CHAPTER 37
Regulation of Respiration 629of the afferent nerve endings. The smooth muscle of pulmo-
nary arteries contains similar O
2
-sensitive K
- channels, which
mediate the vasoconstriction caused by hypoxia. This is in
contrast to systemic arteries, which contain adenosine tri-
phosphate (ATP) dependent K
channels that permit more
K
efflux with hypoxia and consequently cause vasodilation
instead of vasoconstriction.
The blood flow in each 2-mg carotid body is about 0.04
mL/min, or 2000 mL/100 g of tissue/min compared with a
blood flow 54 mL or 420 mL per 100 g/min in the brain and
kidneys, respectively. Because the blood flow per unit of tissue
is so enormous, the O
2
needs of the cells can be met largely by
dissolved O
2
alone. Therefore, the receptors are not stimu-
lated in conditions such as anemia or carbon monoxide poi-
soning, in which the amount of dissolved O
2
in the blood
reaching the receptors is generally normal, even though the
combined O
2
in the blood is markedly decreased. The recep-
tors are stimulated when the arterial P
O 2
is low or when,
because of vascular stasis, the amount of O
2
delivered to the
receptors per unit time is decreased. Powerful stimulation is
also produced by cyanide, which prevents O
2
utilization at the
tissue level. In sufficient doses, nicotine and lobeline activate
the chemoreceptors. It has also been reported that infusion of
K
increases the discharge rate in chemoreceptor afferents,
and because the plasma K
level is increased during exercise,
the increase may contribute to exercise-induced hyperpnea.
Because of their anatomic location, the aortic bodies have
not been studied in as great detail as the carotid bodies. Their
responses are probably similar but of lesser magnitude. In
humans in whom both carotid bodies have been removed but
the aortic bodies left intact, the responses are essentially the
same as those following denervation of both carotid and aor-
tic bodies in animals: little change in ventilation at rest, but
the ventilatory response to hypoxia is lost and the ventilatory
response to CO
2
is reduced by 30%.
Neuroepithelial bodies composed of innervated clusters of
amine-containing cells are found in the airways. These cells
have an outward K
current that is reduced by hypoxia, and
this would be expected to produce depolarization. However,
the function of these hypoxia-sensitive cells is uncertain
because, as noted above, removal of the carotid bodies alone
abolishes the respiratory response to hypoxia.
CHEMORECEPTORS IN THE BRAIN STEM
The chemoreceptors that mediate the hyperventilation pro-
duced by increases in arterial P
CO 2
after the carotid and aortic
bodies are denervated are located in the medulla oblongata and
consequently are called
medullary chemoreceptors.
They are
separate from the dorsal and ventral respiratory neurons and
are located on the ventral surface of the medulla (Figure 37–7).
Recent evidence indicates that additional chemoreceptors are
located in the vicinity of the solitary tract nuclei, the locus cer-
uleus, and the hypothalamus.
The chemoreceptors monitor the H
+
concentration of cere-
brospinal fluid (CSF), including the brain interstitial fluid.
CO
2
readily penetrates membranes, including the blood–
brain barrier, whereas H
+
and HCO
3- penetrate slowly. The
CO
2
that enters the brain and CSF is promptly hydrated. The
H
2
CO
3
dissociates, so that the local H
- concentration rises.
The H
concentration in brain interstitial fluid parallels the
arterial P
CO 2
. Experimentally produced changes in the P
CO 2
of CSF have minor, variable effects on respiration as long as
the H
concentration is held constant, but any increase in spi-
nal fluid H
concentration stimulates respiration. The magni-
tude of the stimulation is proportional to the rise in H
concentration. Thus, the effects of CO
2
on respiration are
mainly due to its movement into the CSF and brain interstitial
fluid, where it increases the H
concentration and stimulates
receptors sensitive to H
.
VENTILATORY RESPONSES TO
CHANGES IN ACID–BASE BALANCEIn metabolic acidosis due, for example, to the accumulation of
acid ketone bodies in the circulation in diabetes mellitus, there
is pronounced respiratory stimulation (Kussmaul breathing).
The hyperventilation decreases alveolar P
CO 2
(“blows off
CO
2
”) and thus produces a compensatory fall in blood H
+
concentration. Conversely, in metabolic alkalosis due, for ex-
ample, to protracted vomiting with loss of HCl from the body,
ventilation is depressed and the arterial P
CO 2
rises, raising the
H
+
concentration toward normal. If there is an increase in
ventilation that is not secondary to a rise in arterial H
+
con-
centration, the drop in P
CO 2
lowers the H
+
concentration be-
low normal
(respiratory alkalosis);
conversely, hypoventilation
that is not secondary to a fall in plasma H
+
concentration
causes
respiratory acidosis.FIGURE 37–7
Rostral (R) and caudal (C) chemosensitive
areas on the ventral surface of the medulla.PonsCCR RVIIV
VIIIIX
X
XIXIIVIPyramid