High Altitude Physiology

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High Altitude Physiology - Thin Air, Big Deal

  • Environment: ↓ Barometric pressure ($P_B$) → ↓ Inspired $P O_2$ ($P_I O_2$) → Alveolar hypoxia.
  • Immediate Response: Hypoxic Ventilatory Response (HVR).

    ⭐ Primary stimulus for HVR at high altitude is hypoxemia sensed by peripheral chemoreceptors (carotid bodies).

    • Hyperventilation → Respiratory alkalosis.
    • Cerebral blood flow initially ↑, then normalizes.
  • Acclimatization (Days to Weeks):
    • Renal compensation for respiratory alkalosis (↑ $HCO_3^-$ excretion).
    • ↑ Erythropoietin → ↑ RBC mass & Hb (takes weeks).
    • ↑ 2,3-DPG → Right shift of ODC (↓ Hb-O₂ affinity, ↑ O₂ unloading).
    • ↑ Mitochondrial density & oxidative enzymes. Physiological responses to hypoxia flow chart

High Altitude Physiology - Gasping For Air

  • Primary Insult: ↓ Barometric pressure ($P_B$) → ↓ Partial pressure of inspired oxygen ($P_{I,O_2}$) → Hypobaric hypoxia.
  • Immediate Physiological Responses (Unacclimatized):
    • Hypoxia Detection: ↓ Alveolar $P_{O_2}$ ($P_{A,O_2}$) stimulates peripheral chemoreceptors (carotid/aortic bodies).
    • Ventilatory Response:
      • Hyperventilation (↑ rate & depth) to ↑ $P_{A,O_2}$.
      • Results in ↓ $P_{A,CO_2}$ → Respiratory Alkalosis (↑ blood pH).
    • Cardiovascular Changes:
      • ↑ Heart rate (tachycardia), ↑ Cardiac output.
    • Pulmonary Circulation:
      • Hypoxic Pulmonary Vasoconstriction (HPV) → ↑ Pulmonary arterial pressure.
    • Symptoms (Acute Mountain Sickness - AMS): Headache, nausea, fatigue, dizziness.

⭐ Immediate ascent leads to respiratory alkalosis due to hyperventilation; renal compensation (bicarbonate excretion) takes days, partially correcting pH.

![Physiological responses](physiological responses high altitude)

![Flowchart diagram](flowchart diagram)

High Altitude Physiology - Becoming a Sherpa

  • Long-Term Acclimatization (Weeks to Months):
    • Hematological:
      • ↑ Erythropoietin (EPO) → Polycythemia (↑ RBC, ↑ Hb) → ↑ Arterial O2 content ($CaO_2$).
      • ↑ 2,3-Diphosphoglycerate (2,3-DPG) → Right shift of ODC → Enhanced O2 unloading to tissues.
    • Cellular:
      • ↑ Muscle myoglobin, tissue capillarity, mitochondrial density & oxidative enzymes.
    • Ventilatory:
      • Sustained ↑ alveolar ventilation; blunted hypoxic ventilatory response (HVR) in natives.
      • Renal compensation: ↑ $HCO_3^-$ excretion normalizes CSF pH.
    • Cardiovascular:
      • Cardiac output & systemic BP normalize.
      • Pulmonary hypertension may persist/develop (Chronic Mountain Sickness - CMS). Skeletal muscle response to hypoxia and exercise

⭐ Erythropoietin (EPO) secretion increases within hours of ascent, stimulating polycythemia over weeks, significantly improving arterial oxygen content. Increased 2,3-DPG shifts ODC to the right.

High Altitude Physiology - When Heights Hurt

↓Barometric pressure at altitude → ↓$P_IO_2$ → Hypoxia. Failure to acclimatize leads to:

  • Acute Mountain Sickness (AMS): Typically >2500m.

    • Symptoms: Headache PLUS fatigue, dizziness, nausea/vomiting, or sleep disturbance.
    • Prevention: Gradual ascent (≤500m/day above 3000m), Acetazolamide.
    • Treatment: Halt ascent, descend if severe, O₂, Acetazolamide, Dexamethasone.
  • High Altitude Cerebral Edema (HACE):

    • Life-threatening progression of AMS.
    • Key signs: Ataxia, altered mental status, confusion, coma.
    • Treatment: IMMEDIATE descent, O₂, Dexamethasone.
  • High Altitude Pulmonary Edema (HAPE):

    • Most lethal. Non-cardiogenic edema.
    • Symptoms: Dyspnea at rest, cough (± frothy/pink sputum), ↓exercise tolerance, rales.
    • Prevention: Gradual ascent, Nifedipine, Tadalafil/Sildenafil.
    • Treatment: IMMEDIATE descent, O₂, Nifedipine, CPAP.

Acetazolamide is a carbonic anhydrase inhibitor used for prophylaxis and treatment of AMS; it induces metabolic acidosis, stimulating ventilation and improving arterial oxygenation.

Pathophysiology of AMS and HACE

High‑Yield Points - ⚡ Biggest Takeaways

  • Hypobaric hypoxia is the primary physiological stressor at high altitude.
  • Immediate acclimatization involves hyperventilation, leading to respiratory alkalosis.
  • Erythropoietin (EPO) levels ↑, stimulating polycythemia (↑ RBC mass) over weeks.
  • Intra-erythrocytic 2,3-DPG ↑, shifting the ODC to the right, enhancing O2 tissue delivery.
  • Hypoxic pulmonary vasoconstriction, if excessive, contributes to High Altitude Pulmonary Edema (HAPE).
  • Cerebral vasodilation due to hypoxia can contribute to High Altitude Cerebral Edema (HACE).
  • Renal compensation (↑ bicarbonate excretion) gradually corrects arterial pH during acclimatization.

Practice Questions: High Altitude Physiology

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Compensating mechanism involved in acclimatization to altitude is:

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Flashcards: High Altitude Physiology

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OSA, causes hypoventilation and resulting _____ hypoxia and hypercapnia

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OSA, causes hypoventilation and resulting _____ hypoxia and hypercapnia

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