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{{Short description|Measure of the transfer of gas from the lung to red blood cells}}
{{Infobox diagnostic
| Name = Diffusing capacity
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| OtherCodes = CPT: 94720
}}
'''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 [[pulmonary function testing|pulmonary function tests]] to determine the overall ability of the [[lung]] to transport gas into and out of the blood. D<sub>L</sub>, especially [[DLCO|D<sub>LCO</sub>]], is reduced in certain diseases of the lung and heart.
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|978-1-60913-640-6}}</ref>
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* 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.
==
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>.
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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}} }}
== 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 Science|date=May 1981|volume=60|issue=5|pages=507–12|pmid=7249536|doi=10.1042/cs0600507}}</ref> [[polycythemia]],<ref>{{cite journal|last=Burgess|first=J. H.|author2=Bishop, J. M.
# [[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==
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