How Fever Occurs: Pathophysiology Of Fever

Body temperature is regulated by hypothalamus. A pyrogen (e.g. tumor necrosis factor alpha, interleukin, interferon alpha etc.) is any chemical, which can cause rising of body temperature. A pyrogen is also a trigger that triggers rise of body temperature by releasing prostaglandin-E2 (PGE2). PGE2 acts on hypothalamus and put the “set-point” of temperature regulating center at hypothalamus at higher level to generate a systemic response in the other body parts to generate more heat to match the new higher level of temperature set point to a higher level. Thus, fever or higher than normal body temperature is produced in an individual. As long as there is presence of PGE2 in blood, the temperature set point remains higher and fever remains. That is why most of anti-pyretic medications (such as acetaminophen, ibuprofen, aspirin etc. acts by inhibiting or blocking synthesis of PGE2).

Hypothalamus acts like a thermostat by controlling the body temperature, by utilizing the temperature regulating set-point to keep body temperature normal or produce fever. Hypothalamus is the highest center, which regulates body temperature.

When temperature set point is raised by a pyrogen by producing PGE2, at hypothalamus, it sends signal to other body parts to increase body temperature by increase heat generation and by retention of heat. Heat is retained in the body by producing peripheral vasoconstriction (constriction or narrowing of blood vessels in the skin and mucous membranes). Because of peripheral vasoconstriction, a person with fever feels cold, despite increase in body temperature. If increased heat production by various body organs and parts and heat retention (by peripheral vasoconstriction) is insufficient to raise temperature of blood reaching hypothalamus (thermoregulation set point) to match the hypothalamic thermoregulation set point, shivering starts. Body tries to produce more heat to match temperature set point by producing heat from muscles by muscular movements (shivering). Hence, shivering during fever is nothing but a patho-physiological process of generating extra heat, because blood, reaching brain can not match the raised temperature set point at hypothalamus.

When fever stops or fever reverses, the entire process reverses i.e. there is peripheral vasodilatation (dilatation of blood vessels in the skin and mucous membranes), stoppage of shivering, stoppage of non-shivering heat production by various body parts and organs. There is also sweating, which helps the body to cool to a new lower temperature set point at hypothalamus.


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