Oxygen Cascade

Describe and explain the oxygen cascade

The oxygen cascade describes the transfer of oxygen from air to mitochondria.

• In each step of the cascade the PaO₂ falls
  It demonstrates that oxygen delivery to tissues relies on the passive transfer of gas down partial pressure gradients.
• The steps of the cascade are:
  • Dry atmospheric gas
  • Humidified tracheal gas
  • Alveolar gas
  • Arterial blood
  • Mitochondria
  • Venous blood

Remember:

• Partial pressure determines rate and extent of gas transfer
• Oxygen content is what is important for cellular function

Atmospheric Gas

Atmospheric partial pressure of oxygen is a function of barometric pressure and the FiO₂:

• $PO_2 = P_B \times FiO_2$, where:
  • $P_B$ is 760mmHg
  • $FiO_2$ is 0.21
• Therefore, $PO_2$ = 160mmHg

Humidified Tracheal Gas

• Gas is humidified during inspiration
• Gas in the proximal trachea is heated to 37°C and has 100% relative humidity
• The saturated vapour pressure of water at 37°C is 47mmHg
• Therefore:
  $PO_2 = (P_B - P_{SVP \ of \ Water}) \times FiO_2$, where:
  • $P_B$ and $FiO_2$ are as above
  • $PO_2$ is 149mmHg

Alveolar Gas

Ideal alveolar PO₂ is calculated using the alveolar gas equation:
$P_AO_2 = P_iO_2 - {P_aCO_2 \over R} + F$, where:

• $P_AO_2$ is the alveolar partial pressure of oxygen
• $P_iO_2$ is the inspired partial pressure of oxygen
• $P_aCO_2$ is the arterial partial pressure of carbon dioxide
• $R$ is the respiratory quotient, where $R = {Volume \ of \ CO_2 \ produced \over Volume \ of \ O_2 \ consumed}$
  • R is used in the alveolar gas equation to correct for the change in inspired relative to expired volume
    As generally less CO₂ is produced than O₂ consumed, expired volumes are typically less than inspired volumes
  • R is dependent on the metabolic substrates used for metabolism:
    • Pure fat ≈ 0.7
    • Pure protein ≈ 0.9
    • Pure carbohydrate ≈ 1
    • The normal value for a Western diet is quoted as 0.8
• $F$ is a correction factor, usually equal to ~2mmHg, and is given by $F = P_ACO_2.FiO_2.{1 - R \over R}$

Alveolar oxygen is therefore dependent on:

• PiO₂, which is a function of:
  • FiO₂
  • Air pressure
• Alveolar ventilation
  As $P_aO_2 \propto {1 \over \dot{V}_A}$.

Arterial Blood

The difference in partial pressure of oxygen between alveolar and arterial blood is called the A-a gradient: $A-a \ gradient = PAO_2 - PaO_2 = PiO_2 - {PaCO_2 \over R} - PaO_2$

• A normal A-a gradient is ${Age \over 4} + 4$
• Normal arterial PO₂ is 100mmHg
• It occurs due to:
  • Shunt/VQ scatter
    A small shunt is normal due to blood from the bronchial circulation and thebesian veins.
  • Diffusion abnormality

Mitochondria

• PO₂ varies with metabolic activity, but typically quoted as 5mmHg
• The Pasteur point is the partial pressure of oxygen at which oxidative phosphorylation ceases, and is ~1mmHg

Venous Blood

• PO₂ is greater than mitochondrial PO₂
  Mixed venous blood typically quoted as 40mmHg.
• Higher than mitochondria as not all arterial blood travels through capillary beds

References

1. Chambers D, Huang C, Matthews G. Basic Physiology for Anaesthetists. Cambridge University Press. 2015.
2. Brandis K. The Physiology Viva: Questions & Answers. 2003.