Respiratory Physiology
473
Of the two sets of receptors involved in this refl ex response
to elevated
P
CO
2
, the central chemoreceptors are the more
important, accounting for about 70 percent of the increased
ventilation.
It should also be noted that the effects of increased
P
CO
2
and decreased
P
O
2
not only exist as independent inputs to the
medulla but potentiate each other’s effects. The acute ventila-
tory response to combined low
P
O
2
and high
P
CO
2
is consider-
ably greater than the sum of the individual responses.
Throughout this section, we have described the stimula-
tory effects of carbon dioxide on ventilation via refl ex input
to the medulla, but very high levels of carbon dioxide actu-
ally
inhibit
ventilation and may be lethal. This is because such
concentrations of carbon dioxide act directly on the medulla
to inhibit the respiratory neurons by an anesthesia-like effect.
Other symptoms caused by very high blood
P
CO
2
include severe
headaches, restlessness, and dulling or loss of consciousness.
Control by Changes in Arterial H
+
Concentration
That Are Not Due to Changes in Carbon Dioxide
We have seen that retention or excessive elimination of carbon
dioxide causes respiratory acidosis and respiratory alkalosis,
respectively. There are, however, many normal and pathologi-
cal situations in which a change in arterial H
+
concentration is
due to some cause other than a primary change in
P
CO
2
. This is
termed
metabolic acidosis
when H
+
concentration is increased
and
metabolic alkalosis
when it is decreased. In such cases,
the peripheral chemoreceptors play the major role in altering
ventilation.
For example, the addition of lactic acid to the blood, as in
strenuous exercise, causes hyperventilation almost entirely
by stimulation of the peripheral chemoreceptors (
Figures
13–38
and
13–39
). The central chemoreceptors are only
minimally stimulated in this case because brain H
+
concentra-
tion is increased to only a small extent, at least early on, by the
hydrogen ions generated from the lactic acid. This is because
hydrogen ions penetrate the blood-brain barrier very slowly.
In contrast, as described earlier, carbon dioxide penetrates the
blood-brain barrier easily and changes brain H
+
concentration.
The converse of the previous situation is also true: When
arterial H
+
concentration is lowered by any means other than
by a reduction in
P
CO
2
(for example, by the loss of hydrogen
ions from the stomach when vomiting), ventilation is refl exly
depressed because of decreased peripheral chemoreceptor
output.
The adaptive value such refl
exes have in regulating arte-
rial H
+
concentration is shown in Figure 13–39. The increased
ventilation induced by a metabolic acidosis reduces arterial
P
CO
2
, which lowers arterial H
+
concentration back toward nor-
mal. Similarly, hypoventilation induced by a metabolic alkalo-
sis results in an elevated arterial
P
CO
2
and a restoration of H
+
concentration toward normal.
Notice that when a change in arterial H
+
concentration
due to some acid unrelated to carbon dioxide infl uences ven-
tilation via the peripheral chemoreceptors,
P
CO
2
is displaced
from normal. This is a refl ex that regulates arterial H
+
concen-
tration at the expense of changes in arterial
P
CO
2
. Maintenance
Minute ventilation (L/min)
40
42
44
46
2.5
5.0
10.0
15.0
Plasma [H
+
] (nmol/L)
Normal resting level
(pH)
(7.4)
(7.33)
Figure 13–38
Changes in ventilation in response to an elevation of plasma hydrogen
ion concentration produced by the administration of lactic acid.
Adapted from Lambertsen.
Figure 13–39
Refl exly induced hyperventilation minimizes the change in arterial
hydrogen ion concentration when acids are produced in excess in
the body. Note that under such conditions, arterial
P
CO
2
is refl exly
reduced below its normal value.
Alveolar
P
CO
2
Return of arterial [H
+
]
toward normal
Arterial
P
CO
2
Ventilation
Respiratory muscles
Contractions
Peripheral chemoreceptors
Firing
Arterial [H
+
]
Production of non-CO
2
acid
Reflex via medullary
respiratory neurons
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