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{{Short description|Measure of the transfer of gas from the lung to red blood cells}}
{{Infobox diagnostic
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| OtherCodes = CPT: 94720
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'''Diffusing capacity''' of the lung (D<sub>L</sub>) (also known as ''transfer factor'') measures the transfer of gas from air in the lung, to the [[red blood cell]]s in lung blood vessels. It is part of a comprehensive series of
In [[respiratory physiology]], the diffusing capacity has a long history of great utility, representing [[Electrical resistance and conductance|conductance]] of gas across the alveolar-capillary membrane and also takes into account factors affecting the behaviour of a given gas with hemoglobin.{{Citation needed|reason=uncited definition|date=March 2014}}
The term may be considered a misnomer as it represents neither [[diffusion]] nor a [[Battery (electricity)|capacity]] (as it is typically measured under submaximal conditions) nor [[capacitance]]. In addition, gas transport is only diffusion limited in extreme cases, such as for oxygen uptake at very low ambient oxygen or very high pulmonary blood flow.{{Citation needed|reason=unproved statement|date=August 2015}}
The diffusing capacity does not directly measure the primary cause of [[hypoxemia]], or low blood oxygen, namely mismatch of [[Ventilation/perfusion ratio|ventilation to perfusion]]:<ref>West, J. 2011. Respiratory Physiology: The Essentials. 9e. {{ISBN
* Not all pulmonary arterial blood goes to areas of the lung where gas exchange can occur (the anatomic or physiologic shunts), and this poorly oxygenated blood rejoins the well oxygenated blood from healthy lung in the pulmonary vein. Together, the mixture has less oxygen than that blood from the healthy lung alone, and so is hypoxemic.
* Similarly, not all inspired air goes to areas of the lung where gas exchange can occur (the [[Dead space (physiology)|anatomic and the physiological dead spaces]]), and so is wasted.
==Testing==
The '''single-breath diffusing capacity test''' is the most common way to determine <math>D_L</math>.<ref name="multiple" /> The test is performed by having the subject blow out all of the air that
The anatomy of the airways
{{NumBlk|::|<math>\dot{V}_{CO} =\frac {\Delta{[CO]} * V_A} {\Delta{t}} </math> . | {{EquationRef|4}} }}▼
::::The pulmonary function equipment monitors the change in the concentration of CO that occurred during the breath hold, <math>\Delta{[CO]}</math>, and also records the time <math>\Delta{t}</math>.▼
::::The volume of the alveoli, <math>V_A</math>, is determined by the degree to which the tracer gas has been diluted by inhaling it into the lung.▼
Similarly,▼
{{NumBlk|::|<math>P_{A_{CO}} = V_B * F_{A_{CO_{O}}} </math> . | {{EquationRef|5}} }}▼
where▼
::::<math>F_{A_{CO_{O}}}</math> is the initial alveolar fractional CO concentration, as calculated by the dilution of the tracer gas.▼
::::<math>V_B</math> is the barometric pressure▼
Other methods that are not so widely used at present can measure the diffusing capacity. These include the steady state diffusing capacity that is performed during regular tidal breathing, or the rebreathing method that requires rebreathing from a reservoir of gas mixtures.▼
== Calculation ==
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Sampling the oxygen concentration in the pulmonary artery is a highly invasive procedure, but fortunately another similar gas can be used instead that obviates this need ([[DLCO]]). [[Carbon monoxide]] (CO) is tightly and rapidly bound to hemoglobin in the blood, so the partial pressure of CO in the capillaries is negligible and the second term in the denominator can be ignored. For this reason, CO is generally the test gas used to measure the diffusing capacity and the <math>D_L</math> equation simplifies to:
{{NumBlk|::|<math>D_{L_{CO}} = \frac {\dot{V}_{CO}} {P_{A_{CO}} }</math>. | {{EquationRef|2}} }}
▲The '''single-breath diffusing capacity test''' is the most common way to determine <math>D_L</math>.<ref name="multiple" /> The test is performed by having the subject blow out all of the air that he/she can, leaving only the [[Lung volumes|residual lung volume]] of gas. The person then inhales a test gas mixture rapidly and completely, reaching the [[Lung volumes|total lung capacity]] as nearly as possible. This test gas mixture contains a small amount of carbon monoxide (usually 0.3%) and a ''tracer gas'' that is freely distributed throughout the alveolar space but which doesn't cross the alveolar-capillary membrane. Helium and methane are two such gasses. The test gas is held in the lung for about 10 seconds during which time the CO (but ''not'' the tracer gas) continuously moves from the alveoli into the blood. Then the subject exhales.
▲The anatomy of the airways brings with it complications, since the inspired air must pass through the mouth, trachea, bronchi and bronchioles before it gets to the alveoli where gas exchange will occur; on exhalation, alveolar gas must return along the same path, and so the exhaled sample will be purely alveolar only after a 500 to 1,000 ml of gas has left the subject. While it is algebraically possible to approximate the effects of anatomy (the ''three-equation method''<ref>{{cite journal |vauthors=Graham BL, Mink JT, Cotton DJ | year = 1981 | title = Improved accuracy and precision of single-breath CO diffusing capacity measurements | url = | journal = J Appl Physiol | volume = 51 | issue = 5| pages = 1306–13 | pmid = 7298468 }}</ref>), disease states introduce considerable uncertainty to this approach. Instead, the first 500 to 1,000 ml of the expired gas is disregarded and the next portion which contain gas that has been in the alveoli is analyzed.<ref name="multiple" /> By analyzing the concentrations of carbon monoxide and inert gas in the inspired gas and in the exhaled gas, it is possible to calculate <math>(D_{L_{CO}})</math> according to Equation {{EquationRef|2}}. First, the ''rate'' at which CO is taken up by the lung is calculated according to:
▲{{NumBlk|::|<math>\dot{V}_{CO} =\frac {\Delta{[CO]} * V_A} {\Delta{t}} </math> . | {{EquationRef|4}} }}
▲::::The pulmonary function equipment monitors the change in the concentration of CO that occurred during the breath hold, <math>\Delta{[CO]}</math>, and also records the time <math>\Delta{t}</math>.
▲::::The volume of the alveoli, <math>V_A</math>, is determined by the degree to which the tracer gas has been diluted by inhaling it into the lung.
▲Similarly,
▲{{NumBlk|::|<math>P_{A_{CO}} = V_B * F_{A_{CO_{O}}} </math> . | {{EquationRef|5}} }}
▲where
▲::::<math>F_{A_{CO_{O}}}</math> is the initial alveolar fractional CO concentration, as calculated by the dilution of the tracer gas.
▲::::<math>V_B</math> is the barometric pressure
▲Other methods that are not so widely used at present can measure the diffusing capacity. These include the steady state diffusing capacity that is performed during regular tidal breathing, or the rebreathing method that requires rebreathing from a reservoir of gas mixtures.
== Interpretation ==
In general, a healthy individual has a value of <math>D_{L_{CO}}</math> between 75% and 125% of the average.<ref name=uppsala>LUNGFUNKTION - Practice compendium for semester 6. Department of Medical Sciences, Clinical Physiology, Academic Hospital, Uppsala, Sweden. Retrieved 2010.</ref> However, individuals vary according to age, sex, height and a variety of other parameters. For this reason, reference values have been published, based on populations of healthy subjects<ref>{{cite journal |vauthors=Miller A, Thornton JC, Warshaw R, Anderson H, Teirstein AS, Selikoff IJ | year = 1983 | title = Single breath diffusing capacity in a representative sample of the population of Michigan, a large industrial state. Predicted values, lower limits of normal, and frequencies of abnormality by smoking history
===Blood CO levels may not be negligible===
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In heavy smokers, blood CO is great enough to influence the measurement of <math>D_{L_{CO}}</math>, and requires an adjustment of the calculation when COHb is greater than 2% of the whole.
While <math>(D_L)</math> is of great practical importance, being the overall measure of gas transport, the interpretation of this measurement is complicated by the fact that it does not measure any one part of a multi-step process. So as a conceptual aid in interpreting the results of this test, the time needed to transfer CO from the air to the blood can be divided into two parts. First CO crosses the alveolar capillary membrane (represented by <math>D_M</math> ) and then CO combines with the hemoglobin in capillary red blood cells at a rate <math>\theta</math> times the volume of capillary blood present (<math>V_c</math>).<ref>{{cite journal |vauthors=Roughton FJ, Forster RE | year = 1957 | title = Relative importance of diffusion and chemical reaction rates in determining rate of exchange of gases in the human lung, with special reference to true diffusing capacity of pulmonary membrane and volume of blood in the lung capillaries
{{NumBlk|::|<math>\frac {1} {D_{L_{CO}}} =\frac {1} {D_M} + \frac {1} {\theta * V_c}</math> . | {{EquationRef|3}} }}
The volume of blood in the lung capillaries, <math>V_c</math>, changes appreciably during ordinary activities such as [[Physical exercise|exercise]]. Simply breathing in brings some additional blood ''into'' the lung because of the negative intrathoracic pressure required for inspiration. At the extreme, inspiring against a closed glottis, the [[Müller's maneuver]], pulls blood ''into'' the chest. The opposite is also true, as exhaling increases the pressure within the thorax and so tends to push blood out; the [[Valsalva maneuver]] is an exhalation against a closed airway which can move blood ''out'' of the lung. So breathing hard during exercise will bring extra blood into the lung during inspiration and push blood out during expiration. But during exercise (or more rarely when there is a [[Atrioventricular septal defect|structural defect]] in the heart that allows blood to be shunted from the high pressure, systemic circulation to the low pressure, pulmonary circulation) there is also increased blood flow throughout the body, and the lung adapts by recruiting extra capillaries to carry the increased output of the heart, further increasing the quantity of blood in the lung. Thus <math>D_{L_{CO}}</math> will appear to increase when the subject is not at rest, particularly during inspiration.
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Finally, <math>V_c</math> is increased in '''[[obesity]]''' and when the subject lies down, both of which increase the blood in the lung by compression and by gravity and thus both increase <math>D_{L_{CO}}</math>.
The rate of CO uptake into the blood, <math>\theta</math>, depends on the concentration of hemoglobin in that blood, abbreviated [[Hemoglobin|Hb]] in the CBC ([[Complete Blood Count]]). More hemoglobin is present in [[polycythemia]], and so <math>D_{L_{CO}}</math> is elevated. In [[anemia]], the opposite is true. In environments with high levels of CO in the inhaled air (such as [[smoking]]), a fraction of the blood's hemoglobin is rendered ineffective by its tight binding to CO, and so is analogous to anemia. It is recommended that <math>D_{L_{CO}}</math> be adjusted when blood CO is high.<ref name="multiple" />
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Varying the ambient concentration of oxygen also alters <math>\theta</math>. At high altitude, inspired oxygen is low and more of the blood's hemoglobin is free to bind CO; thus <math>\theta</math> is increased and <math>D_{L_{CO}}</math> appears to be increased. Conversely, supplemental oxygen increases Hb saturation, decreasing <math>\theta</math> and <math>D_{L_{CO}}</math>.
Diseases that alter lung tissue reduce both <math>D_M</math> and <math>\theta * V_c</math> to a variable extent, and so decrease <math>D_{L_{CO}}</math>.
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# Diseases of the blood vessels in the lung, either inflammatory ([[Vasculitis|pulmonary vasculitis]]) or hypertrophic ([[pulmonary hypertension]]).
# Alveolar hemorrhage [[Goodpasture's syndrome]],<ref>{{cite journal|last=Greening|first=AP|author2=Hughes, JM|title=Serial estimations of carbon monoxide diffusing capacity in intrapulmonary haemorrhage.|journal=Clinical
# [[Asthma]] due to better perfusion of apices of lung. This is caused by increase in pulmonary arterial pressure and/or due to more negative pleural pressure generated during inspiration due to bronchial narrowing.<ref>{{cite journal|last=Collard|first=P|author2=Njinou, B |author3=Nejadnik, B |author4=Keyeux, A |author5= Frans, A |title=Single breath diffusing capacity for carbon monoxide in stable asthma.|journal=Chest|date=May 1994|volume=105|issue=5|pages=1426–9|pmid=8181330|doi=10.1378/chest.105.5.1426}}</ref>
==History==
In one sense, it is remarkable that DL<sub>CO</sub> has retained such clinical utility. The technique was invented to settle one of the great controversies of pulmonary physiology a century ago, namely the question of whether oxygen and the other gases were actively transported into and out of the blood by the lung, or whether gas molecules diffused passively.<ref>{{cite journal | author = Gjedde A | year = 2010 | title = Diffusive insights: on the disagreement of Christian Bohr and August Krogh
==See also==
* [[DLCO]]
==References==
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==Further reading==
* Mason RJ, Broaddus VC, Martin T, King T
* Ruppel, G. L. (2008) Manual of Pulmonary Function Testing. 9e. {{ISBN
* West, J. (2011) Respiratory Physiology: The Essentials. 9e. {{ISBN
* West, J. (2012) Pulmonary Pathophysiology: The Essentials. 8e. {{ISBN
*
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