Editing Diffusing capacity (section)

===Blood CO levels may not be negligible===

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.

{{bold div|The two components of <math>D_{L_{CO}}</math>}}
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 | journal = J Appl Physiol | volume = 11 | issue = 2| pages = 290–302 | pmid = 13475180 | doi = 10.1152/jappl.1957.11.2.290 }}</ref> Since the steps are in series, the conductances add as the sum of the reciprocals:

{{NumBlk|::|<math>\frac {1} {D_{L_{CO}}} =\frac {1} {D_M} + \frac {1} {\theta * V_c}</math> .  | {{EquationRef|3}} }}

{{bold div|Any change in <math>V_c</math> alters <math>D_{L_{CO}}</math>}}

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.

In disease, [[Pulmonary hemorrhage|hemorrhage]] into the lung will increase the number of haemoglobin molecules in contact with air, and so measured <math>D_{L_{CO}}</math> will increase. In this case, the carbon monoxide used in the test will bind to haemoglobin that has bled into the lung. This does not reflect an increase in diffusing capacity of the lung to transfer oxygen to the systemic circulation.

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>.

{{bold div|Reasons why <math>\theta</math> varies}}

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" />

The lung blood volume is also reduced when blood flow is interrupted by blood clots ([[pulmonary emboli]]) or reduced by bone deformities of the thorax, for instance [[scoliosis]] and [[kyphosis]].

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>.

{{bold div|Lung diseases that reduce <math>D_M</math> and <math>\theta * V_c</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>.
# Loss of lung parenchyma in diseases like [[emphysema]].
# Diseases that scar the lung (the [[interstitial lung disease]]), such as [[idiopathic pulmonary fibrosis]], or [[sarcoidosis]]
# Swelling of lung tissue ([[pulmonary edema]]) due to [[heart failure]], or due to an acute inflammatory response to allergens ([[acute interstitial pneumonitis]]).
# Diseases of the blood vessels in the lung, either inflammatory ([[Vasculitis|pulmonary vasculitis]]) or hypertrophic ([[pulmonary hypertension]]).

{{bold div|Lung conditions that increase <math>D_{L_{CO}}</math>.}}
# 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.|journal=Journal of Clinical Investigation|volume=42|issue=7|pages=997–1006|doi=10.1172/JCI104804|pmc=289367|pmid=14016987|title=Pulmonary Diffusing Capacity and ITS Subdivisions in Polycythemia Vera|year=1963}}</ref> left to right [[Cardiac shunt|intracardiac shunts]],<ref>{{cite journal|last=AUCHINCLOSS JH|first=Jr|author2=GILBERT, R |author3=EICH, RH |title=The pulmonary diffusing capacity in congenital and rheumatic heart disease.|journal=Circulation|date=February 1959|volume=19|issue=2|pages=232–41|pmid=13629784|doi=10.1161/01.cir.19.2.232|s2cid=27264342|doi-access=free}}</ref> due increase in volume of blood exposed to inspired gas.
# [[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>