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# 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)**Vgas = (A × D × (P1 − P2)) / T

**A**
membrane area

**D**
diffusion coefficient (solubility / √molecular weight)

**P 1 − P 2**
partial-pressure gradient

**T**
membrane thickness

Area, thickness and gradient are what disease changes.

**Diffusing capacity**DL = Vgas / (PA − Pc)

**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.

## Memory aid

Think of a fence: more gates (area) and a bigger push (gradient) let more through; a thicker fence lets less through.

## 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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## Related topics

- [Diffusion and Fick's law](https://durgical.com/en/physiology/diffusion-and-fick-s-law/)
- [The causes of hypoxemia](https://durgical.com/en/physiology/the-causes-of-hypoxemia/)
- [Obstructive and restrictive patterns, and flow–volume loops](https://durgical.com/en/physiology/obstructive-and-restrictive-patterns-and-flow-volume-loops/)
- [The alveolar gas equation and the A–a gradient](https://durgical.com/en/physiology/the-alveolar-gas-equation-and-the-a-a-gradient/)
- [High altitude and acclimatization](https://durgical.com/en/physiology/high-altitude-and-acclimatization/)

## Related conditions

- [Interstitial lung disease](https://durgical.com/en/conditions/interstitial-lung-disease/)
- [Chronic obstructive pulmonary disease (COPD)](https://durgical.com/en/conditions/chronic-obstructive-pulmonary-disease/)
- [Carbon monoxide poisoning](https://durgical.com/en/conditions/carbon-monoxide-poisoning/)
- [Pulmonary embolism](https://durgical.com/en/conditions/pulmonary-embolism/)
- [Iron deficiency anaemia](https://durgical.com/en/conditions/iron-deficiency-anaemia/)

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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](https://openstax.org/books/anatomy-and-physiology-2e/pages/22-4-gas-exchange) (OpenStax (Rice University), 2022); [Interstitial Lung Disease](https://www.ncbi.nlm.nih.gov/books/NBK541084/) (StatPearls (NCBI Bookshelf), 2026); [Chronic Obstructive Pulmonary Disease (COPD)](https://www.ncbi.nlm.nih.gov/books/NBK559281/) (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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Representative model, for educational purposes only.

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