Page 30 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

2 Temperature, Energy S. Silbernagl

Fever
The aim of thermoregulation is to maintain the As after i.v. injection of lipopolysaccharides
actual core temperature of the body at the set the above-mentioned cytokines are found only
level of about 378C (with diurnal variations). 30 minutes after the onset of the fever and
In contrast to passive hyperthermia (→ p. 22), their appearance can be inhibited by sub-
the set level is raised in fever, and the thermo- diaphragmatic vagotomy, it seems that exo-
regulatory mechanisms are thus responsible genous pyrogens activate the area preoptica
for maintaining the raised temperature and the OVLT also via afferent fibers from the
(→ A5, green line). This becomes noticeable abdomen. It is possible that signaling sub-
when the fever rises: because the actual level stances released from the hepatic Kupffer cells
deviates from the suddenly raised set level, (? cytokines, ? PGE 2 ) activate nearby vagal af-
heat loss is reduced by a decrease in cutaneous ferents that transmit the pyrogenic signal via
blood flow, resulting in cooling of the skin (feel- the nucleus solitarius to the norepinephrine
ing cold). Additionally, heat production is in- cell groups A1 and A2. These in turn project
creased by shivering (tremor). This lasts until from the ventral norepinephrine tract to the
the actual level (→ A5, red line) has approach- fever-regulating neurons in the area preoptica
ed the new set level (plateau). When the fever and OVLT (→ A3). Norepinephrine that has
falls, the set level again falls, so that now the been released there causes the formation of
actual level is too high and cutaneous blood PGE 2 and thus fever. This also brings about the
flow increases, resulting in the person feeling release of adiuretin (ADH; V 1 receptor effect),
hot and sweating profusely (→ A5). α-melanocyte-stimulating hormone (α-MSH),
Fever is particularly common with infec- and the corticotropin-releasing hormone cor-
tions in the course of the acute-phase reaction ticoliberin (CRH), which counteract the fever
(→ p. 49ff.) in which fever-inducing sub- by means of a negative feedback loop in the
stances (pyrogens) cause a change in the set form of endogenous antipyretics (→ A4).
point. Exogenous pyrogens are constituents of As a consequence of fever, heart rate is in-
–1
pathogens, among which the lipopolysaccha- creased (8–12 min /8C) and energy metabo-
ride complexes (endotoxins) of gram-negative lism raised, resulting in fatigue, joint aches
bacteria are particularly effective. Such patho- and headaches (see also p. 49ff.), increase in
gens, or pyrogens, are opsonized by comple- slow-wave sleep (which has a restorative func-
ment (→ p. 42ff.) and phagocytozed by macro- tion for the brain) as well as, in certain circum-
phages, for example, Kupffer cells in the liver stances, disturbances of consciousness and of
(→ A1). These release numerous cytokines, the senses (fever delirium) and seizures (see
among them the endogenous pyrogens inter- below).
leukin 1α, 1β, 6, 8, and 11, interferon α 2 and γ, The value of fever probably lies in its coun-
the tumor necrosis factors TNFα (cachectin) teracting infection. The raised temperature in-
and TNFβ (lymphotoxin), the macrophage-in- hibits the replication of some pathogens, while
flammatory protein MIP 1 and many others. It actually killing others. In addition, the plasma
is thought that these cytokines (M r = ca. 15– concentration of essential metals for bacterial
30 kDa) reach the circumventricular organs of reproduction, namely iron, zinc, and copper,
the brain which do not possess a blood-brain- is reduced. Furthermore, cells damaged by
barrier. The cytokines, therefore, can cause the viruses are destroyed, so that viral replication
fever reaction at these organs or nearby in the is inhibited. For these reasons antipyretics
area preoptica and the organum vasculosum of should in general only be used if the fever
the lamina terminalis (OVLT) by means of pros- leads to febrile convulsions, common in infants
taglandin PGE 2 (→ A2). Fever-reducing drugs and young children, or rises so high (> 398C)
(antipyretics) are effective here. Thus, acetyl- that the onset of seizures is to be feared.
salicylic acid, e.g., inhibits the enzymes that
20 form PGE 2 from arachidonic acid (cyclo-oxy-
genases 1 and 2).
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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