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Fever of Unknown Origin

Overview :

Fever is a natural response of the body that helps in fighting off foreign substances, such as microorganisms, toxins, etc. Body temperature is set by the thermoregulatory center, located in an area in the brain called hypothalamus. Body temperature is not constant all day, but actually is lowest at 6 A.M. and highest around 4-6 P.M. In addition, temperature varies in different regions of the body; for example, rectal and urine temperatures are about one degree Fahrenheit higher than oral temperature and rectal temperature is higher than urine. It is also important to realize that certain normal conditions can effect body temperature, such as pregnancy, food ingestion, age, and certain hormonal changes.

Substances that cause fever are known as "pyrogens." There are two types of pyrogens; exogenous and endogenous. Those that originate outside the body, such as bacterial toxins, are called "exogenous" pyrogens. Pyrogens formed by the body's own cells in response to an outside stimulus (such as a bacterial toxin) are called "endogenous" pyrogens.

Researchers have discovered that there are several "endogenous" pyrogens. These are made up of small groups of amino acids, the building blocks of proteins. These natural pyrogens have other functions in addition to inducing fever; they have been named "cytokines". When cytokines are injected into humans, fever and chills develop within an hour. Interferon, tumor necrosis factor, and various interleukins are the major fever producing cytokines.

The production of fever is a very complex process; somehow, these cytokines cause the thermoregulatory center in the hypothalamus to reset the normal temperature level. The body's initial response is to conserve heat by vasoconstriction, a process in which blood vessels narrow and prevent heat loss from the skin and elsewhere. This alone will raise temperature by two to three degrees. Certain behavioral activities also occur, such as adding more clothes, seeking a warmer environment, etc. If the hypothalamus requires more heat, then shivering occurs.

Fever is a body defense mechanism. It has been shown that one of the effects of temperature increase is to slow bacterial growth. However, fever also has some downsides; the body's metabolic rate is increased and with it, oxygen consumption. This can have a devastating effect on those with poor circulation. In addition, fever can lead to seizures in the very young.

When temperature elevation occurs for an extended period of time and no cause is found, the term FUO is then used. The far majority of these patients are eventually found to have one of several diseases.

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