Contents · 12 sections
In a nutshell. Gas exchange = ventilation + perfusion + diffusion. Diffusion follows Fick's law across the alveolar-capillary membrane (~0.5 µm): O₂ diffuses slower than CO₂ (CO₂ is 20× more soluble). Normal V/Q is ~0.8; extremes are "dead space" (V without Q) and "shunt" (Q without V). A-a gradient = PAO₂ − PaO₂ (normal < 10–15 mm Hg, increases with age); elevated in V/Q mismatch, diffusion impairment, and shunt. O₂ is transported bound to hemoglobin (98.5%) and dissolved (1.5%); the dissociation curve shifts to the right with acidosis, ↑ T, ↑ 2,3-DPG, and ↑ CO₂ (Bohr effect).
1. Stages of gas exchange
- Ventilation — movement of air between the atmosphere and alveoli.
- Diffusion — across the alveolar-capillary membrane.
- Perfusion — pulmonary blood flow.
- Gas transport by the blood.
- Tissue diffusion.
2. Partial pressures and alveolar gas equation
- Atmospheric air: O₂ 21%, N₂ 78%, CO₂ 0.04%.
- Inspired PO₂ (at sea level) = (760 − 47) × 0.21 = 150 mm Hg.
- Alveolar gas equation: PAO₂ = FiO₂ × (Patm − PH₂O) − PaCO₂/R, where R = 0.8.
- Normal PAO₂ is ~100 mm Hg breathing room air at sea level.
- Normal PaO₂ is 80–100 mm Hg (↓ with age by ~3 mm Hg/10 years).
- PaCO₂ is 35–45 mm Hg.
3. Diffusion (Fick's law)
- V = (A × D × ΔP) / T — area, diffusion coefficient, pressure gradient / thickness.
- Alveolar-capillary membrane: ~0.5 µm thick, area 50–100 m².
- CO₂ diffuses ~20 times faster than O₂ (due to higher solubility).
- At rest, a red blood cell spends 0.75 s in the capillary; equilibrium is reached in 0.25 s → large reserve.
- During exercise, transit time drops to 0.25 s — reserve is fully utilized.
- DLCO (CO) diffusion test — assesses the membrane; ↓ in emphysema, fibrosis, anemia; ↑ in polycythemia, pulmonary hemorrhage.
4. Ventilation
- Tidal volume 500 mL, frequency 12 → minute volume 6 L/min.
- Alveolar ventilation VA = (VT − VD) × f = (500 − 150) × 12 ≈ 4.2 L/min.
- Dead space: anatomical (150 mL) and physiological (+ alveolar).
- Ventilation is regulated by: central chemoreceptors (CSF pH ↔ CO₂), peripheral chemoreceptors (carotid bodies — O₂, CO₂, pH), pulmonary mechanoreceptors.
5. Perfusion
- Pulmonary blood flow ≈ cardiac output 5 L/min.
- Low pressure (systolic 25, diastolic 8, mean 15 mm Hg).
- West zones (vertical distribution):
- — Zone 1: PA > Pa > Pv — no blood flow (pathological, e.g., mechanical ventilation + shock).
- — Zone 2: Pa > PA > Pv — pulsatile blood flow.
- — Zone 3: Pa > Pv > PA — continuous blood flow (bases).
- Hypoxic pulmonary vasoconstriction (HPV) — redistributes perfusion away from poorly ventilated alveoli.
6. V/Q ratio
- Normally ~0.8 overall (alveolar ventilation 4 L / perfusion 5 L).
- Higher in apexes ↑ (less perfusion), lower at bases ↓ (more perfusion).
- V/Q = ∞ — dead space (pulmonary embolism).
- V/Q = 0 — shunt (atelectasis, consolidation).
- Causes of hypoxemia: V/Q mismatch (most common), shunt, diffusion impairment, hypoventilation, decreased PiO₂.
7. Alveolar-arterial (A-a) gradient
- A-a = PAO₂ − PaO₂.
- Normal is 5–15 mm Hg in young adults, up to 25 mm Hg in the elderly.
- Normal on 100% O₂ is < 100 mm Hg.
- Elevated in: V/Q mismatch, shunt, diffusion impairment.
- Normal (with hypoxemia): hypoventilation, low PiO₂ (high altitude).
8. O₂ transport
- CaO₂ = (1,34 × Hb × SaO₂) + (0,003 × PaO₂).
- 98.5% of O₂ is bound to hemoglobin, 1.5% is dissolved.
- Dissociation curve is sigmoid (Hb cooperativity).
- P50 — PO₂ at 50% saturation, normal 26.6 mm Hg.
- Right shift (↑ P50): acidosis, ↑ T, ↑ 2,3-DPG, ↑ PaCO₂, Bohr effect — facilitates O₂ release to tissues.
- Left shift (↓ P50): alkalosis, ↓ T, ↓ 2,3-DPG, HbF, CO poisoning, methemoglobin.
- O₂ delivery (DO₂) = CaO₂ × CO; tissue extraction ~25%.
9. CO₂ transport
- 70% — bicarbonate (CO₂ + H₂O ↔ H₂CO₃ ↔ HCO₃⁻ + H⁺; catalyzed by carbonic anhydrase).
- 23% — bound to Hb (carbaminohemoglobin).
- 7% — dissolved.
- Haldane effect: deoxygenated Hb binds CO₂ better.
- Bohr effect: CO₂ and H⁺ shift the O₂ dissociation curve to the right.
10. Hypoxemia and hypercapnia
Mechanisms of hypoxemia
| Mechanism | A-a | O₂ response | Example |
|---|---|---|---|
| Hypoventilation | Normal | Yes | Opioid overdose, acute respiratory failure |
| ↓ PiO₂ | Normal | Yes | Altitude sickness |
| V/Q mismatch | ↑ | Yes | COPD, asthma |
| Shunt | ↑↑ | None/partial | ARDS, pneumonia, atelectasis |
| Diffusion | ↑ | Yes | Interstitial fibrosis, emphysema |
Hypercapnia
- Causes: hypoventilation (alveolar), ↑ CO₂ production, ↑ dead space.
- Clinical features: headache, confusion, flapping tremor (asterixis), coma.
- Chronic hypercapnia (COPD) — renal compensation (↑ HCO₃⁻).
11. Clinical consequences
- CO poisoning: Hb-CO has 200× higher affinity; SpO₂ is falsely normal, co-oximetry is required.
- Methemoglobinemia: SpO₂ plateaus at 85%, does not respond to O₂.
- Anemia: CaO₂ is decreased with normal PaO₂/SaO₂; O₂ therapy is ineffective.
- Cyanosis is visible at > 50 g/L of deoxygenated hemoglobin (may be absent in anemia despite hypoxia).
- ARDS — classic shunt with poor response to O₂; requires PEEP and prone positioning.
12. FAQ
Why is the A-a gradient clinically important?
Helps differentiate mechanisms of hypoxemia. Normal A-a + hypoxemia → hypoventilation or low PiO₂; elevated A-a → V/Q mismatch, shunt, diffusion impairment.
How to differentiate shunt from V/Q mismatch?
100% O₂ test: in V/Q mismatch, PaO₂ increases significantly; in shunt, it remains low (< 550 mm Hg).
Why might SpO₂ be falsely normal in smokers?
COHb is indistinguishable from HbO₂ by pulse oximetry. Arterial co-oximetry is required.
What is the Bohr effect?
At ↑ CO₂, H⁺, T — the dissociation curve shifts to the right, facilitating O₂ release in tissues. The reverse process occurs in the lungs — the "Haldane effect".
Why is DLCO measured?
Assessment of diffusing capacity of the lungs. Decreased in emphysema (↓ surface area), fibrosis (↑ thickness), anemia. Helps differentiate restriction and obstruction from vascular/interstitial diseases.
See also: Pulmonary ventilation · Acid-base balance · COPD · ARDS · Physiology Catalog