Hyperthermia: Characterized on the left. Normal body temperature (thermoregulatory set-point) is shown in green, while the hyperthermic temperature is shown in red. As can be seen, hyperthermia can be conceptualized as an increase above the thermoregulatory set-point. Hypothermia: Characterized in the center: Normal body temperature (thermoregulatory set-point) is shown in green, while the hypothermic temperature is shown in blue. As can be seen, hypothermia can be conceptualized as a decrease below the thermoregulatory set-point. Fever: Characterized on the right: Normal body temperature (thermoregulatory set-point) is shown in green. It reads “New Normal” because the thermoregulatory set-point has risen. This has caused what was the normal body temperature (in blue) to be considered hypothermic.

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°C, 98.6°F). Fever should not be confused with Hyperthermia, which is an increase in body temperature over the body’s thermoregulatory set-point (approximately 37°C). A fever is most accurately characterized as a temporary elevation in the body’s thermoregulatory set-point, which is usually by about 1-2°C. 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. Image File history File links This picture was created by Taylor Sando and is intended to summarize fever conceptually. ... Medicine on the Web NLM (National Library of Medicine, contains resources for patients and healthcare professionals) Virtual Hospital (digital health sciences library by the University of Iowa) Online Medical Dictionary Collection of links to free medical resources Categories: Medicine | Health ... The term symptom (from the Greek syn = con/plus and pipto = fall, together meaning co-exist) has two similar meanings in the context of physical and mental health: A symptom may loosely be said to be a physical condition which shows that one has a particular illness or disorder (see... Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when temperature surrounding is very different. ... Hyperthermia, also known as heat stroke or sunstroke, is an acute condition resulting from the body producing or absorbing more heat than it can dissipate, usually due to excessive exposure to heat. ... Jump to: navigation, search Hypothermia is a medical condition in which the victims core body temperature has dropped to significantly below normal and normal metabolism begins to be impaired. ... Brown fat is a type of adipose tissue present in many newborn or hibernating mammals. ...

An adaptive mechanism, fever is the body's reaction to pathogens; it attempts to raise core body temperature to levels which will denature, debilitate, or kill the pathogen. Most fevers are caused by infections and almost all infectious diseases can cause fever. When a patient has or is suspected of having a fever, that person's body temperature is measured using a thermometer. If successful in ridding the body of an invasive pathogen, fever is an important protective immune mechanism and should generally not be suppressed. However, there are instances when fever escalates to temperatures where the body is at risk of destroying its own cells and must be brought under control with suppressive medication. Jump to: navigation, search A pathogen (literally birth of pain from the Greek παθογένεια) is a biological agent that can cause disease to its host. ... Cheese In biochemistry, denaturation is a structural change in biomolecules such as nucleic acids and proteins, such that they are no longer in their native state (the shape which allows for optimal biological activity). ... In medicine, infectious disease or communicable disease is disease caused by a biological agent (e. ... Jump to: navigation, search A thermometer is a device used to measure temperatures or temperature changes. ... Jump to: navigation, search The immune system is the system of specialised cells and organs that protect an organism from outside biological influences. ... Jump to: navigation, search Cells in culture, stained for keratin (red) and DNA (green) The cell is the structural and functional unit of all living organisms, sometimes called the building blocks of life. ... Jump to: navigation, search A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ...

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. Positive feedback is a type of feedback. ... Jump to: navigation, search Negative feedback is a type of feedback, during which a system responds so as to reverse the direction of change. ... Jump to: navigation, search Homeostasis or homoeostasis is the property of an open system, especially living organisms, to regulate its internal environment so as to maintain a stable condition, by means of multiple dynamic equilibrium adjustments controlled by interrelated regulation mechanisms. ... Jump to: navigation, search Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when temperature surrounding is very different. ...

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). Bacteria that are Gram-negative are not stained dark blue or violet by Gram staining, in contrast to Gram-positive bacteria. ... Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ... The blood-brain barrier is a physical barrier between the blood vessels in the central nervous system, and most parts of the central nervous system itself. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... A phospholipase is an enzyme that converts phospholipids into fatty acids and other lipophilic substances. ... Jump to: navigation, search Cyclooxygenase (COX) is an enzyme (EC 1. ...

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. In the anatomy of mammals, the hypothalamus is a region of the brain located below the thalamus, forming the major portion of the ventral region of the diencephalon and functioning to regulate certain metabolic processes and other autonomic activities. ... Jump to: navigation, search Located at the base of the skull, the pituitary gland is protected by a bony structure called the sella turcica. ... Endocrinology is a branch of medicine dealing with disorders of the endocrine system and its specific secretions called hormones. ... Jump to: navigation, search This article needs a complete rewrite for the reasons listed on the talk page. ... Shivering is a human bodily function in response to cold. ... The blood vessels are part of the circulatory system and function to transport blood throughout the body. ...

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

Types

Pyrexia can be classed as low grade (38 to 39 °C, 100 to 102.2 °F), moderate (39 to 40 °C, 102.2 to 104 °F), or high grade (more than 40 °C or 104 °F) depending on how much the body temperature has deviated from normal.

Fever may be of benefit and is part of the body's response to a disease; however, if the fever goes above 42 °C (107.6 °F) then it may cause significant tissue damage and would most certainly be harmful. This is termed hyperpyrexia. 43.3^oC (110^oF) is considered the upper limit compatible with life. In medicine, hyperpyrexia is an excessive and unusual elevation of body temperature above 42 °C, or high fever (also called a hyperthermia). ...

Temperature normally fluctuates over the day, and the same applies to fever. If this characteristic pattern is lost, the raised body temperature may be due to hyperthermia, a more dangerous disorder. Hyperthermia is commonly caused by overheating or sunstroke, which elevates the body's temperature above the thermoregulatory set-point. Hyperthermia, also known as heat stroke or sunstroke, is an acute condition resulting from the body producing or absorbing more heat than it can dissipate, usually due to excessive exposure to heat. ... Hyperthermia is an acute condition resulting from excessive exposure to heat, it is also known as heat stroke or sunstroke. ...

Treatment

Drugs that reduce fever are known as antipyretics. Common antipyretics are acetaminophen, also called paracetamol, and NSAIDs such as ibuprofen. These drugs act on the cyclooxygenase enzyme used to create prostaglandin E2 synthesis. Therefore, they work as prostaglandin synthesis inhibitors, stopping the creation of PGE2. Vasopressin is also a potential antipyretic, which is released from the Hypothalamus to the posterior pituitary gland, where it then acts on the body through the bloodstream. Antipyretics are drugs that prevent or reduce fever by lowering the body temperature from a raised state. ... Acetaminophen (USAN) or paracetamol (INN), is a popular analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains. ... Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs, are drugs with analgesic, antipyretic and anti-inflammatory effects - they reduce pain, fever and inflammation. ... Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) widely marketed under various trademarks including Act-3, Advil, Brufen, Motrin, Nuprin, and Nurofen; a standing joke about some athletes regular use has produced Vitamin I as a slang term for it. ... Antidiuretic hormone (ADH), or arginine vasopressin (AVP), is a peptide hormone produced by the hypothalamus, and stored in the posterior part of the pituitary gland. ...

A popular household remedy is soaking a cloth in cold water and placing it on the patient's forehead.

Sometimes, for various reasons, mild fevers are intentionally induced. Naturopath Paavo Airola claimed that because cancer cells are known to die at lower temperatures than normal body cells, therefore they can sometimes be fought with fevers. [1] However, Quackwatch has questioned Airola's scientific credentials.[2] Naturopathic medicine is the practice of assisting in the health of patients through the application of natural remedies. ... For other uses, see Cancer (disambiguation). ... Quackwatch is an Internet guide to quackery and health fraud operated by Stephen Barrett, M.D. Quackwatch, Inc. ...

References

Primary Sources

• Cao, C., Matsumura, K., Yamagata, K., and Watanabe, Y., (1996) Endothelial cells of the rat brain vasculature express cyclooxygenase-2 mRNA in response to systemic interleukin-1B: a possible site of prostaglandin synthesis responsible for fever. Brain Res 733, 263-272.
• Castellani JW, Young AJ, Sawka MN, Pandolf KB.(1998) Human thermoregulatory responses during serial cold-water immersions. J Appl Physiol, 85(1), 204-209.
• Feng, JD, Price M, Cohen J, and Satinoff E. (1989) Prostaglandin fevers in rats: regulated change in body temperature or change in regulated body temperature? Am J Physiol Regulatory Integrative Comp Physiol 257: R695-R699.
• Jakobsson, P. J., Thoren, S, Morgenstern, R., and Samuelsson B. (1999) Identification of human prostaglandin E synthase: A microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci U S A. 96, 7220-7225
• Milton, A. S. & Wendlandt, S. (1970). A possible role for prostaglandin E1 as a modulator for temperature regulation in the central nervous system. J Physiol, 207(2), 76P-77P.
• Milton, A. S. & Wendlandt, S. (1971) Effects on body temperature of prostaglandins of the A, E and F series on injection into the third ventricle of unanaesthetized cats and rabbits. J Physiol, 218, 325-336.
• Opp M. R. & Krueger J. M. (1991) Interleukin 1-receptor antagonist blocks interleukin 1-induced sleep and fever. Am J Physiol, 260(2), R453-R457.
• Scammell, T. E., Elmquist, J. K., Griffin, J. D., & Saper, C. B., (1996) Ventromedial preoptic prostaglandin E2 activates fever-producing autonomic pathways. J Neurosci, 16(19), 6246-6254.
• Scammel., T. E., Griffin, J. D., Elquist, J. K. and Saper C. B. (1998) Microinjection of a cyclooxygenase inhibitor into the anteroventral preoptic region attenuates LPS fever. Am J Physiol Regulatory Integrative Comp Physiol. 274 (3), R783-R789.
• Vane, J. R. & Flower, R. J. (1972) Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-Acetamidophenol). Nature, 240, 410-411.

Secondary Sources

• Engblom, D., Ek, M., Saha, Sipra, S., Ericsson-Dahistrand, A., Jakobsson P.J., Blomqvist, A (2002) Prostaglandins as inflammatory messengers across the blood-brain barrier. J Mol Med, 80, 5-15.
• Moltz, H. (1993). Fever: causes and consequences. Neurosci Biobehav Rev. 17(3), 237-69
• Waag T, Hesselberg O, Reinertsen RE. (1995) Heat production during cold water immersion: the role of shivering and exercise in the development of hypothermia. Arctic Med Res. 54(2), 60-64.

See also

• Ague
• Influenza

Ague is an archaic term for fever. ... Jump to: navigation, search Negatively stained flu virions. ...

External links

• US National Institute of Health factsheet
• BUPA factsheet