Pulmonary Gas Exchange: Diffusion, Partial Pressures, and the Alveolar Gas Equation

Pulmonary Gas Exchange: Diffusion, Partial Pressures, and the Alveolar Gas Equation

Why This Matters

Every clinical decision you make as a respiratory therapist — adjusting FiO₂, setting ventilator parameters, interpreting arterial blood gases — rests on understanding how oxygen moves from room air into the bloodstream and how carbon dioxide travels in the opposite direction. Errors in this reasoning can lead to inadequate oxygenation or unnecessary interventions, both of which harm patients. Master these principles before you touch any patient.

Dalton's Law of Partial Pressures

The air we breathe is a mixture of gases. Dalton's Law states that the total pressure of a gas mixture equals the sum of the pressures each gas would exert if it occupied the space alone. Each individual pressure is called a partial pressure.

At sea level, barometric pressure (PB) is approximately 760 mmHg. Dry air is about 21% oxygen (FiO₂ = 0.21). The partial pressure of oxygen in dry air is therefore:

PO₂ = FiO₂ × PB = 0.21 × 760 = 159.6 mmHg

However, air entering the airways is immediately humidified and warmed to body temperature (37 °C). Water vapor at 37 °C exerts a pressure of 47 mmHg (PH₂O). This water vapor dilutes every other gas, so it must be subtracted before calculating partial pressures of inhaled gases:

Inspired PO₂ = FiO₂ × (PB − PH₂O) = 0.21 × (760 − 47) = 0.21 × 713 ≈ 150 mmHg

The Alveolar Gas Equation

Once humidified air reaches the alveoli, oxygen is consumed and carbon dioxide is added. The alveolar gas equation accounts for this and gives us the partial pressure of oxygen in the alveoli (PAO₂):

PAO₂ = FiO₂ × (PB − PH₂O) − PaCO₂ / RQ

• FiO₂: fraction of inspired oxygen (decimal form, e.g., 0.21 for room air)
• PB: barometric pressure (mmHg)
• PH₂O: water vapor pressure at body temperature = 47 mmHg
• PaCO₂: arterial partial pressure of carbon dioxide (a reliable approximation of alveolar CO₂)
• RQ: respiratory quotient — the ratio of CO₂ produced to O₂ consumed; assumed to be 0.8 unless otherwise stated

At sea level on room air with a normal PaCO₂ of 40 mmHg:

PAO₂ = 0.21 × (760 − 47) − 40 / 0.8 = 149.7 − 50 = 99.7 mmHg ≈ 100 mmHg

Henry's Law and Gas Solubility

Henry's Law states that the amount of a gas dissolved in a liquid is proportional to its partial pressure above that liquid (at constant temperature). This explains why oxygen dissolved in plasma is directly tied to PAO₂ — higher alveolar O₂ partial pressure drives more O₂ into the blood. It also explains why CO₂, being about 20 times more soluble than O₂ in blood, diffuses across the alveolar-capillary membrane with relative ease.

Normal Gas Values: Alveolar and Arterial

| Location | PO₂ (mmHg) | PCO₂ (mmHg) |

|---|---|---|

| Alveolar (PAO₂ / PACO₂) | ~100 | ~40 |

| Arterial (PaO₂ / PaCO₂) | 80–100 | 35–45 |

| Mixed venous | ~40 | ~45 |

Note that arterial PaO₂ is slightly lower than PAO₂. This normal difference reflects small amounts of physiologic shunting and ventilation-perfusion (V/Q) mismatch. The difference is quantified as the alveolar-arterial (A-a) oxygen gradient:

A-a gradient = PAO₂ − PaO₂

A normal A-a gradient on room air in a young adult is roughly 5–15 mmHg; it increases with age and with supplemental oxygen. An elevated A-a gradient indicates a problem with gas exchange at the lung level.

Four Causes of Hypoxemia

Hypoxemia is a below-normal PaO₂. Understanding its cause directs your intervention:

1. Hypoventilation: Reduced alveolar ventilation raises PaCO₂, which displaces O₂ in the alveolus. PAO₂ falls even though the lungs themselves are normal. A-a gradient is normal. Treatment: support ventilation.

2. V/Q mismatch: Some lung units are ventilated but poorly perfused, or perfused but poorly ventilated. Most common cause of hypoxemia in clinical practice (pneumonia, COPD, pulmonary embolism). A-a gradient is elevated. Treatment: improve V/Q matching; supplemental O₂ often helps.

3. Diffusion impairment: Thickened alveolar-capillary membrane (pulmonary fibrosis, pulmonary edema) slows gas transfer. A-a gradient is elevated. O₂ usually responds to supplemental oxygen; CO₂ is rarely a problem due to its high solubility.

4. Shunt: Blood bypasses ventilated alveoli (intracardiac shunt, consolidated lung). A-a gradient is elevated. Hypoxemia is refractory to supplemental oxygen — this is an important clinical red flag.

High altitude reduces PB, which lowers PAO₂ even with normal lung function; A-a gradient remains normal.

Safety and Scope of Practice

• Never adjust FiO₂ or ventilator settings without verifying your calculations and confirming with current blood gas data and physician orders.
• Recognize that a normal SpO₂ does not rule out hypercapnia — you must check PaCO₂ separately.
• When you identify a cause of hypoxemia, communicate findings clearly using correct terminology; the physician orders treatment, but accurate assessment is your professional responsibility.
• Errors in applying the alveolar gas equation (wrong units, wrong RQ, forgetting to subtract PH₂O) will produce incorrect PAO₂ values and could contribute to clinical misjudgment. Check your arithmetic.