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The Regulation of Body Temperature*C. Bruce Wenger, Ph.D.29

C H A P T E R

29■ BODY TEMPERATURES AND HEAT TRANSFER IN

THE BODY

■ THE BALANCE BETWEEN HEAT PRODUCTION AND

HEAT LOSS

■ HEAT DISSIPATION

■ THERMOREGULATORY CONTROL

■ THERMOREGULATORY RESPONSES DURING

EXERCISE

■ HEAT ACCLIMATIZATION

■ RESPONSES TO COLD

■ CLINICAL ASPECTS OF THERMOREGULATION

C H A P T E R O U T L I N E

1. The body is divided into an inner core and an outer shell;temperature is relatively uniform in the core and is regu-lated within narrow limits, while shell temperature is per-mitted to vary.

2. The body produces heat through metabolic processes andexchanges energy with the environment as mechanicalwork and heat; it is in thermal balance when the sum ofmetabolic energy production plus energy gain from the en-vironment equals energy loss to the environment.

3. In humans, the chief physiological thermoregulatory re-sponses are the secretion of sweat, which removes heat fromthe skin as it evaporates; the control of skin blood flow, whichgoverns the flow of heat to the skin from the rest of the body;and increasing metabolic heat production in the cold.

4. The thermoregulatory set point (the setting of the body’s“thermostat”) varies cyclically with the circadian rhythmand the menstrual cycle, and is elevated during fever.

5. Core and whole-body skin temperatures govern the reflexcontrol of physiological thermoregulatory responses,which are graded according to disturbances in the body’sthermal state.

6. The control of thermoregulatory responses is accom-plished through reflex signals generated in the CNS ac-cording to the level of the thermoregulatory set point, aswell as signals from temperature-sensitive CNS neuronsand nerve endings elsewhere, chiefly in the skin. The re-sponse of sweat glands and superficial blood vessels tothese signals is modified by local skin temperature.

7. Acclimatization to heat can dramatically increase thebody’s ability to dissipate heat, maintain cardiovascularhomeostasis in hot temperatures, and conserve salt whilesweating profusely. Acclimatization to cold has only mod-est effects, depending on how the acclimatization was pro-duced, and may include increased tissue insulation andvariable metabolic responses.

8. Adverse systemic effects of excessive heat stress includecirculatory instability, fluid-electrolyte imbalance, exer-tional heat injury, and heatstroke. Exertional heat injuryand heatstroke involve organ and tissue injury produced inseveral ways, some of which are not well understood. Theprimary adverse systemic effect of excessive cold stress ishypothermia.

K E Y C O N C E P T S

PART 8 Temperature Regulation and Exercise Physiology

527

*The views, opinions, and findings contained in this chapter are those of the author and should not be construed as officialDepartment of the Army position, policy, or decision unless so designated by other official documentation. Approved forpublic release; distribution unlimited.

528 PART VIII TEMPERATURE REGULATION AND EXERCISE PHYSIOLOGY

Humans, like other mammals, are homeotherms, orwarm-blooded animals, and regulate their internal

body temperatures within a narrow range near 37�C, inspite of wide variations in environmental temperature (Fig. 29.1). Internal body temperatures of poikilotherms, orcold-blooded animals, by contrast, are governed by envi-ronmental temperature. The range of temperatures that liv-ing cells and tissues can tolerate without harm extends fromjust above freezing to nearly 45�C—far wider than the lim-its within which homeotherms regulate body temperature.What biological advantage do homeotherms gain by main-taining a stable body temperature? As we shall see, tissuetemperature is important for two reasons.

First, temperature extremes injure tissue directly. Hightemperatures alter the configuration and overall structure ofprotein molecules, even though the sequence of aminoacids is unchanged. Such alteration of protein structure iscalled denaturation. A familiar example of denaturation byheat is the coagulation of albumin in the white of a cookedegg. Since the biological activity of a protein molecule de-pends on its configuration and charge distribution, denatu-ration inactivates a cell’s proteins and injures or kills thecell. Injury occurs at tissue temperatures higher than about45�C, which is also the point at which heating the skin be-comes painful. The severity of injury depends on the tem-perature to which the tissue is heated and how long theheating lasts.

Cold also can injure tissues. As a water-based solutionfreezes, ice crystals consisting of pure water form, so that alldissolved substances in the solution are left in the unfrozenliquid. Therefore, as more ice forms, the remaining liquid be-comes more and more concentrated. Freezing damages cellsthrough two mechanisms. Ice crystals probably injure thecell mechanically. In addition, the increase in solute concen-tration of the cytoplasm as ice forms denatures the proteinsby removing their water of hydration, increasing the ionicstrength of the cytoplasm, and causing other changes in thephysicochemical environment in the cytoplasm.

Second, temperature changes profoundly alter biologi-cal function through specific effects on such specializedfunctions as electrical properties and fluidity of cell mem-branes, and through a general effect on most chemical re-action rates. In the physiological temperature range, mostreaction rates vary approximately as an exponential func-tion of temperature (T); increasing T by 10�C increases thereaction rate by a factor of 2 to 3. For any particular reac-tion, the ratio of the rates at two temperatures 10�C apart iscalled the Q10 for that reaction, and the effect of tempera-ture on reaction rate is called the Q10 effect. The notion ofQ10 may be generalized to apply to a group of reactionsthat have some measurable overall effect (such as O2 con-sumption) in common and are, thus, thought of as com-prising a physiological process. The Q10 effect is clinicallyimportant in managing patients who have high fevers andare receiving fluid and nutrition intravenously. A com-monly used rule is that a patient’s fluid and calorie needs areincreased 13% above normal for each 1�C of fever.

The profound effect of temperature on biochemical re-action rates is illustrated by the sluggishness of a reptilethat comes out of its burrow in the morning chill and be-comes active only after being warmed by the sun.Homeotherms avoid such a dependence of metabolic rateon environmental temperature by regulating their internalbody temperatures within a narrow range. A drawback ofhomeothermy is that, in most homeotherms, certain vitalprocesses cannot function at low levels of body tempera-ture that poikilotherms tolerate easily. For example, ship-wreck victims immersed in cold water die of respiratory orcirculatory failure (through disruption of the electrical ac-tivity of the brainstem or heart) at body temperatures ofabout 25�C, even though such a temperature produces nodirect tissue injury and fish thrive in the same water.

BODY TEMPERATURES AND HEAT TRANSFER

IN THE BODY

The body is divided into a warm internal core and a coolerouter shell (Fig. 29.2). Because the temperature of the shellis strongly influenced by the environment, its temperatureis not regulated within narrow limits as the internal bodytemperature is, even though thermoregulatory responsesstrongly affect the temperature of the shell, especially itsoutermost layer, the skin. The thickness of the shell de-pends on the environment and the body’s need to conserveheat. In a warm environment, the shell may be less than 1cm thick, but in a subject conserving heat in a cold envi-ronment, it may extend several centimeters below the skin.

Heatstroke,brain lesions

Fever andexercise

Usual rangeof normal at rest

Upper limitof survival?

Lower limitof survival?

Temperatureregulationseriouslyimpaired

Temperatureregulation

effective infever and

health


impaired


lost

Rectal temperature ranges in healthy peo-

ple, patients with fever, and people with

impaired or failed thermoregulation. (Modified from WengerCB, Hardy JD. Temperature regulation and exposure to heat andcold. In: Lehmann JF, ed. Therapeutic Heat and Cold. 4th Ed.Baltimore: Williams & Wilkins, 1990;150–178. Based on DuBoisEF. Fever and the Regulation of Body Temperature. Springfield,IL: CC Thomas, 1948.)

FIGURE 29.1

The internal body temperature that is regulated is the tem-perature of the vital organs inside the head and trunk,which, together with a variable amount of other tissue,comprise the warm internal core.

Heat is produced in all tissues of the body but is lost tothe environment only from tissues in contact with the en-vironment—predominantly from the skin and, to a lesserdegree, from the respiratory tract. We, therefore, need toconsider heat transfer within the body, especially heattransfer (1) from major sites of heat production to the restof the body, and (2) from the core to the skin. Heat istransported within the body by two means: conductionthrough the tissues and convection by the blood, a processin which flowing blood carries heat from warmer tissues tocooler tissues.

Heat flow by conduction varies directly with the ther-mal conductivity of the tissues, the change in temperatureover the distance the heat travels, and the area (perpendi-cular to the direction of heat flow) through which theheat flows. It varies inversely with the distance the heatmust travel. As Table 29.1 shows, the tissues are ratherpoor heat conductors.

Heat flow by convection depends on the rate of bloodflow and the temperature difference between the tissue andthe blood supplying the tissue. Because the vessels of the mi-crovasculature have thin walls and, collectively, a large totalsurface area, the blood comes to the temperature of the sur-rounding tissue before it reaches the capillaries. Changes inskin blood flow in a cool environment change the thicknessof the shell. When skin blood flow is reduced in the cold, theaffected skin becomes cooler, and the underlying tissues—

which in the cold may include most of the limbs and themore superficial muscles of the neck and trunk—becomecooler as they lose heat by conduction to cool overlying skinand, ultimately, to the environment. In this way, these un-derlying tissues, which in the heat were part of the bodycore, now become part of the shell. In addition to the organsin the trunk and head, the core includes a greater or lesseramount of more superficial tissue—mostly skeletal muscle—depending on the body’s thermal state.

Because the shell lies between the core and the environ-ment, all heat leaving the body core, except heat lostthrough the respiratory tract, must pass through the shellbefore being given up to the environment. Thus, the shellinsulates the core from the environment. In a cool subject,the skin blood flow is low, so core-to-skin heat transfer isdominated by conduction; the shell is also thicker, provid-ing more insulation to the core, since heat flow by conduc-tion varies inversely with the distance the heat must travel.Changes in skin blood flow, which directly affect core-to-skin heat transfer by convection, also indirectly affect core-to-skin heat transfer by conduction by changing the thick-ness of the shell. In a cool subject, the subcutaneous fatlayer contributes to the insulation value of the shell becausethe fat layer increases the thickness of the shell and becausefat has a conductivity about 0.4 times that of dermis or mus-cle (see Table 29.1). Thus, fat is a correspondingly betterinsulator. In a warm subject, however, the shell is relativelythin, and provides little insulation. Furthermore, a warmsubject’s skin blood flow is high, so heat flow from the coreto the skin is dominated by convection. In these circum-stances the subcutaneous fat layer, which affects conduc-tion but not convection, has little effect on heat flow fromthe core to the skin.

Core Temperature Is Close to

Central Blood Temperature

Core temperature varies slightly from one site to anotherdepending on such local factors as metabolic rate, bloodsupply, and the temperatures of neighboring tissues. How-ever, temperatures at different places in the core are allclose to the temperature of the central blood and tend to

CHAPTER 29 The Regulation of Body Temperature 529

Distribution of temperatures in the body’s

core and shell. A, During exposure to cold. B,In a warm environment. Since the temperatures of the surface andthe thickness of the shell depend on environmental temperature,the shell is thicker in the cold and thinner in the heat.

FIGURE 29.2

TABLE 29.1Thermal Conductivities and Rates

of Heat Flow

ConductivityRate of Heat Flowa

Material kcal/(s�m�°C) kcal/hr Watts

Copper 0.092 33,120 38,474Epidermis 0.00005 18 21Dermis 0.00009 32 38Fat 0.00004 14 17Muscle 0.00011 40 46Oak (across grain) 0.00004 14 17Glass fiber 0.00001 3.6 4.2

insulation

a Values are calculated for slabs 1 m2 in area and 1 cm thick, with a 1°Ctemperature difference between the two faces of the slab.


change together. The notion of a single uniform core tem-perature, although not strictly correct, is a useful approxi-mation. The value of 98.6�F often given as the normal levelof body temperature may give the misleading impressionthat body temperature is regulated so precisely that it isnot allowed to deviate even a few tenths of a degree. Infact, 98.6�F is simply the Fahrenheit equivalent of 37�C,and body temperature does vary somewhat (see Fig. 29.1).The effects of heavy exercise and fever are familiar; varia-tion among individuals and such factors as time of day (Fig. 29.3), phase of the menstrual cycle, and acclimatiza-tion to heat can also cause differences of up to about 1�Cin core temperature at rest.

To maintain core temperature within a narrow range,the thermoregulatory system needs continuous informa-tion about the level of core temperature. Temperature-sensitive neurons and nerve endings in the abdominal vis-cera, great veins, spinal cord, and, especially, the brainprovide this information. We discuss how the thermoreg-ulatory system processes and responds to this informationlater in the chapter.

Core temperature should be measured at a site whosetemperature is not biased by environmental temperature.Sites used clinically include the rectum, the mouth and, oc-casionally, the axilla. The rectum is well insulated from theenvironment; its temperature is independent of environ-mental temperature and is a few tenths of 1�C warmer thanarterial blood and other core sites. The tongue is richly sup-plied with blood; oral temperature under the tongue is usu-ally close to blood temperature (and 0.4 to 0.5�C belowrectal temperature), but cooling the face, neck, or mouthcan make oral temperature misleadingly low. If a patientholds his or her upper arm firmly against the chest to closethe axilla, axillary temperature will eventually come rea-sonably close to core temperature. However, as this maytake 30 minutes or more, axillary temperature is infre-

quently used. Infrared ear thermometers are convenientand widely used in the clinic, but temperatures of the tym-panum and external auditory meatus are loosely related tomore accepted indices of core temperature, and ear tem-perature in collapsed hyperthermic runners may be 3 to6�C below rectal temperature.

Skin Temperature Is Important in Heat

Exchange and Thermoregulatory Control

Most heat is exchanged between the body and the envi-ronment at the skin surface. Skin temperature is muchmore variable than core temperature; it is affected by ther-moregulatory responses such as skin blood flow and sweatsecretion, the temperatures of underlying tissues, and en-vironmental factors such as air temperature, air move-ment, and thermal radiation. Skin temperature is one ofthe major factors determining heat exchange with the en-vironment. For these reasons, it provides the thermoregu-latory system with important information about the needto conserve or dissipate heat.

Many bare nerve endings just under the skin are sensitiveto temperature. Depending on the relation of discharge rateto temperature, they are classified as either warm or cold re-ceptors (see Chapter 4). Cold receptors are about 10 timesmore numerous than warm receptors. Furthermore, as theskin is heated, warm receptors respond with a transient burstof activity and cold receptors respond with a transient sup-pression; the reverse happens as the skin is cooled. Thesetransient responses at the beginning of heating or coolinggive the central thermoregulatory controller almost imme-diate information about changes in skin temperature andmay explain, for example, the intense, brief sensation of be-ing chilled that occurs during a plunge into cold water.

Since skin temperature usually is not uniform over thebody surface, mean skin temperature (sk) is frequently cal-culated from temperatures at several skin sites, usuallyweighting each temperature according to the fraction ofbody surface area it represents. sk is used to summarize theinput to the CNS from temperature-sensitive nerve endingsin the skin. sk also is commonly used, along with core tem-perature, to calculate a mean body temperature and to esti-mate the quantity of heat stored in the body, since the di-rect measurement of shell temperature would be difficultand invasive.

THE BALANCE BETWEEN HEAT PRODUCTION

AND HEAT LOSS

All animals exchange energy with the environment. Someenergy is exchanged as mechanical work, but most is ex-changed as heat (Fig. 29.4). Heat is exchanged by conduc-tion, convection, and radiation and as latent heat throughevaporation or (rarely) condensation of water. If the sum ofenergy production and energy gain from the environmentdoes not equal energy loss, the extra heat is “stored” in, orlost from, the body. This relationship is summarized in theheat balance equation:

M � E � R � C � K � W � S (1)

37.0

36.8

36.6

36.4

36.2

36.0

Cor

e te

mpe

ratu

re (

°C)

4:00 AM 4:00 PM

Time of day

8:00 PM Midnight8:00 AM Noon

Effect of time of day on internal body tem-

perature of healthy resting subjects. (Drawnfrom data of Mackowiak PA, Wasserman SS, Levine MM. A criti-cal appraisal of 98.6�F, the upper limit of normal body tempera-ture, and other legacies of Carl Reinhold August Wunderlich.JAMA 1992;268:1578–1580; and Stephenson LA, Wenger CB,O’Donovan BH, et al. Circadian rhythm in sweating and cuta-neous blood flow. Am J Physiol 1984;246:R321–R324.)

FIGURE 29.3

where M is metabolic rate; E is rate of heat loss by evapora-tion; R and C are rates of heat loss by radiation and con-vection, respectively; K is the rate of heat loss by conduc-tion; W is rate of energy loss as mechanical work; and S israte of heat storage in the body, manifested as changes intissue temperatures.

M is always positive, but the terms on the right side ofequation 1 represent energy exchange with the environ-ment and storage and may be either positive or negative.E, R, C, K, and W are positive if they represent energylosses from the body and negative if they represent energygains. When S � 0, the body is in heat balance and bodytemperature neither rises nor falls. When the body is notin heat balance, its mean tissue temperature increases if Sis positive and decreases if S is negative. This situationcommonly lasts only until the body’s responses to the tem-perature changes are sufficient to restore balance. How-ever, if the thermal stress is too great for the thermoregu-latory system to restore balance, the body will continue togain or lose heat until either the stress diminishes suffi-ciently or the animal dies.

The traditional units for measuring heat are a potentialsource of confusion, because the word calorie refers to twounits differing by a 1,000-fold. The calorie used in chemistryand physics is the quantity of heat that will raise the tem-perature of 1 g of pure water by 1�C; it is also called thesmall calorie or gram calorie. The Calorie (capital C) used inphysiology and nutrition is the quantity of heat that willraise the temperature of 1 kg of pure water by 1�C; it is alsocalled the large calorie, kilogram calorie, or (the usual prac-tice in thermal physiology) the kilocalorie (kcal). Becauseheat is a form of energy, it is now often measured in joules,the unit of work (1 kcal � 4,186 J), and rate of heat pro-duction or heat flow in watts, the unit of power (1 W � 1J/sec). This practice avoids confusing calories and Calories.However, kilocalories are still used widely enough that it isnecessary to be familiar with them, and there is a certain ad-vantage to a unit based on water because the body itself ismostly water.

Heat Is a By-product of Energy-Requiring

Metabolic Processes

Metabolic energy is used for active transport via membranepumps, for energy-requiring chemical reactions, such as theformation of glycogen from glucose and proteins fromamino acids, and for muscular work. Most of the metabolicenergy used in these processes is converted into heat withinthe body. This conversion may occur almost immediately,as with energy used for active transport or heat produced asa by-product of muscular activity. Other energy is con-verted to heat only after a delay, as when the energy usedin forming glycogen or protein is released as heat when theglycogen is converted back into glucose or the protein isconverted back into amino acids.

Metabolic Rate and Sites of Heat Production at Rest.Among subjects of different body size, metabolic rate atrest varies approximately in proportion to body surfacearea. In a resting and fasting young adult man it is about 45W/m2 (81 W or 70 kcal/hr for 1.8 m2 body surface area),corresponding to an O2 consumption of about 240 mL/min.About 70% of energy production at rest occurs in the bodycore—trunk viscera and the brain—even though they com-prise only about 36% of the body mass (Table 29.2). As aby-product of their metabolic processes, these organs pro-duce most of the heat needed to maintain heat balance atcomfortable environmental temperatures; only in the coldmust such by-product heat be supplemented by heat pro-duced expressly for thermoregulation.

Factors other than body size that affect metabolism atrest include age and sex (Fig. 29.5), and hormones and di-gestion. The ratio of metabolic rate to surface area is high-est in infancy and declines with age, most rapidly in child-hood and adolescence and more slowly thereafter. Childrenhave high metabolic rates in relation to surface area becauseof the energy used to synthesize the fats, proteins, and othertissue components needed to sustain growth. Similarly, awoman’s metabolic rate increases during pregnancy to sup-ply the energy needed for the growth of the fetus. However,a nonpregnant woman’s metabolic rate is 5 to 10% lowerthan that of a man of the same age and surface area, proba-


Exchange of energy with the environment.

This hiker gains heat from the sun by radiationand loses heat by conduction to the ground through the soles ofhis feet, convection into the air, radiation to the ground and sky,and evaporation of water from his skin and respiratory passages.In addition, some of the energy released by his metabolicprocesses is converted into mechanical work, rather than heat,since he is walking uphill.

FIGURE 29.4


bly because a higher proportion of the female body is com-posed of fat, a tissue with low metabolism.

The catecholamines and thyroxine are the hormonesthat have the greatest effect on metabolic rate. Cate-cholamines cause glycogen to break down into glucoseand stimulate many enzyme systems, increasing cellularmetabolism. Hypermetabolism is a clinical feature ofsome cases of pheochromocytoma, a catecholamine-se-creting tumor of the adrenal medulla. Thyroxine magni-fies the metabolic response to catecholamines, increasesprotein synthesis, and stimulates oxidation by the mito-chondria. The metabolic rate is typically 45% above nor-mal in hyperthyroidism (but up to 100% above normal insevere cases) and 25% below normal in hypothyroidism(but 45% below normal with complete lack of thyroidhormone). Other hormones have relatively minor effectson metabolic rate.

A resting person’s metabolic rate increases 10 to 20% af-ter a meal. This effect of food, called the thermic effect offood (formerly known as specific dynamic action), lastsseveral hours. The effect is greatest after eating protein andless after carbohydrate and fat; it appears to be associatedwith processing the products of digestion in the liver.

Measurement of Metabolic Rate. Because so many fac-tors affect metabolism at rest, metabolic rate is often meas-ured under a set of standard conditions to compare it withestablished norms. Metabolic rate measured under theseconditions is called basal metabolic rate (BMR). The com-monly accepted conditions for measuring BMR are that theperson must have fasted for 12 hours; the measurementmust be made in the morning after a good night’s sleep, be-ginning after the person has rested quietly for at least 30minutes; and the air temperature must be comfortable,about 25�C (77�F). Basal metabolic rate is “basal” only dur-ing wakefulness, since metabolic rate during sleep is some-what less than BMR.

Heat exchange with the environment can be measureddirectly by using a human calorimeter. In this insulatedchamber, heat can exit only in the air ventilating the cham-ber or in water flowing through a heat exchanger in thechamber. By measuring the flow of air and water and theirtemperatures as they enter and leave the chamber, one candetermine the subject’s heat loss by conduction, convec-tion, and radiation. And by measuring the moisture contentof air entering and leaving the chamber, one can determineheat loss by evaporation. This technique is called directcalorimetry, and though conceptually simple, it is cumber-some and costly.

Metabolic rate is often estimated by indirect calorime-try, which is based on measuring a person’s rate of O2 con-sumption, since virtually all energy available to the bodydepends ultimately on reactions that consume O2. Con-suming 1 L of O2 is associated with releasing 21.1 kJ (5.05kcal) if the fuel is carbohydrate, 19.8 kJ (4.74 kcal) if thefuel is fat, and 18.6 kJ (4.46 kcal) if the fuel is protein. Anaverage value often used for the metabolism of a mixeddiet is 20.2 kJ (4.83 kcal) per liter of O2. The ratio of CO2

produced to O2 consumed in the tissues is called the res-piratory quotient (RQ). The RQ is 1.0 for the oxidation ofcarbohydrate, 0.71 for the oxidation of fat, and 0.80 forthe oxidation of protein. In a steady state where CO2 is ex-haled from the lungs at the same rate it is produced in thetissues, RQ is equal to the respiratory exchange ratio, R(see Chapter 19). One can improve the accuracy of indi-rect calorimetry by also determining R and either estimat-ing the amount of protein oxidized—which usually issmall compared to fat and carbohydrate—or calculating itfrom urinary nitrogen excretion.

Skeletal Muscle Metabolism and External Work. Evenduring mild exercise, the muscles are the principal source ofmetabolic heat, and during intense exercise, they may ac-count for up to 90%. Moderately intense exercise by ahealthy, but sedentary, young man may require a metabolicrate of 600 W (in contrast to about 80 W at rest), and in-tense activity by a trained athlete, 1,400 W or more. Be-cause of their high metabolic rate, exercising muscles maybe almost 1�C warmer than the core. Blood perfusing thesemuscles is warmed and, in turn, warms the rest of the body,raising the core temperature.

Muscles convert most of the energy in the fuels theyconsume into heat rather than mechanical work. Duringphosphorylation of ADP to form ATP, 58% of the energyreleased from the fuel is converted into heat, and only

TABLE 29.2Relative Masses and Metabolic Heat

Production Rates During Rest and Heavy

Exercise

% of

% ofHeat Production

Body Mass Rest Exercise

Brain 2 16 1Trunk viscera 34 56 8Muscle and skin 56 18 90Other 8 10 1

34363840

4442

464850

5452

62

565860

2830323436384042

4644

48505254

Bas

al m

etab

olic

rat

e (W

/m2 )

Basal m

etabolic rate [kcal/(m2•hr)]

5 10 15 20 25 30 35 40

Age (yr)

45 50 55 60 65 70 750

Males

Females

Effects of age and sex on the basal meta-

bolic rate of healthy subjects. Metabolic ratehere is expressed as the ratio of energy consumption to body sur-face area.

FIGURE 29.5

about 42% is captured in the ATP that is formed in theprocess. When a muscle contracts, some of the energy inthe ATP that was hydrolyzed is converted into heat ratherthan mechanical work. The efficiency at this stage variesenormously; it is zero in isometric muscle contraction, inwhich a muscle’s length does not change while it developstension, so that no work is done even though metabolic en-ergy is required. Finally, some of the mechanical work pro-duced is converted by friction into heat within the body.(This is, for example, the fate of all of the mechanical workdone by the heart in pumping blood.) At best, no more than25% of the metabolic energy released during exercise isconverted into mechanical work outside the body, and theother 75% or more is converted into heat within the body.

Convection, Radiation, and Evaporation Are

the Main Avenues of Heat Exchange With

the Environment

Convection is the transfer of heat resulting from the move-ment of a fluid, either liquid or gas. In thermal physiology,the fluid is usually air or water in the environment or blood,in the case of heat transfer inside the body. To illustrate,consider an object immersed in a fluid that is cooler thanthe object. Heat passes from the object to the immediatelyadjacent fluid by conduction. If the fluid is stationary, con-duction is the only means by which heat can pass throughthe fluid, and over time, the rate of heat flow from the bodyto the fluid will diminish as the fluid nearest the object ap-proaches the temperature of the object. In practice, how-ever, fluids are rarely stationary. If the fluid is moving, heatwill still be carried from the object into the fluid by con-duction, but once the heat has entered the fluid, it will becarried by the movement of the fluid—by convection. Thesame fluid movement that carries heat away from the sur-face of the object constantly brings fresh cool fluid to thesurface, so the object gives up heat to the fluid much morerapidly than if the fluid were stationary. Although conduc-tion plays a role in this process, convection so dominatesthe overall heat transfer that we refer to the heat transfer asif it were entirely convection. Therefore, the conductionterm (K) in the heat balance equation is restricted to heatflow between the body and other solid objects, and it usu-ally represents only a small part of the total heat exchangewith the environment.

Every surface emits energy as electromagnetic radiation,with a power output proportional to the area of the surface,the fourth power of its absolute temperature (i.e., measuredfrom absolute zero), and the emissivity (e) of the surface, anumber between 0 and 1 that depends on the nature of thesurface and the wavelength of the radiation. (In this discus-sion, the term surface is broadly defined, so that a flame andthe sky, for example, are surfaces.) Such radiation, calledthermal radiation, has a characteristic distribution of poweras a function of wavelength, which depends on the temper-ature of the surface. The emissivity of any surface is equalto the absorptivity—the fraction of incident radiant energythe surface absorbs. (For this reason, an ideal emitter, withan emissivity of 1, is called a black body.) If two bodies ex-change heat by thermal radiation, radiation travels in bothdirections, but since each body emits radiation with an in-

tensity that depends on its temperature, the net heat flow isfrom the warmer to the cooler body.

At ordinary tissue and environmental temperatures, vir-tually all thermal radiation is in a region of the infraredrange where most surfaces, other than polished metals, haveemissivities near 1 and emit with a power output near thetheoretical maximum. However, bodies that are hot enoughto glow, such as the sun, emit large amounts of radiation inthe visible and near-infrared range, in which light-coloredsurfaces have lower emissivities and absorptivities than darkones. Therefore, colors of skin and clothing affect heat ex-change only in sunlight or bright artificial light.

When 1 g of water is converted into vapor at 30�C, itabsorbs 2,425 J (0.58 kcal), the latent heat of evaporation,in the process. Evaporation of water is, thus, an efficientway of losing heat, and it is the body’s only means of los-ing heat when the environment is hotter than the skin, asit usually is when the environment is warmer than 36�C.Evaporation must then dissipate both the heat producedby metabolic processes and any heat gained from the en-vironment by convection and radiation. Most water evap-orated in the heat comes from sweat, but even in cold tem-peratures, the skin loses some water by the evaporation ofinsensible perspiration, water that diffuses through theskin rather than being secreted. In equation 1, E is nearlyalways positive, representing heat loss from the body.However, E is negative in the rare circumstances in whichwater vapor gives up heat to the body by condensing onthe skin (as in a steam room).

Heat Exchange Is Proportional to Surface Area

and Obeys Biophysical Principles

Animals exchange heat with their environment throughboth the skin and the respiratory passages, but only the skinexchanges heat by radiation. In panting animals, respira-tory heat loss may be large and may be an important meansof achieving heat balance. In humans, however, respiratoryheat exchange is usually relatively small and (though hy-perthermic subjects may hyperventilate) is not predomi-nantly under thermoregulatory control. Therefore, we donot consider it further here.

Convective heat exchange between the skin and the en-vironment is proportional to the difference between skinand ambient air temperatures, as expressed by this equation:

C � hc � A � (sk � Ta) (2)

where A is the body surface area, sk and Ta are mean skinand ambient temperatures, and hc is the convective heattransfer coefficient.

The value of hc includes the effects of the factors otherthan temperature and surface area that influence convectiveheat exchange. For the whole body, air movement is themost important of these factors, and convective heat ex-change (and, thus, hc) varies approximately as the squareroot of the air speed, except when air movement is slight(Fig. 29.6). Other factors that affect hc include the direc-tion of air movement and the curvature of the skin surface.As the radius of curvature decreases, hc increases, so thehands and fingers are effective in convective heat exchangedisproportionately to their surface area.



Radiative heat exchange is proportional to the differ-ence between the fourth powers of the absolute tempera-tures of the skin and of the radiant environment (Tr) and tothe emissivity of the skin (esk): R ∝ esk � (sk

4 � Tr4). How-

ever, if Tr is close enough to sk that sk � Tr is much smallerthan the absolute temperature of the skin, R is nearly pro-portional to esk � (sk � Tr). Some parts of the body surface(e.g., the inner surfaces of the thighs and arms) exchangeheat by radiation with other parts of the body surface, sothe body exchanges heat with the environment as if it hadan area smaller than its actual surface area. This smallerarea, called the effective radiating surface area (Ar), de-pends on the body’s posture, and it is closest to the actualsurface area in a spread-eagle position and least in a curled-up position. Radiative heat exchange can be represented bythe equation

R � hr � esk � Ar � (T�sk � Tr) (3)

where hr is the radiant heat transfer coefficient, 6.43 W/(m2��C) at 28�C.

Evaporative heat loss from the skin to the environmentis proportional to the difference between the water vaporpressure at the skin surface and the water vapor pressure inthe ambient air. These relations are summarized as:

E � he � A � (Psk � Pa) (4)

where Psk is the water vapor pressure at the skin surface, Pa

is the ambient water vapor pressure, and he is the evapora-tive heat transfer coefficient.

Water vapor, like heat, is carried away by moving air, sogeometric factors and air movement affect E and he in thesame way they affect C and hc. If the skin is completely wet,the water vapor pressure at the skin surface is the saturationwater vapor pressure at the temperature of the skin (Fig. 29.7), and evaporative heat loss is Emax, the maximumpossible for the prevailing skin temperature and environ-mental conditions. This condition is described as:

Emax � he � A � (Psk,sat � Pa) (5)

where Psk,sat is the saturation water vapor pressure at skintemperature. When the skin is not completely wet, it is im-practical to measure Psk, the actual average water vaporpressure at the skin surface. Therefore, a coefficient calledskin wettedness (w) is defined as the ratio E/Emax, with 0 � w� 1. Skin wettedness depends on the hydration of the epi-dermis and the fraction of the skin surface that is wet. Wecan now rewrite equation 4 as:

E � he � A � w � (Psk,sat � Pa) (6)

Wettedness depends on the balance between secretionand evaporation of sweat. If secretion exceeds evaporation,sweat accumulates on the skin and spreads out to wet moreof the space between neighboring sweat glands, increasingwettedness and E; if evaporation exceeds secretion, the re-verse occurs. If sweat rate exceeds Emax, once wettednessbecomes 1, the excess sweat drips from the body, since itcannot evaporate.

Note that Pa, on which evaporation from the skin di-rectly depends, is proportional to the actual moisture con-tent in the air. By contrast, the more familiar quantity rela-tive humidity (rh) is the ratio between the actual moisturecontent in the air and the maximum moisture content pos-sible at the temperature of the air. It is important to recog-

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on air movement. This figure shows the con-vective heat transfer coefficient, hc (left), and the evaporative heattransfer coefficient, he (right) for a standing human as a functionof air speed. The convective and evaporative heat transfer coeffi-cients are related by the equation he � hc � 2.2�C/torr. The hori-zontal axis can be converted into English units by using the rela-tion 5 m/sec � 16.4 ft/sec � 11.2 miles/hr.

FIGURE 29.6

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FIGURE 29.7

nize that rh is only indirectly related to evaporation fromthe skin. For example, in a cold environment, Pa will be lowenough that sweat can easily evaporate from the skin evenif rh equals 100%, since the skin is warm and Psk,sat, whichdepends on the temperature of the skin, will be muchgreater than Pa.

Heat Storage Is a Change in the

Heat Content of the Body

The rate of heat storage is the difference between heat pro-duction and net heat loss (equation 1). (In the unusual cir-cumstances in which there is a net heat gain from the envi-ronment, such as during immersion in a hot bath, storage isthe sum of heat production and net heat gain.) It can be de-termined experimentally from simultaneous measurementsof metabolism by indirect calorimetry and heat gain or lossby direct calorimetry. Storage of heat in the tissues changestheir temperature, and the amount of heat stored is theproduct of body mass, the body’s mean specific heat, and asuitable mean body temperature (Tb). The body’s meanspecific heat depends on its composition, especially theproportion of fat, and is about 3.55 kJ/(kg��C) [0.85kcal/(kg��C)]. Empirical relations of Tb to core temperature(Tc) and T�sk, determined in calorimetric studies, depend onambient temperature, with Tb varying from 0.65 � Tc �0.35 � sk in the cold to 0.9 � Tc � 0.1 � T�sk in the heat.The shift from cold to heat in the relative weighting of Tc

and T�sk reflects the accompanying change in the thicknessof the shell (see Fig. 29.2).

HEAT DISSIPATION

Figure 29.8 shows rectal and mean skin temperatures, heatlosses, and calculated core-to-skin (shell) conductances fornude resting men and women at the end of 2-hour exposuresin a calorimeter to ambient temperatures of 23 to 36�C. Shellconductance represents the sum of heat transfer by two par-allel modes: conduction through the tissues of the shell, andconvection by the blood. It is calculated by dividing heatflow through the skin (HFsk) (i.e., total heat loss from thebody less heat loss through the respiratory tract) by the dif-ference between core and mean skin temperatures:

C � HFsk/(Tc � T�sk) (7)

where C is shell conductance and Tc and T�sk are core andmean skin temperatures.

From 23 to 28�C, conductance is minimal because theskin is vasoconstricted and its blood flow is low. The mini-mal level of conductance attainable depends largely on thethickness of the subcutaneous fat layer, and the women’sthicker layer allows them to attain a lower conductancethan men. At about 28�C, conductance begins to increase,and above 30�C, conductance continues to increase andsweating begins.

For these subjects, 28 to 30�C is the zone of ther-moneutrality, the range of comfortable environmentaltemperatures in which thermal balance is maintained with-out either shivering or sweating. In this zone, heat balanceis maintained entirely by controlling conductance and T�sk

and, thus, R and C. As equations 2 to 4 show, C, R, and E alldepend on skin temperature, which, in turn, depends partlyon skin blood flow. E depends also, through skin wetted-ness, on sweat secretion. Therefore, all these modes of heatexchange are partly under physiological control.

The Evaporation of Sweat Can

Dissipate Large Amounts of Heat

In Figure 29.8, evaporative heat loss is nearly independentof ambient temperature below 30�C and is 9 to 10 W/m2,corresponding to evaporation of about 13 to 15 g/(m2�h),of which about half is moisture lost in breathing and half is


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Heat dissipation. These graphs show the av-erage values of rectal and mean skin tempera-

tures, heat loss, and core-to-skin thermal conductance for nuderesting men and women near steady state after 2 hours at differentenvironmental temperatures in a calorimeter. (All energy ex-change quantities in this figure have been divided by body surfacearea to remove the effect of individual body size.) Total heat lossis the sum of dry heat loss, by radiation (R) and convection (C),and evaporative heat loss (E). Dry heat loss is proportional to thedifference between skin temperature and calorimeter temperatureand decreases with increasing calorimeter temperature. (Based ondata from Hardy JD, DuBois EF. Differences between men andwomen in their response to heat and cold. Proc Natl Acad Sci US A 1940;26:389–398.)

FIGURE 29.8


insensible perspiration. This evaporation occurs independ-ent of thermoregulatory control. As the ambient tempera-ture increases, the body depends more and more on theevaporation of sweat to achieve heat balance.

The two histological types of sweat glands are eccrineand apocrine. In northern Europeans, apocrine glands arefound mostly in the axilla and pigmented skin, such as thelips, but they are more widely distributed in some otherpopulations. Eccrine sweat is essentially a dilute electrolytesolution, but apocrine sweat also contains fatty material.Eccrine sweat glands, the dominant type in all human pop-ulations, are more important in human thermoregulationand number about 2,500,000. They are controlled throughpostganglionic sympathetic nerves that release acetyl-choline (ACh) rather than norepinephrine. A healthy manunacclimatized to heat can secrete up to 1.5 L/hr of sweat.Although the number of functional sweat glands is fixed be-fore the age of 3, the secretory capacity of the individualglands can change, especially with endurance exercisetraining and heat acclimatization; men well acclimatized toheat can attain peak sweat rates greater than 2.5 L/hr. Suchrates cannot be maintained, however; the maximum dailysweat output is probably about 15 L.

The sodium concentration of eccrine sweat ranges fromless than 5 to 60 mmol/L (versus 135 to 145 mmol/L inplasma). In producing sweat that is hypotonic to plasma,the glands reabsorb sodium from the sweat duct by activetransport. As sweat rate increases, the rate at which theglands reabsorb sodium increases more slowly, so thatsodium concentration in the sweat increases. The sodiumconcentration of sweat is affected also by heat acclimatiza-tion and by the action of mineralocorticoids.

Skin Circulation Is Important in Heat Transfer

Heat produced in the body must be delivered to the skinsurface to be eliminated. When skin blood flow is minimal,shell conductance is typically 5 to 9 W/�C per m2 of bodysurface. For a lean resting subject with a surface area of 1.8m2, minimal whole body conductance of 16 W/�C [i.e., 8.9W/(�C � m2) � 1.8 m2] and a metabolic heat production of80 W, the temperature difference between the core and theskin must be 5�C (i.e., 80 W � 16 W/�C) for the heat pro-duced to be conducted to the surface. In a cool environ-ment, T�sk may easily be low enough for this to occur. How-ever, in an ambient temperature of 33�C, T�sk is typicallyabout 35�C, and without an increase in conductance, coretemperature would have to rise to 40�C—a high, althoughnot yet dangerous, level—for the heat to be conducted tothe skin. If the rate of heat production were increased to480 W by moderate exercise, the temperature differencebetween core and skin would have to rise to 30�C—andcore temperature to well beyond lethal levels—to allow allthe heat produced to be conducted to the skin. In the lattercircumstances, the conductance of the shell must increasegreatly for the body to reestablish thermal balance andcontinue to regulate its temperature. This is accomplishedby increasing the skin blood flow.

Effectiveness of Skin Blood Flow in Heat Transfer. As-suming that blood on its way to the skin remains at core

temperature until it reaches the skin, reaches skin tempera-ture as it passes through the skin, and then stays at skintemperature until it returns to the core, we can compute therate of heat flow (HFb) as a result of convection by theblood as

HFb � SkBF � (Tc � Tsk) � 3.85 kJ/(L��C) (8)

where SkBF is the rate of skin blood flow, expressed in L/secrather than the usual L/min to simplify computing HF in W(i.e., J/sec); and 3.85 kJ/(L��C) [0.92 kcal/(L��C)] is the vol-ume-specific heat of blood. Conductance as a result of con-vection by the blood (Cb) is calculated as:

Cb � HFb/(Tc � Tsk) � SkBF � 3.85 kJ/(L��C) (9)

Of course, heat continues to flow by conductionthrough the tissues of the shell, so total conductance is thesum of conductance as a result of convection by the blood,plus that result from conduction through the tissues. Totalheat flow is given by

HF � (Cb � C0) � (Tc � Tsk) (10)

in which C0 is thermal conductance of the tissues when skinblood flow is minimal and, thus, is predominantly due toconduction through the tissues.

The assumptions made in deriving equation 8 are some-what artificial and represent the conditions for maximumefficiency of heat transfer by the blood. In practice, bloodexchanges heat also with the tissues through which itpasses on its way to and from the skin. Heat exchange withthese other tissues is greatest when skin blood flow is low;in such cases, heat flow to the skin may be much less thanpredicted by equation 8, as discussed further below. How-ever, equation 8 is a reasonable approximation in a warmsubject with moderate to high skin blood flow. Althoughmeasuring whole-body SkBF directly is not possible, it isbelieved to reach several liters per minute during heavy ex-ercise in the heat. The maximum obtainable is estimated tobe nearly 8 L/min. If SkBF � 1.89 L/min (0.0315 L/sec), ac-cording to equation 9, skin blood flow contributes about121 W/�C to the conductance of the shell. If conductionthrough the tissues contributes 16 W/�C, total shell con-ductance is 137 W/�C, and if Tc � 38.5�C and Tsk � 35�C,this will produce a core-to-skin heat transfer of 480 W, theheat production in our earlier example of moderate exer-cise. Therefore, even a moderate rate of skin blood flow canhave a dramatic effect on heat transfer.

When a person is not sweating, raising skin blood flowbrings skin temperature nearer to blood temperature andlowering skin blood flow brings skin temperature nearer toambient temperature. Under such conditions, the body cancontrol dry (convective and radiative) heat loss by varyingskin blood flow and, thus, skin temperature. Once sweatingbegins, skin blood flow continues to increase as the personbecomes warmer. In these conditions, however, the ten-dency of an increase in skin blood flow to warm the skin isapproximately balanced by the tendency of an increase insweating to cool the skin. Therefore, after sweating has be-gun, further increases in skin blood flow usually cause littlechange in skin temperature or dry heat exchange and serveprimarily to deliver to the skin the heat that is being removedby the evaporation of sweat. Skin blood flow and sweatingwork in tandem to dissipate heat under such conditions.

Sympathetic Control of Skin Circulation. Blood flow inhuman skin is under dual vasomotor control. In most of theskin, the vasodilation that occurs during heat exposure de-pends on sympathetic nerve signals that cause the bloodvessels to dilate, and this vasodilation can be prevented orreversed by regional nerve block. Because it depends on theaction of nerve signals, such vasodilation is sometimes re-ferred to as active vasodilation. Active vasodilation occursin almost all the skin, except in so-called acral regions—hands, feet, lips, ears, and nose. In skin areas where activevasodilation occurs, vasoconstrictor activity is minimal atthermoneutral temperatures, and active vasodilation duringheat exposure does not begin until close to the onset ofsweating. Therefore, skin blood flow in these areas is notmuch affected by small temperature changes within thethermoneutral range.

The neurotransmitter or other vasoactive substance re-sponsible for active vasodilation in human skin has notbeen identified. Active vasodilation operates in tandemwith sweating in the heat, and is impaired or absent in an-hidrotic ectodermal dysplasia, a congenital disorder inwhich sweat glands are sparse or absent. For these reasons,the existence of a mechanism linking active vasodilation tothe sweat glands has long been suspected, but never estab-lished. Earlier suggestions that active vasodilation ischolinergic or is caused by the release of bradykinin fromactivated sweat glands have not gained general acceptance.More recently, however, nerve endings containing bothACh and vasoactive peptides have been found near eccrinesweat glands in human skin, suggesting that active vasodi-lation may be mediated by a vasoactive cotransmitter thatis released along with ACh from the endings of nerves thatinnervate sweat glands.

Reflex vasoconstriction, occurring in response to coldand as part of certain nonthermal reflexes such as barore-flexes, is mediated primarily through adrenergic sympa-thetic fibers distributed widely over most of the skin. Re-ducing the flow of impulses in these nerves allows theblood vessels to dilate. In the acral regions and superficialveins (whose role in heat transfer is discussed below), vaso-constrictor fibers are the predominant vasomotor innerva-tion, and the vasodilation that occurs during heat exposureis largely a result of the withdrawal of vasoconstrictor ac-tivity. Blood flow in these skin regions is sensitive to smalltemperature changes even in the thermoneutral range, andmay be responsible for “fine-tuning” heat loss to maintainheat balance in this range.

THERMOREGULATORY CONTROL

In discussions of control systems, the words “regulation”and “regulate” have meanings distinct from those of theword “control” (see Chapter 1). The variable that a controlsystem acts to maintain within narrow limits (e.g., temper-ature) is called the regulated variable, and the quantities itcontrols to accomplish this (e.g., sweating rate, skin bloodflow, metabolic rate, and thermoregulatory behavior) arecalled controlled variables.

Humans have two distinct subsystems for regulatingbody temperature: behavioral thermoregulation and physi-ological thermoregulation. Behavioral thermoregulation—

through the use of shelter, space heating, air conditioning,and clothing—enables humans to live in the most extremeclimates in the world, but it does not provide fine controlof body heat balance. In contrast, physiological ther-moregulation is capable of fairly precise adjustments ofheat balance but is effective only within a relatively narrowrange of environmental temperatures.

Behavioral Thermoregulation Is Governed

by Thermal Sensation and Comfort

Sensory information about body temperatures is an essen-tial part of both behavioral and physiological thermoregu-lation. The distinguishing feature of behavioral thermoreg-ulation is the involvement of consciously directed efforts toregulate body temperature. Thermal discomfort providesthe necessary motivation for thermoregulatory behavior,and behavioral thermoregulation acts to reduce both thediscomfort and the physiological strain imposed by astressful thermal environment. For this reason, the zone ofthermoneutrality is characterized by both thermal comfortand the absence of shivering and sweating.

Warmth and cold on the skin are felt as either comfort-able or uncomfortable, depending on whether they de-crease or increase the physiological strain—a shower tem-perature that feels pleasant after strenuous exercise may beuncomfortably chilly on a cold winter morning. The pro-cessing of thermal information in behavioral thermoregula-tion is not as well understood as it is in physiological ther-moregulation. However, perceptions of thermal sensationand comfort respond much more quickly than core tem-perature or physiological thermoregulatory responses tochanges in environmental temperature and, thus, appear toanticipate changes in the body’s thermal state. Such an an-ticipatory feature would be advantageous, since it would re-duce the need for frequent small behavioral adjustments.

Physiological Thermoregulation Operates

Through Graded Control of Heat-Production

and Heat-Loss Responses

Familiar inanimate control systems, such as most refrigera-tors and heating and air-conditioning systems, operate atonly two levels: on and off. In a steam heating system, forexample, when the indoor temperature falls below the de-sired level, the thermostat turns on the burner under theboiler; when the temperature is restored to the desired level,the thermostat turns the burner off. Rather than operating atonly two levels, most physiological control systems producea graded response according to the size of the disturbancein the regulated variable. In many instances, changes in thecontrolled variables are proportional to displacements of theregulated variable from some threshold value; such controlsystems are called proportional control systems.

The control of heat-dissipating responses is an exampleof a proportional control system. Figure 29.9 shows how re-flex control of two heat-dissipating responses, sweating andskin blood flow, depends on body core temperature andmean skin temperature. Each response has a core tempera-ture threshold—a temperature at which the response startsto increase—and this threshold depends on mean skin tem-



perature. At any given skin temperature, the change in eachresponse is proportional to the change in core temperature,and increasing the skin temperature lowers the thresholdlevel of core temperature and increases the response at anygiven core temperature. In humans, a change of 1�C in coretemperature elicits about 9 times as great a thermoregula-tory response as a 1�C change in mean skin temperature.(Besides its effect on the reflex signals, skin temperature hasa local effect that modifies the response of the blood ves-sels and sweat glands to the reflex signal, discussed later.)

Cold stress elicits increases in metabolic heat productionthrough shivering and nonshivering thermogenesis. Shiver-ing is a rhythmic oscillating tremor of skeletal muscles. Theprimary motor center for shivering lies in the dorsomedialpart of the posterior hypothalamus and is normally inhibitedby signals of warmth from the preoptic area of the hypo-thalamus. In the cold, these inhibitory signals are with-drawn, and the primary motor center for shivering sends im-pulses down the brainstem and lateral columns of the spinalcord to anterior motor neurons. Although these impulses arenot rhythmic, they increase muscle tone, thereby increasingmetabolic rate somewhat. Once the tone exceeds a criticallevel, the contraction of one group of muscle fibers stretchesthe muscle spindles in other fiber groups in series with it,eliciting contractions from those groups of fibers via thestretch reflex, and so on; thus, the rhythmic oscillations thatcharacterize frank shivering begin.

Shivering occurs in bursts, and the “shivering pathway”is inhibited by signals from the cerebral cortex, so thatvoluntary muscular activity and attention can suppressshivering. Since the limbs are part of the shell in the cold,trunk and neck muscles are preferentially recruited for

shivering—the centralization of shivering—to help re-tain the heat produced during shivering within the bodycore; and the familiar experience of teeth chattering is oneof the earliest signs of shivering. As with heat-dissipatingresponses, the control of shivering depends on both coreand skin temperatures, but the details of its control are notprecisely understood.

The Central Nervous System Integrates Thermal

Information From the Core and the Skin

Temperature receptors in the body core and skin transmitinformation about their temperatures through afferentnerves to the brainstem and, especially, the hypothalamus,where much of the integration of temperature informationoccurs. The sensitivity of the thermoregulatory system tocore temperature enables it to adjust heat production andheat loss to resist disturbances in core temperature. Sensi-tivity to mean skin temperature lets the system respond ap-propriately to mild heat or cold exposure with little changein body core temperature, so that changes in body heat asa result of changes in environmental temperature take placealmost entirely in the peripheral tissues (see Fig. 29.2). Forexample, the skin temperature of someone who enters a hotenvironment may rise and elicit sweating even if there is nochange in core temperature. On the other hand, an increasein heat production within the body, as during exercise, elic-its the appropriate heat-dissipating responses through a risein core temperature.

Core temperature receptors involved in controllingthermoregulatory responses are unevenly distributed andare concentrated in the hypothalamus. In experimental

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Control of heat-dissipating responses. Thesegraphs show the relations of back (scapular)

sweat rate (left) and forearm blood flow (right) to core temperatureand mean skin temperatures (sk). In these experiments, core temper-ature was increased by exercise. (Left: Based on data from Sawka

FIGURE 29.9 MN, Gonzalez RR, Drolet LL, et al. Heat exchange during upper-and lower-body exercise. J Appl Physiol 1984;57:1050–1054. Right:Modified from Wenger CB, Roberts MF, Stolwijk JAJ, et al. Forearmblood flow during body temperature transients produced by leg exer-cise. J Appl Physiol 1975;38:58–63.)

mammals, temperature changes of only a few tenths of 1�Cin the anterior preoptic area of the hypothalamus elicitchanges in the thermoregulatory effector responses, andthis area contains many neurons that increase their firingrate in response to either warming or cooling. Thermal re-ceptors have been reported elsewhere in the core of labo-ratory animals, including the heart, pulmonary vessels, andspinal cord, but the thermoregulatory role of core thermalreceptors outside the CNS is unknown.

Consider what happens when some disturbance—say,an increase in metabolic heat production resulting from ex-ercise—upsets the thermal balance. Additional heat isstored in the body, and core temperature rises. The centralthermoregulatory controller receives information aboutthese changes from the thermal receptors and elicits appro-priate heat-dissipating responses. Core temperature contin-ues to rise, and these responses continue to increase untilthey are sufficient to dissipate heat as fast as it is being pro-duced, restoring heat balance and preventing further in-creases in body temperatures. In the language of controltheory, the rise in core temperature that elicits heat-dissi-pating responses sufficient to reestablish thermal balanceduring exercise is an example of a load error. A load erroris characteristic of any proportional control system that isresisting the effect of some imposed disturbance or “load.”

Although the disturbance in this example is exercise, thesame principle applies if the disturbance is a decrease inmetabolic rate or a change in the environment. However, ifthe disturbance is in the environment, most of the temper-ature change will be in the skin and shell rather than in thecore; if the disturbance produces a net loss of heat, thebody will restore heat balance by decreasing heat loss andincreasing heat production.

Relation of Controlling Signal to Thermal Integration andSet Point. Both sweating and skin blood flow depend oncore and skin temperatures in the same way, and changes inthe threshold for sweating are accompanied by similarchanges in the threshold for vasodilation. We may, there-fore, think of the central thermoregulatory controller asgenerating one thermal command signal for the control ofboth sweating and skin blood flow (Fig. 29.10). This signalis based on the information about core and skin tempera-tures that the controller receives and on the thermoregula-tory set point—the target level of core temperature, or thesetting of the body’s “thermostat.” In the operation of thethermoregulatory system, it is a reference point that deter-mines the thresholds of all of the thermoregulatory re-sponses. Shivering and thermal comfort are affected bychanges in the set point in the same way as sweating and


Hypothalamictemperature

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Control of human thermoregulatory re-

sponses. The plus and minus signs next to theinputs to Tset indicate that pyrogens raise the set point and heatacclimatization lowers it. Core temperature (Tc) is compared with

FIGURE 29.10 the set point (Tset) to generate an error signal, which is integratedwith thermal input from the skin to produce effector signals forthe thermoregulatory responses.


skin blood flow. However, our understanding of the con-trol of shivering is insufficient to say whether it is con-trolled by the same command signal as sweating and skinblood flow. (Thermal comfort, as we saw earlier, seems notto be controlled by the same command signal.)

Effect of Nonthermal Inputs on Thermoregulatory Responses. Each thermoregulatory response may be af-fected by inputs other than body temperatures and factorsthat influence the set point. We have already noted thatvoluntary activity affects shivering and certain hormonesaffect metabolic heat production. In addition, nonthermalfactors may produce a burst of sweating at the beginningof exercise, and emotional effects on sweating and skinblood flow are matters of common experience. Skin bloodflow is the thermoregulatory response most influenced bynonthermal factors because of its potential involvement inreflexes that function to maintain cardiac output, bloodpressure, and tissue O2 delivery under a variety of distur-bances, including heat stress, postural changes, hemor-rhage, and exercise.

Several Factors May Change the

Thermoregulatory Set Point

Fever elevates core temperature at rest, heat acclimatizationdecreases it, and time of day and (in women) the phase of themenstrual cycle change it in a cyclic fashion. Core tempera-ture at rest varies in an approximately sinusoidal fashion withtime of day. The minimum temperature occurs at night, sev-eral hours before awaking, and the maximum, which is 0.5 to1�C higher, occurs in the late afternoon or evening (see Fig. 29.3). This pattern coincides with patterns of activityand eating but does not depend on them, and it occurs evenduring bed rest in fasting subjects. This pattern is an exampleof a circadian rhythm, a rhythmic pattern in a physiologicalfunction with a period of about 1 day. During the menstrualcycle, core temperature is at its lowest point just before ovu-lation; during the next few days, it rises 0.5 to 1�C to aplateau that persists through most of the luteal phase. Eachof these factors—fever, heat acclimatization, the circadianrhythm, and the menstrual cycle—change the core temper-ature at rest by changing the thermoregulatory set point,producing corresponding changes in the thresholds for all ofthe thermoregulatory responses.

Peripheral Factors Modify the Responses of Skin

Blood Vessels and Sweat Glands

The skin is the organ most directly affected by environ-mental temperature. Skin temperature influences heat lossresponses not only through reflex actions (see Fig. 29.9),but also through direct effects on the skin blood vessels andsweat glands.

Skin Temperature and Cutaneous Vascular and SweatGland Responses. Local temperature changes act on skinblood vessels in at least two ways. First, local cooling poten-tiates (and heating weakens) the constriction of blood vesselsin response to nerve signals and vasoconstrictor substances.(At very low temperatures, however, cold-induced vasodila-

tion increases skin blood flow, as discussed later.) Second, inskin regions where active vasodilation occurs, local heatingcauses vasodilation (and local cooling causes vasoconstric-tion) through a direct action on the vessels, independent ofnerve signals. The local vasodilator effect of skin temperatureis especially strong above 35�C; and, when the skin is warmerthan the blood, increased blood flow helps cool the skin andprotect it from heat injury, unless this response is impaired byvascular disease. Local thermal effects on sweat glands paral-lel those on blood vessels, so local heating potentiates (andlocal cooling diminishes) the local sweat gland response to re-flex stimulation or ACh, and intense local heating elicitssweating directly, even in skin whose sympathetic innerva-tion has been interrupted surgically.

Skin Wettedness and the Sweat Gland Response. Dur-ing prolonged heat exposure (lasting several hours) withhigh sweat output, sweating rates gradually decline and theresponse of sweat glands to local cholinergic drugs is re-duced. This reduction of sweat gland responsiveness issometimes called sweat gland “fatigue.” Wetting the skinmakes the stratum corneum swell, mechanically obstruct-ing the sweat gland ducts and causing a reduction in sweatsecretion, an effect called hidromeiosis. The glands’ re-sponsiveness can be at least partly restored if air movementincreases or humidity is reduced, allowing some of thesweat on the skin to evaporate. Sweat gland fatigue may in-volve processes besides hidromeiosis, since prolongedsweating also causes histological changes, including thedepletion of glycogen, in the sweat glands.

THERMOREGULATORY RESPONSES

DURING EXERCISE

Intense exercise may increase heat production within thebody 10-fold or more, requiring large increases in skinblood flow and sweating to reestablish the body’s heat bal-ance. Although hot environments also elicit heat-dissipat-ing responses, exercise ordinarily is responsible for thegreatest demands on the thermoregulatory system for heatdissipation. Exercise provides an important example of howthe thermoregulatory system responds to a disturbance inheat balance. In addition, exercise and thermoregulationimpose competing demands on the circulatory system be-cause exercise requires large increases in blood flow to ex-ercising muscle, while the thermoregulatory responses toexercise require increases in skin blood flow. Muscle bloodflow during exercise is several times as great as skin bloodflow, but the increase in skin blood flow is responsible fordisproportionately large demands on the cardiovascularsystem, as discussed below. Finally, if the water and elec-trolytes lost through sweating are not replaced, the result-ing reduction in plasma volume will eventually create a fur-ther challenge to cardiovascular homeostasis.

Core Temperature Rises During Exercise,

Triggering Heat-Loss Responses

As previously mentioned, the increased heat production dur-ing exercise causes an increase in core temperature, which in

turn elicits heat-loss responses. Core temperature continuesto rise until heat loss has increased enough to match heat pro-duction, and core temperature and the heat-loss responsesreach new steady-state levels. Since the heat-loss responsesare proportional to the increase in core temperature, the in-crease in core temperature at steady state is proportional tothe rate of heat production and, thus, to the metabolic rate.

A change in ambient temperature causes changes in thelevels of sweating and skin blood flow necessary to maintainany given level of heat dissipation. However, the change inambient temperature also elicits, via direct and reflex effectsof the accompanying skin temperature changes, altered re-sponses in the right direction. For any given rate of heat pro-duction, there is a certain range of environmental conditionswithin which an ambient temperature change elicits the nec-essary changes in heat-dissipating responses almost entirelythrough the effects of skin temperature changes, with virtu-ally no effect on core temperature. (The limits of this rangeof environmental conditions depend on the rate of heat pro-duction and such individual factors as skin surface area andstate of heat acclimatization.) Within this range, the coretemperature reached during exercise is nearly independent ofambient temperature; for this reason, it was once believedthat the increase in core temperature during exercise iscaused by an increase in the thermoregulatory set point, asduring fever. As noted, however, the increase in core tem-perature with exercise is an example of a load error ratherthan an increase in set point.

This difference between fever and exercise is shown inFigure 29.11. Note that, although heat production may in-

crease substantially (through shivering), when core tem-perature is rising early during fever, it need not stay high tomaintain the fever; in fact, it returns nearly to prefebrile lev-els once the fever is established. During exercise, however,an increase in heat production not only causes the elevationin core temperature but is necessary to sustain it. Also,while core temperature is rising during fever, the rate ofheat loss is, if anything, lower than it was before the feverbegan. During exercise, however, the heat-dissipating re-sponses and the rate of heat loss start to increase early andcontinue increasing as core temperature rises.

Exercise in the Heat Can Threaten

Cardiovascular Homeostasis

The rise in core temperature during exercise increases thetemperature difference between the core and the skinsomewhat, but not nearly enough to match the increase inmetabolic heat production. Therefore, as we saw earlier,skin blood flow must increase to carry all of the heat that isproduced to the skin. In a warm environment, where thetemperature difference between core and skin is relativelysmall, the necessary increase in skin blood flow may be sev-eral liters per minute.

Impaired Cardiac Filling During Exercise in the Heat.The work of providing the skin blood flow required forthermoregulation in the heat may impose a heavy burdenon a diseased heart, but in healthy people, the major car-


Heat production

Heat production

Heat loss

Heat loss

Heat loss

esesSustained

errorsignalTc

Tc

Tset

Tset

Heat production

Rate ofheat storage

Correctederrorsignal

In warmenvironment

Fever

In coolenvironment

Rate ofheat storage

Time Time

A ExerciseB

Thermal events during fever and exercise.

A, The development of fever. B, The increasein core temperature (Tc) during exercise. The error signal is thedifference between core temperature (Tc) and the set point (Tset).At the start of a fever, Tset has risen, so that Tset is higher than Tc

and es is negative. At steady state, Tc has risen to equal the newlevel of Tset and es is corrected (i.e., it returns to zero.) At the

FIGURE 29.11 start of exercise, Tc � Tset, so that es � 0. At steady state, Tset hasnot changed but Tc has increased and is greater than Tset, produc-ing a sustained error signal, which is equal to the load error. (Theerror signal, or load error, is here represented with an arrow point-ing downward for Tc � Tset and with an arrow pointing upwardfor Tc � Tset.) (Modified from Stitt JT. Fever versus hyperthermia.Fed Proc 1979;38:39–43.)


diovascular burden of heat stress results from impaired ve-nous return. As skin blood flow increases, the dilated vas-cular bed of the skin becomes engorged with large volumesof blood, reducing central blood volume and cardiac filling(Fig. 29.12). Stroke volume is decreased, and a higher heartrate is required to maintain cardiac output. These effects areaggravated by a decrease in plasma volume if the largeamounts of salt and water lost in the sweat are not replaced.Since the main cation in sweat is sodium, disproportion-ately much of the body water lost in sweat is at the expenseof extracellular fluid, including plasma, although this effectis mitigated if the sweat is dilute.

Compensatory Responses During Exercise in the Heat.Several reflex adjustments help maintain cardiac filling, car-diac output, and arterial pressure during exercise and heatstress. The most important of these is constriction of the re-nal and splanchnic vascular beds. A reduction in blood flowthrough these beds allows a corresponding diversion ofcardiac output to the skin and the exercising muscles. In ad-dition, since the splanchnic vascular beds are compliant, adecrease in their blood flow reduces the amount of bloodpooled in them (see Fig. 29.12), helping compensate fordecreases in central blood volume caused by reducedplasma volume and blood pooling in the skin.

The degree of vasoconstriction is graded according tothe levels of heat stress and exercise intensity. During stren-uous exercise in the heat, renal and splanchnic blood flowsmay fall to 20% of their values in a cool resting subject.Such intense splanchnic vasoconstriction may producemild ischemic injury to the gut, helping explain the intes-tinal symptoms some athletes experience after enduranceevents. The cutaneous veins constrict during exercise; sincemost of the vascular volume is in the veins, constrictionmakes the cutaneous vascular bed less easily distensible andreduces peripheral pooling. Because of the essential role ofskin blood flow in thermoregulation during exercise andheat stress, the body preferentially compromises splanch-nic and renal flow for the sake of cardiovascular homeosta-sis. Above a certain level of cardiovascular strain, however,skin blood flow, too, is compromised.

HEAT ACCLIMATIZATION

Prolonged or repeated exposure to stressful environmentalconditions elicits significant physiological changes, calledacclimatization, that reduce the resulting strain. (Suchchanges are often referred to as acclimation when producedin a controlled experimental setting.) Some degree of heatacclimatization occurs either by heat exposure alone or byregular strenuous exercise, which raises core temperatureand provokes heat-loss responses. Indeed, the first summerheat wave produces enough heat acclimatization that mostpeople notice an improvement in their level of energy andgeneral feeling of well-being after a few days. However, theacclimatization response is greater if heat exposure and ex-ercise are combined, causing a greater rise of internal tem-perature and more profuse sweating. Evidence of acclimati-zation appears in the first few days of combined exerciseand heat exposure, and most of the improvement in heattolerance occurs within 10 days. The effect of heat ac-

climatization on performance can be dramatic, and accli-matized subjects can easily complete exercise in the heatthat earlier was difficult or impossible.

Heat Acclimatization Includes Adjustments in

Heart Rate, Temperatures, and Sweat Rate

Cardiovascular adaptations that reduce the heart rate re-quired to sustain a given level of activity in the heat appearquickly and reach nearly their full development within 1week. Changes in sweating develop more slowly. After ac-climatization, sweating begins earlier and at a lower coretemperature (i.e., the core temperature threshold for sweat-ing is reduced). The sweat glands become more sensitive tocholinergic stimulation, and a given elevation in core tem-perature elicits a higher sweat rate; in addition, the glands be-come resistant to hidromeiosis and fatigue, so higher sweatrates can be sustained. These changes reduce the levels ofcore and skin temperatures reached during a period of exer-

Cardiovascular strain and compensatory re-

sponses during heat stress. This figure firstshows the effects of skin vasodilation on peripheral pooling ofblood and the thoracic reservoirs from which the ventricles arefilled; and second, the effects of compensatory vasomotor adjust-ments in the splanchnic circulation. The valves on the right rep-resent the resistance vessels that control blood flow through theliver/splanchnic, muscle, and skin vascular beds. Arrows show thedirection of the changes during heat stress. (Modified from Row-ell LB. Cardiovascular aspects of human thermoregulation. CircRes 1983;52:367–379.)

FIGURE 29.12

cise in the heat, increase the sweat rate, and enable one to ex-ercise longer. The threshold for cutaneous vasodilation is re-duced along with the threshold for sweating, so heat transferfrom the core to the skin is maintained. The lower heart rateand core temperature and the higher sweat rate are the threeclassical signs of heat acclimatization (Fig. 29.13).

Changes in Fluid and Electrolyte Balance Also

Occur With Heat Acclimatization

During the first week, total body water and, especially,plasma volume increase. These changes likely contribute tothe cardiovascular adaptations. Later, the fluid changesseem to diminish or disappear, although the cardiovascularadaptations persist. In an unacclimatized person, sweatingoccurs mostly on the chest and back, but during acclimati-zation, especially in humid heat, the fraction of sweat se-creted on the limbs increases to make better use of the skinsurface for evaporation. An unacclimatized person who issweating profusely can lose large amounts of sodium. Withacclimatization, the sweat glands become able to conservesodium by secreting sweat with a sodium concentration aslow as 5 mmol/L. This effect is mediated through aldos-terone, which is secreted in response to sodium depletionand to exercise and heat exposure. The sweat glands re-spond to aldosterone more slowly than the kidneys, requir-ing several days; unlike the kidneys, the sweat glands donot escape the influence of aldosterone when sodium bal-ance has been restored, but continue to conserve sodiumfor as long as acclimatization persists.

The cell membranes are freely permeable to water, sothat any osmotic imbalance between the intracellular andextracellular compartments is rapidly corrected by themovement of water across the cell membranes (see Chapter

2). One important consequence of the salt-conserving re-sponse of the sweat glands is that the loss of a given volumeof sweat causes a smaller decrease in the volume of the ex-tracellular space than if the sodium concentration of thesweat is high (Table 29.3). Other consequences are dis-cussed in Clinical Focus Box 29.1.

Heat acclimatization is transient, disappearing in a fewweeks if not maintained by repeated heat exposure. Thecomponents of heat acclimatization are lost in the order inwhich they were acquired; the cardiovascular changes de-cay more quickly than the reduction in exercise core tem-perature and sweating changes.

RESPONSES TO COLD

The body maintains core temperature in the cold by mini-mizing heat loss and, when this response is insufficient, in-creasing heat production. Reducing shell conductance isthe chief physiological means of heat conservation in hu-mans. Furred or hairy animals also can increase the thick-ness of their coat and, thus, its insulating properties bymaking the hairs stand on end. This response, called pilo-erection, makes a negligible contribution to heat conserva-tion in humans, but manifests itself as gooseflesh.

Blood Vessels in the Shell Constrict

to Conserve Heat

The constriction of cutaneous arterioles reduces skin bloodflow and shell conductance. Constriction of the superficiallimb veins further improves heat conservation by divertingvenous blood to the deep limb veins, which lie close to themajor arteries of the limbs and do not constrict in the cold.


37

38

39 140

120

100

80

60

40

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18040R

ecta

l tem

pera

ture

(°C

)

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rt r

ate

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ts/m

in)

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eat r

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r)

0 1 2 3 0 1 2 3 0 1 2 3 444

AcclimatizedUnacclimatized

Time in exercise (hr) Time in exercise (hr)Time in exercise (hr)

Heat acclimatization. These graphs show rec-tal temperatures, heart rates, and sweat rates

during 4 hours’ exercise (bench stepping, 35 W mechanicalpower) in humid heat (33.9�C dry bulb, 89% relative humidity,35 torr ambient vapor pressure) on the first and last days of a 2-week program of acclimatizaton to humid heat. (Modified from

FIGURE 29.13 Wenger CB. Human heat acclimatization. In: Pandolf KB, SawkaMN, Gonzalez RR, eds. Human Performance Physiology and En-vironmental Medicine at Terrestrial Extremes. Indianapolis:Benchmark, 1988;153–197. Based on data from Wyndham CH,Strydom NB, Morrison JF, et al. Heat reactions of Caucasians andBantu in South Africa. J Appl Physiol 1964;19:598–606.)

CLINICAL FOCUS BOX 29.1

Water and Salt Depletion as a Result of Sweating

Changes in fluid and electrolyte balance are probably themost frequent physiological disturbances associated withsustained exercise and heat stress. Water loss via thesweat glands can exceed 1 L/hr for many hours. Salt loss inthe sweat is variable; however, since sweat is more dilutethan plasma, sweating always results in an increase in theosmolality of the fluid remaining in the body, and in-creased plasma [Na�] and [Cl�], as long as the lost water isnot replaced.

Because people who secrete large volumes of sweatusually replace at least some of their losses by drinkingwater or electrolyte solutions, the final effect on body flu-ids may vary. In Table 29.3, the second and third condi-tions (subject A) represent the effects on body fluids ofsweat losses alone and combined with replacement by anequal volume of plain water, respectively, for someoneproducing sweat with a [Na�] and [Cl�] in the upper part ofthe normal range. By contrast, the fourth and fifth condi-tions (subject B) represent the corresponding effects for aheat-acclimatized person secreting dilute sweat. Compar-ing the effects on these two individuals, we note: (1) Themore dilute the sweat that is secreted, the greater the in-crease in osmolality and plasma [Na�] if no fluid is re-placed; (2) Extracellular fluid volume, a major determinantof plasma volume (see Chapter 18), is greater in subject B(secreting dilute sweat) than in subject A (secreting saltiersweat), whether or not water is replaced; and (3) Drinkingplain water allowed subject B to maintain plasma sodiumand extracellular fluid volume almost unchanged while se-creting 5 L of sweat. In subject A, however, drinking thesame amount of water reduced plasma [Na�] by 8 mmol/L,and failed to prevent a decrease of almost 10% in extracel-lular fluid volume. In 5 L of sweat, subject A lost 17.5 g of

salt, somewhat more than the daily salt intake in a normalWestern diet, and he is becoming salt-depleted.

Thirst is stimulated by increased osmolality of the extra-cellular fluid, and by decreased plasma volume via a reduc-tion in the activity of the cardiovascular stretch receptors(see Chapter 18). When sweating is profuse, however, thirstusually does not elicit enough drinking to replace fluid asrapidly as it is lost, so that people exercising in the heat tendto become progressively dehydrated—in some cases losingas much as 7 to 8% of body weight—and restore normalfluid balance only during long periods of rest or at meals.Depending on how much of his fluid losses he replaces,subject B may either be hypernatremic and dehydrated orbe in essentially normal fluid and electrolyte balance. (If hedrinks fluid well in excess of his losses, he may becomeoverhydrated and hyponatremic, but this is an unlikely oc-currence.) However, subject A, who is somewhat salt de-pleted, may be very dehydrated and hypernatremic, nor-mally hydrated but hyponatremic, or somewhat dehydratedwith plasma [Na�] anywhere in between these two ex-tremes. Once subject A replaces all the water lost as sweat,his extracellular fluid volume will be about 10% below its ini-tial value. If he responds to the accompanying reduction inplasma volume by continuing to drink water, he will be-come even more hyponatremic than shown in Table 29.3.

The disturbances shown in Table 29.3, while physiolog-ically significant and useful for illustration, are not likely torequire clinical attention. Greater disturbances, with corre-spondingly more severe clinical effects, may occur. Theconsequences of the various possible disturbances of saltand water balance can be grouped as effects of decreasedplasma volume secondary to decreased extracellular fluidvolume, effects of hypernatremia, and effects of hypona-tremia.

(continued)

TABLE 29.3 Effect of Sweat Secretion on Body Fluid Compartments and Plasma Sodium Concentrationa

Extracellular Space Intracellular Space Total Body Water

Osmotic Osmotic Osmotic PlasmaVolume Content Volume Content Volume Content Osmolality [Na�]

Subject Condition (L) (mOsm) (L) (mOsm) (L) (mOsm) (mOsm/kg) (mmol/L)

Initial 15 4,350 25 7,250 40 11,600 290 140A Loss of 5 L of 11.9 3,750 23.1 7,250 35 11,000 314 151

sweat, 120mOsm/L, 60mmol Na�/L

Above condition 13.6 3,750 26.4 7,250 40 11,000 275 132accompanied byintake of 5 Lwater

B Loss of 5 L of 12.9 4,250 22.1 7,250 35 11,500 329 159sweat, 20mOsm/L, 10mmol Na�/L

Above condition 14.8 4,250 25.2 7,250 40 11,500 288 139accompanied byintake of 5 Lwater

a Each subject has total body water of 40 L. The sweat of subject A has a relatively high [Na�] of 60 mmol/L while that of subject B has a relatively low[Na�] of 10 mmol/L. Volumes of the extracellular and intracellular spaces are calculated assuming that water moves between the two spaces as neededto maintain osmotic balance.

(Many penetrating veins connect the superficial veins tothe deep veins, so that venous blood from anywhere in thelimb potentially can return to the heart via either superficialor deep veins.) In the deep veins, cool venous blood re-turning to the core can take up heat from the warm bloodin the adjacent deep limb arteries. Therefore, some of theheat contained in the arterial blood as it enters the limbstakes a “short circuit” back to the core. When the arterialblood reaches the skin, it is already cooler than the core, soit loses less heat to the skin than it otherwise would. (Whenthe superficial veins dilate in the heat, most venous bloodreturns via superficial veins so as to maximize core-to-skinheat flow.) The transfer of heat from arteries to veins bythis short circuit is called countercurrent heat exchange.This mechanism can cool the blood in the radial artery of acool but comfortable subject to as low as 30�C by the timeit reaches the wrist.

As we saw earlier, the shell’s insulating properties increasein the cold as its blood vessels constrict and its thickness in-creases. Furthermore, the shell includes a fair amount ofskeletal muscle in the cold, and although muscle blood flowis believed not to be affected by thermoregulatory reflexes, itis reduced by direct cooling. In a cool subject, the resultingreduction in muscle blood flow adds to the shell’s insulating

properties. As the blood vessels in the shell constrict, bloodis shifted to the central blood reservoir in the thorax. Thisshift produces many of the same effects as an increase inblood volume, including so-called cold diuresis as the kid-neys respond to the increased central blood volume.

Once skin blood flow is near minimal, metabolic heatproduction increases—almost entirely through shiveringin human adults. Shivering may increase metabolism at restby more than 4-fold—that is, to 350 to 400 W. Althoughit is often stated that shivering diminishes substantially af-ter several hours and is impaired by exhaustive exercise,such effects are not well understood. In most laboratorymammals, chronic cold exposure also causes nonshiveringthermogenesis, an increase in metabolic rate that is notdue to muscle activity. Nonshivering thermogenesis ap-pears to be elicited through sympathetic stimulation andcirculating catecholamines. It occurs in many tissues, espe-cially the liver and brown fat, a tissue specialized for non-shivering thermogenesis whose color is imparted by highconcentrations of iron-containing respiratory enzymes.Brown fat is found in human infants, and nonshiveringthermogenesis is important for their thermoregulation.The existence of brown fat and nonshivering thermogene-sis in human adults is controversial, but there is some evi-


The circulatory effects of decreased volume arenearly identical to the effects of peripheral pooling ofblood (see Fig. 29.12), and the combined effects of pe-ripheral pooling and decreased volume will be greaterthan the effects of either alone. These effects include im-pairment of cardiac filling and cardiac output, and com-pensatory reflex reductions in renal, splanchnic, andskin blood flow. Impaired cardiac output leads to fatigueduring exertion and decreased exercise tolerance; if skinblood flow is reduced, heat dissipation will be impaired.Exertional rhabdomyolysis, the injury of skeletal mus-cle fibers, is a frequent result of unaccustomed intenseexercise. Myoglobin released from injured skeletal mus-cle cells appears in the plasma, rapidly enters theglomerular filtrate, and is excreted in the urine, produc-ing myoglobinuria and staining the urine brown ifenough myoglobin is present. This process may beharmless to the kidneys if urine flow is adequate; how-ever, a reduction in renal blood flow reduces urine flow,increasing the likelihood that the myoglobin will causerenal tubular injury.

Hypernatremic dehydration is believed to predis-pose to heatstroke. Dehydration is often accompanied byboth hypernatremia and reduced plasma volume. Hyper-natremia impairs the heat-loss responses (sweating andincreased skin blood flow) independently of any accompa-nying reduction in plasma volume and elevates the ther-moregulatory set point. Hypernatremic dehydration pro-motes the development of high core temperature inmultiple ways through the combination of hypernatremiaand reduced plasma volume.

Even in the absence of sodium loss, overdrinking thatexceeds the kidneys’ ability to compensate dilutes all thebody’s fluid compartments, producing dilutional hy-ponatremia, which is also called water intoxication if it

causes symptoms. The development of water intoxicationrequires either massive overdrinking, or a condition, suchas the inappropriate secretion of arginine vasopressin, thatimpairs the excretion of free water by the kidneys. Over-drinking sufficient to cause hyponatremia may occur in pa-tients with psychiatric disorders or disturbance of the thirstmechanism, or may be done with a mistaken intention ofpreventing or treating dehydration. However, individualswho secrete copious amounts of sweat with a high sodiumconcentration, like subject A or people with cystic fibrosis,may easily lose enough salt to become hyponatremic be-cause of sodium loss. Some healthy young adults whocome to medical attention for salt depletion after profusesweating are found to have genetic variants of cystic fibro-sis, which cause these individuals to have salty sweat with-out producing the characteristic digestive and pulmonarymanifestations of cystic fibrosis.

As sodium concentration and osmolality of the extra-cellular space decrease, water moves from the extracellu-lar space into the cells to maintain osmotic balance acrossthe cell membranes. Most of the manifestations of hy-ponatremia are due to the resulting swelling of the braincells. Mild hyponatremia is characterized by nonspecificsymptoms such as fatigue, confusion, nausea, andheadache, and may be mistaken for heat exhaustion. Se-vere hyponatremia can be a life-threatening medical emer-gency and may include seizures, coma, herniation of thebrainstem (which occurs if the brain swells enough to ex-ceed the capacity of the cranium) and death. In the settingof prolonged exertion in the heat, symptomatic hypona-tremia is far less common than heat exhaustion, but po-tentially far more dangerous. Therefore, it is important notto treat a presumed case of heat exhaustion with largeamounts of low-sodium fluids without first ruling out hy-ponatremia.


dence for functioning brown fat in the neck and medi-astinum of outdoor workers.

Human Cold Acclimatization Confers a

Modest Thermoregulatory Advantage

The pattern of human cold acclimatization depends on thenature of the cold exposure. It is partly for this reason thatthe occurrence of cold acclimatization in humans was con-troversial for a long time. Our knowledge of human coldacclimatization comes from both laboratory studies andstudies of populations whose occupation or way of life ex-poses them repeatedly to cold temperatures.

Metabolic Changes in Cold Acclimatization. At one timeit was believed that humans must acclimatize to cold as lab-oratory mammals do—by increasing their metabolic rate.There are a few reports of increased basal metabolic rateand, sometimes, thyroid activity in the winter. More often,however, increased metabolic rate has not been observed instudies of human cold acclimatization. In fact, several re-ports indicate the opposite response, consisting of a lowercore temperature threshold for shivering, with a greater fallin core temperature and a smaller metabolic response dur-ing cold exposure. Such a response would spare metabolicenergy and might be advantageous in an environment thatis not so cold that a blunted metabolic response would al-low core temperature to fall to dangerous levels.

Increased Tissue Insulation in Cold Acclimatization. Alower core-to-skin conductance (i.e., increased insulationby the shell) has often been reported in studies of cold ac-climatization in which a reduction in the metabolic re-sponse to cold occurred. This increased insulation is notdue to subcutaneous fat (in fact, it has been observed invery lean subjects), but apparently results from lower bloodflow in the limbs or improved countercurrent heat ex-change in the acclimatized subjects. In general, the coldstresses that elicit a lower shell conductance after acclima-tization involve either cold water immersion or exposure toair that is chilly but not so cold as to risk freezing the vaso-constricted extremities.

Cold-Induced Vasodilation and the Lewis Hunting Re-sponse. As the skin is cooled below about 15�C, its bloodflow begins to increase somewhat, a response called cold-induced vasodilation (CIVD). This response is elicitedmost easily in comfortably warm subjects and in skin rich inarteriovenous anastomoses (in the hands and feet). Themechanism has not been established but may involve a di-rect inhibitory effect of cold on the contraction of vascularsmooth muscle or on neuromuscular transmission. TheCIVD response varies greatly among individuals, and isusually rudimentary in hands and feet unaccustomed tocold exposure. After repeated cold exposure, CIVD beginsearlier during cold exposure, produces higher levels ofblood flow, and takes on a rhythmic pattern of alternatingvasodilation and vasoconstriction. This is called the Lewishunting response because the rhythmic pattern of bloodflow suggests that it is “hunting” for its proper level. This re-sponse is often well developed in workers whose hands are

exposed to cold, such as fishermen working with nets incold water. Since the Lewis hunting response increases heatloss from the body somewhat, whether or not it is truly anexample of acclimatization to cold is debatable. However,the response is advantageous because it keeps the extremi-ties warmer, more comfortable, and functional and proba-bly protects them from cold injury.

CLINICAL ASPECTS OF THERMOREGULATION

Temperature is important clinically because of the presenceof fever in many diseases, the effects of many factors on tol-erance to heat or cold stress, and the effects of heat or coldstress in causing or aggravating certain disorders.

Fever Enhances Defense Mechanisms

Fever may be caused by infection or noninfectious condi-tions (e.g., inflammatory processes such as collagen vasculardiseases, trauma, neoplasms, acute hemolysis, immunologi-cally-mediated disorders). Pyrogens are substances thatcause fever and may be either exogenous or endogenous.Exogenous pyrogens are derived from outside the body;most are microbial products, microbial toxins, or whole mi-croorganisms. The best studied of these is the lipopolysac-charide endotoxin of gram-negative bacteria. Exogenouspyrogens stimulate a variety of cells, especially monocytesand macrophages, to release endogenous pyrogens,polypeptides that cause the thermoreceptors in the hypo-thalamus (and perhaps elsewhere in the brain) to alter theirfiring rate and input to the central thermoregulatory con-troller, raising the thermoregulatory set point. This effect ofendogenous pyrogens is mediated by the local synthesis andrelease of prostaglandin E2. Aspirin and other drugs that in-hibit the synthesis of prostaglandins also reduce fever.

Fever accompanies disease so frequently and is such a re-liable indicator of the presence of disease that body tem-perature is probably the most commonly measured clinicalindex. Many of the body’s defenses against infection andcancer are elicited by a group of polypeptides called cy-tokines; the endogenous pyrogen is usually a member ofthis group, interleukin-1. However, other cytokines, par-ticularly tumor necrosis factor, interleukin-6, and the in-terferons, are also pyrogenic in certain circumstances. Ele-vated body temperature enhances the development ofthese defenses. If laboratory animals are prevented from de-veloping a fever during experimentally induced infection,survival rates may be dramatically reduced. (Although, inthis chapter, fever specifically means an elevation in coretemperature a resulting from pyrogens, some authors usethe term more generally to mean any significant elevationof core temperature.)

Many Factors Affect Thermoregulatory Responses

and Tolerance to Heat and Cold

Regular physical exercise and heat acclimatization increaseheat tolerance and the sensitivity of the sweating response.Aging has the opposite effect; in healthy 65-year-old men,the sensitivity of the sweating response is half of that in 25-

year-old men. Many drugs inhibit sweating, most obvi-ously those used for their anticholinergic effects, such asatropine and scopolamine. In addition, some drugs used forother purposes, such as glutethimide (a sleep-inducingdrug), tricyclic antidepressants, phenothiazines (tranquil-izers and antipsychotic drugs), and antihistamines, alsohave some anticholinergic action. All of these and severalothers have been associated with heatstroke. Congestiveheart failure and certain skin diseases (e.g., ichthyosis andanhidrotic ectodermal dysplasia) impair sweating, and inpatients with these diseases, heat exposure and especiallyexercise in the heat may raise body temperature to danger-ous levels. Lesions that affect the thermoregulatory struc-tures in the brainstem can also alter thermoregulation.Such lesions can produce hypothermia (abnormally lowcore temperature) if they impair heat-conserving re-sponses. However, hyperthermia (abnormally high coretemperature) is a more usual result of brainstem lesions andis typically characterized by a loss of both sweating and thecircadian rhythm of core temperature.

Certain drugs, such as barbiturates, alcohol, and phe-nothiazines, and certain diseases, such as hypothyroidism,hypopituitarism, congestive heart failure, and septicemia,may impair the defense against cold. (Septicemia, espe-cially in debilitated patients, may be accompanied by hy-pothermia, instead of the usual febrile response to infec-tion.) Furthermore, newborns and many healthy olderadults are less able than older children and younger adultsto maintain adequate body temperature in the cold. Thisfailing appears to be due to an impaired ability to conservebody heat by reducing heat loss and to increase metabolicheat production in the cold.

Heat Stress Causes or Aggravates

Several Disorders

The harmful effects of heat stress are exerted through car-diovascular strain, fluid and electrolyte loss and, especiallyin heatstroke, tissue injury whose mechanism is uncertain.In a patient suspected of having hyperthermia secondary toheat stress, temperature should be measured in the rectum,since hyperventilation may render oral temperature spuri-ously low.

Heat Syncope. Heat syncope is circulatory failure result-ing from a pooling of blood in the peripheral veins, with aconsequent decrease in venous return and diastolic fillingof the heart, resulting in decreased cardiac output and a fallof arterial pressure. Symptoms range from light-headednessand giddiness to loss of consciousness. Thermoregulatoryresponses are intact, so core temperature typically is notsubstantially elevated, and the skin is wet and cool. Thelarge thermoregulatory increase in skin blood flow in theheat is probably the primary cause of the peripheral pool-ing. Heat syncope affects mostly those who are not accli-matized to heat, presumably because the plasma-volumeexpansion that accompanies acclimatization compensatesfor the peripheral pooling of blood. Treatment consists inlaying the patient down out of the heat, to reduce the pe-ripheral pooling of blood and improve the diastolic fillingof the heart.

Heat Exhaustion. Heat exhaustion, also called heat col-lapse, is probably the most common heat disorder, and rep-resents a failure of cardiovascular homeostasis in a hot en-vironment. Collapse may occur either at rest or duringexercise, and may be preceded by weakness or faintness,confusion, anxiety, ataxia, vertigo, headache, and nausea orvomiting. The patient has dilated pupils and usually sweatsprofusely. As in heat syncope, reduced diastolic filling ofthe heart appears to have a primary role in the pathogene-sis of heat exhaustion. Although blood pressure may be lowduring the acute phase of heat exhaustion, the baroreflexresponses are usually sufficient to maintain consciousnessand may be manifested in nausea, vomiting, pallor, cool oreven clammy skin, and rapid pulse. Patients with heat ex-haustion usually respond well to rest in a cool environmentand oral fluid replacement. In more severe cases, however,intravenous replacement of fluid and salt may be required.Core temperature may be normal or only mildly elevated inheat exhaustion. However, heat exhaustion accompaniedby hyperthermia and dehydration may lead to heatstroke.Therefore, patients should be actively cooled if rectal tem-perature is 40.6�C (105�F) or higher.

The reasons underlying the reduced diastolic filling inheat exhaustion are not fully understood. Hypovolemiacontributes if the patient is dehydrated, but heat exhaustionoften occurs without significant dehydration. In rats heatedto the point of collapse, compensatory splanchnic vaso-constriction develops during the early part of heating, butis reversed shortly before the maintenance of blood pres-sure fails. A similar process may occur in heat exhaustion.

Heatstroke. The most severe and dangerous heat disorderis characterized by high core temperature and the develop-ment of serious neurological disturbances with a loss ofconsciousness and, frequently, convulsions. Heatstroke oc-curs in two forms, classical and exertional. In the classicalform, the primary factor is environmental heat stress thatoverwhelms an impaired thermoregulatory system, andmost patients have preexisting chronic disease. In exer-tional heatstroke, the primary factor is high metabolic heatproduction. Patients with exertional heatstroke tend to beyounger and more physically fit (typically, soldiers and ath-letes) than patients with the classical form. Rhabdomyoly-sis, hepatic and renal injury, and disturbances of blood clot-ting are frequent accompaniments of exertional heatstroke.The traditional diagnostic criteria of heatstroke—coma,hot dry skin, and rectal temperature above 41.3�C(106�F)—are characteristic of the classical form; however,patients with exertional heatstroke may have somewhatlower rectal temperatures and often sweat profusely. Heat-stroke is a medical emergency, and prompt appropriatetreatment is critically important to reducing morbidity andmortality. The rapid lowering of core temperature is thecornerstone of treatment, and it is most effectively accom-plished by immersion in cold water. With prompt cooling,vigorous hydration, maintenance of a proper airway, avoid-ance of aspiration, and appropriate treatment of complica-tions, most patients will survive, especially if they werepreviously healthy.

The pathogenesis of heatstroke is not well understood,but it seems clear that factors other than hyperthermia are



involved, even if the action of these other factors partly de-pends on the hyperthermia. Exercise may contribute moreto the pathogenesis than simply metabolic heat production.Elevated plasma levels of several inflammatory cytokineshave been reported in patients presenting with heatstroke,suggesting a systemic inflammatory component. No triggerfor such an inflammatory process has been established, al-though several possible candidates exist. One possible trig-ger is some product(s) of the bacterial flora in the gut, per-haps including lipopolysaccharide endotoxins. Severallines of evidence suggest that sustained splanchnic vaso-constriction may produce a degree of intestinal ischemiasufficient to allow these products to “leak” into the circula-tion and activate inflammatory responses.

The preceding diagnostic categories are traditional.However, they are not entirely satisfactory for heat illness as-sociated with exercise because many patients have labora-tory evidence of tissue and cellular injury, but are classified ashaving heat exhaustion because they do not have the seriousneurological disturbances that characterize heatstroke. Somemore recent literature uses the term exertional heat injuryfor such cases. The boundaries of exertional heat injury, withheat exhaustion on one hand and heatstroke on the other, arenot clearly and consistently defined, and these categoriesprobably represent parts of a continuum.

Malignant hyperthermia, a rare process triggered by de-polarizing neuromuscular blocking agents or certain in-halational anesthetics, was once thought to be a form of

CLINICAL FOCUS BOX 29.2

Hypothermia

Hypothermia is classified according to the patient’s coretemperature as mild (32 to 35�C), moderate (28 to 32�C), orsevere (below 28�C). Shivering is usually prominent in mildhypothermia, but diminishes in moderate hypothermiaand is absent in severe hypothermia. The pathophysiologyis characterized chiefly by the depressant effect of cold (viathe Q10 effect) on multiple physiological processes and dif-ferences in the degree of depression of each process.

Other than shivering, the most prominent features ofmild and moderate hypothermia are due to depression ofthe central nervous system. Beginning with mood changes(commonly, apathy, withdrawal, and irritability), theyprogress to confusion and lethargy, followed by ataxia andspeech and gait disturbances, which may mimic a cere-brovascular accident (stroke). In severe hypothermia, vol-untary movement, reflexes, and consciousness are lostand muscular rigidity appears. Cardiac output and respira-tion decrease as core temperature falls. Myocardial irri-tability increases in severe hypothermia, causing a sub-stantial danger of ventricular fibrillation, with the riskincreasing as cardiac temperature falls. The primary mech-anism presumably is that cold depresses conduction ve-locity in Purkinje fibers more than in ventricular muscle, fa-voring the development of circus-movement propagationof action potentials. Myocardial hypoxia also contributes.In more profound hypothermia, cardiac sounds become in-audible and pulse and blood pressure are unobtainable be-cause of circulatory depression; the electrical activity of theheart and brain becomes unmeasurable; and extensivemuscular rigidity may mimic rigor mortis. The patientmay appear clinically dead, but patients have been revivedfrom core temperatures as low as 17�C, so that “no one isdead until warm and dead.” The usual causes of death dur-ing hypothermia are respiratory cessation and the failureof cardiac pumping, because of either ventricular fibrilla-tion or direct depression of cardiac contraction.

Depression of renal tubular metabolism by cold impairsthe reabsorption of sodium, causing a diuresis and leadingto dehydration and hypovolemia. Acid-base disturbancesin hypothermia are complex. Respiration and cardiac out-put typically are depressed more than metabolic rate, anda mixed respiratory and metabolic acidosis results, be-cause of CO2 retention and lactic acid accumulation and

the cold-induced shift of the hemoglobin-O2 dissociationcurve to the left. Acidosis aggravates the susceptibility toventricular fibrillation.

Treatment consists of preventing further cooling andrestoring fluid, acid-base, and electrolyte balance. Patientsin mild to moderate hypothermia may be warmed solelyby providing abundant insulation to promote the retentionof metabolically produced heat; those who are more se-verely affected require active rewarming. The most seriouscomplication associated with treating hypothermia is thedevelopment of ventricular fibrillation. Vigorous handlingof the patient may trigger this process, but an increase inthe patient’s circulation (e.g., associated with warming orskeletal muscle activity) may itself increase the suscepti-bility to such an occurrence, as follows. Peripheral tissuesof a hypothermic patient are, in general, even cooler thanthe core, including the heart, and acid products of anaero-bic metabolism will have accumulated in underperfusedtissues while the circulation was most depressed. As thecirculation increases, a large increase in blood flowthrough cold, acidotic peripheral tissue may return enoughcold, acidic blood to the heart to cause a transient drop inthe temperature and pH of the heart, increasing its suscep-tibility to ventricular fibrillation.

The diagnosis of hypothermia is usually straightfor-ward in a patient rescued from the cold but may be far lessclear in a patient in whom hypothermia is the result of a se-rious impairment of physiological and behavioral defensesagainst cold. A typical example is the older person, livingalone, who is discovered at home, cool and obtunded orunconscious. The setting may not particularly suggest hy-pothermia, and when the patient comes to medical atten-tion, the diagnosis may easily be missed because standardclinical thermometers are not graduated low enough (usu-ally only to 34.4�C) to detect hypothermia and, in any case,do not register temperatures below the level to which themercury has been shaken. Because of the depressant ef-fect of hypothermia on the brain, the patient’s conditionmay be misdiagnosed as cerebrovascular accident or otherprimary neurological disease. Recognition of this condi-tion depends on the physician’s considering it when ex-amining a cool patient whose mental status is impairedand obtaining a true core temperature with a low-readingglass thermometer or other device.

heatstroke but is now known to be a distinct disorder thatoccurs in people with a genetic predisposition. In 90% ofsusceptible individuals, biopsied skeletal muscle tissue con-tracts on exposure to caffeine or halothane in concentra-tions having little effect on normal muscle. Susceptibilitymay be associated with any of several myopathies, but mostsusceptible individuals have no other clinical manifesta-tions. The control of free (unbound) calcium ion concen-tration in skeletal muscle cytoplasm is severely impaired insusceptible individuals; and when an attack is triggered,calcium concentration rises abnormally, activating myosinATPase and leading to an uncontrolled hypermetabolicprocess that rapidly increases core temperature. Treatmentwith dantrolene sodium, which appears to act by reducingthe release of calcium ions from the sarcoplasmic reticulum,has dramatically reduced the mortality rate of this disorder.

Aggravation of Disease States by Heat Exposure. Otherthan producing specific disorders, heat exposure aggravatesseveral other diseases. Epidemiological studies show thatduring unusually hot weather, mortality may be 2 to 3 timesthat normally expected for the months in which heat wavesoccur. Deaths ascribed to specific heat disorders accountfor only a small fraction of the excess mortality (i.e., the in-crease above the expected mortality). Most of the excessmortality is accounted for by deaths from diabetes, variousdiseases of the cardiovascular system, and diseases of theblood-forming organs.

Hypothermia Occurs When the Body’s Defenses

Against Cold Are Disabled or Overwhelmed

Hypothermia reduces metabolic rate via the Q10 effect andprolongs the time tissues can safely tolerate a loss of bloodflow. Since the brain is damaged by ischemia soon after cir-culatory arrest, controlled hypothermia is often used toprotect the brain during surgical procedures in which itscirculation is occluded or the heart is stopped. Much of ourknowledge about the physiological effects of hypothermiacomes from observations of surgical patients.

During the initial phases of cooling, stimulation of shiv-ering through thermoregulatory reflexes overwhelms theQ10 effect. Metabolic rate, therefore, increases, reaching apeak at a core temperature of 30 to 33�C. At lower coretemperatures, however, metabolic rate is dominated by theQ10 effect, and thermoregulation is lost. A vicious circle de-velops, wherein a fall in core temperature depresses metab-olism and allows core temperature to fall further, so that at17�C, the O2 consumption is about 15%, and cardiac out-put 10%, of precooling values.

Hypothermia that is not induced for therapeutic pur-poses is called accidental hypothermia (Clinical Focus Box29.2). It occurs in individuals whose defenses are impairedby drugs (especially ethanol, in the United States), disease,or other physical conditions and in healthy individuals whoare immersed in cold water or become exhausted workingor playing in the cold.


DIRECTIONS: Each of the numbereditems or incomplete statements in thissection is followed by answers or bycompletions of the statement. Select theONE lettered answer or completion that isBEST in each case.

1. Antipyretics such as aspirin effectivelylower core temperature during fever,but they are not used to counteract theincrease in core temperature thatoccurs during exercise. Which of thefollowing best explains why it isinappropriate to use antipyretics forthis purpose?(A) The increase in core temperatureduring exercise stimulates metabolismvia the Q10 effect, helping to supportthe body’s increased metabolic energydemands(B) A moderate increase in coretemperature during exercise isharmless, so there is no benefit inpreventing it(C) Antipyretics are ineffective duringexercise because they act on amechanism that operates during fever,but not to a significant degree duringexercise

(D) Antipyretics increase skin bloodflow so as to dissipate more heat,increasing circulatory strain duringexercise(E) The increased heat productionduring exercise greatly exceeds theability of antipyretics to stimulate theresponses for heat loss

2. A surgical sympathectomy hascompletely interrupted thesympathetic nerve supply to a patient’sarm. How would one expect thethermoregulatory skin blood flow andsweating responses on that arm to beaffected?

Vasoconstriction Vasodilation in the Cold in the Heat Sweating(A) Abolished Intact Intact(B) Abolished Intact Abolished(C) Abolished Abolished Intact(D) Abolished Abolished Abolished(E) Intact Abolished Abolished3. A person resting in a constant ambient

temperature is tested in the earlymorning at 4:00 AM, and again in theafternoon at 4:00 PM. Compared tomeasurements made in the morning,one would expect to find in theafternoon:

Threshold forCore Sweating CutaneousTemperature Threshold Vasodilation

(A) Unchanged Higher Lower(B) Unchanged Unchanged Unchanged(C) Higher Higher Higher(D) Higher Unchanged Lower(E) Lower Lower Lower4. Compared to an unacclimatized

person, one who is acclimatized tocold has(A) Higher metabolic rate in the cold,to produce more heat(B) Lower metabolic rate in the cold,to conserve metabolic energy(C) Lower peripheral blood flow in thecold, to retain heat(D) Higher blood flow in the handsand feet in the cold, to preserve theirfunction(E) Various combinations of the above,depending on the environment thatproduced acclimatization

5. Which statement best describes howthe elevated core temperature duringfever affects the outcome of mostbacterial infections?(A) Fever benefits the patient becausemost pathogens thrive best at thehost’s normal body temperature

R E V I E W Q U E S T I O N S

(continued)


(B) Fever is beneficial because it helpsstimulate the immune defenses againstinfection(C) Fever is harmful because theaccompanying protein catabolismreduces the availability of amino acidsfor the immune defenses(D) Fever is harmful because thepatient’s higher temperature favorsgrowth of the bacteria responsible forinfection(E) Fever has little overall effect eitherway

6. A manual laborer moves in March fromCanada to a hot, tropical country andbecomes acclimatized by workingoutdoors for a month. Compared withhis responses on the first few days inthe tropical country, for the sameactivity level after acclimatization onewould expect higher(A) Core temperature(B) Heart rate(C) Sweating rate(D) Sweat salt concentration(E) Thermoregulatory set pointIn questions 7 to 8, assume a 70-kg

young man with the following baselinecharacteristics: total body water (TBW) �40 L, extracellular fluid (ECF) volume �15 L, plasma volume � 3 L, body surfacearea � 1.8 m2, plasma [Na�] � 140mmol/L. Heat of evaporation of water �2,425 kJ/kg � 580 kcal/kg.7. Our subject begins an 8-hour hike in

the desert carrying 5 L of water incanteens. During the hike, he sweats ata rate of 1 L/hr, his sweat [Na�] is 50mmol/L, and he drinks all his water.After the end of his hike he rests andconsumes 3 L of water. (For simplicityin calculations, assume that the plasma

osmolality equals 2 times the plasma[Na�].) What are his plasma sodiumconcentration and ECF volume after hehas replaced all the water that he lost?Plasma [Na�](mmol/L) ECF Volume (L)(A) 140.5 12.1(B) 130 13.1(C) 122.3 13.9(D) 113.3 15.(E) 113.3 13.9

8. Our subject is bicycling on a long roadwith a slight upward grade. Hismetabolic rate (M in the heat-balanceequation) is 800 W (48 kJ/min). Heperforms mechanical work (againstgravity, friction, and wind resistance)at a rate of 140 W. Air temperature is20�C and hc, the convective heattransfer coefficient, is 15 W/(m2•�C).Assume that his mean skin temperatureis 34�C, all the sweat he secretes isevaporated, respiratory water loss canbe ignored, and net heat exchange byradiation is negligible. How rapidlymust he sweat to achieve heat balance?(Remember that 1 W � 1 J/sec �60 J/min.)(A) 3.9 g/min(B) 7.0 g/min(C) 11.1 g/min(D) 13.9 g/min(E) 15.0 g/min

SUGGESTED READING

Boulant JA. Hypothalamic neurons regu-lating body temperature. In: Fregly MJ,Blatteis CM, eds. Handbook of Physi-ology. Section 4. Environmental Physi-ology. New York: Oxford UniversityPress, 1996;105–126.

Danzl DF. Hypothermia and frostbite. In:

Braunwald E, Fauci AS, Kasper DL, etal., eds. Harrison’s Principles of InternalMedicine. 15th Ed. New York: Mc-Graw-Hill, 2001;107–111.

Dinarello CA. Cytokines as endogenouspyrogens. J Infect Dis 1999;179(Suppl2):S294–S304.

Dinarello CA, Gelfand JA. Fever and hy-perthermia. In: Braunwald E, Fauci AS,Kasper DL, et al., eds. Harrison’s Prin-ciples of Internal Medicine. 15th Ed.New York: McGraw-Hill, 2001;91–94.

Gagge AP, Gonzalez RR. Mechanisms ofheat biophysics and physiology. In:Fregly MJ, Blatteis CM, eds. Handbookof Physiology. Section 4. Environmen-tal Physiology. New York: OxfordUniversity Press, 1996;45–84.

Jessen C. Interaction of body temperaturesin control of thermoregulatory effectormechanisms. In: Fregly MJ, BlatteisCM, eds. Handbook of Physiology.Section 4. Environmental Physiology.New York: Oxford University Press,1996;127–138.

Johnson JM, Proppe DW. Cardiovascularadjustments to heat stress. In: FreglyMJ, Blatteis CM, eds. Handbook ofPhysiology. Section 4. EnvironmentalPhysiology. New York: Oxford Uni-versity Press, 1996;215–243.

Knochel JP, Reed G: Disorders of heatregulation. In: Narins RG, ed. Maxwell& Kleeman’s Clinical Disorders of Fluidand Electrolyte Metabolism. 5th Ed.New York: McGraw-Hill,1994;1549–1590.

Pandolf KB, Sawka MN, Gonzalez RR,eds. Human Performance Physiologyand Environmental Medicine at Terres-trial Extremes. Indianapolis: Bench-mark, 1988.

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