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❖ CASE 50 A 16-year-old high school student is brought to the emergency department by the emergency medical service after being found lying in the front yard of a neighbor’s house, where he was mowing the lawn. The patient has a regular yard service and has been mowing for several months without problems. The patient was finishing his sixth yard for the day during a summer month with temperatures exceeding 37.8°C. His mowing partner noticed that the patient had been complaining of fatigue, light-headedness, nausea, and profuse sweating in the previous yard. While mowing the last yard, he became very confused and behaved oddly before finally losing consciousness. In the emergency department, he is tachycardic, with a temperature of 40.6°C. He is lethargic, and his skin is dry. He is diagnosed with heat stroke, and therapy is begun immediately. ◆ What physical processes are used physiologically to dissipate heat from the body? ◆ In what part of the brain is the set-point temperature represented? ◆ How does aspirin or ibuprofen reduce fever? 402 CASE FILES: PHYSIOLOGY ANSWERS TO CASE 50: REGULATION OF BODY TEMPERATURE Summary: A 16-year-old boy is brought to the emergency department after having a heat stroke. ◆ Heat loss mechanisms: Evaporation, radiation, conduction, and convection. ◆ ◆ Part of brain concerned with set-point temperature: Hypothalamus. Nonsteroidal medications and fever: Block the production of prostaglandins, which increase the set-point temperature. CLINICAL CORRELATION Recognition and early treatment are important when a heat stroke is suspected. Hyperthermia results when the normal heat-reducing mechanisms cannot respond to the heat adequately. A patient’s initial response to hyperthermia includes shunting warm blood flow to the surface of the skin to increase heat loss by radiation, conduction, and convection. The most important heat loss mechanism is evaporation. If it is prolonged, copious sweating leads to volume depletion and tissue hypoperfusion. Symptoms of fatigue, light-headedness, nausea and/or vomiting, and hypotension may be present, and the patient will suffer from heat exhaustion. If the hyperthermia is not resolved, heat stroke occurs. This occurs when the temperature exceeds 40°C because the temperature-integrative center in the hypothalamus is inactivated and the normal responses to hyperthermia (most importantly, sweating) cease. Death occurs rapidly unless the body is cooled, for example, by ice water baths or by removing clothing and sponging if an ice water bath is not available. Treatment of a heat stroke includes intravenous (IV) fluid replacement and, because damage may occur in various organs, including the kidneys and liver, close observation of electrolytes and other laboratory values (liver function tests, clotting studies, creatine phosphokinase [CPK], and complete blood count [CBC]). Recognition of heat exhaustion before the development of heat stroke is an important topic to teach workers, athletes, and patients who are at risk of heat exhaustion (eg, from manual labor or intense exercise outdoors during summer months). APPROACH TO BODY TEMPERATURE PHYSIOLOGY Objectives 1. 2. 3. Understand heat exchange between the body and its environment. Know about the regulation of heat exchange and heat production. Describe human adaptations to heat and cold. CLINICAL CASES 403 Definition Fever: A regulated increase in core temperature caused by elevation of the temperature set-point in the hypothalamus, usually during infection or disease. DISCUSSION Maintenance of constant body temperature requires that heat production from metabolism be balanced by heat exchange with the environment. The ability to dissipate heat to the environment is vital because even under resting conditions in a temperate environment, if the heat generated by the body is not dissipated, body temperature will reach lethal levels. Heat exchange with the environment occurs by three processes: conduction to or from molecules in contact with the skin (or gastrointestinal [GI] or pulmonary epithelia), radiation by infrared rays to or from bodies at different temperatures from that of the skin, and evaporation of sweat or respiratory secretions from the body. Radiation and conduction can increase or decrease total body heat content, whereas evaporation always decreases body heat content. Both conduction and evaporative heat loss are increased by convection of air around the body. The body regulates heat content by regulating skin temperature, sweat production, and heat production. Skin temperature depends on the insulating properties of subcutaneous fat, which is not subject to rapid regulation, and cutaneous blood flow. Through changes in the diameter of arterioles and precapillary sphincters, blood flow into the cutaneous circulation can be regulated dramatically, from slightly more than 0% up to 30% of cardiac output. Local heating (or cutaneous irritation) dilates the precapillary sphincters, increasing cutaneous blood flow locally. Cutaneous heating or irritation also triggers spinal reflexes that dilate arterioles across a wider area. Thermoreceptors are found not only in the skin but also in the preoptic anterior hypothalamus, where the thermoreceptors are much more sensitive to small changes in temperature than the peripheral thermoreceptors are. An increase in core temperature warms the hypothalamus and evokes a reduction in tonic activity in the sympathetic fibers innervating cutaneous arterioles, permitting the arterioles to dilate all over the body surface. The increased blood flow to the skin shifts part of the heat content of the body to the surface, where it can be lost by conduction, convection, evaporation, and radiation. Cooling has the opposite effects. Local cooling of the skin causes precapillary sphincters to constrict, whereas a drop in core temperature increases sympathetic outflow to cutaneous arterioles, with the resulting constriction reducing cutaneous blood flow and thus heat loss to the environment. Increased sympathetic activity also causes piloerection (gooseflesh). The control of sweat production is critical for survival under conditions in which conduction, convection, and radiation of heat from the skin cannot offset heat absorption and heat production (eg, when the environment is hotter 404 CASE FILES: PHYSIOLOGY than the body or during intense exercise). Eccrine sweat glands are activated by sympathetic fibers, which release acetylcholine (ACh) rather than norepinephrine (NE), and can secrete up to approximately 1.5 L/h in normal adults. After chronic adaptation to a hot climate, this rate can increase to 4 L/h. This is accompanied by increases in plasma aldosterone levels to reduce the loss of Na+ and water. Heat production in a normal adult during maximal exercise can be 20 times the level at rest. During extreme heat, behavioral changes (lethargy) that lead to decreased physical activity reduce heat production. During cold exposure, behavioral changes such as stomping the feet and clapping the hands increase heat production. In addition, shivering occurs by involuntary asynchronous contraction of skeletal muscles. This is produced, at least in part, by facilitation of the stretch reflex and can increase heat production fivefold to sixfold. Release of epinephrine and NE from the adrenal medulla also occurs during cold exposure, and this increases metabolic heat production (chemical thermogenesis), especially in brown adipose tissue (in humans this is abundant only in infants). Chronic cold exposure also causes a persistent increase in thyroxin production, which uncouples oxidative phosphorylation and increases the metabolic rate in many tissues (as catecholamines do in brown adipose tissue). If body temperature falls below 33°C, mental confusion occurs as central nervous system (CNS) function begins to be impaired. Below 30°C, thermoregulatory control by the CNS is lost, shivering stops, consciousness is lost, and muscular rigidity and collapse occur. With further cooling, slow atrial fibrillation and, finally, ventricular fibrillation occur. Body temperature is regulated by a temperature-integrative center in the hypothalamus. The temperature set point varies slightly (by ~0.6°C) each day in a circadian rhythm, with the lowest temperature occurring just before waking in the morning. In women, a small monthly elevation (0.2°C-0.6°C) is associated with ovulation. Fever, which can be triggered by infection, dehydration, or thyrotoxicosis, involves an elevation of the temperature set point in the hypothalamus. During infection, exogenous pyrogens associated with invading microorganisms trigger the release of endogenous pyrogens such as interleukin 1β (IL-1β), IL-6, and tumor necrosis factor (TNF) from leukocytes; this causes the production of prostaglandin E2 and thromboxanes, which elevate the set-point temperature. Heat conservation responses (cutaneous vasoconstriction, inhibition of sweating), increased heat production (shivering), and behavioral responses (eg, pulling on covers) continue until the new set-point temperature is attained. CLINICAL CASES 405 COMPREHENSION QUESTIONS [50.1] An increase in sympathetic activity involving axons going to the skin is noted. Which of the following is most likely to occur? A. B. C. D. E. [50.2] A 32-year-old man has lived for many years in Death Valley, California, mostly outdoors. Which of the following include adaptations he exhibits to this very hot environment ? A. B. C. D. E. [50.3] Constriction of capillaries Increased blood flow through the skin Increased release of NE at eccrine sweat glands Inhibition of sweating Piloerection A large increase in the maximal rate of sweating Decreases in the mass of brown adipose tissue Decreases in plasma aldosterone levels Facilitation of the stretch reflex Increases in plasma thyroxine levels A 28-year-old woman has a fever of 40°C as a result of influenza. Which of the following is likely to occur during the fever? A. B. C. D. E. Cutaneous vasoconstriction Reduction of hypothalamic set-point temperature Decrease in shivering Increase in sweating Strong subjective sensation of increased heat Answers [50.1] E. Some sympathetic fibers going to the skin release NE onto pilomotor muscles, causing piloerection. Sympathetic activity also decreases blood flow through the skin by releasing NE onto smooth muscles in cutaneous arterioles (not capillaries), which then constrict. Under hot conditions, a separate set of sympathetic axons in the skin stimulates the secretion of sweat from eccrine sweat glands (these sympathetic terminals release ACh rather than NE). [50.2] A. The rate of sweat production by existing sweat glands increases dramatically after a couple of months in a hot climate. In addition, over longer periods, sweat production increases because the number of sweat ducts increases. Aldosterone production increases (not decreases, as in answer C), and this increases the reabsorption of Na+ from sweat ducts, conserving Na+. Brown adipose tissue is not found in adults (answer B), whereas facilitation of the stretch reflex and increases in plasma thyroxin levels (answers D and E) are adaptations to prolonged cold exposure rather than heat exposure. 406 [50.3] CASE FILES: PHYSIOLOGY A. Fever elevates the hypothalamic set-point temperature, activating heat conservation responses, which include cutaneous vasoconstriction. Sweating is inhibited, and shivering occurs. There is a strong subjective sensation of cold, leading to behavioral efforts to warm the body such as pulling on blankets. PHYSIOLOGY PEARLS ❖ ❖ ❖ ❖ ❖ ❖ ❖ ❖ Heat exchange with the environment occurs by conduction to or from molecules contacting the skin, by radiation via infrared rays to or from bodies at temperatures different from that of the skin, and evaporation of sweat and other secretions from the body surface. The efficiency of conduction and evaporation from the body surface is increased by convection of air around the body. Heat exchange across the skin is regulated by controlling the amount of blood flowing (and carrying heat) into the cutaneous circulation. Cutaneous blood flow is decreased by direct contractile responses of precapillary sphincters to cold as well as by increased sympathetic input to cutaneous arterioles, whereas elevation of local or core temperature produces the opposite effects. Core temperature is monitored by sensitive thermoreceptors in the hypothalamus, and this temperature is compared to the hypothalamic set point, with any discrepancy triggering appropriate autonomic and behavioral responses to bring the core temperature to the set point. Evaporation of sweat released by eccrine sweat glands is the only physiological mechanism available for cooling the body when the environmental temperature exceeds body temperature. Physiologic heat production is decreased during heat stress (primarily by behavioral changes such as lethargy) and increased during cold stress by facilitation of motor activity, shivering, and (in infants) enhancement of metabolic heat production in brown adipose tissue in response to epinephrine and NE release. Long-term adaptations to hot environments include a large increase in the maximal rate of sweating and increased aldosterone production, whereas adaptations to cold environments include an increase in thyroxine production. CLINICAL CASES 407 REFERENCES Nadel E. Regulation of body temperature. In: Boron WF, Boulpaep EL, eds. Medical Physiology. Philadelphia, PA: Saunders Elsevier Science; 2003: 1231-1241. Schafer JA. Body temperature regulation. In: Johnson LR, ed. Essential Medical Physiology. San Diego, CA: Elsevier Academic Press; 2003: 921-932. This page intentionally left blank