Contours of Breathing - Diffusion
8.1 Diffusion of gases
Partial gas pressure and solubility: The partial pressure (Pi) of a gas i in a gas mixture is
equal to the product of the total gas pressure (PB) and the volume fraction of the gas (Fi)
(Dalton’s law): Pi = Fi · PB. When the gas mixture contains water vapour a correction
must be made: Pi = (PB - PH2O) (see part I, A9).
The quantity of gas in solution per unit volume of liquid at constant temperature is
directly proportional to the gas pressure (Pi) at the surface of the liquid (Henry’s law).
The factor of proportionality is the Bunsen solubility coefficient (α) when the volume of
dissolved gas (Vi) is given in mL STPD per mL of liquid per atmosphere pressure. The
factor of proportionality is the capacitance coefficient (β) when the quantity of dissolved
gas (ni) is given in mmol per litre of liquid per kilopascal. The coefficient depends on the
temperature and type of liquid. For example: αO2 (blood, 37°C): 0.0239 mLSTPD · mL-1 ·
atm-1. βO2 (blood, 37°C): 0.0107 mmol · L-1 · kPa-1.
Diffusion in the gas phase: The movement of molecules from an area of high concentration to one of low concentration as a result of their kinetic energy (Brownian movement)
is called diffusion. The rate of diffusion (mass flow) of a gas is described by the following
equation:
.
n = dm/dt = - D · A · dc/dx (1)
Here, dm/dt is the mass flow of the gas (mol/s), D the diffusion coefficient (cm2/s), A
the diffusion surface (cm2) and dc/dx the concentration coefficient over the distance x
(mol/cm4). The diffusion coefficient D is inversely proportional to the square root of the
molecular weight (Graham’s law) and depends on the diffusion medium and the tem-.
.
perature. The gas flow can be expressed as a mass flow n (mol/s) or as a volume flow V
(mLSTPD/min)
.
.
nO2 = TL,O2 · PA-c. It follows from this that: TL,O2 = nO2/PA-c (mmol · min-1 · kPa-1).
TL is the gas flow per unit of pressure difference and thus has the dimension of conductance; thus
1/TL has the dimension of resistance (see 8.2). The transfer factor is often quoted per unit of lung
(alveolar) volume: TL/VA.
References
Altman PL, Ditmer DS. Respiration and circulation. Feder Amer Soc Exp Biol, Bethesda, Maryland, 1971.
Cotes JE. Lung function, 4th edition. Blackwell, Oxford, 1979.
Cotes JE. The transfer factor (diffusing capacity). In: ‘Standardized lung function testing (Quanjer PhH, editor). Report of the working party of the European Community for Coal and Steel, Luxembourg, June 1982.
Dejours P. Respiration. Oxford University Press, New York, 1966.
Huber GL. Arterial blood gases and acid-base physiology. Upjohn Company, 1978.
Kao FF. An introduction to respiratory physiology. Excerpta Medica, Amsterdam, 1972.
Werner FM. Determination of the alveolar capillary blood volume (Vcv) and the transfer factor of the alveolo-capillary membrane (Dmv) by the single breath method. Thesis, Nijmegen, 1979.
Diffusion in the liquid phase: The diffusion of gases in a liquid depends on the solubility coefficient a or the capacitance coefficient β. The concentration of the gas is usually
expressed as the product of the coefficient and the partial gas pressure: c = α·P or c = β·P.
As the direction of mass flow is not important, the negative sign in equation (1) can be
.
ignored, thus: n = K · A · dP/dx (2)
where K = β · D and K is the diffusion conductivity power. On the basis of molecular
weight (MW) and solubility coefficient the diffusion rates of gases in a liquid can be
compared, for example:
.
.
nCO2/nO2 = (βCO2 · MWO20.5)/(βO2 · MWCO20.5) = 20.2
Diffusion in the lung: In lung physiology the diffusion gradient is the quotient of the difference in gas pressure on either side of the alveolar capillary membrane (PA-c) and the
thickness of the membrane (x): dP/dx = PA-c/x. The unit of gas transport is mmol/min. It
follows from (2) that:
.
n = (K’ · A/x) · PA-c (mmol/min)(3)
The components A and x are unknown and incalculable. Since alveolar-capillary gas
transport is not exclusively determined by diffusion, the transfer factor is used as a measure of the transport characteristics: TL = K’ · A/x.
G.J. Tammeling and Ph.H. Quanjer
Contours of Breathing - Diffusion
8.2 Components of alveolar- capillary diffusion
Membrane factor. The greater proportion of the area of the alveolar-capillary membrane
is involved in gas exchange; the rest constitutes only a boundary of gases and interstitial
fluid. Visser has calculated that the total area of the membranes of the erythrocytes in the
pulmonary capillaries is about the same as that of the alveolar-capillary membrane, i.e.
some 50 m2. The capillary bed contains about 3.1011 erythrocytes with a surface area of
160 μm2 each. Both the alveoli and the respiratory bronchioles and pulmonary arterioles
are involved in gas exchange. The volume of the interstitial space is about 200 mL. The
diffusion process is influenced by fluid movement (e.g. pulsations) and alveolar metabolism (thermic effects). The transport of gas through the alveolar-capillary membrane
(nm) is determined by the following factors:
- The alveolar-capillary gas pressure gradient (PA-c)
- The solubility and molecular weight of the gas, and
- The thickness, surface area and composition of the alveolar-capillary membrane.
The latter two factors are represented by the diffusion coefficient Dm. The relationship
.
between these factors is as follows: nm = Dm · PA-c-
in series, which determine the total pulmonary gas transfer factor (see 8.1):
.
1/TL = 1/Dm + 1/(β · Qc + θ · Qc)
where 1/TL is the total pulmonary transfer resistance
1/Dm is. the membrane resstance and
1/(β · Qc + θ · Qc) the blood circulation resistance.
The contribution of each of these components to the pulmonary transfer factor is a function of the
characteristics of the gas concerned (see 8.3, 8.4 and 8.5).
References
Cotes JE. The transfer factor (diffusing capacity). In: ‘Standardized lung function testing (Quanjer PhH, editor). Report of the working party of the European Community for Coal and Steel, Luxembourg, June 1982.
Kreuzer F, Hoofd LJ. Resp Physiol 1970; 8: 280.
Roughton FJ. Transport of oxygen andcarbon dioxide. Handbook of Physiology (Fenn WO, Rahn H, editors),
section 3, vol. I, pag. 767. Am Physiol Soc, Washington D.C., 1964,
Visser BF, Maas AHJ. Physics in Med and Biol 1959; 3: 264.
Werner FM. Determination of the alveolar capillary blood volume and the transfer factor of the alveolo-capillary membrane by the single breath method. Thesis, Nijmegen, 1979.
Blood factor. Equilibration of the gases in the capillary blood is almost instantaneous as
a result of gas diffusion and the movement of the blood cells. With gases which combine
with haemoglobin there is a pressure gradient between plasma and erythrocyte which is
a function of the combining rate and, to a lesser extent, of the diffusion of the gas within
the erythrocyte, which is facilitated by haemoglobin (Kreuzer). The following factors
determine the volume of gas, e.g. carbon monoxide, bound to haemoglobin:
- The rate at which the gas (carbon monoxide) combines with haemoglobin (θ);
- The capillary blood volume (Qc), and
- The venous-capillary gas pressure gradient
.
-The relationship between these factors is as follows: nbl = θ · Qc · Pv-c
The rate at which carbon monoxide combines with haemoglobin differs from that of
oxyhaemoglobin. Use is made of this fact in distinguishing the membrane component
(Dm) from the capillary blood volume (Qc).
Circulation factor. The rate at which the dissolved gases leave the alveolar vascular bed
depends on the capillary blood flow. The transport of the dissolved gas with the circulation (ncirc) depends on the following factors:
- The capacitance coefficient (β);
- The blood flow in the alveolar capillaries (Qc), and
- The arterial-venous gas pressure gradient.
.
.
The relationship between these factors is as follows: ncirc = β · Qc · Pa-vConnection between the factors. The volume of gas transported from the alveolar space to
the capillary blood across the alveolar-capillary membrane (nm) is equal to the volume of
gas taken up in the capillary blood (nbl) plus the volume of gas carried away by the capillary circulation (ncirc). These three components can be regarded as conductances linked
G.J. Tammeling and Ph.H. Quanjer
Contours of Breathing - Diffusion
8.3 Alveolar-capillary transport of carbon dioxide
Carbon dioxide is transported in the blood as physically dissolved gas (8%), carbamino-haemoglobin (HHbCO2) (12%) and as bicarbonate (HCO3-) buffered by protein
(80%). The partial pressure of carbon dioxide in the arterial blood is 5.3 kPa (40 mmHg)
and its concentration is 22mmol/l (50 vol %). In venous blood the partial pressure is 6.1
kPa (45 mmHg) and the concentration 24 mmo1/L (54 vol %). Carbon dioxide transport
is linked to oxygen transport (see 9.3 and 9.13) and is mainly determined by chemical
reactions. During respiration there are only small fluctuations in the CO2 transport system because fluctuations in CO2 tension are leveled down by the presence of lung water.
The carbonic acid dissociation curve, showing the relationship between CO2 content and
CO2 pressure, is almost linear in the physiological range (see 9.13). This is a favourable
situation when there are large differences in ventilation/perfusion ratios. A rectilinear
relationship makes it difficult to reach gas equilibrium during passage through the capillaries, especially as the rate of combining CO2 is a limiting factor.
The membrane factor (see 8.2) plays only a limited part in the alveolar-capillary transport of carbon dioxide, despite the gas pressure gradient (PA-c-) only being 5 mmHg (0.8
kPa). This is associated with the high solubility of CO2, giving a rate of diffusion (Dm)
about 20 times that of oxygen and nitrogen (see 8.1). The blood factor is a limiting factor
in CO2 gas exchange due to the chemical binding to haemoglobin. The circulation factor,
i.e. the volume of CO2 leaving the capillary bed per unit time, is also important. The mutual relationship of these factors is established in the equation for the alveolar-capillary
transfer of carbon dioxide (compare 8.2):
.
1/TL = 1/Dm + 1/(β · Qc + θ · Qc)
Under normal conditions of rest there is no measurable PCO2 gradient between the alveolar gas and the end-capillary blood (see figure). In pathological conditions a small A-c’
CO2 gradient can occur. This indicates a serious disturbance of alveolar-capillary diffusion or very rapid perfusion of the alveolar capillary bed. Even in normal circumstances
there is a small A-c’ CO2 gradient during work, probably due to the blood factor and the
circulation factor. In lung function disturbances this gradient increases with exertion.
Unlike the end-capillary CO2 tension, the arterial CO2 tension deviates slightly from the
alveolar CO2 tension (Pa-A,CO2 > 0), even under normal conditions at rest.
References
Cotes JE. Lung function, 4th edition. Blackwell, Oxford, 1979
Wagner PD, West JB. J Appl Physiol 1972; 33: 62.
G.J. Tammeling and Ph.H. Quanjer
Contours of Breathing - Diffusion
8.4 Alveolar-capillary oxygen transport
Oxygen transport is determined by the following factors:
- The membrane factor: the diffusion of oxygen across the alveolar-capillary membrane
is a limiting factor because of the low rate of diffusion, which is a function of its comparatively low solubility (see 8.1).
- The blood factor: the combination of oxygen with haemoglobin is an important limiting factor (θ · Qc factor). The diffusion and convection of oxygen molecules in the
plasma and erythrocytes plays no part in the rate of combining of oxygen;
- And the circulation factor: the
. transport of oxygen in the blood stream is also an
important limiting factor (β · Qc factor).
Between the mixed venous blood and the alveolar gas there is a steep oxygen gradient,
about 8.7 kPa (65 mmHg). This, combined with gas exchange on the steep part of the oxyhaemoglobin dissociation curve, causes a large oxygen flow immediately the gas enters
the blood in the alveolar capillary bed. This produces a rapid rise in oxygen pressure in
the capillary blood, displacing the gas exchange to the flat part of the dissociation curve.
There, a limited flow of oxygen brings about a large increase in oxygen pressure in the
blood. The gas flow is then well within the diffusion capacity of the membrane and the
speed with which oxygen combines with haemoglobin, so that pressure balance is rapidly reached. In normal circumstances, balance is nearly reached in the first third of the
contact time. During work, oxygen flow is much greater than at rest and the membrane
factor is relatively important: balance is not reached until immediately before the blood
leaves the pulmonary capillaries. As the combination of oxygen and carbon dioxide with
haemoglobin effect each other, CO2 transport is a limiting factor: “oxygen has to wait for
the CO2 and vice versa” (Visser).
Neither at rest nor during work is there an oxygen gradient between the alveolar gas
and the end-capillary blood (Pc’,O2 ≈ PA,O2)). The normal A-a gradient is almost entirely
the result of venous mixing or of unequal ventilation/perfusion ratios. During work, the
inequality diminishes. Under hypoxic conditions the oxygen gradient is small and gas
exchange continues to take place on the steep part of the oxyhaemoglobin dissociation
curve (West). The oxygen flow across the membrane and the rate at which the oxygen
combines are then too low for equilibrium to arise between the alveolar gas and the
capillary blood before the blood leaves the pulmonary capillaries.
In various lung function disturbances the alveolar-capillary transport of oxygen is
disturbed, bringing about an abnormally large oxygen gradient between the alveoli and
the end-capillary blood. Oxygen transport is most sensitive to disturbances in lung
function (see 1.4-1.6), as a result of the gas transfer properties of this gas. The transfer
factor of oxygen (TL,O2) cannot be determined directly, since the end-capillary oxygen
pressure and mean capillary oxygen pressure cannot be measured (see 8.5). In addition,
oxygen transport is strongly influenced by disturbances leading to uneven lung function, especially unequal gas exchange/perfusion ratios (TL/Qc inequality) (Cotes). It is
therefore sufficient for clinical lung function examinations to measure the transfer factor of carbon
monoxide. This is technically simpler because of the specific properties of carbon monoxide (see
8.6) and the fact that the TL,O2 can be deduced from it: TL,O2 = 1.23 · TL,CO (see 8.1).
References:
Cotes JE. Lung function, 4th edition. Blackwell, Oxford, 1979.
Wagner PD, West JB. J Appl Physiol 1972; 33: 62.
West JB. Ventilation/blood flow and gas exchange, 3rd edition. Blackwell, Oxford, 1977.
G.J. Tammeling and Ph.H. Quanjer
Contours of Breathing - Diffusion
8.5 Alveolar-capillary transport of carbon monoxide and
nitrous oxide
The molecular weight of carbon monoxide, and its solubility in the body fluids, differ but
little from those of oxygen (see 8.1). The affinity of carbon monoxide for haemoglobin is,
however, 230 times that of oxygen (Haldane’s constant). Carboxyhaemoglobin (COHb)
cannot combine with oxygen and is therefore unable to transport oxygen. Also, in the
presence of carbon monoxide the dissociation curve of the oxyhaemoglobin still present
is displaced in an unfavorable direction. In normal circumstances, minimal quantities
of carbon monoxide are formed in the body during the breakdown of haem (about 18
mmol per hour). The normal carboxyhaemoglobin concentration in the blood is 0.7%
whilst the carbon monoxide concentration of the air is less than 0.0001% (1 ppm). The
CO content of continuously inspired gas should not be greater than 25 ppm (25 · 10-4
%), this leads to a carboxy-haemoglobin concentration of 4% at most (WHO, 1972). Air
pollution, especially inhalation of cigarette smoke, can cause the percentage of COHb in
the blood to rise to 14% (1.3 mmol/L). A COHb content of only 10% has harmful effects,
e.g. on the nervous system or by promoting atherosclerosis. The rate of dissociation
of carboxyhaemoglobin and the level of ventilation determine the speed at which CO
intoxication can be reversed. During air breathing at rest its half-life is about 4 hours;
while breathing oxygen it is considerably less. The carbon monoxide pressure in the
blood is very low compared with that in alveolar gas, because carbon monoxide in the
plasma is almost instantly “captured” by hemoglobin. Carbon monoxide combines much
more with hemoglobin. than it is carried away as .a dissolved gas by the circulation. The
circulation factor (β · Qc) can thus be ignored.
Carbon monoxide is very suitable for measurement of pulmonary gas transfer
because at low concentrations the average capillary CO tension (Pc,CO) can be equalized with the mixed venous CO concentration (Pv,CO). In persons who have not been
exposed to CO the Pv,CO is negligible; in smokers the Pv,CO can rise to as much as 0.007
kPa (0.05 mmHg). The carbon monoxide transfer factor (TL,CO) thus depends on the
membrane factor and the blood factor alone (see 8.2):
1/TL,CO = 1/Dm + 1/(θCO · Qc)
The coefficient of rate of reaction of CO with HbO2 is indirectly proportional to the
oxygen tension. The value of the TL,CO thus depends on the oxygen tension at which the
measurement takes place. When the TL,CO is measured at two different oxygen tensions
(e.g. ambient air and pure oxygen) the membrane factor (Dm) and the capillary blood
volume (Qc) can be calculated separately.
Nitrous oxide (N2O, laughing gas) does not form compounds in the blood and is very
soluble in body fluids. The rate of diffusion of N2O is high and its transport is not limited
by the diffusion capacity of the alveolar-capillary membrane. The membrane factor (Dm)
and the blood factor play no part in the transport of nitrous oxide; the only determining
factor is that of circulation. Thus for nitrous oxide:
.
1/TL,N2O = βN2O · Qc
This makes it suitable for measuring alveolar capillary circulation. This applies even more to acetylene (C2H2), which has an even lower molecular weight and a higher solubility coefficient than
N2O and also does not form compounds in the blood (θ = 0).
References
Coburn RF, Forster RE, Kane PB. J Clin Invest 1965; 44: 1899.
Cotes JE. Lung function: Assessment and application in medicine. Blackwell, Oxford, 1979.
Cotes JE. The transfer factor (diffusing capacity). In: Standardized lung function testing (Quanjer PhH, editor). Report of the European Community for Coal and Steel, Luxembourg, 1982.
Forbes WH, Sargent F, Roughton FJW. Am J Physiol 1945; 143: 594.
Wald NJ, Idle M, Boreham J, Bailey A. Thorax 1981; 36: 366.
WHO: Air qualitiy criteria and guides for urban air pollutants. Technical reports nr. 506, Geneva, 1972.
G.J. Tammeling and Ph.H. Quanjer
Contours of Breathing - Diffusion
8.6 Assessment of the carbon monoxide transfer factor
There are various ways of measuring the transfer factor of carbon monoxide (TL,CO): the
multi-breath “steady state” method, the “rebreathing” method, and the “single breath”
method, developed by Krogh in 1910. The latter method is widely used (see figure):
A)The subject breathes quietly into a closed spirometer system and then breathes out to
the fullest possible extent.
B) The test gas is inhaled from the level of residual volume to the level of total lung capacity, using a “bag in box” system connected to a spirometer. The composition of the
test gas is as follows: FCO = 0.003; FHe = 0.29; FO2 = 0.18; FN2 = the rest. The following
variables are determined: FI,CO; FI,He; FO2 if appropriate and the IVC using a spirometer.
C)The breath is held for 10 seconds at TLC level; the spirometer connection is then
closed.
D)The subject breathes out slowly at an even rate. The first 0.75 L is expired into the
spirograph and serves to flush out the airway dead space; the following 0.5 or 1.0 I is
expired into the gas sample bag, the contents of which are analyzed: FA,CO, FA,He and
FA,O2.
The carbon monoxide transfer factor is calculated as follows (Cotes):
TL,CO = constant · alveolar volume/measuring time ·
10log(initial CO concentration/final CO concentration)
- The constant is associated with the units: mmol · min-1 · kPa-1: 53.6; ml · min-1 ·
mmHg-1: 160; μmol s-1 · Pa-1: 895.
- The alveolar volume is the sum of the inspired vital capacity and the residual volume,
minus the volume of the dead space: VA = IVC + RV - VD. The RV is determined separately by the closed system method (see 3.3) or by body plethysmography (see 5.22).
When the RV is calculated from single breath helium dilution, we get the effective
alveolar volume (VA,eff). In the event of airflow obstruction, calculation on the basis
of VA,eff leads to underestimation and, on the basis of thoracic gas volume measured
using a body plethysmograph, to overestime the carbon monoxide transfer factor. The
measurement is unreliable when the IVC is under 1.3 litres and/or the effective time
for which the breath is held is under 5 seconds.
- Besides the 10 seconds breathholding, the effective measuring time (t seconds)
includes two thirds of the inspiration time plus the expiration time up to half way
through taking the sample (see figure).
- The initial concentration of the alveolar carbon monoxide is calculated from that
of the inhaled gas and the alveolar dilution factor. This latter is deduced from the
dilution of a fairly insoluble inert gas like helium which is added to the test gas: FA,He/
FI,He. The initial concentration is also corrected for carbon monoxide in the mixed
- ). After the end of measurement this is determined by rebreathvenous blood (Fv,CO
ing into a small closed system (not shown in figure). Correction for Fv,CO
is especially
necessary for smokers. The initial concentration of the alveolar carbon monoxide is
thus as follows: FI,CO · (FA,He/FI,He) - Fv,CO
- The final concentration of the alveolar carbon monoxide is mea¬sured directly in the expired
gas and is also corrected with the fractional concentration of carbon monoxide in the mixed
- .
venous blood: FA,CO - Fv,CO
The single breath method is also suitable for distinguishing between the membrane factor (Dm)
and the capillary blood volume (Qc) (see 8.2). For this, the measurement of TL,CO is repeated while
breathing an oxygen-rich gas mixture, FCO= 0.003; FHe ≈ 0.20; FO2 = the rest. The reaction rate
Continued next page
G.J. Tammeling and Ph.H. Quanjer
Contours of Breathing - Diffusion
of carbon monoxide with oxyhaemoglobin is indirectly proportional to the oxygen
tension: at an oxygen tension of 13.6 kPa (102 mmHg) 1/θ is 2.5 (kPa · L · min · mmol-1)
and at a PA,O2 of 74 kPa (550 mmHg) 1/θ is about 10.3. Thus we get two equations with
two unknowns from which Dm and Qc can be calculated graphically or algebraically:
References
Cotes JE. Lung function, 4th edition. Blackwell, Oxford, 1979.
Cotes JE, et al. Standardization of the measurement of transfer factor (diffusing capacity). Eur
Respir J 1993; 6,
suppl 16: 41-52.
G.J. Tammeling and Ph.H. Quanjer
Contours of Breathing - Diffusion
8.7 Carbon monoxide gas transfer (reference values)
Alveolar-capillary gas exchange is assessed by the carbon monoxide transfer factor, and
depends on anthropometric data and the circumstances in which the measurement is
carried out. The way the various components (membrane, blood volume, blood flow)
contribute to the alveolar-capillary gas transfer is only partially known:
- The transfer factor increases with the size of the lung, which is determined by
height, age and sex. The transfer factor is therefore calculated per litre of alveolar
volume and called the transfer coefficient: KCO = TL,CO/VA (mmol . min-1 . kPa-1 .
L-1).
- The transfer factor increases with the degree of inflation of the lung tissue by 10%
per litre of alveolar volume. This change is mainly caused by the membrane component.
- The transfer coefficient depends on the body posture; the KCO is higher when lying
than when sitting. This is probably largely due to changes in capillary blood volume.
- The transfer coefficient can increase during work to twice the value at rest, mainly as
the result of an increase in the capillary blood volume.
- Through the accumulation of blood in the peripheral circulation, and as a result of
cigarette smoking, the transfer coefficient drops. This is mainly due to a decrease of
the capillary blood volume. In the case of smoking, the membrane factor possibly
also plays a part.
- The transfer factor is markedly dependent on the combining of carbon monoxide
with haemoglobin and thus on the degree of oxygenation, the quantity, and the type
of haemoglobin.
Over the years, a large number of regression equations have been published from which
the reference values for TL,CO and KCO are calculated. They are different in children
and in adults. In adults, the reference values are calculated on the basis of height, sex
and age. Quanjer has derived regression equations from data from a large number of
authors (see Cotes et al.). Up to date reference equations derived by an ERS Task Force
will be published in 2017.
References
Cotes JE et al. Standardization of the measurement of transfer factor (diffusing capacity). Eur Respir J 1993;6, suppl 16: 41-52.
Cotes JE. Lung function, 4th edition. Blackwell, Oxford 1979
Forrest JB. Resp Physiol 1976; 27: 223-239
Quanjer PhH (editor). Standardized lung function testing. Eur Respir J 1993; 6, suppl 16
Roughton FJW, Forster RE. J Appl Physiol 1957; 11:2 91-302
Salorinne Y. Single breath pulmonary diffusing capacity. Scand J Resp Dis suppl. 96, 1976
Please note that these prediction equations will be superseded by those from an ERS Task Force, which will publish new
reference equations in 2017.
G.J. Tammeling and Ph.H. Quanjer
Contours of Breathing - Diffusion
8.8 Disturbances of alveolar-capillary gas transport
A. The normal alveolar-capillary membrane is uniform in structure, although there are
regional variations based on gravity (body position) and lung inflation (see 6.5 and
6.6). The major portion of the alveolar-capillary surface is effectively involved in gas
exchange.
B. The increase in pulmonary blood flow during physical exertion arises mainly from
an increase in the number of functioning capillaries, and to a lesser extent from the
degree of filling of perfused capillaries. During exertion the effective surface area of
the alveolar-capillary membrane increases, shown as a rise in the transfer coefficient
(see 8.7). An increase in pulmonary blood flow as the result of abnormality in the circulation (e.g. Fallot’s tetralogy) is also associated with a rise in the transfer coefficient.
C. Where pathology occurs in the alveolar-capillary membrane (inflammation, fibrosis,
oedema, embolism) the gas transfer properties are reduced and distributed unequally.
The transfer coefficient is then abnormally low.
D. Where there is a local loss of function of the lung tissue (atelectasis, tumours, inflammation, resection) the effective alveolar surface area is abnormally small, whereas
transfer in the remaining normal alveoli may not be disturbed. The latter compensate
for the loss of function of the diseased alveoli. The transfer coefficient is usually normal.
E. Where there is an obstruction in the pulmonary circulation, e.g. through stenosis of
the mitral valve, the blood volume per alveolus increases; filling of the capillaries is
greater and so closed capillaries open. This is associated with a decrease in pulmonary blood flow and thus an abnormally low transfer factor and transfer coefficient.
Where there is long-standing obstruction the gas transfer disturbance is exacerbated
by parenchymal abnormalities of the membrane (see H and I).
F. In emphysema the degenerative processes affect the capillary network, considerably
reducing the effective alveolar-capillary surface area. The transfer factor is abnormally
low through reduction of the membrane factor and the capillary blood volume. The
abnormally large alveolar volume accentuates the disturbance in the transfer coefficient: TL/ VA is greatly reduced.
G. The combination of respiratory gas with haemoglobin (θ) is one of the determining
factors in pulmonary gas transfer. An abnormal haemoglobin molecule (methhemoglobin or some other haemoglobin variant) or an abnormal quantity of haemoglobin
(anaemia, polycythaemia) influence alveolar-capillary gas transfer.
H.Thickening of the alveolar-capillary membrane is caused by: (a) an increase in the
quantity of interstitial fluid, e.g. uncompensated heart failure; (b) interstitial alveolar fibrosis, e.g. sarcoidosis, or (c) primary pulmonary hypertension; collagen loss
between the basal membranes, capillary obliteration and alveolar elastin loss. These
abnormalities cause disturbances to gas transfer, initially without measurable disturbance to ventilation (Bates). In such cases, determination of the TL,CO is a necessary
supplement to the usual ventilation measurements.
I. In pulmonary oedema, the alveolar-capillary membrane is covered with a layer of fluid. The
distance across which diffusion has to take place is thus abnormally great and alveolar-capillary
gas transfer is seriously impeded: both the transfer factor and the transfer coefficient are greatly
reduced. This disturbance is accentuated when the raised hydrostatic pressure of the interstitial
fluid causes capillary filling to be abnormally low (see 7.7).
A disturbance of the membrane factor (Dm) can be masked by a disturbance in capillary blood
volume (Qc) with the opposite effect. In that case TL is disturbed little, if at all. An abnormality of
Qc is often reversible, unlike a disturbance of Dm.
References
Bates DV, Macklem PT, Christie RV. Respiratory function in disease. W.B. Saunders, Philadelphia, 1971
Roughton FJW, Forster JE. J Appl Physiol 1957;11:291
Visser BF. Introduction to SI-units with special reference to pulmonary function. Biomed Techn 1976;21:206
Werner F. M.; Determination of the alveolar capillary blood volume (Vc) and the transfer factor of the alveo
lar-capillary membrane (Dm) by the single breath method. Thesis, Nijmegen, 1979
G.J. Tammeling and Ph.H. Quanjer