Human Physiology, 14th edition (2016)

556 Chapter 16

chemoreceptors. Carbon dioxide in the arterial blood can cross

the blood-brain barrier and lower the pH of cerebrospinal fluid

(CSF) and brain interstitial fluid ( fig.  16.29 ). Also CO 2 pro-

duced by brain metabolism can contribute to the lower pH of

the interstitial fluid.

The chemoreceptors in the medulla are ultimately respon-

sible for 70% to 80% of the increased ventilation that occurs

in response to a sustained rise in arterial P^ CO 2. This response,

however, takes several minutes. The immediate increase in

ventilation that occurs when P^ CO 2 rises is produced by stimula-

tion of the peripheral chemoreceptors.

Peripheral Chemoreceptors

The aortic and carotid bodies are not stimulated directly by

blood CO 2. Instead, they are stimulated by a rise in the H^1

concentration (fall in pH) of arterial blood, which occurs when

the blood CO 2 (and thus carbonic acid) is raised. In summary,

For these reasons, the blood P^ CO 2 and pH are more immedi-
ately affected by changes in ventilation than is the oxygen content.
Indeed, changes in P^ CO 2 provide a sensitive index of ventilation, as
shown in figure  16.27. Changes in plasma P^ CO 2 also serve as the
most potent stimulus for the reflex control of ventilation, providing
precise negative feedback regulation. Ventilation, in other words,
is adjusted to maintain a constant P^ CO 2 proper oxygenation of the
blood occurs naturally as a side product of this reflex control.
The rate and depth of ventilation are normally adjusted to
maintain an arterial P^ CO 2 of 40 mmHg. Hypoventilation causes
a rise in P^ CO 2 —a condition called hypercapnia. Hyperventila-
tion, conversely, results in hypocapnia. Chemoreceptor regula-
tion of breathing in response to changes in P^ CO 2 is illustrated in
figure 16.28.

Chemoreceptors in the Medulla

The chemoreceptors most sensitive to changes in the arterial
P^ CO 2 are located on the ventrolateral surface of the medulla
oblongata, near the exit of the ninth and tenth cranial nerves.
The neurons here are sensitive to pH, but the exact identity of
the central chemoreceptors and the mechanisms involved are
still not fully understood. There are several sites on the ventral
medulla where a fall in pH elicits an increase in ventilation.
An increase in arterial P^ CO 2 causes a rise in the H^1 con-
centration of the blood as a result of increased carbonic acid
concentrations. The H^1 in the blood, however, cannot cross the
blood-brain barrier, and thus cannot influence the medullary

Figure 16.27 The relationship between total minute
volume and arterial PCO 2. These are inversely related: when the
total minute volume increases by a factor of 2, the arterial PCO 2
decreases by half. The total minute volume measures breathing,
and is equal to the amount of air in each breath (the tidal
volume) multiplied by the number of breaths per minute. The PCO 2
measures the CO 2 concentration of arterial blood plasma.

Hypoventilation

Hyperventilation

Normal

ventilation (PCO 2 = 40 ± 2)

Arterial P

CO

(mmHg) 2

Total minute volume (L/min)

0

10

20

30

40

50

60

70

80

2468

Figure 16.28 Chemoreceptor control of

breathing. This figure depicts the negative feedback control

of ventilation through changes in blood PCO 2 and pH. The blood-

brain barrier, represented by the gold box, allows CO 2 to pass

into the brain interstitial fluid but prevents the passage of H^1.

Sensor

Integrating center

Effector

Decreased ventilation

Increased arterial PCO 2

Plasma CO 2 Blood pH

Blood

Brain Peripheral

chemoreceptors

in aortic and

carotid bodies

Sensory

Central neurons

chemoreceptors

in medulla oblongata

Respiratory center

in medulla oblongata

Spinal cord

motor neurons

Respiratory

muscles

Increased ventilation

Negative

feedback

pH of

interstitial fluid