Can you teach me the oxygen cascade?

The Oxygen Cascade

The oxygen cascade describes the stepwise decline in oxygen partial pressure (PO2) as oxygen moves from atmospheric air through the respiratory system into the blood and ultimately to the mitochondria where it is consumed for cellular energy production. 1, 2

The Sequential Steps of Oxygen Decline

Step 1: Atmospheric Air to Alveolar Gas

• Atmospheric PO2 at sea level: ~150 mmHg (21 kPa) 3
• Alveolar PO2: Drops to approximately 100-120 mmHg due to:
  • Humidification of inspired air in the airways 1
  • Mixing with residual gas containing CO2 from the previous breath 1
  • Continuous oxygen extraction by pulmonary capillary blood 2

Step 2: Alveolar Gas to Arterial Blood

• Pulmonary capillary end PO2: Rises to ~16 kPa (120 mmHg) as venous blood (PO2 ~6 kPa or 45 mmHg) passes through well-ventilated alveoli 1
• Arterial blood PO2: Falls to ~13 kPa (100 mmHg or 90-110 mmHg in young adults) due to:
  • V/Q mismatch—not all alveolar-capillary units are perfectly matched for ventilation and perfusion 1
  • Physiological shunt from poorly ventilated lung regions 1
  • The non-linear oxygen-hemoglobin dissociation curve prevents full compensation by well-oxygenated blood mixing with deoxygenated blood 1

Step 3: Arterial Blood to Tissue Capillaries

• Capillary PO2: Oxygen tension decreases as hemoglobin releases O2 to tissues 2
• Venous blood PO2: Returns to ~6 kPa (45 mmHg) in mixed venous blood 1
• This step is determined by:
  • Cardiac output (Q) 1
  • Arterial oxygen content (CaO2) 1
  • Tissue oxygen consumption (VO2) 2

Step 4: Capillary to Mitochondria

• Interstitial and intracellular PO2: Oxygen diffuses across multiple barriers:
  • Red cell membrane 4
  • Plasma and endothelial surface layer 4
  • Endothelial cell 4
  • Interstitial space (typically <50 µm distance) 4
  • Myocyte sarcolemma and cytoplasm 4
  • Mitochondrial outer and inner membranes 4
• Mitochondrial PO2: Falls to very low levels (single-digit mmHg) where oxygen reacts with cytochrome c oxidase 4

Key Physiological Principles

Oxygen Content vs. Partial Pressure

• Oxygen content (CaO2) is determined by: 1
  • Hemoglobin concentration
  • Oxygen saturation (normally 95-98% at sea level) 1
  • A negligible amount dissolved in plasma 1
• Oxygen delivery (DO2) = CaO2 × Cardiac Output 1

The Oxygen-Hemoglobin Dissociation Curve

• The relationship between PaO2 and oxygen saturation is non-linear 1
• At normal saturation (97%), increasing PO2 with supplemental oxygen only marginally increases oxygen content (maximum 100% saturation) 1
• Below 90% saturation, small decreases in PO2 cause large drops in oxygen content 1

Compensatory Mechanisms Along the Cascade

Ventilatory Response:

• Peripheral chemoreceptors in the carotid body sense falling PaO2 (not oxygen content) 1
• Increased ventilation raises alveolar PO2, particularly benefiting poorly ventilated lung units 1

Hypoxic Pulmonary Vasoconstriction:

• Unique to the lungs—pulmonary arterioles constrict when sensing low alveolar PO2 (~8 kPa or 60 mmHg threshold) 1
• Diverts blood flow to well-ventilated areas, optimizing V/Q matching 1
• Contrast: All other organs (brain, heart, kidneys) vasodilate in response to hypoxia to increase blood flow 1, 5

Cardiac Response:

• Heart increases output within seconds to boost oxygen delivery when oxygen levels fall 1

Renal Response:

• Kidneys produce erythropoietin over days to weeks, stimulating red blood cell production 1, 5

Clinical Implications

Target Oxygen Saturations

• Most acutely ill patients: Target SpO2 94-98% to mirror normal physiological range with safety margin above the critical 90% threshold 1
• Patients at risk of hypercapnic respiratory failure (COPD, obesity hypoventilation, neuromuscular disease): Target SpO2 88-92% 1, 6

Critical Pitfall: Rebound Hypoxemia

• Never abruptly discontinue supplemental oxygen—PO2 can fall below pre-treatment levels, potentially causing death 6
• Oxygen must be weaned gradually with continuous saturation monitoring 6

Limitations of Oxygen Therapy

• Supplemental oxygen primarily corrects hypoxemia from V/Q mismatch 1
• Less effective when the problem is: 1
  • Anemia (low oxygen-carrying capacity)
  • Carbon monoxide poisoning (blocked hemoglobin binding sites)
  • Low cardiac output
  • Impaired tissue oxygen extraction (sepsis)
• Address these factors directly rather than relying solely on oxygen therapy 1