Understanding What is the Pathophysiology of Temperature?

September 30, 2025 •

4 min read

A healthy human body tightly maintains its core temperature within a narrow range of about 36.5 to 37.5°C (97.7 to 99.5°F), despite fluctuating external conditions. This article explains what is the pathophysiology of temperature, detailing the complex mechanisms that keep us warm or cool and what happens when they go wrong due to disease or other stressors.

Quick Summary

The pathophysiology of temperature involves the hypothalamus as the body's thermostat, regulating thermal balance through heat production and loss. Dysfunctions include fever, an elevation of the hypothalamic set-point, and hyperthermia, an uncontrolled temperature rise due to overwhelmed regulatory mechanisms.

Key Points

Hypothalamic control: The hypothalamus acts as the body's central thermostat, receiving signals from thermoreceptors and controlling heat production and loss.
Fever is regulated: Fever is a controlled elevation of the body's temperature set-point, triggered by pyrogens during an immune response.
Hyperthermia is unregulated: Hyperthermia is an uncontrolled rise in body temperature due to overwhelmed heat dissipation, where the hypothalamic set-point remains normal.
Hypothermia is uncontrolled heat loss: Hypothermia is a drop in core temperature caused by heat loss surpassing the body's ability to generate heat.
CNS damage impairs regulation: Damage to the central nervous system from injury or stroke can directly affect the hypothalamus and disrupt thermoregulation, leading to poikilothermia.
Heat generation involves multiple systems: To generate heat, the body uses shivering, non-shivering thermogenesis, vasoconstriction, and hormones like catecholamines.
Heat dissipation involves multiple systems: To lose heat, the body relies on sweating and vasodilation to transfer heat away from the core.

The Body's Thermostat: The Hypothalamus

The regulation of internal body temperature, known as thermoregulation, is a finely tuned process centered in the hypothalamus of the brain. This almond-sized structure acts like a biological thermostat, receiving constant thermal information from the body's core and periphery. Specialized nerve cells, or thermoreceptors, located in the skin, spinal cord, and visceral organs continuously monitor temperature changes and relay this data to the hypothalamus. The hypothalamus processes this input and initiates autonomic and behavioral responses to maintain the core temperature within its narrow, optimal range.

The Mechanisms of Normal Thermoregulation

When the hypothalamus detects a temperature deviation, it triggers a series of coordinated responses to either generate or dissipate heat.

To combat cold (heat generation and conservation):

Shivering: The posterior hypothalamus signals the skeletal muscles to contract rapidly, an involuntary process that increases metabolic heat production.
Non-shivering thermogenesis: Especially in infants, brown adipose tissue (BAT) can generate heat by uncoupling oxidative phosphorylation from ATP production.
Vasoconstriction: The sympathetic nervous system constricts blood vessels in the skin, reducing blood flow to the surface and minimizing heat loss.
Piloerection: 'Goosebumps' trap a layer of air close to the skin, providing insulation.
Hormonal changes: Adrenal glands release catecholamines (epinephrine, norepinephrine), and the thyroid releases hormones to increase the metabolic rate and heat production.

To combat heat (heat dissipation):

Sweating: Sympathetic nerves stimulate sweat glands, and as the sweat evaporates from the skin, it transfers heat away from the body.
Vasodilation: Blood vessels in the skin dilate, increasing blood flow to the surface, where heat can be released to the environment via radiation and convection.
Behavioral changes: The hypothalamus drives behaviors such as seeking shade, removing clothing, or reducing physical activity.

The Pathophysiology of Fever (Pyrexia)

Fever is a regulated elevation of the body's core temperature in response to a pathogen or inflammatory stimulus. It is not an uncontrolled overheating but a deliberate change orchestrated by the hypothalamus.

The Febrile Response

Fever begins when exogenous pyrogens (from sources like bacteria or viruses) and endogenous pyrogens (immune-derived cytokines) stimulate the production of prostaglandin E2 (PGE2) in the hypothalamus. PGE2 acts to raise the body's temperature set-point. In response, the body conserves and generates heat through mechanisms like shivering and vasoconstriction until the new set-point is reached. As the cause of the fever is resolved or treated, the hypothalamic set-point returns to normal, triggering heat-dissipating responses such as sweating.

Hyperthermia vs. Fever

It is critical to distinguish fever from hyperthermia, as their underlying pathophysiology and clinical management differ.


Feature	Fever (Pyrexia)	Hyperthermia
Thermoregulatory control	Regulated; hypothalamus raises the set-point.	Unregulated; hypothalamus set-point remains normal.
Underlying mechanism	Immune response to infection or inflammation, mediated by pyrogens.	Overwhelmed heat dissipation mechanisms, external or internal heat overload.
Initial body response	Heat-generating/conserving mechanisms (shivering, vasoconstriction).	Heat-dissipating mechanisms (vasodilation, sweating) become ineffective.
Causes	Infection, inflammation, cancer, certain medications.	Environmental heat (heatstroke), excessive exertion, certain drugs (stimulants, anesthetics), endocrine disorders.
Treatment approach	Antipyretics (e.g., NSAIDs) that block PGE2 synthesis are effective.	Rapid physical cooling is the priority; antipyretics are ineffective.

Pathophysiology of Hyperthermia

Hyperthermia occurs when the body's heat load exceeds its ability to dissipate heat, leading to an uncontrolled rise in temperature.

Types of Hyperthermia

Hyperthermia can manifest in different forms. Heatstroke is the most severe, characterized by a core temperature above 40°C (104°F) and central nervous system dysfunction. It can be caused by intense exercise in heat (exertional) or prolonged exposure during heat waves (classic). The damage results from high temperatures, inflammation, and potential multiorgan failure. Drug-induced hyperthermia can occur with substances like stimulants or certain anesthetics that increase heat production or prevent heat loss. Malignant hyperthermia is a rare genetic reaction to anesthetics, causing severe muscle contractions and excessive heat generation.

Pathophysiology of Hypothermia

Hypothermia is a decrease in core body temperature below 35°C (95°F), happening when heat loss outpaces production. Causes include cold exposure without proper insulation, impaired heat generation due to conditions like hypothyroidism or malnutrition, or increased heat loss from factors such as alcohol consumption. In some vulnerable individuals, like the elderly or infants, severe infections can paradoxically lead to hypothermia, often indicating a poor prognosis.

Neurological Conditions Affecting Thermoregulation

Damage to the central nervous system can disrupt thermoregulation. For example, traumatic brain injury can harm the hypothalamic thermostat, potentially causing neurogenic fever. Spinal cord injuries, particularly those affecting the upper spine, can impair autonomic control over heat conservation below the injury level, making individuals more susceptible to environmental temperature changes (poikilothermia). Strokes and other brain lesions can also lead to abnormal thermal responses.

Conclusion

The pathophysiology of temperature involves the complex coordination of heat production and loss by the hypothalamus. Disturbances can result in regulated responses like fever, where the set-point is elevated, or unregulated conditions like hyperthermia and hypothermia. Accurate identification of the underlying cause is essential for effective treatment. For more detailed information, consult {Link: NCBI Bookshelf https://www.ncbi.nlm.nih.gov/books/NBK507838/}.

Frequently Asked Questions

Fever is a regulated increase in the body's temperature set-point, driven by the hypothalamus during an immune response. Hyperthermia is an unregulated rise in body temperature that occurs when the body's heat-dissipating mechanisms are overwhelmed and the set-point is unchanged.

The hypothalamus receives sensory information from thermoreceptors about the body's internal and external temperature. It then sends signals to initiate heat-generating responses (like shivering and vasoconstriction) or heat-dissipating responses (like sweating and vasodilation) to maintain a stable core temperature.

Pyrogens are fever-producing substances, including both exogenous (microorganisms like bacteria and viruses) and endogenous (immune cytokines like IL-1, IL-6). They trigger the release of prostaglandin E2 (PGE2) in the brain, which in turn raises the hypothalamic temperature set-point.

Common causes of hyperthermia include environmental heat stress (heatstroke), intense physical exertion, certain medications (like stimulants or anesthetics), and conditions that increase metabolic heat production.

Hypothermia is a dangerous drop in core body temperature below 35°C (95°F). It is caused by prolonged exposure to cold, decreased heat production due to illness or age, or conditions that increase heat loss, such as alcohol use.

Some medications can affect thermoregulation. Antipyretics like aspirin reduce fever by blocking the synthesis of PGE2. Other drugs, such as stimulants, can cause hyperthermia by increasing metabolic heat production or inhibiting heat dissipation.

Yes. Central nervous system injuries, including traumatic brain injury, spinal cord injury, or stroke, can damage the hypothalamic thermostat and disrupt the body's ability to properly regulate its temperature, a condition known as poikilothermia.