Physiology of breathing I

Abstract

Central and peripheral chemoreflexes are the first line of defence against disturbances in arterial blood-gas and acid-base status. Central chemoreceptors (located on the ventral medullary surface and possibly at other brainstem sites) respond to a decrease in intracellular pH by involving M 2 muscarinic receptors. This can result from an increase in arterial CO 2 partial pressures (PCO 2) or cerebral metabolic acidosis (caused by severe hypoxia), but not systemic metabolic acidosis (the blood-brain barrier being impermeable to hydrogen ions (H +)). Peripheral chemoreceptors are located in carotid-body type I cells. They respond to decreases in intracellular O 2 partial pressure (PO 2) and pH (the latter resulting from an increase in arterial PCO 2 or a systemic metabolic acidosis), whose effects potentiate each other. Hypoxia acts through O 2-sensitive potassium channels, and H + through sodium-dependent calcium (Ca 2+) influx; increased intracellular [Ca 2+] elicits exocytotic neurotransmitter release and excitation of carotid sinus nerve afferents. Brainstem regions (e.g. dorsal respiratory group) process afferent chemosensory inputs to influence respiratory rhythm generation (possibly in the preBötzinger complex) and the magnitude and timing of the final motor output (in the ventral respiratory group) to respiratory-muscle motoneurons and ventilation. Central chemoreflex responsiveness is estimated as the slope of the relationship between ventilation and alveolar (or arterial) PCO 2 using progressive CO 2 rebreathing against a hyperoxic background (to inactivate carotid chemoreceptors); and carotid chemoreflex responsiveness as the slope of the relationship between ventilation and arterial O 2 saturation using progressive isocapnic hypoxia (the substitution of O 2 saturation for PO 2 is a simple linearising expedient).