Human Physiology, 14th edition (2016)

Respiratory Physiology 557

low P^ O 2 (so ventilation is increased at a high altitude, for exam-

ple) and is decreased by a high P^ O 2. If the blood P^ O 2 is raised

by breathing 100% oxygen, therefore, the breath can be held

longer because the response to increased P^ CO 2 is blunted.

When the blood P^ CO 2 is held constant by experimental tech-

niques, the P^ O 2 of arterial blood must fall from 100 mmHg to

below 70 mmHg before ventilation is significantly stimulated

( fig. 16.30 ). This stimulation—called a hypoxic drive —is appar-

ently due to a direct effect of P^ O 2 on the carotid bodies. The carotid

bodies contain neuron-like glomus cells and glia-like susten-

tacular cells. In response to hypoxia, the glomus cells become

depolarized, which opens voltage-sensitive Ca^2 1 channels in the

plasma membrane. The entry of Ca^2 1 stimulates the release of

neurotransmitters and leads to an increase in ventilation.

The carotid bodies respond to the oxygen dissolved in

the plasma (as measured by the blood P^ O 2 ), not to the oxy-

gen bound by hemoglobin in the red blood cells. Because this

degree of hypoxemia, or low blood oxygen, does not normally

occur at sea level, P^ O 2 does not normally exert this direct effect

on breathing.

However, there are interactions between the sensitivities

of the carotid bodies to a fall in P^ O 2 and a rise in P^ CO 2. Hypoxia

(low oxygen) promotes the carotid bodies’ responses to a rise

in arterial P^ CO 2 and fall in pH. This effect becomes important

in the regulation of breathing at higher altitudes with low

P^ O 2 (section 16.9). Indeed, the carotid bodies are essential for

the retention of CO 2 during hypoventilation rapidly stimulates
the peripheral chemoreceptors through a lowering of blood pH.
This is responsible for the immediate response to the elevated
arterial CO 2. Then the central chemoreceptors respond to the
fall in the pH of their surrounding interstitial fluid, stimulating
a steady-state increase in ventilation if the blood CO 2 remains
elevated.

Figure 16.29 How blood CO 2 affects
chemoreceptors in the medulla oblongata. An increase in
blood CO 2 stimulates breathing indirectly by lowering the pH of
blood and brain interstitial fluid. This figure illustrates how a rise
in blood CO 2 increases the H^1 concentration (lowers the pH) of
CSF and interstitial fluid and thereby stimulates chemoreceptor
neurons in the medulla oblongata.

H O

CO

H

HCO

CO

H CO 2

2

2

2

3

3

+

+

Chemoreceptor

neurons

Medulla

oblongata

Brain

interstitial fluid

Cerebrospinal

fluid (CSF)

Blood-CSF

barrier

Capillary

blood

Figure 16.30 Comparing the effects of blood

CO 2 and O 2 on breathing. The graph depicts the effects of

increasing blood concentrations of CO 2 (see the scale at the

top of the graph) on breathing, as measured by the total minute

volume. The effects of decreasing concentrations of blood O 2

(see the scale at the bottom of the graph) on breathing are also

shown for comparison. Notice that breathing increases linearly

with increasing CO 2 concentration, whereas O 2 concentrations

must decrease to half the normal value before breathing is

stimulated.

80

60

40

20

80

60

40

Total minute volume^20

(liters/min)

18 16 14 12 10 8 6 4 2 0

%O 2

%CO 2

12345678910

O 2 varied

(CO 2 constant)

CO 2 varied

(O 2 constant)

CLINICAL APPLICATION

Hypocapnia (low plasma PCO 2 ) due to hyperventilation

causes cerebral vasoconstriction, which results in inade-

quate brain perfusion and hypoxia that can produce diz-

ziness. The hypocapnia of hyperventilation also raises the

blood pH (produces a respiratory alkalosis; section 16.8),

which lowers plasma Ca^2 1. This can result in neuromuscu-

lar irritability and muscle spasms (tetany) in the legs, feet,

and hands. People can raise their plasma PCO 2 and alleviate

these symptoms by breathing into a paper bag, but this

could be dangerous for people hyperventilating because

of asthma or because they have angina and myocardial

infarction.

Effects of Blood PO

2

on Ventilation

Under normal conditions, blood P^ O 2 affects breathing only indi-
rectly by influencing the chemoreceptor sensitivity to changes
i n P^ CO 2. Chemoreceptor sensitivity to P^ CO 2 is augmented by a