Thrill-seeking Science: How Does the Body Cope With Altitude?

Human beings seek the thrills of life. We enjoy pushing our bodies to the limit, conquering challenges, exposing ourselves to potential danger. Rollercoasters? We love the adrenaline rush. Mountain climbing is one such challenge.

For those of us who have not been exposed to extreme altitudes, mountain climbing is a feat which can be conquered, but it must not be a race. As we climb higher, the air becomes thinner and the oxygen availability falls. The human body needs time to acclimatise to the reduced oxygen availability at higher altitudes, otherwise there is a risk of mountain sickness. It is impossible to predict who will succumb to mountain sickness, an individual’s fitness is irrelevant. If not quickly treated, mountain sickness can be deadly.

Oxygen is carried around the body bound to haemoglobin in red blood cells of the blood. When the partial pressure of oxygen falls, haemoglobin increases its affinity for the bound oxygen. This means that, as we climb higher up the mountain, haemoglobin in our blood will hold onto its oxygen with increasing strength, and there will be less oxygen released for use by organs. Hence the body needs to adapt to maintain adequate tissue oxygen perfusion, especially for the brain and the heart.

SHORT TERM RESPONSE

In the short-term, when we are faced with a lower oxygen availability at higher altitudes, carotid body chemoreceptors detect this sudden decrease in oxygen availability. The chemoreceptors signal to the brainstem to increase the rate of breathing. However, although an increased rate of breathing increases the overall amount of oxygen uptake in the lungs, it also drives an increased loss of carbon dioxide from the lungs. As carbon dioxide is acidic, excess loss can lead to the blood becoming more alkaline than usual, which inhibits the action of the carotid body chemoreceptors. This can lead to a temporary period of no breathing at all, which leads to another decrease in blood oxygen availability. Re-activation of carotid body chemoreceptors again leads to an increased rate of breathing and this breathing cycle is repeated. This is known as a Cheyne-Stokes breathing rhythm.

LONG TERM RESPONSE

In the long term, more permanent body adaptations include changed kidney functioning and increased numbers of red blood cells containing haemoglobin in the blood. The kidney excretes more alkaline compounds into the urine, which offsets the increased alkalisation of the blood due to carbon dioxide loss from increased rates of breathing. Kidney adaptation is the most important acclimatisation mechanism.

However, the body also needs a way to increase oxygen offloading at tissue per unit of blood. Increasing the number of red blood cells per unit of blood achieves this. Hypoxia-inducible factor 1 (HIF1) is a transcription factor which is activated in low oxygen conditions. Activated HIF1 causes an increase in red blood cell production through the transcription factor erythropoietin (EPO), which is released from the kidney. EPO causes proliferation of red blood cell precursors in the bone marrow, leading to increased red blood cell production. HIF-1 also causes an increase in blood vessel density through activation of growth factors including vascular endothelial growth factor and angiogenin.

Some athletes train at high altitude to increase their body EPO levels and hence red blood cell count. This increases blood oxygenation during exercise and hence improves their strength, endurance and performance. EPO can also be doped illegally as a performance- enhancing drug.

In 2019, the Nobel Prize for Medicine was won by William G. Kaelin, Sir Peter J. Ratcliffe and Gregg L. Semenza for discovering how cells sense and adapt to oxygen availability. Their research involved uncovering elegant details of the HIF transcription pathway- fascinating and ground-breaking work!

Diseases associated with altitude

There are two main categories of diseases associated with altitude- chronic mountain sickness and acute mountain sickness.

CHRONIC MOUNTAIN SICKNESS

Chronic mountain sickness occurs due to an excessive increase in the number of red blood cells per unit of blood- known as polycythemia. This leads to an increased blood viscosity, which increases the chance of blood clots forming inappropriately. If such blood clots (thrombi) break off and lodge in another vessel (embolism), there could be fatal consequences. For example, an embolism in a coronary artery could lead to a heart attack as it could block of the heart blood supply, and an embolism in the lungs could also be deadly. Furthermore, increased blood viscosity also increases the strain put on the heart.

Chuvash polycythemia is a genetic form of chronic mountain sickness which is endemic to the mid-Volga region of Russia. Due to a missense mutation in one of the HIF transcription factor subunits, HIF is always active and hence there is raised levels of active EPO. This leads to increased red blood cells per unit of blood and increased blood viscosity. Patients with Chuvash polycythemia may need to be bled to reduce their risk of heart failure.

ACUTE MOUNTAIN SICKNESS

Symptoms of acute mountain sickness can be experiences from around 2500m above sea level, and include fatigue, headache, drowsiness and nausea. The first line of treatment for acute mountain sickness is immediate descent to sea level and, in more serious cases, it may be necessary to give patients pressurised oxygen.

Acute mountain sickness mainly effects the brain and lungs. Blood vessels to the brain dilate with altitude, which increases the supply of oxygen to the brain. However, increased arterial blood flow can cause compression of the veins which drain blood from the brain, and lead to an accumulation of blood in the brain capillary beds. Plasma from the blood can lead out and cause an increase of pressure in the brain, which can compress structures and cause cerebral dysfunction. This is known as high altitude cerebral oedema, and can cause confusion, extreme nausea, drowsiness, fatigue and headaches. In extreme cases, compression of a vital brain structure could be deadly.

A similar phenomenon can occur in the lungs, leading to high altitude pulmonary oedema, which is the major cause of fatalities at high altitudes. A leakage of fluid in the lungs can reduce lung capacity so cause fatigue, a dry cough and a fever. In extreme cases, high altitude pulmonary oedema can also cause heart failure and respiratory failure. If a person has recently had a respiratory tract infection, inflammation in the lungs may make them more susceptible to developing pulmonary oedema at altitudes.

OTHER CHALLENGES

Low oxygen availability is not the only challenged faced by the body at altitude. With altitude, there is an approximate drop in temperature of 1 degree Celsius with every 150m ascent, plus increasing wind chill factor. There is also an increase in exposure to ultraviolet radiation due to decreased cloud coverage, which increases the change of sunburn and snow blindness. Snow blindness can be avoided by wearing snow goggles which have ultraviolet filters.

If you have found this blog fascinating and inspiring, and would like to read more about how animals cope with other challenges, including extreme temperatures, depth and speed, I would recommend reading Frances Ashcroft’s “Life at the Extremes: The Science of Survival”.