Thermoregulation is a mechanism by which mammals maintain body temperature with tightly controlled self-regulation independent of external temperatures. Temperature regulation is a type of homeostasis and a means of preserving a stable internal temperature in order to survive. Ectotherms are animals that depend on their external environment for body heat, while endotherms are animals that use thermoregulation to maintain a somewhat consistent internal body temperature even when their external environment changes. Humans and other mammals and birds are endotherms. Human beings have a normal core internal temperature of around 37 degrees Celsius (98.6 degrees Fahrenheit) measured most accurately via a rectal probe thermometer. This is the optimal temperature at which the human body’s systems function. Thermoregulation is crucial to human life; without thermoregulation, the human body would cease to function. Thermoregulation also plays an adaptive role in the body's response to infectious pathogens. 
Issues of Concern
The body's core internal temperature has a narrow range and typically ranges 97-99 F with tight regulation. When the body’s ability to thermoregulate becomes disrupted it can result in overheating (hyperthermia) or being too cool (hypothermia). Either state can have deleterious effects on the various body systems, most significantly reduced blood flow leading to ischemia and multiple organ failure.
Viral illness or another infectious disease can cause a person to develop a fever, raising the core temperature above 37 degrees Celsius. Fever is a result of the body releasing pyrogens such as cytokines, prostaglandins, and thromboxane. These pyrogens induce cyclooxygenase 2 (COX2) to convert arachidonic acid to prostaglandin E2 (PGE2). PGE2 binds to receptors in the hypothalamus, increasing the thermogenic set point. This elevated temperature set point results in the body working to achieve a higher internal temperature. 
The brain, more specifically the hypothalamus, controls thermoregulation. If the hypothalamus senses internal temperatures growing too hot or too cold, it will automatically send signals to the skin, glands, muscles, and organs. For example, if the body is generating heat during high-level exercise or if the external ambient temperature is elevated enough to cause a rise in the core temperature, afferent signals to the hypothalamus result in efferent signals to the cells of the skin to produce sweat. Sweating is one mechanism the body can use to cool itself as heat is lost through the process of sweat evaporation. In contrast, when the body experiences a cold environment, a shivering reflex results in skeletal muscles contracting and generating heat; additionally, the arrector pili muscles (a type of smooth muscle) raise the bodily hair follicles to trap the heat generated.
Organ Systems Involved
Multiple organs and body systems are affected when thermoregulation is impaired. During a heat-related illness, insufficient thermoregulation can result in multiple organ and system impairment. (Notice that many of these issues are interconnected.)
- The heart experiences increased work as it increases both heart rate and cardiac output.
- The circulatory system can experience intravascular volume depletion.
- The brain can experience ischemia and/or edema.
- The gastrointestinal tract is vulnerable to hemorrhage and infection as the intestinal mucosa becomes increasingly permeable.
- The lungs become impaired if sustained hyperventilation, hyperpnea, and pulmonary vasodilation lead to ARDS.
- Acute renal failure is an effect of intravascular volume depletion and impaired circulation.
- Liver cells suffer because of the fever, ischemia, and cytokine increase in the intestinal tract.
- Various organs can become ischemic from microthrombi or DIC.
- Electrolyte abnormalities are likely as well as hypoglycemia, metabolic acidosis, and respiratory alkalosis.
When body temperatures are severely decreased in hypothermia, the body’s systems are also adversely affected. The cardiovascular system is susceptible to dysrhythmias such as ventricular fibrillation. The central nervous system's (CNS) electrical activity is noticeably diminished. Noncardiogenic pulmonary edema can occur as well as cold diuresis. Additionally, hypothermia causes preglomerular vasoconstriction which leads to decreased glomerular filtration rate (GFR) and decreased renal blood flow (RBF). 
The core body temperature is tightly controlled in a narrow range although slight changes in core body temperature occur every day, depending upon variables such as circadian rhythm and menses. When a person is unable to regulate his or her body temperature, various pathologies ensue. The human body has four different methods for maintaining core temperature: vaporization, radiation, convection, and conduction. To keep the body functioning, it must be at its ideal temperature. This requires sufficient intravascular volume and cardiovascular function as the body must be able to transport the rising internal heat to its surface for release. Elderly people are at increased risk for disorders of thermoregulation due to a generally decreased intravascular volume and decreased cardiac function.
Thermoregulation has three mechanisms: afferent sensing, central control, and efferent responses. There are receptors for both heat and cold throughout the human body. Afferent sensing works through these receptors to determine if the body core temperature is too hold or cold. The hypothalamus is the central controller of thermoregulation. There is also an efferent behavioral component that responds to fluctuations in body temperature. For example, if a person is feeling too warm, the normal response is to remove an outer article of clothing. If a person is feeling too cold, they choose to wear more layers of clothing. Efferent responses also consist of automatic responses by the body to protect itself from extreme changes in temperature, such as sweating, vasodilation, vasoconstriction, and shivering.
The thermoregulatory sweat test (TST) is a specific clinical test that is used to diagnose certain conditions that cause abnormal temperature regulation and defects in sweat production in the body. It measures a patient’s ability to produce sweat in a controlled, heated and humidified environment and assesses the patient's central and autonomic nervous systems to determine if the thermoregulatory centers are working correctly.
To perform the thermoregulatory sweat test, the patient is placed in a chamber that slowly rises in temperature. Before the chamber is heated, the patient is coated with a special kind of indicator powder that will change in color when sweat is produced. This powder, when changing color, will be useful in visualizing which skin is sweating versus not sweating. Results of the patient’s sweat pattern will be documented by digital photography, and abnormal TST patterns can indicate if there is dysfunction in the autonomic nervous system. Certain differentials can be made depending on the type of sweat pattern found from the TST (along with history and clinical presentation) including hyperhidrosis, small fiber and autonomic neuropathies, multiple system atrophy, Parkinson disease with autonomic dysfunction, and pure autonomic failure.
When external environments are exceedingly warm, or a person is engaging in strenuous physical activity, the heat that is produced inside his or her body is typically transported to the blood. The blood then carries the heat through numerous capillaries that are located directly under the skin. Near the surface, the blood can lose heat. This cooled blood can then be transported back through the body to prevent the body temperature from becoming too high. Sweat is also a means by which the body cools itself down. Sweat is produced by glands and through evaporation at the topmost skin layer (the epidermis) can release heat. This describes vaporization, one of the four mechanisms used to maintain core body temperature. Radiation occurs when the heat that is released from the body’s surface is moved into the surrounding air; convection occurs when cooler air surrounds the body’s surface, and conduction is when heat is transferred by direct contact with a cooler object (such an ice pack). Hydration is paramount while exposed to environmental heat or during physical activity—not only to maintain adequate circulating intravascular fluid volume but also, to aid in conduction processes that cool the body down. When cold fluids are ingested, the heat is released into the fluid and excreted out of the body as sweat or urine.
While infection is a central mechanism for raising the core body temperature, several peripheral mechanisms can also result in elevated body temperature. As previously discussed, multiple diseases with dysfunctional thermoregulatory mechanisms including small fiber and autonomic neuropathies, radiculopathies, and central autonomic disorders such as multiple system atrophy, Parkinson disease with autonomic dysfunction, and pure autonomic failure. Decreased cardiac function is also a notable risk factor for dysfunctional thermoregulation as the body depends on the heart to efficiently pump blood to the surface as a cooling mechanism. Without this mechanism patients with impaired cardiac function are at risk of having heat-related illnesses, including those whose medications exert therapeutic effects through negative inotropic and chronotropic properties. 
Volume depletion in conditions such as dehydration is another risk factor for dysfunctional thermoregulation. Without sufficient intravascular fluid the body loses a mechanism for cooling as well as increased blood viscosity and the resultant strain on the cardiovascular system.
In contrast, hypothermia is defined as low internal body temperature, or a temperature less than 35 degrees Celsius (95 degrees Fahrenheit). It is usually caused by too much heat loss from cold weather exposure or cold water immersion. During cold water immersion, the diving reflex causes vasoconstriction in the visceral muscles as a mechanism to keep a person’s essential organs, like their heart and brain, supplied with blood and protected from hypoxia and ischemia.
There are two different types of hypothermia: primary and secondary. Primary hypothermia is when the cold environment is the direct cause and secondary hypothermia is when a patient’s illness causes hypothermia. Conduction, convection, and radiation also come into play with hypothermia; this is how the rate of heat loss is determined. Hypothermia decelerates all physiologic roles include metabolic rate, mental awareness, nerve conduction, neuromuscular reaction times, and both the cardiovascular and respiratory systems. As previously mentioned, the vasoconstriction caused by hypothermia induces renal dysfunction and cold diuresis due to the decreased levels of ADH. These decreased levels of antidiuretic hormone result in dilute urine. The vasoconstriction during hypothermia can mask concomitant hypovolemia. During rewarming, the subsequent vasodilation results in a redistribution of fluid which can cause cardiac arrest or abrupt shock, known as rewarming collapse. 
A multiple organ approach is indicated when treating patients with heat-related illnesses. Respiratory, hepatic, renal, and circulatory support must be initiated with potentially multiple cooling methods. Giving fresh frozen plasma and blood platelets as needed is also recommended. Previous animal studies have also shown that the administration of thrombomodulin can be helpful because it demonstrates anti-DIC and anti-inflammatory properties.
Malignant hyperthermia is a rare, but life-threatening. Susceptible patients typically have an inherited mutation that results in abnormal ryanodine receptors (RYR-1) or have other myopathies such as Duchenne muscular dystrophy, central core disease, neuroleptic malignant syndrome, and King-Denborough syndrome. When a susceptible patient is given certain anesthetic agents, notably halogenated or neuromuscular depolarizing agents, the abnormal RYR-1 cause an unregulated release of calcium ion resulting in excessive skeletal muscle contraction and increased metabolism. The initial clinical features present as muscle rigidity elevated heart rate and elevated end-tidal carbon dioxide. The person’s temperature becomes elevated along with a metabolic acidosis.
The rapid treatment of malignant hyperthermia is paramount to prevent fatality. Once malignant hyperthermia is suspected, dantrolene must be given intravenously as it is a ryanodine receptor antagonist. It is also important to rapidly cool the patient, give 100% oxygen, and regulate metabolic acidosis.
Serotonin syndrome and neuroleptic malignant syndrome are other disorders of temperature regulation. Although they both present with hyperthermia and are both due to adverse drug reactions, it is important to distinguish them from one another. Neuroleptic malignant syndrome (NMS) persists over many days and is depicted by rigidity or the complete loss of voluntary movements. Serotonin syndrome is much more rapid, happening over a timespan of hours, and can present with fast movements such as tremor, muscular spasms, and hyperactive reflexes. These two reactions must be managed emergently to avoid organ failure, especially if the patient’s temperature goes past 40.5 degrees Celsius. There are both physical and pharmaceutical ways to cool the affected patients. Physical methods include providing cool towels, ice packs, cooling blanket systems, and intravenous infusion of fluids. Pharmaceuticals include sedatives and antipyretics such as paracetamol and NSAIDs. (Note that in critically ill patients, it is important to consider the individual patient’s renal function and gastric function before administering NSAIDs.)
Hyperthyroidism is another disorder of thermoregulation. In this endocrine disease, the thyroid is overactive resulting in increased metabolic pathways. The core temperature is elevated due to an elevated basal metabolic rate with resultant increased heat production, as well as increased oxygen consumption and ATP turnover.
In contrast, some diseases that can cause decreased heat production, or hypothermia include endocrinological diseases such as diabetes, hypothyroidism, hypoadrenalism, and hypopituitarism. Those who are most at risk for hypothermia are elderly patients, trauma patients, those who are mentally ill, those who are abusing alcohol or drugs, and those with low socioeconomic status. Ordinarily, people who get hypothermia have an underlying issue—either from a disease or surgery.
When a patient with one of these diseases presents with hypothermia, it is imperative to treat the underlying disease to effectively treat the hypothermia. This includes treatments with pharmaceuticals including triiodothyronine and steroids. Other causes of hypothermia from decreased metabolic rates include malnourishment, severe burns, and hypoglycemia.
Hypothermia, like hyperthermia, affects all of the human body’s systems. When the core temperature drops below 30 degrees Celsius, the heart is vulnerable to developing arrhythmias. Hypothermia can cause hypovolemia and electrolyte disturbances; therefore, it is important to keep the patient hydrated and to manage their electrolyte disturbances.
Central pathology can also result in impaired thermoregulation. Patients with traumatic brain injury are likely to have impaired thermoregulation due to the hypothalamus's key role in regulating core body temperature. Other problems in the CNS that affect thermoregulation can include tumors in the CNS, spinal cord injuries, intracranial hemorrhage, and diseases such as Parkinson, Wernicke encephalopathy, and multiple sclerosis.
Patients who are on the extreme spectrums of age (such as infants and elderly persons) are at higher risk for disorders of thermoregulation, especially when ill. The very young and the very old cannot easily increase their metabolic rates given their lower muscle mass and decreased shivering reflex. Senescent changes include those affecting vasomotor sweating function, skeletal muscle response, and temperature perception. Elderly persons have lower than normal internal body temperatures and decreased immunity; when they have an infection they may not mount a normal pyretic response. Instead, they may present with hypothermia secondary to infection. Studies have shown that the core temperatures of elderly patients with sepsis within their first 24 hours of presentation are a predictor of mortality. 
Hypothermia is not always deleterious and it can be useful in treatments. Certain patients who have endured hypoxic-ischemic brain injuries or suffered from cardiac arrests may benefit from therapeutic hypothermia (TH). Elevated body temperatures in the setting of brain injury or post-cardiac arrest is associated with higher mortality rates and slower recovery. Thus, hypothermia in post-cardiac arrest patients and perinatal hypoxic patients is used to prevent neuronal injury by lowering the demand for metabolic oxygen.
When TH is recommended, it should proceed very rapidly. Ice packs and intravenous administration of cold fluids are utilized to cool the patient. Cooling blanket systems, cooling suits, and cooling helmets or caps may also be effective. For post-cardiac arrest patients, intranasal cooling using nasal probes also may be utilized.