F7b Diffusion of respiratory gasses

Vivian Imbriotis | Nov. 24, 2025

Fick's law of diffusion

$$\frac{dV}{dt} = k \cdot \frac{\Delta P \cdot SA \cdot \text{solubility}}{\text{thickness} \cdot \sqrt{MW}}$$



If a gas is perfusion-limited, then \(t_{\text{equilibrium}} < t_{\text{transit}}\) and increases in perfusion will result in increased rate of transfer. (Normally oxygen is perfusion limited, where \(t_{transit} \approx 4t_{equilibrium}\).


If a gas is diffusion-limited, then \(t_{\text{equilibrium}} > t_{\text{transit}}\), i.e. there is still a persisting gradient at the end of the capillary. Increases in perfusion will not increase the rate of transfer. CO is an example, because \(P_aCO \approx 0\) always, due to its aggressive binding to Hb.




$$\frac{dV}{dt} = \frac{\Delta P \cdot SA \cdot \text{solubility}}{\text{thickness} \cdot \sqrt{MW}}$$

or

$$\dot{V} = \text{DL} \cdot \Delta P$$


In words, diffusing capacity of the lung = "volume of gas that will diffuse over the membrane per minute per mmHg"

CO is used to measure this because \(P_aCO_2\) is always almost zero due to its Hb affinity. Therefore

$$\frac{V_\text{CO exhaled} - V_\text{CO inhaled}}{\text{time}} = \text{DLCO} \cdot (P_ACO - P_aCO)$$

$$\frac{V_\text{CO exhaled} - V_\text{CO inhaled}}{\text{time}} = \text{DLCO} \cdot P_ACO$$

Measured thusly:

  1. Exhale to RV
  2. Inhale mix of oxygen, helium, and CO to TLC
  3. Allow time for equilibrium
  4. Exhale, discarding dead space gas
  5. Measure \(P_{exhaled}He\) and \(P_{exhaled}CO\)
  6. Compute the TLC from \(P_{exhaled}He\)
  7. Compute the uptake of CO from the difference in CO partial pressure and then the DLCO

Factors affecting diffusing capacity are:

Gas factors: molecular weight, solubility, temperature

Surface area factors: age (\(\downarrow\)), lung volume (\(\uparrow\)) and therefore position, lung disease, obesity, pregancy. Shunt and dead space both decrease effective SA; V/Q scatter decreases efficiency.

Membrane thickness factors: pulmonary oedema, interstitial lung disease

Erythocyte uptake factors: [Hb], cardiac output (in low output states Hb can become more saturated with CO)

Sources of error: alveolar haemorrhage, endogenous CO from smoking or haemolysis, high FiO2 (competes)

Significant increase with exercise!