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Fever (also known as pyrexia, or a febrile response from the Latin word febris, meaning fever, and archaically known as ague) is a frequent medical symptom that describes an increase in internal body temperature to levels that are above normal (37°C, 98.6°F). Fever is most accurately characterized as a temporary elevation in the body’s thermoregulatory set-point, usually by about 1-2°C. Fever differs from hyperthermia, which is an increase in body temperature over the body’s thermoregulatory set-point (due to excessive heat production or insufficient thermoregulation, or both). Carl Wunderlich discovered that fever is not a disease but a symptom of disease.
The elevation in thermoregulatory set-point means that the previous "normal body temperature" is considered hypothermic, and effector mechanisms kick in. The person who is developing the fever has a cold sensation, and an increase in heart rate, muscle tone and shivering attempt to counteract the perceived hypothermia, thereby reaching the new thermoregulatory set-point.
When a patient has or is suspected of having a fever, that person's body temperature is measured using a thermometer. At a first glance, fever is present if:
However, there are many variations in normal body temperature, and this needs to be considered when measuring fever. Body temperature normally fluctuates over the day, with the lowest levels at 4 A.M. and the highest at 6 P.M.. Therefore, an oral temperature of 37.5°C would strictly be a fever in the morning, but not in the afternoon. Normal body temperature may differ as much as 0.4°C (0.7°F) between individuals. In women, temperature differs at various points in the menstrual cycle, and this can be used for family planning (although it is only one of the variables of temperature). Temperature is increased after meals, and psychological factors (like the first day in the hospital) also influence body temperature.
There are different locations where you can measure temperature, and these differ in temperature variability. Tympanic membrane thermometers measure radiant heat energy from the tympanic membrane (=infrared). These may be very convenient, but may also show more variability.
Children develop higher temperatures with activities like playing, but this is not fever because their set-point is normal. Elderly patients may have a decreased ability to generate body heat during a fever, so even a low-grade fever can have serious underlying causes in geriatrics.
Temperature is ideally always measured the same moment of the day, in the same way, after the same amount of activity.
Temperature is regulated in the hypothalamus. Substances that induce fever are called pyrogens. These are both external or exogenous, such as the bacterial substance LPS, and internal or endogenous. The endogenous pyrogens (such as interleukin 1) are a part of the innate immune system, produced by phagocytic cells, and cause the increase in the thermoregulatory set-point in the hypothalamus. The endogenous pyrogens may also come directly from tissue necrosis.
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 (IL-1), interleukin 6 (IL-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 prostaglandin E2 synthase (membrane-associated protein involved in eicosanoid and glutathione metabolism, also known as mPEGS-1). These enzymes ultimately mediate the synthesis and release of PGE2.
PGE2 is the ultimate mediator of the febrile response. The set-point temperature of the body will remain elevated until PGE2 is no longer present. PGE2 acts near the ventromedial preoptic area (VMPO) of the anterior hypothalamus and the parvocellular portion of the periventricular nucleus (PVN), where the thermal properties of fever emerge. It is presumed that the elevation in thermoregulatory set-point is mediated by the VMPO, whereas the neuroendocrine effects of fever are mediated by the PVN, pituitary gland, and various endocrine organs.
The brain ultimately orchestrates heat effector mechanisms. These may be
Pyrexia (fever) can be classed as
Most of the time, fever types can't be used to find the underlying cause. However, there are specific fever patterns that may occasionally hint the diagnosis:
Febricula[1] is a mild fever of short duration, of indefinite origin, and without any distinctive pathology.
Fever is a common symptom of many medical conditions:
Persistent fever which cannot be explained after repeated routine clinical inquiries, is called fever of unknown origin.
There are arguments for and against, and the issue is controversial[2][3]. There are studies using warm-blooded vertebrates[4] and humans [5] in vivo, with some suggesting that they recover more rapidly from infections or critical illness due to fever.
Theoretically, fever has been conserved during evolution because of its advantage for host defense[2]. There are certainly some important immunological reactions that are sped up by temperature, and some pathogens with strict temperature preferences could be hindered[6]. The overall conclusion seems to be that both aggressive treatment of fever[5] and too little fever control[2] can be detrimental. This depends on the clinical situation, so careful assessment is needed.
Fevers may be useful to some extent since they allow the body to reach high temperatures. This causes an unbearable environment for some pathogens. White blood cells also rapidly proliferate due to the suitable environment and can also help fight off the harmful pathogens and microbes that invaded the body.
Fever should not necessarily be treated. Fever is an important signal that there's something wrong in the body, and it can be used for follow-up. Moreover, not all fevers are of infectious origin.
Even when treatment is not indicated, however, febrile patients are generally advised to keep themselves adequately hydrated, as the dehydration produced by a mild fever can be more dangerous than the fever itself. Water is generally used for this purpose, but there is always a small risk of hyponatremia if the patient drinks too much water. For this reason, some patients drink sports drinks or products designed specifically for this purpose.
Most people take medication against fever because the symptoms cause discomfort. Fever increases heart rate and metabolism, thus potentially putting an additional strain on elderly patients, patients with heart disease, etc. This may even cause delirium. Therefore, potential benefits must be weighed against risks in these patients. In any case, fever must be brought under control in instances when fever escalates to hyperpyrexia and tissue damage is imminent.
Treatment of fever should be based primarily on lowering the setpoint, but facilitating heat loss may also contribute. The former is accomplished with antipyretics. Wet cloth or pads are also used for treatment, and applied to the forehead. Heat loss may be an effect of (possibly a combination of) heat conduction, convection, radiation or evaporation (sweating, perspiration). This may be particularly important in babies, where drugs should be avoided. However, if water that is too cold is used, it induces vasoconstriction and prevents adequate heat loss.