FEVER

Fever (also known as pyrexia, from the Greek pyretos meaning fire, 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 above normal (the common oral measurement of normal human body temperature is 36.8±0.7 °C or 98.2±1.3 °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; hyperthermia 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.

However, there are many variations in normal body temperature, and this needs to be considered when measuring fever. The values given are for an otherwise healthy, non-fasting adult, dressed comfortably, indoors, in a room that is kept at a normal room temperature, during the morning, but not shortly after arising from sleep. Furthermore, for oral temperatures, the subject must not have eaten, drunk, or smoked anything in at least the previous fifteen minutes.

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 (99.5°F) 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 or from day to day. In women, temperature differs at various points in the menstrual cycle, and this can be used for family planning (although temperature is only one of the variables). Temperature is increased after meals, and psychological factors (like the first day in the hospital) also influence body temperature.

There are different locations where temperature can be measured, 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 regulated in the hypothalamus, in response to PGE2. PGE2 release, in turn, comes from a trigger, a pyrogen. The hypothalamus generates a response back to the rest of the body, making it increase the temperature set-point.

A pyrogen is a substance that induces fever. These can be either internal (endogenous) or external (exogenous). The bacterial substance lipopolysaccharide (LPS) is an example of an exogenous pyrogen.

The cytokines (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. Other examples of endogenous pyrogens are 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.

One model for the mechanism of fever caused by exogenous pyrogens includes 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 endogenous cytokine factors, such as interleukin 1 (IL-1), interleukin 6 (IL-6), and the tumor necrosis factor-alpha. In other words, exogenous factors cause release of endogenous factors, which, in turn, activate the arachidonic acid pathway.

PGE2 release comes from 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. 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 on neurons in the preoptic area (POA) through the prostaglandin E receptor 3 (EP3). EP3-expressing neurons in the POA innervate the dorsomedial hypothalamus (DMH), the rostral raphe pallidus nucleus in the medulla oblongata (rRPa) and the paraventricular nucleus of the hypothalamus (PVN). Fever signals sent to the DMH and rRPa lead to stimulation of the sympathetic output system, which evokes non-shivering thermogenesis to produce body heat and skin vasoconstriction to decrease heat loss from the body surface. It is presumed that the innervation from the POA to the PVN mediates the neuroendocrine effects of fever through the pathway involving pituitary gland and various endocrine organs.

The autonomic nervous system may also activate brown adipose tissue to produce heat (non-exercise-associated thermogenesis, also known as non-shivering thermogenesis), but this seems mostly important for babies. Increased heart rate and vasoconstriction contribute to increased blood pressure in fever.

Pel-Ebstein fever: A specific kind of fever associated with Hodgkin's lymphoma, being high for one week and low for the next week and so on. However, there is some debate as to whether this pattern truly exists.

Continuous fever: Temperature remains above normal throughout the day and does not fluctuate more than 1°C in 24 hours, e.g. lobar pneumonia, typhoid, urinary tract infection, brucellosis, or typhus. Typhoid fever may show a specific fever pattern, with a slow stepwise increase and a high plateau.

Intermittent fever: Elevated temperature is present only for some hours of the day and becomes normal for remaining hours, e.g. malaria, kala-azar, pyaemia, or septicemia. In malaria, there may be a fever with a periodicity of 24 hours (quotidian), 48 hours (tertian fever), or 72 hours (quartan fever, indicating Plasmodium malariae). These patterns may be less clear in travelers.

There are arguments for and against the usefulness of fever, and the issue is controversial. There are studies using warm-blooded vertebrates and humans in vivo, with some suggesting that they recover more rapidly from infections or critical illness due to fever.

Theoretically, fever can aid in host defense. There are certainly some important immunological reactions that are sped up by temperature, and some pathogens with strict temperature preferences could be hindered. The overall conclusion seems to be that both aggressive treatment of fever and too little fever control 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 set-point, 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.

Your body temperature is usually highest in the evening. It can be raised by physical activity, strong emotion, eating, heavy clothing, medications, high room temperature, and high humidity. This is especially true in children.

A rectal temperature up to 100.4°F (38°C) may be entirely normal. A rectal temperature of 100.5°F or above should always be considered a fever. Lower values might be a fever, depending on the person.

Fever is not an illness. Far from being an enemy, it is an important part of the body's defense against infection. Many infants and children develop high fevers with minor viral illnesses. While a fever signals to us that a battle might be going on in the body, the fever is fighting for the person, not against.

Most bacteria and viruses that cause infections in people thrive best at 98.6°F. Raising the temperature a few degrees can give your body the winning edge. In addition, a fever activates the body's immune system to make more white blood cells, antibodies, and other infection-fighting agents.

Many parents fear that fevers will cause brain damage. Brain damage from a fever generally will not occur unless the fever is over 107.6°F (42°C). Many parents also fear that untreated fevers will keep going higher and higher. Untreated fevers caused by infection will seldom go over 105°F unless the child is overdressed or trapped in a hot place.

Some parents fear that fevers will cause seizures. For the great majority of children, this is not the case. However, febrile seizures do occur in some children. Once a child is already known to have a high fever, a febrile seizure is unlikely with the current illness. In any event, simple febrile seizures are over in moments with no lasting consequences.

Heatstroke is a particularly dangerous type of high temperature, because the body is not able to stop the temperature from continuing to rise. It can happen when a child is left in a hot car or when you exercise too strenuously without enough to drink.