goitre in the neck). This results in inspiratory collapse of the airway below the obstruction (but still outside the thorax), attenuating maximum inspiratory flow rate to a greater degree than maximum expiratory flow rate.
Total lung capacity
The measurement of TLC is not considered in detail here; the interested reader is referred to the reading list at the end of the chapter.
Figure 3.7 Relative effects on expiratory and inspiratory flow of intra‐ and extrathoracic large airway obstruction. Top: Large airway obstruction within the thorax. (a) Positive intrathoracic (alveolar) pressure generated during expiration acts to compress the airway and further narrow the point of obstruction. (b) Negative intrathoracic pressure during inspiration acts to reduce narrowing at the point of obstruction. Therefore, in large airway obstruction within the thorax, expiratory flow is diminished to a greater degree than inspiratory flow (see Fig. 3.6d). Bottom: Large airway obstruction outside the thorax. (c) Positive pressure within the airway during expiration in relation to atmospheric (‘zero’) pressure outside acts to reduce narrowing at the point of obstruction. (d) Negative pressure within the airway during inspiration acts to compress the airway and further narrow the point of obstruction. Therefore, in large airway obstruction outside the thorax, inspiratory flow is diminished to a greater degree than expiratory flow (see Fig. 3.6e).
Whereas VC and its subdivisions can be measured directly by spirometry, measurement of residual volume and TLC requires the use of helium dilution or plethysmography methods. In the dilution technique, a gas of known helium concentration is breathed through a closed circuit and the volume of gas in the lungs is calculated from a measure of the dilution of the helium, which, being an inert gas, is neither absorbed nor metabolised. This dilution method measures only gas in communication with the airways and tends to underestimate TLC in patients with severe airway obstruction, because of the presence of poorly ventilated bullae.
The body plethysmograph is a large airtight box that allows pressure–volume relationships in the thorax to be determined. When the plethysmograph is sealed, changes in lung volume are reflected by a change in pressure within the box. Plethysmography tends to overestimate TLC, because it measures all intrathoracic gas, including that in the bullae, cysts, stomach and oesophagus. Chest X‐ray can be used to give a very rough estimate of TLC. In airway disease, TLC is increased as a manifestation of hyperinflation and as a result of increased lung compliance in emphysema (see Chapter 1). TLC is reduced in restrictive lung disease (by definition).
Respiratory muscle function tests
Weakness of the respiratory muscles causes a restrictive ventilatory defect, with reduced TLC and VC. Comparison of VC in the erect and supine positions is useful, because the pressure of the abdominal contents on a weak diaphragm typically causes a fall of around 30% in supine VC. Chest X‐ray often shows small lung volumes with basal atelectasis and high hemi‐diaphragms. Ultrasound screening may show paradoxical upward movement of a paralysed diaphragm during inspiration. Global respiratory muscle function may be assessed by measuring mouth pressures. Maximum inspiratory mouth pressure, P I max, is measured during maximum inspiratory effort from residual volume against an obstructed airway using a mouthpiece and transducer device, and maximum expiratory mouth pressure, P E max, is measured during a maximal expiratory effort from TLC. When there is severe respiratory muscle weakness, ventilatory failure develops with hypercapnia.
Gas transfer (transfer factor for carbon monoxide)
At one time, the rate at which gases diffused across the alveolar–capillary membrane was thought to be the principal factor limiting gas exchange. The term diffusing capacity was thus coined, defined as ‘The quantity of gas transported across in each minute for every unit of pressure gradient’. Although the measurement proved to be very useful clinically, it was later realised that it was affected by many other factors in addition to diffusion, particularly V/Q matching. It was therefore renamed transfer factor.
Clearly, it is the transfer of oxygen that is of most interest to clinicians. This is very difficult to measure in practice, however, as transfer of oxygen into the blood quickly becomes limited by the saturation of haemoglobin. Carbon monoxide is thus used as a surrogate for oxygen in this measurement. Very low concentrations are used so that haemoglobin remains avid for the gas as it passes through the alveolar capillary (and of course high concentrations would be dangerous).
The term ‘diffusion capacity’ (D L CO) can still be found in some texts; this is synonymous with ‘transfer factor’ (T L CO).
To measure TLCO, we need to know:
1 the amount of CO transferred per minute, and
2 the pressure gradient across the alveolar membrane (in effect, the alveolar partial pressure, as the partial pressure in blood is essentially zero).
Single‐breath method
The single‐breath method is shown in Fig. 3.8. The patient inspires a gas mixture of helium and carbon monoxide, holds their breath for 10 seconds and then breathes out. An initial volume equivalent to the dead space (the part of the respiratory tract not involved in gas exchange) is discarded and a sample of the expired gas is collected and analysed for alveolar concentrations of helium and carbon monoxide. The change in concentration of helium (which, being an inert gas, is neither absorbed nor metabolised) between the inspired and alveolar samples is the result of gas dilution and gives a measurement of the alveolar gas volume (VA). The expired concentration of carbon monoxide is also lower than the inspired level, but the fall is proportionately greater than in the case of helium because some of the carbon monoxide is absorbed into the bloodstream. The rate of uptake of carbon monoxide can then be calculated as the uptake per minute per unit of partial pressure of carbon monoxide (mmol/min/kPa).
Many factors influence TLCO, including:
V/Q imbalance (disturbed in many diseases, affecting lung parenchyma or vasculature)
the surface area of the membrane for diffusion (reduced in emphysema)Figure 3.8 Measurement of transfer factor by the single‐breath method. Schematic representation of the helium and carbon monoxide concentrations in the inspired mixture and in alveolar air during breath holding.
the thickness of the alveolar capillary membrane (increased in fibrotic lung disease)
the pulmonary capillary blood volume (increased in high cardiac output states)
the haemoglobin concentration.
Free blood in the lungs from pulmonary haemorrhage will also avidly absorb carbon monoxide and lead to an elevated TLCO.
Transfer coefficient
Clearly, TLCO can be reduced by a number of disease processes within the lung. It is also reduced if there is simply ‘less lung’ (a reduced lung volume) participating in gas transfer (e.g. respiratory