CHAPTER 37Regulation of Respiration 631occur lowers the alveolar PCO 2 , and this also tends to inhibit
respiration. Therefore, the stimulatory effects of hypoxia on
ventilation are not clearly manifest until they become strong
enough to override the counterbalancing inhibitory effects of a
decline in arterial H+ concentration and PCO 2.
The effects on ventilation of decreasing the alveolar PO 2
while holding the alveolar PCO 2 constant are shown in Figure
37–10. When the alveolar PCO 2 is stabilized at a level 2 to 3
mm Hg above normal, there is an inverse relationship
between ventilation and the alveolar PO 2 even in the 90 to 110
mm Hg range; but when the alveolar PCO 2 is fixed at lower
than normal values, there is no stimulation of ventilation by
hypoxia until the alveolar PO 2 falls below 60 mm Hg.
EFFECTS OF HYPOXIA ON THE CO 2
RESPONSE CURVE
When the converse experiment is performed—that is, when
the alveolar PO 2 is held constant while the response to varying
amounts of inspired CO 2 is tested—a linear response is ob-
tained (Figure 37–11). When the CO 2 response is tested at dif-
ferent fixed PO 2 values, the slope of the response curve changes,
with the slope increased when alveolar PO 2 is decreased. In oth-
er words, hypoxia makes the individual more sensitive to in-
creases in arterial PCO 2. However, the alveolar PCO 2 level at
which the curves in Figure 37–11 intersect is unaffected. In the
normal individual, this threshold value is just below the normal
alveolar PCO 2 , indicating that normally there is a very slight but
definite “CO 2 drive” of the respiratory area.
EFFECT OF H
+
ON THE CO 2 RESPONSEThe stimulatory effects of H+ and CO 2 on respiration appear
to be additive and not, like those of CO 2 and O 2 , complexly in-
terrelated. In metabolic acidosis, the CO 2 response curves are
similar to those in Figure 37–11, except that they are shifted to
the left. In other words, the same amount of respiratory stim-
ulation is produced by lower arterial PCO 2 levels. It has been
calculated that the CO 2 response curve shifts 0.8 mm Hg to the
left for each nanomole rise in arterial H+. About 40% of the
ventilatory response to CO 2 is removed if the increase in arte-
rial H+ produced by CO 2 is prevented. As noted above, the re-
maining 60% is probably due to the effect of CO 2 on spinal
fluid or brain interstitial fluid H+ concentration.BREATH HOLDING
Respiration can be voluntarily inhibited for some time, but
eventually the voluntary control is overridden. The point at
which breathing can no longer be voluntarily inhibited is
called the breaking point. Breaking is due to the rise in arterial
PCO 2 and the fall in PO 2. Individuals can hold their breath
longer after removal of the carotid bodies. Breathing 100%
oxygen before breath holding raises alveolar PO 2 initially, so
that the breaking point is delayed. The same is true of hyper-
ventilating room air, because CO 2 is blown off and arterial
PCO 2 is lower at the start. Reflex or mechanical factors appear
to influence the breaking point, since subjects who hold their
breath as long as possible and then breathe a gas mixture low
in O 2 and high in CO 2 can hold their breath for an additional
20 s or more. Psychological factors also play a role, and sub-
jects can hold their breath longer when they are told their per-
formance is very good than when they are not.FIGURE 37–10 Ventilation at various alveolar PO 2 values
when PCO 2 is held constant at 49, 44, or 37 mm Hg. Note the
dramatic effect on the ventilatory response to PO 2 when PCO is
increased above normal. (Data from Loeschke HH and Gertz KH.)
010203040506020 40 60 80 100 120 140Ventilation (L /min, BTPS)PAO 2 (mm Hg)PACO 249PACO 244PACO 237FIGURE 37–11 Fan of lines showing CO 2 response curves at
various fixed values of alveolar PO 2. Decreased PAO 2 results in a
more sensitive response to PACO 2.Ventilation (L /min BTPS)40 502505075100PAO 2100PAO 255PAO 240PACO 2 (mm Hg)