Encyclopedia
Fever is a frequent
medical symptom that describes an increase in internal
body temperature to levels that are above normal . Fever is most accurately characterized as a temporary elevation in the body’s thermoregulatory set-point, which is usually by about 1-2°C. Fever differs from hyperthermia, which is an increase in body temperature over the body’s thermoregulatory set-point .
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.
Measurement
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:
- rectal temperature is at, or higher than 38 degrees Celsius
- oral temperature is at, or higher than 37.5 degrees Celsius
- axillar temperature is at, or higher than 37.2 degrees Celsius
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 between individuals. In women, temperature differs at various points in the
menstrual cycle, and this can be used for
family planning . Temperature is increased after meals, and psychological factors 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 . 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 decreased ability to generate body heat during fever, so even a low-grade fever can have serious underlying causes in geriatrics.
In conclusion, temperature is ideally always measured the same moment of the day, in the same way, after the same amount of activity.
Mechanism
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 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 , which is a cell wall component of gram-negative bacteria. An immunological protein called Lipopolysaccharide-Binding Protein 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 , interleukin 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 , is mediated by the
enzymes
phospholipase A2 ,
cyclooxygenase-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 near the ventromedial preoptic area of the anterior
hypothalamus and the parvocellular portion of the periventricular nucleus , 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 PVH, pituitary gland, and various
endocrine organs.
The brain ultimately orchestrates
heat effector mechanisms. These may be
- increased heat production by increased muscle tone, shivering and hormones like epinephrine and thyroid hormones, or,
- prevention of heat loss, such as vasoconstriction or crawling under a blanket.
The
autonomic nervous system may also activate brown adipose tissue to produce heat , but this seems mostly important for babies. Increased heart rate and vasoconstriction contribute to increased
blood pressure in fever.
Types
Pyrexia can be classed as
- low-grade: 38 - 39 °C
- moderate: 39 - 40 °C
- high-grade: > 40 °C
- Hyperpyrexia: > 42 °C
The last is clearly a medical emergency because it approaches the upper limit compatible with human life.
Most of the times, fever types can't be used to find the underlying cause. However, there are specific fever patterns that may occasionally hint the diagnosis:
- Pel-Ebstein fever is a specific kind of fever associated with Hodgkin disease, being high for one week and low for the next week and so on. However, there is some debate whether this pattern truly exists.
- Typhoid fever may show a specific fever pattern, with a slow stepwise increase and a high plateau.
- In malaria, there may be a fever with a periodicity of 48 hours or 72 hours . These patterns may be less clear in travelers.
Febricula is a mild fever of short duration, of indefinite origin, and without any distinctive pathology.
Causes
Fever is a common symptom of many medical conditions:
- infectious disease, e.g. common cold, HIV, malaria, infectious mononucleosis, gastroenteritis, etc..
- Immunological diseases like lupus erythematosus, sarcoidosis, inflammatory bowel diseases, etc..
- Tissue destruction, which can occur in hemolysis, surgery, infarction, crush syndrome, rhabdomyolysis, cerebral hemorrhage, etc..
- Drug fever
- directly caused by the drug
- as an adverse reaction to drugs
- after drug discontinuation, like with heroin withdrawal
- Cancers such as Hodgkin disease
- Metabolic disorders like gout, porphyria, etc..
- Thrombo-embolic processes
Persistent fever which cannot be explained after repeated routine clinical inquiries, is called fever of unknown origin.
Is fever useful?
There are arguments for and against, 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 has been conserved during evolution because of its advantage for 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.
Treatment
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. Fever might help the immune system or hinder specific pathogens, but this is generally considered of little importance. 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, such as Pedialyte.
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 primarily be based on lowering the setpoint, but facilitating heat loss may contribute. The former is accomplished with antipyretics. Heat loss may be an effect of
heat conduction,
convection, radiation or
evaporation . This may be particularly important in babies, where drugs should be avoided. However, when someone would use
water that is too cold, this induces vasoconstriction and prevents adequate heat loss.
References
Articles
Books
- Rhoades, R and Pflanzer, R. Human physiology, third edition, chapter 27 Regulation of body temperature, p. 820 Clinical focus: pathogenesis of fever. ISBN 0-03-005159-2
- Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL. Harrison's Principles of Internal Medicine. New York: McGraw-Hill, 2005. ISBN 0-07-139140-1.
External links
- from Seattle Children's Hospital
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