High-altitude illnesses

• Underlying Pathophysiology
  • Hypobaric hypoxia: ↓ barometric pressure at high altitude → ↓ partial pressure of inspired O2 (PiO2) → ↓ arterial O2 saturation (SaO2).
  • The primary insult is hypoxia. Illnesses result from failed or incomplete acclimatization.
• Physiologic Acclimatization
  • Immediate (minutes to hours):
    • Hyperventilation: Hypoxia stimulates peripheral chemoreceptors → ↑ respiratory rate → respiratory alkalosis.
    • ↑ Sympathetic activity: Tachycardia, ↑ cardiac output.
  • Intermediate (days):
    • ↑ 2,3-BPG: Right-shifts the O2-hemoglobin dissociation curve, facilitating O2 unloading to tissues.
    • Renal compensation: ↑ HCO3⁻ excretion to correct respiratory alkalosis.
  • Long-term (weeks to months):
    • ↑ Erythropoietin (EPO): Secreted by kidneys in response to hypoxia → ↑ hematocrit and hemoglobin concentration.
• Prophylaxis
  • Primary method: Gradual ascent (allows for acclimatization).
  • Pharmacologic: Acetazolamide. c
    • Mechanism: Carbonic anhydrase inhibitor. Causes metabolic acidosis by promoting renal HCO3⁻ excretion. This acidosis offsets respiratory alkalosis and stimulates ventilation.
    • Started 24-48 hours before ascent.

Spectrum of High-Altitude Illnesses

• Acute Mountain Sickness (AMS)
  • Pathophysiology: Mild cerebral edema. Hypoxia → cerebral vasodilation → ↑ capillary pressure → fluid leak.
  • Clinical Features: Occurs >6-12 hours after ascent.
    • Headache is the hallmark symptom.
    • PLUS ≥1 of the following: fatigue/weakness, dizziness, nausea/vomiting, anorexia, sleep disturbance.
  • Treatment:
    • Halt ascent. Descend if symptoms worsen.
    • Symptomatic Tx: NSAIDs (for headache), antiemetics.
    • Acetazolamide can be used for treatment as well as prophylaxis.
• High-Altitude Cerebral Edema (HACE)
  • Pathophysiology: Severe, life-threatening progression of AMS. Worsening vasogenic cerebral edema.
  • Clinical Features:
    • AMS symptoms PLUS neurologic dysfunction.
    • Ataxia (key finding; difficulty with heel-to-toe walk).
    • Confusion, altered mental status, drowsiness, progressing to coma.
  • Treatment:
    • IMMEDIATE DESCENT is life-saving.
    • Dexamethasone: Potent anti-inflammatory, reduces vasogenic edema.
    • Supplemental O2.
• High-Altitude Pulmonary Edema (HAPE)
  • Pathophysiology: Most lethal form. Non-cardiogenic pulmonary edema.
    • Hypoxia → uneven pulmonary vasoconstriction → ↑ pulmonary artery pressure → endothelial damage → alveolar fluid leakage.
  • Clinical Features
    • Early: dyspnea on exertion → dyspnea at rest, dry cough, ↓ exercise tolerance.
    • Late: pink/frothy sputum, cyanosis, tachypnea, tachycardia, low-grade fever.
      • Compared to pneumonia, HAPE may also present with a low-grade fever and leukocytosis. However, unlike pneumonia, HAPE symptoms typically resolve rapidly within a few hours following supplemental O2 treatment. c
    • PE: crackles/rales (often R mid-lung first), ↓ SpO₂ out of proportion to altitude.
    • May coexist with AMS (HA, N/V) or HACE (ataxia, AMS, encephalopathy).
  • Treatment:
    • IMMEDIATE DESCENT.
    • Supplemental O2.
    • Pharmacologic Tx to ↓ pulmonary artery pressure:
      • Nifedipine (calcium channel blocker).
      • Sildenafil/Tadalafil (phosphodiesterase-5 inhibitors).