Fever, which means a body temperature above the usual range of normal, can be caused by abnormalities in the brain itself or by toxic substances that affect the temperature-regulating centers. Some causes of fever (and also of subnormal body temperatures) are presented in Figure 73-10.They include bacterial diseases,
Body temperatures under different conditions. (Redrawn from DuBois EF: Fever. Springfield, IL: Charles C Thomas, 1948.)
brain tumors, and environmental conditions that may terminate in heatstroke.
Resetting the Hypothalamic Temperature-Regulating Center in Febrile Diseases— Effect of Pyrogens
Many proteins, breakdown products of proteins, and certain other substances, especially lipopolysaccharide toxins released from bacterial cell membranes, can cause the set-point of the hypothalamic thermostat to rise. Substances that cause this effect are called pyrogens. Pyrogens released from toxic bacteria or those released from degenerating body tissues cause fever during disease conditions. When the set-point of the hypothalamic temperature-regulating center becomes higher than normal, all the mechanisms for raising the body temperature are brought into play, including heat conservation and increased heat production. Within a few hours after the set-point has been increased, the body temperature also approaches this level, as shown in Figure 73-11.
Mechanism of Action of Pyrogens in Causing Fever—Role of Interleukin-1. Experiments in animals have shown that some pyrogens, when injected into the hypothalamus, can act directly and immediately on the hypothalamic temperature-regulating center to increase its set-point. Other pyrogens function indirectly and may require several hours of latency before causing their effects. This is true of many of the bacterial pyrogens, especially the endotoxins from gram-negative bacteria.
When bacteria or breakdown products of bacteria are present in the tissues or in the blood, they are phagocytized by the blood leukocytes, by tissue macrophages, and by large granular killer lymphocytes. All these cells digest the bacterial products and then
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