carotid body chemoreceptors. conversely, carotid body chemoreceptors can be stimulated at higher Po2 levels if Paco2 is increased. The interaction between Po2 and Pco2 at carotid body chemoreceptors is synergistic, so hypoxia and hypercapnia increase the effect of each other as chemoreceptor stimuli. This synergistic, or multiplicative, effect at arterial chemoreceptors is important because it explains the multiplicative effect of Pao2 and Paco2 on ventilation, as described later (see Ventilatory Response to Pao2 section).

The lower panel of Fig. 5 shows the effect of pH and Pco2 on carotid body chemoreceptors. Paco2 changes can affect chemoreceptor activity even if pHa is held constant, and vice versa. Aortic bodies in humans do not respond to pHa changes, and this is one exception to remember about the aortic bodies being qualitatively different from the carotid bodies. Therefore, the carotid bodies are the only chemoreceptors that respond to metabolic changes in pHa when Paco2 is constant.

The mechanism of CO2 and pH sensitivity may be a common response to intracellular pH. Pco2 can diffuse into chemoreceptor cells and cause large changes in intracellular pH to stimulate the cells. Extracellular pH changes in blood cause smaller changes in intracellular pH, consistent with a smaller arterial chemoreceptor response to a metabolic pH change, compared with an equivalent respiratory pH change.

Arterial chemoreceptors respond rapidly within seconds to changes in Pao2, Paco2, and pH. Changes in arterial blood gases that occur in phase with breathing, especially during conditions such as exercise, can be sensed by arterial chemoreceptors and may stimulate ventilation. This rapid response explains how ventilation can be altered within a single breath when arterial blood gases change. carotid body chemoreceptors contain carbonic anhydrase, which will increase the speed of response to Paco2 according to the intracellular pH sensing mechanisms described earlier.

Ventilatory Response to Paco2

In healthy humans under normal resting conditions, Paco2 is the most important stimulus for ventilatory reflexes. Figure 6 shows the ventilatory response to changes in inspired co2 for normal individuals and how the response varies between individuals. The hypercapnic ventilatory response is plotted as expired ventilation versus Paco2, which is a noninvasive measure of the actual physiologic stimulus, i.e., Paco2. Ventilation approximately doubles when Paco2 increases 5 mm Hg above the control value (0% inspired CO2). The average increase in ventilation is about 2 L/(min • mm Hg) over the physiologic range of 40-50 mm Hg Paco2. The two dashed lines in Fig. 6 show the ventilatory response to

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