Humans are endotherms, animals that keep their body temperature within a stable range using heat production and heat dissipation. The ability to produce heat from calories is an essential mechanism all endotherms need to survive. For life-sustaining cellular reactions to take place, there needs to be sufficient intake of calories. The molecules in food contain energy, or calories, stored in chemical bonds. Metabolic reactions, such as the Kreb’s cycle, can extract energy from these chemical bonds and use it to power other metabolic reactions that maintain the body’s homeostasis. 
Calories are a measure of energy. The lowercase “c” calories (cal) is the amount of energy to raise the temperature of one gram of water by one degree Celsius at one atmospheric pressure. Likewise, the uppercase “C” Calories (kcal) is the amount of energy needed to raise the temperature of one kilogram of water by one degree Celsius. When referring to food, the Calorie (Kcal) is used. Proteins and carbohydrates both contain 4 kcal/g. Fats provide 9 kcal/g. The U.S. Dietary Guidelines say 45-65% of calories should come from carbohydrates, 20-35% should come from total fat, and 10-35% should come from protein.
Another important concept is the metabolic rate. Metabolic rate is the amount of energy expended by an animal over a period. The rate is measured in joules, cal’s, or Kcal’s per unit time. The Basal Metabolic Rate (BMR) is an animal’s baseline metabolic rate. BMR is measured in a thermoneutral environment, or a situation where an animal’s temperature is maintained without energy consumption. Adult human females and males have an average BMR of 1300-1500 kcal/day and 1600-1800 kcal/day, respectively. With stress, activity, and energy expenditure the metabolic rate rises, but the BMR remains the same. On average, the daily metabolic rate is 150 percent of one’s BMR, 1950-2250 kcal/day for adult females and 2400-2700 kcal/day for adult males. 
The mitochondria control cellular metabolism and produce most of the heat in the body. This control is because of the Kreb’s Cycle, and the Electron Transport Chain occur inside this important organelle. The Kreb’s Cycle, also known as the TCA cycle or Citric Acid cycle, is a central driver of cellular respiration and takes place in the matrix of the mitochondria. It begins when pyruvate, derived initially from glucose, is oxidized to acetyl CoA. Acetyl CoA then undergoes a series of redox reactions resulting in high energy bonds in the form of NADH, FADH2, and ATP molecules. The NADH and FADH2 will then pass through the Electron Transport Chain. This action takes place in the inner membrane of the mitochondria. The Electron Transport Chain, through oxidative phosphorylation, will generate more ATP. Finally, this ATP is then used to molecular power reactions throughout the body which creates heat. 
If the heat produced by these reactions is exceeded by total body heat loss, the body is in a state of hypothermia. Hypothermia is defined as a core body temperature below 35 degrees Celsius (95 degrees F). Three classifications of hypothermia are mild, moderate, or severe. Mild hypothermia is characterized by substantial shivering and behavior changes. It is defined as a core temperature between 32-35 degrees C (89.6-95 degrees F). A core body temperature between 28-32 degrees C (82.4-89.6 degrees F) is defined as moderate hypothermia. It is characterized by dilation of pupils, cardiac arrhythmias, confusion, possible loss of consciousness, and lack of shivering. Severe hypothermia is defined as a core temperature below 28 degrees C (82.4 degrees F). Severe bradycardia and ventricular fibrillation can occur at this stage. Cardiac arrest becomes more likely as the body becomes colder. To counteract hypothermia, the hypothalamus can increase the body’s overall metabolic rate generating more heat. Shivering is an involuntary response to cold temperatures that uses muscle contractions to generate heat. It can increase the basal metabolic rate by as much as 5 to 6 times. The intensity of shivering depends on the core temperature and a person’s BMI. Studies show that decreased shivering is correlated with increased body fat. Additionally, peripheral vessels can vasoconstrict keeping blood centrally and minimizing heat loss to the environment. The outer body then acts as a barrier between the body’s core and the environment. Frostbite risk increases as peripheral vasoconstriction increases. The treatment of mild to moderate hypothermia is the removal of cold, wet clothing and rapid-rewarming with a hot bath at 37-39 degrees C. If the hypothermia is severe, active internal rewarming is indicated. The treatment process is often painful and may require pain medication. 
The opposite of hypothermia is hyperthermia. Hyperthermia is the state of increased core body temperature resulting from the body creating more heat than it can dissipate. The most tested example is Malignant Hyperthermia (MH). Malignant Hyperthermia is a disorder of skeletal muscle that presents as a hypermetabolic response to Anesthetic gases and depolarizing muscle relaxants such as succinylcholine. MH is described as hyperthermia, acidosis, hyperkalemia, muscle rigidity, rhabdomyolysis, tachypnea, and tachycardia. Genetic abnormalities can predispose one to MH. The majority of cases are caused by an autosomal dominant mutation in the ryanodine receptor resulting in an uncontrolled release of intracellular Ca2+ from the skeletal muscle sarcoplasmic reticulum. The increase in Ca2+ stimulates muscle contractions, ATP hydrolysis, CO2 production, O2 consumption, and heat production. It is hypothesized that the decrease in levels of ATP results in worsened integrity of the cell membrane resulting in Potassium and Creatine Kinase release. Treatment involves the immediate cessation of the causative agent, hyperventilation, cooling if hyperthermic (38.5 degrees C), and dantrolene. Cooling can be done with whatever methods are available (4 degrees C normal saline IV, ice packs). Dantrolene binds to the ryanodine receptor and reduces its activity decreasing the amount of Ca2+ released into the sarcoplasmic reticulum. The patient should also be observed for at least 24 hours in an intensive care unit. In the 1970s, the mortality rate of Malignant Hyperthermia was 80%. Because of increased knowledge and understanding, it is below 5%. 
A stable body temperature requires sufficient intake of calories and proper metabolic response to outside stimuli. If either of these requirements is not met, the body will be unable to maintain homeostasis. Sufficient intake of calories involves the body absorbing nutrients, such as glucose, and transforming them into useable end products, ATP. The mitochondria do this in a series of reactions known as the Kreb’s Cycle and Electron Transport Chain. This energy fuels the metabolic processes that maintain a stable temperature. If the heat produced by these metabolic reactions is exceeded by the heat lost, the body is in a state of hypothermia. On the contrary, hyperthermia is when more heat is generated than lost. A stable balance is required for the body to remain in homeostasis.
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