Applied Resp – Other Physiology

Master answer

Changes in Inspired and Alveolar PO2

PAO₂ used as surrogate for PaO₂

Alveolar PO2 can be described by the alveolar gas equation

Where

• FiO₂ is the fraction of inspired O2
  • 0.21 when breathing room air
• P_ATM is the atmospheric pressure which changes with altitude
  • 760mmHg at sea-level
  • 560mmHg in pressurized cabin of commercial aircraft (610mmHg in Boeing 787)
  • Approx. 240mmHg at the summit of Everest
• SVP_H2O is the saturated vapour pressure of water (47mmHg)
  • ↓’s with ↑ing altitude → small ↑ in PAO₂
• PaCO₂ is the arterial partial pressure of CO₂
• Respiratory exchange ratio
• P is a correction factor

High Altitudes

• With ascension in altitude, P_ATM decreases therefore, P_AO₂ will decrease
• A-VO₂ gradient is lower
• Rate of O₂ dissolving in blood ↓’s at altitude → ↓ Diffusion by Fick
  • PvO2 sits in the lower portion of the OHDC → ↓O₂ Affinity → ↑PaO2 to get same HbO2 carriage
• CaO2 rises much slower and may become diffusion limited with any exertion

Physiological Response to Altitude

Serum

• If there is no change in the diffusion of O2 PaO2 will similarly decrease proportionally
• Tissues will have a greater reliance on anaerobic metabolism, with an increase production of lactate, and decrease in pH.

Control of ventilation

• Peripheral chemoreceptors in the aortic bodies, sense changes in paO2, paCO2, [H+].
• Central chemoreceptors in the retrotrapezoidal nucleus (RTN) in the medulla sense changes in paCO2, once CO2 diffuses across the BBB and converts to H+ via carbonic anhydrase.
• Both signal to the medullary respiratory centre leading to an increase in ventilation (RR and tidal volume) via ventral group CPG
• There is an increase sensitivity of the respiratory centre to pO2 that is poorly understood
• Ventilation is more sensitive to changes in pCO2, usually maintained within 35~45mmHg.
• Response to hypoxia occurs once paO2 drops below 50~60mmHg and occurs in 3 stages

Three Phases:

1. Acute Hypoxic Response
   • ↑ altitude causes hypoxaemia
     • ↓barometric pressure → ↓PiO2 → ↓PAO2 → ↓ PaO2
   • ↓ PaO2 stimulates Peripheral Chemo Receptors (in CB and AB)
   • ↑ MV significantly
2. Hypoxic ventilatory decline (HVD)
   • ↑ MV then ↓ PaCO2 causing
   • ↓ brain ECF [H+] → ↓Central CR stimulation (in medulla) (→ response curve reset to left)
   • limits any further ↑ MV due to hypoxaemia
3. Ventilatory response to sustained hypoxia
   • Brain ECF [H+] returns to normal (3 days)
   • HCO3 rapidly equilibrates across the BBB
   • hypoxic ventilatory drive is restored
   • allows further ↑ MV to occur

↑ MV causes

• ↑venous return → ↑ CO → ↑ pulmonary Blood volume
  • May ↑/↓ V/Q matching → ↑/↓ PaO₂
  • ↓ pulmonary compliance → ↑WOB
  • ↑ risk of diffusion limitation on exercise

Other Important Physiological Changes

• Hypoxia → ↑2,3DPG → ↓ HbO₂ affinity → ↑delivery
• Hypoxia Inducible Factors in the kidneys upregulate production of EPO, increasing O₂ carriage.
• Alkalosis → ↓ammoniogesis → ↓HCO3 reabsorption → ↑ effective bicarb secretion which tends to return pH to normal
• High-Altitude Pulmonary Oedema may occur
  • Poorly understood, however throught to be due, in part, to hypoxic pulmonary vasoconstriction
  • This inhibits diffusion of O₂ across the alveolar membrane, increasing the A-a gradient

Sakurai / Gladwin 2016

Answer by Gladwin, Sakurai