Hypothermia and Frostbite

Temperature Control in Mammals

Human body temperature is 37°C but this number is really just an average temperature for a healthy individual who is not sleeping. Normal temperature varies from 35.8°C to 37.8° with activity and sleep. Body temperature is normally lowest in the early morning, before awakening; Napoleon's "4 o'clock in the morning courage" is aptly named, as mountaineers who have to make an "alpine start" are all too aware. During sustained and vigorous exercise, especially in hot, humid weather, body temperatures can easily rise to 40°C, where heat stroke becomes likely.

One of the original Fermi problems actually looked at the power required to maintain a human at 37°C. Fermi's reasoning went something like the following:

"From reading many detective novels, I know that a body will cool by about 10°C in 6 hours. If we consider the body to be a 100 kg bag of water, then this heat loss corresponds to 1.5°C/min or 1°C/40s. We know that a calorie is the amount of heat required to raise the temperature of 1 g of water by 1°C, so we have 100 kcal/40s. This gives 4180 J/40s or 104 J/s. So we can deduce that a human puts out about 100 watts of heating power."

Most heat loss occurs through the skin, with perhaps 5% occuring through the lungs, except during aerobic exercise, where there is more heat loss from the lungs. Heat is moved around the body in the blood, and the subcutaneous blood flow can be regulated over a range of about 100 times, allowing heat loss to be controlled through vasoconstriction and vasodilation. Heat loss is also facilitated by evaporation of water from the surface of the skin (sweating). Heat production comes from the work done by muscles and nerves, and from chemical reactions in the liver.

Thermoregulation is accomplished in the hypothalamus, although there are also subcutaneous thermoregulatory components that work in denervated tissue. The posterior part of the hypothalamus controls heat retention and production when the organism is placed in a cold environment and the anterior region controls heat loss when in a hot environment. These systems operate independently of each other.

Humans have a limited capacity to adapt to extreme temperatures. Those who live at very cold temperatures are able to function more readily in the cold than those who are recently exposed. Similarly, people who live in very hot regions are able to function better in the heat than others. Cold or hot adaptation seems to impair function at the opposite extreme but the mechanisms are not well understood.

Heat Loss

Heat is lost from the surface of the body by conduction, convection, evaporation, and radiation. At room temperature, most heat loss is through evaporation and radiation. Evaporative heat loss can only be controlled by controlling the humidity of the environment. Paradoxically, evaporative heat loss can increase in cold weather due to the low humidity. Air taken into the lungs must be brought to 100% humidity and there is always some residual moistening of the surface of the skin ("insensible" perspiration). Anything that leads to more rapid breathing, such as exercise or the lowering of pO₂ at altitude, will increase evaporative cooling. Radiative heat loss is controlled by wearing mirrored clothing (space blankets) or by putting radiative barriers between ourselves and cold black-bodies (space, at 3K, is the coldest that we usually see). In a cold environment, however, conductive and convective heat loss will usually dominate, unless specialized clothing is worn to prevent it.

Convection and conduction refer to the same mechanism of heat loss, the familiar transfer of kinetic energy from one medium to another that it is in contact with through molecular motion. Convection is simply conduction in which the heat lost is only partially transferred to the cold body. For example, when two bodies of different temperatures are brought in contact with each other, the hot body loses heat to the cold body at a rate that is proportional to the temperature difference at the interface. Since heat diffusion has to occur within the cold body in order to bring it to equilibrium, the rate of this process may limit heat transfer from the hot body by the development of a thermal gradient within the cold body. Convective heat loss refers to a situation in which the cold body is a fluid with an infinite resevoir at the cold temperature. The faster the fluid in contact with the hot body is replaced, the faster the rate of heat transfer, up to the limit specified by the thermal conductivity of the materials.

For a human in the cold, convective heat loss occurs when a wind is blowing. At low wind speeds, heat diffusion within the air limits cooling, but it is still faster than with no wind. The rate of cooling reaches a maximum at wind speeds between 30 to 50 km/h and then begins to fall off because the air is not in contact with the skin long enough to heat up appreciably. Paul Siple, working in Antarctica, studied the rate of freezing of water at various temperatures and wind speeds. He published the now infamous Wind Chill Chart in 1945 as a rough indicator of how wind might speed up tissue freezing. Unfortunately, we see this chart abused every night on the evening news, where the weather person intimates that the apparent temperature from the wind chill chart is an indication of how cold it should feel. This might be true for nude humans, but very few people are willing to make the comparison between -40°C with no wind and a -40°C windchill while utterly naked.


Fig. 11.1.1 Wind Chill - Apparent temperature as a function of wind velocity.

Convective heat loss in water is a more serious problem, due to the high thermal conductivity and the larger specific heat capacity of water (it takes a lot of heat to warm up water and heat loss is proportional to the temperature difference). In fact, an active person in cold water will lose heat faster than someone who moves as little as possible because the metabolic heat production cannot keep pace with convective heat loss.

Heat Production

Though there is a significant thermal output from chemical reactions in the body during normal metabolism, it is not controllable for purposeful heat production in humans. Changes in heat production can only be brought about by muscular activity, either voluntary (work or activity) or involuntary (shivering). Voluntary activity will always produce more heat than simply shivering.

In order to produce heat, the body must have metabolic substrates available for burning. Sugars and fats are the body's fuel and without a proper supply, its ability to do work, and thereby generate heat, will be limited. Although the body can metabolize its stores of fat, as well as functional components such as muscle, to generate energy, this process takes a long time and cannot be used to fight hypothermic heat loss.

Metabolic activity will increase by a factor of about 3-4 fold during conditions of significant heat loss without apparently increasing the activity of the individual. This has the effect of lowering the maximum activity that the individual can achieve to generate heat or to move to a warmer environment.

Physiological Response to Cooling

Low temperatures slow down the rates of chemical reactions due to the lower kinetic energy of the molecules. Even though the free energy of the products of a reaction is less than that of the reactants, and hence should drive the reaction forward, there is an activation energy associated with a chemical reaction that must be overcome for the reaction to proceed. When the molecules are less energetic, it takes longer for the activation energy to be reached.


Fig. 11.1.2 Energy diagram for a chemical reaction.

The rate of the reaction is given by an Arrhenius relation which is dependent on temperature and the activation energy (E_a).

(11.1.1)
Where r is the rate at temperature T, r_g is the rate at temperature T_g, and R is the gas constant.

The activation energy is not the same for all reactions, thus a few biochemical reactions will become rate-limiting as the temperature drops. This will manifest itself as the loss of certain biological functions within the organ systems. Initially, however, lowering the body temperature will simply slow down all systems somewhat equally. For example, although the blood carries less oxygen, the colder organ systems require less oxygen since they are less active.

The muscles react to a lowering of body temperature by shivering. This is an involuntary response in which alternating contraction and relaxation of skeletal muscles generates heat. There is a loss of muscle strength and coordination that accompanies hypothermia, both due to shivering and the decrease in the rate of nerve impulses and muscle response. Shivering starts off as an intermittant response and becomes more sustained and violent as the body temperature is lowered further. There is an accumulation of lactic acid and a depletion of glucose in the muscles due to excessive shivering. Shivering will cease when the body temperature falls below 32°C. At this point, only external heat can revive the hypothermic victim even if all heat loss is prevented.

Brain function is impaired by low temperatures as well. With mild cooling, the person becomes apathetic and disagreeable, and slow to make decisions. As the core temperature becomes lower, confusion and disorientation become pronounced, and decision making ability takes a turn toward the bizarre, however the hypothermic victim is unable to notice this behavior in himself. If there are several people similarly affected, the behavior can be seen in the others--poor coordination (stumbling, drunkard-like behavior), foolish actions, etc.--but the person can not make the connection that they too are suffering and the apathy that accompanies hypothermia doesn't stir the victim to take corrective measures. Speech becomes slurred, but again, it seems anomolous to the victim, and uncorrelated with danger (unlike alcohol induced stupidity, which is expected). Hypothermia gives an intensely painful sensation throughout the body (again, unlike the alcohol produced symptoms) that intensifies as core temperature drops and is probably most responsible for the apathy that accompanies the condition. Personal experience tells me that there is no respite from this pain up to the point where uncontrolled shivering ceases. This is contrary to the prevailing wisdom imparted to every Canadian schoolchild with their yearly analysis of London's short story, "To Build a Fire", where the protagonist falls toward the ecstasy of sleep. In the real world, consciousness is probably lost somewhere in the depths of agony.

The increase in blood viscosity as well as the decrease in the strength and rate of pumping of the heart leads to a marked decline in the volume of blood that is pumped throughout the body as temperature declines. Often, hypothermia is a result of dehydration, in which the blood viscosity is increased due to water loss and this accelerates the loss of heat from the body since the blood cannot supply oxygen to the muscles or transport heat efficiently. Initial lowering of the core temperature causes the constriction of peripheral blood vessels, shunting blood to the core. This increase in blood pressure lowers production of antidiuretic hormone causing the kidneys to remove water from the blood. The viscosity of blood can increase by almost a factor of two during hypothermia.

Hypothermia

Injury

The injury associated with hypothermia is often death, hence its classification as a serious condition despite the fact that almost all the changes associated with a lowering of body temperature are completely reversible. It seems that the cause of death is usually from the heart beating slower and slower until it eventually doesn't pump enough blood to itself to allow the energy to be produced for another pump.

Factors that hasten hypothermia in otherwise healthy people are:

• Immersion - Immersion in cold water rapidly lowers the core temperature. In shipping accidents, this is a serious concern. Temporary immersion in cold water during cold weather can also lead to hypothermia. Dry clothing and shelter should be sought as quickly as possible.
• Injury - An injured person can lose heat faster due to shock and blood loss.
• Immobilization - Heat production is severely curtailed if activity cannot be maintained.
• Dehydration - An increase in blood viscosity leads to a decrease in the transport of oxygen and glucose to the muscles.

Survival and Treatment

Hypothermia is diagnosed by measuring the core body temperature. If it is below 32°C, then it is classified as profound hypothermia which is considered a medical emergency requiring immediate intensive care. Since most people don't have thermometers with them in situations where hypothermia develops, profound hypothermia is more easily diagnosed by noticing unexpected stupidity, slurred speech, and a lack of coordination. Hypothermia caused by immersion in cold water is sometimes mistaken for death, as the symptoms are identical. Due to the decreased requirement for oxygen in the hypothermic state, a pronouncement of death should await rewarming to 37°C.

Treatment of mild hypothermia consists of adding heat to the victim and reducing heat loss. Wet clothing must be removed and replaced with dry clothing or further heat loss will occur. Warm liquids can be consumed to make the victim feel better but will have little effect on the core temperature. Interestingly, tea can make a substantial difference in the rewarming process due to its content of theophylline, a structural analog of caffeine. Theophylline acts on the cyclic AMP/phosphodiesterase signalling pathway to make more metabolic substrates available to the cells. The asthma medication aminophylline, two theophyllines joined by an amide bond, is even more effective. These drugs are better used as a prophylactic, though, since hypothermia usually diminishes the body's ability to generate heat. Alcoholic beverages, though they may make the victim feel better, will not assist recovery. Another person in a sleeping bag will be sufficient for treatment, but it is slow and can be either pleasant or unpleasant depending on circumstances. If it is certain that the victim is not suffering from profound hypothermia, then the quickest way to treat the condition is with a hot bath.

Mortality for profound hypothermia varies between 50 to 80%, even with treatment in a hospital environment but there is no reason for any previously healthy person to die from hypothermia provided they can be transported to a hospital; the current mortality is principally due to innapropriate treatment.

The treatment for profound hypothermia consists of preventing (or reversing) ventricular fibrillation while slowly rewarming the victim. Some of the events that are known to trigger ventricular fibrillation in a profoundly hypothermic patient are:

1. Intubation
2. Mouth-to-mouth resuscitation
3. Alkalosis (sodium bicarb in the blood)
4. Precordial thump
5. Insertion of a large bore needle into central veins
6. Physical exertion
7. Rough handling
8. Catheterization
9. Rapid external warming
10. Adrenaline

No warming of a profoundly hypothermic victim should be attempted outside of a hospital. The victim should be transported as gently as possible and the core temperature should be maintained at the level upon discovery (further heat loss should be prevented). The victim should be prevented from any physical activity that will lead to exertion (i.e. the victim should not be allowed to move under his own power).

Some of the complications associated with hypothermia are the following, although they are more indicative of pre-existing health problems that are likely to correlate with hypothermia (e.g. homeless people get cold because they don't have a home).

1. Pneumonia
2. Acute Pancreatitis
3. Thrombosis (myocardial infarcts and stroke)
4. Pulmonary Edema
5. Acute Renal Failure
6. Alkalosis
7. Hemolysis
8. Depressed bone marrow function
9. Decreased blood clotting
10. Low serum phosphorous
11. Seizures
12. Hematuria (blood in urine)
13. Myoglobinuria
14. Simian deformity of the hand
15. Temporary adrenal insufficiency
16. Ulcers

Medical Uses

Hypothermia is used extensively to lower metabolic function during organ transplantation. For example, when performing a heart transplant, cutting the blood supply during the transfer of the pumping function from the heart to an artificial pump is inevitable. At normal body temperature, brain injury would necessarily result. By cooling the body before the surgery, the time that the body can go without fresh blood is increased. This allows the surgeon to perform these procedures without any apparent brain damage. The chest cavity is usually packed with ice during these procedures.

A Cryobiologist in the Cold: A personal encounter with hypothermia.

Frostbite

Injury

Although it is common for toes, fingers, and even feet to go numb in cold weather, and stay numb for hours, it is possible for freezing of the tissue to occur under these conditions without any further warning. Intracellular freezing does not usually occur in frostbite, although skin cells can freeze intracellularly if they contact a cold metal. Direct cellular injury, as in cryosurgery, is due to the osmotic effects and dehydration that accompanies freezing.

The primary mechanism of injury from frostbite is due to the vascular injury that accompanies tissue freezing. After thawing, the blood vessels become highly permeable and both solutes and water begin leaking into the interstitial compartment (edema). The remaining blood becomes viscous and the damaged endothelial cells release factors that promote clotting. Once clots begin to form, occluding the capillary beds completely, then the blood supply to parts of the tissue is stopped.

Unlike cryosurgery, which often must be performed next to critical organs or tissues, frostbite injury almost always occurs in tissues that are not necessary for life. Following the injury, swelling and discoloration of the skin will occur (much of the area turns purple from sludging of the blood), accompanied by the formation of large blisters. Necrosis will begin to show within a few days of the injury.

Fortunately, severe frostbite also kills the nerve cells at the site of injury, so there is no acute pain associated with it (mild frostbite can be quite painful, though). There is a low-level chronic pain that can last for years afterward.

Frostbite is easily diagnosed as the frozen tissue has the hardness of wood, is pale and almost waxy in appearance, and is cold.

Treatment

Severe hypothermia, which sometimes accompanies frostbite, must be treated immediately, if present. Otherwise, the treatment for frostbite is to warm the extremity in a 40°C water bath (hand hot). Thawing should be as rapid as possible, but control over the temperature is paramount. An overly warm, dry heat, such as that produced by a campfire, will cause much additional injury and should not be used. It was due to the devastation of fireside warming during the Napoleonic campaigns that led to the ridiculous technique of treating frostbite by rubbing the exposed areas with snow. Frostbitten regions should never be massaged at all, especially not with snow!

Frequently frostbite occurs in situations where the victim must travel a great distance to receive help. Since there may be excessive swelling upon thawing, it may not be possible for the victim to put his footwear back on after thawing. In such cases, the extremity should not be thawed as re-freezing can significantly increase the severity of the injury (compared to walking on the frozen tissue). This must be weighed against the possibility of increasing the amount of frozen tissue. Since the victim is unlikely to have thermocouples inside his extremities, a choice must be made. If thawing is decided upon, it should be as fast as possible without risking the drying/burning injury that can accompany a fireside warming (contact with the skin of a warm person may be the only practical option).

After thawing, the skin over the injured area will be dead and will have to be debrided or will eventually slough off. The risk of infection is severe at this point, so care should be taken to prevent any tearing of the skin or blisters until proper, aseptic care can be administered. During this lengthy rehabilitation, the line of demarcation between necrotic and live tissue may move either way significantly, thus if intravenous antibiotics are available, it is best to wait until this line stabilizes (weeks, at least) before amputations are performed. Although the necrotic tissue will fall off on its own (not quite as aesthetic as the Autumn colours in New England when the leaves turn and begin to fall off), but failure to amputate may result in gangrene, necessitating more aggressive amputations or death. The prognosis, however, is notoriously difficult in the early stages.

Treatment for frostbite is strictly palliative, at this point in time. One suggestion for active treatment, however, comes from the finding that there are prostaglandins and other clotting factors found in the blisters that appear following thawing. These factors are secreted by injured endothelial cells lining the blood vessels. Keeping a residual level of aspirin in the blood might counteract these factors and result in a better recovery. At any rate, there seems to be no indication that this would impair recovery. As always, the best treatment is avoidance.

A Cryobiologist gets even Colder: A personal encounter with frostbite.

Trenchfoot, Paddyfoot, and the Chilblains

Paddyfoot refers to a condition endemic to more recent military conflicts that were fought in locations where low-level flooding was common (such as rice paddies). It is not a cold injury but simply due to constant immersion for 48-72 hours.

The chilblains is a charmingly named condition that seems to crop up in older literature. It is a drying and reddening of the skin caused by exposure to cold, wet, and windy conditions. Lee's Priceless Recipies, published in 1899 gives a treatment: "Flexible colodion 4 drams, castor oil 4 drams, spirits of turpentine 4 drams. Use 3 times daily with camel's hair brush." Just above this entry, a cure for cancer is provided (boiled red oak bark mixed with sheep fat).