Regulation of Body Temperature

Homeotherms maintain their activities over a wide range of environmental temperatures

The ability to regulate internal body temperature has provided higher organisms independence from the environment. Because the rates of most physical and chemical reactions depend on temperature, most physiological functions are sensitive to temperature changes. Thus, the activity levels of poikilotherms (species that do not regulate internal body temperature) generally depend on environmental temperature, whereas homeotherms (species that do regulate internal body temperature) can engage in most normal activities independent of ambient temperature. A lizard, for example, is capable of relatively less movement away from its lair on a cold, overcast day than on a hot, sunny day, whereas a prairie dog may be equally mobile on either day. An arctic fox acclimatizes to the extreme cold of winter by maintaining a thick, insulating coat that enables it to resist body cooling and minimizes the necessity to increase metabolic heat generation, which would require increased food intake.

The stable body temperature of homeotherms is the consequence of designated neural networks that incor­porate both anticipatory and negative-feedback controls. This arrangement creates an internal environment in which chemical reaction rates are relatively high and optimal and avoids the pathological consequences of wide fluctuations in body temperature ( Table 59-1 ). The fundamental thermoregulatory system includes (1) thermal sensors; (2) thermosensory afferent pathways; (3) an integration system in the central nervous system (CNS); (4) efferent pathways; and (5) thermal effectors capable of heat generation (i.e., thermogenesis), such as brown adipose tissue and skeletal muscle (shivering), or effectors that modulate heat transfer, such as the circulation to the skin (which dissipates heat) and the sweat glands (which augment heat loss).

In this chapter, we describe the physical aspects of heat transfer both within the homeotherm's body and between the body and the environment. We also provide a framework for understanding the major integrative role played by the CNS in regulating body temperature and consider the physiological mechanisms involved in altering rates of heat transfer and in producing extra heat in a cold environment or during fever. Finally, we look at the consequences of extreme challenges to the thermoregulatory mechanism, such as hypothermia, hyperthermia, and dehydration.

Body core temperature depends on time of day, physical activity, time in the menstrual cycle, and age

Temperature is a measure of heat content. The “normal” body temperature of an adult human is ~37°C (98.6°F) but it may be as low as 36°C or as high as 37.5°C in active, healthy people. Body temperature usually refers to the temperature of the internal body core, N59-1 measured under the tongue (sublingually), in the ear canal, or in the rectum. For clinical purposes, the most reliable (although the least practical) among these three is the last, because it is least influenced by ambient (air) temperature. Measurement devices range from traditional mercury-in-glass thermometers to electronic digital-read-out thermistors. Nearly all such instruments are accurate to 0.1°C. The least invasive approach uses an infrared thermometer to measure the radiant temperature (see p. 1196 ) over the temporal artery. N59-1

Body core temperature (T _core ) depends on many factors that alter either the activity of the CNS thermoregulatory network or the level of metabolism and heat content of the body, including the time of day, the stage of the menstrual cycle in women, and the individual's age.

All homeotherms maintain a circadian rhythm (~24-hour cycle) of body temperature, with variations of ~1°C. In humans, body temperature is usually lowest between 3:00 and 6:00 am and peaks at 3:00 to 6:00 pm . The circadian rhythmicity in physiological variables is governed by groups of neurons in the suprachiasmatic nucleus in the anterior hypothalamus, whose activity is entrained by light-dark cues to a ~24-hour cycle but is independent of the sleep-wake cycle. The influence of these neurons on the CNS thermoregulatory network produces the circadian rhythmicity in body temperature.

Reproductive hormones, and the CNS circuits that govern their production, influence the CNS thermoregulatory network. Indeed, in many women, body temperature increases ~0.5°C during the postovulatory phase of the menstrual cycle (see pp. 1110–1111 ). An abrupt increase in body temperature of 0.3°C to 0.5°C accompanies ovulation and may be useful as a fertility guide.

Infants and older people are less able than other age groups to maintain a stable normal body temperature, particularly in the face of external challenges. Newborns do not readily shiver or sweat and have a high surface-to-mass ratio, which renders them more susceptible to fluctuations in core temperature when exposed to hot or cold environments. However, they have large deposits of brown adipose tissue, which the sympathetic nervous system can stimulate to generate heat for cold defense. Moreover, newborns can implement a modest degree of sympathetic vasoconstriction of the skin to reduce heat loss in the cold.

Older people are also subject to greater fluctuations in core temperature. Aging is associated with a progressive deficit in the ability to sense heat and cold (see p. 1244 ), as well as reduced ability to generate heat (reduced metabolic rate and metabolic potential because of lower muscle mass) and to dissipate heat (reduced cardiovascular reserve and sweat gland atrophy from disuse).

The body's rate of heat production can vary from ~70 kcal/hr at rest to 600 kcal/hr during exercise

Because the chemical reactions are inefficient, cellular functions produce heat (see p. 1173 ). The body's rate of heat production depends on the rate of energy consumption and thus of O ₂ consumption ( ) because nearly all energy substrates derived from food are oxidized. Minor variations occur, depending on the mixture of fuels (foods) being oxidized, a process that determines the respiratory quotient (RQ; see p. 681 and Table 58-6 ).

The body's metabolic rate, and thus its rate of heat production, is not constant. The resting metabolic rate ( RMR; see p. 1170 ) is the energy consumption necessary to maintain the basal functions of resting cells, such as active solute transport across membranes as well as the activity of cardiac and respiratory muscles necessary for organismal survival. RMR is influenced by age, sex, circadian phase, season, digestive state, phylogeny, body size, and habitat. Voluntary or involuntary (e.g., postural and shivering) muscular activity adds to the overall metabolic heat production. Even digesting a meal increases the metabolic rate (see p. 1179 ). An increase in tissue temperature itself raises the metabolic rate, according to the van't Hoff relation (i.e., a 10°C increase in tissue temperature more than doubles the metabolic rate). Furthermore, certain hormones, notably thyroxine and epinephrine, increase the cellular metabolic rate. At an RQ of 0.8 (see p. 681 and Table 58-6 ), the average person under sedentary (i.e., RMR) conditions has a resting of 250 mL/min, which corresponds to an energy production of 72 kcal/hr (~85 watts). Because the body at RMR, by definition, performs no work on the environment, all of this energy production ultimately is dissipated as heat—as if the body were a zero-efficiency, 85-watt incandescent light bulb.

During physical exercise, the rate of energy consumption—and hence, heat generation—increases in proportion to the intensity of exercise. An average adult can comfortably sustain an energy-consumption rate of 400 to 600 kcal/hr (e.g., a fast walk or a modest jog) for extended periods. Nearly all increased heat generation during exercise occurs in active skeletal muscle, although a portion arises from increased activity of cardiac and respiratory muscles. A thermal load of this magnitude would raise core temperature by 1.0°C every 8 to 10 minutes if the extra heat could not escape the body. Physical activity would be limited to 25 to 30 minutes, at which time the effects of excessive hyperthermia (>40°C) would begin to impair body function. This impairment, of course, does not usually occur, primarily because of the effectiveness of the thermoregulatory heat-defense system. Within a relatively short period, the increase in body temperature resulting from exercise leads to an increased rate of heat dissipation from the skin and the respiratory system commensurate with the rate of heat production. Thereafter, the body maintains a new, but slightly elevated, steady temperature. When exercise ceases, body temperature gradually decreases to its pre-exercise level.

Maintaining a relatively constant body temperature requires a fine balance between heat production and heat losses

If body temperature is to remain unchanged, increases or decreases in heat production must be balanced by increases or decreases in heat loss, resulting in negligible heat storage within the body. If the body is at constant mass, the whole-body heat-balance equation expresses this concept as follows:

All terms in the foregoing equation have the units kcal/hr.

Several physiological processes contribute to temperature homeostasis, including modulation of metabolic heat production, physical heat transfer, and elimination of heat. These processes operate at the level of cells, tissues, and organ systems. Let us discuss in order the terms in Equation 59-1 .

Metabolism (M) is the consumption of energy from the cellular oxidation of carbohydrates, fats, and proteins. For an athlete, the useful work on the environment (W) might be the energy imparted to an iron ball during the shot put event. However, because of a long list of inefficiencies—the inherent inefficiency of metabolic transformations (see pp. 1173–1174 ) as well as frictional losses (e.g., blood flowing through vessels, air flowing through airways, tissues sliding passed one another)—most metabolic energy consumption ends up as heat production ( H = M − W). Table 59-2 shows the fractional contributions of different body systems to total heat production under sedentary, resting conditions.

Under conditions of maximal exercise, (see pp. 1213–1215 ) may correspond to a total energy expenditure (M in Equation 59-1 ) of 1300 kcal/hr for an endurance athlete. If 60% of this energy evolves as heat—so that the athlete does ~500 kcal/hr of useful work on the environment—the rate of heat production will be 1300 − 500 = 800 kcal/hr (~960 watts) for a brief period of time. This change is equivalent to changing from an 85-watt light bulb to a 1000-watt space heater. Unless the body can dissipate this heat, death from hyperthermia and heat stroke ( Box 59-1 ) would ensue rapidly.

Virtually all heat leaving the body must exit through the skin surface. In the following three sections, we consider the three major routes of heat elimination: radiation (R), convection (C), and evaporation (E). As the heat-balance equation shows, the difference between heat production (M − W) and heat losses (R + C + E) is the rate of heat storage (S) within the body. The value of S may be positive or negative, depending on whether (M − W) > (R + C + E) or vice versa. A positive value of S results in a rise of T _core , such as during exercise, whereas a negative value of S results in a fall in T _core , as would occur shortly after entering very cold water.

Heat moves from the body core to the skin, primarily by convection

Generally, all heat production occurs within the body's tissues, and all heat elimination occurs at the body surface. Figure 59-1 illustrates a passive system in which heat flows depend on the size, shape, and composition of the body, as well as on the laws of physics. The circulating blood carries heat away from active tissues, such as muscle, to the body core—represented by the heart, lungs, and their central circulating blood volume. N59-2 How does the body prevent its core from overheating? The answer is that the core transfers this heat to a dissipating heat sink. The organ serving as the body's greatest potential heat sink is the relatively cool skin, which is the largest organ in the body. Only a minor amount of the body's generated heat flows directly from the underlying body core to the skin by conduction across the body tissues. Most of the generated body heat flows in the blood—by convection —to the skin, and blood flow to the skin can increase markedly during heat defense. There, nearly all heat transferred to the skin will flow to the environment, as discussed in the next section.

N59-2

Heat Transfer from Muscle to Body Core

In the simplest analysis, the rate of heat transfer from any tissue to the blood depends on (1) the rate of tissue energy production, (2) the temperature of the tissue, (3) the temperature of the incoming blood, and (4) blood flow through the tissue.

Inactive skeletal muscle, for example, has a low blood flow and a correspondingly low rate of metabolism. The rate of O ₂ consumption ( )—a measure of metabolic rate—averages 1.5 to 2.0 mL of O ₂ consumed per minute for each kilogram of muscle tissue. Because the temperature of resting muscle (33°C to 35°C) is lower than that of the body core (37°C), heat flows from arterial blood to inactive skeletal muscle. A similar analysis shows that heat moves from a highly active tissue such as the liver (38°C) to the blood, which distributes the heat to the other tissues of the body core.

The body's greatest potential heat source is skeletal muscle, which has a relatively large mass and can increase its rate of heat production >100-fold. Because skeletal muscle has such potential, it is useful for modeling heat transfer and changes in tissue temperature ( eFig. 59-1 ). The energy balance equation for skeletal muscle is as follows:

$\begin{array}{c}\left[\begin{array}{c}\text{Heat}\\ \text{generated by}\\ \text{muscle}\\ \text{metabolism}\end{array}\right]-\left[\begin{array}{c}\text{Heat convected}\\ \text{from}\\ \text{muscle to}\\ \text{blood}\end{array}\right]-\left[\begin{array}{c}\text{Heat}\\ \text{conducted}\\ \text{from muscle}\\ \text{to skin}\end{array}\right]\\ =\left[\begin{array}{c}\text{Heat}\\ \text{excess that}\\ \text{produces an}\\ \text{increase in}\\ \text{muscle}\\ \text{temperature}\end{array}\right]\end{array}$

The three terms on the left describe all the heat that the muscle gains or loses. If they add up to a positive number, muscle temperature increases. In the steady state, these three terms add up to zero, and muscle temperature is stable.

During the onset of exercise, the heat produced by metabolism increases rapidly. If the three terms on the left side of Equation NE 59-1 sum to a very positive number (which implies a large energy excess), muscle temperature rises rapidly. However, the dramatic increase in the rate of warming is relatively short-lived because of two factors: (1) The increase in muscle temperature reverses the temperature gradient between muscle and the blood perfusing it, so that heat now flows from muscle to blood. (2) Muscle vascular resistance decreases and cardiac output increases rapidly (see p. 581 ), so that blood flow through the muscle increases proportionally with the intensity of exercise. These adjustments are relatively complete within a few minutes. Increases of up to 30-fold in blood flow account for a proportional increase in heat transfer from active muscle to blood.

As exercise continues, muscle temperature increases to a new steady-state level, which causes more heat transfer from muscle to blood. The result is an increase in core temperature as warm venous blood leaving the muscles enters the body core.

The transfer of heat from core to skin occurs by two routes:

Both the conduction and convection terms in the previous equation are proportional to the temperature gradient from core to skin (T _core −
), where
is the average skin temperature, usually obtained from at least four skin sites. The proportionality constant for passive conduction across the subcutaneous fat (the body's insulation) is relatively fixed. However, the proportionality constant for heat convection by blood is a variable term, reflecting the variability of the blood flow to the skin. The ability to alter skin blood flow, under autonomic control, is therefore the primary determinant of heat flow from core to skin. The capacity to limit blood flow to the skin is an essential defense against body cooling (hypothermia) in the cold. A side effect, however, is that skin temperature falls. Conversely, the capacity to elevate skin blood flow is an essential defense against hyperthermia. On very hot days when skin temperature may be very high and close to T _core , even high skin blood flow may not be adequate to transfer sufficient heat to allow T _core to stabilize because the temperature gradient (T _core −
) is too small.

Although most of the heat leaving the core moves to the skin, a small amount also leaves the body core by the evaporation of water from the respiratory tract. The evaporative rate is primarily a function of the rate of ventilation (see p. 675 ), which in turn increases linearly with the metabolic rate over a wide range of exercise intensities.

Heat moves from the skin to the environment by radiation, conduction, convection, and evaporation

Figure 59-2 is a graphic summary of the heat-balance equation (see Equation 59-1 ) for an athlete exercising in an outdoor environment. This illustration depicts the movement of heat within the body, its delivery to the skin surface, and its subsequent elimination to the environment by radiation, convection, and evaporation.