What is the pathophysiology of high altitude sickness?

Pathophysiology of High Altitude Sickness

High altitude sickness occurs primarily due to hypoxia resulting from decreased barometric pressure and oxygen partial pressure at elevated altitudes, leading to inadequate compensation mechanisms that cause elevated intracranial pressure, brain swelling, and edema formation. 1, 2

Primary Pathophysiological Mechanisms

• Exposure to high altitudes (generally above 2,500 meters) causes a decrease in barometric pressure and oxygen partial pressure, resulting in hypoxia hypobárica 1
• The risk of acute mountain sickness (AMS) increases significantly at altitudes above 4,500 meters, affecting more than 50% of unacclimatized individuals 3
• When physiological responses fail to adequately compensate for high-altitude-induced hypoxemia, pathological processes begin 3

Key Physiological Responses to Altitude

• Hyperventilation occurs as an immediate response to compensate for reduced oxygen availability 3
• Hemoconcentration develops to improve oxygen-carrying capacity 3
• Sympathetic activation leads to increased heart rate and cardiac output 3
• Pulmonary vasoconstriction and elevated pulmonary arterial pressure develop, contrasting with vasodilation in peripheral and cerebral circulation 3
• Activation of the trigemino-vascular system by both mechanical factors (intracranial pressure) and chemical factors (oxidative stress, inflammation) contributes to headache development 3

Pathophysiology of Specific High Altitude Illnesses

Acute Mountain Sickness (AMS)

• Represents the milder, more common form of altitude illness 3
• Characterized by headache, nausea, dizziness, fatigue, and sleep disturbances 2
• Involves elevated intracranial pressure and brain swelling 3
• Usually self-limiting and benign when properly managed 3

High Altitude Cerebral Edema (HACE)

• Represents the severe end of the spectrum that begins with AMS 3
• Results from dysfunction or disruption of the blood-brain barrier 3
• Associated with 50% mortality when untreated 3
• Characterized by severe headache unresponsive to analgesics, ataxia, and mental deterioration 4

High Altitude Pulmonary Edema (HAPE)

• Characterized by exaggerated hypoxic pulmonary vasoconstriction 4
• Pulmonary hypertension is crucial for its development 4
• May occur with or without symptoms of AMS 4
• Presents with fatigue, dyspnea, chest tightness, and potentially hemoptysis 4

Sex-Specific Considerations in Pathophysiology

• Women may experience a more pronounced initial reduction in oxygen saturation (SpO₂) following hypoxia exposure 3
• This can potentially result in elevated pulmonary vascular resistance and pulmonary arterial pressure 3
• Higher prevalence of high-altitude pulmonary edema has been observed in female pilgrims 3
• Sex hormones influence hypoxia responses, with estrogen having complex effects on the pulmonary vasculature 3
• The "estrogen paradox" refers to the observation that pulmonary hypertension occurs more frequently in women despite estrogen's generally beneficial effects on pulmonary vasculature 3

Risk Factors for High Altitude Illness

• Rapid ascent (>300 m/day above 2,500m) without sufficient acclimatization time 2
• Individual susceptibility, which is variable but generally reproducible 5
• Women may have statistically higher risk of developing AMS 2
• Pre-existing conditions, particularly cardiovascular and pulmonary disorders 2
• Iron deficiency, which is more common in women and can impair optimal acclimatization 2

Prevention Mechanisms

• Slow ascent allowing proper acclimatization is the most effective prevention strategy 2
• Targeted training of respiratory musculature may be particularly valuable for women 1
• Prophylactic medications like acetazolamide can be effective for those with previous episodes 2
• Pre-acclimatization using hypoxic facilities may benefit those with access to such resources 2

Understanding these pathophysiological mechanisms is crucial for effective prevention, early recognition, and appropriate management of high altitude illnesses, ultimately reducing morbidity and mortality associated with these conditions.