Physiology for MRCEM Primary

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Respiratory physiology

Alveolar diffusion

[box type=”download”] — Relation of gas flow to membrane area, permeability and partial pressure differences — Transfer factor as an indicator of rate of gas transfer (detail of calculation not required) — Clinical implications of reductions in membrane area and/ or thickness — Limitations of gas transfer by diffusion (eg CO) or perfusion (oxygen) [/box]

Diffusion across the alveolar–capillary membrane

The rate of gas flow across the alveolar–capillary membrane = permeability × area × (difference in partial pressures).
The permeability depends on the membrane thickness, gas molecular weight and its solubility in the membrane.
Although CO2 is larger than O2, it crosses the membrane faster because it is more soluble in biological membranes.
The permeability and area dictate diffusing capacity (DL) for a gas, a measure of alveolar–capillary membrane function.
Thus, the rate of O2 transfer = DLO2 × (alveolar PO2 – lung capillary PO2),
or DLO2 = O2 uptake from lungs/(alveolar Po2 – lung capillary PO2).
DLO2 is sometimes called the transfer factor.
DLO2 cannot be estimated directly, because capillary PO2 cannot be measured.
However, the factors affecting O2 diffusion also affect carbon monoxide (CO) diffusion.
CO binds strongly to haemoglobin, and so, if low concentrations of CO are inhaled, CO diffusing into the blood is completely bound to haemoglobin and capillary PCO remains close to zero.
Thus, DLCO = CO uptake from lungs/alveolar PCO, and can be easily measured as an estimate of alveolar–capillary transfer function.
DLCO is reduced by a decrease in lung exchange area (e.g. emphysema) or an increase in alveolar–capillary membrane thickness (e.g. lung fibrosis, oedema).

Diffusion and perfusion limitation

Because CO binds so avidly and rapidly to haemoglobin, at low concentrations its rate of transfer into the blood is not affected by the blood flow, and is limited solely by its rate of diffusion across the alveolar–capillary membrane, i.e. transfer is diffusion limited.
For a poorly soluble gas, however (e.g. the anaesthetic nitrous oxide, N2O), the partial pressure in the blood rapidly reaches equilibrium with alveolar air, preventing further diffusion. In this case, increased blood flow will increase the rate of transfer, i.e. transfer is perfusion limited. O2 transfer is normally perfusion limited.