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Updated: Feb 16 2021

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 ↓ PaCO2respiratory 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
        • synthesis of erythropoietin in kidneys
          • erythropoietin acts on bone marrow to stimulate RBC synthesis
        • ↑ hemoglobin concentration → ↑ O2 carrying capacity and ↑ total O2 content
      • synthesis of erythropoietin in kidneys
        • erythropoietin acts on bone marrow to stimulate RBC synthesis
      • ↑ hemoglobin concentration → ↑ O2 carrying capacity and ↑ total O2 content
      • ↑ mitochondria
    • synthesis of erythropoietin in kidneys
      • erythropoietin acts on bone marrow to stimulate RBC synthesis
    • ↑ hemoglobin concentration → ↑ O2 carrying capacity and ↑ total O2 content
    • Oxygen-hemoglobin dissocation curve
      • ↑ 2,3-BPG → shifts to right
        • ↓ hemoglobin affinity for O2 → ↑ O2 unloading
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