[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Physiology](https://durgical.com/en/physiology/) › [Temperature, exercise and metabolism](https://durgical.com/en/physiology/#s-integrative) › Fever

[Physiology](https://durgical.com/en/physiology/) · [Temperature, exercise and metabolism](https://durgical.com/en/physiology/#s-integrative)

# Fever

- Mechanism
- Exam priority: high

In fever the brain turns its thermostat up: the body feels cold and makes heat until it reaches the new temperature.

Updated 2026-11-01

Also called: Pyrexia

**See it in 3D:** [Hypothalamus](https://durgical.com/en/anatomy/hypothalamus/)

## Key points

- Exogenous pyrogens (Gram-negative LPS) induce endogenous pyrogens: IL-1, IL-6 and TNF-α.
- Cytokines induce COX-2 in the endothelium of circumventricular organs (OVLT): PGE₂ acts on EP3 receptors in the preoptic area.
- NSAIDs and aspirin lower fever by inhibiting COX; they do not cool hyperthermia (normal set point).
- Fever = high set point; hyperthermia = normal set point with heat loss overwhelmed (heat stroke). Antipyretics only help the first.
- Chills and cold skin as fever rises; sweating and vasodilation («crisis») as it breaks.

## What it is

Fever is a regulated rise in the hypothalamic set point caused by pyrogens. Unlike hyperthermia, the control system works normally but defends a higher temperature. Prostaglandin E₂ in the preoptic area is the final common mediator.

## How it works, step by step

- Macrophages sense microbial products (e.g. LPS via TLR4) and release IL-1, IL-6 and TNF-α.
- Circulating cytokines reach the OVLT, which lacks a complete blood–brain barrier, and induce COX-2.
- The PGE₂ produced acts on EP3 receptors in the preoptic area and raises the set point.
- Actual temperature is now below the new set point: the patient feels cold, skin vessels close and shivering starts.
- Once temperature reaches the new set point, heat production and loss balance (plateau).
- When the stimulus fades the set point returns to 37 °C: temperature is now too high for it, so vasodilation and sweating follow.

### Oxygen–hemoglobin dissociation curve

**P50** 31.6 mmHg **Arterial blood** 96 % **Mixed venous blood** 65 % **O₂ given up to the tissues** 30 %

Right shift (P50 31.6 mmHg): Hb has less affinity and gives up more O₂ in the tissues. Acid, CO₂, heat and 2,3-BPG cause it.

- Current curve
- Normal curve (pH 7.40 · 37 °C)
- Arterial blood (PO₂ 100)
- Mixed venous blood (PO₂ 40)
- O₂ given up to the tissues

Fever shifts the curve right: tissues get more O₂. Compare with «Normal».

## Approximate ranges

| Parameter | Value | Note |
| --- | --- | --- |
| Normal oral temperature | ≈36.5–37.3 °C | |
| Fever | ≥38.0 °C | usual definition (oral or rectal) |
| Hyperpyrexia | >41 °C | rare in pure fever; consider hyperthermia or CNS injury |
| Rise in metabolism | ≈10–13% per °C | more O₂ use and more fluid needs |

Approximate values for a healthy adult at rest; each laboratory sets its own ranges.

## Clinical notes

- Dengue: high fever for 2–7 days; the critical phase (capillary leak) usually starts as the fever settles, not at its peak.
- Malaria (P. vivax or P. falciparum), common in parts of Colombia below ~1600 m: fever in paroxysms with rigors, sometimes every 48 h.
- Sepsis in older adults: may present without fever or with hypothermia, which carries a worse prognosis.
- Each degree of fever adds insensible water loss and ≈10/min of tachycardia.

## Memory aid

«Fever turns the thermostat up; hyperthermia breaks the air conditioner».

## Test yourself

Think of the answer, then tap the question to see it.

## Why does a patient whose fever is rising shiver and ask for blankets at 39 °C?

The set point has risen (e.g. to 40 °C): the hypothalamus reads 39 °C as cold and triggers vasoconstriction and shivering to make heat.

## Why don't NSAIDs lower temperature in heat stroke?

They work by blocking PGE₂ synthesis, which raises the set point. In heat stroke the set point is normal; heat loss simply cannot keep up.

## Which structure lets blood cytokines act on the hypothalamus without crossing the blood–brain barrier?

The organum vasculosum of the lamina terminalis (OVLT), a circumventricular organ with fenestrated capillaries where COX-2 is induced and PGE₂ made.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/physiology/fever/)

## See it in 3D

The structures of Durgical's 3D anatomy where it happens.

- [Hypothalamus](https://durgical.com/en/anatomy/hypothalamus/)

## Related topics

- [Body temperature regulation](https://durgical.com/en/physiology/body-temperature-regulation/)
- [Heat exhaustion and heat stroke](https://durgical.com/en/physiology/heat-exhaustion-and-heat-stroke/)
- [Physiology of the vital signs (including blood pressure measurement)](https://durgical.com/en/physiology/physiology-of-the-vital-signs/)

## Related conditions

- [Sepsis and septic shock](https://durgical.com/en/conditions/sepsis-and-septic-shock/)
- [Dengue](https://durgical.com/en/conditions/dengue/)
- [Malaria](https://durgical.com/en/conditions/malaria/)

## In Biochemistry

- [Eicosanoids: prostaglandins, thromboxanes and leukotrienes](https://durgical.com/en/biochemistry/topics/eicosanoids-prostaglandins-thromboxanes-and-leukotrienes/)

## In Pharmacology

- [Nonsteroidal anti-inflammatory drugs (NSAIDs)](https://durgical.com/en/pharmacology/classes/nonsteroidal-anti-inflammatory-drugs/)
- [Ibuprofen](https://durgical.com/en/pharmacology/ibuprofen/)
- [Acetylsalicylic acid](https://durgical.com/en/pharmacology/acetylsalicylic-acid/)

[← All of physiology](https://durgical.com/en/physiology/)

Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: [Fever: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/003090.htm) (MedlinePlus, US National Library of Medicine, 2026); [24.6 Energy and Heat Balance](https://openstax.org/books/anatomy-and-physiology-2e/pages/24-6-energy-and-heat-balance) (OpenStax (Rice University), 2022); [Dengue Fever](https://www.ncbi.nlm.nih.gov/books/NBK430732/) (StatPearls (NCBI Bookshelf), 2025); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 74). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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Representative model, for educational purposes only.

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