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Understanding the pathophysiology of fever

doi: 10.1097/01.NURSE.0000327497.08688.47
CRITICAL care
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Learn about the clues that can help you identify a fever's cause.

Fever, or pyrexia, is an elevation in body temperature caused by a cytokine-induced upward displacement of the set point of the hypothalamic thermoregulatory center. The purpose of fever isn't completely understood, but small elevations in body temperature appear to enhance immune function and inhibit pathogen growth.

Fever is resolved or “broken” when the factor that caused the set point increase is removed. Fevers that are regulated by the hypothalamus usually don't rise above 105.8° F (41° C), suggesting a built-in thermostatic safety mechanism. Temperatures above that level usually are the result of superimposed activity, such as seizures.

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Causes of fever

Fever can be caused by various microorganisms and substances collectively called pyrogens. Many proteins, breakdown products of proteins, and certain other substances, including lipopolysaccharide toxins released from bacterial cell membranes, can cause the set point of the hypothalamic thermoregulatory center to increase. Some pyrogens can act directly and immediately on the hypothalamic thermoregulatory center. Other pyrogens act indirectly and take longer to produce their effect.

Exogenous pyrogens induce host cells, such as leukocytes and macrophages, to release fever-producing mediators called endogenous pyrogens (for example, interleukin-1). The phagocytosis of bacteria and breakdown products of bacteria present in the blood lead to the release of endogenous pyrogens into the circulation. These endogenous pyrogens are thought to increase the set point of the hypothalamic thermoregulatory center through the action of prostaglandin E2. In response to the sudden increase in set point, the hypothalamus initiates heat production behaviors (shivering and vasoconstriction) that raise the core body temperature to the new set point, establishing fever.

Fever in noninfectious disorders. Many noninfectious disorders, such as myocardial infarction, pulmonary emboli, and neoplasms, produce fever. In these conditions, the injured or abnormal cells incite the production of pyrogens. For example, trauma and surgery can be associated with several days of fever. Some malignant cells, such as those of leukemia and Hodgkin's disease, secrete pyrogens.

Neurogenic fever. Originating in the central nervous system (CNS), a neurogenic fever usually is caused by damage to the hypothalamus from CNS trauma, intracerebral bleeding, or an increase in intracranial pressure. Neurogenic fevers are characterized by a high temperature that's resistant to antipyretic therapy and isn't associated with sweating.

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Fever patterns

The pattern of a fever can give you information about the fever's cause.

In an intermittent fever, the patient's temperature returns to normal at least once every 24 hours. This type of fever is associated with Gram-negative or Gram-positive sepsis, abscesses, and infective endocarditis.

In a remittent fever, the patient's temperature doesn't return to normal, although it varies a few degrees in either direction. Remittent fevers are associated with viral upper respiratory tract, legionella, and mycoplasma infections.

In a sustained or continuous fever, the patient's temperature remains above normal with minimal variations (usually less than 1° F or 0.55° C). These fevers may be caused by drugs.

A recurrent or relapsing fever consists of one or more episodes of fever, each as long as several days, with one or more days of normal temperature between episodes. Relapsing fevers can be caused by various infectious diseases, including fungal.

A second clue to the cause of the fever is the relation of the patient's heart rate to the level of temperature elevation. Normally, a 1° F increase in temperature produces a 10-beat/minute increase in heart rate, and a 1° C increase in temperature produces a 15-beat/minute increase in heart rate. If the temperature increase isn't accompanied by the anticipated change in heart rate, you may have another clue to the fever's cause. For example, a heart rate that's more rapid than expected for the patient's temperature increase may indicate hyperthyroidism or pulmonary embolus.

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Stages of fever

Your patient's signs and symptoms depend on which stage of fever he's in. However, not all patients proceed through the four stages described below: Fever may develop gradually, without chills or shivering, or the patient may not sweat. Let's take a closer look at each stage.

  • Prodromal stage. The patient will have nonspecific symptoms such as mild headache, fatigue, general malaise, and fleeting aches and pains.
  • Second stage or chill. The patient will feel chilled and develop generalized shaking despite his rising temperature. Vasoconstriction and piloerection precede the onset of shivering. The patient's skin will be pale and covered with gooseflesh. He may put on more clothes or curl up in a position to conserve body heat. Pyrogens typically enter the bloodstream during this stage, so blood samples for culturing are usually drawn during the first signs of a chill. When the shivering has caused the body temperature to reach the new set point, the shivering stops and the patient again feels warm.
  • Third stage or flush. Cutaneous vasodilation leads to the skin becoming warm and flushed. Now the patient is too hot.
  • Defervescence. This stage is characterized by sweating. The fever breaks, and the patient's body temperature returns to normal.

Common signs and symptoms of fever worsen if the patient's temperature rises rapidly or if it exceeds 103.1° F (39.5° C). Tachypnea and tachycardia develop, and the patient becomes dehydrated because of sweating and vapor losses from the increased respiratory rate.

Many manifestations of fever are related to the increased metabolic rate, increased need for oxygen, and use of body proteins as an energy source. During fever, the body switches from using glucose to metabolism based on protein and fat breakdown. Prolonged fever causes breakdown of endogenous fat stores. If fat breakdown is rapid, the patient may develop metabolic acidosis.

Source: Essentials of Pathophysiology: Concepts of Altered Health States, CM Porth, Lippincott Williams & Wilkins, 2004.

© 2008 Lippincott Williams & Wilkins, Inc.