In the body, heat is produced by muscular exercise, assimilation of food, and all the vital processes that contribute to the basal metabolic rate. It is lost from the body by radiation, conduction, and vaporization of water in the respiratory passages and on the skin. Small amounts of heat are also removed in the urine and feces. The balance between heat production and heat loss determines the body temperature. Because the speed of chemical reactions varies with temperature and because the enzyme systems of the body have narrow temperature ranges in which their function is optimal, normal body function depends on a relatively constant body temperature.
Invertebrates generally cannot adjust their body temperatures and so are at the mercy of the environment. Vertebrates have evolved mechanisms for maintaining body temperature by adjusting heat production and heat loss. In reptiles, amphibians, and fish, the adjusting mechanisms are relatively rudimentary, and these species are called “cold-blooded” (poikilothermic) because their body temperature fluctuates over a considerable range. In birds and mammals, the “warm-blooded” (homeothermic) animals, a group of reflex responses that are primarily integrated in the hypothalamus operate to maintain body temperature within a narrow range in spite of wide fluctuations in environmental temperature. The hibernating mammals are a partial exception. While awake they are homeothermic, but during hibernation their body temperature falls.
In homeothermic animals, the actual temperature at which the body is maintained varies from species to species and, to a lesser degree, from individual to individual. In humans, the traditional normal value for the oral temperature is 37°C (98.6°F), but in one large series of normal young adults, the morning oral temperature averaged 36.7°C, with a standard deviation of 0.2°C. Therefore, 95% of all young adults would be expected to have a morning oral temperature of 36.3–37.1°C (97.3–98.8°F; mean ± 1.96 standard deviations). Various parts of the body are at different temperatures, and the magnitude of the temperature difference between the parts varies with the environmental temperature. The extremities are generally cooler than the rest of the body. The temperature of the scrotum is carefully regulated at 32°C. The rectal temperature is representative of the temperature at the core of the body and varies least with changes in environmental temperature. The oral temperature is normally 0.5°C lower than the rectal temperature, but it is affected by many factors, including ingestion of hot or cold fluids, gum chewing, smoking, and mouth breathing.
The normal human core temperature undergoes a regular circadian fluctuation of 0.5–0.7°C. In individuals who sleep at night and are awake during the day (even when hospitalized at bed rest), it is lowest at about 6:00 AM and highest in the evenings (Figure 17–12). It is lowest during sleep, is slightly higher in the awake but relaxed state, and rises with activity. In women, an additional monthly cycle of temperature variation is characterized by a rise in basal temperature at the time of ovulation (Figure 22–14). Temperature regulation is less precise in young children and they may normally have a temperature that is 0.5°C or so above the established norm for adults.
Typical temperature chart of a hospitalized patient who does not have a febrile disease. Note the slight rise in temperature, due to excitement and apprehension, at the time of admission to the hospital, and the regular circadian temperature cycle.
During exercise, the heat produced by muscular contraction accumulates in the body and the rectal temperature normally rises as high as 40°C (104°F). This rise is due in part to the inability of the heat-dissipating mechanisms to handle the greatly increased amount of heat produced, but evidence suggests that during exercise in addition there is an elevation of the body temperature at which the heat-dissipating mechanisms are activated. Body temperature also rises slightly during emotional excitement, probably owing to unconscious tensing of the muscles. It is chronically elevated by as much as 0.5°C when the metabolic rate is high, as in hyperthyroidism, and lowered when the metabolic rate is low, as in hypothyroidism (Figure 17–12). Some apparently normal adults chronically have a temperature above the normal range (constitutional hyperthermia).
A variety of basic chemical reactions contribute to body heat production at all times. Ingestion of food increases heat production, but the major source of heat is the contraction of skeletal muscle (Table 17–3). Heat production can be varied by endocrine mechanisms in the absence of food intake or muscular exertion. Epinephrine and norepinephrine produce a rapid but short-lived increase in heat production; thyroid hormones produce a slowly developing but prolonged increase. Furthermore, sympathetic discharge decreases during fasting and is increased by feeding.
TABLE 17–3Body heat production and heat loss. ||Download (.pdf) TABLE 17–3 Body heat production and heat loss.
Body heat is produced by:
Basic metabolic processes
Food intake (specific dynamic action)
Body heat is lost by:
Radiation and conduction
Vaporization of sweat
Urination and defecation
Percentage of heat lost at 21°C
A source of considerable heat, particularly in infants, is brown fat. This fat has a high rate of metabolism and its thermogenic function has been likened to that of an electric blanket.
The processes by which heat is lost from the body when the environmental temperature is below body temperature are listed in Table 17–3. Conduction is heat exchange between objects or substances at different temperatures that are in contact with one another. A basic characteristic of matter is that its molecules are in motion, with the amount of motion proportional to the temperature. These molecules collide with the molecules in cooler objects, transferring thermal energy to them. The amount of heat transferred is proportional to the temperature difference between the objects in contact (thermal gradient). Conduction is aided by convection, the movement of molecules away from the area of contact. Thus, for example, an object in contact with air at a different temperature changes the specific gravity of the air, and because warm air rises and cool air falls, a new supply of air is brought into contact with the object. Of course, convection is greatly aided if the object moves about in the medium or the medium moves past the object, for example, if a subject swims through water or a fan blows air through a room. Radiation is the transfer of heat by infrared electromagnetic radiation from one object to another at a different temperature with which it is not in contact. When an individual is in a cold environment, heat is lost by conduction to the surrounding air and by radiation to cool objects in the vicinity. Conversely, of course, heat is transferred to an individual and the heat load is increased by these processes when the environmental temperature is above body temperature. Note that because of radiation, an individual can feel chilly in a room with cold walls even though the room is relatively warm. On a cold but sunny day, the heat of the sun reflected off bright objects exerts an appreciable warming effect. It is the heat reflected from the snow, for example, that in part makes it possible to ski in fairly light clothes even though the air temperature is below freezing.
Because conduction occurs from the surface of one object to the surface of another, the temperature of the skin determines to a large extent the degree to which body heat is lost or gained. The amount of heat reaching the skin from the deep tissues can be varied by changing the blood flow to the skin. When the cutaneous vessels are dilated, warm blood wells into the skin, whereas in the maximally vasoconstricted state, heat is held centrally in the body. The rate at which heat is transferred from the deep tissues to the skin is called the tissue conductance. Further, birds have a layer of feathers next to the skin, and most mammals have a significant layer of hair or fur. Heat is conducted from the skin to the air trapped in this layer and from the trapped air to the exterior. When the thickness of the trapped layer is increased by fluffing the feathers or erection of the hairs (horripilation), heat transfer across the layer is reduced and heat losses (or, in a hot environment, heat gains) are decreased. “Goose pimples” are the result of horripilation in humans; they are the visible manifestation of cold-induced contraction of the piloerector muscles attached to the rather meager hair supply. Humans usually supplement this layer of hair with one or more layers of clothes. Heat is conducted from the skin to the layer of air trapped by the clothes, from the inside of the clothes to the outside, and from the outside of the clothes to the exterior. The magnitude of the heat transfer across the clothing, a function of its texture and thickness, is the most important determinant of how warm or cool the clothes feel, but other factors, especially the size of the trapped layer of warm air, are also important. Dark clothes absorb radiated heat and light-colored clothes reflect it back to the exterior.
The other major process transferring heat from the body in humans and other animals that sweat is vaporization of water on the skin and mucous membranes of the mouth and respiratory passages. Vaporization of 1 g of water removes about 0.6 kcal of heat. A certain amount of water is vaporized at all times. This insensible water loss amounts to 50 mL/h in humans. When sweat secretion is increased, the degree to which the sweat vaporizes depends on the humidity of the environment. It is common knowledge that one feels hotter on a humid day. This is due in part to the decreased vaporization of sweat, but even under conditions in which vaporization of sweat is complete, an individual in a humid environment feels warmer than an individual in a dry environment. The reason for this difference is unknown, but it seems related to the fact that in the humid environment sweat spreads over a greater area of skin before it evaporates. During muscular exertion in a hot environment, sweat secretion reaches values as high as 1600 mL/h, and in a dry atmosphere, most of this sweat is vaporized. Heat loss by vaporization of water therefore varies from 30 to over 900 kcal/h.
Some mammals lose heat by panting. This rapid, shallow breathing greatly increases the amount of water vaporization in the mouth and respiratory passages and therefore the amount of heat lost. Because the breathing is shallow, it produces relatively little change in the composition of alveolar air (see Chapter 34).
The relative contribution of each of the processes that transfer heat away from the body (Table 17–3) varies with the environmental temperature. At 21°C, vaporization is a minor component in humans at rest. As the environmental temperature approaches body temperature, radiation losses decline and vaporization losses increase.
The reflex and semireflex thermoregulatory responses in humans are listed in Table 17–4. They include autonomic, somatic, endocrine, and behavioral changes. One group of responses increases heat loss and decreases heat production; the other decreases heat loss and increases heat production. In general, exposure to heat stimulates the former group of responses and inhibits the latter, whereas exposure to cold does the opposite.
TABLE 17–4Temperature-regulating mechanisms. ||Download (.pdf) TABLE 17–4 Temperature-regulating mechanisms.
|Mechanisms activated by cold |
|Increased voluntary activity |
|Increased secretion of norepinephrine and epinephrine |
|Decreased heat loss |
|Cutaneous vasoconstriction |
|Curling up |
|Mechanisms activated by heat |
|Increased heat loss |
|Cutaneous vasodilation |
|Increased respiration |
|Decreased heat production |
|Apathy and inertia |
Curling up “in a ball” is a common reaction to cold in animals and has a counterpart in the position some people assume on climbing into a cold bed. Curling up decreases the body surface exposed to the environment. Shivering is an involuntary response of the skeletal muscles, but cold also causes a semiconscious general increase in motor activity. Examples include foot stamping and dancing up and down on a cold day. Increased catecholamine secretion is an important endocrine response to cold. Mice unable to make norepinephrine and epinephrine because their dopamine β-hydroxylase gene is knocked out do not tolerate cold; they have deficient vasoconstriction and are unable to increase thermogenesis in brown adipose tissue through UCP 1. TSH secretion is increased by cold and decreased by heat in laboratory animals, but the change in TSH secretion produced by cold in adult humans is small and of questionable significance. It is common knowledge that activity is decreased in hot weather—the “it’s too hot to move” reaction.
Thermoregulatory adjustments involve local responses as well as more general reflex responses. When cutaneous blood vessels are cooled they become more sensitive to catecholamines and the arterioles and venules constrict. This local effect of cold directs blood away from the skin. Another heat-conserving mechanism that is important in animals living in cold water is heat transfer from arterial to venous blood in the limbs. The deep veins (venae comitantes) run alongside the arteries supplying the limbs and heat is transferred from the warm arterial blood going to the limbs to the cold venous blood coming from the extremities (countercurrent exchange; see Chapter 37). This limits the ability to maintain heat in the tips of the extremities but conserves body heat.
The reflex responses activated by cold are controlled from the posterior hypothalamus. Those activated by warmth are controlled primarily from the anterior hypothalamus, although some thermoregulation against heat still occurs after decerebration at the level of the rostral midbrain. Stimulation of the anterior hypothalamus causes cutaneous vasodilation and sweating, and lesions in this region cause hyperthermia, with rectal temperatures sometimes reaching 43°C (109.4°F). Posterior hypothalamic stimulation causes shivering, and the body temperature of animals with posterior hypothalamic lesions falls toward that of the environment.
The hypothalamus is said to integrate body temperature information from sensory receptors (primarily cold receptors) in the skin, deep tissues, spinal cord, extrahypothalamic portions of the brain, and the hypothalamus itself. Each of these five inputs contributes about 20% of the information that is integrated. There are threshold core temperatures for each of the main temperature-regulating responses and when the threshold is reached the response begins. The threshold is 37°C for sweating and vasodilation, 36.8°C for vasoconstriction, 36°C for nonshivering thermogenesis, and 35.5°C for shivering.
Fever is perhaps the oldest and most universally known hallmark of disease. It occurs not only in mammals but also in birds, reptiles, amphibia, and fish. When it occurs in homeothermic animals, the thermoregulatory mechanisms behave as if they were adjusted to maintain body temperature at a higher than normal level, that is, “as if the thermostat had been reset” to a new point above 37°C. The temperature receptors then signal that the actual temperature is below the new set point, and the temperature-raising mechanisms are activated. This usually produces chilly sensations due to cutaneous vasoconstriction and occasionally enough shivering to produce a shaking chill. However, the nature of the response depends on the ambient temperature. The temperature rise in experimental animals injected with a pyrogen is due mostly to increased heat production if they are in a cold environment and mostly to decreased heat loss if they are in a warm environment.
The pathogenesis of fever is summarized in Figure 17–13. Toxins from bacteria, such as endotoxin, act on monocytes, macrophages, and Kupffer cells to produce cytokines that act as endogenous pyrogens (EPs). There is good evidence that IL-1β, IL-6, IFN-β, IFN-γ, and TNF-α (see Chapter 3) can act independently to produce fever. These circulating cytokines are polypeptides and it is unlikely that they penetrate the brain. Instead, evidence suggests that they act on the OVLT, one of the circumventricular organs (see Chapter 33). This in turn activates the preoptic area of the hypothalamus. Cytokines are also produced by cells in the central nervous system (CNS) when these are stimulated by infection, and these may act directly on the thermoregulatory centers.
The fever produced by cytokines is probably due to local release of prostaglandins in the hypothalamus. Intrahypothalamic injection of prostaglandins produces fever. In addition, the antipyretic effect of aspirin is exerted directly on the hypothalamus, and aspirin inhibits prostaglandin synthesis. PGE2 is one of the prostaglandins that causes fever. It acts on four subtypes of prostaglandin receptors—EP1, EP2, EP3, and EP4—and knockout of the EP3 receptor impairs the febrile response to PGE2, IL-1β, and endotoxin, or bacterial lipopolysaccharide (LPS).
The benefit of fever to the organism is uncertain. A beneficial effect is assumed because fever has evolved and persisted as a response to infections and other diseases. Many microorganisms grow best within a relatively narrow temperature range and a rise in temperature inhibits their growth. In addition, antibody production is increased when body temperature is elevated. Before the advent of antibiotics, fevers were artificially induced for the treatment of neurosyphilis and proved to be beneficial. Hyperthermia also benefits individuals infected with anthrax; pneumococcal pneumonia; leprosy; and various fungal, rickettsial, and viral diseases. Hyperthermia also slows the growth of some tumors. However, very high temperatures are harmful. A rectal temperature over 41°C (106°F) for prolonged periods results in some permanent brain damage. When the temperature is over 43°C, heat stroke develops and death is common.
In malignant hyperthermia, various mutations of the gene coding for the ryanodine receptor (see Chapter 5) lead to excess Ca2+ release during muscle contraction triggered by stress. This in turn leads to contractures of the muscles, increased muscle metabolism, and a great increase in heat production in muscle. The increased heat production causes a marked rise in body temperature that is fatal if not treated.
Periodic fevers also occur in humans with mutations in the gene for pyrin, a protein found in neutrophils; the gene for mevalonate kinase, an enzyme involved in cholesterol synthesis; and the gene for the type 1 TNF receptor, which is involved in inflammatory responses. However, how any of these three mutant gene products cause fever is unknown.
In hibernating mammals, body temperature drops to low levels without causing any demonstrable ill effects on subsequent arousal. This observation led to experiments on induced hypothermia. When the skin or the blood is cooled enough to lower the body temperature in nonhibernating animals or in humans, metabolic and physiologic processes slow down. Respiration and heart rate are very slow, blood pressure is low, and consciousness is lost. At rectal temperatures of about 28°C, the ability to spontaneously return the temperature to normal is lost, but the individual continues to survive and, if rewarmed with external heat, returns to a normal state. If care is taken to prevent the formation of ice crystals in the tissues, the body temperature of experimental animals can be lowered to subfreezing levels without producing any detectable damage after subsequent rewarming.
Humans tolerate body temperatures of 21–24°C (70–75°F) without permanent ill effects, and induced hypothermia has been used in surgery. On the other hand, accidental hypothermia due to prolonged exposure to cold air or cold water is a serious condition and requires careful monitoring and prompt rewarming.