OXYGEN Starved!
Feature

OXYGEN Starved!

Every year, in the first half of October, someone in Stockholm gives a few eminent people across the globe an overwhelming start to their day. This year, hypoxia researchers William G. Kaelin, Peter J. Ratcliffe and Gregg L. Semenza, were among those who received those life-changing calls. They were jointly awarded the Nobel Prize for Physiology or Medicine, for their discoveries of the molecular system by which cells sense and adapt to varying levels of oxygen availability.

Suneetha Balakrishnan

Cut back to May 2019. It’s high season at Mount Everest. This year has been the busiest since 1953, seeing a record headcount, but also documenting as many as eleven casualties. And most of these deaths have been due to hypoxia.

Mount Everest, unconquerable

Indomitable Mt. Everest, at 8848 metres, has always been the ultimate challenge for the alpinist. The extreme climate of Mt. Everest hardly sustains living things, let alone humans. July is the warmest, with an average daytime temperature of approximately −2 °F (−19 °C) at the peak; summit temperatures average −33 °F (−36 °C) and can dip to a scary −76 °F (−60 °C) in January, the coldest month. Other than low oxygen levels, sudden storms and a nosediving mercury are routine. Windspeed can go higher than 160 kmph.

But, below the mountain, there are valleys with human occupation. Tibetan-speaking people, like the Sherpas, are seen to live at altitudes of up to 4270 m. The Sherpas, who have a semi-nomadic way of living, graze their cattle at altitudes like 4880m in summer, and go down the slope for the winter.

Sherpas, logistic partners of the snowland

Sherpas, who are now the inevitable logistics partners of any mountaineering team, once never climbed the mountains at one time. Himalaya, their sacred land, is up where their gods and demons, and the fearful snowman Yeti are believed to live. But this changed in the 20th century, when British mountaineering expeditions commenced. Sherpas, who are well-adapted genetically to high altitudes, began to be in demand in what was seen as almost their natural habitat. There was no looking back for them.

Mountaineering logistics support has eventually become their foremost livelihood, especially in the light of the high degree of endurance they seem to have for the extreme cold on the Himalayan slopes. What makes the highlander Sherpas withstand what the lowlander mountaineers cannot, at high altitudes?

This biological secret was unknown, at least till recently. Thanks to a team of researchers led by scientists at the University of Cambridge who ventured a study on the metabolic differences between the Sherpas and the lowlanders. This project, Xtreme Everest, aimed to improve outcomes for people who become critically ill by understanding how human bodies respond to the extreme altitude on the world’s highest mountain.

Indian Everest climber Ameesha Chauhan rests on her bed as she dips her frost-bitten feet in a warm solution at a hospital in Kathmandu on May 27, 2019.
Indian Everest climber Ameesha Chauhan rests on her bed as she dips her frost-bitten feet in a warm solution at a hospital in Kathmandu on May 27, 2019.

Xtreme Everest, the world’s highest lab

The Everest Base Camp is at an altitude of 5300 metres, and the two teams of lowlanders and Sherpas, followed by the dedicated team of intensive care doctors, nurses and scientists from Xtreme Everest, ascended up to the location. Blood and muscle samples of the 10 lowlanders were taken at London (50 metres), at the Base Camp, and again at the Base Camp after two months of acclimatization. The Sherpas chosen, 15 of them, were those who lived in lowlands; and their baseline measurements were taken at Kathmandu (1300 metres).

The baseline measurement itself revealed how the mitochondria of the Sherpas were more efficient at using oxygen to produce ATP (Adenosine triphosphate), the energy-carrying molecule found in the cells of all living things. The Sherpas also had lower levels of fat oxidation, suggesting that they generated energy more efficiently. Their Base Camp measurements again were almost similar to that taken at Kathmandu. Which meant that, this energy efficiency was natural to them. The lowland- ers found their measurements mimicking those of the Sherpas only after they had spent time acclimatizing themselves at the Base Camp.

But what was different among the two was phosphocreatine level. After two months at high altitudes, these levels crashed for lowlanders, and shot up for the Sherpas. The latter also had very low levels of free radicals, unlike the lowlanders whose free radical levels bounced up. Research also revealed that at high altitudes, Sherpas had normal microcirculation. The same process slowed down in the others at the heights.

The biological secrets of Sherpas

Lhakpa Sherpa - a Nepalese Sherpa mountain climber posing for photo with her two daughters. Between raising two daughters and working as a dishwasher at Whole Foods Supermarket, Lhakpa Sherpa
climbed Mount Everest nine times, the most
of any woman in the world.
Lhakpa Sherpa - a Nepalese Sherpa mountain climber posing for photo with her two daughters. Between raising two daughters and working as a dishwasher at Whole Foods Supermarket, Lhakpa Sherpa climbed Mount Everest nine times, the most of any woman in the world. Photography By Bess Adler

Sherpas have evolved to become superhuman mountain climbers, extremely efficient at producing the energy to power their bodies even when oxygen is scarce. The Sherpa people are an ethnic group from Nepal who have lived in the high altitudes of the Himalayas for generations. They have long served as guides and porters, whose local expertise has been invaluable for foreigners attempting climbs in the area.

Studies have suggested differences between Sherpas and people living in non- high-altitude areas, known collectively as ‘lowlanders’, including fewer red blood cells in Sherpas at altitude, but higher levels of nitric oxide, a chemical that opens up blood vessels and keeps blood flowing.

Evidence suggests that the first humans were present on the Tibetan Plateau around 30,000 years ago, with the early permanent settlers appearing between 6,000- 9,000 years ago. This raises the possibility that they have evolved to adapt to the extreme environment. This is supported by recent DNA studies, which have found clear genetic differences between Sherpa and Tibetan populations on the zone and lowlanders on the other. Some of these differences were in their mitochondrial DNA – the genetic code that programmes mitochondria, the body’s ‘batteries’ that generate our energy.

The researchers found that the Sherpas’ mitochondria were more efficient at using oxygen to produce ATP, the energy that powers our bodies. As predicted from genetic differences, they also found lower levels of fat oxidation in the Sherpas.

Muscles have two ways to get energy– from sugars, such as glucose, or burning fat (fat oxidation). Mostly, we get our energy from the latter source; however, this is inefficient, so at times of physical stress, such as when exercising, we take our energy from sugars.The low levels of fat oxidation again suggest that the Sherpas are more efficient at generating energy.

One of the key differences, however, was in phosphocreatine levels. Phosphocreatine is an energy reserve that acts as a buffer to help muscles contract when no ATP is present. In lowlanders, after two months at high altitude, phosphocreatine levels crash, whereas in Sherpas levels increase. Besides, the Xtreme Everest team found that while levels of free radicals increase rapidly at high altitude, at least initially, levels in Sherpas are very low. Free radicals are molecules created by a lack of oxygen that can be potentially damaging to cells and tissue.

Hypoxia research

The observations explained why different people suffering from hypoxia demonstrated different reactions in emergency situations. The Sherpas, with several generations of acclimatization at high altitude, are able to survive low levels of oxygen. Understanding why this is so would lead to a better understanding of why people in ICUs sometimes die, sometimes survive to a low quality of life and sometimes recover well. The differences detected between participants were attributed to their individual physiology rather than variation in the magnitude or duration of exposure to low levels of oxygen at high altitude.

But it was the blood sample of the Sherpas taken near the summit that was the scoop. The Xtreme Everest team had already noted how the Sherpas were breathing easy at that height, while the others were taking 15 deep breaths per step taken. They took the blood sample after descending 400 metres. These samples remain the least oxygenated human blood ever collected in healthy humans – comparable to that observed in people suffering cardiac arrest or after an opiate overdose. Almost equal to that of a dead man.

And that’s exactly where the conversations turn to the Nobel Prize this year, awarded for research into how cells detect oxygen and react to hypoxia, and then on to the casualties on the slope of the world’s tallest peak. It was once thought that one could not climb to the summit of the Everest without oxygen support. Messner and Habeler proved in 1978 that it was possible without oxygen. Over the years, equipment improved, routes were charted with more precision, more help was available, and the oxygen cylinders became lighter. But the death rate is still about one per 10 summits. And the summit is not the end point of the journey. The deaths happen while they descend too, when exhaustion and low oxygen consumption at the summit for more than an endurable time damages the possibility of a healthy descent. And only one in twenty people who make it to the summit return home safely.

The Everest Industry

It’s only since the nineties that Everest has transformed into a veritable industry sending up inexperienced climb- ers intent on that summit claim or that selfie on the peak. Unscrupulous companies, spawned by aspirations of incompetent climbers aid these aspirants, and seasoned climbers say how most of them do not even know the basics of climbing technique or etiquette. Many do not know even how to tie their crampons or fix their oxygen cylinder. The etiquette of taking care of the fallen while on a snow trek is never their priority, because all they are intent on is the summit.

A picture that surfaced in the media captured the season’s climbers stepping over a dead body as they waited in a slow-moving and serpentine queue headed up the slope. Yet another photograph captured the massive volume of trash left behind by climbers.

There was actually a human traffic jam up there on one of the days. During the week beginning May 20, crowds of climbers became stuck in a queue to the summit, above the mountain's highest camp at 8,000 meters. Most of these aspirants are not fully aware of the risks of the climb, and are inexperienced. This renders them slow to move, thereby creating bottlenecks on the track. They grapple with the hard realities of unpredictable weather, limited oxygen supply, and the effect of high altitude on the human body, only as they come face to face with the issues. Reuters reports that the Nepal government had issued 381 permits this year and that meant approxi- mately 800 climbers if you count the support personnel with each team, and that too in a year when the climate limited the number of days of ascent. The result? Death on the slopes are on the rise.

Veteran alpinists quote a rule of thumb while ascending. You should know when to turn back. There isn’t enough oxygen out there any way. But for first timers, it’s now or never. They may never get another chance, and have paid so much, so they don’t stop and turn back while there is still a chance. Most of these people never make it.

The 11 people who have died in 2019 alone have died in just 16 days. And a total of approximately 300 out of the official 4800 climbers chasing the summit over the years from 1953 have died or disappeared without trace. Only a third of the dead have been brought down. Others, frozen, have sometimes remained as markers on an ascent. Add to that the dead bodies from yesteryears exposed by melting glaciers, global warming is contributing to the corpse count. In fact, the place on the North East Ridge Route known as Rainbow Valley is hardly the happy place indicated by the moniker. Although its rendered colourful by the bright jackets and climbing gear left behind by previous mountaineers, quite possibly, some of the colour is still wrapped round the frozen corpses.

Xtreme Everest: Doctors in the 'Death Zone'

Xtreme Everest is a dedicated research team of intensive care doctors, nurses and scientists. Hypoxia, lack of oxygen reaching the body's cells and organs, is a common problem for patients who are critically ill. It is very difficult to carry out research on these patients, not least because they are so ill.

The team conduct experi- ments on both themselves and other volunteers at high altitude and in chambers, exploiting the oxygen-thin air, to provide critical insights into how intensive care patients might be helped in the future to improve their survival rates and recovery long-term.

In order to simulate the critical conditions of intensive care, the team have organised several medical research expeditions to Everest, the world's highest mountain.The team have even performed tests on themselves in the "DeathZone" above 8000 metres on Everest, a height where there is barely enough oxygen to support life. Here the team measured the lowest levels of oxygen ever reported in blood in a healthy human volunteer. In all, more than 500 volunteer research participants have joined Xtreme Everest expeditions, on Everest and other mountains in the Alps and Himalayas so that they could provide invaluable data about how they adapted to low levels of oxygen similar to those seen in critically ill patients.

In 2013 the volunteer groups joining the Xtreme Everest scientists included identical twins, children, and Sherpas, as well as some of the volunteers who took part in the 2007 expedition. Data from all of the expeditions continue to be published in a variety of journals. Xtreme Everest is a not-for-profit organisation, led by doctors and scientists from UCL, University of Southampton and Duke University in the United States, conducting this innovative, cutting edge research.

Aster Medical Journal
www.theamj.org