Maintenance of the Body
this level by an exquisitely sensitive homeostatic mechanism that
is mediated mainly by the eﬀect of rising CO
levels on the central
chemoreceptors of the brain stem
levels rise in the blood, a condition referred to as
accumulates in the brain.
accumulates, it is hydrated to form carbonic acid. Te
acid dissociates, H
is liberated, and the pH drops. Tis is the
same reaction that occurs when CO
enters RBCs (see p. 829).
Te increase in H
excites the central chemoreceptors,
which make abundant synapses with the respiratory regulatory
centers. As a result, the depth and rate of breathing increase.
Tis enhanced alveolar ventilation quickly ﬂushes CO
the blood, raising blood pH.
An elevation of only 5 mm Hg in arterial P
ventilation, even when arterial O
levels and pH haven’t changed.
and pH are below normal, the response to elevated P
is even greater. Increased ventilation is normally self-limiting, end-
ing when homeostatic blood P
levels are restored.
Notice that while rising blood CO
levels act as the initial
stimulus, it is rising levels of H
generated within the brain that
prod the central chemoreceptors into increased activity. (CO
readily diﬀuses across the blood brain barrier between the brain
and the blood, but H
does not.) In the ﬁnal analysis, control
of breathing during rest is aimed primarily at
regulating the H
concentration in the brain
is an increase in the rate and depth of breath-
ing that exceeds the body’s need to remove CO
. A person expe-
riencing an anxiety attack may hyperventilate involuntarily. As
they blow oﬀ CO
, the low CO
levels in the blood (
constrict cerebral blood vessels. Tis reduces brain perfusion,
producing cerebral ischemia that causes dizziness or fainting.
Earlier symptoms of hyperventilation are tingling and invol-
untary muscle spasms (tetany) in the hands and face caused by
levels falling as pH rises.
Te symptoms of hyperventilation may be averted by breath-
ing into a paper bag. Te air being inspired from the bag is ex-
pired air, rich in carbon dioxide, which causes carbon dioxide to
be retained in the blood.
is abnormally low, respiration is inhibited and
becomes slow and shallow. In fact, periods of
cessation) may occur until arterial P
rises and again stimu-
Sometimes swimmers voluntarily hyperventilate so they can
hold their breath longer during swim meets. Tis is danger-
ous. Blood O
content rarely drops much below 60% of normal
during regular breath-holding, because as P
enough to make breathing unavoidable. However, strenuous hy-
perventilation can lower P
so much that a lag period occurs
rebounds enough to stimulate respiration again. Tis
lag may allow oxygen levels to fall well below 50 mm Hg, causing
the swimmer to black out (and perhaps drown) before he or she
has the urge to breathe.
Inﬂuence of P
Te peripheral chemoreceptors—found in
of the aortic arch and in the
at the bifurcation of the common carotid arteries—contain cells
sensitive to arterial O
. Te main oxygen
sensors are in the carotid bodies.
Under normal conditions, declining P
has only a slight ef-
fect on ventilation, mostly limited to enhancing the sensitiv-
ity of peripheral receptors to increased P
. Arterial P
, to at least 60 mm Hg, before O
come a major stimulus for increased ventilation.
Tis is not as strange as it may appear. Remember, there is a
huge reservoir of O
bound to Hb, and Hb remains almost en-
tirely saturated unless or until the P
of alveolar gas and arterial
blood falls below 60 mm Hg. Te brain stem centers then begin
to suﬀer from O
starvation, and their activity is depressed. At
the same time, the peripheral chemoreceptors become excited
and stimulate the respiratory centers to increase ventilation,
return to normal
Central chemoreceptors in
brain stem respond to H
in brain ECF (mediate
70% of the CO
in carotid and aortic bodies
(mediate 30% of the CO
in brain extracellular
Changes in P
and blood pH regulate
ventilation by a negative feedback mechanism.