Premed · Premed · Anatomy Physiology 2
Lecture 17: Energy Balance and Thermoregulation
Anatomy and Physiology II
Learning Objectives
By the end of this lecture, students will be able to:
- Define metabolic rate and distinguish between basal metabolic rate (BMR) and total metabolic rate
- Explain the concept of energy balance and its relationship to body weight
- Describe the hormonal regulation of appetite and food intake
- Explain the mechanisms of heat production and heat loss in the body
- Describe the role of the hypothalamus in thermoregulation
- Differentiate between fever, hyperthermia, and hypothermia
Lecture Content
I. Metabolic Rate
Metabolic rate refers to the total amount of energy expended, or heat produced, by the body per unit time. It is measured in kilocalories per hour (kcal/h) or kilojoules per day (kJ/day) and can be assessed either directly through direct calorimetry, which measures heat output, or indirectly through indirect calorimetry, which measures oxygen consumption.
The basal metabolic rate (BMR) is the rate of energy expenditure at rest, in a fasting state, within a thermoneutral environment. It reflects the energy required to sustain basic life functions such as cellular metabolism, cardiac activity, brain function, and breathing, and accounts for approximately 60 to 75% of daily energy expenditure. The average BMR ranges from about 1,200 to 1,800 kcal/day, varying with age, sex, body size, and thyroid status.
Several factors influence BMR. A greater body surface area is associated with a higher BMR. Age causes BMR to decline at a rate of approximately 2 to 3% per decade after age 20. Males generally have a higher BMR than females owing to greater muscle mass. Thyroid hormones (T3 and T4) are the most important hormonal regulators of BMR, while sympathetic nervous system activation increases BMR through the effects of catecholamines. Body temperature also plays a role, with BMR rising approximately 7% for every 0.5 degrees Celsius increase in core temperature. Lean body mass is another important factor because muscle is considerably more metabolically active than adipose tissue.
The total metabolic rate (TMR) equals the BMR plus the energy used for physical activity plus the thermic effect of food. The thermic effect of food, also called diet-induced thermogenesis, represents the energy required to digest, absorb, and process nutrients and accounts for roughly 10% of caloric intake. Physical activity is the most variable component, contributing 15 to 30% of TMR in sedentary individuals and substantially more in athletes.
II. Energy Balance and Body Weight
Energy balance describes the relationship between energy intake from food and energy output through metabolic rate, physical activity, and heat loss. A positive energy balance exists when intake exceeds output, resulting in weight gain as excess energy is stored as fat. A negative energy balance occurs when output exceeds intake, leading to weight loss as body stores are mobilized. Energy equilibrium, where intake equals output, produces a stable body weight. As a general approximation, 3,500 kcal of excess energy corresponds to about one pound (0.45 kg) of body fat.
The regulation of food intake involves complex neural and hormonal signals converging on the hypothalamus.
Hypothalamic Appetite Centers
The feeding (hunger) center in the lateral hypothalamus stimulates appetite and food-seeking behavior through neurotransmitters such as neuropeptide Y (NPY) and orexin, which are potent appetite stimulators. The satiety center in the ventromedial hypothalamus inhibits food intake when stimulated and responds to rising blood glucose and nutrient signals. The arcuate nucleus serves as the primary integrator of peripheral hunger and satiety signals, containing both orexigenic (appetite-stimulating) and anorexigenic (appetite-suppressing) neurons.
Key Hormones Regulating Appetite
Leptin is produced by adipose tissue in proportion to fat stores and acts on the hypothalamus to suppress appetite and increase energy expenditure, thereby signaling long-term energy status. Leptin resistance, in which the hypothalamus becomes less responsive to leptin despite elevated levels, is a characteristic feature of obesity. Ghrelin, often called the "hunger hormone," is produced by the stomach when it is empty and stimulates appetite via the hypothalamus; its levels rise before meals and fall after eating. Insulin, secreted by pancreatic beta cells, acts on the hypothalamus to reduce appetite, functioning as a long-term satiety signal. Cholecystokinin (CCK) is released by the duodenum in response to fats and proteins and promotes short-term satiety. Peptide YY (PYY) is released by the ileum and colon after meals and suppresses appetite. Glucagon-like peptide 1 (GLP-1), released by intestinal L-cells, promotes satiety, slows gastric emptying, and enhances insulin secretion.
<image>A multi-panel diagram of appetite regulation. Panel A: A sagittal brain section highlighting the hypothalamic nuclei involved in appetite control — the lateral hypothalamus (feeding center), ventromedial hypothalamus (satiety center), and arcuate nucleus. Orexigenic neurons (NPY/AgRP) and anorexigenic neurons (POMC/CART) are shown in the arcuate nucleus with their respective projections. Panel B: A schematic of the peripheral hormonal signals converging on the hypothalamus — ghrelin from the empty stomach (stimulatory, shown with upward arrows before meals), leptin from adipose tissue (inhibitory, proportional to fat mass), insulin from the pancreas (inhibitory), CCK from the duodenum (inhibitory, postprandial), and PYY from the distal gut (inhibitory, postprandial). Arrows indicate stimulatory or inhibitory effects on food intake. Panel C: A graph showing blood levels of ghrelin (peaking before meals and dropping after) and leptin (relatively stable, proportional to adiposity) over a 24-hour cycle with three meals marked.</image>
III. Heat Production (Thermogenesis)
All metabolic reactions produce heat as a byproduct of the inherent inefficiency of energy conversion. The major sources of body heat include the basal metabolism of all organs, with the liver, brain, heart, and endocrine glands being particularly significant contributors. Skeletal muscle activity represents another major heat source, and exercise can increase heat production 10 to 40 times above resting levels.
Shivering thermogenesis consists of involuntary, rhythmic muscle contractions that generate heat without producing useful work. Non-shivering thermogenesis generates heat through metabolic activity without muscle contraction and is mediated primarily by brown adipose tissue (BAT), which contains abundant mitochondria equipped with uncoupling protein 1 (UCP1, also called thermogenin). UCP1 allows protons to re-enter the mitochondrial matrix without passing through ATP synthase, so the energy of the proton gradient is released as heat rather than being captured in ATP. Brown adipose tissue is particularly important in neonates, who have significant BAT deposits, although adults retain small amounts. Additional sources of heat include the thermic effect of food and the metabolic effects of hormones such as thyroid hormones and catecholamines (epinephrine and norepinephrine), which increase cellular metabolic rate.
IV. Heat Exchange Mechanisms
The body exchanges heat with the environment through four physical mechanisms. Radiation is the emission of infrared thermal energy from the body surface to surrounding objects, does not require direct contact, and accounts for approximately 50% of heat loss at rest. Conduction is the direct transfer of heat between objects in physical contact, such as from the body to clothing or a chair, and is notable because water conducts heat approximately 25 times faster than air, creating a significant risk of hypothermia in cold water. Convection involves the transfer of heat by movement of air or water over the body surface; warmed air rises away from the skin and is replaced by cooler air, with wind and fans accelerating convective heat loss. Evaporation is the conversion of water to vapor, consuming latent heat from the skin, with approximately 0.58 kcal of heat lost per milliliter of water evaporated. Insensible water loss of about 600 mL per day occurs from the skin and lungs without being perceived as sweating. Sensible perspiration, or sweating, becomes the major cooling mechanism when ambient temperature approaches or exceeds body temperature and is the only effective heat dissipation mechanism when the environmental temperature exceeds body temperature.
<image>A four-panel figure illustrating the mechanisms of heat exchange between the body and the environment. Panel A (Radiation): A human figure emitting infrared waves toward cooler surrounding walls, floor, and objects, with a thermographic overlay showing heat distribution on the body surface. Panel B (Conduction): A person sitting on a chair with direct heat transfer arrows at contact points between skin and chair surface. Panel C (Convection): A standing figure with arrows showing warmed air rising from the skin surface and cooler air moving in to replace it; an inset shows the effect of wind increasing convective heat loss. Panel D (Evaporation): A close-up of the skin surface showing sweat glands producing sweat, water evaporating from the skin, and heat energy being carried away in the water vapor. A bar graph summarizes the relative contribution of each mechanism at rest in a thermoneutral environment: radiation ~50%, evaporation ~20%, convection ~15%, conduction ~15%.</image>
V. Thermoregulation by the Hypothalamus
Core body temperature is normally maintained at approximately 37 degrees Celsius (98.6 degrees Fahrenheit) within a narrow range of 36.1 to 37.8 degrees Celsius. The hypothalamus serves as the body's thermostat, specifically the preoptic area and anterior hypothalamus. It receives input from central thermoreceptors, which are neurons in the hypothalamus itself that monitor blood temperature, and from peripheral thermoreceptors, which are temperature-sensitive nerve endings in the skin that detect surface temperature changes.
Response to Cold (Below Set Point)
When body temperature falls below the set point, the hypothalamus initiates both heat conservation and heat generation responses. Heat conservation is achieved through cutaneous vasoconstriction, in which sympathetic stimulation constricts dermal arterioles to reduce blood flow to the skin and minimize radiant heat loss, as well as through behavioral responses such as putting on clothing, curling up, and seeking shelter. Heat generation involves shivering thermogenesis driven by somatic motor signals to skeletal muscles, non-shivering thermogenesis through sympathetic activation of brown fat (norepinephrine activating UCP1), increased thyroid hormone release during chronic cold exposure (T3 and T4 gradually increase BMR over days to weeks), and epinephrine release from the adrenal medulla to increase metabolic rate.
Response to Heat (Above Set Point)
When body temperature rises above the set point, the hypothalamus activates heat dissipation mechanisms. Cutaneous vasodilation results from inhibition of sympathetic vasoconstrictor tone, allowing dilation of dermal arterioles so that more blood flows to the skin surface, increasing radiative and convective heat loss. Sweating is triggered by sympathetic cholinergic stimulation of eccrine sweat glands for evaporative cooling, with sweat rates reaching 1 to 2 liters per hour during intense exercise in the heat. Behavioral responses such as removing clothing, seeking shade, and reducing activity also contribute to cooling.
<image>A thermoregulation feedback loop diagram. Center: the hypothalamic thermostat with the set point at 37°C. Left pathway (cold response): peripheral and central thermoreceptors detect a decrease in temperature and send afferent signals to the hypothalamus. Efferent outputs include sympathetic signals to cutaneous blood vessels (vasoconstriction shown with narrowed arterioles in a skin cross-section), somatic motor signals to skeletal muscles (shivering), sympathetic activation of brown adipose tissue (non-shivering thermogenesis), and release of thyroid hormones (increased BMR). Right pathway (heat response): thermoreceptors detect an increase in temperature. Efferent outputs include reduced sympathetic tone to cutaneous blood vessels (vasodilation shown with widened arterioles in a skin cross-section and flushed skin), sympathetic cholinergic signals to eccrine sweat glands (sweating and evaporative cooling). Both pathways include negative feedback arrows returning core temperature toward the set point.</image>
VI. Fever, Hyperthermia, and Hypothermia
Fever
A fever represents an upward resetting of the hypothalamic thermostat set point in response to pyrogens. Exogenous pyrogens include bacterial endotoxins and viral particles. Endogenous pyrogens are cytokines released by immune cells, including interleukin-1, interleukin-6, TNF-alpha, and prostaglandin E2. Prostaglandin E2 (PGE2) directly acts on the hypothalamus to raise the set point, and aspirin and NSAIDs reduce fever by inhibiting cyclooxygenase (COX), thereby blocking PGE2 synthesis.
Fever progresses through three phases. During the onset (chill phase), the set point rises and the body feels cold relative to the new set point, triggering vasoconstriction and shivering as body temperature climbs. In the stadium (plateau) phase, body temperature reaches the new set point and heat production equals heat loss at the elevated level. During defervescence (crisis), the set point returns to normal, the body feels hot, and vasodilation and sweating bring the temperature back down. Moderate fever up to approximately 39 degrees Celsius is beneficial because it enhances immune function and inhibits bacterial growth. Fever becomes dangerous above about 41 degrees Celsius and potentially fatal above 43 degrees Celsius due to protein denaturation.
Hyperthermia
Hyperthermia is an elevated body temperature that occurs without resetting of the hypothalamic set point. Heat exhaustion results from volume depletion due to excessive sweating and manifests as weakness, dizziness, and nausea. Heat stroke occurs when the core temperature exceeds 40 degrees Celsius and thermoregulatory mechanisms fail, constituting a medical emergency characterized by cessation of sweating, confusion, organ damage, and potential death.
Hypothermia
Hypothermia is defined as a core temperature below 35 degrees Celsius and can be caused by prolonged cold exposure, immersion in cold water, or impaired thermoregulation in the elderly or intoxicated individuals. The condition progresses from shivering to confusion, then loss of shivering, followed by cardiac arrhythmias and ultimately cardiac arrest. Mild hypothermia ranges from 32 to 35 degrees Celsius, moderate hypothermia from 28 to 32 degrees Celsius, and severe hypothermia occurs below 28 degrees Celsius.
VII. Clinical Correlations
Obesity results from chronic positive energy balance and is defined as a BMI of 30 kg/m squared or greater. It is associated with type 2 diabetes, cardiovascular disease, hypertension, and certain cancers, and frequently involves leptin resistance, in which leptin levels are elevated but the hypothalamic response is diminished. Anorexia nervosa involves severe caloric restriction leading to negative energy balance, low BMR, hypothermia, and amenorrhea. Thyroid disorders significantly affect metabolic rate: hyperthyroidism produces an elevated BMR, heat intolerance, and weight loss, while hypothyroidism results in a reduced BMR, cold intolerance, and weight gain. Malignant hyperthermia is a rare genetic condition triggered by certain anesthetics that produces uncontrolled skeletal muscle metabolism and heat production, constituting a medical emergency treated with dantrolene.
