Questions: Gas Exchange: Alveoli and Diffusion Across the Respiratory Membrane

Question 1

A patient with pulmonary fibrosis (thickened respiratory membrane) develops hypoxemia (low blood O₂) but maintains normal blood CO₂ levels. The best explanation is:

• A. CO₂ is a smaller molecule than O₂ and therefore crosses the thickened membrane more easily
• B. CO₂'s approximately 20-fold greater solubility in tissue fluid allows it to maintain adequate diffusion across a thickened membrane even as O₂ diffusion becomes significantly impaired
• C. The patient hyperventilates in response to hypoxemia, which removes CO₂ faster and compensates for the thickened membrane
• D. CO₂ is produced at a much lower rate than O₂ is consumed, reducing its diffusion burden

Answer: (B)

The key is solubility. CO₂ is approximately 20 times more soluble in tissue fluid than O₂, making it far more diffusible per unit of partial pressure gradient. When membrane thickness increases, the diffusion rate of both gases falls (by Fick's law), but CO₂'s solubility advantage compensates — it continues to clear adequately. O₂, lacking this advantage, becomes diffusion-limited much sooner, causing hypoxemia. Hyperventilation (option C) can partially compensate for hypoxemia but is a consequence, not the primary explanation for why CO₂ is maintained.

Question 2

A pulmonary embolism blocks blood flow to a region of the lung that continues to receive ventilation. This creates:

• A. A shunt — blood that bypasses the gas exchange surface entirely
• B. Dead space — ventilated alveoli with no perfusion, so the fresh air cannot contribute to gas exchange
• C. Increased diffusion distance due to clot material lining the alveolar walls
• D. Pulmonary hypertension from redistribution of flow to the remaining lung

Answer: (B)

Dead space is ventilation without perfusion: air reaches the alveoli but no blood is present to pick up the oxygen, so that ventilatory effort is wasted. A shunt is the opposite — perfusion without ventilation (e.g., a blocked airway), where blood flows past an alveolus without gas exchange. A pulmonary embolism blocks the arterial supply to a lung region, leaving ventilation intact but eliminating perfusion — this is dead space. Both V/Q mismatches impair overall gas exchange efficiency even when the membrane itself is normal.

Question 3

Carbon dioxide has a larger partial pressure gradient across the respiratory membrane than oxygen, which is why it diffuses more rapidly despite being a larger molecule.

• T. True
• F. False

Answer: False

The partial pressure gradient for CO₂ is actually smaller: about 5 mmHg (45 mmHg in venous blood vs 40 mmHg in alveolar air), compared to about 60 mmHg for O₂ (40 mmHg in blood vs 100 mmHg in alveoli). CO₂ diffuses more rapidly not because of a larger gradient but because it is approximately 20 times more soluble in tissue fluid than O₂. Solubility — not gradient size — is the dominant factor explaining CO₂'s superior diffusibility across the respiratory membrane.

Question 4

According to Fick's law, reducing the surface area of the respiratory membrane (as occurs in emphysema) decreases the rate of gas diffusion.

• T. True
• F. False

Answer: True

Fick's law states that diffusion rate is proportional to surface area × concentration gradient / membrane thickness. Emphysema destroys alveolar walls, collapsing multiple small alveoli into larger but fewer air spaces, reducing the total surface area (normally ~70 m²) substantially. With less surface area available, the total diffusion capacity falls — less O₂ can cross per breath even if the remaining membrane is of normal thickness. This is distinct from fibrosis, which thickens the membrane; emphysema reduces surface area while leaving membrane thickness relatively normal.

Question 5

Explain why a patient with pulmonary fibrosis typically develops hypoxemia before hypercapnia, despite the fact that CO₂ has a smaller partial pressure gradient across the respiratory membrane than O₂.

Model answer: CO₂ is approximately 20 times more soluble in tissue fluid than O₂, which means its effective diffusivity is far greater even across a thickened membrane. When fibrosis increases membrane thickness (reducing diffusion rate by Fick's law for both gases), CO₂'s superior solubility compensates — it continues to diffuse adequately despite the thicker barrier and the smaller partial pressure gradient. O₂ has no such solubility advantage: its diffusion rate is limited by the thickened membrane without compensation, causing blood O₂ to fall. The result is that hypoxemia (low O₂) appears well before hypercapnia (elevated CO₂) in restrictive lung disease. Only when fibrosis or respiratory muscle failure severely limits ventilation does CO₂ accumulate.

This distinction is clinically important for diagnosis. Isolated hypoxemia with normal CO₂ in a patient with breathing difficulty suggests a diffusion or V/Q mismatch problem, not ventilatory failure. Combined hypoxemia and hypercapnia suggests ventilatory failure or very severe disease.