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Altitude Illness

Chapter 475 | Harrison's 22e · Parts 15-16 – Genetics, Genomics & Precision Medicine · Chapter 475

Key Clinical Points

  1. Hypobaric hypoxia is the primary trigger for altitude-related illnesses.
  2. Acute mountain sickness (AMS) is common, while high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE) are life-threatening but less frequent (0.1–4%).
  3. Acclimatization involves a 'struggle response' of increased ventilation leading to respiratory alkalosis.
  4. The EPAS1 gene acts as a master switch for transcriptional responses to hypoxia, including erythropoiesis and VEGF expression.
  5. HAPE can be misdiagnosed as viral illness in highlanders due to rapid air, train, and new motorable-road access to high-altitude settlements.
  6. Oxygen saturation via pulse oximetry is generally sufficient for HAPE evaluation; arterial blood gas analysis is not required.
  7. High oxygen desaturation and low ventilatory response to hypoxia during exercise are independent predictors of severe altitude illness.
  8. Hyperbaric bags can simulate descent by increasing barometric pressure (e.g., 2 psi increase).

EPIDEMIOLOGY

• Population Exposure: Mountains cover one-fifth of the earth's surface. 140 million people live permanently at altitudes ≥2500 m. 100 million people travel to high-altitude locations each year (e.g., skiers, tourists, religious pilgrims, trekkers, miners, military personnel). • Incidence of Altitude Illness: AMS is the benign form of altitude illness. HACE and HAPE are life-threatening. AMS incidence: ~50% of trekkers who walk to altitudes >4000 m over ≥5 days develop AMS. 84% of people who fly directly to 3860 m develop AMS. HACE and HAPE incidence: Lower than AMS, estimated in the range of 0.1–4%. • Clinical Trends: HAPE is increasingly seen in Himalayan and Tibetan highlanders—and often misdiagnosed as a viral illness—as a result of recent rapid air, train, and new motorable-road access to high-altitude settlements.

PHYSIOLOGY

• Primary Response to Altitude: Ascent leads to decreased barometric pressure → decreased partial pressure of oxygen in the inspired gas in the lungs. This change leads in turn to less pressure driving oxygen diffusion from the alveoli and throughout the oxygen cascade. Initial "struggle response": Increased ventilation (mediated by the carotid bodies) → respiratory alkalosis and dehydration. Respiratory Alkalosis: Can be extreme, with an arterial blood pH of >7.7 (e.g., at the summit of Everest). Alkalosis impact: May depress the ventilatory drive during sleep, with consequent periodic breathing involving trekkers and climbers who ascended to altitudes between 4000 and 8848 m. • Acclimatization Process: Renal suppression of carbonic anhydrase and excretion of dilute alkaline urine combat alkalosis and tend to bring the pH of the blood to normal. Other adaptations: Increased sympathetic tone; increased erythropoietin levels, leading to increased hemoglobin and red blood cell mass; increased tissue capillary density and mitochondrial numbers; higher levels of 2,3-bisphosphoglycerate, enhancing oxygen utilization. • Performance & Risk: Exercise capacity: Decreases by ~1% for every 100 m gained above 1500 m. Risk factors for death: High oxygen desaturation and low ventilatory response to hypoxia during exercise are independent predictors of severe altitude illness. Diagnostic limitations: Pulse oximeter readings alone should not be used to predict AMS due to a large overlap between groups of susceptible and nonsusceptible individuals.

ETIOLOGY & PATHOPHYSIOLOGY

• Primary Trigger: Hypobaric hypoxia is the main trigger for altitude-related disease states. • AMS Pathophysiology: Raised intracranial pressure; increased sympathetic activity; relative hypoventilation; fluid retention and redistribution; impaired gas exchange. • HACE & HAPE Pathophysiology: Severe hypoxemia → greater than normal increase in cerebral blood flow. • Genetics: Hypoxia-inducible factor acts as a master switch in high-altitude adaptation, controlling transcriptional responses to hypoxia throughout the body (including erythropoiesis and pulmonary/cardiac functions). The gene EPAS1 is involved in the release of vascular in cerebral blood flow.

DIAGNOSTIC APPROACH

• HAPE Assessment: Assessment of arterial blood gases is not necessary; an oxygen saturation reading with a pulse oximeter is generally adequate. • Risk Factors for Severity: High oxygen desaturation and low ventilatory response to hypoxia during exercise → independent predictors of severe altitude illness.

MANAGEMENT & TREATMENT

• Acute mountain sickness (AMS), mild: 1. Discontinuation of ascent 2. Treatment with acetazolamide (250 mg q12h) 3. Descent • High-altitude cerebral edema (HACE): 1. Immediate descent or evacuation 2. Administration of oxygen (2–4 L/min) 3. Treatment with dexamethasone (8 mg PO/IM/IV; then 4 mg q6h) 4. Hyperbaric therapy if descent is not possible

Reference Tables

TABLE 475-1 Management of Altitude Illness CONDITION Acute mountain sickness (AMS), mild a AMS, moderate a

Harrison's 22e, p.3756

CONDITION MANAGEMENT
Acute mountain sickness
(AMS), milda		 Discontinuation of ascent
Treatment with acetazolamide (250 mg q12h)
Descentb
High-altitude cerebral
edema (HACE)		 Immediate descent or evacuation
Administration of oxygen (2–4 L/min)
Treatment with dexamethasone (8 mg PO/IM/IV;
then 4 mg q6h)
Hyperbaric therapy if descent is not possible