- 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.
- 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: Typically develops 2-4 days after ascent.
- Dyspnea at rest (most common early Sx).
- Non-productive cough → pink, frothy sputum.
- Rales/crackles on lung auscultation, tachypnea, tachycardia, low-grade fever.
- Treatment:
- IMMEDIATE DESCENT.
- Supplemental O2.
- Pharmacologic Tx to ↓ pulmonary artery pressure:
- Nifedipine (calcium channel blocker).
- Sildenafil/Tadalafil (phosphodiesterase-5 inhibitors).