Hyperthermia

Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. According to the International Emergency Medicine Education Project, severe hyperthermia "becomes a medical emergency requiring immediate treatment to prevent disability or death". Almost half a million deaths are recorded every year from hyperthermia.
The most common causes include heat stroke and adverse reactions to drugs. Heat stroke is an acute temperature elevation caused by exposure to excessive heat, or combination of heat and humidity, that overwhelms the heat-regulating mechanisms of the body. The latter is a relatively rare side effect of many drugs, particularly those that affect the central nervous system. Malignant hyperthermia is a rare complication of some types of general anesthesia. Hyperthermia can also be caused by a traumatic brain injury.
Hyperthermia differs from fever in that the body's temperature set point remains unchanged. The opposite is hypothermia, which occurs when the temperature drops below that required to maintain normal metabolism. The term is from Greek ὑπέρ, hyper, meaning "above", and θέρμος, thermos, meaning "heat".
The highest recorded body temperature recorded in a patient who survived hyperthermia is, measured on 10 July 1980 from a man who had been admitted to hospital for serious heat stroke.

Classification

In humans, hyperthermia is defined as a temperature greater than, depending on the reference used, that occurs without a change in the body's temperature set point.
The normal human body temperature can be as high as in the late afternoon. Hyperthermia requires an elevation from the temperature that would otherwise be expected. Such elevations range from mild to extreme; body temperatures above can be life-threatening.

Signs and symptoms

An early stage of hyperthermia can be "heat exhaustion", whose symptoms can include heavy sweating, rapid breathing and a fast, weak pulse. If the condition progresses to heat stroke, then hot, dry skin is typical as blood vessels dilate in an attempt to increase heat loss. An inability to cool the body through perspiration may cause dry skin. Hyperthermia from neurological disease may include little or no sweating, cardiovascular problems, and confusion or delirium.
Other signs and symptoms vary. Accompanying dehydration can produce nausea, vomiting, headaches, and low blood pressure and the latter can lead to fainting or dizziness, especially if the standing position is assumed quickly.
In severe heat stroke, confusion and aggressive behavior may be observed. Heart rate and respiration rate will increase as blood pressure drops and the heart attempts to maintain adequate circulation. The decrease in blood pressure can then cause blood vessels to contract reflexively, resulting in a pale or bluish skin color in advanced cases. Young children, in particular, may have seizures. Eventually, organ failure, unconsciousness, and death will result.

Causes

occurs when thermoregulation is overwhelmed by a combination of excessive metabolic production of heat, excessive environmental heat, and insufficient or impaired heat loss, resulting in an abnormally high body temperature. In severe cases, temperatures can exceed. Heat stroke may be non-exertional or exertional.

Exertional

Significant physical exertion in hot conditions can generate heat beyond the ability to cool because, in addition to the heat, humidity of the environment may reduce the efficiency of the body's normal cooling mechanisms. Human heat-loss mechanisms are limited primarily to sweating and vasodilation of skin vessels. Other factors, such as insufficient water intake, consuming alcohol, or lack of air conditioning, can worsen the problem.
The increase in body temperature that results from a breakdown in thermoregulation affects the body biochemically. Enzymes involved in metabolic pathways within the body such as cellular respiration fail to work effectively at higher temperatures, and further increases can lead them to denature, reducing their ability to catalyse essential chemical reactions. This loss of enzymatic control affects the functioning of major organs with high energy demands such as the heart and brain. Loss of fluid and electrolytes causes heat cramps – slow muscular contraction and severe muscular spasm lasting between one and three minutes. Almost all cases of heat cramps involve vigorous physical exertion. Body temperature may remain normal or a little higher than normal and cramps are concentrated in heavily used muscles.

Situational

Situational heat stroke occurs in the absence of exertion. It mostly affects the young and elderly. In the elderly in particular, it can be precipitated by medications that reduce vasodilation and sweating, such as anticholinergic drugs, antihistamines, and diuretics. In this situation, the body's tolerance for high environmental temperature may be insufficient, even at rest.
Heat waves are often followed by a rise in the death rate, and these 'classical hyperthermia' deaths typically involve the elderly and infirm. This is partly because thermoregulation involves cardiovascular, respiratory, and renal systems which may be inadequate for the additional stress because of the existing burden of aging and disease, further compromised by medications. During the July 1995 heatwave in Chicago, there were at least 700 heat-related deaths. The strongest risk factors were being confined to bed, and living alone, while the risk was reduced for those with working air conditioners and those with access to transportation. Even then, reported deaths may be underestimated as diagnosis can be misclassified as stroke or heart attack.

Drugs

Some drugs cause excessive internal heat production. The rate of drug-induced hyperthermia is higher where use of these drugs is higher.

Many psychotropic medications, such as selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, and tricyclic antidepressants, can cause hyperthermia. Serotonin syndrome is a rare adverse reaction to overdose of these medications or the use of several simultaneously. Similarly, neuroleptic malignant syndrome is an uncommon reaction to neuroleptic agents. These syndromes are differentiated by other associated symptoms, such as tremor in serotonin syndrome and "lead-pipe" muscle rigidity in neuroleptic malignant syndrome.
Recreational drugs such as amphetamines and cocaine, PCP, dextromethorphan, LSD, and MDMA may cause hyperthermia.
Malignant hyperthermia is a rare reaction to common anesthetic agents or the paralytic agent succinylcholine. Those who have this reaction, which is potentially fatal, have a genetic predisposition.
The use of anticholinergics, more specifically muscarinic antagonists are thought to cause mild hyperthermic episodes due to its parasympatholytic effects. The sympathetic nervous system, also known as the "fight-or-flight response", dominates by raising catecholamine levels by the blocked action of the "rest and digest system".
Drugs that decouple oxidative phosphorylation may also cause hyperthermia. From this group of drugs the most well-known is 2,4-dinitrophenol which was used as a weight loss drug until dangers from its use became apparent.
Personal protective equipment

Those working in industry, in the military, or as first responders may be required to wear personal protective equipment against hazards such as chemical agents, gases, fire, small arms and improvised explosive devices. PPE includes a range of hazmat suits, firefighting turnout gear, body armor, and bomb suits, among others. Depending on design, the wearer may be encapsulated in a microclimate, due to an increase in thermal resistance and decrease in vapor permeability. As physical work is performed, the body's natural thermoregulation becomes ineffective. This is compounded by increased work rates, high ambient temperature and humidity levels, and direct exposure to the sun. The net effect is that desired protection from some environmental threats inadvertently increases the threat of heat stress.
The effect of PPE on hyperthermia has been noted in fighting the 2014 Ebola virus epidemic in Western Africa. Doctors and healthcare workers were only able to work for 40 minutes at a time in their protective suits, fearing heat stroke.

Other

Other rare causes of hyperthermia include thyrotoxicosis and an adrenal gland tumor, called pheochromocytoma, both of which can cause increased heat production. Damage to the central nervous system from brain hemorrhage, traumatic brain injury, status epilepticus, and other kinds of injury to the hypothalamus can also cause hyperthermia.

Pathophysiology

A fever occurs when the core temperature is set higher, through the action of the pre-optic region of the anterior hypothalamus. For example, in response to a bacterial or viral infection, certain white blood cells within the blood will release pyrogens which have a direct effect on the anterior hypothalamus, causing body temperature to rise, much like raising the temperature setting on a thermostat.
In contrast, hyperthermia occurs when the body temperature rises without a change in the heat control centers.
Some of the gastrointestinal symptoms of acute exertional heatstroke, such as vomiting, diarrhea, and gastrointestinal bleeding, may be caused by barrier dysfunction and subsequent endotoxemia. Ultraendurance athletes have been found to have significantly increased plasma endotoxin levels. Endotoxin stimulates many inflammatory cytokines, which in turn may cause multiorgan dysfunction. Experimentally, monkeys treated with oral antibiotics prior to induction of heat stroke do not become endotoxemic.
There is scientific support for the concept of a temperature set point; that is, maintenance of an optimal temperature for the metabolic processes that life depends on. Nervous activity in the preoptic-anterior hypothalamus of the brain triggers heat losing or heat generating activities through stimulation of the autonomic nervous system. The pre-optic anterior hypothalamus has been shown to contain warm sensitive, cool sensitive, and temperature insensitive neurons, to determine the body's temperature setpoint. As the temperature that these neurons are exposed to rises above, the rate of electrical discharge of the warm-sensitive neurons increases progressively. Cold-sensitive neurons increase their rate of electrical discharge progressively below.