FIGURE 7 Ventilatory response to hypoxia plotted as a function of Pao2 (~Pao2 in these normal subjects). Nonisocapnic curve: Paco2 decreases when hypoxia stimulates increases in ventilation. Normo-capnic curve: Hypoxic ventilatory response is increased if Paco2 is held constant, by adding CO2 to inspired gas. Hypercapnic curve: The ventilatory response to increased Paco2 and decreased Pao2 is greater than the sum of the individual stimuli, as explained in the text. (After Loeschke et al, Pflug Arch Ges Physiol 1958;267: 460.)

ventilatory response is explained completely by arterial chemoreceptor stimulation. In fact, patients with both of their carotid bodies removed have no hypoxic ventilatory response.

Figure 7 illustrates the important interactions that occur between Pao2 and Paco2 as ventilatory stimuli. The lower response curve shows a normal ventilatory response to hypoxia where Paco2 is decreasing as a result of hypoxic ventilatory stimulation. This noniso-capnic hypoxic ventilatory response would occur, for example, during exposure to progressively higher altitudes. As Pao2 decreases below 60 mm Hg, the arterial chemoreceptors are stimulated and cause a small increase in ventilation. This decreases Paco2 and, thereby, ventilatory drive from central and arterial chemoreceptor stimulation. The net effect on ventilation is the result of stimulation by hypoxia and inhibition from decreased Paco2 (i.e., 37 mm Hg). As Pao2 decreases more, hypoxic ventilatory stimulation increases, and this causes further reductions in Paco2. Ventilation remains a compromise between hypoxic stimulation and hypocapnic inhibition on the noniso-capnic hypoxic ventilatory response.

In contrast, if Paco2 is held constant during hypoxia, for example, by increasing inspired Pco2, then the hypoxic ventilatory response is increased. This is shown on the middle normocapnic curve in Fig. 7. Although this curve is normocapnic, in the sense of maintaining Paco2 at a normal value (42 mm Hg in this case), note that it is not the normal hypoxic ventilatory response;

hypoxic stimulation of ventilation normally decreases Paco2, as shown on the nonisocapnic curve. The increase in ventilation between the nonisocapnic and normocapnic curves is explained by the removal of hypocapnic inhibition and reflects the pure excitatory response to hypoxia.

Increasing Paco2 above normal reveals a synergistic interaction between Pao2 and Paco2. On Fig. 7, the pure effect of increasing Paco2 from 42 to 48 mm Hg equals the change in ventilation between the normocapnic and hypercapnic curves, at least at high Pao2 levels when there is no hypoxic stimulation. This 6 mm Hg increase in Paco2 causes ventilation to increase, equaling 16 L/min at Pao2 =140 mm Hg. The independent effect of decreasing Pao2 from 140 to 60 mm Hg equals the increase in ventilation along the normocapnic curve, which is about 10 L/min in Fig. 7. The combined effect of hypercapnia and hypoxia equals the increase in ventilation between the normocapnic and hypercapnic curves as Pao2 decreases from 140 to 60 mm Hg. The combined effect equals 42 L/min, which is greater than the sum of the individual effects (26 L/min). Therefore, the Pao2-Paco2 interaction is said to be synergistic, or multiplicative. The physiologic advantage of this multiplicative effect is that combined hypoxia and hypercap-nia, which usually occur together with physiologic or pathologic limitations of gas exchange, increases ventilation more than either stimulus could alone.

The time course of the ventilatory response to changes in Pao2 begins within a single breath of breathing a low o2 mixture, as expected, given the rapid response of arterial chemoreceptors. If hypoxemia persists for several minutes, ventilation may show a decrease relative to the acute increase but this varies between individuals. This secondary decrease in ventilation occurs when hyperventilation decreases Paco2, which induces slower changes in ventilation (see Venti-latory Response to Paco2 section). However, even when Paco2 is held constant, this secondary decrease in ventilation is observed, and it involves a process called hypoxic ventilatory decline. The physiologic mechanism of hypoxic ventilatory decline is not known yet. The time course of the ventilatory response to hours to years of hypoxia (at altitude) are considered in the Integrated Ventilatory Responses section.

Getting to Know Anxiety

Getting to Know Anxiety

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