Response to High Altitude

Overview

• High altitude → ↓ atmospheric pressure (Patm) and ↓ alveolar PO₂
• Ventilation
  • ↓ alveolar PO₂ → ↑ respiratory rate (hyperventilation) 
    • ↓ alveolar PO₂ stimulates peripheral chemoreceptors in aortic bodies and carotid bodies to instruct medullary inspiration center to increase respiratory rate
• Arterial blood
  • ↑ ventilation rate → ↑ PaO₂ and ↓ PaCO₂ → respiratory alkalosis  
    • CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃^–
      • ↓ CO₂ shifts equilibrium left
        • ↓ H⁺→ ↑ pH
  • respiratory alkalosis → ↑ renal HCO₃^– excretion 
    • carbonic anhydrase inhibitors (e.g., acetazolamide) → ↑ renal HCO₃^– excretion and create a metabolic acidosis, which can be used to “acclimate” someone going to a higher altitude because they will naturally increase ventilation to compensate for metabolic acidosis
• Pulmonary blood flow
  • ↓ alveolar PO₂ → hypoxic vasoconstriction of pulmonary vasculature → ↑ pulmonary vasculature resistance → ↑ pulmonary arterial pressure
    • pulmonary arterial pressure increases to maintain a constant blood flow
      • right ventricle pumps against ↑ pulmonary arterial pressure (↑ afterload)
        • chronic hypoxic vasoconstriction of pulmonary vasculature causes cor pulmunale (right ventricular hypertrophy (RVH))
• Cerebral blood flow 
  • primarily controlled by PCO₂
    • ↓ PCO₂ → vasoconstriction
    • therapeutic hyperventilation (↓ PCO₂) → ↓ intracranial pressure by decreasing cerebral perfusion
      • used in cases of cerebral edema
      • effect is usually only temporary
  • PO₂ can have effects during severe hypoxic events
    • ↓ PO₂ → vasodilation and ↑ cerebral perfusion pressure
• Cellular changes
  • chronic hypoxia → ↑ erythropoietin → ↑ hemoglobin concentration and ↑ hematocrit
    • synthesis of erythropoietin in kidneys
      • erythropoietin acts on bone marrow to stimulate RBC synthesis
    • ↑ hemoglobin concentration → ↑ O₂ carrying capacity and ↑ total O₂ content
  • ↑ mitochondria
• Oxygen-hemoglobin dissocation curve
  • ↑ 2,3-BPG → shifts to right
    • ↓ hemoglobin affinity for O₂ → ↑ O₂ unloading