Regulation of Breathing
BRAIN STEM CONTROL OF BREATHING
Breathing is an involuntary process that is controlled by the
medulla and pons of the brain stem. The frequency of normal,
involuntary breathing is controlled by three groups of neurons
or brain stem centers: the medullary respiratory center, the
apneustic center, and the pneumotaxic center.
Medullary Respiratory Center
The medullary respiratory center is located in the reticular
formation and is composed of two groups of neurons that are
distinguished by their anatomic location: the inspiratory
center (dorsal respiratory group) and the expiratory center
(ventral respiratory group).
Inspiratory center. The inspiratory center is located in the
dorsal respiratory group of neurons and controls the basic
rhythm for breathing by setting the frequency of inspiration.
This group of neurons receives sensory input from peripheral
chemoreceptors via the glossopharyngeal (CN IX) and vagus
(CN X) nerves and from mechanoreceptors in the lung via the
vagus nerve. The inspiratory center sends its motor output to
the diaphragm via the phrenic nerve.
The pattern of activity in the phrenic nerve includes a period
of quiescence, followed by a burst of action potentials that
increase in frequency for a few seconds, and then a return to
quiescence. Activity in the diaphragm follows this same
pattern: quiescence, action potentials rising to a peak
frequency (leading to contraction of the diaphragm), and
quiescence.
Inspiration can be shortened by inhibition of the inspiratory
center via the pneumotaxic center (see subsequent discussion).
Expiratory center. The expiratory center (not shown in Fig.
5-30) is located in the ventral respiratory neurons and is
responsible primarily for expiration. Since expiration is
normally a passive process, these neurons are inactive during
quiet breathing. However, during exercise when expiration
becomes active, this center is activated.
Apneustic Center
Apneusis is an abnormal breathing pattern with prolonged
inspiratory gasps, followed by brief expiratory movement.
Stimulation of the apneustic center in the lower pons produces
this breathing pattern in experimental subjects. Stimulation of
these neurons apparently excites the inspiratory center in the
medulla, prolonging the period of action potentials in the
phrenic nerve, and thereby prolonging the contraction of the
diaphragm.
The pneumotaxic center turns off inspiration, limiting the
burst of action potentials in the phrenic nerve. In effect, the
pneumotaxic center, located in the upper pons, limits the size
of the tidal volume, and secondarily, it regulates the
respiratory rate. A normal breathing rhythm persists in the
absence of this center.
CEREBRAL CORTEX
Commands from the cerebral cortex can temporarily override
the automatic brain stem centers. For example, a person can
voluntarily hyperventilate (i.e., increase breathing frequency
and volume). The consequence of hyperventilation is a
decrease in PaCO2, which causes arterial pH to increase.
Hyperventilation is self-limiting, however, because the
decrease in PaCO2 will produce unconsciousness and the
person will revert to a normal breathing pattern. Although
more difficult, a person may voluntarily hypoventilate (i.e.,
breath-holding). Hypoventilation causes a decrease in PaO2
and an increase in PaCO2, both of which are strong drives for
ventilation. A period of prior hyperventilation can prolong the
duration of breath-holding.
CHEMORECEPTORS
The brain stem controls breathing by processing sensory
(afferent)
information
and
sending
motor
(efferent)
information to the diaphragm. Of the sensory information
arriving at the brain stem, the most important is that
concerning PaO2, PaCO2, and arterial pH.
Central Chemoreceptors
The central chemoreceptors, located in the brain stem, are the
most important for the minute-to-minute control of breathing.
These chemoreceptors are located on the ventral surface of the
medulla, near the point of exit of the glossopharyngeal (CN
IX) and vagus (CN X) nerves and only a short distance from
the medullary inspiratory center. Thus, central chemoreceptors
communicate directly with the inspiratory center.
The brain stem chemoreceptors are exquisitely sensitive to
changes in the pH of cerebrospinal fluid (CSF).
Decreases in the pH of CSF produce increases in breathing
rate (hyperventilation), and increases in the pH of CSF
produce decreases in breathing rate (hypoventilation).
The medullary chemoreceptors respond directly to changes in
the pH of CSF and indirectly to changes in arterial PCO2 (Fig.
5-31). The circled numbers in the figure correspond with the
following steps:
1. In the blood, CO2 combines reversibly with H2O to form H+
and HCO3- by the familiar reactions. Because the blood-brain
barrier is relatively impermeable to H+ and HCO3-, these ions
are trapped in the vascular compartment and do not enter the
brain. CO2, however, is quite permeable across the bloodbrain barrier and enters the extracellular fluid of the brain.
2. CO2 also is permeable across the brain-CSF barrier and
enters the CSF.
3. In the CSF, CO2 is converted to H+ and HCO3-. Thus,
increases in arterial PCO2 produce increases in the PCO2 of
CSF, which results in an increase in H+ concentration of CSF
(decrease in pH). 4 and 5. The central chemoreceptors are in
close proximity to CSF and detect the decrease in pH. A
decrease in pH then signals the inspiratory center to increase
the breathing rate (hyperventilation).
In summary, the goal of central chemoreceptors is to keep
arterial PCO2 within the normal range, if possible. Thus,
increases in arterial PCO2 produce increases in PCO2 in the
brain and the CSF, which decreases the pH of the CSF. A
decrease in CSF pH is detected by central chemoreceptors for
H+, which instruct the inspiratory center to increase the
breathing rate. When the breathing rate increases, more CO2
will be expired and the arterial PCO2 will decrease toward
normal.
Peripheral Chemoreceptors
There are peripheral chemoreceptors for O2, CO2, and H+ in
the carotid bodies located at the bifurcation of the common
carotid arteries and in the aortic bodies above and below the
aortic arch (see Fig. 5-30).
Information about arterial PO2, PCO2, and pH is relayed to the
medullary inspiratory center via CN IX and CN X, which
orchestrates an appropriate change in breathing rate.
Each of the following changes in arterial blood composition is
detected by peripheral chemoreceptors and produces an
increase in breathing rate:
Decreases in arterial PO2. The most important responsibility
of the peripheral chemoreceptors is to detect changes in
arterial
PO2.
Surprisingly,
however,
the
peripheral
chemoreceptors are relatively insensitive to changes in PO2:
They respond when PO2 decreases to less than 60 mm Hg.
Thus, if arterial PO2 is between 100 mm Hg and 60 mm Hg,
the breathing rate is virtually constant. However, if arterial
PO2 is less than 60 mm Hg, the breathing rate increases in a
very steep and linear fashion. In this range of P O2,
chemoreceptors are exquisitely sensitive to O2; in fact, they
respond so rapidly that the firing rate of the sensory neurons
may change during a single breathing cycle.
Increases in arterial PCO2. The peripheral chemoreceptors
also detect increases in PCO2, but the effect is less important
than their response to decreases in PO2. Detection of changes
in PCO2 by the peripheral chemoreceptors also is less
important than detection of changes in PCO2 by the central
chemoreceptors.
Decreases in arterial pH. Decreases in arterial pH cause an
increase in ventilation, mediated by peripheral chemoreceptors
for H+. This effect is independent of changes in the arterial
PCO2 and is mediated only by chemoreceptors in the carotid
bodies (not by those in the aortic bodies). Thus, in metabolic
acidosis, in which there is decreased arterial pH, the peripheral
chemoreceptors are stimulated directly to increase the
ventilation rate.
OTHER RECEPTORS
In addition to chemoreceptors, several other types of receptors
are involved in the control of breathing, including lung stretch
receptors, joint and muscle receptors, irritant receptors, and
juxtacapillary (J) receptors.
Lung stretch receptors. Mechanoreceptors are present in the
smooth muscle of the airways. When stimulated by distention
of the lungs and airways, mechanoreceptors initiate a reflex
decrease in breathing rate called the Hering-Breuer reflex.
The reflex decreases breathing rate by prolonging expiratory
time.
Joint and muscle receptors. Mechanoreceptors located in the
joints and muscles detect the movement of limbs and instruct
the inspiratory center to increase the breathing rate.
Information from the joints and muscles is important in the
early (anticipatory) ventilatory response to exercise.
Irritant receptors. Irritant receptors for noxious chemicals
and particles are located between epithelial cells lining the
airways. Information from these receptors travels to the
medulla via CN X and causes a reflex constriction of
bronchial smooth muscle and an increase in breathing rate.
J receptors. Juxtacapillary (J) receptors are located in the
alveolar walls and, therefore, are near the capillaries.
Engorgement of pulmonary capillaries with blood and
increases in interstitial fluid volume may activate these
receptors and produce an increase in the breathing rate. For
example, in left-sided heart failure, blood "backs up" in the
pulmonary circulation, and J receptors mediate a change in
breathing pattern, including rapid shallow breathing and
dyspnea (difficulty in breathing).
Integrative Functions
Examples are the responses to exercise and the adaptation to
high altitude and.
RESPONSES TO EXERCISE
The response of the respiratory system to exercise is
remarkable. As the body's demand for O2 increases, more O2
is supplied by increasing the ventilation rate: Excellent
matching occurs between O2 consumption, CO2 production,
and the ventilation rate.
For example, when a trained athlete is exercising, his O2
consumption may increase from its resting value of 250
mL/min to 4000 mL/min, and his ventilation rate may increase
from 7.5 L/min to 120 L/min. Both O2 consumption and
ventilation rate increase more than 15 times the resting level!
An interesting question is What factors ensure that the
ventilation rate will match the need for O2? At this time, there
is no completely satisfactory answer to this question.
P50. A significant point on the O2-hemoglobin dissociation
curve is the P50. By definition, P50 is the PO2 at which
hemoglobin is 50% saturated (i.e., where two of the four
heme groups are bound to O2). A change in the value of P50 is
used as an indicator for a change in affinity of hemoglobin for
O2. An increase in P50 reflects a decrease in affinity, and a
decrease in P50 reflects an increase in affinity.
Remarkably, mean values for arterial PO2 and PCO2 do not
change during exercise. An increased ventilation rate and
increased efficiency of gas exchange ensure that there is
neither a decrease in arterial PO2 nor an increase in arterial
PCO2. (The arterial pH may decrease, however, during
strenuous exercise because the exercising muscle produces
lactic acid. Recalling that the peripheral and central
chemoreceptors respond, respectively, to changes in Pa O2 and
PaCO2, it is a mystery, therefore, how the ventilation rate can
be altered so precisely to meet the increased demand when
these parameters seem to remain constant. One hypothesis
states that although mean values of arterial PO2 and PCO2 do
not change, oscillations in their values do occur during the
breathing cycle. These oscillatory changes may, via the
chemoreceptors, produce such immediate adjustments in
ventilation that mean values in arterial blood remain constant.
Venous PCO2
The PCO2 of mixed venous blood must increase during
exercise because skeletal muscle is adding more CO2 than
usual to venous blood. However, since mean arterial P CO2
does not increase, the ventilation rate must increase
sufficiently to rid the body of this excess CO2 (i.e., the "extra"
CO2 is expired by the lungs and never reaches systemic
arterial blood).
Muscle and Joint Receptors
Muscle and joint receptors send information to the medullary
inspiratory center and participate in the coordinated response
to exercise. These receptors are activated early in exercise, and
the inspiratory center is commanded to increase the ventilation
rate.
Cardiac Output and Pulmonary Blood Flow
Cardiac output increases during exercise to meet the tissues'
demand for O2. Since pulmonary blood flow is the cardiac
output of the right heart, pulmonary blood flow increases.
There is a decrease in pulmonary resistance associated with
perfusion of more pulmonary capillary beds, which also
improves gas exchange. As a result, pulmonary blood flow
becomes more evenly distributed throughout the lungs, and the
ratio becomes more "even," producing a decrease in the
physiologic dead space.
O2-Hemoglobin Dissociation Curve
During exercise, the O2-hemoglobin dissociation curve shifts
to the right. There are multiple reasons for this shift,
including increased tissue PCO2, decreased tissue pH, and
increased temperature. The shift to the right is advantageous,
of course, since it is associated with an increase in P50 and
decreased affinity of hemoglobin for O2, making it easier to
unload O2 in the exercising skeletal muscle.
ADAPTATION TO HIGH ALTITUDE
Ascent to high altitude is one of several causes of hypoxemia.
The respiratory responses to high altitude are the adaptive
adjustments a person must make to the decreased P O2 in
inspired and alveolar air.
The decrease in PO2 at high altitudes is explained as follows:
At sea level, the barometric pressure is 760 mm Hg; at 18,000
feet above sea level, the barometric pressure is one-half that
value, or 380 mm Hg. To calculate the PO2 of humidified
inspired air at 18,000 feet above sea level, correct the
barometric pressure of dry air by the water vapor ressure of 47
mm Hg, then multiply by the fractional concentration of O2,
which is 21%. Thus, at 18,000 feet, PO2 = 70 mm Hg ([380
mm Hg - 47 mm Hg] × 0.21 = 70 mm Hg). A similar
calculation for pressures at the peak of Mount Everest yields a
PO2 of inspired air of only 47 mm Hg!
Despite severe reductions in the PO2 of both inspired and
alveolar air, it is possible to live at high altitudes if the
following adaptive responses occur:
Hyperventilation
The
most
significant
response
to
high
altitude
is
hyperventilation, an increase in ventilation rate. For example,
if the alveolar PO2 is 70 mm Hg, then arterial blood, which is
almost perfectly equilibrated, also will have a P O2 of 70 mm
Hg, which will not stimulate peripheral chemoreceptors.
However, if alveolar PO2 is 60 mm Hg, then arterial blood will
have a PO2 of 60 mm Hg, in which case the hypoxemia is
severe enough to stimulate peripheral chemoreceptors in the
carotid and aortic bodies. In turn, the chemoreceptors instruct
the medullary inspiratory center to increase the breathing rate.
A consequence of the hyperventilation is that "extra" CO2 is
expired by the lungs and arterial PCO2 decreases, producing
respiratory alkalosis. However, the decrease in PCO2 and the
resulting increase in pH will inhibit central and peripheral
chemoreceptors and offset the increase in ventilation rate.
These offsetting effects of CO2 and pH occur initially, but
within several days HCO3- excretion increases, HCO3- leaves
the CSF, and the pH of the CSF decreases toward normal.
Thus, within a few days, the offsetting effects are reduced and
hyperventilation resumes.
The respiratory alkalosis that occurs as a result of ascent to
high altitude can be treated with carbonic anhydrase
inhibitors (e.g., acetazolamide ). These drugs increase
HCO3- excretion, creating a mild compensatory metabolic
acidosis.
Polycythemia
Ascent to high altitude produces an increase in red blood cell
concentration (polycythemia) and, as a consequence, an
increase in hemoglobin concentration. The increase in
hemoglobin concentration means that the O2-carrying capacity
is increased, which increases the total O2 content of blood in
spite of arterial PO2 being decreased. Polycythemia is
advantageous in terms of O2 transport to the tissues, but it is
disadvantageous in terms of blood viscosity. The increased
concentration of red blood cells increases blood viscosity,
which increases resistance to blood flow.
The stimulus for polycythemia is hypoxemia, which increases
the synthesis of erythropoietin in the kidney. Erythropoietin
acts on bone marrow to stimulate red blood cell production.
Clinical uses and unwanted effects
One of the most interesting features of the body's adaptation to
high altitude is an increased synthesis of 2,3-DPG by red
blood cells. The increased concentration of 2,3-DPG causes
the O2 hemoglobin dissociation curve to shift to the right.
This right shift is advantageous in the tissues, since it is
associated with increased P50, decreased affinity, and
increased unloading of O2. However, the right shift is
disadvantageous in the lungs because it becomes more
difficult to load the pulmonary capillary blood with O2.
Pulmonary Vasoconstriction
At high altitude, alveolar gas has a low Po2, which has a direct
vasoconstricting effect on the pulmonary vasculature (i.e.,
hypoxic vasoconstriction). As pulmonary vascular resistance
increases, pulmonary arterial pressure also must increase to
maintain a constant blood flow. The right ventricle must pump
against this higher pulmonary arterial pressure and may
hypertrophy in response to the increased afterload.
Acute Altitude Sickness
The initial phase of ascent to high altitude is associated with a
constellation of complaints, including headache, fatigue,
dizziness, nausea, palpitations, and insomnia. The symptoms
are attributable to the initial hypoxia and respiratory alkalosis,
which abate when the adaptive responses are established.
Hypoxemia and Hypoxia
Hypoxemia is defined as a decrease in arterial P O2. Hypoxia is
defined as a decrease in O2 delivery to, or utilization by, the
tissues. Hypoxemia is one cause of tissue hypoxia, although it
is not the only cause.
High altitude
Hypoventilation
Diffusion defects
V/Q defects
Right-to-left shunts
HYPOXIA
Table 5-6. Causes of Hypoxia
Cause
Mechanism
PaO2
↓ Cardiac output
↓ Blood flow
-
Hypoxemia
↓ PaO2
↓
↓ O2 saturation of hemoglobin
↓ O2 content of blood
Anemia
↓ Hemoglobin concentration
-
↓ O2 content of blood
Carbon monoxide poisoning
↓
O2
content
of
blood
Left shift of O2-hemoglobin curve
-
Cyanide poisoning
↓ O2 utilization by tissues
-
Hypoxia is decreased O2 delivery to the tissues. Since O2
delivery is the product of cardiac output and O2 content of
blood, hypoxia is caused by decreased cardiac output (blood
flow) or decreased O2 content of blood. Recall that O2 content
of blood is determined primarily by the amount O2hemoglobin. Causes of hypoxia are summarized in Table 5-6.
A decrease in cardiac output and a decrease in regional
(local) blood flow are self-evident causes of hypoxia.
Hypoxemia (due to any cause; see Table 5-5) is a major cause
of hypoxia. The reason that hypoxemia causes hypoxia is that
a PaO2 of less than 60 mm Hg reduces the percent saturation of
hemoglobin (see Fig. 5-20). O2-hemoglobin is the major form
of O2 in blood; thus, a decrease in the amount of O2hemoglobin means a decrease in total O2 content. Anemia, or
decreased hemoglobin concentration, also decreases the
amount of O2-hemoglobin in blood. Carbon monoxide (CO)
poisoning causes hypoxia because CO occupies binding sites
on hemoglobin that normally are occupied by O2; thus, CO
decreases the O2 content of blood. Cyanide poisoning
interferes with O2 utilization of tissue; it is one cause of
hypoxia that does not involve decreased blood flow or
decreased O2 content of blood.
Summary

Lung volumes and capacities are measured with a
spirometer (except for those volumes and capacities that
include the residual volume).

Dead space is the volume of the airways and lungs
that does not participate in gas exchange. Anatomic dead
space is the volume of conducting airways. Physiologic dead
space includes the anatomic dead space plus those regions of
the respiratory zone that do not participate in gas exchange.

The alveolar ventilation equation expresses the
inverse relationship between PACO2 and alveolar ventilation.
The alveolar gas equation extends this relationship to predict
PAO2.

In quiet breathing, respiratory muscles (diaphragm)
are used only for inspiration; expiration is passive.

Compliance of the lungs and the chest wall is
measured as the slope of the pressure-volume relationship. As
a result of their elastic forces, the chest wall has a tendency to
spring out, and the lungs have a tendency to collapse. At FRC,
these two forces are exactly balanced, and intrapleural
pressure is negative. Compliance of the lungs increases in
emphysema and with aging. Compliance decreases in fibrosis
and when pulmonary surfactant is absent.

Surfactant, a mixture of phospholipids produced by
type II alveolar cells, reduces surface tension so that the
alveoli can remain inflated despite their small radii. Neonatal
respiratory distress syndrome occurs when surfactant is
absent.

Airflow into and out of the lungs is driven by the
pressure gradient between the atmosphere and the alveoli and
is inversely proportional to the resistance of the airways.
Stimulation of β2-adrenergic receptors dilates the airways, and
stimulation of cholinergic muscarinic receptors constricts the
airways.

Diffusion
of
O2
and
CO2
across
the
alveolar/pulmonary capillary barrier is governed by Fick's law
and driven by the partial pressure difference of the gas. Mixed
venous blood enters the pulmonary capillaries and is
"arterialized" as O2 is added to it and CO2 is removed from it.
Blood leaving the pulmonary capillaries will become systemic
arterial blood.

Diffusion-limited gas exchange is illustrated by CO
and by O2 in fibrosis or strenuous exercise. Perfusion-limited
gas exchange is illustrated by N2O, CO2, and O2 under normal
conditions.

O2 is transported in blood in dissolved form and
bound to hemoglobin. One molecule of hemoglobin can bind
four molecules of O2. The sigmoidal shape of the O2hemoglobin dissociation curve reflects increased affinity for
each successive molecule of O2 that is bound. Shifts to the
right of the O2-hemoglobin dissociation curve are associated
with decreased affinity, increased P50, and increased unloading
of O2 in the tissues. Shifts to the left are associated with
increased affinity, decreased P50, and decreased unloading of
O2 in the tissues. CO decreases the O2-binding capacity of
hemoglobin and causes a shift to the left.

CO2 is transported in blood in dissolved form, as
carbaminohemoglobin, and as HCO3-. HCO3- is produced in
red blood cells from CO2 and H2O, catalyzed by carbonic
anhydrase. HCO3- is transported in the plasma to the lungs
where the reactions occur in reverse to regenerate CO2, which
then is expired.

Pulmonary blood flow is the cardiac output of the
right heart, and it is equal to the cardiac output of the left
heart. Pulmonary blood flow is regulated primarily by P AO2,
with alveolar hypoxia producing vasoconstriction.

Pulmonary blood flow is unevenly distributed in the
lungs of a person who is standing: Blood flow is lowest at the
apex of the lung and highest at the base. Ventilation is
similarly
distributed,
although
regional
variations
in
ventilatory rates are not as great as for blood flow. Thus, V/Q
is highest at the apex of the lung and lowest at the base, with
an average value of 0.8. Where V/Q is highest, PaO2 is highest
and PaCO2 is lowest.

V/Q defects impair gas exchange. If ventilation is
decreased relative to perfusion, then PaO2 and PaCO2 will
approach their values in mixed venous blood. If perfusion is
decreased relative to ventilation, then PAO2 and PACO2 will
approach their values in inspired air.

Breathing is controlled by the medullary respiratory
center, which receives sensory information from central
chemoreceptors
in
the
brain
stem,
from
peripheral
chemoreceptors in the carotid and aortic bodies, and from
mechanoreceptors
in
the
lungs
and
joints.
Central
chemoreceptors are sensitive primarily to changes in the pH of
CSF, with decreases in pH causing hyperventilation.
Peripheral chemoreceptors are sensitive primarily to O2, with
hypoxemia causing hyperventilation.

During exercise, the ventilation rate and cardiac
output increase to match the body's needs for O2 so that mean
values for PaO2 and PaCO2 do not change. The O2-hemoglobin
dissociation curve shifts to the right as a result of increased
tissue PCO2, increased temperature, and decreased tissue pH.

At high altitude, hypoxemia results from the
decreased PO2 of inspired air. Adaptive responses to
hypoxemia include hyperventilation, respiratory alkalosis,
pulmonary vasoconstriction, polycythemia, increased 2,3-DPG
production, and a right shift of the O2-hemoglobin dissociation
curve.

Hypoxemia, or decreased PaO2, is caused by high
altitude, hypoventilation, diffusion defects, V/Q defects, and
right-to-left shunts. Hypoxia, or decreased O2 delivery to
tissues, is caused by decreased cardiac output or decreased O 2
content of blood.
Chronic Obstructive Pulmonary Disease (COPD)
DESCRIPTION OF CASE. A 65-year-old man has smoked
2 packs of cigarettes a day for more than 40 years. He has a
long history of producing morning sputum, cough, and
progressive shortness of breath on exertion (dyspnea). For the
past decade, each fall and winter he has had bouts of
bronchitis with dyspnea and wheezing, which have gradually
worsened over the years. When admitted to the hospital, he is
short of breath and cyanotic. He is barrel-chested. His
breathing rate is 25 breaths/min, and his tidal volume is 400
mL. His vital capacity is 80% of the normal value for a man
his age and size, and FEV1 is 60% of normal. The following
arterial blood values were measured (normal values are in
parentheses):

pH, 7.47 (normal, 7.4)

PaO2, 60 mm Hg (normal, 100 mm Hg)

PaCO2, 30 mm Hg (normal, 40 mm Hg)

Hemoglobin saturation, 90%

Hemoglobin concentration, 14 g/L (normal, 15 g/L)
EXPLANATION OF CASE. The man's history of smoking
and bronchitis suggests severe lung disease. Of the arterial
blood values, the one most notably abnormal is the PaO2 of 60
mm Hg. Hemoglobin concentration (14 g/L) is normal, and the
percent saturation of hemoglobin of 90% is in the expected
range for a PaO2 of 60 mm Hg (see Fig. 5-20).
The low value for PaO2 at 60 mm Hg can be explained in terms
of a gas exchange defect in the lungs. This defect is best
understood by comparing PaO2 (measured as 60 mm Hg) to
PAO2 (calculated with the alveolar gas equation). If the two are
equal, then gas exchange is normal and there is no defect. If
PaO2 is less than PAO2 (i.e., there is an A - a difference), then
there is a V/Q defect, with insufficient amounts of O2 being
added to pulmonary capillary blood.
The alveolar gas equation can be used to calculate PAO2, if the
PIO2, PACO2, and respiratory quotient are known. P IO2 is
calculated from the barometric pressure (corrected for water
vapor pressure) and the percent O2 in inspired air (21%).
PACO2 is equal to PaCO2, which is given. The respiratory
quotient is assumed to be 0.8. Thus,
Since the measured PaO2 (60 mm Hg) is much less than the
calculated PAO2 (113 mm Hg), there must be a mismatch of
ventilation and perfusion. Some blood is perfusing alveoli that
are not ventilated, thereby diluting the oxygenated blood and
reducing arterial PO2.
The man's PaCO2 is lower than normal because he is
hyperventilating and blowing off more CO2 than his body is
producing. He is hyperventilating because he is hypoxemic.
His PaO2 is just low enough to stimulate peripheral
chemoreceptors, which drive the medullary inspiratory center
to increase the ventilation rate. His arterial pH is slightly
alkaline because his hyperventilation has produced a mild
respiratory alkalosis.
The man's FEV1 is reduced more than his vital capacity; thus,
FEV1/FVC is decreased, which is consistent with an
obstructive lung disease in which airway resistance is
increased. His barrel-shaped chest is a compensatory
mechanism for the increased airway resistance: High lung
volumes exert positive traction on the airways and decrease
airway resistance; by breathing at a higher lung volume, he
can partially offset the increased airway resistance from his
disease.
TREATMENT. The man is advised to stop smoking
immediately. He is given an antibiotic to treat a suspected
infection and an inhalant form of albuterol
dilate his airways.
(a β2 agonist) to