CHAPTER 40

UNIT VII
Principles of Gas Exchange; Diffusion of
Oxygen and Carbon Dioxide Through
the Respiratory Membrane

After the alveoli are ventilated with fresh air, the next step
ing on the surfaces of the respiratory passages and alveoli
in respiration is diffusion of oxygen (O2) from the alveoli
is proportional to the summated force of impact of all the
into the pulmonary blood and diffusion of carbon diox- molecules of that gas striking the surface at any given in-
ide (CO2) in the opposite direction, out of the blood into stant. This means that the pressure is directly proportional
the alveoli. The process of diffusion is simply the random to the concentration of the gas molecules.
motion of molecules in all directions through the respira- In respiratory physiology, one deals with mixtures of
tory membrane and adjacent fluids. However, in respira- gases, mainly oxygen, nitrogen, and carbon dioxide. The rate
tory physiology, we are concerned not only with the basic of diffusion of each of these gases is directly proportional
mechanism by which diffusion occurs but also with the to the pressure caused by that gas alone, which is called the
rate at which it occurs, which is a much more complex partial pressure of that gas. The concept of partial pressure
issue, requiring a deeper understanding of the physics of can be explained as follows.
diffusion and gas exchange. Consider air, which has an approximate composition of
79% nitrogen and 21% oxygen. The total pressure of this
Physics of Gas Diffusion and Gas Partial Pressures mixture at sea level averages 760 mm Hg. It is clear from
the preceding description of the molecular basis of pres-
Molecular Basis of Gas Diffusion sure that each gas contributes to the total pressure in direct
All the gases of concern in respiratory physiology are sim- proportion to its concentration. Therefore, 79% of the 760
ple molecules that are free to move among one another by mm Hg is caused by nitrogen (600 mm Hg) and 21% by
diffusion. This is also true of gases dissolved in the fluids O2 (160 mm Hg). Thus, the partial pressure of nitrogen in
and tissues of the body. the mixture is 600 mm Hg, and the partial pressure of O2
For diffusion to occur, there must be a source of energy. is 160 mm Hg; the total pressure is 760 mm Hg, the sum
This source of energy is provided by the kinetic motion of the individual partial pressures. The partial pressures of
of the molecules. Except at absolute zero temperature, all individual gases in a mixture are designated by the symbols
molecules of all matter are continually undergoing motion. Po2, Pco2, Pn2, Phe, and so forth.
For free molecules that are not physically attached to oth-
Pressures of Gases Dissolved in Water and Tissues
ers, this means linear movement at high velocity until they
strike other molecules. They then bounce away in new di- Gases dissolved in water or in body tissues also exert pres-
rections and continue moving until they strike other mol- sure because the dissolved gas molecules are moving ran-
ecules again. In this way, the molecules move rapidly and domly and have kinetic energy. Furthermore, when the gas
randomly among one another. dissolved in fluid encounters a surface, such as the mem-
Net Diffusion of a Gas in One Direction—Effect of a brane of a cell, it exerts its own partial pressure in the same
Concentration Gradient. If a gas chamber or solution has a way as a gas in the gas phase. The partial pressures of the
high concentration of a particular gas at one end of the cham- separate dissolved gases are designated the same as the par-
ber and a low concentration at the other end, as shown in tial pressures in the gas state—that is, Po2, Pco2, Pn2, Phe,
Figure 40-1, net diffusion of the gas will occur from the high- and so forth.
concentration area toward the low-concentration area. The Factors That Determine Partial Pressure of a Gas
reason is obvious. There are far more molecules at end A of the Dissolved in a Fluid. The partial pressure of a gas in a so-
chamber to diffuse toward end B than there are molecules to lution is determined not only by its concentration but also
diffuse in the opposite direction. Therefore, the rates of diffu- by the solubility coefficient of the gas. That is, some types
sion in each of the two directions are proportionately different, of molecules, especially CO2, are physically or chemically
as demonstrated by the lengths of the arrows in the figure. attracted to water molecules, whereas other types of mol-
ecules are repelled. When molecules are attracted, far more
Gas Pressures in a Mixture of Gases—Partial Pressures of of them can be dissolved without building up excess par-
Individual Gases tial pressure within the solution. Conversely, in the case of
Pressure is caused by multiple impacts of moving mole- molecules that are repelled, high partial pressure will devel-
cules against a surface. Therefore, the pressure of a gas act- op with fewer dissolved molecules. These relationships are

511
UNIT VII Respiration

Dissolved gas molecules

exert to escape through the surface is called the vapor pres-
sure of the water. At normal body temperature, 37°C (98.6°F),
this vapor pressure is 47 mm Hg. Therefore, once the gas
mixture has become fully humidified—that is, once it is in
equilibrium with the water—the partial pressure of the water
vapor in the gas mixture is 47 mm Hg. This partial pressure,
like the other partial pressures, is designated as Ph2o.
The vapor pressure of water depends entirely on the tem-
perature of the water. The higher the temperature, the great-
Figure 40-1. Diffusion of oxygen from one end of a chamber to the
other. The difference between the lengths of the arrows represents
er the kinetic activity of the molecules and, therefore, the
net diffusion. greater the likelihood that the water molecules will escape
from the surface of the water into the gas phase. For example,
the water vapor pressure at 0°C is 5 mm Hg, and at 100°C it
expressed by the following formula, which is Henry’s law: is 760 mm Hg. The most important value to remember is the
vapor pressure at body temperature, 47 mm Hg. This value
$PODFOUSBUJPOyPGyEJTTPMWFEyHBT appears in many of our subsequent discussions.
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Pressure Difference Causes Net Diffusion of Gases
When partial pressure is expressed in atmospheres (1 Through Fluids
atmosphere [1 atm] pressure equals 760 mm Hg) and con- From the preceding discussion, it is clear that when the par-
centration is expressed in volume of gas dissolved in each tial pressure of a gas is greater in one area than in another
volume of water, the solubility coefficients for important area, there will be net diffusion from the high-pressure area
respiratory gases at body temperature are the following: toward the low-pressure area. For example, returning to
Figure 40-1, one can readily see that the molecules in the
Oxygen: 0.024
area of high pressure, because of their greater number, have a
Carbon dioxide: 0.57 greater chance of moving randomly into the area of low pres-
Carbon monoxide: 0.018 sure than do molecules attempting to go in the other direc-
tion. However, some molecules do bounce randomly from
Nitrogen: 0.012
the low-pressure area toward the high-pressure area. There-
Helium: 0.008 fore, the net diffusion of gas from the area of high pressure
to the area of low pressure is equal to the number of mol-
From this list, one can see that CO2 is more than 20 ecules bouncing in this forward direction minus the number
times as soluble as O2. Therefore, the partial pressure of bouncing in the opposite direction, which is proportional to
CO2 for a given concentration is less than one-twentieth the gas partial pressure difference between the two areas,
(5%) of that exerted by O2. called simply the pressure difference for causing diffusion.
Diffusion of Gases Between Gas Phase in Alveoli and
Quantifying Net Rate of Diffusion in Fluids. In addition
Dissolved Phase in Pulmonary Blood. The partial pressure of to the pressure difference, several other factors affect the
each gas in the alveolar respiratory gas mixture tends to force rate of gas diffusion in a fluid: (1) the solubility of the gas in
molecules of that gas into solution in the blood of the alveo- the fluid; (2) the cross-sectional area of the fluid; (3) the dis-
lar capillaries. Conversely, the molecules of the same gas that tance through which the gas must diffuse; (4) the molecular
are already dissolved in the blood are bouncing randomly in weight of the gas; and (5) the temperature of the fluid. In
the fluid of the blood, and some of these bouncing molecules the body, the temperature remains reasonably constant and
escape back into the alveoli. The rate at which they escape usually need not be considered.
is directly proportional to their partial pressure in the blood. The greater the solubility of the gas, the greater the num-
But, in which direction will net diffusion of the gas oc- ber of molecules available to diffuse for any given partial
cur? The answer is that net diffusion is determined by the pressure difference. The greater the cross-sectional area of
difference between the two partial pressures. If the partial the diffusion pathway, the greater the total number of mol-
pressure is greater in the gas phase in the alveoli, as is nor- ecules that diffuse. Conversely, the greater the distance the
mally true for oxygen, then more molecules will diffuse into molecules must diffuse, the longer it will take the molecules
the blood than in the other direction. Alternatively, if the to diffuse the entire distance. Finally, the greater the veloc-
partial pressure of the gas is greater in the dissolved state in ity of kinetic movement of the molecules, which is inversely
the blood, which is normally true for CO2, then net diffu- proportional to the square root of the molecular weight, the
sion will occur toward the gas phase in the alveoli. greater the rate of diffusion of the gas. All these factors can
Vapor Pressure of Water
be expressed in a single formula, as follows:

When nonhumidified air is breathed into the respiratory ɳ1 ° " ° 4

%г √
passageways, water immediately evaporates from the surfac- E ° .8
es of these passages and humidifies the air. This results from
the fact that water molecules, like different dissolved gas in which D is the diffusion rate, ΔP is the partial pres-
molecules, are continually escaping from the water surface sure difference between the two ends of the diffusion path-
into the gas phase. The partial pressure that water molecules way, A is the cross-sectional area of the pathway, S is the

512
Chapter 40 Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane

Table 40-1 Partial Pressures (in mm Hg) and

solubility of the gas, d is the distance of diffusion, and MW
composition (in percentages) of Respiratory Gases as
is the molecular weight of the gas.
They Enter and Leave the Lungsa
It is obvious from this formula that the characteristics
of the gas determine two factors of the formula—solubility Atmo-
and molecular weight. Together, these two factors deter- spheric Humidi- Alveolar Expired

UNIT VII
mine the diffusion coefficient of the gas, which is propor- Air fied Air Air Air
√
tional to 4 .8; that is, the relative rates at which differ- N2 597 563.4 569 566
ent gases at the same partial pressure levels will diffuse are (78.62) (74.09) (74.9) (74.5)
proportional to their diffusion coefficients. Assuming that O2 159 149.3 104 120
the diffusion coefficient for O2 is 1, the relative diffusion (20.84) (19.67) (13.6) (15.7)
coefficients for different gases of respiratory importance in
CO2 0.3 (0.04) 0.3 (0.04) 40 (5.3) 27 (3.6)
the body fluids are as follows:
H2O 3.7 (0.50) 47 (6.20) 47 (6.2) 47 (6.2)
Oxygen: 1.0 Total 760 (100) 760 (100) 760 (100) 760 (100)
Carbon dioxide: 20.3 aAt sea level.
Carbon monoxide: 0.81
Nitrogen: 0.53
Helium: 0.95

Diffusion of Gases Through Tissues

The gases that are of respiratory importance are all highly 1st breath 2nd breath 3rd breath
soluble in lipids and, consequently, are highly soluble in cell
membranes. Because of this, the major limitation to move-
ment of gases in tissues is the rate at which the gases can
diffuse through the tissue water instead of through the cell
membranes. Therefore, diffusion of gases through tissues, in-
cluding through the respiratory membrane, is almost equal to
4th breath 8th breath 12th breath 16th breath
the diffusion of gases in water, as given in the preceding list.
Figure 40-2. Expiration of a gas from an alveolus with successive
breaths.

COMPOSITIONS OF ALVEOLAR AIR AND

the air dilutes the oxygen partial pressure at sea level from
ATMOSPHERIC AIR ARE DIFFERENT
an average of 159 mm Hg in atmospheric air to 149 mm
Alveolar air does not have the same concentrations of Hg in the humidified air, and it dilutes the nitrogen partial
gases as atmospheric air (Table 40-1). There are several pressure from 597 to 563 mm Hg.
reasons for the differences. First, alveolar air is only par-
tially replaced by atmospheric air with each breath. Sec- Alveolar Air Is Slowly Renewed by
ond, O2 is constantly being absorbed into the pulmonary Atmospheric Air
blood from the alveolar air. Third, CO2 is constantly dif- In Chapter 38, we pointed out that the average functional
fusing from the pulmonary blood into the alveoli. And residual capacity of the lungs (the volume of air remain-
fourth, dry atmospheric air that enters the respiratory ing in the lungs at the end of normal expiration) measures
passages is humidified even before it reaches the alveoli. about 2300 ml in men. Yet only 350 ml of new air is brought
into the alveoli with each normal inspiration, and this same
Air Is Humidified in the Respiratory amount of old alveolar air is expired. Therefore, the volume
Passages of alveolar air replaced by new atmospheric air with each
Table 40-1 shows that atmospheric air is composed almost breath is only one-seventh of the total, so multiple breaths
entirely of nitrogen and O2; it normally contains almost no are required to exchange most of the alveolar air. Figure 40-2
CO2 and little water vapor. However, as soon as the atmo- shows this slow rate of renewal of the alveolar air. In the first
spheric air enters the respiratory passages, it is exposed to alveolus of the figure, excess gas is present in the alveoli, but
the fluids that cover the respiratory surfaces. Even before the note that even at the end of 16 breaths, the excess gas still has
air enters the alveoli, it becomes almost totally humidified. not been completely removed from the alveoli.
The partial pressure of water vapor at a normal body Figure 40-3 demonstrates graphically the rate at which
temperature of 37°C is 47 mm Hg, which is therefore the excess gas in the alveoli is normally removed, showing
partial pressure of water vapor in the alveolar air. Because that with normal alveolar ventilation, about half the gas is
the total pressure in the alveoli cannot rise to more than removed in 17 seconds. When a person’s rate of alveolar
the atmospheric pressure (760 mm Hg at sea level), this ventilation is only half-normal, half of the gas is removed
water vapor simply dilutes all the other gases in the in 34 seconds, and when the rate of ventilation is twice
inspired air. Table 40-1 also shows that humidification of normal, half is removed in about 8 seconds.
513
UNIT VII Respiration

100 Upper limit at maximum ventilation

150

(% of original concentration)
250 ml O2/min

Alveolar partial pressure

Concentration of gas
80 1 /2 125

of oxygen (mm Hg)

no
rm
al 100 A Normal alveolar PO2

No
60 alv
eo

r
al lar

m
al ven
2×
ve tilat 75
40 ola ion
no
r ve
rm
ntil 50
atio
20 al al
ve n 1000 ml O2/min
ola 25
r ven
tilation
0 0
0 10 20 30 40 50 60 0 5 10 15 20 25 30 35 40
Time (seconds) Alveolar ventilation (L/min)
Figure 40-3. Rate of removal of excess gas from alveoli. Figure 40-4. Effect of alveolar ventilation on the alveolar partial pres-
sure of oxygen (PO2) at two rates of oxygen absorption from the alveo-
li—250 ml/min and 1000 ml/min. Point A is the normal operating point.
Slow Replacement of Alveolar Air Helps Stabilize Res-
piratory Control. The slow replacement of alveolar air is
of particular importance in preventing sudden changes in 175
gas concentrations in the blood. This makes the respira-

Alveolar partial pressure

150
tory control mechanism much more stable than it would

of CO2 (mm Hg)

be otherwise, and it helps prevent excessive increases and 125
800 ml CO2/min
decreases in tissue oxygenation, tissue CO2 concentration, 100
and tissue pH when respiration is temporarily interrupted.
75
Oxygen Concentration and Partial
Pressure in Alveoli 50 Normal alveolar PCO2

Oxygen is continually being absorbed from the alveoli into A

25 200 ml CO2/min
the blood of the lungs, and new O2 is continually being
0
breathed into the alveoli from the atmosphere. The more
0 5 10 15 20 25 30 35 40
rapidly O2 is absorbed, the lower its concentration in the
Alveolar ventilation (L/min)
alveoli becomes; conversely, the more rapidly new O2 is
Figure 40-5. Effect of alveolar ventilation on the alveolar partial
breathed into the alveoli from the atmosphere, the higher
pressure of carbon dioxide (PCO2) at two rates of carbon dioxide ex-
its concentration becomes. Therefore, O2 concentration cretion from the blood—800 ml/min and 200 ml/min. Point A is the
in the alveoli, as well as its partial pressure, is controlled normal operating point.
by the following: (1) the rate of absorption of O2 into the
blood; and (2) the rate of entry of new O2 into the lungs
by the ventilatory process. CO2 Concentration and Partial Pressure in
Figure 40-4 shows the effect of alveolar ventilation Alveoli
and rate of O2 absorption into the blood on the alveolar Carbon dioxide is continually formed in the body and
Po2. One curve represents O2 absorption at a rate of 250 then carried in the blood to the alveoli; it is continually
ml/min, and the other curve represents a rate of 1000 ml/ removed from the alveoli by ventilation. Figure 40-5
min. At a normal ventilatory rate of 4.2 L/min and an O2 shows the effects on the alveolar partial pressure of Pco2
consumption of 250 ml/min, the normal operating point of both alveolar ventilation and two rates of CO2 excre-
in Figure 40-4 is point A. The figure also shows that when tion, 200 and 800 ml/min. One curve represents a normal
1000 ml of O2 is being absorbed each minute, as during rate of CO2 excretion of 200 ml/min. At the normal rate of
moderate exercise, the rate of alveolar ventilation must alveolar ventilation of 4.2 L/min, the operating point for
increase fourfold to maintain the alveolar Po2 at the nor- alveolar Pco2 is at point A in Figure 40-5 (i.e., 40 mm Hg).
mal value of 104 mm Hg. Two other facts are also evident from Figure 40-5.
Another effect shown in Figure 40-4 is that even an First, the alveolar Pco2 increases directly in proportion to
extreme increase in alveolar ventilation can never increase the rate of CO2 excretion, as represented by the fourfold
the alveolar Po2 above 149 mm Hg as long as the person elevation of the curve (when 800 ml of CO2 are excreted
is breathing normal atmospheric air at sea level pressure, per minute). Second, the alveolar Pco2 decreases in
because 149 mm Hg is the maximum Po2 in humidified inverse proportion to alveolar ventilation. Therefore, the
air at this pressure. If the person breathes gases that con- concentrations and partial pressures of both O2 and CO2
tain partial pressures of O2 higher than 149 mm Hg, the in the alveoli are determined by the rates of absorption or
alveolar Po2 can approach these higher pressures at high excretion of the two gases and by the amount of alveolar
rates of ventilation. ventilation.

514
Chapter 40 Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane

160
Pressures of O2 and CO2 140

120
Oxygen (Po2)

UNIT VII
100
(mm Hg)

Dead Alveolar air

80
space and dead Alveolar air
60 air space air
Carbon dioxide (Pco2)
40

20

0 100μ
0 100 200 300 400 500
Air expired (milliliters)
Figure 40-6. Oxygen and carbon dioxide partial pressures (PO2 and A
PCO2) in the various portions of normal expired air.

Alveolus

Terminal
bronchiole

Alveolus
Interstitial space
Smooth
Capillaries
muscle
Lymphatic Alveolus
vessel

Respiratory
bronchiole
Perivascular
Vein Artery interstitial space
Alveolus
Alveolar duct B
Elastic Figure 40-8. A, Surface view of capillaries in an alveolar wall. B,
fibers Cross-sectional view of alveolar walls and their vascular supply. (A,
Alveolar sacs
From Maloney JE, Castle BL: Pressure-diameter relations of capillar-
ies and small blood vessels in frog lung. Respir Physiol 7:150, 1969.)

alveolar air is expired at the end of expiration. Therefore,

the method of collecting alveolar air for study is simply to
collect a sample of the last portion of the expired air after
forceful expiration has removed all the dead space air.
Normal expired air, containing both dead space air and
alveolar air, has gas concentrations and partial pressures ap-
proximately as shown in Table 40-1 (i.e., concentrations be-
Figure 40-7. Respiratory unit. tween those of alveolar air and humidified atmospheric air).

Expired Air Is a Combination of Dead Space Air and DIFFUSION OF GASES THROUGH THE
Alveolar Air
RESPIRATORY MEMBRANE
The overall composition of expired air is determined by
the following: (1) the amount of the expired air that is dead Respiratory Unit. Figure 40- 7 shows the respira-
space air; and (2) the amount that is alveolar air. Figure tory unit (also called respiratory lobule), which is
40-6 shows the progressive changes in O2 and CO2 partial composed of a respiratory bronchiole, alveolar
pressures in the expired air during the course of expiration. ducts, atria, and alveoli. There are about 300 mil-
The first portion of this air, the dead space air from the res- lion alveoli in the two lungs, and each alveolus has
piratory passageways, is typical humidified air, as shown an average diameter of about 0.2 millimeter. The
in Table 40-1. Then, progressively more and more alveo- alveolar walls are extremely thin, and between the
lar air becomes mixed with the dead space air until all the
alveoli is an almost solid network of interconnect-
dead space air has finally been washed out, and nothing but
ing capillaries, shown in Figure 40- 8. Because of

515
UNIT VII Respiration

Epithelial 5. A capillary basement membrane that in many places

Alveolar basement fuses with the alveolar epithelial basement membrane
epithelium membrane
6. The capillary endothelial membrane
Despite the large number of layers, the overall thick-
ness of the respiratory membrane in some areas is as
little as 0.2 micrometer and averages about 0.6 microm-
eter, except where there are cell nuclei. From histological
Fluid and studies, it has been estimated that the total surface area
surfactant
layer of the respiratory membrane is about 70 square meters in
Capillary healthy men, which is equivalent to the floor area of a 25 ×
30-foot room. The total quantity of blood in the capillar-
Alveolus ies of the lungs at any given instant is 60 to 140 ml. Now,
imagine this small amount of blood spread over the entire
Diffusion O2 surface of a 25 × 30-foot floor, and it is easy to understand
the rapidity of the respiratory exchange of O2 and CO2.
Diffusion CO2 The average diameter of the pulmonary capillaries is
only about 5 micrometers, which means that red blood
cells must squeeze through them. The red blood cell
membrane usually touches the capillary wall, so O2 and
CO2 need not pass through significant amounts of plasma
as they diffuse between the alveolus and red blood cell.
This, too, increases the rapidity of diffusion.
Red blood cell
Factors Affecting Rate of Gas Diffusion
Through the Respiratory Membrane
Referring to the earlier discussion of diffusion of gases in
Capillary endothelium water, one can apply the same principles to diffusion of
Interstitial space Capillary basement membrane gases through the respiratory membrane. Thus, the fac-
Figure 40-9. Ultrastructure of the alveolar respiratory membrane,
tors that determine how rapidly a gas will pass through
shown in cross section. the membrane are the following: (1) the thickness of the
membrane; (2) the surface area of the membrane; (3) the
the extensiveness of the capillary plexus, the flow diffusion coefficient of the gas in the substance of the
of blood in the alveolar wall has been described as membrane; and (4) the partial pressure difference of the
a sheet of flowing blood. Thus, it is obvious that gas between the two sides of the membrane.
the alveolar gases are in very close proximity to the The thickness of the respiratory membrane occasionally
blood of the pulmonary capillaries. Furthermore, increases—for example, as a result of edema fluid in the
gas exchange between the alveolar air and pulmo- interstitial space of the membrane and in the alveoli—so
nary blood occurs through the membranes of all the the respiratory gases must then diffuse not only through
terminal portions of the lungs, not merely in the al- the membrane but also through this fluid. Also, some pul-
veoli. All these membranes are collectively known monary diseases cause fibrosis of the lungs, which can
as the respiratory membrane, also called the pulmo- increase the thickness of some portions of the respira-
nary membrane. tory membrane. Because the rate of diffusion through the
membrane is inversely proportional to the thickness of the
Respiratory Membrane. Figure 40-9 shows the ultra- membrane, any factor that increases the thickness to more
structure of the respiratory membrane drawn in cross than two to three times normal can interfere significantly
section on the left and a red blood cell on the right. It with normal respiratory exchange of gases.
also shows diffusion of O2 from the alveolus into the red The surface area of the respiratory membrane can
blood cell and diffusion of CO2 in the opposite direc- be greatly decreased by many conditions. For example,
tion. Note the following different layers of the respiratory removal of an entire lung decreases the total surface area
membrane: to half-normal. Also, in emphysema, many of the alveoli
1. A layer of fluid containing surfactant that lines the al- coalesce, with dissolution of many alveolar walls. There-
veolus and reduces the surface tension of alveolar fluid fore, the new alveolar chambers are much larger than the
2. The alveolar epithelium, composed of thin epithelial original alveoli, but the total surface area of the respira-
cells tory membrane is often decreased as much as fivefold
3. An epithelial basement membrane because of loss of the alveolar walls. When the total sur-
4. A thin interstitial space between the alveolar epi- face area is decreased to about one-third to one-fourth
thelium and capillary membrane normal, exchange of gases through the membrane is

516
Chapter 40 Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane

substantially impeded, even under resting conditions, and 1300

Resting
during competitive sports and other strenuous exercise, 1200 Exercise
even the slightest decrease in surface area of the lungs can
be a serious detriment to respiratory exchange of gases. 1100
The diffusion coefficient for transfer of each gas through

UNIT VII
Diffusing capacity (ml/min/mm Hg)
1000
the respiratory membrane depends on the gas’s solubility
in the membrane and, inversely, on the square root of the 900
gas’s molecular weight. The rate of diffusion in the respira- 800
tory membrane is almost exactly the same as that in water,
700
for reasons explained earlier. Therefore, for a given pres-
sure difference, CO2 diffuses about 20 times as rapidly as 600
O2. Oxygen diffuses about twice as rapidly as nitrogen.
500
The pressure difference across the respiratory membrane
is the difference between the partial pressure of the gas in 400
the alveoli and the partial pressure of the gas in the pul-
300
monary capillary blood. Therefore, the difference between
these two pressures is a measure of the net tendency for the 200
gas molecules to move through the membrane. 100
When the partial pressure of a gas in the alveoli is
greater than the pressure of the gas in the blood, as is true 0
for O2, net diffusion from the alveoli into the blood occurs. CO O2 CO2
When the pressure of the gas in the blood is greater than Figure 40-10. Diffusing capacities for carbon monoxide, oxygen,
the partial pressure in the alveoli, as is true for CO2, net and carbon dioxide in the normal lungs under resting conditions and
diffusion from the blood into the alveoli occurs. during exercise.

Diffusing Capacity of the Respiratory blood, called the ventilation-perfusion ratio, explained later
Membrane in this chapter. Therefore, during exercise, oxygenation of
The ability of the respiratory membrane to exchange a gas the blood is increased not only by increased alveolar venti-
between the alveoli and pulmonary blood is expressed in lation but also by greater diffusing capacity of the respira-
quantitative terms by the respiratory membrane’s diffusing tory membrane for transporting O2 into the blood.
capacity, which is defined as the volume of a gas that will
Diffusing Capacity for Carbon Dioxide. The diffusing
diffuse through the membrane each minute for a partial
pressure difference of 1 mm Hg. All the factors discussed capacity for CO2 has never been measured because CO2
earlier that affect diffusion through the respiratory mem- diffuses through the respiratory membrane so rapidly that
brane can affect this diffusing capacity. the average Pco2 in the pulmonary blood is not very dif-
ferent from the Pco2 in the alveoli—the average difference
Diffusing Capacity for Oxygen. In the average young
is less than 1 mm Hg. With currently available techniques,
man, the diffusing capacity for O2 under resting conditions this difference is too small to be measured.
averages 21 ml/min per mm Hg. In functional terms, what Nevertheless, measurements of diffusion of other gases
does this mean? The mean O2 pressure difference across have shown that the diffusing capacity varies directly with
the respiratory membrane during normal quiet breathing is the diffusion coefficient of the particular gas. Because the
about 11 mm Hg. Multiplying this pressure by the diffusing diffusion coefficient of CO2 is slightly more than 20 times
capacity (11 × 21) gives a total of about 230 ml of oxygen that of O2, one would expect a diffusing capacity for CO2
diffusing through the respiratory membrane each minute, under resting conditions of about 400 to 450 ml/min per
which is equal to the rate at which the resting body uses O2. mm Hg and during exercise of about 1200 to 1300 ml/
min per mm Hg. Figure 40-10 compares the measured
Increased Oxygen Diffusing Capacity During Exercise.
or calculated diffusing capacities of carbon monoxide, O2,
During strenuous exercise or other conditions that greatly and CO2 at rest and during exercise, showing the extreme
increase pulmonary blood flow and alveolar ventilation, the diffusing capacity of CO2 and the effect of exercise on the
diffusing capacity for O2 increases to about three times the diffusing capacity of each of these gases.
diffusing capacity under resting conditions. This increase
is caused by several factors, including the following: (1) Measurement of Diffusing Capacity—Carbon Monox-
opening up of many previously dormant pulmonary capil- ide Method. The O2 diffusing capacity can be calculated
from measurements of the following: (1) alveolar Po2; (2)
laries or extra dilation of already open capillaries, thereby
Po2 in the pulmonary capillary blood; and (3) the rate of
increasing the surface area of the blood into which the O2
O2 uptake by the blood. However, measuring the Po2 in the
can diffuse; and (2) a better match between the ventilation pulmonary capillary blood is so difficult and imprecise that
of the alveoli and perfusion of the alveolar capillaries with

517
UNIT VII Respiration

50 v VA/Q = 0
it is not practical to measure oxygen diffusing capacity by VA/Q = Normal
such a direct procedure, except on an experimental basis.
40 (PO2 = 40)
To obviate the difficulties encountered in measuring ox- (PCO2 = 45)

PCO2 (mm Hg)

ygen diffusing capacity directly, physiologists usually meas- Normal
30 alveolar air
ure carbon monoxide (CO) diffusing capacity instead and
then calculate the O2 diffusing capacity from this. The prin- (PO2 = 104)
20 (PCO2 = 40)
ciple of the CO method is as follows. A small amount of CO
is breathed into the alveoli, and the partial pressure of the
CO in the alveoli is measured from appropriate alveolar air
10 (PO2 = 149) VA/Q = ∞
(PCO2 = 0) I
samples. The CO pressure in the blood is essentially zero
because hemoglobin combines with this gas so rapidly that 0 20 40 60 80 100 120 140 160
its pressure never has time to build up. Therefore, the pres- PO2 (mm Hg)
sure difference of CO across the respiratory membrane is
equal to its partial pressure in the alveolar air sample. Then, Figure 40-11. Normal partial pressure of oxygen (PO2)–partial pres-
by measuring the volume of CO absorbed in a short period sure of carbon dioxide (PCO2) ventilation-perfusion ( 6̇! 1̇) ratio (PO2-
PCO2, ( 6̇! 1̇) diagram.
and dividing this by the alveolar CO partial pressure, one
can determine the CO diffusing capacity accurately.
To convert CO diffusing capacity to O2 diffusing capac- cause these gases diffuse between the blood and alveolar air.
ity, the value is multiplied by a factor of 1.23 because the Because the blood that perfuses the capillaries is venous blood
diffusion coefficient for O2 is 1.23 times that for CO. Thus, returning to the lungs from the systemic circulation, it is the
the average diffusing capacity for CO in healthy young men gases in this blood with which the alveolar gases equilibrate.
at rest is 17 ml/min per mm Hg, and the diffusing capacity In Chapter 41, we describe how the normal venous blood ( V )
for O2 is 1.23 times this, or 21 ml/min per mm Hg. has a Po2 of 40 mm Hg and a Pco2 of 45 mm Hg. Therefore,
these are also the normal partial pressures of these two gases
Effect of Ventilation-Perfusion Ratio on Alveolar Gas
in alveoli that have blood flow but no ventilation.
Concentration
Alveolar Oxygen and Carbon Dioxide Partial Pressures
Earlier in this chapter, we learned that two factors deter- When V̇A /Q̇ Equals Infinity. The effect on the alveolar gas
mine the Po2 and Pco2 in the alveoli: (1) the rate of alveo- partial pressures when 7̇" 2̇ equals infinity is entirely dif-
lar ventilation; and (2) the rate of transfer of O2 and CO2 ferent from the effect when 7̇" 2̇ equals zero because now
through the respiratory membrane. This discussion made there is no capillary blood flow to carry O2 away or to bring
the assumption that all the alveoli are ventilated equally, CO2 to the alveoli. Therefore, instead of the alveolar gases
and that blood flow through the alveolar capillaries is the coming to equilibrium with the venous blood, the alveolar
same for each alveolus. However, even normally to some air becomes equal to the humidified inspired air. That is,
extent, and especially in many lung diseases, some areas the air that is inspired loses no O2 to the blood and gains
of the lungs are well ventilated but have almost no blood no CO2 from the blood. Furthermore, because normal
flow, whereas other areas may have excellent blood flow inspired and humidified air has a Po2 of 149 mm Hg and
but little or no ventilation. In either of these conditions, a Pco2 of 0 mm Hg, these will be the partial pressures of
gas exchange through the respiratory membrane is seri- these two gases in the alveoli.
ously impaired, and the person may suffer severe respira- Gas Exchange and Alveolar Partial Pressures When
tory distress, despite normal total ventilation and normal 6̇! 1̇ Is Normal. When there is both normal alveolar
total pulmonary blood flow, but with the ventilation and ventilation and normal alveolar capillary blood flow
blood flow going to different parts of the lungs. Therefore, (normal alveolar perfusion), exchange of O2 and CO2
a highly quantitative concept has been developed to help us through the respiratory membrane is nearly optimal,
understand respiratory exchange when there is imbalance and alveolar Po2 is normally at a level of 104 mm Hg,
between alveolar ventilation and alveolar blood flow. This which lies between that of the inspired air (149 mm Hg)
concept is called the ventilation-perfusion ratio. and that of venous blood (40 mm Hg). Likewise, alveolar
In quantitative terms, the ventilation-perfusion ratio is ex- Pco2 lies between two extremes; it is normally 40 mm
pressed as 7̇" 2̇ . When 7̇" (alveolar ventilation) is normal Hg, in contrast to 45 mm Hg in venous blood and 0 mm
for a given alveolus, and 2̇ (blood flow) is also normal for the Hg in inspired air. Thus, under normal conditions, the
same alveolus, the ventilation-perfusion ratio (7̇" 2̇ ) is also alveolar air Po2 averages 104 mm Hg and the Pco2 aver-
said to be normal. When the ventilation (7̇") is zero, yet there ages 40 mm Hg.
is still perfusion (2̇ ) of the alveolus, the 7̇" 2̇ is zero. Or, at
the other extreme, when there is adequate ventilation (7̇") but Po2-Pco2, V̇A/Q̇ Diagram
zero perfusion (2̇ ), the ratio 7̇" 2̇ is infinity. At a ratio of ei- The concepts presented in the preceding sections are
ther zero or infinity, there is no exchange of gases through the shown in graphic form in Figure 40-11, called the Po2-
respiratory membrane of the affected alveoli. Therefore, let us Pco2, 7̇" 2̇ diagram. The curve in the diagram represents
explain the respiratory consequences of these two extremes. all possible Po2 and Pco2 combinations between the limits
Alveolar Oxygen and Carbon Dioxide Partial Pres- of 7̇" 2̇ equals zero and 7̇" 2̇ equals infinity when the gas
sures When 6̇! 1̇ Equals Zero. When 7̇" 2̇ is equal to pressures in the venous blood are normal, and the person is
zero—that is, without any alveolar ventilation—the air in the breathing air at sea level pressure. Thus, point 7̇" 2̇ is the
alveolus comes to equilibrium with the blood O2 and CO2 be- plot of Po2 and Pco2 when 7̇" 2̇ equals zero. At this point,

518
Chapter 40 Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane

_
the Po2 is 40 mm Hg, and the Pco2 is 45 mm Hg, which are arterial blood, and Pe co2 is the average partial pressure of
the values in normal venous blood. CO2 in the entire expired air.
At the other end of the curve, when 7̇" 2̇ equals infin- When the physiological dead space is great, much of the
ity, point I represents inspired air, showing Po2 to be 149 work of ventilation is wasted effort because so much of the
mm Hg while Pco2 is zero. Also plotted on the curve is ventilating air never reaches the blood.

UNIT VII
the point that represents normal alveolar air when 7̇" 2̇
is normal. At this point, Po2 is 104 mm Hg, and Pco2 is 40 Abnormalities of Ventilation-Perfusion Ratio
mm Hg. Abnormal 6̇! 1̇ in Upper and Lower Normal Lung. In
a healthy person in the upright position, both pulmonary
Concept of Physiological Shunt (When V̇A/Q̇ Is Below
capillary blood flow and alveolar ventilation are consider-
Normal)
ably less in the upper part of the lung than in the lower
Whenever 7̇" 2̇ is below normal, there is inadequate ven- part; however, the decrease of blood flow is considerably
tilation to provide the O2 needed to fully oxygenate the greater than the decrease in ventilation. Therefore, at the
blood flowing through the alveolar capillaries. Therefore, top of the lung, 7̇" 2̇ is as much as 2.5 times as great as the
a certain fraction of the venous blood passing through the ideal value, which causes a moderate degree of physiologi-
pulmonary capillaries does not become oxygenated. This cal dead space in this area of the lung.
fraction is called shunted blood. Also, some additional At the other extreme, at the bottom of the lung, there
blood flows through bronchial vessels rather than through is slightly too little ventilation in relation to blood flow,
alveolar capillaries, normally about 2% of the cardiac out- with 7̇" 2̇ as low as 0.6 times the ideal value. In this area,
put; this, too, is unoxygenated, shunted blood. a small fraction of the blood fails to become normally oxy-
The total quantitative amount of shunted blood per min- genated, and this represents a physiological shunt.
ute is called the physiological shunt. This physiological shunt In both extremes, inequalities of ventilation and perfu-
is measured in clinical pulmonary function laboratories by sion slightly decrease the lung’s effectiveness for exchang-
analyzing the concentration of O2 in both mixed venous ing O2 and CO2. However, during exercise, blood flow to
blood and arterial blood, along with simultaneous measure- the upper part of the lung increases markedly, so far less
ment of cardiac output. From these values, the physiological physiological dead space occurs, and the effectiveness of
shunt can be calculated by the following equation: gas exchange now approaches optimum.

Q̇PS CiO2 − CaO2 Abnormal V̇A/Q̇ in Chronic Obstructive Lung Disease

=
Q̇T CiO2 − CvO2 Most people who smoke for many years develop various
degrees of bronchial obstruction; in many of them, this
in which 2̇14 is the physiological shunt blood flow per condition eventually becomes so severe that serious al-
minute, 2̇5 is cardiac output per minute, CiO2 is the concen- veolar air trapping develops, with resultant emphysema.
tration of oxygen in the arterial blood if there is an “ideal” The emphysema, in turn, causes many of the alveolar walls
ventilation-perfusion ratio, CaO2 is the measured concen- to be destroyed. Thus, two abnormalities occur in smok-
_
tration of oxygen in the arterial blood, and Cv O2 is the meas- ers to cause abnormal 7̇" 2̇ . First, because many of the
ured concentration of oxygen in the mixed venous blood. small bronchioles are obstructed, the alveoli beyond the
The greater the physiological shunt, the greater the obstructions are unventilated, causing a 7̇" 2̇ that ap-
amount of blood that fails to be oxygenated as it passes proaches zero. Second, in the areas of the lung where the
through the lungs. alveolar walls have mainly been destroyed but there is
still alveolar ventilation, most of the ventilation is wasted
Concept of Physiological Dead Space When V̇A/Q̇ because of inadequate blood flow to transport the blood
Greater Than Normal
gases.
When ventilation of some of the alveoli is great but alveo- Thus, in chronic obstructive lung disease, some areas of
lar blood flow is low, there is far more available oxygen in the lung exhibit serious physiological shunt, and other areas
the alveoli than can be transported away from the alveoli exhibit serious physiological dead space. Both conditions
by the flowing blood. Thus, the ventilation of these alve- tremendously decrease the effectiveness of the lungs as gas
oli is said to be wasted. The ventilation of the anatomical exchange organs, sometimes reducing their effectiveness to
dead space areas of the respiratory passageways is also as little as one-tenth normal. In fact, this condition is the
wasted. The sum of these two types of wasted ventila- most prevalent cause of pulmonary disability today.
tion is called the physiological dead space. This space is
measured in the clinical pulmonary function laboratory
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