Hypoxia sensing in the body: An update on the peripheral and central mechanisms

Abstract An adequate supply of O 2 is essential for the maintenance of cellular activity. Systemic or local hypoxia can be experienced during decreased O 2 availability or associated with diseases, or a combination of both. Exposure to hypoxia triggers adjustments in multiple physiological systems in the body to generate appropriate homeostatic responses. However, with significant reductions in the arterial partial pressure of O 2 , hypoxia can be life‐threatening and cause maladaptive changes or cell damage and death. To mitigate the impact of limited O 2 availability on cellular activity, O 2 chemoreceptors rapidly detect and respond to reductions in the arterial partial pressure of O 2 , triggering orchestrated responses of increased ventilation and cardiac output, blood flow redistribution and metabolic adjustments. In mammals, the peripheral chemoreceptors of the carotid body are considered to be the main hypoxic sensors and the primary source of excitatory feedback driving respiratory, cardiovascular and autonomic responses. However, current evidence indicates that the CNS contains specialized brainstem and spinal cord regions that can also sense hypoxia and stimulate brain networks independently of the carotid body inputs. In this manuscript, we review the discoveries about the functioning of the O 2 chemoreceptors and their contribution to the monitoring of O 2 levels in the blood and brain parenchyma and mounting cardiorespiratory responses to maintain O 2 homeostasis. We also discuss the implications of the chemoreflex‐related mechanisms in paediatric and adult pathologies.