Diffusion across the respiratory membrane and DLCO !

Mechanism
Exam priority: medium

Oxygen crosses from the air sac into the blood through a very thin wall. If the wall thickens or surface is lost, less gets through.

Updated 2026-11-01

Also called: Diffusing capacity, Fick's law, DLCO

Key points

Fick's law: gas flow rises with area and gradient and falls with membrane thickness.
CO₂ diffuses about 20 times faster than O₂ because it is far more soluble, so a diffusion defect causes hypoxemia long before hypercapnia.
At rest O₂ equilibrates within the first third of the capillary (≈0.25 of ≈0.75 s): there is reserve. Exercise shortens transit and unmasks desaturation in interstitial disease.
Low DLCO: emphysema, interstitial lung disease, pulmonary embolism and pulmonary hypertension, anemia. Normal or high DLCO: asthma, polycythemia, alveolar hemorrhage, obesity.
Obstructive spirometry + low DLCO points to emphysema; obstructive + normal DLCO points to asthma.
Resting O₂ uptake is perfusion-limited; CO uptake is diffusion-limited (which is why CO measures diffusion).

What it is

O₂ and CO₂ cross the alveolar–capillary membrane by passive diffusion, down their partial-pressure gradients. The rate depends on surface area, membrane thickness and each gas's solubility. The DLCO test measures how well a tracer gas (carbon monoxide) diffuses, and separates diseases that damage the membrane from those that only narrow the airways.

How it works, step by step

Alveolar PO₂ (≈100 mmHg at sea level) is higher than mixed venous PO₂ (≈40 mmHg).
That gradient drives O₂ through the surfactant layer, type I epithelium, fused basement membrane and endothelium.
In plasma, O₂ binds hemoglobin, which keeps plasma PO₂ low and sustains the gradient.
A thickened membrane (fibrosis) or lost area (emphysema, embolism) lowers O₂ transfer per unit time.
With normal transit time there is still time to equilibrate; when exercise shortens transit, blood leaves unsaturated.

Equations

Fick's law (diffusion of a gas)V_gas = (A × D × (P₁ − P₂)) / T

A: membrane area
D: diffusion coefficient (solubility / √molecular weight)
P₁ − P₂: partial-pressure gradient
T: membrane thickness

Area, thickness and gradient are what disease changes.

Diffusing capacityDL = V_gas / (P_A − P_c)

DL: diffusing capacity (mL/min/mmHg)
P_A: alveolar partial pressure of the gas
P_c: mean capillary partial pressure of the gas

For CO, capillary pressure is near zero because hemoglobin takes it up at once.

Reference values (resting adult, sea level)

Parameter	Value	Note
Exchange surface area	≈50–100 m²	both lungs
Membrane thickness	≈0.2–0.6 µm
Capillary transit time	≈0.75 s	shorter during exercise
Normal DLCO	≈75–120 % of predicted	corrected for hemoglobin

Approximate values for a healthy adult at rest; each laboratory sets its own ranges.

Clinical notes

Interstitial lung disease: saturation is fine at rest and drops on walking; DLCO falls early.
Anemia lowers DLCO without lung disease, which is why DLCO is corrected for hemoglobin.
In Bogotá (≈2,600 m) alveolar PO₂ is lower, the gradient is smaller and a diffusion defect shows up sooner.

Test yourself

Think of the answer, then tap the question to see it.

Why does a diffusion defect cause hypoxemia without hypercapnia?

CO₂ is about 20 times more diffusible than O₂, so it keeps leaving even through a thickened membrane; the hypoxemia also drives ventilation, which lowers PaCO₂.

Why does a patient with pulmonary fibrosis desaturate on exercise but not at rest?

At rest the capillary has ample time to equilibrate O₂. On exercise cardiac output rises, transit shortens and the thickened membrane can no longer finish equilibration.

Which lung function finding separates emphysema from asthma?

Both are obstructive on spirometry, but emphysema destroys alveolar surface and lowers DLCO; in asthma DLCO is normal or high.

Why is carbon monoxide used to measure diffusion?

Hemoglobin binds it so avidly that its capillary pressure stays near zero, so only the membrane, not blood flow, limits its uptake.

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Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: 22.4 Gas Exchange (OpenStax (Rice University), 2022); Interstitial Lung Disease (StatPearls (NCBI Bookshelf), 2026); Chronic Obstructive Pulmonary Disease (COPD) (StatPearls (NCBI Bookshelf), 2026); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 40). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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