Oxygen and carbon dioxide are transported in the body by a mixture of bulk ﬂow and diffusion. Bulk flow, generated by differences in total fluid pressure, is important in most of the airways and in transporting blood containing these gases between pulmonary and tissue capillaries. Diffusion, driven by partial pressure differences, is important in the last few millimetres of the airways, across the alveolar-capillary membrane and between tissue capillaries and mitochondria.
The alveolar–capillary membrane (Fig. 5a) Adult male lungs contain about 300 million alveoli, approximately 0.2 mm in diameter. Between neigh bouring alveoli are two layers of alveolar epithelium each resting on a basement membrane, enclosing the interstitial space, containing pulmonary capillaries, elastin and collagen ﬁbres. The alveolar epithelium and capillary endothelium form the alveolar–capillary membrane, through which gases diffuse. It is very thin (<0.4 μm), except where collagen and elastin fibre are concentrated, with a total surface area of about 85 m2. There are two types of alveolar epithelial cells. Type I pneumocytes line the alveoli and are relatively devoid of organelles. The round type II pneumocytes have large nuclei, microvilli and contain striated osmiophilic lamellar bodies storing surfactant, an important component of alveolar lining fluid (Chapter 6).
Diffusion and perfusion limitation (Fig. 5b)
If gas containing the poorly soluble gas nitrous oxide (N2O) is inhaled, pulmonary capillary Pn2o rises and quickly equilibrates with alveolar Pn2o. With no alveolar-capillary partial pressure gradient remaining, diffusion ceases along the rest of the pulmonary capillary and uptake can only be increased by increasing pulmonary capillary blood flow. N2O uptake is said to be perfusion-limited. In contrast, when breathing a carbon monoxide (CO) containing mixture, the CO combines so avidly with haemoglobin that pulmonary capillary Pco rises little. The pressure gradient driving diffusion is preserved along the capillary, and CO uptake would not be increased by increased perfusion. Improved ease of diffusion, with reduced thickness or increased area of the alveolar-capillary membrane, would increase CO uptake. CO transfer is diffusion-limited. Oxygen transfer lies between these two extremes, but is normally perfusion-limited.
Factors affecting diffusion across a membrane (Fick and Graham’s laws)
For a sheet of tissue of area A and thickness T through which gas g is passing (Fig. 5c):
A Rate of transfer of gas, g ∝ ( P1 – P2 )
The constant of proportionality
Although the molecular weight of CO2 is about 1.4 times that of O2, it is about 20 times more soluble, and so diffuses more easily.
For the alveolar-capillary membrane, the pressure gradient driving diffusion is alveolar (PA) minus mean pulmonary capillary (PC-). The constants (s, mw, A and T) can be combined to give a single constant, the diffusing capacity (DLg) of the lungs for gas, g:
Rate of transfer of gas, g = DLg( PA − PC-) Oxygen diffusing capacity, DLo2
= Oxygen uptake from the lungs (Y- o2 )
PAo2 − PC-o2
Although measurement of DLo2 is desirable, it is not possible because mean capillary Po2 ( PC-o2) cannot be measured. CO diffuses through the same pathway as O2, and its rate of diffusion is affected by the same factors that affect oxygen transfer. However, unlike DLo2, DLco is measurable. Once CO arrives in the pulmonary capillary blood, it too combines with haemoglobin. Haemoglobin has approximately 240 times the affinity for CO than it does for O2, and consequently as CO is transferred, almost all of it enters chemical combination and the mean pulmonary capillary Pco can be assumed to be zero.
This simplifie the equation to:
DLco = Carbon monoxide uptake from the lungs (Vco)
Several methods are used for measuring DLco, but all involve breathing a low level of CO (e.g. 0.3%). By sampling exhaled gas, CO uptake and mean alveolar Pco can be calculated. The normal value depends on the method used, but is about 15-30 mL/min per mmHg (112-225 mL/min per kPa). A tracer gas, such as helium, is included in the gas mixture so that alveolar volume can also be measured (see Chapter 20). DLco is divided by alveolar volume to give an index (Kco) that corrects for different lung volumes. As both DLo2 and DLco are affected by the rate of gas combination with haemoglobin in addition to factors affecting diffusion, the alternative term, transfer factor (TLo2 and TLco), is more commonly used in Europe.
Factors affecting DLco (TLco)
DLco is lowered by reduced alveolar-capillary membrane area in emphysema, pulmonary emboli or lung resection and by increased thick- ness in pulmonary oedema. In pulmonary fibrosi the alveolar-capillary membrane is both thickened and reduced in area giving a low DLco with a low but less affected Kco. Increased pulmonary blood volume in exercise increases the effective area increasing DLco. DLco is increased with polycythaemia and reduced in anaemia. DLco is therefore non-specific but it is sensitive and may reveal abnormalities when other lung function tests are normal. Hypoventilation does not affect DLco because the reduced CO uptake is caused by reduced PAco.
The oxygen cascade (Fig. 5e) shows how Po2 falls between air and mitochondria. Mitochondrial oxidative phosphorylation will cease when Po2 falls below 1 mmHg (0.13 kPa), and this ultimately limits the capillary Po2 that can be tolerated and therefore the amount of oxygen that can be removed as blood passes through the tissues. Capillary Po2 must remain high enough to drive diffusion to cells at a rate sufficien to match oxygen consumption and maintain mitochondrial Po2 above ritical level.