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

New FindingsWhat is the topic of this review?Hypoxia is a life-threatening condition. Specialized sensory mechanisms in the periphery and CNS respond to reduced O2 levels, triggering ventilatory and haemodynamic responses to enhance O2 uptake and delivery to the tissues.What advances does it highlight?Although anatomically distinct, both peripheral and central mechanisms should be considered when examining the homeostatic responses to hypoxia. Herein, we review past and current research on O2 monitoring in the periphery and CNS, discussing how their sensing mechanisms, pathways and interactions modify respiratory and sympathetic activities.AbstractAn adequate supply of O2 is essential for the maintenance of cellular activity. Systemic or local hypoxia can be experienced during decreased O2 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 O2, hypoxia can be life-threatening and cause maladaptive changes or cell damage and death. To mitigate the impact of limited O2 availability on cellular activity, O2 chemoreceptors rapidly detect and respond to reductions in the arterial partial pressure of O2, 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 O2 chemoreceptors and their contribution to the monitoring of O2 levels in the blood and brain parenchyma and mounting cardiorespiratory responses to maintain O2 homeostasis. We also discuss the implications of the chemoreflex-related mechanisms in paediatric and adult pathologies.