High Altitude Physiology

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.

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.



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).

⭐ 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.

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.