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Altitude Research: A Steep Learning Curve

British mountaineer George Mallory was once asked, “Why do you want to climb Everest?”, to which he gave the immortal retort, “Because it’s there.” Since then, countless enthusiasts have followed in that same spirit of adventure by climbing to the world’s loftiest points for the challenge and exhilaration. While the equipment that climbers sport these days may make the ascent safer, the body still suffers from the same treacherous low-oxygen conditions that would have blighted Mallory. Next summer, a group of Edinburgh students will be leading an expedition to a high-altitude laboratory to study this.

Altitude illness is common in travellers who venture above 2,500 metres without allowing time to acclimatise. For most this means a mild but varied cocktail of potential symptoms, such as headache, nausea, tiredness and dizziness, known as acute mountain sickness or altitude illness. As nasty as this sounds, the dangers become more critical for those who climb higher and do so more rapidly. Two of the worst outcomes are high altitude cerebral oedema, a potentially fatal swelling of the brain, and high altitude pulmonary oedema, where the lungs accumulate fluid, making breathing increasingly difficult. The example of Peter Kinloch, the British mountaineer who died last summer after going blind on the descent from Everest, tragically illustrates the effects of cerebral oedema.

The reality is that altitude research is a poorly understood field. Low oxygen levels stimulate blood vessels to dilate, increasing blood flow, which is thought to contribute to cerebral swelling, though the mechanism is unclear. The blood-brain barrier normally tightly regulates what may enter the brain, but it can undergo alterations that lead to fluid leakage into the brain. This results in symptoms such as nausea and headaches due to increased pressure on the brain. Mediators in the bloodstream such as vascular endothelial growth factor (VEGF) may also play a role, namely in controlling the permeability or ‘leakiness’ of blood vessel walls. Excessive permeability means fluid leaks into surrounding organs, which is particularly critical in the lungs.

Another question is why some, even the most physically fit, are more sensitive than others. One recent discovery suggests that in the 2,750 years that Tibetans have inhabited the 4,000 metre Tibetan plateau, a genetic mutation that allows for greater adaptation to altitude evolved in 87% of the population. The affected gene, named Epas1, codes for a protein involved in responding to low oxygen levels, regulating the balance between aerobic and anaerobic respiration. The mutation subtly changes the protein’s function through a mechanism yet to be uncovered. This offers an explanation as to how Tibetans function efficiently without having to acclimatise through the normal mechanism of producing more haemoglobin, a protein which transports oxygen in the blood. According to Professor Nielson, who took part in the study, “It is the fastest change in the frequency of a mutation described in humans.”

Next June, an eight-strong team of University of Edinburgh medical students is undertaking an expedition to investigate the effects of altitude for themselves. This will mean organising the recruitment of 40 lowland volunteers from the local Edinburgh student population and their safe passage to a Bolivian laboratory perched at 5,000 metres, followed by two weeks of amassing data on the participants’ reactions to altitude. The study will build on existing research into changes in blood vessel walls, but whereas there is already extensive study of the lungs, experiments will delve into more widespread changes in the permeability of blood vessels. This will require blood samples to test for mediators such as VEGF, a forearm cuff to investigate changes in blood pressure and heart rate, and urine samples to examine a protein called albumin that may indicate an increase in blood vessel permeability.

Alongside the challenge of collecting reliable data in the unreliable conditions of high altitude, there are the logistical feats of transporting personnel overseas and, more dramatically, local jeep hire to a laboratory that is by necessity off the beaten track. To make ends meet, expedition members will need to fundraise in advance as a team, but they are also hoping to apply for the small number of grants available for such research.

As long as mountaineering continues to grow as a desirable leisure pursuit, there will be a need for greater insight into what drives altitude illness. It is a welcome bonus for potential student researchers that study of such a poorly understood field requires travel to the Earth’s more colourful locations.

James Barclay is a medical student intercalating in physiology

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