Physiology · Temperature, exercise and metabolism
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
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 mmHgArterial 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
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.
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.
See it in 3D
The structures of Durgical's 3D anatomy where it happens.
Related topics
- Body temperature regulation
- Heat exhaustion and heat stroke
- Physiology of the vital signs (including blood pressure measurement)
Related conditions
In Biochemistry
In Pharmacology
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 (MedlinePlus, US National Library of Medicine, 2026); 24.6 Energy and Heat Balance (OpenStax (Rice University), 2022); Dengue Fever (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.