Regulation of Respiration pdf - Respiration

tory muscles, mainly the diaphragm, is not an instantaneous burst of action

The nervous signal that is transmitted to the inspira-

Inspiratory “Ramp” Signal.

the medulla as well, and is responsible for the basic rhythm of respiration.

neurons is present in the human being, located entirely within the medulla; it

fore, most respiratory physiologists believe that some similar network of

mechanism repeats itself, continuing throughout the life of the animal. There-

a second set, which in turn inhibits the first. Then, after a period of time, the

basic cause of these repetitive discharges is unknown. In primitive animals,

The

inspiratory neuronal action potentials.

and the brain stem transected both above and below the medulla, this group of

of respiration is generated mainly in the dorsal respiratory group of neurons.

The basic rhythm

Rhythmical Inspiratory Discharges from the Dorsal Respiratory Group.

receptors in the lungs.

from (1) peripheral chemoreceptors, (2) baroreceptors, and (3) several types of

sopharyngeal nerves, which transmit sensory signals into the respiratory center

medulla also play important roles in respiratory control. The nucleus of the

tarius,

medulla. Most of its neurons are located within the

The dorsal respiratory group of neurons extends most of the length of the

of Inspiration and of Respiratory Rhythm

fundamental role in the control of respiration. Therefore, let us discuss its func-

and depth of breathing. The dorsal respiratory group of neurons plays the most

located dorsally in the superior portion of the pons, which mainly controls rate

pneumotaxic center,

the medulla, which mainly causes expiration; and (3) the

ventral respiratory group,

inspiration; (2) a

located in the dorsal portion of the medulla, which mainly causes

tory group,

41–1. It is divided into three major collections of neurons: (1) a

and pons of the brain stem, as shown in Figure

The

Respiratory Center

most other types of respiratory stress. This chapter

are hardly altered even during heavy exercise and

The nervous system normally adjusts the rate of

514

Regulation of Respiration

alveolar ventilation almost exactly to the demands
of the body so that the oxygen pressure (Po

) and

carbon dioxide pressure (Pco

) in the arterial blood

describes the function of this neurogenic system for
regulation of respiration.

respiratory center is composed of several groups of neurons located bilat-

erally in the medulla oblongata

dorsal respira-

located in the ventrolateral part of

tion first.

Dorsal Respiratory Group of Neurons—Its Control

nucleus of the tractus soli-

although additional neurons in the adjacent reticular substance of the

tractus solitarius is the sensory termination of both the vagal and the glos-

Even when all the peripheral nerves entering the medulla have been sectioned

neurons still emits repetitive bursts of

neural networks have been found in which activity of one set of neurons excites

probably involves not only the dorsal respiratory group but adjacent areas of

brain stem, sensory nerve signals from the lungs also

during heavy exercise.

pulmonary ventilation are required, especially

Thus, this area operates more or less as an

expiration. They are especially important in

stimulation of others causes expiration. Therefore,

the ventral group causes inspiration, whereas

4. Electrical stimulation of a few of the neurons in

area. As a consequence, the ventral respiratory

normal, respiratory signals spill over into the

3. When the respiratory drive for increased

2. There is no evidence that the ventral respiratory

recoil of the lungs and thoracic cage.

the diaphragm, and expiration results from elastic

respiration. Therefore, normal quiet breathing is

1. The neurons of the ventral respiratory group

caudally. The function of this

ventral respiratory group of neurons,

of neurons, is the

Located in each side of the medulla, about 5 millime-

Functions in Both

Ventral Respiratory Group of

minute.

breaths per minute, whereas a weak pneumotaxic

period of each respiration. A strong pneumotaxic

increasing the rate of breathing, because limitation

to limit inspiration. This has a secondary effect of

The function of the pneumotaxic center is primarily

excess of air.

or more seconds, thus filling the lungs with a great

taxic signal is weak, inspiration might continue for 5

thus filling the lungs only slightly; when the pneumo-

strong, inspiration might last for as little as 0.5 second,

of the lung cycle. When the pneumotaxic signal is

ramp, thus controlling the duration of the filling phase

is to control the “switch-off” point of the inspiratory

the inspiratory area. The primary effect of this center

of the upper pons, transmits signals to

parabrachialis

pneumotaxic center,

Duration of Inspiration and Increases

A Pneumotaxic Center Limits the

expiration. Thus, the frequency of respiration is

of inspiration. This also shortens the duration of

earlier the ramp ceases, the shorter the duration

controlling the rate of respiration; that is, the

This is the usual method for

suddenly ceases.

limiting point at which the ramp

2. Control of the

rapidly.

so that during heavy respiration, the ramp

1. Control of the

are controlled, as follows:

There are two qualities of the inspiratory ramp that

during inspiration, rather than inspiratory gasps.

The obvious advantage of the ramp is that it

ring in between. Thus, the inspiratory signal is a

cycle repeats again and again, with expiration occur-

inspiratory signal begins again for another cycle; this

lungs and the chest wall to cause expiration. Next, the

mately the next 3 seconds, which turns off the excita-

about 2 seconds. Then it ceases abruptly for approxi-

potentials. Instead, in normal respiration, it begins

Chapter 41

Regulation of Respiration

515

weakly and increases steadily in a ramp manner for

tion of the diaphragm and allows elastic recoil of the

ramp

signal.
causes a steady increase in the volume of the lungs

rate of increase of the ramp signal,

increases rapidly and therefore fills the lungs

increased.

the Respiratory Rate

located dorsally in the nucleus

of inspiration also shortens expiration and the entire

signal can increase the rate of breathing to 30 to 40

signal may reduce the rate to only 3 to 5 breaths per

Neurons

—

Inspiration and Expiration

ters anterior and lateral to the dorsal respiratory group

found in the nucleus ambiguus rostrally and the
nucleus retroambiguus
neuronal group differs from that of the dorsal respi-
ratory group in several important ways:

remain almost totally inactive during normal quiet

caused only by repetitive inspiratory signals from
the dorsal respiratory group transmitted mainly to

neurons participate in the basic rhythmical
oscillation that controls respiration.

pulmonary ventilation becomes greater than

ventral respiratory neurons from the basic
oscillating mechanism of the dorsal respiratory

area contributes extra respiratory drive as well.

these neurons contribute to both inspiration and

providing the powerful expiratory signals to the
abdominal muscles during very heavy expiration.

overdrive mechanism when high levels of

Lung Inflation Signals Limit
Inspiration—The Hering-Breuer
Inflation Reflex

In addition to the central nervous system respiratory
control mechanisms operating entirely within the

Pneumotaxic center

Fourth ventricle

Dorsal respiratory

group (inspiration)

Vagus and

glossopharyngeal

? Apneustic center

Inhibits

Ventral respiratory
group (expiration
and inspiration)

Respiratory motor
pathways

Organization of the respiratory center.

Figure 41–1

stimulating the neurons in the chemosensitive area, it

Chemosensitive Area

arily by changing the hydrogen ion concentration, as

changes in blood carbon dioxide, even though carbon

barrier. For this reason, changes in hydrogen ion con-

tant direct stimulus for these neurons. However,

especially excited by hydrogen ions; in fact, it is

The sensor neurons in the chemosensitive area are

Hydrogen Ions Is Likely the Primary Stimulus

Excitation of the Chemosensitive Neurons by

other portions of the respiratory center.

hydrogen ion concentration, and it in turn excites the

beneath the ventral surface of the medulla. This area

41–2, is located bilaterally, lying only 0.2 millimeter

shown in Figure

chemosensitive area,

neuronal area, a

hydrogen ion concentration. Instead, an additional

respiratory group, and the pneumotaxic center. It

the dorsal respiratory group of neurons, the ventral

We have dis-

Chemosensitive Area of the Respiratory Center.

Respiratory Center Activity by Carbon

center itself by carbon dioxide and hydrogen ions.

aortic bodies,

chemoreceptors

controlling respiration. Instead, it acts almost entirely

Oxygen, in contrast, does not have a significant

respiratory muscles.

itself, causing greatly increased strength of both the

each of these.

gen ions in the tissues. It is fortunate, therefore, that

concentrations of oxygen, carbon dioxide, and hydro-

The ultimate goal of respiration is to maintain proper

Chemical Control

needs of the body.

increases in pulmonary ventilation. The major purpose

much as 20 times normal, requiring commensurate

during heavy exercise, the rates of oxygen usage and

match the ventilatory needs of the body. For example,

nisms for causing inspiration and expiration, but it is

Up to this point, we have discussed the basic mecha-

Center Activity

Control of Overall Respiratory

liters per breath). Therefore, this reflex appears to be

In human beings, the Hering-Breuer reflex probably

motaxic center.

rate of respiration, as is true for signals from the pneu-

This reflex also increases the

thus stops further inspiration. This is called the

response that “switches off” the inspiratory ramp and

that is, when the lungs become overly inflated, the

overstretched. These signals affect inspiration in much

stretch receptors

help control respiration. Most important, located in

516

Unit VII

Respiration

the muscular portions of the walls of the bronchi and
bronchioles throughout the lungs are
that transmit signals through the vagi into the dorsal
respiratory group of neurons when the lungs become

the same way as signals from the pneumotaxic center;

stretch receptors activate an appropriate feedback

Hering-

Breuer inflation reflex.

is not activated until the tidal volume increases to
more than three times normal (greater than about 1.5

mainly a protective mechanism for preventing excess
lung inflation rather than an important ingredient in
normal control of ventilation.

also important to know how the intensity of the respi-
ratory control signals is increased or decreased to

carbon dioxide formation are often increased to as

of the remainder of this chapter is to discuss this
control of ventilation in accord with the respiratory

of Respiration

respiratory activity is highly responsive to changes in

Excess carbon dioxide or excess hydrogen ions in

the blood mainly act directly on the respiratory center

inspiratory and the expiratory motor signals to the

direct effect on the respiratory center of the brain in

on peripheral

located in the carotid

and

and these in turn transmit appropri-

ate nervous signals to the respiratory center for
control of respiration.

Let us discuss first the stimulation of the respiratory

Direct Chemical Control of

Dioxide and Hydrogen Ions

cussed mainly three areas of the respiratory center:

is believed that none of these is affected directly by
changes in blood carbon dioxide concentration or

is highly sensitive to changes in either blood Pco

believed that hydrogen ions may be the only impor-

hydrogen ions do not easily cross the blood-brain

centration in the blood have considerably less effect
in stimulating the chemosensitive neurons than do

dioxide is believed to stimulate these neurons second-

explained in the following section.

Carbon Dioxide Stimulates the

Although carbon dioxide has little direct effect in

Chemosensitive
area

Inspiratory area

HCO

but carbon dioxide in the fluid gives rise to most of the hydrogen

Note also that hydrogen ions stimulate the chemosensitive area,

a fraction of a millimeter beneath the ventral medullary surface.

chemosensitive area

area by signals from the

brain stem inspiratory

Figure 41–2

Stimulation of the

located bilaterally in the medulla, lying only

ions.

70 mm Hg, as explained in the next section.

blood oxygen falls too low, mainly below a P

piratory center; this mechanism responds when the

the peripheral chemoreceptors, outside the brain res-

get into trouble for lack of oxygen, the body has a

Yet, for those special conditions in which the tissues

dioxide the major controller of respiration, not

inversely with the rate of pulmonary ventilation; thus,

more times normal. This is not true for carbon dioxide,

under special conditions, adequate delivery of oxygen

up to a value as high as 1000 mm Hg. Therefore, except

We learned in Chapter 40 that the hemoglobin-

chemoreceptors, as explained in the next section).

an indirect effect, acting through the peripheral

Respiratory Center

Unimportance of Oxygen for Control of the

ration. By contrast, the change in respiration in the

75 mm Hg. This demonstrates the tremendous effect

tration) on alveolar ventilation. Note especially the

Figure 41–3 shows quantitatively the approximate

Alveolar Ventilation

and Hydrogen Ion Concentration on

Quantitative Effects of Blood P

chronic

normal. A change in blood carbon dioxide concentra-

as well, thus reducing the hydrogen ions back to near

over a period of hours, the bicarbonate ions also

reduce their concentrations. But even more important,

increasing the blood bicarbonate, which binds with the

hydrogen concentration. The kidneys achieve this by

about one fifth the initial effect. Part of this decline

ually declines over the next 1 to 2 days, decreasing to

blood carbon dioxide first increases, but then it grad-

Decreased Stimulatory Effect of Carbon Dioxide After the First

quantitatively.

carbon dioxide, a fact that we subsequently discuss

tration increases. For this reason, respiratory center

Thus, paradoxically, more hydrogen ions are released

ately reacts with the water to form new hydrogen ions.

fluid. In both these fluids, the carbon dioxide immedi-

increases, so does the P

as if the barrier did not exist. Consequently, whenever

brain barrier is not very permeable to hydrogen ions,

do blood hydrogen ions? The answer is that the blood-

Why does blood carbon dioxide have a more potent

in Figure 41–2.

tory effect on respiration. These reactions are shown

does have a potent indirect effect. It does this by react-

Chapter 41

Regulation of Respiration

517

ing with the water of the tissues to form carbonic acid,
which dissociates into hydrogen and bicarbonate ions;
the hydrogen ions then have a potent direct stimula-

effect in stimulating the chemosensitive neurons than

but carbon dioxide passes through this barrier almost

the blood Pco

of both the

interstitial fluid of the medulla and the cerebrospinal

into the respiratory chemosensitive sensory area of the
medulla when the blood carbon dioxide concentration
increases than when the blood hydrogen ion concen-

activity is increased very strongly by changes in blood

1 to 2 Days.

Excitation of the respiratory center by

carbon dioxide is great the first few hours after the

results from renal readjustment of the hydrogen ion
concentration in the circulating blood back toward
normal after the carbon dioxide first increases the

hydrogen ions in the blood and cerebrospinal fluid to

slowly diffuse through the blood-brain and blood–
cerebrospinal fluid barriers and combine directly with
the hydrogen ions adjacent to the respiratory neurons

tion therefore has a potent acute effect on controlling
respiratory drive but only a weak

effect after

a few days’ adaptation.

effects of blood Pco

and blood pH (which is an

inverse logarithmic measure of hydrogen ion concen-

very marked increase in ventilation caused by an
increase in Pco

in the normal range between 35 and

that carbon dioxide changes have in controlling respi-

normal blood pH range between 7.3 and 7.5 is less than
one tenth as great.

Changes in oxygen concentration have virtually no
direct effect on the respiratory center itself to alter
respiratory drive (although oxygen changes do have

oxygen buffer system delivers almost exactly normal
amounts of oxygen to the tissues even when the pul-
monary Po

changes from a value as low as 60 mm Hg

can occur despite changes in lung ventilation ranging
from slightly below one half normal to as high as 20 or

because both the blood and tissue Pco

changes

the processes of animal evolution have made carbon

oxygen.

special mechanism for respiratory control located in

7.6

7.5

7.4

7.3

7.2

7.1

7.0

6.9

100

Alveolar ventilation (basal rate = 1)

Normal

(mm Hg)

(increased hydrogen ion concentration) on the rate of alveolar

and decreased arterial pH

Effects of increased arterial blood P

Figure 41–3

ventilation.

bodies is still unknown. However, these bodies have

The exact means by which low P

Oxygen Deficiency.

response to carbon dioxide at the onset of exercise.

ulation, so that the peripheral chemoreceptors might

peripheral and central effects of carbon dioxide: the

considered. Yet there is one difference between the

seven times as powerful) that, for practical purposes,

indirectly increases respiratory activity. However, the

also excites the chemoreceptors and, in this way,

Chemoreceptor Activity.

Effect of Carbon Dioxide and Hydrogen Ion Concentration on

saturation with oxygen decreases rapidly.

60 down to 30 mm Hg, a range in which hemoglobin

a carotid body. Note that the impulse rate is particu-

41–5, which shows the effect of different levels of

strongly stimulated. This is demonstrated in Figure

blood falls below normal, the chemoreceptors become

When the oxygen concentration in the arterial

blood, and their P

the chemoreceptors

is virtually zero. This means that

of the bodies themselves each minute. Therefore, the

through these bodies is extreme, 20 times the weight

from the adjacent arterial trunk. Further, blood flow

located along the arch of the aorta; their afferent

respiratory area of the medulla. The

afferent nerve fibers pass through Hering’s nerves to

bifurcations of the common carotid arteries. Their

The

ies of the thoracic and abdominal regions.

shown in the lower part of Figure 41–4, and a very few

aortic bodies,

However, a few are also in the

bodies.

regulate respiratory activity.

concentrations. The chemoreceptors transmit nervous

in the blood, although they also respond to a lesser

located in several areas outside the brain. They are

chemoreceptors,

nervous chemical receptors, called

shown in Figure 41–4. Special

chemoreceptor system,

able for controlling respiration. This is the

piratory center itself, still another mechanism is avail-

Oxygen in Respiratory Control

Respiratory Activity—Role of

System for Control of

Peripheral Chemoreceptor

518

Unit VII

Respiration

In addition to control of respiratory activity by the res-

peripheral

are

especially important for detecting changes in oxygen

extent to changes in carbon dioxide and hydrogen ion

signals to the respiratory center in the brain to help

Most of the chemoreceptors are in the carotid

are located elsewhere in association with other arter-

carotid bodies are located bilaterally in the

the glossopharyngeal nerves and then to the dorsal

aortic bodies are

nerve fibers pass through the vagi, also to the dorsal
medullary respiratory area.

Each of the chemoreceptor bodies receives its own

special blood supply through a minute artery directly

percentage of oxygen removed from the flowing blood

are exposed at all times to arterial blood, not venous

s are arterial Po

Stimulation of the Chemoreceptors by Decreased Arterial
Oxygen.

arte-

rial Po

on the rate of nerve impulse transmission from

larly sensitive to changes in arterial Po

in the range of

An increase in either carbon

dioxide concentration or hydrogen ion concentration

direct effects of both these factors in the respiratory
center itself are so much more powerful than their
effects mediated through the chemoreceptors (about

the indirect effects of carbon dioxide and hydrogen
ions through the chemoreceptors do not need to be

stimulation by way of the peripheral chemoreceptors
occurs as much as five times as rapidly as central stim-

be especially important in increasing the rapidity of

Basic Mechanism of Stimulation of the Chemoreceptors by

excites the nerve endings in the carotid and aortic

Aortic bodies

Medulla

Glossopharyngeal nerve

Vagus nerve

Carotid body

and aortic bodies.

Respiratory control by peripheral chemoreceptors in the carotid

Figure 41–4

100

200

300

400

500

Carotid body nerve

impulses per second

200

400

600

800

Arterial P

(mm Hg)

on impulse rate from the carotid body of a

Effect of arterial P

Figure 41–5

cat.

changed from lower to higher levels. Thus, this

100 mm Hg. For each of these curves, the P

—40 mm Hg, 50 mm Hg, 60 mm Hg, and

These curves were recorded at different levels of

this diagram, first observe the four red curves.

together—affect alveolar ventilation. To understand

, and pH—

Figure 41–7 gives a quick overview of the manner in

on Alveolar Ventilation

, pH, and

Composite Effects of P

mountain climber.

to 500 per cent after 2 to 3 days of low oxygen; this

oxygen, the alveolar ventilation often increases 400

conditions. Instead of the 70 per cent increase in ven-

an increase in respiration fails to occur, and low

and hydrogen ions. Therefore, the excess ventilatory

days, the respiratory center in the brain stem loses

The reason for acclimatization is that, within 2 to 3

concentrations than when they ascend rapidly. This is

period of hours, they breathe much more deeply and

a mountain slowly, over a period of days rather than a

Respiration Even More—The Phenomenon

Chronic Breathing of Low Oxygen Stimulates

process quite strongly.

tions, low arterial P

s. Under these condi-

falls to 60 mm Hg and can increase as

100 mm Hg, ventilation approximately doubles when

greater than 100 mm Hg. But at pressures lower than

chemoreceptors is active. The figure shows almost no

levels. In other words, in this figure, only the ventila-

Figure 41–6 shows the effect of low arterial P

Remain Normal

Dioxide and Hydrogen Ion Concentrations

Alveolar Ventilation When Arterial Carbon

Effect of Low Arterial P

chemoreceptors and then stimulate the nerve endings.

with the nerve endings. Some investigators have sug-

glomus cells,

multiple highly characteristic glandular-like cells,

Chapter 41

Regulation of Respiration

519

called

that synapse directly or indirectly

gested that these glomus cells might function as the

But other studies suggest that the nerve endings them-
selves are directly sensitive to the low Po

to Stimulate

alveolar ventilation when the Pco

and the hydrogen

ion concentration are kept constant at their normal

tory drive due to the effect of low oxygen on the

effect on ventilation as long as the arterial Po

remains

the arterial Po

much as fivefold at very low Po

obviously drives the ventilatory

of “Acclimatization”

Mountain climbers have found that when they ascend

therefore can withstand far lower atmospheric oxygen

called acclimatization.

about four fifths of its sensitivity to changes in Pco

blow-off of carbon dioxide that normally would inhibit

oxygen can drive the respiratory system to a much
higher level of alveolar ventilation than under acute

tilation that might occur after acute exposure to low

helps immensely in supplying additional oxygen to the

which the chemical factors Po

, Pco

arterial Po

was

Ventilation

140 120 100

160

Alveolar ventilation (normal = 1)

Arterial P

(mm Hg)

Arterial P

(mm Hg)

at a constant level during the measurements of this study; pH also

to 20 mm Hg. The upper line shows that the arterial P

decreases from the normal level of 100 mm Hg

on alveolar ventilation, showing a sixfold increase in ven-

The lower curve demonstrates the effect of different levels of arte-

Figure 41–6

rial P

tilation as the P

was kept

was kept constant.

50 60

100

pH = 7.4
pH = 7.3

100

(mm Hg)

Alveolar ventilation (L/min)

Alveolar P

(mm Hg)

DJC, Lloyd BB: The Regulation of Human Respiration. Oxford:

and pH on alveolar ventilation. (Drawn from data in Cunningham

Composite diagram showing the interrelated effects of P

Figure 41–7

, P

Blackwell Scientific Publications, 1963.)

. In fact, this

cise, the alveolar ventilation increases instantaneously,

. Note that at the onset of exer-

This is demonstrated in Figure 41–9, which shows in

tions of the body fluids as nearly normal as possible.

oxygen, carbon dioxide, and hydrogen ion concentra-

are either too strong or too weak. Then chemical

ally, however, the nervous respiratory control signals

cise and to blow off extra carbon dioxide. Occasion-

person exercises, direct nervous signals presumably

When a

Interrelation Between Chemical Factors and Nervous: Factors

chemicals have had time to change. It is likely that

diately on initiation of the exercise, before any blood

Actually, when a person begins to exercise, a large

taneous increase in arterial pressure.

the brain stem to excite the respiratory center. This is

motor impulses to the exercising muscles, is believed

seems to be predominant. The brain, on transmitting

intense ventilation during exercise? At least one effect

Therefore, the question must be asked: What causes

significantly during exercise, so that none of them

pH, and P

questionable, because measurements of arterial P

ions, plus a decrease in blood oxygen. However, this is

tilation during exercise, one is tempted to ascribe this

, and pH remain

The arterial P

as illustrated in Figure 41–8, in the healthy athlete,

dioxide formation can increase as much as 20-fold.Yet,

In strenuous exercise, oxygen consumption and carbon

During Exercise

, and arterial pH.

, alveolar P

Thus, using this diagram, one can predict the level of

at higher pHs and displaced to the left at lower pHs.

on ventilation at two different pH values. Still

measured at a pH of 7.3. We now have two families of

measured at a blood pH of 7.4; the green curves were

Now observe the green curves. The red curves were

“family” of red curves represents the combined effects

520

Unit VII

Respiration

of alveolar Pco

and Po

on ventilation.

curves representing the combined effects of Pco

and

other families of curves would be displaced to the right

alveolar ventilation for most combinations of alveolar
Pco

Regulation of Respiration

alveolar ventilation ordinarily increases almost exactly
in step with the increased level of oxygen metabolism.

, Pco

almost exactly

normal.

In trying to analyze what causes the increased ven-

to increases in blood carbon dioxide and hydrogen

show that none of these values changes

becomes abnormal enough to stimulate respiration.

to transmit at the same time collateral impulses into

analogous to the stimulation of the vasomotor center
of the brain stem during exercise that causes a simul-

share of the total increase in ventilation begins imme-

most of the increase in respiration results from neuro-
genic signals transmitted directly into the brain stem
respiratory center at the same time that signals go to
the body muscles to cause muscle contraction.

in the Control of Respiration During Exercise.

stimulate the respiratory center almost the proper
amount to supply the extra oxygen required for exer-

factors play a significant role in bringing about the
final adjustment of respiration required to keep the

the lower curve changes in alveolar ventilation during
a 1-minute period of exercise and in the upper curve
changes in arterial Pco

without an initial increase in arterial Pco

110

2.0

3.0

4.0

1.0

Moderate

exercise

Severe

exercise

Total ventilation (L/min)

100

120

consumption (L/min)

(From Gray JS: Pulmonary Ventilation and Its Physiological Regu-

Effect of exercise on oxygen consumption and ventilatory rate.

Figure 41–8

lation. Springfield, Ill: Charles C Thomas, 1950.)

Arterial P

(mm Hg)

Exercise

Minutes

Alveolar ventilation

(L/min)

ventilation in dogs during active exercise. J Appl Physiol 33:778,

in dogs in Bainton CR: Effect of speed vs grade and shivering on

mination of exercise. (Extrapolated to the human being from data

during a 1-minute period of exercise and also after ter-

and arterial P

Figure 41–9

Changes in alveolar ventilation (bottom curve)

(top curve)

1972.)

piration within a few minutes.

remove some of the fluids of the brain, thus relieving

trated mannitol solution. These solutions osmotically

Occasionally, respiratory depression resulting from

vault and thus partially blocking cerebral blood supply.

object, after which the damaged brain tissues swell,

instance, the head might be struck against some solid

brain edema resulting from brain concussion. For

The activity of the respiratory

the J receptors is not clear, their excitation may give the

congestive heart failure. Although the functional role of

name “J receptors.” They are stimulated especially when

coughing and sneezing, as discussed in Chapter 39. They

that are stimulated by many incidents. These cause

the trachea, bronchi, and bronchioles is supplied with

The epithelium of

Effect of Irritant Receptors in the Airways.

, pH, and P

time, respiration can be controlled voluntarily and that

ration. However, we all know that for short periods of

Thus far, we have dis-

Voluntary Control of Respiration.

Affect Respiration

learned response.

the cerebral cortex is involved in this learning, because

normal level. Also, there is reason to believe that even

at its

That is, with repeated periods of exercise, the brain

response.

in Figure 41–10, is at least partly a

ventilatory response curve during exercise, as shown

ments suggest that the brain’s ability to shift the

Possibility That the Neurogenic Factor for Control of Ventila-

less than 40 mm Hg.

greater than 40 mm Hg and a depres-

40 mm Hg, it has an extra stimulatory effect on venti-

Figure 41–10 also shows that if, during exercise, the

near its normal value. The upper curve of

the rate of carbon dioxide release, thus keeping arte-

upward direction, so that ventilation almost matches

is at the normal level of 40 mm Hg. In other words, the

exercising state. Note in both instances that the P

cise. The points indicated on the two curves show the

cising. The upper curve shows the approximate shift of

ventilation when the body is at rest—that is, not exer-

quantitatively. The lower curve of this figure shows the

during exercise in still another way, this time more

Figure 41–10 summarizes the control of respiration

of exercise in the figure.

tinues, as shown toward the end of the 1-minute period

increased rate of ventilation, and the arterial P

is needed. However, after about 30 to 40 seconds,

cise, causing extra alveolar ventilation even before it

tory” stimulation of respiration at the onset of exer-

carbon dioxide is that the brain provides an “anticipa-

as shown in the figure. The presumed reason that the

Chapter 41

Regulation of Respiration

521

increase in ventilation is usually great enough so that
at first it actually decreases arterial Pco

below normal,

ventilation forges ahead of the buildup of blood

the amount of carbon dioxide released into the blood
from the active muscles approximately matches the

returns essentially to normal even as the exercise con-

effect of different levels of arterial Pco

on alveolar

this ventilatory curve caused by neurogenic drive from
the respiratory center that occurs during heavy exer-

arterial Pco

first in the resting state and then in the

neurogenic factor shifts the curve about 20-fold in the

rial Pco

arterial Pco

does change from its normal value of

lation at a Pco

sant effect at a Pco

tion During Exercise Is a Learned Response.

Many experi-

learned

becomes progressively more able to provide the
proper signals required to keep the blood Pco

experiments that block only the cortex also block the

Other Factors That

cussed the involuntary system for the control of respi-

one can hyperventilate or hypoventilate to such an
extent that serious derangements in Pco

can occur in the blood.

sensory nerve endings called pulmonary irritant recep-
tors

may also cause bronchial constriction in such diseases
as asthma and emphysema.

Function of Lung “J Receptors.”

A few sensory nerve

endings have been described in the alveolar walls in
juxtaposition to the pulmonary capillaries—hence the

the pulmonary capillaries become engorged with blood
or when pulmonary edema occurs in such conditions as

person a feeling of dyspnea.

Effect of Brain Edema.

center may be depressed or even inactivated by acute

compressing the cerebral arteries against the cranial

brain edema can be relieved temporarily by intravenous
injection of hypertonic solutions such as highly concen-

intracranial pressure and sometimes re-establishing res-

100

Exercise

Alveolar ventilation (L/min)

Arterial P

(mm Hg)

140

120

100

Resting
Normal

during heavy exercise.

at the normal level of 40 mm Hg both in the resting state and

factors, is almost exactly the right amount to maintain arterial P

than normal. The shift, believed to be caused by neurogenic

-ventilation response curve to a level much higher

Approximate effect of maximum exercise in an athlete to shift the

Figure 41–10

alveolar P

adequate airflow. Some individuals have an especially

inspiration. During sleep, these muscles usually relax,

The muscles of the pharynx normally keep this

Airway.

Obstructive Sleep Apnea Is Caused by Blockage of the Upper

impaired central nervous system respiratory drive.

of the upper airways, especially the pharynx, or by

each night. Sleep apneas can be caused by obstruction

are greatly increased, with episodes of apnea lasting for

the frequency and duration

sleep apnea,

ing. Occasional apneas occur during normal sleep, but

The term

occurring.

in the brain, not with the

the respiratory neurons. But the depth of respiration

shown in Figure 41–11. Note that the P

Typical records of changes in pulmonary and respira-

with great force. Cheyne-Stokes breathing of this

entirely for a few seconds; then an extra intense

. The brain

brain. This type of Cheyne-Stokes breathing occurs

tendency for periodic breathing is now strong

ventilation 10- to 20-fold. The brain feedback

3 mm Hg, the same 3 mm Hg rise might increase

change in ventilation than normally. For instance,

control areas. This means that a change in blood

increased negative feedback gain

2. A second cause of Cheyne-Stokes breathing is

sometimes occur on and off for months.

heart failure, Cheyne-Stokes breathing can

lungs to the brain. In fact, in patients with chronic

because blood flow is slow,

severe cardiac failure

Stokes breathing begins. This type of Cheyne-

respiratory drive becomes extreme, and Cheyne-

then, after a few more seconds, the periodic

conditions, the storage capacities of the alveoli and

for many more seconds than usual. Under these

long delay occurs for transport of blood

1. When a

ridden, and Cheyne-Stokes breathing does occur:

separate conditions, the damping factors can be over-

the next cycle of the periodic breathing. But under two

carbon dioxide and oxygen. Therefore, normally, the

mechanism is highly “damped.” That is, the fluids of the

in everyone. However, under normal conditions, this

The basic cause of Cheyne-Stokes breathing occurs

cycle repeats.

respond, the person breathes hard once again, and the

respond to these new changes. When the brain does

Again, it takes a few seconds before the brain can

amount. Then the opposite cycle begins. That is, carbon

center, the center becomes depressed an excessive

for an extra few seconds. Therefore, when the overven-

tion. By this time, the person has already overventilated

same time increasing blood oxygen, it takes several

When a person overbreathes, thus blowing off too much

The basic

ring about every 40 to 60 seconds, as illustrated in Figure

ized by slowly waxing and waning respiration occur-

Cheyne-Stokes breathing,

odic breathing,

cycle repeating itself over and over. One type of peri-

slightly or not at all for an additional interval, with the

occurs in a number of disease conditions. The person

one time, morphine was used as an anesthetic, but this

more than many other anesthetics, such as halothane. At

with anesthetics or narcotics. For instance, sodium pen-

522

Unit VII

Respiration

Anesthesia.

Perhaps the most prevalent cause of respi-

ratory depression and respiratory arrest is overdosage

tobarbital depresses the respiratory center considerably

drug is now used only as an adjunct to anesthetics
because it greatly depresses the respiratory center while
having less ability to anesthetize the cerebral cortex.

Periodic Breathing

An abnormality of respiration called periodic breathing

breathes deeply for a short interval and then breathes

is character-

41–11.

Basic Mechanism of Cheyne-Stokes Breathing.

cause of Cheyne-Stokes breathing is the following:

carbon dioxide from the pulmonary blood while at the

seconds before the changed pulmonary blood can be
transported to the brain and inhibit the excess ventila-

tilated blood finally reaches the brain respiratory

dioxide increases and oxygen decreases in the alveoli.

blood and the respiratory center control areas have
large amounts of dissolved and chemically bound

lungs cannot build up enough extra carbon dioxide or
depress the oxygen sufficiently in a few seconds to cause

from the lungs to the brain, changes in carbon
dioxide and oxygen in the alveoli can continue

pulmonary blood for these gases are exceeded;

Stokes breathing often occurs in patients with

thus delaying the transport of blood gases from the

in the respiratory

carbon dioxide or oxygen causes a far greater

instead of the normal 2- to 3-fold increase in
ventilation that occurs when the Pco

rises

enough to cause Cheyne-Stokes breathing without
extra blood flow delay between the lungs and

mainly in patients with brain damage
damage often turns off the respiratory drive

increase in blood carbon dioxide turns it back on

type is frequently a prelude to death from brain
malfunction.

tory center Pco

during Cheyne-Stokes breathing are

of the

pulmonary blood changes in advance of the Pco

corresponds with the Pco

Pco

in the pulmonary blood where the ventilation is

Sleep Apnea

apnea means absence of spontaneous breath-

in persons with

10 seconds or longer and occurring 300 to 500 times

passage open to allow air to flow into the lungs during

but the airway passage remains open enough to permit

Depth of

respiration

respiratory
neurons

lung blood

Respiratory
center excited

fluids of the respiratory center

(red line)

monary blood

Cheyne-Stokes breathing, showing changing P

Figure 41–11

in the pul-

and delayed changes in the P

of the

(blue line).

tory neurons. Respir Physiol Neurobiol 131:121, 2002.

Zuperku EJ, McCrimmon DR: Gain modulation of respira-

sleep apnea in adults. JAMA 291:2013, 2004.

Young T, Skatrud J, Peppard PE: Risk factors for obstructive

apnea, and hypertension. Hypertension 42:1067, 2003.

Wolk R, Shamsuzzaman AS, Somers VK: Obesity, sleep

Lippincott Williams & Wilkins, 2003.

West JB: Pulmonary Physiology—The Essentials. Baltimore:

in vertebrates. Physiol Rev 79:855, 1999.

Taylor EW, Jordan D, Coote JH: Central control of the car-

brain. Nat Rev Neurosci 5:437, 2004.

Sharp FR, Bernaudin M: HIF1 and oxygen sensing in the

Physiol 96:1173, 2004.

control of cardiorespiratory physiology by HIF-1. J Appl

-regulated gene expression: transcriptional

Semenza GL: O

5:449, 2004.

sensors that maintain pH homeostasis. Nat Rev Neurosci

Richerson GB: Serotonergic neurons as carbon dioxide

Physiol 62:847, 2000.

temperature in mammals and other vertebrates.Annu Rev

Mortola JP, Frappell PB: Ventilatory responses to changes in

plasticity in respiratory control. J Appl Physiol 94:1242,

Morris KF, Baekey DM, Nuding SC, et al: Neural network

377, 2003.

ology and clinical implications. Acta Physiol Scand 177:

Kara T, Narkiewicz K, Somers VK: Chemoreflexes—physi-

airways. Respir Physiol 125:67, 2001.

Jordan D: Central nervous pathways and control of the

grad Med J 77:700, 2001.

ological and clinical aspects of breathing after stroke. Post-

Howard RS, Rudd AG, Wolfe CD, Williams AJ: Pathophysi-

rhythm in adult mammals. News Physiol Sci 18:23, 2003.

Hilaire G, Pasaro R: Genesis and control of the respiratory

sensory denervation. J Appl Physiol 94:784, 2003.

Forster HV: Plasticity in the control of breathing following

plasticity, chemosensitivity. Annu Rev Neurosci 26:239,

Feldman JL, Mitchell GS, Nattie EE: Breathing: rhythmicity,

biol 131:57, 2002.

regulating upper airway patency. Respir Physiol Neuro-

Dutschmann M, Paton JF: Inhibitory synaptic mechanisms

J Physiol Lung Cell Mol Physiol 283:L665, 2002.

chemoreception and respiratory control. Am

Dean JB, Ballantyne D, Cardone DL, et al: Role of gap junc-

necessary.

helpful, but ventilation with CPAP at night is usually

the stimulatory effects of carbon dioxide. Medications

even small doses of sedatives or narcotics, which further

stimulatory effects of carbon dioxide and hydrogen ions.

unknown, although instability of the respiratory drive

In most patients, the cause of central sleep apnea is

reached that eventually stimulates respiration. These

During sleep, their breathing disorders usually worsen,

they are fully capable of normal voluntary breathing.

decreased ventilation when they are awake, although

. Patients affected by central sleep apnea may have

the ventilatory muscles transiently ceases. Disorders

with sleep apnea, the central nervous system drive to

tory Muscles Is Transiently Abolished.

airway pressure (CPAP)

sleep, and (2) nasal ventilation with

adenoids, or to create an opening in the trachea (tra-

), to remove enlarged tonsils or

tion. The most common treatments of obstructive sleep

nasal obstruction, a very large tongue, enlarged tonsils,

In a few individuals, sleep apnea may be associated with

older, obese persons in whom there is increased fat dep-

cardiovascular disease.

systemic hypertension, and a greatly elevated risk for

pathetic activity, high heart rates, pulmonary and

as well as other disorders, including increased sym-

drowsi-

ing in fragmented, restless sleep. Therefore, patients

repeated several hundred times during the night, result-

apnea. The periods of apnea and labored breathing are

sudden attempts to breathe, which result in loud snorts

which greatly stimulate respiration. This, in turn, causes

ing (apnea) occurs. These periods of apnea result

proceeds, often becoming louder, and is then inter-

occur soon after falling asleep. The snoring

In persons with sleep apnea, loud

cannot flow into the lungs.

narrow passage, and relaxation of these muscles during

Chapter 41

Regulation of Respiration

523

sleep causes the pharynx to completely close so that air

snoring and labored

breathing

rupted by a long silent period during which no breath-

in significant decreases in Po

and increases in Pco

and gasps followed by snoring and repeated episodes of

with sleep apnea usually have excessive daytime
ness

Obstructive sleep apnea most commonly occurs in

osition in the soft tissues of the pharynx or compression
of the pharynx due to excessive fat masses in the neck.

or certain shapes of the palate that greatly increase
resistance to the flow of air to the lungs during inspira-

apnea include (1) surgery to remove excess fat tissue
at the back of the throat (a procedure called uvu-
lopalatopharyngoplasty

cheostomy) to bypass the obstructed airway during

continuous positive

“Central” Sleep Apnea Occurs When the Neural Drive to Respira-

In a few persons

that can cause cessation of the ventilatory drive during
sleep include damage to the central respiratory centers
or abnormalities of the respiratory neuromuscular appa-
ratus

resulting in more frequent episodes of apnea that
decrease Po

and increase Pco

until a critical level is

transient instabilities of respiration cause restless sleep
and clinical features similar to those observed in
obstructive sleep apnea.

can result from strokes or other disorders that make the
respiratory centers of the brain less responsive to the

Patients with this disease are extremely sensitive to

reduce the responsiveness of the respiratory centers to

that stimulate the respiratory centers can sometimes be

References

tions in CO

2003.

diovascular and respiratory systems and their interactions