On the up

Climbers have to hurdle more than just sheer rock faces before reaching the summit--their bodies have to overcome lower oxygen concentrations too. Peter Hall and Colin Selby explains the body's response to a high altitude

Many of us will have experienced that moment of inspiration on reaching a long strived for mountain summit. The crisp thin air adds a lot to the special atmosphere as you gaze at a stunning view. The obstacles have been overcome, but at altitude it is not just climbing that provides the challenge. Your body itself must cope with lower oxygen concentrations. It can in fact do so with amazing fortitude due to complex systems of physiological adaptation.

This first recorded description of the adverse effects of high altitude on humans dates back to 30 bc, when Tsee Hsn Shoo described the journey along the Silk Road in Karakorm.

Today, despite advances in the field of high altitude medicine, there is much morbidity and death due to high altitude. The primary cause of these problems is a shortage of oxygen available, or hypoxia. An increase in altitude changes the atmospheric environment around you; the higher you go the less oxygen there is. This reduced partial pressure of oxygen is due to a fall in overall barometric pressure in a logarithmic relationship to altitude (figure 1).

At 5500 m the barometric pressure and therefore partial pressure of oxygen is half that at sea level. The partial pressure of oxygen at a constant altitude also varies slightly with temperature, time of day, season, and other environmental changes. But these factors pose problems of their own to a mountaineer, such as dehydration, cold injuries, sunburn, and snow blindness.

The main life threatening effects of hypoxia are summarised by specific syndromes--acute mountain sickness, pulmonary and cerebral oedema, and, over a longer term, chronic mountain sickness. Sudden exposure to the oxygen levels on the summit of Mount Everest would lead to rapid loss of consciousness and death in only a few minutes.

But mountaineers are able to ascend to the summit of Mount Everest at 8000 m over a number of weeks with only minor symptoms of illness. This remarkable ability of the human body to adapt to hypoxia is termed "acclimatisation." The initial acclimatisation protects the body against altitude illness and over a number of weeks, longer acclimatisation improves a mountaineers exercise tolerance and sleep. The lower partial pressure of oxygen is compensated for by reduced metabolic tissue demand for oxygen and adjustment of the oxygen transport system.

The physiological process of acclimatisation can be broken down into four levels--ventilatory, circulatory, haemopoietic, and metabolic.

Ventilatory response
After a few hours at altitude, a degree of hyperventilation is apparent. This will increase during the week after. Ventilation is controlled at low altitude by the body's carbon dioxide. The sensor is a paired region beneath the surface of the fourth ventricle in the medulla. The sensitivity of the response to carbon dioxide change is increased by low partial pressure of oxygen. This sensitivity is increased between 15 hours and 8 days at altitude and then reaches a plateau. It seems that there is an increase in tidal volume while the respiratory rate stays constant.

Physiologically, initial hyperventilation starts after a fall in the arterial partial pressure of oxygen. This is triggered by stimulus of the peripheral arterial chemoceptors--specifically the carotid and aortic bodies. The increase in ventilation follows an exponential increase with decreasing oxygen tension after an initial lag.

This response is known as the hypoxic ventilatory response (HVR). It starts when the arterial oxygen tension falls below 7.3 kPa, which occurs when the partial pressure of oxygen in the air is at about 13.6 kPa (the equivalent of an altitude of about 4000 m).

There is much variation between different individuals and their hypoxic ventilatory response. This seems to be largely genetic, but external factors have an influence. Depression of the hypoxic ventilatory response is caused by alcohol, soporifics, and sleep. It is stimulated by caffeine and cocoa (by increasing the general metabolic rate), progesterone (so the menstrual cycle may have influence), and acetazolamide. This is relevant, as a low hypoxic ventilatory response may increase susceptibility to altitude related illness.

Metabolic response
Activation of the hypoxic ventilatory response leads to serious further effects in the physiological response to hypoxia. Hyperventilation leads not only to increased alveolar and, therefore, cerebral oxygen concentrations, but also increases carbon dioxide clearance leading to hypocapnia. The consequent low concentration of hydrogen ions in the cerebrospinal fluid results in an inhibitory effect on ventilation via the chemoreceptors within the medulla. This is a valuable control mechanism of oxygenation and respiratory effort at sea level, but is unhelpful at altitude as it prevents further increase in ventilation.

The alkalosis is systemic, and, therefore, systemic control measures act. After an initial response of the buffer systems of the body, the kidneys try to excrete bicarbonate to restore normal pH. Removal of the alkalosis allows further ventilatory stimulation. A balance is reached after 4-7days. A further gain in altitude accentuates the whole process, resulting in a further loss of plasma bicarbonate and increased ventilation. This will substantially deplete total body bicarbonate levels. As water is excreted with bicarbonate, this also facilitates dehydration, which is a recognised problem of altitude.

The circulatory response
Circulatory efficiency is increased by three mechanisms:

1. An immediate increase in cardiac output.
2. Increased tissue capillarity.
3. Increased red cell 2,3-diphosphoglycerate (DPG) concentration.

Release of catecholamine with hypoxia is an instigating factor in circulatory changes, increasing blood pressure, heart rate, and cardiac output. Tissue changes include alteration of capillary perfusion, diffusion distance, and driving pressure of oxygen from capillaries to cells. The diffusing pressure from the venous end of capillaries to mitochondria is about 30 mm Hg. At high altitude this is more like 10-15 mm Hg. Factors appear to operate at the level of tissue diffusion to complete the process of acclimatisation. Increased capillary density diminishes the distance over which oxygen has to diffuse in the tissues. An increased amount of myoglobin in the cells constitutes a reservoir of oxygen and aids its passage to mitochondria.

Central to understanding the mechanisms that deal with hypoxia is the oxygen dissociation curve. Its position shifts right or left depending on pH, the ratio of DPG to haemoglobin (Hb), or the partial pressure of carbon dioxide. At moderate altitude, initial left shift caused by respiratory alkalosis (hyperventilation causing low concentrations of carbon dioxide) is compensated for by increasing DPG concentrations. DPG is increased by hypoxia at altitude due to preferential DPG binding to deoxygenated haemoglobin producing low DPG concentrations which stimulates its synthesis. In addition, haemopoietic stimulation increases "young" DPG rich cells.

Increased DPG shifts the oxygen dissociation curve to the right, counteracting the opposite effect of alkalosis and low carbon dioxide concentrations. [DPG]/[Hb] ratio shifts from 0.80 at sea level to 1.36 at 6450 m.

The right shift of the oxygen dissociation curve increases the ease of oxygen unloading at the tissue level. Because haemoglobin is loading on the wide "shoulder" region of the oxygen dissociation curve, only a small degree of desaturation of the arterial blood is seen.

figure 1

A rightward shift in the oxygen dissociation curve gives an increased arterial to venous oxygen gradient, but only below 5400 m. This leads to maladaptation above 5400 m, as a rightward shift provides a decrease in arterial to venous oxygen gradient. Therefore alkalosis is good at high altitude as it keeps the oxygen dissociation curve to the left as opposed to the normal right shift below 5400 m. A problem then occurs because long term alkalosis is not compatible with body function, so the decreased alkalosis with acclimatisation is necessary.

There is also a marked change in pulmonary circulation on ascent to altitude. An increase in pulmonary vascular resistance occurs as a result of hypoxic pulmonary vasoconstriction. Resulting pulmonary hypertension is greatly augmented by exercise, as seen in mountaineers. This is a large problem in subjects susceptible to high altitude pulmonary oedema.

Exhaustive activity at altitude produces lower lactate concentrations in the blood and muscle than exercise at sea level. We would expect this to be higher at altitude due to limited oxygen uptake and increased reliance on anaerobic energy production. Studies in the 1980s showed remarkably lower concentrations of peak blood lactate values during exhaustive exercise at high altitude. This may be related to decreased muscle glycolytic enzyme activities, reduced buffering capacity, or the reduced power output that occurs in an all out effort at altitude rather than at sea level.

The haemopoietic response
Hypoxia stimulates the spleen and liver to produce larger quantities of haemoglobin. This takes place on secretion of erythropoietin, which stimulates production of erythrocytes by the bone marrow. Increased erythrocyte numbers are detectable after 4-5 days. The concentration increases over months spent at altitude. The result is increased oxygen carrying capacity of the blood but with the disadvantage of increased blood viscosity, which is amplified by effects of dehydration. Eventually erythrocytes are replaced by new ones with more favourable oxygen transport characteristics.

SWISS TOURIST OFFICE

High altitude illness
Together these adaptive responses allow the human body to endure the low oxygen environment at altitude. The limits of our abilities continue to be tested by climbers who show new feats of endurance in the highest peaks of the world. But when those limits are reached the consequences can be severe.

Acute mountain sickness describes the collection of symptoms that develop when we fail to acclimatise sufficiently. In severe cases, the potentially fatal conditions of high altitude pulmonary or cerebral oedema develop. This is still a poorly understood area of medicine in which there has been a recent surge of interest. More and more of us are taking to the remote wilderness of high altitude, whether to test ourselves, or simply to enjoy some stunning scenery. As a result high altitude medicine is becoming an important and relevant field of medicine.

       

           

Responses published this month Articles Responses EDUCATION On the up       Peter Hall and Colin Selby (July 2004) Matiram Pun (July 27, 2004) Read this response EDUCATION On the up       Peter Hall and Colin Selby (July 2004) Laxmi Vilas Ghimire (July 28, 2004) Read this response EDUCATION On the up       Peter Hall and Colin Selby (July 2004) Matiram Pun (July 27, 2004)       III Year student of Medicine [MBBS] Institute of Medicine ,Nepal mati@iom.edu.np Thanks to Peter Hall and Colin Selby for their explanation about the Altitude illness .Definitely Mountains have been great attractions for the people around the world and as you have mentioned more and more medics are also interested recently. This country Nepal where I belong, has its economy dependent on the tourists who come to trek or climb the mountain. Recently we celebrated the 50th year of ascent on top of the mount Everest by Edmund Hilary and Tenzing Norgey .It is definitely more than fifty year of human being having been exposed to such hypoxic condition and bodily response. The physiological response has been more of enigma to the researchers. More than that recent trends have shown towards the prevention and cure mountain sickness . Had Peter Hall and Colin Selby discussed about the prevention part , this article could be complete and useful for the readers from mountain countries like me. The myth about mountain sickness and different substances used locally should also be highlighted .The acute mountain sickness , High Altitude Cerebral Oedema and High Altitude Pulmonary Oedema ,of course , are common problems but we should not forget Monge’s Disease as well EDUCATION On the up       Peter Hall and Colin Selby (July 2004) Laxmi Vilas GhimireMatiram Pun (July 28, 2004)       fourth year medical student TUTH, Kathmanduvilas_laxmi@iom.edu.np Dear Hall and friends, It was very interesting to go through your article on high altitude physiology and sickness. Living in the mountainous country Nepal we have been seeing the people with this common problem and hearing tales about this illness. Every year we encounter many trekkers and pilgrims who suffer from it and die from it. my question is: 1. As the human physiolgy changes while going up, would the human physiology change when one climbs down too? can any illness occur if one climbs down at higher speed ? thank you, laxmi