Diffusing capacity

Diffusing capacity of the lung (DL) (also known as transfer factor) measures the transfer of gas from air in the lung, to the red blood cells in lung blood vessels. It is part of a comprehensive series of pulmonary function tests to determine the overall ability of the lung to transport gas into and out of the blood. DL, especially DLCO, is reduced in certain diseases of the lung and heart. DLCO measurement has been standardized according to a position paper by a task force of the European Respiratory and American Thoracic Societies.

In respiratory physiology, the diffusing capacity has a long history of great utility, representing conductance of gas across the alveolar-capillary membrane and also takes into account factors affecting the behaviour of a given gas with hemoglobin.

The term may be considered a misnomer as it represents neither diffusion nor a 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.

The diffusing capacity does not directly measure the primary cause of hypoxemia, or low blood oxygen, namely mismatch of ventilation to perfusion:

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 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>.), 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. 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 as well as measurements made at altitude, for children and some specific population groups.

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.

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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>). Since the steps are in series, the conductances add as the sum of the reciprocals:

} =\frac {1} {D_M} + \frac {1} {\theta * V_c}</math> . |

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The volume of blood in the lung capillaries, <math>V_c</math>, changes appreciably during ordinary activities such as 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 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, 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>.

The rate of CO uptake into the blood, <math>\theta</math>, depends on the concentration of hemoglobin in that blood, abbreviated 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. polycythemia, left to right intracardiac shunts, 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.

History

In one sense, it is remarkable that DLCO 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. Remarkable too is the fact that both sides used the technique to gain evidence for their respective hypotheses. To begin with, Christian Bohr invented the technique, using a protocol analogous to the steady state diffusion capacity for carbon monoxide, and concluded that oxygen was actively transported into the lung. His student, August Krogh developed the single breath diffusion capacity technique along with his wife Marie, and convincingly demonstrated that gasses diffuse passively, a finding that led to the demonstration that capillaries in the blood were recruited into use as needed – a Nobel Prize–winning idea.

References

External links

American Association for Respiratory Care Clinical Practice Guidelines
The American Physiological Society home page
The American Thoracic Society home page
The European Respiratory Society home page

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