained at 40 mm Hg with small fluctuations within 38-42 mm Hg. An increase in PCO2 levels, known as hypercapnia, leads to an accumulation of CO2 in the brain. This CO2 is hydrated to form carbonic acid, which dissociates to liberate H+, causing a drop in pH. This rise in H+ stimulates central chemoreceptors, closely linked with respiratory regulatory centers. The result is an increase in the depth and rate of breathing facilitated by both central and peripheral chemoreceptors. This increased ventilation rapidly eliminates CO2 from the blood, raising the blood's pH. Conversely, when pCO2 is abnormally low, respiration slows and becomes shallow.
Changes in arterial pH can alter the respiratory rate and rhythm, independent of CO2 and O2 levels. If arterial pH falls, the respiratory system attempts to compensate by increasing the respiratory rate and depth to eliminate CO2 from the blood. This process is mediated through the peripheral chemoreceptors, as H+ does not cross the blood-brain barrier.
Peripheral chemoreceptors are sensitive to arterial O2 levels and become the primary driver of respiration when arterial pO2 falls below 60 mm Hg. The peripheral chemoreceptors respond by reflexively increasing ventilation. Although increased ventilation can lead to hypocapnia and an increase in blood pH, which could inhibit respiration, the drive to correct severe hypoxia typically prevails, maintaining elevated ventilation until O2 levels are restored.
