Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 37Regulation of Respiration 635

unit of blood and the pulmonary blood flow per minute are in-

creased. The PO 2 of blood flowing into the pulmonary capil-

laries falls from 40 to 25 mm Hg or less, so that the alveolar–

capillary PO 2 gradient is increased and more O 2 enters the

blood. Blood flow per minute is increased from 5.5 L/min to as

much as 20 to 35 L/min. The total amount of O 2 entering the

blood therefore increases from 250 mL/min at rest to values as

high as 4000 mL/min. The amount of CO 2 removed from each

unit of blood is increased, and CO 2 excretion increases from

200 mL/min to as much as 8000 mL/min. The increase in O 2

uptake is proportional to work load, up to a maximum. Above

this maximum, O 2 consumption levels off and the blood lac-

tate level continues to rise (Figure 37–13). The lactate comes

from muscles in which aerobic resynthesis of energy stores

cannot keep pace with their utilization, and an oxygen debt is

being incurred.

Ventilation increases abruptly with the onset of exercise,

which is followed after a brief pause by a further, more gradual

increase (Figure 37–14). With moderate exercise, the increase

is due mostly to an increase in the depth of respiration; this is

accompanied by an increase in the respiratory rate when the

exercise is more strenuous. Ventilation abruptly decreases

when exercise ceases, which is followed after a brief pause by a

CLINICAL BOX 37–3

Periodic Breathing in Disease

Cheyne–Stokes Respiration
Periodic breathing occurs in various disease states and is
often called Cheyne–Stokes respiration. It is seen most
commonly in patients with congestive heart failure and
uremia, but it occurs also in patients with brain disease and
during sleep in some normal individuals. Some of the pa-
tients with Cheyne–Stokes respiration have increased sen-
sitivity to CO 2. The increased response is apparently due to
disruption of neural pathways that normally inhibit respira-
tion. In these individuals, CO 2 causes relative hyperventila-
tion, lowering the arterial PCO 2. During the resultant apnea,
the arterial PCO 2 again rises to normal, but the respiratory
mechanism again overresponds to CO 2. Breathing ceases,
and the cycle repeats.
Another cause of periodic breathing in patients with car-
diac disease is prolongation of the lung-to-brain circulation
time, so that it takes longer for changes in arterial gas ten-
sions to affect the respiratory area in the medulla. When in-
dividuals with a slower circulation hyperventilate, they
lower the PCO 2 of the blood in their lungs, but it takes
longer than normal for the blood with a low PCO 2 to reach
the brain. During this time, the PCO 2 in the pulmonary capil-
lary blood continues to be lowered, and when this blood
reaches the brain, the low PCO 2 inhibits the respiratory area,
producing apnea. In other words, the respiratory control
system oscillates because the negative feedback loop from
lungs to brain is abnormally long.

Sleep Apnea
Episodes of apnea during sleep can be central in origin;
that is, due to failure of discharge in the nerves producing
respiration, or they can be due to airway obstruction (ob-
structive sleep apnea). This can occur at any age and is
produced when the pharyngeal muscles relax during sleep.
In some cases, failure of the genioglossus muscles to con-
tract during inspiration contributes to the blockage; these
muscles pull the tongue forward, and when they do not
contract the tongue falls back and obstructs the airway.
After several increasingly strong respiratory efforts, the pa-
tient wakes up, takes a few normal breaths, and falls back
to sleep. Not surprisingly, the apneic episodes are most
common during REM sleep, when the muscles are most hy-
potonic. The symptoms are loud snoring, morning head-
aches, fatigue, and daytime sleepiness. When severe and
prolonged, the condition apparently causes hypertension
and its complications. In addition, the incidence of motor
vehicle accidents in sleep apnea patients is 7 times greater
than it is in the general driving population.

FIGURE 37–13 Relation between work load, blood lactate

level, and O 2 uptake. I–VI, increasing work loads produced by in-

creasing the speed and grade of a treadmill on which the subjects

worked. (Reproduced with permission from Mitchell JH, Blomqvist G: Maximal

oxygen uptake. N Engl J Med 1971;284:1018.)

FIGURE 37–14 Diagrammatic representation of changes in

ventilation during exercise. See text for details.

4

3

2

1

0

Rest I II III IV V VI

0

3

6

9

12

Maximal

work loads

Work load

Submaximalwork loads

Blood lactate

Blood lactate (meq/L)

O 2 uptake

O

uptake (L /min) 2

Rest Exercise Recovery

Time

Ventilation (L/min)