Physiological adaptations of acclimatisation

AUTHOR: DR JENNY BAKER

“The mountains are calling, and I must go.” 

John Muir

If you’re reading this, you’re probably in the sub-section of the population that is enticed by the challenge of a summit, that craves the sight of snow-capped peaks and who thrives on what others might call ‘type 2 fun’. While many of us enjoy being in the mountains, only a small part of the world’s population lives at an altitude that equips them to withstand the changes to the air inspired at altitude. The rest of us must undergo acclimatisation in order to overcome the challenges that altitude presents to the body. In this article we shall discuss the physiological adaptations which occur due to acclimatisation.

Levels of altitude are defined as below:

High 1500-3500m

Very High 3500-5500m

Extreme 5500 – 8000m

Death Zone      >8000m

• long term survival is not possible at this altitude without supplemental oxygen

The problem: 

At altitude, the percentage of oxygen within the air doesn’t change, but as barometric pressure drops the particles of oxygen within any given volume of air decrease. This reduction in the partial pressure of inhaled oxygen (PaO2) reduces alveolar gas exchange, which in turn results in hypoxaemia that progresses with decreasing barometric pressure. This is known as hypobaric hypoxia. 

Partial pressure of oxygen is also affected by temperature and proximity to the North and South poles (for an explanation of how this works, see Dr Lucy Oblensky’s post about this!).

How we adapt to the problem:

Hypobaric hypoxia triggers acclimatisation; physiological responses to altitude that compensate for the reduction in oxygen availability.

Figure 1: taken from Peacock’s ‘Oxygen at High Altitude’2

Hyperventilation and renal compensation

The acute decrease in arterial oxygen saturation that accompanies increasing altitude triggers hypoxic chemoreceptors in the carotid bodies. This causes an increase in rate and depth of ventilation to increase oxygen saturations. Above 3000m, increases in hypoxia cause an exponential rise in minute ventilation. The extent to which this occurs depends on an individual’s Hypoxic Ventilatory Response (HVR), which is genetically determined. This increase in alveolar ventilation increases respiratory CO2 excretion and results in hypocapnia and a respiratory alkalosis. Central chemoreceptors detect this alkalaemia and act to reduce ventilation. The action of central chemoreceptors restricts the effect of hypoxia induced hyperventilation. 

In the renal tubules, carbonic anhydrase is inhibited by the respiratory alkalosis, increasing bicarbonate excretion and retaining hydrogen ions. This results in an increase in arterial pH. The normalising of blood pH reduces chemoreceptor-mediated restrictions on ventilation and allows an increase in hypoxia-induced hyperventilation. 

Renal compensatory mechanisms develop over a few days, and by 2 weeks will have acted to normalise arterial pH. At this point ventilation reaches its peak with minimal constraints and oxygen saturations may reach normal levels.

Circulatory

Hypobaric hypoxia also triggers the sympathetic nervous system. The consequential tachycardia causes an increase in cardiac output, maintaining tissue oxygen delivery despite hypoxaemia. It also results in hypertension. Hyperventilation and renal bicarbonate excretion increase fluid losses and can cause hypovolaemia, which may reduce the effect of an increased cardiac output.  

Systemically, hypoxia causes vasodilation, but in pulmonary circulation it causes vasoconstriction. This is thought to reduce V/Q mismatch and is known as hypoxic pulmonary vasoconstriction (HPV). Like HVR, HPV is genetically determined and the extent to which it occurs varies between individuals. However, this is also a factor in the development of high-altitude pulmonary oedema (to understand HAPE and how to prevent it, read Dr Persia Bowater’s review).  

Cerebral

In the brain, hypoxia causes vasodilation, increasing cerebral blood flow to maintain O2 delivery. Unfortunately, this is rarely adequate and it’s well documented that hypoxaemia prevails, resulting in impaired cerebral function, especially at extreme altitudes. This vasodilation also leads to an increase in the volume of brain tissue, which is one theory as to why some people develop high altitude cerebral oedema (for more on  HACE, see our review by Dr Jenny Baker).

Haematological

A slower adaptation to hypoxia at altitude comes from renal erythropoietin release. The subsequent erythropoiesis increases haemoglobin within 2 weeks. Haemoglobin levels of 180 in females and 200+ in males is not uncommon at 5000m above sea level! This increases gas exchange and, consequently, arterial oxygen content. However, the combination of increased haemoglobin and decreased blood volume increase viscosity and risk of thrombosis. Although studies show significantly increased incidence of both venous and arterial thrombosis at altitude, most of these studies are performed in military personnel or residents, who spend extended periods of time at these altitudes. 

At higher altitudes, the same increase in altitude (and therefore decrease in PaO2) causes a large drop in oxygen saturations because of the oxygen dissociation curve. To account for this, alkalaemia shifts the curve to the left, increasing haemoglobin oxygen affinity and resulting in higher saturations at any given altitude. However, alkalaemia also causes release of 2,3-diphosphoglycerate from red blood cells. This shifts the dissociation curve to the right. These forces balance out, until extreme altitudes are reached.

Figure 2: taken from Chris Nickson’s ‘Oxygen-Haemoglobin Dissociation Curve’8

At high altitude (3000m-5000m) full renal compensation of respiratory alkalosis occurs, oxygen saturations normalise, and circulation can return to normal. At extreme altitudes (>5000m) the low availability of oxygen prevents these parameters from being maintained; alkalosis, hypoxia, tachycardia and hypertension remain. 

Furthermore, at this altitude, VO2 max decreases significantly, reducing performance capabilities and reserves. Also decreases body heat production – increased risk of hypothermia (check out Dr Lucy Longbottom’s post all about hypothermia).

Sleep at altitude 

Whilst sleeping our drive to breathe is reduced. Meanwhile, the hyperventilation triggered by hypobaric hypoxia continues to produce a hypocapnia. Without the wakeful stimulation to breathe, the level of hypocapnia can reach that below the apnoea threshold, causing a central apnoea. This allows an increase in PaCO2 stimulating a period of hyperventilation. These alternating periods of apnoea and hyperventilation are known as periodic breathing. 

This reduces with acclimatisation, and, at extreme altitudes, can be reduced by oxygen supplementation while sleeping.  

How to aid acclimatisation

The best way to aid the acclimatisation process is through optimisation of the individual’s health; careful route and ascent planning; and consideration of chemoprophylaxis.

As we have seen, the body expends a lot of energy and resources to acclimatise to higher altitudes. Those ascending to altitude must make sure they are taking on board enough nutrients as well as staying hydrated to compensate for the increased diuresis and increase in insensible fluid losses. Whilst this sounds relatively simple, it’s important to note that altitude can cause nausea, reduced appetite and fatigue which all make the task that much harder.

Interestingly, whilst underlying health and fitness are important in any activity at altitude, no link has been identified between a person’s fitness and their likelihood of developing HAI.

Route planning should aim for a slow ascent with an increase in sleeping altitude of approximately 500m per day once beyond an altitude of 3000m, with rest days every three to four days. This is where the mountaineering maxim of ‘climb high, sleep low’ comes from. These guidelines give time for the body to acclimatise to the relative increases in altitude whilst also balancing the conflicting needs of progress and recovery time in mountaineers. Unfortunately, it is sometimes not possible to follow these guidelines due to time constraints, logistics or camp options. In these circumstances, stick to the guidelines as much as possible and be mindful of when they are being exceeded. 

Finally, chemoprophylaxis is an option, particularly for those who may not know their response to high-altitude, have suffered from HACE previously or have to sustain a more gruelling ascent profile. The most well-known and well-studied option is acetazolamide (Diamox). Acetazolamide is a carbonic anhydrase inhibitor which works at the renal tubules to increase renal losses of bicarbonate through diuresis. This causes a weak metabolic acidosis which the body compensates through increased respiration.  It ultimately accelerates the hyperventilatory and renal compensatory mechanisms of acclimatisation. Other medications such as dexamethasone don’t aid acclimatisation so much as mask the effects of altitude. Other alternatives have a more equivocal or poor evidence base. 

When it goes wrong 

It’s another one of the human body’s amazing feats to accomplish everything above to allow us to scratch the itch of getting to the top! But when our adaptation techniques don’t occur adequately, we develop high altitude illnesses (HAI): acute mountain sickness, high-altitude pulmonary oedema and high-altitude cerebral oedema. The latter two can be very serious, and often occur together, complicating the presentation and management. 

Unfortunately, some individuals are more susceptible to HAI than others. Pre-expedition evaluation can be important here, to identify susceptible individuals and consider ways to minimise their risk whilst also having the means to address HAI should it occur.