Oxygen Cascade

Definition

Steps of the Oxygen Cascade

Step 1: Atmosphere → Humidified Inspired Air (PO₂: 159 → ~149 mmHg)

• Dry atmospheric air at sea level: PO₂ = FiO₂ × Pbar = 0.209 × 760 = 159 mmHg
• On entering the upper airway, air is warmed to 37°C and fully humidified. Water vapour pressure (PH₂O) = 47 mmHg
• Effective dry gas pressure falls to 760 - 47 = 713 mmHg
• PO₂ of humidified inspired air = 0.209 × 713 = ~149 mmHg

Step 2: Inspired Air → Alveolar Gas (PO₂: 149 → ~100 mmHg)

• This is the largest step drop in the cascade
• Alveolar PO₂ is governed by a balance between:
  • Oxygen added by alveolar ventilation
  • Oxygen removed by pulmonary capillary blood flow
• CO₂ diffuses in from pulmonary blood (PAco₂ ~40 mmHg), diluting alveolar oxygen
• Described by the Alveolar Gas Equation:

  PAO₂ = PiO₂ - (PaCO₂ / R)

  where R = respiratory quotient (~0.8)

  PAO₂ = 149 - (40/0.8) = 149 - 50 ≈ 100 mmHg

Step 3: Alveolar Gas → Pulmonary End-Capillary Blood (PO₂: 100 → ~100 mmHg in ideal lung)

• Oxygen crosses the blood-gas barrier by diffusion (barrier thickness only ~0.3 µm; area 50-100 m²)
• In an ideal lung with perfect V/Q matching, end-capillary PO₂ = alveolar PO₂ (~100 mmHg)
• In reality, small V/Q inequality and physiological shunt (~2%) cause a tiny drop
• Systemic arterial PO₂ = ~95-100 mmHg (A-a gradient ~5-15 mmHg in normal young adults)

Step 4: Arterial Blood → Tissues/Microvessels (PO₂: 95 → ~40 mmHg)

• Oxygen is unloaded from haemoglobin in systemic capillaries down a diffusion gradient
• Mixed venous PO₂ (PvO₂) ~40 mmHg under resting conditions
• This step is governed by: cardiac output, haemoglobin concentration, oxygen-haemoglobin affinity (influenced by pH, temperature, 2,3-DPG - the Bohr effect), and metabolic demand

Step 5: Tissue Microvessels → Mitochondria (PO₂: ~40 → <5 mmHg)

• Final step: oxygen diffuses from capillary blood into cells and then to mitochondria
• Mitochondrial PO₂ is estimated at 1-3 mmHg under normal resting conditions
• This is the minimum threshold needed for oxidative phosphorylation (cytochrome c oxidase has a very high affinity for O₂)
• Mitochondrial PO₂ varies considerably between tissues depending on metabolic rate

Summary Table

Clinical Relevance

• High altitude: Reduced barometric pressure reduces PiO₂, shifting the entire cascade downward and threatening mitochondrial O₂ supply
• Anaemia: Does not affect PO₂ but reduces oxygen content (CaO₂ = SaO₂ × Hb × 1.34), affecting tissue delivery without directly altering the cascade pressures
• V/Q mismatch, shunt, diffusion limitation, hypoventilation: All widen the alveolar-arterial (A-a) O₂ gradient, reducing arterial PO₂ and downstream tissue PO₂
• Supplemental oxygen: Raises PiO₂, boosting each step - especially effective for hypoventilation and diffusion limitation, but less effective for true shunt

Sources: Murray & Nadel's Textbook of Respiratory Medicine (Fig. 10.14, GAS EXCHANGE chapter); Harrison's Principles of Internal Medicine 22E (Altitude Illness - Physiology section); Medical Physiology (Boron & Boulpaep)