Physiology of Thermoregulation 150 150 Endeavour Medical

Physiology of Thermoregulation

Thermoregulation is a homeostatic mechanism within the body which, under hypothalamic control and via negative feedback, strives to maintain constant internal conditions, regardless of external factors such as environmental temperature. This requires a constant balancing act between heat gain and heat loss, with failure of thermoregulation leading to medical conditions such as hypothermia or hyperthermia. Although definitions vary, current NICE guidelines suggest normothermia is between 36.5-37.5°C (1). Deviations from this normothermic state can have drastic consequences on enzymatic function, affecting many of the biochemical pathways keeping the body alive. 

This article will explore the underlying physiological pathways of thermoregulation to maintain the optimum temperature range. Additional articles will explore the spectrum of heat illness which may occur when adequate thermoregulation does not occur; please see our Endeavour Education Hub here.

Homeostasis of thermoregulation

Broadly speaking, as with all homeostatic mechanisms, the process of thermoregulation relies upon the following components, with neural pathways connecting each of the separate elements:

  • Controlled variable (temperature in this case)
  • Receptors (peripheral and central)
  • Processor and pre-determined set point (hypothalamus)
  • Effector mechanisms (behavioural and physiological responses)

Applying the above to thermoregulation, a change in external environmental temperature is detected by peripheral and central thermoreceptors. Peripheral thermoreceptors are free nerve endings of both A and C type fibres which are found in the dermis and detect a change in external body temperature, whereas central thermoreceptors are located in the preoptic nucleus of the anterior hypothalamus and detect change in internal body temperature. From here, both peripheral and central thermoreceptors transmit action potentials directly to the posterior hypothalamus. The posterior hypothalamus could be considered the processor or integrating centre for all temperature related stimuli; it also functions as the body’s ‘thermostat’, determining the set point for temperature (2). Deviations from this set point result in the initiation of effector mechanisms to either promote heat loss or heat gain, depending on the initial stimulus. Effector mechanisms comprise both behavioural changes and physiological responses, depending on the external environment. If thermoregulation is successful these behavioural and physiological responses result in effective heat gain or heat loss, which, via a negative feedback loop, either inhibits or stimulates thermoreceptors and therefore input to the hypothalamus.

Before exploring specific mechanisms of heat loss or gain, it is important to appreciate the four main ways in which heat may be exchanged from the surface of the skin (3)

  • Radiation
    • Transfer of heat via infrared waves without direct contact, occurring where a temperature difference exists. For example, this is how the sun heats the earth.
  • Evaporation
    • Transfer of heat by the evaporation of water. For example, perspiration.
  • Conduction
    • Transfer of heat by two objects which are in direct contact with each other. For example, sitting on a cold rock on a warm day.
  • Convection
    • Transfer of heat to the air surrounding the skin. For example, movement of air due to wind prevents the build up of heat near the skin surface by displacing warm air with cooler air. Wind chill increases the speed of heat loss through convection and can thus lead to greatly reduced relative temperatures.

Mechanisms for heat loss

Although the body can tolerate larger deviations in temperature decrease, relatively mild increases in internal body temperature result in massive change in enzymatic function, multiorgan failure and ultimately death (4). It is therefore of critical importance that thermoregulation maintains the delicate balance between environmental temperature and core body temperature through heat loss mechanisms. 

Mechanisms of heat loss can be divided into physiological and behavioural adaptations. Depending on the external temperature, some or all of these heat loss mechanisms may be employed.

Physiological changes

  • Vasodilation of arterioles
    • Inhibition of sympathetic centres in the posterior hypothalamus lead to vasodilation of blood vessels (2)
    • This results in an increase in blood flow to capillaries, bringing warmer blood closer to the skin
    • Heat may then be lost via radiation to the environment, ensuring a cooler temperature of venous return
  • Sweating
    • When the external environment becomes warmer than the skin, the body gains heat through both radiation and conduction. This means that evaporation is the main way in which heat loss can occur
    • Stimulation of the anterior hypothalamus by heat results in the activation of sweat glands. These sweat glands can also be stimulated by adrenaline and noradrenaline during exercise
    • There are two types of sweat glands; eccrine and apocrine. Eccrine glands are located throughout most of the body, with the majority on the soles of the feet and function by releasing water to the skin surface with sweat ducts (5). Apocrine sweat glands produce malodorous sweat and are located predominantly in the axillary and perineal regions. For further information on this process, please see this excellent article by Yousef, Ahanger and Varacallo (2)
    • Evaporative heat loss results in cooling of the skin and underlying blood (5)
    • The energy required for evaporation is called ‘the latent heat of vapourisation’; this describes the process of turning water into gas and requires a significant amount of heat energy. In this way, sweating is one of the most efficient forms of heat dissipation in humans, in environments with low humidity (6)
    • In humid environments, sweating becomes much less effective due to the relativity of water content in the air
    • Although evaporation heat loss can be an incredibly useful mechanism for heat loss, it is important to always be aware of the accompanying risk of dehydration

Behavioural changes

  • Moving into the shade
  • Removing layers of clothing
  • Stopping exertion and resting
  • Ensuring adequate hydration

Mechanisms for heat gain

After the hypothalamus has received impulses from cold peripheral thermoreceptors and central thermoreceptors, it sets into motion a number of heat gain mechanisms. Similarly to heat loss, these can be divided into physiological and behavioural responses.

Physiological responses

  • Vasoconstriction
    • Stimulation of the posterior hypothalamus leads to vasoconstriction of blood vessels
    • This minimises radiation heat loss by reducing blood flow to peripheral tissues including the skin
  • Skeletal muscle contraction (also known as shivering)
    • Increases the metabolic rate, leading to heat production by the combustion of metabolic substrates (7)
  • Piloerection (also known as goosebumps)
    • Arrector pili muscles at the base of hairs in the skin contract causing hairs to straighten and trap a layer of air around the body, reducing heat loss by convection
  • Non-shivering thermogenesis (3)
    • An increase in metabolic heat production which is not associated with muscle activity
    • This is predominantly associated with an increase of metabolism of brown fat which is found in neonates. For further information on brown fat metabolism, please see Luginbuehl & Bissonnette (2009) (8) here

Behavioural changes

  • Moving around more 
  • Adding layers of clothing
  • Curling up into a small shape to minimise exposed surface area
  • Standing near to a heat source

Application to expedition medicine and global health

A clear understanding of the process of thermoregulation and conditions that may arise when this homeostatic mechanism fails are crucial in the arsenal of an expedition medic. Heat illness occurs throughout all environments and may occur when least expected, for example hypothermia in the desert at night. Consideration must also be given to other causes of impaired thermoregulation which may not be due to environmental factors, for example medications (eg. neuroleptic malignant syndrome), traumatic brain injuries, spinal cord injuries, and alcohol to name a few. It is also important for the medic to remember to also look after themself in extreme temperatures – please see our article on hypothermia which discusses this concept further here.

Are you interested in learning more about thermoregulation?

If so, why not check out our Altitude Medicine in Practice: Alpine Ski Touring Expedition course? Whilst you’re there, why don’t you take a look at our other courses too?

Useful resources

Hypothermia 150 150 Endeavour Medical



Cold injury is a serious danger at high altitude, particularly in winter seasons but with appropriate training, can be quickly recognised and managed or prevented with adequate preparation. Pathologically, cold injury can be divided into accidental hypothermia and localised non-freezing injuries or frostbite; we will focus on accidental hypothermia which refers to an involuntary drop in core body temperature below 35°C, a potentially fatal condition. Accidental is used to distinguish it from induced or therapeutic hypothermia (1).



Pathophysiology of hypothermia

Thermoregulation is a homeostatic mechanism within the body, under hypothalamic control, that strives to maintain constant internal conditions, regardless of external factors such as environmental temperature. Peripheral temperature receptors send signals to the hypothalamus which relays signals via the sympathetic nervous system to the brain stem to initiate responses such as shivering (involuntary thermogenesis), and peripherally to pilo-erector muscles, peripheral vasculature and sweat glands. In cold environments, the body uses negative feedback to attempt to prevent further heat loss in the form of peripheral vasoconstriction and redistribution of blood centrally, and shivering to generate further heat production.2 In mild environments, core body temperature can be maintained by behavioural responses i.e. wearing more layers, finding shelter and exercising (voluntary non-shivering thermogenesis).

What are causes of hypothermia

Accidental hypothermia develops when one or more of the following principles occur: 

  • Decreased heat production: e.g. hypoglycaemia, dehydration, exhaustion, age, hypothyroidism, lack of adaptation
  • Increased heat loss: e.g. immersion/exposure to cold, alcohol, burns, heatstroke 
  • Impaired thermoregulation: e.g. trauma, drug & alcohol, TBI (traumatic brain injury), hypothyroidism, hypovolaemia, low BMI, children (high SA(surface area):vol) (2)

Further factors can be present which will increase the risk of an individual to become cold: 

  • Mental state – fear and low mood
  • Physiological condition – unwell, slim individuals, physical fitness 
  • Team morale – lack of group communication and encouraging morale
  • Nutrition – lack of energy, lack of warm food to warm person from inside
  • Kit & equipment – poor quality, not enough layers

Symptoms typically present at temperatures <35°C and develop insidiously over several hours, however the onset can be rapid if the body is immersed into cold water or snow. Thus, on expeditions we refer to two hypothermic categories:

  • Exposure hypothermia: insidious onset over several hours following exposure to cold environment. Casualty often becomes exhausted as their energy reserves are depleted and they are no longer able to shiver and re-warm themselves. 
  • Immersion hypothermia: rapid onset following sudden immersion in cold water or snow (3)

When exposed to cold, heat can be lost from the body through 5 mechanisms: 

  • Radiation: Body heat transferred to another surface nearby such as cold rocks without touching them but instead via photons independent of the temperature of the intervening air. Most heat is lost in this manner. 
  • Convection: Heat is lost when a temperature gradient exists between internal and ambient temperature. Movement of air due to wind prevents the buildup of heat near the skin surface by displacing warm air with cooler air. Wind chill increases the speed of heat loss through convection and can thus lead to greatly reduced relative temperatures. 
  • Evaporation: Heat is lost when moisture dissipates into the surrounding air, taking heat with it e.g. perspiration when exercising and carrying a pack or wet skin or clothing.
  • Conduction: Body heat is lost to rocks and cold ground through direct physical touch
  • Respiration: Heat is lost when respiring, respiration rate increases when walking up at high altitude, thus increasing rate of heat loss

When mobility and conscious level are compromised, the core body temperature could drop at a significant rate. This depends on clothing, physiological factors, such as blood glucose and fatigue, and environmental factors, such as the temperature gradient between body and surrounding environment, wind and wet conditions. Cooling rates have been shown to vary from <1°C to 9.4°C per hour when temperature was measured continuously in simulated scenarios (1-3).

Physiological effects of cold


Within the heart, the electrical system cools down faster than the myocardium, and as this occurs the heart rate slows, leading to bradycardia. As it cools, the myocardium becomes progressively more unstable leading to arrhythmias. As long as the heart is still beating the casualty can tolerate these arrhythmias, however, any sudden movements or further cooling of the myocardium will put the heart at high risk of going into ventricular fibrillation. Thus, caution must be exercised when managing and handling hypothermic casualties, particularly when trying to evacuate them. At temperatures less than 28°C the heart rate will slow considerably culminating in extreme bradycardia and subsequent asystole (4).

Peripheral vasoconstriction and thermogenesis are important mechanisms that occur almost immediately in response to heat losses. Cutaneous vasoconstriction minimises peripheral blood flow, thus reducing the flow of convective heat loss to the surrounding environment. However, this can be at detriment to a loss of dexterity which can increase further risks for the individual in managing their condition. Consequently, blood flow is redirected and the volume of blood circulating in the central system increases. As more blood flows through the renal system, the kidneys initiate cold diuresis which culminates in the excretion of warm urine and thus loss of warm blood (aka the internal hot water bottle!). Diuresis can predispose the casualty to hypovolaemia during rewarming when the peripheral circulation opens up again leading to the ‘afterdrop’ phenomenon which will be discussed later (2-4).

Trauma in a cold environment can be catastrophic as cold negatively impacts coagulation thus increasing the risk of further blood loss and subsequent hypovolaemia. At 33°C coagulation is thought to be reduced by 50%. Coagulopathy can also lead to an increase in lactic acidosis thus lowering the pH of the blood which can negatively impact cardiac function. Subsequent hypovolaemia and reduced cardiac output will increase the risk of hypothermia and further cooling. This cascade of events is often referred to using the “trauma triad of death” (5) as shown in figure 1.

hypothermia trauma - triad of death

Figure 1: Trauma triad of death

Taken from: persysmedical.com


Neurological electrical impulses slow significantly in the cold and we call this the “umbles” phenomenon: 

  • Mumbles: dysarthria, confusion, sleepiness,
  • Stumbles: ataxia, stiffness in extremities, reduced control and coordination
  • Grumbles: apathy, altered behaviour,
  • Fumbles: slow reaction time, reduced dexterity, poor coordination, dropping things

These symptoms can lead to dangers for both the casualty and the group as they become less physically and mentally capable to perform simple tasks. At temperatures less than 33°C brain electrical activity becomes abnormal. As the medic of the group, you must also remember that you are at risk of these dangers too and must protect yourself from further cooling as well as your group. 


Thermogenesis refers to heat production by voluntary behavioural (exercising) or involuntary(shivering) response mechanisms. Metabolic heat production during physical exercise can be significant as almost 70% of energy expended during muscle contraction is expelled as heat production. Shivering effectively increases heat generation by 6 times more than the basal metabolic rate. However, this also increases energy consumption at a cost of 5 times that of the resting metabolic rate (6) Thus, fatigue can limit the body’s ability to generate heat through thermogenesis. It is therefore unlikely for severe hypothermia to occur in a healthy responsive person who still has the ability to move. Although body habitus can affect this, those with an enlarged body habitus are considered to be better insulated by subcutaneous fat, whereas others are predisposed to accidental hypothermia and must rely on shivering and behavioural insulation using clothing and shelter (7). 

Furthermore, insulin has a reduced efficiency in cold environments thus it is important to maintain a high level of awareness of any individuals with a diagnosis of diabetes as they can be at an increased risk of hyperglycaemic events. There is currently little research on the effects of other hormones in cold environments (8).

In a similar vein, the cold affects the efficiency of medications as drug metabolism slows. For example, when following the ALS algorithm for a hypothermic cardiac arrest, you are advised to allow double the time between administration of adrenaline doses in comparison to a normothermic casualty.


Symptoms progress relative to the drop in core body temperature. Due to this, hypothermia can be classified in stages based upon physiological response and subsequent presenting symptoms:

Core TemperaturePhysiologyPresentation
Pre-hypothermia (>35°C)ShiveringConsciously cold
Peripheral vasoconstriction
Mild Hypothermia (33-34°C)Cold diuresisAtaxia
Progressive bradycardiaWorsening coordination
Reduced cerebral metabolism Reduced mental state
Shallow breathingDysarthria
Moderate hypothermia (30-32°C)PolkiothermicParadoxical undressing
Unable to shiverReduced consciousness
Oxygen consumption decreasesPossible deterioration to coma
Severe hypothermia (28°C)Acid-base disturbance
Reduced cerebral flow ~30%
20°CHR 20% of normal

The polikilothermic line occurs between 30-32°C and refers to the point at which the casualty is no longer able to rewarm themselves e.g. unable to initiate further shivering, and thus will need to be managed with active rewarming (1,3, 9).

The Swiss model (figure 2) is considered the internationally accepted staging criteria for hypothermia and its use has been advocated to estimate actual body temperature due to the symptoms the casualty is displaying. This then impacts on patient treatment and management without the need for a working thermometer.  However it is important to recognise that each casualty is individual and their physiological response to exposure to the cold environment may differ slightly to the arbitrary temperature readings in the model (10).

StageClinical SymptomsTypical Core Temp (°C)
Hypothermia IConscious35-32
Hypothermia IIImpaired consciousness32-28
No shivering
Hypothermia IIIUnconscious28-24
No shivering
Vital signs present
Hypothermia IVNo or minimal vital signs<24

Figure 2: The Swiss model of the staging and classification of hypothermia

Using the Swiss staging one can often assess a casualty’s degree of hypothermia base upon their presenting symptoms and physiological observations (9-12).

It is frequently difficult to get an accurate measurement of a casualty’s true core temperature in the remote setting. Core temperature is most accurately measured in the pulmonary artery however, it is difficult to access invasive thermometers in the field. Rectal, axilla and tympanic membranes can be used on expedition but it can take up to an hour for rectal temperatures to adjust for changes in core temperature and measurements from tympanic membrane and axillae are even less accurate.

In the field, we must also consider the ‘After drop’ phenomenon

During rewarming, warm blood is drawn from the central body and then travels through the cold peripheral circulation. As it does so, the blood loses heat to the surrounding peripheral tissues and returns to the heart much colder than when it left through the aorta. This then cools the core body temperature further than before rewarming began and is thus termed “afterdrop.” As rewarming is already underway, casualties may begin to feel warmer at this time as their peripheries are perfused and subsequently start to remove layers which can lead to a further drop in the core body temperature. To this extent, after drop can lead to sudden clinical deterioration and subsequent death (1).

Hypothermia : how to manage the cold casualty

Management of a hypothermic casualty in the field revolves around the prevention of further heat loss and initiation of active rewarming. The extent to which you can initiate rewarming will be dependent on the kit that is available to you. Firstly, you must ensure that as the rescuer or medic, you must protect yourself from further cooling. Cooling causes ataxia and loss of fine motor control which you can’t afford to lose when caring for a hypothermic team member. Mental capacity, especially short term memory, decreases so we would advise taking an aide memoire with you on expedition and encouraging another team member to scribe so that there is a comprehensive record of information to handover to any emergency services should you require casualty evacuation. One must also consider the impact of the cold environment on your medical kit – many medications are prone to freezing , stuffing these inside your underwear can keep them from freezing! Or is there an alternative product you could take? (Questions to ask before you leave as frozen meds are heavy and useless!) 

There are several methods of rewarming but they all boil down to 3 principles; passive external rewarming,  active external rewarming and active internal rewarming (11-12). Treatment will be dependent on the degree of hypothermia that the casualty is experiencing. However, the initial management steps will remain the same for all casualties. Firstly, remove any wet clothing and replace this with dry clothing and insulation as soon as possible to prevent further deterioration.

A hypothermic ‘burrito’ wrap can be used for any degree of hypothermia to provide external insulation and prevent further heat loss through convection, conduction, radiation and evaporation. A hypothermic wrap has several layers; firstly, as the most external layer, a tarp is used to provide external protection from the environmental elements. A roll mat then provides insulation between the casualty and the wet or cold ground thus reducing heat loss via conduction. An aluminium foil blanket provides a layer of insulation by reflecting heat back towards the person inside the wrap and acting as a layer to avoid the casualty getting wet due to evaporation. Finally a sleeping bag is used to provide the innermost layers of insulation within which the casualty lies wearing dry clothes and any insulated jackets or layers available to them. A hat is used to cover the casualties head to prevent further heat loss as a large proportion of heat can be lost from the head due to its surface area. The layers of the wrap can be prepared in advance and rolled up together then strapped on the back of someone’s pack or even stuffed into the boat as a backrest on a kayak expedition – anywhere where it will be easily accessible! A demonstration of a hypothermic wrap is shown in the pictures below.

hypothermia during our expedition medicine summer course

Figure 3: demonstration of a hypothermic wrap from a session on hypothermia during our Expedicine Medicine and Leadership Summer course

Mild hypothermia can be treated with passive external rewarming. Insulation is placed on the casualty to minimise further heat loss and retain any heat produced in shivering thermogenesis. It is recommended to aim to warm them by 0.5 to 2°C per hour. Equipment such as bivvi bag and storm shelter can be used to protect the casualty, and the rest of the team from the surrounding environment. Warm sweet drinks can further improve rewarming in conscious mild hypothermic casualties and can help to replace energy lost through shivering. 

Moderate hypothermia will require passive and active external rewarming with minimal movement of the casualty where possible to reduce the risk of cardiac arrhythmias. Heat pad or water bottles filled with hot water can be used to warm central areas of increased blood flow such as the groin, axillae, and lateral bases of the neck. If bailable, blizzard blankets can be used for a combination of passive and active external rewarming with heat bands inserted inside the blanket. Sleeping bags can also be used but consideration must be taken over the type of material. Down provides effective insulation but only when pre-warmed (ask another warmer member of the team to wear it first and exercise in e.g. push ups to warm the down before allowing the cold casualty to wear it).

Severe hypothermia may require more invasive treatment involving active internal rewarming methods ranging from humidified air to cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO). Evacuation to definitive care will be required for intraperitoneal or intra pleural fluid rewarming before consideration for ECMO. Knowledge of the nearest ECMO can be crucial information at this stage and is worth investigating prior to starting the expedition. 

As with casualties deemed to be suffering from moderate hypothermia, extra care should be taken with casualties with severe hypothermia and those with reduced consciousness to not move them if possible due to progressive cardiac instability and any jostle may precipitate a cardiac arrest. If casualty is in cardiac arrest then consider starting CPR. This is a much debated decision and is one that we would advise you to discuss with reach back or top cover if possible. Mountain Rescue England & Wales have produced really useful guidelines on when to start CPR which are a good resource to have to hand if this situation did arise (13). The ALS algorithm can be followed as with a normothermic casualty, however, the casualty may need warming before return of spontaneous circulation (ROSC) is achieved. To this extent, it is well known that “a casualty is not dead, until they are warm and dead!” These casualties should be warmed to normal body temperature at 37.5°C before a definitive decision is made regarding death. Full recovery can be possible in hypothermic cardiac arrest with ECMO if there was no preceding hypoxia or serious trauma and this has been witnessed in accidental hypothermia of temperatures as low as 14°C (14,15).

How to prevent hypothermia ?

Mountainous expeditions are becoming more accessible and popular and with that, the risk of cold injuries including hypothermia is also climbing. Thorough preparation can prevent hypothermia and thus save lives. Prior to embarking on an expedition, research the environment in which you will be situated. Use this knowledge to prepare a kit list for personal kit, group kit and medical kit. Consider the properties of items you are packing- are they going to be prone to freezing? If so, is there an alternative you could pack instead? Or could you store it in a particular way to ensure it doesn’t freeze? When preparing for an expedition where there may be an increased risk of  hypothermia such as in the mountains, consider the following: 

  • Quantity and quality of clothing and insulation including sleeping equipment
  • Quantity and properties of food -what is the estimated calorie requirement for each participant for the expedition,  will you still be able to eat your snacks in freezing conditions etc? 
  • Rewarming kit – hypothermic wrap, storm shelter, bivvi bag, stove, heat packs, spare layers etc
  • Shelter options en route
  • Group’s knowledge of cold injuries and how to manage them – consider providing everyone with an aide memoire and an educational brief 
  • Group awareness – consider a buddy system so that team members check in regularly on one another to ensure any suspicious signs are spotted early and dealt with promptly to prevent further clinical deterioration.

Take home messages

  • Hypothermia occurs when the rate of heat loss is greater than the rate of heat production 
  • Hypothermia can be prevented with thoughtful preparation of personal kit, medical kit and team awareness 
  • Have a low threshold of suspicion of slow, confused or withdrawn members of the team
  • Build a hypothermic wrap into kit and ensure it is easily accessible 
  • Always consider cardiac instability when handling hypothermic patients 
  • Nobody is dead until they are warm and dead!


  1. Procter E, Brugger H, Burtscher M. Accidental hypothermia in recreational activities in the mountains: A narrative review. Scand J Med Sci Sports. 2018;28: 2464– 2472. Available at: https://doi.org/10.1111/sms.13294
  2. J. Enrique Silva. Thermogenic Mechanisms and Their Hormonal Regulation. Physiological Reviews. 2006;86:2,435-464. Available at: https://journals.physiology.org/doi/full/10.1152/physrev.00009.2005
  3. Duong H, Patel G. Hypothermia. [Updated 2022]. Treasure Island (FL): StatPearls Publishing. 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK545239/
  4. Dietrichs E, Håheim B, Kondratiev T, Traasdahl E, et al. Effects of hypothermia and rewarming on cardiovascular autonomic control in vivo. J Appl Physiol. 2018;124:850–859.
  5. Moore E, Moore H, Kornblith L, et al. Trauma-induced coagulopathy. Nat Rev Dis Primers. 2021;7:30. Available at: https://doi.org/10.1038/s41572-021-00264-3.
  6. Haman F, Blondin DP. Shivering thermogenesis in humans: Origin, contribution and metabolic requirement. Temperature (Austin). 2017;4(3):217-226. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605160/
  7. Haman F, Souza S, Castellani J, Dupuis M, Friedl K, Sullivan-Kwantes W, Kingma B. Human vulnerability and variability in the cold: Establishing individual risks for cold weather injuries. Temperature (Austin). 2022;9(2):158-195. Available at: https://www.tandfonline.com/doi/full/10.1080/23328940.2022.2044740
  8. Cueni-Villoz N, Devigili A, Delodder F, Cianferoni S, Feihl F, Rossetti A, Eggimann P, Vincent J, Taccone F, Oddo M. Increased blood glucose variability during therapeutic hypothermia and outcome after cardiac arrest. Crit Care Med. 2011;39(10):2225-31.
  9. Grant I, Cosgrove H, Thomson L, Guly H et al. Kurafid – The British Antarctic Survey Medical Handbook. BASMU: Plymouth: British Antarctic Survey; 2005.
  10. Pasquier M, Carron P, Rodrigues A, et al. An evaluation of the Swiss staging model for hypothermia using hospital cases and case reports from the literature. Scand J Trauma Resusc Emerg Med. 2019;27:60. Available at: https://doi.org/10.1186/s13049-019-0636-0
  11. Zafren K. Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia. Emerg Med Clin North Am. 2017;35(2):261-279. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0733862717300032?via%3Dihub
  12. Dow J, Giesbrecht G, Danzl D, Brugger H, Sagalyn E, Walpoth B, et al. Wilderness Medical Society Clinical Practice Guidelines for the Out-of-Hospital Evaluation and Treatment of Accidental Hypothermia: 2019 Update. Wilderness & Environmental Medicine. 2019;30:4:S47-S69.
  13. Caple A. Casualty Care revision in Mountain  Rescue. LAMRT. 2019 (digital edition). 
  14. Štěpán J, Šulda M, Tesařík R, Zmeko D, Kutab B, Schaffelhoferová D, Foral D. Hypothermic Cardiac Arrest Managed Successfully by Changing ECMO Configurations. Journal of Cardiothoracic and Vascular Anaesthesia. 2022;36:12:4413-4419. Available at: https://www.sciencedirect.com/science/article/abs/pii/S1053077022005742
  15. J. Hilmo et al.“Nobody is dead until warm and dead”: prolonged resuscitation is warranted in arrested hypothermic victims also in remote areas—a retrospective study from northern Norway Resuscitation. 2014. Available at: https://www.sciencedirect.com/science/article/pii/S0300957214005243
snow mountain peak

Are you interested in learning more about hypothermia and other high altitude conditions?

If so, why not check out our Altitude Medicine Course ? Whilst you’re there, why don’t you take a look at our other courses too?

High Altitude Pulmonary Oedema (HAPE) 150 150 Endeavour Medical

High Altitude Pulmonary Oedema (HAPE)


Ascending to altitude can come with a range of issues, some more serious than others. In this post, we will discuss one of the two major high altitude illnesses that you may unfortunately come across; high altitude pulmonary oedema or edema (HAPE), and how you may avoid or manage it.

What is High Altitude Pulmonary Oedema ?

HAPE is a condition which can occur in climbers who have rapidly ascended in altitude and must be considered in all individuals who develop shortness of breath and a cough.


The pathophysiology of High Altitude Pulmonary Oedema (HAPE) is thought to be multifactorial. The trigger is the rapid change in atmospheric composition accompanied by change in altitude. As we ascend, atmospheric pressure decreases, and therefore the partial pressure of oxygen in the atmospheric pressure decreases. This results in effective hypoxia. 

Atmospheric hypoxia leads to a reduction in nitric oxide production in the pulmonary circulation, as the body attempts to increase flow of deoxygenated blood to the lungs by increasing the pulmonary pressure. Although this is an important physiological element of altitude acclimatisation, during rapid ascent it can cause inappropriate vasoconstriction in the pulmonary capillaries, leading to an increase in pressure and resultant leakage of fluid into the alveolar and interstitial spaces.(1,2,4)

There is also evidence that some people are more likely to suffer from High Altitude Pulmonary Oedema (HAPE) through a genetic predisposition to impairment in alveolar transepithelial sodium transport, which is aggravated at high altitudes and causes reduced alveolar water clearance.(3)

A combination of these factors leads to pulmonary hypertension and oedema.


Climbers who have rapidly ascended to greater than 2500m may experience a sudden worsening of their functional ability, accompanied by shortness of breath and a cough. As High Altitude Pulmonary Oedema (HAPE) progresses, this is followed by the other hallmark features of pulmonary oedema – a ‘wet’ sounding chest, coughing up pink, frothy sputum, cyanosis and orthopnoea. Without rapid treatment, hypoxia is inevitable and HAPE can prove fatal in 50% of cases if not treated. 

This ‘textbook’ presentation of High Altitude Pulmonary Oedema (HAPE) may not always be the case, and it can be far more insidious with mountaineers or trekkers having a shortness of breath as the predominant symptom, associated with general lethargy and mild cough. As an expedition medic, one should be wary of anyone who cannot, for example, do up their shoe lace, or is persistently lagging behind the group. 


On the mountain, recognition of the clinical signs mentioned above and basic observations are the most important and often only form of investigation.

Once in hospital, a chest x-ray to confirm and quantify the pulmonary oedema may be useful – ‘cotton wool’ infiltrates in the mid and lower zones may be seen. Arterial blood gases may show respiratory alkalosis. Cardiac ECHO may have comet tail artefacts, and ECG will likely show sinus tachycardia and signs suggestive of pulmonary hypertension (right axis deviation and bundle branch block; peaked P waves in leads II, III, and aVF; and an increase in the depth of precordial S waves).

High Altitude Pulmonary Oedema X-ray Chest

Figure 1: Chest X-ray showing cotton wool infiltrates in HAPE. (10)


Prevention is always better than cure. A slow ascent allows the body to acclimatise to changes in atmospheric oxygen. Initially, the Hypoxic Ventilatory Response (HVR) increases the rate and depth of respiration, raising alveolar ventilation by 25–30%. Hypoxic Pulmonary Vasoconstriction (HPV), which can also be a main contributor to High Altitude Pulmonary Oedema, is essential in improving blood oxygenation. Cardiac output increases due to increased rate and stroke volume. The kidneys produce more erythropoietin to stimulate production of red blood cells, and diuresis also increases to concentrate the blood – together these processes improve the oxygen transport capacity of the blood. However, all these processes take time. If acclimatisation is given time to occur, the risk of all major high altitude sicknesses are significantly reduced.

Of all the altitude illnesses, High Altitude Pulmonary Oedema is known to catch people out: those who have previously ascended to altitude, or have followed a very conservative ascent profile can experience High Altitude Pulmonary Oedema later in their trip, thus catching expedition medics unaware until the HAPE is severe. 

If symptoms appear and if it is possible, Descent is the first-line treatment.

If immediate descent is not possible, the Wilderness Medical Society (WMS) recommend giving oxygen to saturations of >90% if available, or during descent if the patient is severely unwell. A portable hyperbaric/altitude chamber (PAC) can be used if oxygen is not available – this has a greater impact on patients with HACE, but guidelines have suggested the PAC can also be of benefit in HAPE. If none of these options are available, Pharmacological Management is recommended. The first line drug is Nifedipine MR 20mg TDS – a calcium channel blocker which induces pulmonary vasodilation. Tadalafil or Sildenafil can be used if Nifedipine is not available – these are Phosphodiesterase 5- inhibitors which increase availability of nitric oxide.

If climbers have previously suffered from High Altitude Pulmonary Oedema (HAPE), Pharmacological Prophylaxis may be indicated as the likelihood of recurrence is as high as 60%. Nifedipine is again the drug of choice and should be taken from the day before ascent begins, to the day of descent.

A patient’s symptoms must have completely resolved, and they should have stable oxygenation levels during exercise, before considering whether they can continue to ascend.

Differentials to consider

It is important to remember that there are other causes of illness that are not due to high altitude, and you should always consider other causes of respiratory distress such as pneumonia, asthma exacerbation, pulmonary embolism, pleural effusion and pneumothorax. Also consider alternative causes for pulmonary oedema, such as an acute exacerbation of chronic heart failure. Past medical history and adequate pre screening should have been undertaken prior to departure. 

Take home messages

  • High Altitude Pulmonary Oedema (HAPE) is pulmonary oedema which occurs as a result of physiological pulmonary vasoconstriction in response to altitude related hypoxia.
  • A slow ascent is key to prevention – above 3000m, do not increase sleeping elevation by more than 500m each day. Try to include a rest day every 3-4 days. Avoid overexertion, alcohol and sleeping pills.
  • If signs of High Altitude Pulmonary Oedema (HAPE) appear (sudden onset cough, shortness of breath or severe fatigue), do not ascend further! Descend if possible as first line treatment.
  • Nifedipine is the first line pharmacological treatment and prophylaxis.
  • Pharmacological prophylaxis is only indicated if patients have previously had HAPE.
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