from Guyton and Hall Textbook of Medical Physiology 4th South Asia Edi

from Guyton and Hall Textbook of Medical Physiology (4th South Asia Edition) write a proper 5 mark short note on fever

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fever pathogenesis pyrogen

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Fever

Definition Fever is a body temperature above the normal range caused by upward resetting of the hypothalamic thermostat, rather than a failure of temperature regulation itself. Causes include bacterial and viral infections, tissue destruction, brain tumors/lesions near the hypothalamus, dehydration, and other toxic conditions (Guyton and Hall Textbook of Medical Physiology, p. 899).

Mechanism - role of pyrogens

Exogenous pyrogens: bacterial products, especially lipopolysaccharide (endotoxin) from gram-negative bacteria, and other proteins/toxins.
These are phagocytosed by blood leukocytes, tissue macrophages, and large granular (killer) lymphocytes, which then release cytokines, chiefly interleukin-1 (IL-1), also called leukocyte or endogenous pyrogen.
IL-1 reaches the hypothalamus and induces formation of prostaglandin E2, which acts on the thermoregulatory center to raise the set point (fever can appear within 8-10 minutes of IL-1 release).
Because the set point is now higher than the actual body temperature, all heat-gain mechanisms (vasoconstriction, shivering, cessation of sweating) are activated until body temperature rises to match the new set point. - Guyton and Hall, p. 900

Fever due to brain lesions Hypothalamic surgery, hemorrhage, or compression by a tumor commonly produces fever (rarely hypothermia), illustrating the potency of hypothalamic control over body temperature.

Clinical stages

Chills - when the set point suddenly rises, actual temperature is still below the new set point, so the person feels cold, has vasoconstriction, and shivers until temperature rises to the new set point.
Plateau - temperature is regulated normally, but at the elevated set point.
Crisis ("flush") - when the causative factor is removed, the set point falls back to normal; the body is now hotter than the set point, triggering intense sweating and vasodilation ("breaking" of the fever).

Antipyretics Drugs such as aspirin reduce fever by blocking prostaglandin synthesis from arachidonic acid, thereby preventing the IL-1-mediated rise in hypothalamic set point.

Reference: Guyton and Hall Textbook of Medical Physiology, "Fever" and "Resetting the Hypothalamic Temperature-Regulating Center in Febrile Diseases", pp. 899-901.

Note: recent systematic reviews (e.g., PMID 39063086 on monocyte activation testing for pyrogens, PMID 37690845 on drug fever) refine detection methods and clinical subtypes of fever but do not contradict this core physiological mechanism described in Guyton and Hall.

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