Regulation Of Body Temperature And Heat –Related Illness: Heat Exhaustion And Heat Stroke

Discussion points:

• How can atropine injection precipitate heat stroke? Why was it likened to gold painting the skin? What are other common medications and behaviours which can precipitate or worsen heat disorders?
• Under the circumstances, were the cooling methods used commendable?

THERMOREGULATION IN MAN

Thermal balance

The balance between heat production (heat gain) and heat loss determines the body temperature.
In the body, heat is produced by physical activity (skeletal muscle contraction), thermic effect of food (to assimilate an amount of protein sufficient to provide 100 kcal, the body has to use 30 kcal of energy; for carbohydrate and fat, 6 and 5 kcal respectively), and all the vital processes that contribute to the basal metabolic rate (e.g. activity of cardiac and respiratory muscles, active transport).
Heat is lost to orgained from the environment by 3 physical means:
Radiation (transfer of heat by infrared electromagnetic radiation from one object to another at a different temperature with which it is not in contact);
Conduction – heat exchange between objects at different temperatures that are in contact with one another (the degree of conduction is dependent on the temperature gradient, the conductive properties of the object contacting the body, and the percentage of surface area is in contact).
Convection – transfer of heat energy by air currents e.g. heat is carried away by warm air rising from the body surface.

Heat is lost from the body by vaporization of water in the respiratory passages and on the skin (insensible perspiration) and by vaporization of sweat.When water evaporates from the body surface, the heat energy required to transform water to a gaseous state is absorbed from the body surface, thereby cooling the body (evaporative heat loss). Vaporization of 1 g of water removes 0.58 kcal of heat.

Because the speed of chemical reactions varies with temperature and because the enzyme systems of the body have narrow temperature ranges in which their function is optimal, normal body function depends on a relatively constant body temperature.

A group of reflex responses that are primarily integrated in the hypothalamus operate to maintain core body temperature (that of deep tissues: the brain, viscera, skeletal muscles) within a narrow range (36.3–37.1°C (97.3–98.8°F) despite wide fluctuations in environmental temperature. Because normal body temperature is much closer to the deadly temperature of enzyme denaturation (41-42°C) than to that of water crystallization, low body temperatures are less dangerous than high ones. ⁽¹⁾⁽²⁾

Temperature-regulating mechanisms (figure1)

The reflex and semi reflex thermoregulatory responses in humans include autonomic (sweating, vasodilation or vasoconstriction), somatic (skeletal muscle tone, muscle contraction, shivering), endocrine (production of catecholamines and thyroid hormones), and behavioral changes (the most powerful means to defend body temperature; involves sensory cortex for thermal perception, and the motor cortex for motor response; e.g. putting on warm clothing when cold, switching on fans when hot).

Thermoregulatory mechanisms work to maintain thermal balance by adjusting heat production or heat loss.In general, exposure to heat stimulates the group of responses that increases heat loss and decreases heat production, whereas exposure to cold does the opposite.

The responses activated by cold (mainly peripheral thermoreceptors in the skin) are controlled by the posterior hypothalamus (‘heat conservation centre”). Those activated by warmth (detected by central thermoreceptors in the hypothalamus) are controlled primarily by the preoptic area of the anterior hypothalamus (‘heat loss centre”).⁽¹⁾

Heat loss mechanisms:

Thermal sweating (sudomotor mechanism)

The secretory coil of an eccrine sweat gland produces primary sweat, an ultra-filtrate nearly isotonic with blood plasma. As most of the NaCl is reabsorbed along the ducts, the final sweat is hypotonic.⁽³⁾

Sweating is mediated predominately by sympathetic cholinergic stimulation (acetylcholine released of from sympathetic postganglionic fibers, binds to muscarinic (subtype 3) receptors on the sweat gland).⁽¹⁾⁽³⁾

Sweat must be evaporated from the skin surface for heat loss to occur.The thermal gradient established by the evaporationof sweat is critical for the transfer of heat from thebody to the environment

In high ambient temperatures, heat loss is almost solely based on the rate of sweating. Evaporation depends on the water vapour pressure of the air. As humidity increases, evaporation becomes increasingly ineffective.

Aging attenuates the sudomotor function. Short-term heat acclimation increases sweat gland activity. Long-term heat acclimation results in a reduction in the sweating response to stimuli.⁽⁴⁾

Cutaneous vasodilation (vasomotormechanism)

The efficacy of sweating is precapillary vasodilation, as a brisk blood flow is needed to deliver the heat (to be dissipated) and water (to be vaporized) to the skin. This occurs due to a decrease in tone of the arterioles as the sympathetic noradrenergic discharge is inhibited. Whether sympathetic cholinergic nerves are involved is disputed. ⁽²⁾

Heat conserving mechanisms:

Cutaneous vasoconstriction – In the skin, the arteriovenous anastomoses connect arterioles directly to the venous plexus. Increased sympathetic tone (noradrenaline acting on alpha 1 receptors) inresponse to a decrease in core temperature constricts arterioles and reduces blood flow through arteriovenous anastomoses, therebyreducing heat loss from the surface of the skin.

Shivering (through somatic nervous system- extrapyramidal pathway) – rhythmic, oscillating clonic skeletal muscle contractions; almost all energy liberated is converted to heat as no external work is done.

Brown fat thermogenesis – Noradrenaline causes lipolysis in cells of brown adipose tissue in neonates (between scapula, nape of neck, around aorta). Released free fatty acids are oxidized in mitochondria where there is decreased ATP synthesis and more heat production.⁽¹⁾

HEAT –RELATED ILLNESS: HEAT EXHAUSTION AND HEAT STROKE

Heat-related illnesses comprise a spectrum of syndromes resulting from disruption of thermoregulation in people exposed to high environmental heat. Heat syncope and heat cramps will not be discussed here.

Heat exhaustion is characterized by rectal core temperature up to 104°F(40°C) and tissue hypoperfusion without central nervous dysfunction.⁽⁵⁾⁽⁶⁾ The hypothalamic thermoregulatory mechanism is intact but because of the fall in circulating blood volume as a result of profuse sweating, heat dissipation at the skin surface becomes less efficient giving rise to hyperthermia. It is usually seen in people undertaking prolonged vigorous physical work in a hot environment. The symptoms – dizziness, thirst, weakness, headache, and malaise – typically resolve promptly with proper hydration and cooling.⁽⁵⁾

Heat stroke is a medical emergency characterized by rectal core temperature of 104°F (40°C) or greater, multiorgan damage, and central nervous dysfunction (confusion, loss of consciousness, aggression) with hypothalamic thermoregulatory failure (hot and dry skin due to absence of sweating). ^(7)(8)(9)

Classic heat stroke often develops slowly over days. It predominantly occurs in older persons and those with chronic illness.^{(7) (9)}

Exertional heat stroke has a more rapid onset and is associated with higher core temperatures. It generally occurs in young, healthy persons who engage in strenuous physical exercise during hot weather.^{(7) (9)}

The primary pathogenic mechanism of heat stroke involves transition to impaired thermoregulation when cardiac output is insufficient to cope with the high thermoregulatory needs. Consequently, core body temperature continues to rise, leading to a direct cytotoxic effect and an inflammatory response, creating a vicious cycle, and eventually causing multiorgan failure. Hyperthermia triggers a coordinated stress response involving endothelial cells, leukocytes, and epithelial cells. This reaction is mediated by heat-shock proteins and by changes in plasma and tissue levels of proinflammatory and anti inflammatory cytokines. The heatstroke-induced reduction in intestinal blood flow causes gastrointestinal ischemia. The oxidative stress damages cell membranes and opens tight cell-to-cell junctions, allowing endotoxins to leak into the systemic circulation.⁽⁶⁾⁽⁹⁾

Management of heat exhaustion

Heat exhaustion can usually be managed conservatively. The individual should rest in a cool, shaded environment and replace fluid and electrolytes orally. Cooling may be facilitated by theuse of misting fans to moisten and blow a current of air across skin surfaces (evaporative heat loss).⁽⁷⁾ Ice packs may be applied to the forehead, neck, axillae, and groin.

Management of heat stroke

The primary objective is alleviation of hyperthermia. Rapid and effective cooling is the corner stone of treatment.⁽⁶⁾ Vigorous cooling efforts should be withdrawn once the rectal temperature reaches 38 °C–39 °C.^(6)(7)(10)
Full body Immersion in cold water when available, is the method of choice ^{(5)(6)(8)(9)(10)}. Alternative methods⁽⁵⁾ include: pouring copious amounts of water over the body and fanning (evaporative cooling)⁽⁶⁾ , Internal cooling (gastric, bladder, and rectal cold-water lavage)⁽⁷⁾, infusion of coldfluids (intravascular temperature management)⁽⁶⁾; application of ice packs, cold packs, or wet gauze sheets; and fanning.

No pharmacologic agents accelerate cooling.⁽⁶⁾ Antipyretic agents (aspirin, paracetamol) are ineffective in patients with heatstroke, since fever and hyperthermia raise the core bodytemperature through different pathways.⁽⁶⁾

Patients with heat stroke generally require hospitalization to monitor for medical complications. They should refrain from physical activity for at least seven days after release from medical care. ⁽⁸⁾

Prevention (in warm weather and during heat waves)

Public education
1. Stay in shade. Wear white or light coloured loose clothing, hat and umbrellas and avoid darker or black ones when going out in the sun. Darker objects heat up faster in the sun than white ones do – because they absorb many of the different wavelengths of light energy, and convert them into heat, while white objects reflect most of the wavelengths.

2. Stay hydrated. Replace water and salt loss from sweating so that circulating blood volume is adequate to maintain blood flow to the skin to meet the demands of sweating. Provide ample fluid to those working near boilers, fires or hot surfaces to prevent heat exhaustion.

3. Not to immerse oneself in water (streams, ponds) during the hot daytime. Heat from water flows into the body by conduction, while sweat will not be able to evaporate into the surrounding water. Without evaporation heat is not dissipated. Sweat flow to the skin surface stops as hydrostatic pressure load increases.The rising body temperature activates cell enzymes speed up chemical reactions; increased metabolic heat production further raises the body temperature, and this vicious cycle leads to temperatures at which enzymes are denatured; heat stroke ensues.

4. Not to take cold bath or shower immediately after being exposed to hot environment.Receiving the same sensory information (warmth) from central and skin thermoreceptors facilitates sweating by lowering the sweating threshold. Applying cold water to the skin reduces skin temperature and the contrasting input from the cold receptors in the skin raises the sweating threshold. It also directly causes skin vasoconstriction which impairs sweating and heat conductance to the skin. This might lead to the vicious cycle culminating in hyperthermia if there has been a heat load in the body.

5. For primary care givers:
It helps to be aware of medications that could impair heat loss: tranquilizers (affecting thermoregulatory centre), vasoconstrictors: alpha-receptor agonists, beta-receptor blockers (impair skin vasodilation and secondarily sweating), muscarinic receptor blockers- atropine and other anticholinergics, and first generation antihistamines with anticholinergic properties (impair sweating).⁽¹²⁾(Figure 2).
Anticholinergic Syndrome Mnemonic: “Blind as a bat” (Blurred vision, dilated pupils); “Dry as a bone” (Dry mouth and skin), “Hot as a hare” (Hyperthermia).⁽¹³⁾

References

1. Barrett KE, Barman SM,Brooks HL, Yuan JX-J.Ganong’s Review of Medical Physiology, 26e. 2019; Lange, McGraw Hill. Access Medicine. Chapter 17: Hypothalamic Regulation of Hormonal Functions; Thermoregulation.https://accessmedicine.mhmedical.com/content.aspx?bookid=2525&sectionid=204292033
2. Tansey EA, Johnson CD.Recent advances in thermoregulation. AdvPhysiolEduc2015; 39: 139–148,doi:10.1152/advan.00126.2014.
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9. Glazer JL. Management of Heatstroke and Heat Exhaustion. Am Fam Physician. 2005;71:2133-40, 2141-2.
10. Pryor RR,Casa DJ, Holschen JC, O’Connor FG, Lesley W. Vandermark, LW. Exertional Heat Stroke: Strategies for Prevention and Treatment from the Sports.Clinical Pediatric Emergency Medicine. 2013; 14(4): 267-27 https://doi.org/10.1016/j.cpem.2013.10.005
11. Bendall JC, Berry DC, Chang WT et al. First aid cooling techniques for heat stroke and exertional hyperthermia: A systematic review and meta-analysis. Resuscitation, 2020; 148: 173-190. https://doi.org/10.1016/j.resuscitation.2020.01.007.
12. Gerretsen P, Pollock BG. Drugs with anticholinergic properties: a current perspective on use and safety. Expert Opin Drug Saf. 2011;10(5):751-65. doi: 10.1517/14740338.2011.579899. Epub 2011 Jun 2.
13. Coggins MD. Antihistamine Risks. In: Aging Well. Vol. 6 No. 2, p.6. https://www.todaysgeriatricmedicine.com/archive/0313p6.shtml

Nyunt Wai,
MBBS (Ygn) M.Med.Sc (Ygn) PhD (Lond),
Professor and Head (retired), Honorary Professor,
Physiology Department,
University of Medicine 1, Yangon.