How Does the Human Body Regulate Temperature?

The human body normally maintains a set body temperature. How does this happen? How do we generate additional heat when our body is too cold, and how do we cool off when we are too hot? Although part of this response is voluntary, how do we really know that we are cold, and what is our brain doing involuntarily to keep temperatures constant. At times our temperature will move away from the set point, whether through environmental effects such as exposure to cold or internal processes including fever and exercise. How is Heat Distributed Throughout the Body? Humans are homeotherms, maintaining an average core temperature of 37 +/- 0.5 degrees Celsius. Core temperature varies slightly due to environmental and metabolic factors. Exercise or fever may raise core temperature by up to three degrees, while exposure to cold may lower core temperature by a degree. Beyond these boundaries, the human is susceptible to heat stroke (elevated temperature) or hypothermia, both of which are life threatening conditions. While core temperature is tightly regulated, skin temperature varies greatly in response to metabolism and the environment. Temperature receptors in the skin (cold and hot) detect these changes, initiating compensatory mechanisms through the central nervous system. How Does the Body Produce Heat? Energy in the form of heat is gained by two methods: production (metabolic) and acquisition (environmental). Heat production and retention are elevated by a number of factors. 1. Muscular Activity and Shivering the conversion of stored chemical energy results in a net increase in heat throughout the skeletal muscle, which spreads through the body. 2. Thyroxin effect on cells thyroid hormones increase the basal metabolic rate in cells throughout the body, resulting in thermogenesis through increased conversion of chemical energy 3. Epinephrine, Norepinephrine and Sympathetic Innervation effect on cells sympathetic effects include the following: Piloerection contraction of body hair muscles, trapping air next to the skin and reducing heat loss (small effect in humans) Increased Metabolic Rate Brown Fat Oxidation In brown fat cells, oxidative phosphorylation is uncoupled from ATP production,

resulting in complete conversion of chemical energy to heat energy (little brown fat remaining in adults) Skin Vasoconstriction decrease in radiation of heat from skin

How Does the Body Remove Heat? Heat is transferred from the body to the environment through a range of mechanisms. Mode of Heat Transfer Percentage Loss (Normal Conditions) Radiation 60% Conduction 15% to air 3% to other objects Evaporation 22% The body can increase the rate of heat transfer by either increasing its conduction rate (movement of heat from core to surface) or transfer rate (movement of heat from surface to environment). Conduction rate is greatly effected by the dilation and constriction of vessels, while transfer rate is a function of air temperature, perspiration, clothing, food and body position among other factors (learn more about body thermodynamics). When environmental temperature is above that of the core, sweating rates can be modified to achieve desired cooling. Sweat glands are stimulated by sympathetic cholinergic fibers as well as by epinephrine in the blood. In times of rapid temperature change, reabsorption of sodium and chloride is compromised during perspiration. Sweat glands may excrete as high as 60 mEq/L of Na and Cl ions (as opposed to 5 mEq/L during times of optimal reabsorption). If the body is exposed to heat for long periods of time, electrolyte levels may fall, leading to systemic dehydration.Given time, the human body compensates for this effect through the process of acclimatization. Through an increase in aldosterone levels, sweat glands are capable of increasing reabsorption of electrolytes at high temperatures. How Does the Body Know What to Do? Temperature receptors are located throughout the skin, as well as in the spinal cord, abdominal viscera, and in and around the great veins. Stimuli to these receptors triggers heat and cold sensitive neurons in the hypothalamus as well as higher cortical centers in the cerebrum. The hypothalamic receptors are part of the brains thermostat center, which regulates responses that promote gain and loss of heat. Sympathetic Response TRH secretion from the hypothalamus

 Stimulation of the hypothalamic shivering center. Cerebral stimulation elicits a voluntary response. Curling up to reduce exposed surface area Change in muscular activity Food consumption Change of environment (moving from a cold room to a warm room) Change of clothing What Causes a Change in the Set Point? Infection may provide the stimulus required to initiate fever. It is believed that the presence of bacteria or virus stimulates the release of endogenous pyrogen (a small molecular weight protein) from macrophages. Although no individual endogenous pyrogen causes all fever, studies have shown a high correlation with interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, and interferons beta and gamma, each cytokine independently capable of causing the febrile state. Endogenous pyrogen travels through the blood, arriving at the hypothalamus to cause an increase in the set-point, possibly through a subsequent increase in prostaglandin levels. The brain appears to recognize the presence of endogenous pyrogens at certain sites known as circumventricular organs that lack a blood-brain barrier. How does the body protect itself from high fever? It remains unclear as to the mechanism of regulating a new set-point. Arginine vasopressin and alpha-melanocyte-stimulating hormone are two peptides that have been shown to reduce fever, but there are many candidates for the process of controlling fever levels, either by mediating effects of endogenous pyrogens or acting independently to reduce the set-point. What Are the Effects of Fever? Is it Beneficial? Fever is an energetically costly process, especially in the compromised state of infection, and some studies have shown that the administration of antipyretic (fever-reducing) drugs appear to have little effect on the course of certain diseases. However, the fever state is shown to have a number of effects on hostdefense. Enhanced neutrophil migration Increased production of antibacterial substances by neutrophils (eg, superoxide anion) Increased production of interferon Increased antiviral and antitumor activity of interferon Increased T-cell proliferation Decreased growth of microorganisms in iron-poor environment

How Does Aspirin Lower Fever? Hippocrates wrote of a bitter powder extracted from willow bark that eased aches and pains and reduce fevers as long ago as the fifth century B.C. Eventually, it was discovered that the active ingredient in willow bark is salycin, which is converted by the body into salycilic acid. Aspirin works by inhibiting the effects of pyrogens on the hypothalamus. Aspirin is acetylsalycilic acid, used because it is believed to be less harmful to the stomach. Acetylsalycilic Acid References: Guyton, A.C., M.D and J.E. Hall M.D., Textbook of Medical Physiology (9th Edition). W.B. Saunders Company, 1996. Kapit, Macey and Meisami. The Physiology Coloring Book. Pp. 133-134. 1987. Harper Collins Publishing. Klugger, Mathew J. Fever Revisited. Pediatrics 1992; 90: 846-850. Saper, Clifford B.; Breder, Christopher D. The Neurologic Basis Of Fever. N Engl J Med 1994; 330: 1880-1886.

KEY CONCEPTS 1. Energy balance occurs when the energy going into a system equals that coming out. If energy in (dietary intake) exceeds energy out (exercise, metabolism, processing of food, etc), weight gain occurs. The international unit of heat is the calorie, which is defined as the amount of heat needed to raise 1 gram of water 1o C. Usually energy units are expressed in Kilocalories (=1,000 calories); a Kilocalorie is also called a Calorie (Note the capital C to distinguish it from calorie). 2. Food intake is regulated by the "satiety" center in the hypothalamus and involves both short term (hunger bouts between meals) and long term (overall weight regulation) control. Short term responses include hormonal release (CCK) from the small intestine and distention of the stomach to inhibit feeding following a meal, as well as Neuropeptide Y (NPY) release in the hypothalamus between meals to stimulate feeding. Long term regulation of weight involves Leptin, a hormone secreted by white fat cells, which inhibits feeding. Leptin acts by inhibiting a stimulatory brain neuropeptide, Melanocortin. Orexin A and B are other brain neuropeptides that stimulate feeding. 3. Metabolism is the sum of all of the cellular reactions in the body. At the level of the organism, metabolism is usually measured as the rate of oxygen consumption. A standardized estimate of metabolism is Basal Metabolic Rate (BMR), which is the minimal rate of energy expenditure in an awake individual. To obtain an accurate BMR, energy requiring activities are minimized (e.g., absence of physical activity, sweating, shivering, food processing, etc.). 4. Core body temperature is tightly regulated at about 99oF even under cold and hot environmental conditions. The preoptic/anterior hypothalamus is responsible for regulating body temperature. This brain area contains a thermostat which acts like a set point to control various effector systems. Constant body temperature is achieved by balancing heat gain with heat loss effector systems. When body temperature is slightly elevated relative to the set point, heat loss mechanisms are stimulated (sweating, shallow and more rapid breathing, increased blood flow to the skin). When body temperature decreases relative to the set point, heat production or heat conservation mechanisms are activated (shivering, nonshivering thermogenesis-NST, peripheral cooling of the limbs, and modification of behavior, such as putting on a sweater). The hypothalamic set point, however, can change (e.g., during a fever) due to infective agents, such as bacterial pyrogens. LECTURE OBJECTIVES

1. What is energy balance and how is it important? 2. Establish how set point is important to temperature regulation 3. Describe how the body actively maintains a constant body temperature despite changes in ambient temperature LECTURE OUTLINE

I. ENERGY BALANCE A. Energy Balance is when energy in = energy out 1. Most of our daily energy budget goes to maintaining Tb 2. Calorie, a measure of heat quantity B. Regulation of food intake is a complex of interactions 1. Neuropeptides are important in long term regulation of body weight a. NPY and the Orexins stimulate feeding b. Melanocortin inhibits feeding 2. Leptin, a hormone, regulates these neuropeptides a. Parabiosis experiment (Ob/Ob mice) 3. Summary of short & long term regulation of body weight C. Metabolic rate 1. Oxygen consumption as an measure of metabolism 2. Stadardizing metabolic measurements 3. Basal metabolic rate (BMR) a. Conditions that have to be meet for an accurate BMR (inactive, thermoneutral, fasted, etc.) b. Scaling 4. Ambient temperature has a major effect on metabolism D. Daily energy balance II. TEMPERATURE REGULATION--GENERAL CONCEPTS A. Heat exchange and the individual 1. Heat flux goes down a temperature gradient 2. Modes of heat transfer (Radiation, Conduction, Convection, and Evaporation)

B. Body temperature is regulated at 99oF C. Energy expenditure changes with environmental temperature 1. Zone of thermoneutrality 2. Sweating in the hot and shivering in the cold use energy III. THERMOREGULATORY CENTER AND SET POINT A. Thermostat is in PO/AH region of hypothalamus B. Set Point Theory 1. Deviations from set point 2. Shifts in the set point a. Fever as a change in set point b. Causes of fever--roles of pyrogens and Prostaglandins IV. PHYSIOLOGICAL MECHANISMS -- THE SPECIFICS A. Heat gain and heat loss determine body temperature 1. Only core temperature is regulated at 99oF B. Specific Physiological Mechanisms 1. Vasoconstriction and vasodilation of vessels 2. Shivering 3. Nonshivering thermogenesis (NST) a. Role of brown fat b. Molecular mechanism for heat production-Thermogenin 4. Sweating a. Heat acclimation and Aldosterone

Internal Regulation: Temperature Regulation & Thirst

How do human beings adapt to the differences in the environmental extremes represented by the images above (desert) and below (Le Moyne)? For about five minutes in small groups, the class should list as many adaptations as you can think of for living in each of these environmental settings.

I. Temperature Regulation A. Basal Metabolism = energy used each day to maintain constant body temperature while at rest

1700 calories (kcal) of 2600 calories of average total daily energy expenditure goes to basal metabolism.

B. Homeostasis = biological processes which keep temperature & other body variables within a certain range For example, temperature, weight, hydration (fluids; H2O) content of blood (acidity, oxygen, fat, glucose) Homeostasis is maintained by both (1) internal biological processes and (2) external behaviors. Set Point: homeostasis relies upon set points for each body variable, that is, a specific narrow range of acceptable values which the body must maintain. For example, the human body temperature generally stay between roughly 36.5 and 37.5 degrees Celsius (97.7 and 99.5 degrees Fahrenheit) Negative Feedback: The processes the body uses to maintain set points relies upon reducing the discrepancy between the current value of the variable and the set point value. This approach is called negative feedback. (See graphic and example on right).

C. Controlling Body Temperature

Poikilothermic Animals: their body temperature is the same as the environment's Reptiles, amphibians (turtles, etc.), and most marine animals like fish

They do not have internal mechanisms (generally) to affect their body temperature, e.g., they lack the ability to shudder or sweat They move within the environment (use behavioral means) to keep their body temperature in proper range. Some poikilothermic animals such as frogs, fish, and insects use molecules of antifreeze (glycerol and others) to survive in temperatures at 40 degrees F. Others effectively dehydrate their tissues before actually freezing and minimize tissue damage due to ice crystals.

Homeothermic Animals: Maintain an almost constant body temperature despite variations in the environment's by use of physical mechanisms Birds, mammals, humans Homeothermic animals employ energy requiring fuel (food) in order to maintain their body temperature, a major component of basal metabolism. In humans the constant body temperature hovers near 37.0 C (98.6 F) Cattle = 38.0 C (100.4 F) Horse = 38.3 C (100.9 F) Dog = 39.0 C (102.2 F) Mongolian Gerbil = 37.5 C (99.5 F) Goat = 39.0 C (102.2 F) Mouse = 36.9 C (98.4 F)

The Advantages of Constant High Body Temperature (ca. 37 Celsius) 1. Mechanisms for cooling are less efficient than for heating. It is important for body to be warmer than air. 2. High body heat keeps animal ready for rapid movement.

Note: Above 40 C (104 F) some proteins become unstable. Hence, body heat needs to be lower than 40 C. Cells for reproduction (esp. sperm in males) must be kept cooler than rest of body.

Mechanisms for raising heat include going to a warmer place, putting on more clothing, shivering, decreasing blood flow to skin, becoming more active, increasing metabolic rate, huddling with others, etc. Mechanisms for lowering heat include finding a cooler place, becoming less active, sweating or panting, taking off clothing or shedding coat of fur, and diverting blood to the skin. Physiological Mechanisms of Temperature Regulation

The major brain mechanisms for heat regulation are found in two nuclei of the hypothalamus: (2) preoptic area (POA) and (2) anterior hypothalamus (AH) = POA/AH (treated as one area)

POA/AH monitors its own temperature + receives input from receptors in skin & spinal cord. It then sends signals to the body to engage in activities like shivering, raising body metabolism, etc. Mechanisms for heat control -- shivering, sweating, etc., -- gradually develop in maturing mammal and are not present at birth. For example, room temperature of 68-73 F is comfortable for people, but too cold for newborn rat.

Fever & Infection

Infection > Leukocytes > interleuken-1 > Prostaglandins > POA/AH > Body temperature goes up Moderate temperature rise may help to kiss or weaken some bacteria. Fevers of 105-109 F can be fatal

II. Thirst Water = 70% of the body of a mammal. The chemical processes of the body require that there be different concentrations of fluid. Thus, water is necessary for all bodily functions. Mechanisms of Water Regulation

When body needs water, posterior pituitary gland releases vasopressin (= antidiruetic hormone [ADH]) which causes the kidneys to reabsorb water & increases concentration of urine. Most humans drink more water than we need and excrete the excess.

It is possible to drink so much water to cause hyponatremia (lack of sodium) and, possibly, death.

Police investigating death of fraternity pledge

By GREG WELTER - Staff Writer

"Thursday, February 03, 2005 - A Chico State University student died Wednesday morning following what police have termed "fraternity pledge activities." Matthew William Carrington, 21, formerly of Concord, was pledging Chi Tau fraternity and collapsed in the basement of the house at 440 W. Fourth St. sometime before 5 a.m. Authorities are looking into reports that he and other pledges may have been forced to drink large quantities of water and exercise heavily, inducing a sometimes deadly condition called hyponatremia." --Chico (CA) Enterprise-Record
Two types of thirst: Osmotic (due to eating salty foods) and hypovolemic (due to loss of fluids) Osmotic Thirst

The set point for solutes (molecules in fluid) in body is constant at ca. 0.1 M Osmotic Pressure = water tends to flow across a semipermeable membrane from area of low solute concentration to high solute concentration. (The membrane is "semipermeable" because the water can pass through but the solute

can't.)

Cell membranes are semipermeable When a person eats very salty food, the result is a higher concentration of sodium ion solutes in the extracellular fluid. Osmotic pressure draws water out of cells. Certain neurons detect the lowering of their water content and this triggers osmotic thirst. We tend to drink more water and kidneys excrete more salt. Where are the osmotic pressure detectors? o OVLT (organum vasculosum laminae terminalis) -- a set of neurons in the third ventricle. o Stomach receptors detect high levels of sodium Detectors affect (1) the supraoptic nucleus & paraventricular nucleus of the hypothalamus which, in turn, signal the posterior pituitary to control release of vasopressin, and (2) the lateral preoptic area of the hypothalamus which controls drinking.

Hypovolemic Thirst

= thirst based on low blood volume (therefore, low blood pressure) so that nutrients & water cannot get to body's cells. Need to replenish water and lost solutes (e.g., salt). Sodium craving => Aldosterone released => kidneys, salivary glands, sweat glands preserve sodium & excrete less concentrated urine. Mechanisms in hypovolemic thirst
o

Baroreceptors: receptors attached to large veins detece pressure of blood returning to the heart Kidneys: release the hormone renin when blood volume is low => splits a blood protein, angiotensinogen to form angiotensin I => converted to the hormone angiotensin II => constricts blood vessels Subfonical organ (SFO) = neurons near the third ventricle of the brain signal the preoptic area when they are stimulated by angiotensin. Synergistic effect: if baroreceptors signal very low blood pressure, much less angiotensin is required to stimulate thirst.