Porth's Essentials of Pathophysiology, 4e

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Inflammation, the Inflammatory Response, and Fever

C h a p t e r 3

for energy. The rise in fibrinogen causes red blood cells to form stacks (rouleaux) that settle or sediment more rapidly than individual erythrocytes. This is the basis for the accelerated erythrocyte sedimentation rate (ESR) that occurs in disease conditions characterized by the systemic inflammatory response. White Blood Cell Response Leukocytosis , or the increase in white blood cells, is a fre- quent sign of an inflammatory response, especially those caused by bacterial infection. In acute inflammatory condi- tions, the white blood cell count commonly increases from a normal value of 4000 to 10,000 cells/ μ L to 15,000 to 20,000 cells/ μ L. After being released from the bone mar- row, circulating neutrophils have a life span of only about 10 hours and therefore must be constantly replaced if their numbers are to be adequate. With excessive demand for phagocytes, immature forms of neutrophils (bands) are released from the bone marrow. The phrase “a shift to the left” in a white blood cell differential count refers to the increase in immature neutrophils seen in severe infections. Bacterial infections produce a relatively selective increase in neutrophils (neutrophilia), while parasitic and allergic responses induce eosinophilia. Viral infec- tions tend to produce a decrease in neutrophils (neutro- penia) and an increase in lymphocytes (lymphocytosis). 3 A decrease in white blood cells (leukopenia) may also occur in persons with overwhelming infections or impaired ability to produce white blood cells. Systemic Inflammatory Response In severe bacterial infections (sepsis), the large quantities of microorganisms in the blood result in an uncontrolled inflammatory response with the production and release of enormous quantities of inflammatory cytokines (most notably IL-1 and TNF- α ) and development of what is referred to as the systemic inflammatory response syn- drome (see Chapter 20). 30 A decrease in total white blood cells (leukopenia) may occur in persons with overwhelming infections or impaired ability to produce white blood cells. Fever Fever (pyrexia) is an elevation in body temperature caused by an upward displacement of the set point of the thermoregulatory center in the hypothalamus. 31–33 It is one of the most prominent manifestations of the acute-phase response. 1,2 BodyTemperature Regulation The temperature in the deep tissues of the body (core temperature) is normally maintained within a range of 36.0°C to 37.5°C (97.0°F to 99.5°F). 31,32 Within this range, there are individual differences and diurnal variations; internal core temperatures reach their high- est point in late afternoon and evening and their lowest point in the early morning hours (Fig. 3-7). Virtually all biochemical processes in the body are affected by

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37 Rectal temperature ° C 36 35

Noon

6 PM Time

Midnight

6 AM

6 AM

FIGURE 3-7. Normal diurnal variations in body temperature.

changes in temperature. Metabolic processes speed up or slow down depending on whether body temperature is rising or falling. Body temperature, which reflects the difference between heat production and heat loss, is regulated by the thermoregulatory center in the hypothalamus. Body heat is generated in the tissues of the body, transferred to the skin surface by the blood, and then released into the environment surrounding the body. The thermoregula- tory center regulates the temperature of the deep body tissues, or “core” of the body, rather than the surface temperature. It does so by integrating input from cold and warmth receptors located throughout the body and participating in negative feedback mechanisms. The thermostatic set point of the thermoregulatory center is the level at which body temperature is regu- lated so that core temperature is maintained within the normal range. When body temperature begins to rise above this set point, heat-dissipating behaviors are initiated, and when the temperature falls below the set point, heat production is increased. A core temperature greater than 41°C (105.8°F) or less than 34°C (93.2°F) usually indicates that the body’s thermoregulatory abil- ity is impaired (Fig. 3-8). Body responses that produce, conserve, and dissipate heat are described in Table 3-1. Spinal cord injuries that transect the cord at T6 or above can seriously impair temperature regulation because the hypothalamus no longer can control skin blood flow or sweating. In addition to physiologic thermoregulatory mecha- nisms, humans engage in voluntary behaviors to help regulate body temperature. These behaviors include the selection of proper clothing and regulation of environ- mental temperature through heating systems and air conditioning. Body positions that hold the extremities close to the body (e.g., huddling) prevent heat loss and are commonly assumed in cold weather. Mechanisms of Heat Production. Metabolism is the body’s main source of heat production. The sympathetic neurotransmitters epinephrine and norepinephrine, which are released when an increase in body temperature is needed, act at the cellular level to shift body metabo- lism to heat production rather than energy generation. This may be one of the reasons fever tends to produce feelings of weakness and fatigue. Thyroid hormone