The Science of Altitude Sickness:What Happens When You Climb TooHigh Too Fast

Fig 1: Classification of high altitude illnesses¹ 

Imagine gearing up for the climb of a lifetime on Mount Everest (8,848 m) or even Kilimanjaro (5,895 m),² and just as you make it to base camp, you begin to experience severe headaches, dizziness, and nausea within hours of your arrival. This is the experience of millions of people traveling to high altitudes annually for tourism, sport, and work.³ 

What happens at high altitude 

To understand what happens at high altitude, we must go back to the beginning and define altitude. High altitude is defined as an elevation of 1,500 meters (5,000 feet) and above. At this elevation, declining barometric pressure begins to have noticeable physiologic effects on the body. 

The human body undergoes a complex series of integrated responses across multiple organ systems in response to changes in altitude.⁴ As altitude increases, atmospheric pressure decreases, so the partial pressure of oxygen¹ available in the

atmosphere decreases in proportion to the change in altitude. Therefore, in response to low oxygen (hypoxia) and reduced atmospheric pressure (hypobaric pressure), the respiratory, cardiovascular, and renal systems undergo changes collectively known as acclimatization, aimed at enhancing oxygen delivery¹to cells despite the lower ambient pressure. 

Physiological changes at high altitude 

In response to hypoxia, the lungs engage the body's hypoxic ventilatory response (HVR) within minutes of arrival.³ Unlike other blood vessels, pulmonary arteries constrict in response to low oxygen, a phenomenon known as Hypoxic pulmonary vasoconstriction (HPV).⁴ This increases pulmonary arterial pressure (pulmonary hypertension), redistributing blood to better-oxygenated areas of the lung. 

The carotid bodies detect low oxygen levels and signal the brain's medulla to increase the rate and depth of breathing.^3,4 This action causes respiratory alkalosis by blowing off large amounts of carbon dioxide,^3,4 a signal the body uses to adjust breathing in its absence, especially during sleep.² There is oscillation in breathing between hyperventillation and hypoventillation, and sometimes even apnoea, often causing frequent arousal and vivid dreams. 

Meanwhile, in the cardiovascular system, the heart rate and cardiac output increase to maintain tissue oxygen delivery.^1,3,4 The work of circulation is made harder by the decrease in plasma volume² as part of the diuresis response, which initially increases the concentration of red blood cells. 

In the kidneys, within minutes of ascent, the work of compensation has already begun through the loss of bicarbonate ions³to conserve hydrogen ions, counter alkalosis, and maintain the normal pH altered by hyperventilation. It is a process that starts from a few hours to days.² 

One of the normal adaptations to altitude is hypoxia-mediated urination,² which increases urination, reducing plasma volume and concentrating red blood cells to improve oxygen transport in the body. Within about two hours, the kidney senses low oxygen levels. It secretes a hormone called erythropoietin (EPO)⁴that stimulates the bone marrow to produce more red blood cells, thereby further improving oxygen-carrying capacity.³ 

Altitude sickness 

It is also known as high-altitude illness, a collective term for pulmonary and cerebral syndromes that occur in non-acclimatized individuals shortly after a rapid ascent to

high altitude.^1,3,4 The illness is a direct consequence of low oxygen levels and low barometric pressure, reducing oxygen availability in the body.¹ 

The timing of symptom onset in altitude sickness varies by syndrome.^1,2 Acute mountain sickness (AMS) is the most common form and starts within six to 12 hours in about two-thirds of susceptible individuals, with symptoms appearing within 12 hours; the rest become symptomatic in 36 hours.^2,3It is characterized by a bitemporal, throbbing headache that is worse at night or upon waking, accompanied by at least one other symptom, such as nausea, vomiting, dizziness, fatigue, or loss of appetite.^1–4 

High-altitude pulmonary edema (HAPE) is a delayed response that usually occurs two to five days after arrival at high altitude.²It is a potentially fatal condition where fluid accumulates in the lungs, causing severe breathlessness even at rest.^1,3,4It begins with a cough associated with breathlessness at rest, shortness of breath on lying flat, and a bluish tint to the skin, nail beds, or lips. The cough can then become productive, with pink, frothy sputum.^1,4 

High-altitude cerebral edema (HACE) is often a progression of severe AMS, though its specific timing is less fixed; it's often considered the end-stage manifestation of AMS.^1–4Its hallmark signs involve brain swelling that leads to loss of coordination and altered mental status that includes hallucinations, extreme drowsiness, stupor, and eventually coma.^1–4 

Treatment of altitude sickness 

Acute mountain sickness is generally self-limiting.^3,4If recognized early, the most appropriate management is to stop ascending for about one to three days until symptoms resolve. However, if symptoms worsen,⁴ descending about 500 -1000m is required.^1,2,4 

In cases of worsening acute mountain sickness, high-altitude pulmonary edema, or high-altitude cerebral edema, medications may be required, including acetazolamide, dexamethasone, nifedipine, and supplemental oxygen.^2,4 Oxygen can be delivered to symptomatic climbers via an oxygen mask or nasal prongs.¹In extreme cases, a portable hyperbaric chamber may be required to alleviate severe symptoms of altitude sickness.^1–4

References 

1. Cai C, Ni G, Chen L, et al. Altitude hypoxia and hypoxemia: pathogenesis and management. Signal Transduct Target Ther. 2026;11(1):27. 

doi:10.1038/s41392-025-02531-1 

2. Luks AM. Physiology in Medicine: A physiologic approach to prevention and treatment of acute high-altitude illnesses. J Appl Physiol. 2015;118(5):509-519. doi:10.1152/japplphysiol.00955.2014 

3. Taylor A. High-altitude illnesses: Physiology, risk factors, prevention, and treatment. Rambam Maimonides Med J. 2011;2(1). doi:10.5041/RMMJ.10022 

4. Paralikar S, Paralikar J. High-altitude medicine. Indian J Occup Environ Med. 2010;14(1):6. doi:10.4103/0019-5278.64608

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