Abstract
So, for a given clinical situation, the only factor that can be altered is the concentration gradient; for example, by increasing the inspired fraction FiO2 in the case of O2.
Which factors affect the rate of diffusion across a biological membrane?
The diffusion of molecules across a biological membrane is governed by five factors:
Fick’s law. The rate of diffusion of a substance across a membrane is directly proportional to the concentration gradient (or partial pressure gradient for gases).
Graham’s law. The rate of diffusion of a substance across a membrane is inversely proportional to the square root of its molecular weight (MW).
Surface area. The rate of diffusion is directly proportional to the surface area of the membrane.
Membrane thickness. The rate of diffusion is inversely proportional to the thickness of the membrane.
Solubility. The rate of diffusion of a substance is directly proportional to its solubility.
Combining all these factors:
Key equation: rate of alveolar diffusion
Of the five factors:
Two factors relate to the diffusion barrier: surface area and thickness.
Two factors are inherent properties of the substance diffusing: solubility and MW.
So, for a given clinical situation, the only factor that can be altered is the concentration gradient; for example, by increasing the inspired fraction FiO2 in the case of O2.
How is the lung alveolus designed for efficient gas diffusion?
Two aspects of lung anatomy are responsible for efficient gas exchange:
A large surface area for diffusion. The lungs contain around 300 million alveoli, which provide a massive 70 m2 surface area for gas exchange.
A thin alveolar–capillary barrier, as little as 200 nm in some places.
It takes an average of 0.75 s for a red blood cell (RBC) to pass through a pulmonary capillary at rest, so the time available for diffusion is limited. However, gaseous diffusion within the lung is so efficient that O2 diffusion is usually complete within 0.25 s: at rest, there is normally a threefold safety factor for diffusion. The high degree of safety for O2 diffusion means that hypoxaemia is rarely due to a diffusion defect when compared with other factors such as V̇/Q̇ mismatch.
How do diffusion of oxygen and carbon dioxide compare in the lungs?
As discussed above, the rate of diffusion is affected by two factors specific to the substance diffusing: MW and solubility. Despite O2 and CO2 having similar MWs (32 Da and 44 Da, respectively), the rate of diffusion of CO2 is 20 times higher than that of O2 owing to the much higher solubility coefficient of CO2. Therefore, in clinical situations where there is a diffusion defect (e.g. in pulmonary fibrosis), O2 diffusion is more likely to be limited than CO2 diffusion, resulting in type 1 respiratory failure. Thus, clinically significant hypercapnoea is never caused by impaired diffusion.
How does the diffusion of oxygen compare with the diffusion of other gases?
Comparing the diffusion of O2 with other gases is complicated. As O2 diffuses into the blood, most is bound to Hb, but some is dissolved in the plasma (see Chapter 8). It is the O2 dissolved in the plasma that determines its partial pressure PO2. At rest, an RBC takes 0.75 s to traverse a pulmonary capillary. As the RBC transits through the pulmonary capillary, diffusion of O2 into the plasma increases its PO2, which in turn reduces the pressure gradient across the alveolar–capillary barrier. An equilibrium is reached between the alveolar and plasma PO2 after 0.25 s, after which net diffusion ceases (Figure 10.1).
