Physiology chapters
Alveolar gas exchange and diffusion
The partial pressures of oxygen and carbon dioxide from air to tissues, why alveolar air differs from room air, the factors that govern diffusion across the respiratory membrane, and the diffusing capacity of the lung.
- Gases move by diffusion from high to low partial pressure: alveolar PO2 about 104 mmHg, PCO2 about 40 mmHg; venous blood arrives with PO2 about 40 and PCO2 about 45.
- Diffusion rate rises with surface area, pressure difference and solubility, and falls with membrane thickness (Fick's law).
- CO2 diffuses about 20 times faster than O2 because it is far more soluble; DLCO measures the lung's diffusing capacity.
On this page
Overview
Oxygen moves from the alveoli into the blood, and carbon dioxide moves from the blood into the alveoli, by simple diffusion. Gases always move from a region of higher partial pressure to one of lower partial pressure.
Gas exchange takes place across the thin respiratory membrane between alveolar air and pulmonary capillary blood.
Partial pressures
Dalton's law: in a mixture of gases, each gas exerts its own pressure, its partial pressure, in proportion to its concentration.
At sea level, total pressure is 760 mmHg. Oxygen is about 21% of dry air, so dry room air has a PO2 of about 160 mmHg.
Why alveolar air is different
- Humidification: inspired air is saturated with water vapour (47 mmHg at body temperature), which dilutes the other gases. Tracheal PO2 is about 149 mmHg.
- Mixing with old air: each breath replaces only about one seventh of the alveolar air.
- Constant exchange: O2 is continually removed and CO2 added by the blood.
| Site | PO2 (mmHg) | PCO2 (mmHg) |
|---|---|---|
| Dry room air | 160 | 0.3 |
| Humidified tracheal air | 149 | 0.3 |
| Alveolar air | 104 | 40 |
| Mixed venous blood (entering lungs) | 40 | 45 |
| Pulmonary capillary blood (leaving) | 104 | 40 |
| Systemic arterial blood | 95 | 40 |
| Tissue cells (approx.) | 23 (or less) | 46 |
Arterial PO2 (95) is a little lower than alveolar PO2 (104) because about 2% of blood (bronchial circulation, some coronary veins) bypasses the alveoli. This is physiological shunt (venous admixture).
The respiratory membrane
The layers between alveolar air and red cells:
- Fluid and surfactant lining the alveolus.
- Alveolar epithelium (type I cells).
- Epithelial basement membrane.
- Thin interstitial space.
- Capillary basement membrane (often fused with the epithelial one).
- Capillary endothelium.
It is very thin (about 0.6 µm) and has a huge total area (about 70 m² in an adult).
Factors that affect diffusion (Fick's law)
The rate at which a gas diffuses across the membrane is:
- Proportional to the surface area.
- Proportional to the partial pressure difference.
- Proportional to the solubility of the gas (divided by the square root of its molecular weight: the diffusion coefficient).
- Inversely proportional to the thickness of the membrane.
| Factor | Example of disease |
|---|---|
| Reduced area | Emphysema (alveolar walls destroyed), lung removal |
| Increased thickness | Pulmonary fibrosis, pulmonary oedema, pneumonia |
| Reduced pressure gradient | High altitude (low inspired PO2) |
CO2 diffuses about 20 times faster than O2, mainly because it is far more soluble. So CO2 exchange is rarely limited in lung disease; low O2 appears first.
The pressure gradient for CO2 (45 → 40 mmHg, about 5 mmHg) is much smaller than for O2 (40 → 104), yet CO2 still exchanges easily because of its solubility.
Time for exchange
At rest, blood spends about 0.75 seconds in a pulmonary capillary. It is fully oxygenated in about the first third of this time. This gives a large safety margin.
During heavy exercise the transit time can shorten to under half this, but oxygenation is still nearly complete in healthy lungs. In thickened membranes (fibrosis), exercise may cause desaturation because there is not enough time.
Perfusion-limited and diffusion-limited gases
- Perfusion-limited: the gas equilibrates quickly, so the amount taken up depends on blood flow. Examples: N2O, and O2 in normal conditions.
- Diffusion-limited: the gas does not reach equilibrium during transit, so uptake depends on diffusion. Example: carbon monoxide (binds so tightly to haemoglobin that its plasma pressure stays low); O2 in fibrosis, strenuous exercise or high altitude.
Diffusing capacity
The diffusing capacity is the volume of gas that crosses the membrane per minute for each mmHg of pressure difference.
- For O2 at rest: about 21 mL/min/mmHg; it can rise about threefold in exercise as more capillaries open.
- For CO2: about 20 times more.
It is measured clinically using carbon monoxide (DLCO, transfer factor), because CO is diffusion-limited and its pressure in the blood is near zero, so the uptake reflects the membrane alone.
| DLCO decreased | DLCO increased |
|---|---|
| Emphysema (less area) | Polycythaemia (more haemoglobin) |
| Pulmonary fibrosis (thicker membrane) | Pulmonary haemorrhage (blood in alveoli) |
| Pulmonary embolism, anaemia | Exercise, asthma (sometimes) |
Clinical relevance
Pulmonary fibrosis
How it happens: the interstitium thickens with scar tissue.
What you see: breathlessness and desaturation on exercise, low DLCO, and a restrictive pattern on spirometry.
Pulmonary oedema
How it happens: fluid fills the interstitium and alveoli (heart failure).
What you see: greater diffusion distance and hypoxaemia; crackles on listening.
Expect: the partial pressures at each stage, why alveolar PO2 is lower than room air, why arterial PO2 is slightly lower than alveolar, Fick's law factors, why CO2 diffuses faster, the transit time safety margin, perfusion- vs diffusion-limited gases, and what changes DLCO.
Quick revision
- Alveolar PO2 104, PCO2 40; venous PO2 40, PCO2 45; arterial PO2 95.
- Water vapour (47 mmHg) lowers inspired PO2 from 160 to 149.
- Fick: area × gradient × solubility ÷ thickness.
- CO2 diffuses about 20 times faster than O2.
- Blood is oxygenated in the first third of its 0.75 s transit.
- DLCO falls in emphysema and fibrosis; rises in polycythaemia and haemorrhage.
Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).
FAQ
What is the normal alveolar PO2?
About 104 mmHg.
Why does CO2 diffuse faster than O2?
CO2 is about 20 times more soluble in the membrane and body fluids, so it diffuses much faster despite a smaller pressure gradient.
What factors affect diffusion across the respiratory membrane?
Surface area, membrane thickness, the partial pressure difference and the solubility of the gas.
Why is carbon monoxide used to measure diffusing capacity?
Its uptake is limited only by diffusion across the membrane, because it binds so tightly to haemoglobin that its blood partial pressure stays near zero.