Fever

Fever, also known as pyrexia, or a febrile response, is a medical symptom which describes an increase in internal body temperature to levels which are above normal (37 degrees Celsius, 98.6 degrees Fahrenheit). Fever should not be confused with Hyperthermia, which is an increase in body temperature over the body?s thermoregulatory set-point (approximately 37 degrees Celsius). A fever is most accurately characterized as a temporary elevation in the body?s thermoregulatory set-point, which is usually by about 1-2 degrees Celsius. This elevation in thermoregulatory set-point means that the previous "normal body temperature" would be considered hypothermic. Effector mechanisms, such as increased blood pressure, increased heart rate, activation of brown adipose tissue and muscular shivering attempt to counteract the perceived hypothermia, thereby reaching the new thermoregulatory set-point.

Mechanism

Fever is a positive feedback mechanism which acts towards the direction of change (as opposed to negative feedback which acts opposite to change to maintain homeostasis). Therefore, fever is the opposite of thermoregulation. Substances which induce fever are called pyrogens. Although external pathogens may be the ultimate reason for a fever, it is the internal or endogenous pyrogens that ultimately cause the increase in the thermoregulatory set-point.

Related Topics:
Positive feedback - Negative feedback - Homeostasis - Thermoregulation

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One model for the mechanism of fever is the detection of lipopolysaccharide (LPS), which is a cell wall component of gram negative bacteria. An immunological protein called Lipopolysaccharide Binding Protein (LBP) binds to LPS. The LBP-LPS complex then binds to the CD14 receptor of a nearby macrophage. This binding results in the synthesis and release of various cytokine factors, such as interleukin 1, 6 and the tumor necrosis factor alpha. These cytokine factors are released into general circulation where they migrate to the circumventricular organs of the brain, where the blood-brain barrier is reduced. The cytokine factors bind with endothelial receptors on vessel walls, or interact with local microglial cells. When these cytokine factors bind, they activate the arachidonic acid pathway. This pathway (as it relates to fever), is mediated by the enzymes phospholipase A2 (PLA2), cyclooxygenase-2 (COX-2) and PGE2 synthase (membrane-associated protein involved in eicosanoid and glutathione metabolism, also known as mPEGS-1). These enzymes ultimately mediate the synthesis and release of prostaglandin E2 (PGE2).

Related Topics:
Gram negative bacteria - Macrophage - Blood-brain barrier - Endothelial receptor - Phospholipase A2 - Cyclooxygenase-2

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PGE2 is the ultimate mediator of the febrile response. It acts near the ventromedial preopic area (VMPO) of the anterior hypothalamus and the parvocellular portion of the periventricular nucleus (PVH). It is in these areas that the thermal properties of fever emerge. Presumably, the elevation in thermoregulatory set-point is mediated by the VMPO, whereas the neuroendocrine effects of fever are mediated by the PVH, pituitary gland and various endocrine organs. Other heat effector mechanisms are mediated by the brain stem/medullary premotor sympathetic activation to the autonomic nervous system, which ultimately leads to the activation of brown adipose Tissue. The body can also induce shivering, or raise blood pressure through a mechanism of vasoconstriction.

Related Topics:
Hypothalamus - Pituitary gland - Endocrine organs - Autonomic nervous system - Shivering - Vasoconstriction

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The set-point temperature of the body will remain elevated until PGE2 (through ultimately the foreign pathogen) is no longer present.

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