Physical Principles of Gas Exchange pdf - Respiration

proportional to the concentration of the gas molecules.

gas striking the surface at any given instant. This means that

fore, the pressure of a gas acting on the surfaces of the respiratory passages and

Pressure is caused by multiple impacts of moving molecules against a surface. There-

of Individual Gases

ately different, as demonstrated by the lengths of the arrows in the figure.

tion. Therefore, the rates of diffusion in each of the two directions are proportion-

area. The reason is obvious: There are far more molecules at end A of the chamber

and a low concentration at the other end, as shown in Figure 39–1, net diffusion of

rapidly and randomly among one another.

continue until striking other molecules again. In this way, the molecules move

ity until they strike other molecules. Then they bounce away in new directions and

that are not physically attached to others, this means linear movement at high veloc-

all molecules of all matter are continually undergoing motion. For free molecules

kinetic motion of the molecules themselves. Except at absolute zero temperature,

For diffusion to occur, there must be a source of energy. This is provided by the

of gases dissolved in the fluids and tissues of the body.

to move among one another, which is the process called “diffusion.” This is also true

Molecular Basis of Gas Diffusion

Partial Pressures

Physics of Gas Diffusion and Gas

physics of diffusion and gas exchange.

this is a much more complex problem, requiring a deeper understanding of the

However, in respiratory physiology, one is concerned not only with the basic

the respiratory membrane and adjacent fluids.

direction, out of the blood. The process of diffusion

After the alveoli are ventilated with fresh air, the

and Carbon Dioxide Through

Exchange; Diffusion of Oxygen

491

Physical Principles of Gas

the Respiratory Membrane

next step in the respiratory process is diffusion of
oxygen from the alveoli into the pulmonary blood
and diffusion of carbon dioxide in the opposite

is simply the random motion of molecules inter-
twining their way in all directions through

mechanism by which diffusion occurs but also with the rate at which it occurs;

All the gases of concern in respiratory physiology are simple molecules that are free

Net Diffusion of a Gas in One Direction—Effect of a Concentration Gradient.

If a gas chamber

or a solution has a high concentration of a particular gas at one end of the chamber

the gas will occur from the high-concentration area toward the low-concentration

to diffuse toward end B than there are molecules to diffuse in the opposite direc-

Gas Pressures in a Mixture of Gases—“Partial Pressures”

alveoli is proportional to the summated force of impact of all the molecules of that

the pressure is directly

Henry’s

are expressed by the following formula, which is

develop with fewer dissolved molecules. These relations

those that are repelled, high partial pressure will

pressure within the solution. Conversely, in the case of

are repelled. When molecules are attracted, far more of

chemically attracted to water molecules, whereas others

molecules, especially carbon dioxide, are physically or

of the gas. That is, some types of

The partial pressure of a gas in a solution is

e, and so forth.

in the gas state, that is, P

does. The partial pressures of the separate dissolved

such as the membrane of a cell, it exerts its own partial

when the gas dissolved in fluid encounters a surface,

moving randomly and have kinetic energy. Further,

pressure, because the dissolved gas molecules are

Water and Tissues

e, and

The partial pressures of individual gases in a mixture are

760 mm Hg, the sum of the individual partial pressures.

pressure” of oxygen is 160 mm Hg; the total pressure is

nitrogen in the mixture is 600 mm Hg, and the “partial

oxygen (160 mm Hg). Thus, the “partial pressure” of

caused by nitrogen (600 mm Hg) and 21 per cent by

tration. Therefore, 79 per cent of the 760 mm Hg is

760 mm Hg. It is clear from the preceding description of

of 79 per cent nitrogen and 21 per cent oxygen. The

Consider air, which has an approximate composition

concept of partial pressure can be explained as follows.

of that gas. The

proportional to the pressure caused by that gas alone,

The rate of diffusion of each of these gases is directly

carbon dioxide.

oxygen, nitrogen,

gases, mainly of

In respiratory physiology, one deals with mixtures of

492

Unit VII

Respiration

and

which is called the partial pressure

total pressure of this mixture at sea level averages

the molecular basis of pressure that each gas contributes
to the total pressure in direct proportion to its concen-

designated by the symbols Po

, Pco

, Pn

, Ph

o, Ph

so forth.

Pressures of Gases Dissolved in

Gases dissolved in water or in body tissues also exert

pressure in the same way that a gas in the gas phase

gases are designated the same as the partial pressures

, Pco

, Pn

, Ph

Factors That Determine the Partial Pressure of a Gas Dissolved in
a Fluid.

determined not only by its concentration but also by the
solubility coefficient

them can be dissolved without building up excess partial

law:

Partial pressure

Concentration of dissolved gas

Solubility coefficient

each volume of water, the solubility coef

(1 atmosphere pressure equals 760 mm Hg) and con-

When partial pressure is expressed in atmospheres

centration is expressed in volume of gas dissolved in

ficients for

important respiratory gases at body temperature are the
following:

Nitrogen

0.012

Carbon monoxide

0.018

Carbon dioxide

0.57

Oxygen

0.024

in many of our subsequent discussions.

sure at body temperature, 47 mm Hg; this value appears

C it is 760 mm Hg. But the

C is 5 mm Hg, and at 100

gas phase. For instance, the water vapor pressure at

therefore, the greater the likelihood that the water mol-

temperature of the water. The greater the temperature,

The vapor pressure of water depends entirely on the

pressure, like the other partial pressures, is designated

water vapor in the gas mixture is 47 mm Hg. This partial

that is, once it is in

pressure is 47 mm Hg. Therefore, once the gas mixture

C, this vapor

water. At normal body temperature, 37

from the water surface into the gas phase. The partial

ferent dissolved gas molecules, are continually escaping

results from the fact that water molecules, like the dif-

es the air. This

passageways, water immediately evaporates from the

When nonhumidi

Vapor Pressure of Water

for carbon dioxide, then net diffusion will occur toward

the dissolved state in the blood, which is normally true

natively, if the partial pressure of the gas is greater in

diffuse into the blood than in the other direction. Alter-

as is normally true for oxygen, then more molecules will

the difference between the two partial pressures. If the

occur? The answer is that net diffusion is determined by

alveoli. The rate at which they escape is directly pro-

uid of the blood, and

of the alveolar capillaries. Conversely, the molecules of

The partial pressure

Dissolved Phase in the Pulmonary Blood.

more than 20 times as soluble as oxygen. Therefore, the

From this table, one can see that carbon dioxide is

Helium

0.008

partial pressure of carbon dioxide (for a given concen-
tration) is less than one twentieth that exerted by
oxygen.

Diffusion of Gases Between the Gas Phase in the Alveoli and the

of each gas in the alveolar respiratory gas mixture tends
to force molecules of that gas into solution in the blood

the same gas that are already dissolved in the blood
are bouncing randomly in the fl
some of these bouncing molecules escape back into the

portional to their partial pressure in the blood.

But in which direction will net diffusion of the gas

partial pressure is greater in the gas phase in the alveoli,

the gas phase in the alveoli.

fied air is breathed into the respiratory

surfaces of these passages and humidifi

pressure that the water molecules exert to escape
through the surface is called the vapor pressure of the

has become fully humidified—

“equi-

librium” with the water—the partial pressure of the

the greater the kinetic activity of the molecules and,

ecules will escape from the surface of the water into the

0°

most important value to remember is the vapor pres-

Dissolved gas molecules

net diffusion.

(B). The difference between the lengths of the arrows represents

Diffusion of oxygen from one end of a chamber (A) to the other

Figure 39–1

in which D is the diffusion rate,

expressed in a single formula, as follows:

the rate of diffusion of the gas. All these factors can be

to the square root of the molecular weight, the greater

ment of the molecules, which is inversely proportional

tance. Finally, the greater the velocity of kinetic move-

the greater the distance the molecules must diffuse, the

total number of molecules that diffuse. Conversely,

sectional area of the diffusion pathway, the greater the

partial pressure difference. The greater the cross-

The greater the solubility of the gas, the greater the

factors, the temperature, remains reasonably constant

uid. In the body, the last of these

diffuse, (4) the molecular weight of the gas, and (5) the

uid, (3) the distance through which the gas must

uid, (2) the cross-sectional area of

uid. They are (1) the solubil-

the pressure difference, several other factors affect the

between the two areas, called simply the

sure. Therefore, the

However, some molecules do bounce randomly from

greater number, have a greater statistical chance of

ecules in the area of high pressure, because of their

1, one can readily see that the mol-

turning to Figure 39

area toward the low-pressure area. For instance, re-

area, there will be net diffusion from the high-pressure

preceding discussion, it is clear that when the partial

Now, let us return to the problem of diffusion. From the

Diffusion of Gases Through

Physical Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide

Chapter 39

493

Fluids—Pressure Difference Causes
Net Diffusion

pressure of a gas is greater in one area than in another

–

moving randomly into the area of low pressure than
do molecules attempting to go in the other direction.

the area of low pressure toward the area of high pres-

net diffusion of gas from the area of

high pressure to the area of low pressure is equal to the
number of molecules bouncing in this forward direction
minus the number bouncing in the opposite direction;
this is proportional to the gas partial pressure difference

pressure dif-

ference for causing diffusion.

Quantifying the Net Rate of Diffusion in Fluids.

In addition to

rate of gas diffusion in a fl
ity of the gas in the fl
the fl

temperature of the fl

and usually need not be considered.

number of molecules available to diffuse for any given

longer it will take the molecules to diffuse the entire dis-

DP is the partial pres-

sure difference between the two ends of the diffusion

for oxygen is 1, the

cients. Assuming that the diffusion coef

which is proportional to S/

. That is, the relative

diffusion coefficient of the gas,

solubility and molecular weight. Together, these two

and MW is the molecular weight of the gas.

is the solubility of the gas, d is the distance of diffusion,

pathway, A is the cross-sectional area of the pathway, S

It is obvious from this formula that the characteristics

of the gas itself determine two factors of the formula:

factors determine the

rates at which different gases at the same partial pres-
sure levels will diffuse are proportional to their diffu-
sion coeffi

ficient

relative diffusion coefficients for dif-

ferent gases of respiratory importance in the body fluids
are as follows:

Nitrogen

0.53

Carbon monoxide

0.81

Carbon dioxide

20.3

Oxygen

1.0

the pulmonary blood into the alveoli. And fourth, dry

air. Third, carbon dioxide is constantly diffusing from

with each breath. Second, oxygen is constantly being

are several reasons for the differences. First, the alve-

1 with that of atmospheric air. There

sition in Table 39

gases as atmospheric air by any means, which can

sion of gases in water, as given in the preceding list.

the respiratory membrane, is almost equal to the diffu-

fusion of gases through the tissues, including through

instead of through the cell membranes. Therefore, dif-

soluble in cell membranes. Because of this, the major

highly soluble in lipids and, consequently, are highly

The gases that are of respiratory importance are all

Diffusion of Gases Through Tissues

Helium

0.95

limitation to the movement of gases in tissues is the rate
at which the gases can diffuse through the tissue water

Composition of Alveolar
Air—Its Relation to
Atmospheric Air

Alveolar air does not have the same concentrations of

readily be seen by comparing the alveolar air compo-

–

olar air is only partially replaced by atmospheric air

absorbed into the pulmonary blood from the alveolar

Table 39–1

0.3

(0.04%)

0.3

(0.04%)

40.0

(5.3%)

27.0

(3.6%)

159.0

(20.84%)

149.3

(19.67%)

104.0

(13.6%)

120.0

(15.7%)

597.0

(78.62%)

563.4

(74.09%)

569.0

(74.9%)

566.0

(74.5%)

(mm Hg)

Atmospheric Air*

Humidified Air

Alveolar Air

Expired Air

Partial Pressures of Respiratory Gases as They Enter and Leave the Lungs (at Sea Level)

TOTAL

760.0

(100.0%)

760.0

(100.0%)

760.0

(100.0%)

760.0

(100.0%)

3.7

(0.50%)

47.0

(6.20%)

47.0

(6.2%)

47.0

(6.2%)

* On an average cool, clear day.

the ventilatory process.

alveoli, and its partial pressure as well, is controlled by

tion becomes. Therefore, oxygen concentration in the

alveoli from the atmosphere, the higher its concentra-

its concentration in the alveoli becomes; conversely,

phere. The more rapidly oxygen is absorbed, the lower

into the blood of the lungs, and new oxygen is contin-

Pressure in the Alveoli

Oxygen Concentration and Partial

tion, and tissue pH when respiration is temporarily

tissue oxygenation, tissue carbon dioxide concentra-

nism much more stable than it would be otherwise, and

the blood. This makes the respiratory control mecha-

The slow

Importance of the Slow Replacement of Alveolar Air.

is removed in about 8 seconds.

when the rate of ventilation is twice normal, one half

normal, one half the gas is removed in 34 seconds, and

one half the gas is removed in 17 seconds. When a

showing that with normal alveolar ventilation, about

Figure 39

note that even at the end of 16 breaths, the excess

excess amount of a gas is present in the alveoli, but

gure, an

the alveolar air. In the

olar air. Figure 39

breath is only one seventh of the total, so that multi-

alveolar air is expired. Therefore, the volume of alve-

each normal inspiration, and this same amount of old

ration) measures about 2300 milliliters. Yet only 350

In Chapter 37, it was pointed out that the average male

Rate at Which Alveolar Air Is Renewed

sure from 597 to 563 mm Hg.

ed air, and it dilutes the nitrogen partial pres-

of 159 mm Hg in atmospheric air to 149 mm Hg in the

oxygen partial pressure at sea level from an average

all the other gases in the inspired air. Table 39

(760 mm Hg at sea level), this water vapor simply

lar air. Because the total pressure in the alveoli

C is 47 mm Hg, which is there-

The partial pressure of water vapor at a normal

alveoli, it becomes (for all practical purposes) totally

the respiratory surfaces. Even before the air enters the

piratory passages, it is exposed to the

However, as soon as the atmospheric air enters the res-

almost no carbon dioxide and little water vapor.

entirely of nitrogen and oxygen; it normally contains

Table

Humidification of the Air in the Respiratory Passages.

494

Unit VII

Respiration

atmospheric air that enters the respiratory passages is
humidified even before it reaches the alveoli.

39–1 shows that atmospheric air is composed almost

fluids that cover

humidified.

body temperature of 37°
fore the partial pressure of water vapor in the alveo-

cannot rise to more than the atmospheric pressure

dilutes

–1

also shows that humidification of the air dilutes the

humidifi

by Atmospheric Air

functional residual capacity of the lungs (the volume
of air remaining in the lungs at the end of normal expi-

milliliters of new air is brought into the alveoli with

olar air replaced by new atmospheric air with each

ple breaths are required to exchange most of the alve-

–2 shows this slow rate of renewal of

first alveolus of the fi

gas still has not been completely removed from the
alveoli.

–3 demonstrates graphically the rate at

which excess gas in the alveoli is normally removed,

person’s rate of alveolar ventilation is only one half

replacement of alveolar air is of particular importance
in preventing sudden changes in gas concentrations in

it helps prevent excessive increases and decreases in

interrupted.

Oxygen is continually being absorbed from the alveoli

ually being breathed into the alveoli from the atmos-

the more rapidly new oxygen is breathed into the

(1) the rate of absorption of oxygen into the blood and
(2) the rate of entry of new oxygen into the lungs by

4th breath

12th breath

16th breath

1st breath

2nd breath

3rd breath

8th breath

Expiration of a gas from an alveolus with successive breaths.

Figure 39–2

100

Concentration of gas

(per cent of original concentration)

Time (seconds)

1/2

nor

l alv

eola

r v

ntilati

alv

eola

r ventilati

orm

alv

lar

entil

Rate of removal of excess gas from alveoli.

Figure 39–3

olar air; its overall composition is therefore determined

Therefore, the concentrations and

are excreted per minute). Second,

to the rate of carbon dioxide excretion,

First,

Two other facts are also evident from Figure 39

that is, 40 mm Hg.

Figure 39

is at point A in

At the normal rate of alveolar ventilation of 4.2 L/min,

tion, 200 and 800 ml/min. One curve represents a

lation. Figure 39

body and then carried in the blood to the alveoli; it is

Pressure in the Alveoli

higher than 149 mm Hg, the alveolar P

ed air at this pressure. If the person

air at sea level pressure, because this is the maximum

above 149 mm Hg as

Another effect shown in Figure 39

value of 104 mm Hg.

exercise, the rate of alveolar ventilation must increase

absorbed each minute, as occurs during moderate

4 is point A. The

operating point in Figure 39

and an oxygen consumption of 250 ml/min, the normal

1000 ml/min. At a normal ventilatory rate of 4.2 L/min

250 ml/min, and the other curve represents a rate of

). One

Figure 39

Physical Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide

Chapter 39

495

–4 shows the effect of both alveolar venti-

lation and rate of oxygen absorption into the blood on
the alveolar partial pressure of oxygen (Po

curve represents oxygen absorption at a rate of

–

figure

also shows that when 1000 milliliters of oxygen is being

fourfold to maintain the alveolar Po

at the normal

–4 is that an

extremely marked increase in alveolar ventilation can
never increase the alveolar Po

long as the person is breathing normal atmospheric

in humidifi

breathes gases that contain partial pressures of oxygen

can approach

these higher pressures at high rates of ventilation.

Concentration and Partial

Carbon dioxide is continually being formed in the

continually being removed from the alveoli by venti-

–5 shows the effects on the alveolar

partial pressure of carbon dioxide (Pco

) of both alve-

olar ventilation and two rates of carbon dioxide excre-

normal rate of carbon dioxide excretion of 200 ml/min.

the operating point for alveolar Pco

–5—

–5:

the alveolar P

increases directly in proportion

as represented

by the fourfold elevation of the curve (when 800
milliliters of CO

the alveolar P

decreases in inverse proportion to

alveolar ventilation.
partial pressures of both oxygen and carbon dioxide in
the alveoli are determined by the rates of absorption
or excretion of the two gases and by the amount of
alveolar ventilation.

Expired Air

Expired air is a combination of dead space air and alve-

150

125

100

Upper limit at maximum ventilation

250 ml O

/min

1000 ml O

/min

Normal alveolar P

Alveolar partial pressure

of oxygen (mm Hg)

Alveolar ventilation (L/min)

250 ml/min and 1000 ml/min. Point A is the normal

two rates of oxygen absorption from the alveoli—

Effect of alveolar ventilation on the alveolar P

Figure 39–4

operating point.

Normal alveolar P

175

150

125

100

200 ml CO

/min

800 ml CO

/min

Alveolar partial pressure

of CO

(mm Hg)

Alveolar ventilation (L/min)

min. Point A is the normal operating point.

carbon dioxide excretion from the blood—800 ml/min and 200 ml/

Effect of alveolar ventilation on the alveolar P

Figure 39–5

at two rates of

pulmonary membrane.

respiratory membrane,

merely in the alveoli themselves. All these membranes

branes of all the terminal portions of the lungs, not

laries. Further, gas exchange between the alveolar air

Thus, it is obvious that the alveolar gases are in very

the capillary plexus, the

8. Indeed, because of the extensiveness of

Figure 39

network of interconnecting capillaries, shown in

thin, and between the alveoli is an almost solid

about 0.2 millimeter. The alveolar walls are extremely

lungs, and each alveolus has an average diameter of

There are about 300 million alveoli in the two

respiratory bronchiole, alveolar ducts, atria,

), which is composed

7 shows the

Figure 39

Respiratory Unit.

the Respiratory Membrane

Diffusion of Gases Through

ed atmospheric air.

is, concentrations between those of alveolar air and

pressures approximately as shown in Table 39

and alveolar air, has gas concentrations and partial

Normal expired air, containing both dead space air

air.

expired at the end of expiration. Therefore, the method

1. Then, pro-

ed air, as shown in Table 39

dead space air from the respiratory passageways, is

rst portion of this air, the

course of expiration. The

air and (2) the amount that is alveolar air. Figure 39

496

Unit VII

Respiration

by (1) the amount of the expired air that is dead space

–6

shows the progressive changes in oxygen and carbon
dioxide partial pressures in the expired air during the

typical humidifi

–

gressively more and more alveolar air becomes mixed
with the dead space air until all the dead space air has
finally been washed out and nothing but alveolar air is

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

–1—that

humidifi

–

respiratory unit

(also called “respiratory lobule”
of a

and

alveoli.

–

flow of blood in the alveolar

wall has been described as a “sheet” of flowing blood.

close proximity to the blood of the pulmonary capil-

and the pulmonary blood occurs through the mem-

are collectively known as the
also called the

100

200

Carbon dioxide (P

)

Oxygen (P

)

160

140

120

100

Milliliters of air expired

Pressures of O

and CO

(mm Hg)

500

400

300

Alveolar air

and dead

space air

Dead

space

air

various portions of normal expired air.

Oxygen and carbon dioxide partial pressures in the

Figure 39–6

Terminal bronchiole

Atrium

Alveoli

Alveolar

duct

Alveolar sacs

Respiratory bronchiole

Respiratory unit. (Redrawn from Miller WS: The Lung. Springfield,

Figure 39–7

Ill: Charles C Thomas, 1947.)

the alveolus and the red cell. This, too, increases the

cell membrane usually touches the capillary wall, so

blood cells must squeeze through them. The red blood

is only about 5 micrometers, which means that red

The average diameter of the pulmonary capillaries

of oxygen and carbon dioxide.

oor, and it is easy

lungs at any given instant is 60 to 140 milliliters. Now

The total quantity of blood in the capillaries of the

square meters in the normal adult human male. This is

histological studies, it has been estimated that the total

micrometer, except where there are cell nuclei. From

is as little as 0.2 micrometer, and it averages about 0.6

Despite the large number of layers, the overall

6. The capillary endothelial membrane

5. A capillary basement membrane that in many

4. A thin interstitial space between the alveolar

3. An epithelial basement membrane

2. The alveolar epithelium composed of thin

1. A layer of

in the opposite direction. Note the following different

section on the left and a red blood cell on the right. It

Figure 39

Respiratory Membrane.

Physical Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide

Chapter 39

497

–9 shows the ultrastruc-

ture of the respiratory membrane drawn in cross

also shows the diffusion of oxygen from the alveolus
into the red blood cell and diffusion of carbon dioxide

layers of the respiratory membrane:

fluid lining the alveolus and containing

surfactant that reduces the surface tension of the
alveolar fluid

epithelial cells

epithelium and the capillary membrane

places fuses with the alveolar epithelial basement
membrane

thickness of the respiratory membrane in some areas

surface area of the respiratory membrane is about 70

equivalent to the floor area of a 25–by-30–foot room.

imagine this small amount of blood spread over the
entire surface of a 25–by-30–foot fl
to understand the rapidity of the respiratory exchange

that oxygen and carbon dioxide need not pass through
significant amounts of plasma as they diffuse between

rapidity of diffusion.

Lymphatic

Vein

Artery

Perivascular
interstitial space

Interstitial space

Capillaries

vessel

Alveolus

North-Holland Division.)

Reproduced by permission of ASP Biological and Medical Press,

and small blood vessels in frog lung. Respir Physiol 7:150, 1969.

Maloney JE, Castle BL: Pressure-diameter relations of capillaries

From

tional view of alveolar walls and their vascular supply. (

Cross-sec-

Surface view of capillaries in an alveolar wall.

Figure 39–8

Diffusion

Alveolus

Capillary

Capillary basement membrane

Capillary endothelium

Epithelial

basement

membrane

Alveolar

epithelium

Fluid and

surfactant

layer

Interstitial space

Oxygen

Red blood
cell

Carbon dioxide

cross section.

Ultrastructure of the alveolar respiratory membrane, shown in

Figure 39–9

The diffusing capac-

this chapter. Therefore, during exercise, oxygenation of

perfusion ratio,

alveolar capillaries with blood, called the

oxygen can diffuse; and (2) a better match between

extra dilation of already open capillaries, thereby

several factors, among which are (1) opening up of

under resting conditions. This increase is caused by

mm Hg, which is three times the diffusing capacity

in young men to a maximum of about 65 ml/min/

ventilation, the diffusing capacity for oxygen increases

normal, quiet breathing is about 11 mm Hg. Multipli-

what does this mean? The mean oxygen pressure

. In functional terms,

21 ml/min/mm Hg

diffusing capacity for oxygen

In the average young man,

this diffusing capacity.

1 mm Hg.

brane each minute for a partial pressure difference of

membrane’s diffusing capacity,

The ability of the respiratory membrane to exchange

Diffusing Capacity of the

from the blood into the alveoli occurs.

the alveoli, as is true for carbon dioxide, net diffusion

alveoli into the blood occurs; when the pressure of the

the blood, as is true for oxygen, net diffusion from the

membrane. When the partial pressure of a gas in the

in the opposite direction. Therefore, the difference

alveolar surface of the membrane in unit time, and the

gas in the pulmonary capillary blood. The partial pres-

The

oxygen. Oxygen diffuses about twice as rapidly as

earlier. Therefore, for a given pressure difference,

exactly the same as that in water, for reasons explained

The rate

in the membrane and, inversely, on the

The

gases.

competitive sports and other strenuous exercise, even

even under resting conditions,

cant degree,

about one third to one fourth normal, exchange of

walls. When the total surface area is decreased to

larger than the original alveoli, but the total surface

walls. Therefore, the new alveolar chambers are much

the alveoli coalesce, with dissolution of many alveolar

area to one half normal. Also, in

greatly decreased by many conditions. For instance,

The

cantly with normal respiratory exchange of gases.

membrane, any factor that increases the thickness to

brane. Because the rate of diffusion through the mem-

brosis of the lungs, which can increase the

uid. Also, some pulmonary diseases

for instance, as a result of edema

thickness of the respiratory membrane

The

the two sides of the membrane.

of the gas in the substance of the membrane, and

surface area of the membrane,

thickness of the membrane,

respiratory membrane. Thus, the factors that deter-

in water, one can apply the same principles and math-

Factors That Affect the Rate

498

Unit VII

Respiration

of Gas Diffusion Through the
Respiratory Membrane

Referring to the earlier discussion of diffusion of gases

ematical formulas to diffusion of gases through the

mine how rapidly a gas will pass through the mem-
brane are (1) the

(2) the

(3) the diffusion coeffi-

cient
(4) the partial pressure difference of the gas between

occa-

sionally increases—
fluid in the interstitial space of the membrane and in
the alveoli—so that the respiratory gases must then
diffuse not only through the membrane but also
through this fl
cause fi
thickness of some portions of the respiratory mem-

brane is inversely proportional to the thickness of the

more than two to three times normal can interfere sig-
nifi

surface area of the respiratory membrane can be

removal of an entire lung decreases the total surface

emphysema, many of

area of the respiratory membrane is often decreased
as much as fivefold because of loss of the alveolar

gases through the membrane is impeded to a signifi-

and during

the slightest decrease in surface area of the lungs can
be a serious detriment to respiratory exchange of

diffusion coefficient for transfer of each gas

through the respiratory membrane depends on the
gas’s solubility
square root of the gas’s molecular weight.
of diffusion in the respiratory membrane is almost

carbon dioxide diffuses about 20 times as rapidly as

nitrogen.

pressure difference across the respiratory mem-

brane is the difference between the partial pressure of
the gas in the alveoli and the partial pressure of the

sure represents a measure of the total number of mol-
ecules of a particular gas striking a unit area of the

pressure of the gas in the blood represents the number
of molecules that attempt to escape from the blood

between these two pressures is a measure of the net
tendency for the gas molecules to move through the

alveoli is greater than the pressure of the gas in

gas in the blood is greater than the partial pressure in

Respiratory Membrane

a gas between the alveoli and the pulmonary blood
is expressed in quantitative terms by the respiratory

which is defined as

the volume of a gas that will diffuse through the mem-

All the factors discussed earlier that affect

diffusion through the respiratory membrane can affect

Diffusing Capacity for Oxygen.

the

under resting condi-

tions averages

difference across the respiratory membrane during

cation of this pressure by the diffusing capacity (11

21) gives a total of about 230 milliliters of oxygen dif-
fusing through the respiratory membrane each minute;
this is equal to the rate at which the resting body uses
oxygen.

Change in Oxygen Diffusing Capacity During Exercise.

During strenuous exercise or other conditions that
greatly increase pulmonary blood flow and alveolar

many previously dormant pulmonary capillaries or

increasing the surface area of the blood into which the

the ventilation of the alveoli and the perfusion of the

ventilation-

which is explained in detail later in

the blood is increased not only by increased alveolar
ventilation but also by greater diffusing capacity of
the respiratory membrane for transporting oxygen into
the blood.

Diffusing Capacity for Carbon Dioxide.

ity for carbon dioxide has never been measured

the respiratory membrane of the affected alveoli, which

nity, there is no exchange of gases through

nity. At a ratio of either

), the ratio V

is zero. Or, at the other extreme,

alveolus, the V

) is zero, yet there is still perfusion (Q

lation (V

) is also said to be normal. When the venti-

normal for the same alveolus, the ventilation-perfusion

. When V

is expressed as V

In quantitative terms, the ventilation-perfusion ratio

ventilation-perfusion ratio.

ow. This

parts of the lungs. Therefore, a highly quantitative

ow, but

brane is seriously impaired, and the person may suffer

conditions, gas exchange through the respiratory mem-

ow but little or no ventilation. In either of these

ow, whereas other areas may have excellent

some extent, and especially in many lung diseases, some

the same for each alveolus. However, even normally to

tory membrane. These earlier discussions made the

in the alveoli: (1)

In the early part of this chapter, we learned that two

Perfusion Ratio on Alveolar

Effect of the Ventilation-

21 ml/min/mm Hg.

diffusing capacity for oxygen is 1.23 times this, or

in young men at rest is 17 ml/min/mm Hg, and the

oxygen is 1.23 times that for carbon monoxide. Thus,

oxygen diffusing capacity, the value is multiplied by a

To convert carbon monoxide diffusing capacity to

capacity.

alveolar carbon monoxide partial pressure, one can

Then, by measuring the volume of carbon monoxide

equal to its partial pressure in the alveolar air sample.

has time to build up. Therefore, the pressure difference

sure in the blood is essentially zero, because hemoglobin

priate alveolar air samples. The carbon monoxide pres-

breathed into the alveoli, and the partial pressure of the

the following: A small amount of carbon monoxide is

this. The principle of the carbon monoxide method is

oxygen diffusing capacity directly, physiologists usually

To obviate the dif

imental basis.

capacity by such a direct procedure, except on an exper-

uptake by the blood. However, measuring the P

pulmonary capillary blood, and (3) the rate of oxygen

, (2) P

The oxygen diffusing capacity can be calculated

capacity of each of these gases.

oxygen, and carbon dioxide at rest and during exercise,

calculated diffusing capacities of carbon monoxide,

min/mm Hg. Figure 39

mm Hg and during exercise of about 1200 to 1300 ml/

is slightly more than 20 times that of oxygen, one

gas. Because the diffusion coef

Nevertheless, measurements of diffusion of other

available techniques, this difference is too small to be

average difference is less than 1 mm Hg

culty: Carbon

Physical Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide

Chapter 39

499

because of the following technical diffi
dioxide diffuses through the respiratory membrane so
rapidly that the average Pco

in the pulmonary blood

is not far different from the Pco

in the alveoli—the

—and with the

measured.

gases have shown that the diffusing capacity varies
directly with the diffusion coefficient of the particular

ficient of carbon dioxide

would expect a diffusing capacity for carbon dioxide
under resting conditions of about 400 to 450 ml/min/

–10 compares the measured or

showing the extreme diffusing capacity of carbon
dioxide and the effect of exercise on the diffusing

Measurement of Diffusing Capacity—The Carbon Monoxide
Method.

from measurements of (1) alveolar Po

in the

pulmonary capillary blood is so difficult and so impre-
cise that it is not practical to measure oxygen diffusing

ficulties encountered in measuring

measure carbon monoxide diffusing capacity instead
and then calculate the oxygen diffusing capacity from

carbon monoxide in the alveoli is measured from appro-

combines with this gas so rapidly that its pressure never

of carbon monoxide across the respiratory membrane is

absorbed in a short period and dividing this by the

determine accurately the carbon monoxide diffusing

factor of 1.23 because the diffusion coefficient for

the average diffusing capacity for carbon monoxide

Gas Concentration

factors determine the Po

and the Pco

the rate of alveolar ventilation and (2) the rate of trans-
fer of oxygen and carbon dioxide through the respira-

assumption that all the alveoli are ventilated equally
and that blood flow through the alveolar capillaries is

areas of the lungs are well ventilated but have almost
no blood fl
blood fl

severe respiratory distress despite both normal total
ventilation and normal total pulmonary blood fl
with the ventilation and blood flow going to different

concept has been developed to help us understand res-
piratory exchange when there is imbalance between
alveolar ventilation and alveolar blood fl
concept is called the

a/Q

a (alveolar ventilation) is

normal for a given alveolus and Q

(blood flow) is also

ratio (V

a/Q

) of the

a/Q

when there is adequate ventilation (V

a) but zero perfu-

sion (Q

a/Q

is infi

zero or infi

1300

1200

1100

1000

900

800

700

600

500

400

300

200

100

Resting

Exercise

Diffusing capacity (ml/min/mm Hg)

exercise.

dioxide in the normal lungs under resting conditions and during

Diffusing capacities

Figure 39–10

for carbon monoxide, oxygen, and carbon

ow is low, there is far more available

When ventilation of some of the alveoli is great but

(When V

through the lungs.

amount of blood that fails to be oxygenated

The greater the physiologic shunt, the greater the

concentration of oxygen in the arterial blood, and C

ventilation-perfusion ratio, Ca

is cardiac output per minute, Ci

minute, Q

these values, the physiologic shunt can be calculated by

simultaneous measurement of cardiac output. From

both mixed venous blood and arterial blood, along with

This physiologic

The total quantitative amount of shunted blood per

too, is unoxygenated, shunted blood.

ies, normally about 2 per cent of the cardiac output; this,

Also, some additional blood

not become oxygenated. This fraction is called

laries. Therefore, a certain fraction of the venous

is below normal, there is inadequate

Whenever V

Is Below Normal)

is 40 mm Hg.

is 104 mm Hg and

is normal. At this point, P

is zero. Also plotted on the curve

mm Hg while P

to be 149

ity, point I represents inspired air, showing P

At the other end of the curve, when V

is 45 mm Hg, which are the

is 40 mm Hg and the P

equals zero. At this point, the P

air at sea-level pressure. Thus, point v

binations between the limits of V

diagram. The curve in

11, called the P

shown in graphical form, as demonstrated in Figure

The concepts presented in the preceding sections can be

averages 40 mm Hg.

averages 104 mm Hg and the P

0 mm Hg in inspired air. Thus, under normal conditions,

40 mm Hg, in contrast to 45 mm Hg in venous blood and

lies between two extremes; it is normally

and that of venous blood (40 mm Hg). Likewise,

which lies between that of the inspired air (149 mm Hg)

is normally at a level of 104 mm Hg,

olar perfusion), exchange of oxygen and carbon dioxide

When there is both normal alveolar ventilation

of 0 mm Hg, these will be the partial pressures of these

of 149 mm Hg and a P

ed air has a P

dioxide from the blood. And because normal inspired

ed inspired air. That is, the air that is inspired

venous blood, the alveolar air becomes equal to the

to bring carbon dioxide to the alveoli. Therefore, instead

from the effect when V

sures when V

The effect on the alveolar gas partial pres-

Equals Infinity.

Therefore, these are also the normal partial pressures of

of 45 mm Hg.

of 40 mm Hg and a P

Chapter 40, we will learn that the normal venous blood

blood with which the alveolar gases equilibrate. In

from the systemic circulation, it is the gases in this

and the alveolar air. Because the blood that perfuses

that is, without

When V

extremes.

explains the importance of this concept. Therefore, let

500

Unit VII

Respiration

us explain the respiratory consequences of these two

Alveolar Oxygen and Carbon Dioxide Partial Pressures When V

Equals Zero.

a/Q

is equal to zero—

any alveolar ventilation—the air in the alveolus
comes to equilibrium with the blood oxygen and carbon
dioxide because these gases diffuse between the blood

the capillaries is venous blood returning to the lungs

(v¯) has a Po

these two gases in alveoli that have blood flow but no
ventilation.

Alveolar Oxygen and Carbon Dioxide Partial Pressures When V

a/Q

equals infinity is entirely different

a/Q

equals zero because now

there is no capillary blood flow to carry oxygen away or

of the alveolar gases coming to equilibrium with the

humidifi
loses no oxygen to the blood and gains no carbon

and humidifi

two gases in the alveoli.

Gas Exchange and Alveolar Partial Pressures When V

Normal.

and normal alveolar capillary blood flow (normal alve-

through the respiratory membrane is nearly optimal,
and alveolar Po

alveolar Pco

the alveolar air Po

-P

, V

Diagram

39–

-Pco

, V

a/Q

the diagram represents all possible Po

and Pco

com-

a/Q

equals zero and

a/Q

equals infinity when the gas pressures in the

venous blood are normal and the person is breathing

¯ is the plot of Po

and Pco

when V

a/Q

values in normal venous blood.

a/ Q

equals infin-

is the point that represents normal alveolar air when
V

a/Q

Pco

Concept of “Physiologic Shunt”
(When V

a/Q

ventilation to provide the oxygen needed to fully oxy-
genate the blood flowing through the alveolar capil-

blood passing through the pulmonary capillaries does

shunted

blood.

flows through

bronchial vessels rather than through alveolar capillar-

minute is called the physiologic shunt.
shunt is measured in clinical pulmonary function labo-
ratories by analyzing the concentration of oxygen in

the following equation:

in which Q

ps is the physiologic shunt blood flow per

is the con-

centration of oxygen in the arterial blood if there is an
“ideal”

is the measured

v¯

is the measured concentration of oxygen in the mixed
venous blood.

as it passes

Concept of the “Physiologic Dead
Space”

Is Greater

Than Normal)

alveolar blood fl
oxygen in the alveoli than can be transported away from

80 100 120 140 160

= 40)

= 45)

Normal alveolar
air
(P

= 104)

= 40)

= 149)

= 0)

/Q = 0

/Q = Normal

/Q =

∞

(mm Hg)

Normal P

Figure 39–11

-P

, V

diagram.

causes many of the alveolar walls to be destroyed. Thus,

and resultant emphysema. The emphysema in turn

these persons, this condition eventually becomes so

degrees of bronchial obstruction; in a large share of

space occurs, and the effectiveness of gas exchange now

increases markedly, so that far less physiologic dead

during exercise, blood

for exchanging oxygen and carbon dioxide. However,

In both extremes, inequalities of ventilation and

normally oxygenated, and this represents a

area, a small fraction of the blood fails to become

as low as 0.6 times the ideal value. In this

ow,

At the other extreme, in the bottom of the lung, there

in this area of the lung.

ideal value, which causes a moderate degree of

the lung, V

ably more than ventilation is. Therefore, at the top of

lower part; however, blood

normal person in the upright position, both pulmonary

In a

Abnormalities of Ventilation-

When the physiologic dead space is great, much of the

air.

dioxide in the arterial blood, and

is the average

tidal volume, Pa

is the physiologic dead space, V

in which V

This is measured in the clinical pulmonary function lab-

physiologic dead space.

sageways is also wasted. The sum of these two types of

The ventilation of the

owing blood. Thus, the ventilation of

Physical Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide

Chapter 39

501

the alveoli by the fl
these alveoli is said to be wasted.
anatomical dead space areas of the respiratory pas-

wasted ventilation is called the

oratory by making appropriate blood and expiratory
gas measurements and using the following equation,
called the Bohr equation:

phys

t is the

is the partial pressure of carbon

partial pressure of carbon dioxide in the entire expired

work of ventilation is wasted effort because so much of
the ventilating air never reaches the blood.

Perfusion Ratio

Abnormal V

in the Upper and Lower Normal Lung.

capillary blood flow and alveolar ventilation are con-
siderably less in the upper part of the lung than in the

flow is decreased consider-

a/Q

is as much as 2.5 times as great as the

physio-

logic dead space

is slightly too little ventilation in relation to blood fl
with V

a/Q

physiologic

shunt.

perfusion decrease slightly the lung’s effectiveness

flow to the upper part of the lung

approaches optimum.

Abnormal V

in Chronic Obstructive Lung Disease.

Most

people who smoke for many years develop various

severe that they develop serious alveolar air trapping

phys

development. Annu Rev Physiol 65:669, 2003.

Williams MC:Alveolar type I cells: molecular phenotype and

Lippincott Williams & Wilkins, 2003.

The Essentials. Baltimore:

West JB: Pulmonary Physiology

cott Williams & Wilkins, 2001.

Integrated, Case-Based Approach. Philadelphia: Lippin-

West JB: Pulmonary Physiology and Pathophysiology: An

Birkhauser Verlag, 1998.

Uhlig S, Taylor AE: Methods in Pulmonary Research. Basel:

& Wilkins, 1964, p 125.

Handbook of Physiology. Sec 3, Vol 1. Baltimore: Williams

the Va/Q concept. In: Fenn WO, Rahn H (eds):

Rahn H, Farhi EE: Ventilation, perfusion, and gas

Sci 19:55, 2004.

complexity: implications for gas exchange. News Physiol

Powell FL, Hopkins SR: Comparative physiology of lung

mice. Am J Physiol Lung Cell Mol Physiol 286:L231, 2004.

Parker JC,Townsley MI: Evaluation of lung injury in rats and

iology. Sec 3, Vol 1. Baltimore: Williams & Wilkins, 1964,

exchange. In: Fenn WQ, Rahn H (eds): Handbook of Phys-

Otis AB: Quantitative relationships in steady-state gas

ogy 8:432, 2003.

and functional properties in health and disease. Respirol-

Knight DA, Holgate ST: The airway epithelium: structural

concept and application. Chest 122:1774, 2002.

Hsia CC: Recruitment of lung diffusing capacity: update of

124:1090, 2003.

heart failure: evidence of a pathophysiologic role. Chest

Guazzi M: Alveolar-capillary membrane dysfunction in

tion. Crit Care Med 32:1240, 2004.

Cole RP: CO

cine. Philadelphia: Mosby, 2002.

Albert R, Spiro S, Jett J: Comprehensive Respiratory Medi-

ability today.

fact, this is the most prevalent cause of pulmonary dis-

their effectiveness to as little as one tenth normal. In

the lungs as gas exchange organs, sometimes reducing

serious physiologic dead space.

Thus, in chronic obstructive lung disease, some areas

gases.

alveolar ventilation, most of the ventilation is wasted

Second, in those areas of the lung where the alveolar

that approaches zero.

unventilated, causing a V

obstructed, the alveoli beyond the obstructions are

. First, because many of the small bronchioles are

two abnormalities occur in smokers to cause abnormal
V

a/Q

walls have been mainly destroyed but there is still

because of inadequate blood flow to transport the blood

of the lung exhibit serious physiologic shunt, and other
areas exhibit

Both these

conditions tremendously decrease the effectiveness of

References

and lung mechanical or gas exchange func-

p 681.

exchange—

—