Body temperature regulation mechanisms
Body temperature is regulated almost exclusively by negative feedback nervous mechanisms that operate, for the most part, through thermoregulatory centers located in the hypothalamus. In addition to neural control, hormones affect thermoregulation, but in general they are associated with long-term acclimatization.[5] Three models have been proposed that explain the mechanism of thermal homeostasis in humans. The first two propose that temperature is the regulated variable. These models consider that thermoregulatory mechanisms try, at all times, to bring body temperature to the set point. The third model is fundamentally different from the first two, as it proposes that the regulated variable is heat content rather than temperature per se, in this model body temperature is considered to be a byproduct of regulation.[6].
The most recent and apparently most accepted models are the "balanced point" theory[7] and the "proportional control" theory.[8] Both theories postulate that body temperature is controlled by a "multi-sensor", "multi-processor", "multi-effector" proportional feedback control system.
Two sources of heat alter body temperature: internal heat generation and environmental heating or cooling. Due to exothermic chemical reactions, all organs produce metabolic heat, even when the body is at rest. During exercise, muscles produce several times more heat than they produce at rest. Heat is dissipated from the skin to the environment if the skin surface temperature is higher than the ambient temperature, otherwise heat is absorbed by the skin.
To maintain temperature homeostasis, humans use two mechanisms: behavioral thermoregulation and autonomous thermoregulation. Behavioral thermoregulation consists of the conscious adjustment of the thermal environment in order to maintain comfort. It is achieved by altering the degree of insulation of the body (clothing) or the environmental temperature. Autonomous thermoregulation is the process by which, through the autonomic nervous system, internal mechanisms control body temperature subconsciously and precisely. This control involves two mechanisms, one associated with heat dissipation, and the other with its production and conservation. Elevated ambient temperature produces heat loss through cutaneous vasodilation, sweating, and lower heat production. When the ambient temperature drops, additional heat is produced by shivering thermogenesis and non-shivering thermogenesis, and heat loss is decreased by constriction of cutaneous blood vessels. Long-term exposure to cold increases the release of thyroxine, which increases body heat by stimulating tissue metabolism.[9] Technical thermoregulation constitutes a third mechanism, which can be considered part of behavioral thermoregulation. It involves the use of a system that maintains the ambient temperature constant. An example is an air conditioner that monitors the temperature of a room and adjusts the heat flow while keeping the temperature constant. It is noteworthy that both autonomous, behavioral and technical thermoregulation constitute negative feedback control systems.
The thermoneutral zone or, referred to in humans, thermal comfort zone, is the environmental temperature range in which metabolic expenditure is kept at a minimum, and temperature regulation is carried out by non-evaporative physical mechanisms, maintaining the core body temperature in normal ranges.[10] This means that thermoregulation in the thermoneutral zone occurs only by vasomotor control. The lower and upper limits of the thermoneutral zone are called the lower critical temperature and the upper critical temperature, respectively. Due to differences in thermal properties, the thermoneutral zone in water is shifted upward compared to that in air (33 to 35.5. C in water vs. 28.5 to 32. C in air).[11].
Thermoregulatory functions are divided according to their purpose and physiological mechanism into two categories. The first comprises thermoregulation that counteracts changes in temperature that would produce serious disturbances in thermal homeostasis, imposing a danger to life. The second comprises a special type of thermoregulation, its function is to level out comparatively small but continuously occurring thermal fluctuations. These temperature fluctuations that occur even in the thermoneutral zone are an inherent part of the normal life of animals and humans. In the absence of abrupt changes in temperature, the latter is the main function of the thermoregulation system.[12].
Overheating of the thermostatic area of the hypothalamus increases the rate of heat loss by two essential processes:
When the body becomes excessively hot, information is sent to the preoptic area, located in the brain, in front of the hypothalamus. This triggers sweat production. Humans can lose up to 1.5 l of sweat per hour. Through it, water loss occurs which leads to a decrease in our body temperature.
When body temperature increases, peripheral vessels dilate and blood flows in greater quantities near the skin, favoring the transfer of heat to the environment. Therefore, after exercise the skin turns red, since it is more irrigated.
When the body is cooled below normal temperature, the following mechanisms reduce heat loss:.
Vasoconstriction of epidermal vessels is one of the first processes that improve heat conservation. When the temperature decreases, the posterior hypothalamus is activated and, through the sympathetic nervous system, the diameter of the cutaneous blood vessels decreases; This is the reason why people turn pale in the cold. This effect decreases heat conduction from the inner core to the skin. Consequently, the skin temperature decreases and approaches the ambient temperature, thus reducing the gradient that favors heat loss. Vasoconstriction can decrease heat loss by about eight-fold.[4].
Many animals, including humans, have a mechanism called a countercurrent exchanger to conserve heat. The arteries of the arms and legs run parallel to a set of deep veins but their flow is opposite. So the heat of the arterial blood (flowing from the core to the periphery) diffuses into the venous blood (flowing from the periphery to the core). In this way the heat is returned to the central region of the body.[13].
Stimulation of the sympathetic nervous system causes contraction of the erector muscles, located at the base of the hair follicles, causing the hair to stand up. The erection of the hair expands the layer of air in contact with the skin, decreasing air convection movements and therefore reducing heat loss. In humans, lacking fur, this mechanism is not important and produces what is commonly called goosebumps.
In general terms, energy expenditure can be subdivided into two categories of thermogenesis: obligatory thermogenesis and facultative thermogenesis. Mandatory thermogenic processes are essential for the life of all cells in the body and include the processes that maintain constant and normal body temperature. The major component of obligatory thermogenesis is provided by the basal metabolic rate. Food-induced thermogenesis, which derives from the digestion, absorption and metabolism of dietary nutrients, is also considered an obligatory thermogenic process. Unlike obligatory thermogenesis that occurs continuously in all organs of the body, facultative thermogenesis can be rapidly activated or deactivated and takes place mainly in two tissues, skeletal muscle and brown fat.[14] Body temperature, which in homeothermic animals, as in humans, is generally several degrees higher than that of the environment, requires for its maintenance the activation of heat production and conservation mechanisms that compensate for its constant loss due to dissipation to the external environment. At thermoneutral temperature, the thyroid is the main regulator of energy expenditure through mechanisms that modulate oxygen consumption in the mitochondria of various tissues, particularly skeletal muscle and the liver.[15] The thyroid also participates in the regulation of adaptive or facultative thermogenesis, acting synergistically with norepinephrine (norepinephrine) in situations in which the body requires additional heat to maintain normothermia during exposure to cold.[16].
When the ambient temperature is below the lower critical temperature, endothermic organisms produce heat in skeletal muscle and brown fat by two mechanisms:
The primary motor center for shivering thermogenesis is located in the posterior hypothalamus. Cold stress stimulates and heat inhibits this nervous center. When, in response to cold stress, muscle tone increases up to 5 times over normal production. Shivering thermogenesis consists of the involuntary, synchronous and rhythmic contraction of the motor units of the opposing muscles and, consequently, large movements are avoided and external work is not performed. Since no external work is done, all the energy released when shivering appears as heat.
In small mammals and neonatal humans, non-shivering thermogenesis occurs mainly by mitochondrial uncoupling in brown adipose tissue or brown fat and is regulated by the sympathetic nervous system.
After a few hours of cold exposure, heat production in brown fat plays a dominant role in replacing shivering thermogenesis with non-shivering thermogenesis as the main source of additional heat to prevent hypothermia.
The ability of brown fat to generate heat is due to the existence of a unique protein in the mitochondria of the adipose cells of this tissue: the uncoupling protein UCP1. This protein has the ability to permeabilize the mitochondrial membrane to protons. In this way, the oxidation of metabolites in mitochondrial respiration and the proton pump that this generates are not invested in the generation of ATP, as in normal mitochondria, but is dissipated as heat.[17] Non-shivering thermogenesis is facultative, only activated when the organism needs additional heat, and is adaptive, in the sense that weeks are required to recruit thermogenic tissue. The process of adaptation to cold is under the control of the hypothalamus, which activates the sympathetic nervous system and the secretion of norepinephrine and promotes the expression of UCP1. Uncoupling does not occur without sympathetic stimulation, but it also does not occur in the absence of thyroid hormone. Other hormones, such as leptin and insulin, are potent stimulators of UCP1 expression and thermogenesis in brown fat.[16] The distinction between adrenergic thermogenesis and non-shivering thermogenesis is important. Although all mammals respond to norepinephrine by increasing metabolism, in animals not adapted to cold this increase mainly represents the response of organs that are not involved in non-shivering thermogenesis. Only the increase in metabolism after adaptation to cold represents thermoregulatory non-shivering thermogenesis.[18].
As shivering thermogenesis is poorly developed in neonates, the main mechanism of heat production in these children is non-shivering thermogenesis. In neonates, brown fat is located in the subcutaneous tissue, adjacent to the main vessels of the neck, abdomen and thorax, around the scapula, and in large quantities in the adrenal areas.[19].
Traditionally, it was thought that brown fat in humans was only found in the neonatal stage. It was considered that brown fat regresses with age and that adult humans practically lack it. However, since the 1970s, several independent works have demonstrated the presence of active brown fat in adult humans, its activity is adjustable by thermogenic stimuli, and it is found in quantities that could have a considerable effect on thermogenesis. The activity of brown fatty tissue decreases with age, from 50% activity in subjects aged 20 years to 10% in subjects aged 50-60 years. In this sense, it was also found that brown fat is more prevalent in children than in adults, and that its activity increases in adolescence where it could have a specific metabolic function.[20] On the other hand, recent work suggests that mitochondrial uncoupling not only occurs in brown fat, but also in skeletal muscle tissue. Both tissues would be involved in non-shivering thermogenesis induced by cold and regulated by the sympathetic nervous system.[21].
Although the activation of shivering and non-shivering thermogenesis reactions does not require the expression of thermogenic genes, chronic exposure to cold activates the expression of several genes important in the thermoregulatory process.[14].