Temperature Regulation and the Pathogenesis of Fever

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some of Wunderlich’s cherished dictums regarding body temperature (e.g., the special significance of 37° C [98.6° F]) have had to be revised. [8] TERMINOLOGY Of the many definitions of fever promulgated over the centuries, the one proposed by the International Union of Physiological Sciences Commission for Thermal Physiology in 2001 [9] is the one most consistent with current concepts. It defines fever as “a state of elevated core temperature, which is often, but not necessarily, part of the defensive responses of multicellular organisms (host) to the invasion of live (microorganisms) or inanimate matter recognized as pathogenic or alien by the host.” The febrile response (of which the temperature rise is a component) is a complex physiologic reaction to disease, involving not only a cytokine-mediated rise in core temperature but also the generation of acute-phase reactants, and the activation of numerous physiologic, endocrinologic, and immunologic systems. The rise in temperature during fever is to be distinguished from that occurring during episodes of hyperthermia. Unlike fever, hyperthermia involves an unregulated rise in body temperature, in which pyrogenic cytokines are not directly involved and against which standard antipyretics are generally ineffective. Only in the most extreme cases, complicated by gut-derived endotoxemia, do pyrogenic cytokines appear to play a role. In contrast to fever, hyperthermia represents a failure of thermoregulatory homeostasis, in which there is either uncontrolled heat production, inadequate heat dissipation, or defective thermoregulation. In the clinical setting, fever is typically defined as a pyrogenmediated rise in body temperature above the normal range. Although consistent with the public’s perception of fever, the definition ignores the fact that a rise in body temperature is but one component of this multifaceted response. This standard clinical definition is further flawed, because it implies that “body temperature” is a single entity when, in fact, it is a pastiche of many different temperatures, each representative of a particular body part, and each varying throughout the day in response to both activities of daily living and the influence of endogenous diurnal rhythms. CLINICAL THERMOMETRY For over a century, the thermometer has been preeminent among clinical instruments used to distinguish health from disease and to monitor the course of illness. Unfortunately, thermometric measurements are influenced by a host of variables, all too frequently ignored when interpreting the significance of clinical temperature readings. Observer Variability Thermometric measurements are generally simple to perform but involve a number of technical details that, if not attended to, can invalidate estimates of body temperature. Few physicians, for example, ever take the time to ensure the reliability or proper calibration of thermometers used in clinical examinations. And yet Abbey and colleagues [10] found that a quarter of mercury-in-glass thermometers obtained from four different manufacturers were inaccurate after 8 months of use or storage.
Likewise, proper positioning of the temperature probe at the anatomic site employed is all too often given less than careful attention. Erickson has reported that oral thermometric readings vary by as much as 0.95° C (1.7° F) from the rear sublingual pocket to the area beneath the frenum in the anterior floor of the mouth. [11] Interestingly, regional differences in readings obtained within the oral cavity were more pronounced with electronic than with mercury thermometers, perhaps because of differences in the dwell times required when taking measurements with the two types of thermometers. It is also pertinent, in this regard, that studies performed earlier in the 20th century indicated that from the anus inward, the temperature gradually rises, reaching its zenith at a depth of approximately 2.5 inches (6.4 cm), and then gradually falls as the probe is advanced beyond 6 inches (15.2 cm). [12] More recent studies, however, found no significant differences between temperature readings obtained with rectal probes inserted to depths of 5, 9, and 13 cm. [13] With today’s electronic thermometers, equilibration times are relatively brief and, hence, thought not to influence the results of clinical thermometric measurements. As noted earlier, this conclusion is not necessarily justified. With mercury thermometers, opinions regarding proper placement times have varied from 2 to 12 minutes for axillary recordings and 1 to 9 minutes for rectal readings. [14][15] In a series of studies, Nichols and Kucha determined that 1 to 12 minutes are required for equilibration of mercury-in-glass thermometers during measurements of oral temperature. [16] In these studies, only 13% of the temperature readings reached their maximum after 3 minutes, whereas 90% did so after 8 minutes. Anatomic Variability Although clinicians frequently regard temperature readings from various anatomic sites as equivalent approximations of “body temperature,” [1] no one temperature characterizes the thermal status of the human body. This is because the body has many different temperatures, each representative of a particular body part. Nevertheless, within the body, there are two basic thermal compartments worthy of special consideration—the core and the shell. The shell, which consists of skin and subcutaneous fat, insulates the core from the external environment. The core, of which the viscera and muscles are major components, although insulated by the shell, has temperature gradients of its own, resulting from differences in the metabolic rates and blood flow patterns of the various organs contained therein. Even during baseline conditions, organs with higher metabolic rates have slightly higher temperatures than those with lower metabolic rates; in general, tissues close to the skin have lower temperatures than those at deeper locations. [17] Although such differences are normally small, during vigorous exercise, muscle temperatures rise markedly in comparison with those of less metabolically active organs. During shock and under extreme environmental conditions, regional anatomic variations in temperature may also be exaggerated. Rectal measurements have long been regarded as the most practical and accurate means of obtaining routine estimates of core temperature. Benzinger and Benzinger, however, have pointed out that no known thermoregulatory system exists at this particular anatomic site. [17] Rectal temperature readings are consistently higher than those obtained at other sites (even pulmonary artery blood), which some authorities have suggested might be due to heat generated as a result of the metabolic activity of fecal bacteria. [18] However, an early study showed no significant decrease
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Page 5 and 6: infrared TM thermometers, have made
Page 7 and 8: Thermoregulation has also been repo
Page 9 and 10: Figure 47-2 Mean oral temperatures
Page 11 and 12: young adults (six male and three fe
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Page 15 and 16: to induce fever. On the basis of th
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Page 21 and 22: Nevertheless, the febrile response
Page 23 and 24: TNF-α acts to lower, rather than t
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Page 27 and 28: Although clinicians have long had a
Page 29 and 30: induce shivering. [227] However, ca
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