Energy metabolism and heat balance

Nutritional components supplied to the body are gradually broken down into lower-energy forms as part of metabolism. The energy released in this process is used by the body to form ATP (adenosine triphosphate), which plays a central role in powering cellular activities. ATP is the universal energy carrier of the human body, usable by every cell, and is synthesized during cellular energy production. The sum of all cellular energy production processes constitutes the energy turnover of the entire body. The total energy requirement depends on various factors: The basal metabolic rate, for example, is defined as the minimum amount of energy the body requires at rest to maintain basic life processes, such as circulation and respiration. This basal metabolic rate can increase severalfold during physical exertion.

Energy metabolism is closely linked to heat balance: Every energy conversion process also releases energy as heat. This waste heat is the primary mechanism for heat production in the human body. Body temperature must be kept constant within a narrow range. If it deviates even slightly, many metabolic processes cannot function optimally; large deviations can cause them to stop completely. The center for temperature regulation is located in the hypothalamus; it receives input from temperature-sensitive neurons and can initiate regulatory mechanisms if the temperature deviates from the set point. To dissipate heat, the anterior hypothalamus triggers cutaneous vasodilation and stimulates eccrine sweat glands via sympathetic cholinergic fibers, utilizing evaporative cooling as the primary defense when ambient temperature exceeds body temperature. Conversely, to conserve heat and defend the core temperature, the posterior hypothalamus mediates peripheral vasoconstriction and the shivering reflex, though this balance can be pathologically disrupted by pyrogens (IL-1, TNF) that elevate the hypothalamic set-point during a fever.

The main energy-yielding nutrients in our food are carbohydrates, lipids, and proteins. They are absorbed by the body and are either stored (anabolism) or gradually broken down into lower-energy forms (catabolism). During breakdown, energy is released, which is primarily used to synthesize the universal energy currency, ATP, largely through the mitochondrial respiratory chain. The caloric value of a nutrient indicates how much energy is released during its breakdown.

Energy

• Definition
  • The chemical, thermal, mechanical, and electrical power that drives and sustains all physical functions.
  • In a biological system, energy is ingested in the form of chemical energy stored in food and translated into other forms of energy that are either stored or used to perform and maintain physical functions.
• Unit: kilocalories (kcal) or kilojoules (kJ)

Caloric value

• Definition: a measure of the chemical energy stored in a substance (e.g., a glucose molecule) that can be released as heat during the complete combustion of the substance
• Unit: kilojoules/g (SI unit); kilocalories/g (unit commonly used in everyday life; 1 kcal corresponds to 4.184 kJ)
• Physical caloric value: the energy that is released during the complete breakdown of a substance in an experimental setting (e.g., bomb calorimeter)
• Physiological caloric value: the energy that can actually be used by human metabolism
  • Atwater factor: a standardized energy conversion factor applied to macronutrients to calculate the caloric content of foods; used with kcal

The physiological caloric value is always lower than the physical caloric value because of energy lost through unabsorbed nutrients in the stool and incomplete protein breakdown, where nitrogen is discarded as urea instead of being fully oxidized for energy.

Other substances, such as alcohol, are also metabolized by cells: The physiological caloric value of alcohol is 29 kJ/g (7 kcal/g)!

To calculate a patient’s total daily caloric intake for metabolic assessments, remember the 4-4-9 Atwater factors: multiply grams of carbohydrates by 4, proteins by 4, and fats by 9 to determine the total kilocalories.

Energy balance

• Definition: the balance of energy intake, generation, and expenditure
• Positive energy balance: more energy intake than expenditure → energy storage → weight gain
• Negative energy balance: less energy intake than expenditure → energy store depletion → weight loss

Efficiency

• Definition: During work, energy is always lost as heat (so-called waste heat). In humans, efficiency describes the proportion of the total energy expended that is converted into external physical work. It ranges between 0 and 100%.
• Unit: none (proportion)
• Normal value: During physical work, efficiency is typically about 25% (i.e., three-quarters of the energy is released as waste heat).

Energy expenditure is measured in energy unit per time, e.g., kcal/day or J/day.

Total daily energy expenditure (TDEE) ^[1]

• Definition: the total amount of energy the body requires to maintain all metabolic processes
• Composition ^[2]
  • Basal metabolic rate (60–80% of TDEE)
  • Thermogenesis (approx. 10% of TDEE)
  • Physical activity (10–30% of TDEE)

Metabolic rate

• Definition
  • The rate of energy consumed to perform physical functions, measured in unit time, e.g., kJ/day or kcal/day
  • The metabolic rate is affected by genes, age, sex, race, diet, exercise, and disease (e.g., hyperthyroidism, sepsis).
• Basal metabolic rate (BMR)
  • The amount of energy required to maintain basic life-sustaining functions at rest in a temperate environment during digestive inactivity
  • Typically measured in the morning, after an overnight fast and 24 hours of no exercise
• Resting metabolic rate (RMR) ^[3]
  • The amount of energy required to maintain basic life-sustaining functions at rest in a temperate environment during digestive activity
  • Typically measured during the day after 12 hours of no exercise

Metabolic states of the body

During the postabsorptive state, the liver prioritizes maintaining blood glucose specifically for the brain and red blood cells. To do this, other tissues (like muscle) undergo "glucose sparing" by switching to fatty acid oxidation for their own energy needs.

The body's energy metabolism is founded on converting nutrients to ATP, which then provides the energy necessary for all cellular processes. The synthesis of ATP is typically classified by the type of metabolic processes based on oxygen demand and triggering activity. For further information, see “Electron transport chain and oxidative phosphorylation.”

Proteins and ketones are only used during catabolic states.

If the body is supplied with more energy than it needs, it creates energy stores, first in the form of glycogen, then in the form of triacylglycerols (TAGs) in adipose tissue.

Hormonal control of metabolism

• Thyroid hormones (T3 and T4): primarily regulate the basal metabolic rate (BMR)
  • Primary forms: thyroxine (T4) and triiodothyronine (T3); T3 is the more metabolically active form
  • Mechanism of action: increase BMR by stimulating metabolism, oxygen consumption, and heat production (thermogenesis) in most tissues
  • Metabolic effects
    • Carbohydrates: increase gluconeogenesis and glycogenolysis
    • Lipids: stimulate lipolysis
    • Proteins: primarily catabolic, leading to protein breakdown
• Glucocorticoids (e.g., cortisol): increase energy availability, particularly in response to stress
  • Mechanism of action: increase blood glucose concentrations
  • Metabolic effects
    • Carbohydrates: stimulate hepatic gluconeogenesis and decrease glucose uptake in peripheral tissues (e.g., muscle, adipose)
    • Proteins: promote proteolysis (muscle breakdown) to supply amino acid substrates for gluconeogenesis
    • Lipids: stimulate lipolysis, although chronic excess can cause fat redistribution (e.g., to the face and trunk)

Hormonal control of appetite

Also see "Regulation of appetite and satiety" in the "General endocrinology" article.

• Overview: Appetite and energy balance are regulated by hormones, primarily leptin and ghrelin, which act on the hypothalamus.
• Leptin (satiety hormone)
  • Source: adipose tissue (adipocytes)
  • Function: anorexigenic signal; suppresses appetite and signals energy abundance
  • Regulation: plasma levels are proportional to total body fat mass
• Ghrelin (hunger hormone)
  • Source: primarily endocrine cells in the stomach
  • Function: orexigenic signal; stimulates appetite
  • Regulation: levels rise before meals (anticipating food) and fall after eating

Ghrelin makes your stomach Growl (hunger). Leptin makes you feel Less hungry (satiety).

Calorimetry

• Definition: measures the amount of heat that is absorbed or released during physical, chemical, or biological processes
• Physiological application: determines an organism's metabolic rate (energy turnover) via heat release (direct calorimetry) or gas exchange (indirect calorimetry)

Direct calorimetry

• Definition: measures energy turnover via direct heat dissipation from the body
• Mechanism: Based on the first law of thermodynamics, all metabolic work eventually degrades into heat. To maintain a constant core temperature, this heat must be released.
• Procedure: A test person is placed in a closed chamber (so-called calorimeter or "Atwater-Rosa-Benedict" chamber). The change in temperature of the surrounding medium (air or water) after a certain time reflects the metabolic rate.
• Clinical reality: the gold standard for accuracy, but rarely used clinically due to cost, complexity, and inability to track rapid metabolic shifts

Indirect calorimetry

• Definition: measures energy turnover via O₂ consumption and CO₂ production
• Physiological basis: Since the body does not store significant O₂, consumption reflects immediate mitochondrial oxidative phosphorylation.
• Formula: energy turnover = (O₂ uptake/min) × caloric equivalent
• Unit: kJ/min
• Auxiliary variables
  • Caloric equivalent: the amount of energy (heat) released per liter of O₂ consumed; also see "Overview of the caloric equivalent and the respiratory quotient of various nutrients"
    • Unit: kJ/L or kcal/L
    • Problem: For an exact determination of the energy turnover, the precise proportion of nutrients in the food would have to be known. This can be determined using the respiratory quotient. If this is not possible, an average value for a so-called mixed diet is used.
  • Respiratory quotient (RQ): the quotient of CO₂ release and O₂ uptake
    • Basic consideration: Each nutrient has a specific RQ (see "Overview of the caloric equivalent and the respiratory quotient of various nutrients"). This is because the metabolism of the different nutrients consumes different amounts of O₂ and produces different amounts of CO₂.
    • Formula: RQ = VCO₂/ VO₂
    • Conclusion: If the RQ is known, the predominant nutrient being metabolized can be inferred. With a normal mixed diet, it is about 0.82. With a higher RQ, the predominant nutrients are more likely to be carbohydrates; with a lower RQ, more likely fats and proteins.

If RQ > 1.0, it suggests lipogenesis (overfeeding) or hyperventilation. If RQ < 0.7, it suggests gluconeogenesis or extreme starvation/ketosis.

• Example calculation: A patient has an O₂ uptake of 300 mL/min on a standard hospital (mixed) diet. Calculate the energy turnover in kJ/min and find the basal metabolic rate per day.
  • Formula: energy turnover = O₂ uptake/min × caloric equivalent
  • Given
    • O₂ uptake = 300 mL/min = 0.3 L/min
    • Caloric equivalent for a mixed diet ≈ 20 kJ/L O₂(or 4.82 kcal/L)
  • Calculation: energy turnover = 0.3 L O₂/min × 20 kJ/L O₂ = 6 kJ/min
  • To find the basal metabolic rate (BMR) per 24 hours: 6 kJ/min × 1440 minutes/day = 8,640 kJ/day

The body temperature of an organism must be kept constant within narrow limits. Even small deviations can impair the optimal function of many metabolic processes. The heat balance describes the mechanisms available to the body to regulate body temperature.

Body temperature

• Definitions
  • Core body temperature: the temperature inside the trunk, skull, and viscera; is kept constant at about 37°C (98.6°F) via a control loop to protect vital organs
  • Body shell temperature: the temperature of the skin and limbs is variable; it depends on the outside temperature
• Body temperature over the course of the day: The body temperature fluctuates by about 1 °C due to circadian rhythms regulated by the suprachiasmatic nucleus.
  • Minimum: around 4 a.m.
  • Maximum: around 6 p.m.

Thermoregulation

• Control center
  • Hypothalamus: acts as the body’s thermostat, maintaining a set-point of approximately 36.5°C (97.7°F) to 37.5°C (99.5°F); integrates central (blood) and peripheral (skin) temperature data
    • Anterior hypothalamus (preoptic area): responds to heat via vasodilation, sweating, and behavioral changes (seeking shade, removing clothes) → heat dissipation
    • Posterior hypothalamus: responds to cold via vasoconstriction, shivering, and non-shivering thermogenesis → heat conservation
• Temperature sensors
  • Central sensors: temperature-sensitive neurons in the anterior hypothalamus (preoptic area), in the lower brainstem, and in the spinal cord, monitoring the temperature of the blood
  • Peripheral sensors: located in the skin (Aδ and C-fibers); provide early warning signals to the hypothalamus before the core temperature actually drops

Remember "A/C"—Anterior = Cooling. If the anterior hypothalamus is lesioned, the patient will develop hyperthermia.

To maintain the set point temperature, the organism has several regulatory mechanisms at its disposal.

Heat production

The majority of heat in the organism is generated by the "waste heat" released during metabolic processes. If this is not sufficient, the following mechanisms are initiated:

1. Increased muscle activity: most important mechanism for heat production in adults
   • Voluntary: e.g., by walking around in the cold
   • Involuntary: through muscle shivering
2. Non-shivering thermogenesis: heat production through lipolysis in brown adipose tissue; important in infants
   • Mechanism: mitochondrial thermogenesis
     • Brown adipose tissue uncouples the electron transport chain via thermogenin (UCP-1) to produce heat instead of ATP

Heat loss and heat gain

Evaporation is the only way to lose heat when the ambient temperature is higher than body temperature. However, this also depends on the humidity: If the humidity is 100%, heat loss via evaporation is only possible up to an ambient temperature of 37°C! Conduction and convection only work if the air is cooler than the body temperature.

Pathomechanism of fever
In fever, there is an increase in the set point temperature in the hypothalamus under the influence of so-called pyrogens. Pyrogens can be endogenous substances, such as interleukin-1 or prostaglandin E₂ secreted by leukocytes (endogenous pyrogens), or foreign substances, such as bacterial components (exogenous pyrogens). During fever onset, one feels cold because the set point in the hypothalamus is suddenly higher than the core body temperature. To heat up the body, muscle shivering ("chills") and reduced cutaneous blood flow (pallor) occur. During fever reduction, on the other hand, the set point temperature in the hypothalamus drops again, the body is hotter than it should be, and heavy sweating and dilation of the skin vessels (reddened, moist skin) occur.

Heat loss via convection and conduction is only possible because the bloodstream transports heat from the body core to the periphery. The blood flow to the skin thus has a special regulatory function for body temperature. In the cold, cutaneous blood flow is reduced so that less heat is lost, whereas in the heat, the skin is increasingly perfused. The following mechanisms for cutaneous blood flow temperature regulation are possible:

• Sympathetic nervous system
  • In the cold (heat conservation)
    • System: sympathetic adrenergic
    • Mechanism: increased sympathetic activity → release of norepinephrine → activation of α₁-adrenoceptors on skin blood vessels → vasoconstriction → ↓ cutaneous blood flow → ↓ heat loss
  • In the heat (heat dissipation)
    • Phase 1 (passive vasodilation): mild heat
      • Mechanism: decreased sympathetic adrenergic activity → decreased norepinephrine release → decreased activation of α₁-adrenoceptors → blood vessels relax passively → ↑ cutaneous blood flow → ↑ heat loss
    • Phase 2 (active vasodilation): intense heat/exercise
      • System: sympathetic cholinergic
      • Mechanism: increased sympathetic activity → release of acetylcholine and co-transmitters (like VIP/nitric oxide) → activation of M3 muscarinic receptors → active vasodilation of skin blood vessels and sweating → ↑↑ cutaneous blood flow → ↑↑ heat loss
• Arteriovenous anastomoses (AVAs)
  • In the cold: AVAs are closed, blood can only flow through the capillary bed → ↓ heat loss
  • In the heat: AVAs are open, blood flows through the AVAs and through the capillaries, thereby increasing the surface area for heat loss → ↑ heat loss
• Countercurrent principle of arteries and veins
  • Principle
    • General: two material flows are guided past each other for heat or substance exchange
    • In relation to blood: Arteries and veins run parallel to the periphery and can exchange heat in the process.
      • Arterial blood flowing from the center to the periphery is cooled by the venous blood flowing past.
      • Venous blood flowing from the periphery to the center is warmed by the arterial blood.
  • Benefit
    • In the cold: vessels are constricted → improved heat exchange of the blood flows passing each other in the sense of the countercurrent principle → heat remains in the body core and very little is lost in the periphery
    • In the heat: vessels are dilated → blood flows passing each other in the sense of the countercurrent principle can exchange heat less effectively → arteries carry more heat to the periphery
• Lewis reaction (Hunting response): local protective reaction of the skin vessels in the cold
  • Principle: dilation of the skin vessels and thus an increase in blood flow for a short moment at regular intervals; prevents permanent damage by the constant hypothermia and the associated reduced perfusion

Glabrous skin (i.e., the palms and soles) only uses phase 1 (adrenergic withdrawal/passive vasodilation) for cooling.

If the skin stays below 10°C for too long, the body periodically dilates vessels to prevent frostbite (necrosis).

The pampiniform plexus utilizes a countercurrent heat exchange mechanism where warm arterial blood transfers thermal energy to the cooler, returning venous blood. This "pre-cooling" of arterial blood maintains the scrotal environment at approximately 34°C (2-3°C below core temperature), which is the physiological requirement for successful spermatogenesis.

There is only a relatively narrow temperature range in which we perceive the ambient temperature as comfortable. If the temperature deviates from this so-called indifference temperature, the body's regulatory mechanisms are activated. Long-term changes are also possible if one lives in areas with extreme temperature conditions for an extended period.

• Indifference temperature
  • Definition: The temperature range that we perceive as comfortable
  • Conditions: dependent on the ambient temperature, humidity, wind speed, thermal radiation, clothing, and activity

The indifference temperature is higher, the more heat loss is promoted! Since heat loss in water via conduction is significantly stronger, one gets cold faster in water than in air!