BODY TEMPERATURE AND MECHANISM FEVER 27 Feb'12

Body Temperature
“Core Temperature”

• Aortic blood temperature
• Esophageal temperature
• Tympanic membrane temperature

Clinical Approximates

• Sublingual (oral) temperature    = 0.7o F < core
• Axillary temperature        = 1.8o F < core
• Rectal temperature        = 0.9o F > core

Normal Thermoregulation
Afferent Sensing

• Cold receptors –> A delta fibers
• Warm receptors –> C fibers
• Integrated in spinal cord and CNS –> hypothalamus

Central Integration

• 20% each contribution from: skin, deep chest and abdomen, spinal cord, CNS, hypothalamus
• Skin input predominates behavioral responses
• Cold and warm response thresholds only 0.4º apart

Efferent Responses

• Behavioral (clothing, adjusting environment)
• Response to heat: sweat, cutaneous dilation
• Response to cold: digital vasoconstriction

Endogenous Pyrogens

• Interleukin–1 (alpha*, beta)
• Interleukin–6
• Interleukin–11
• Tumor necrosis factor (alpha)
• Interferon (alpha, beta, gamma)
• Prostaglandin–E2
• Platelet activating factor
• Ciliary neurotropic factor (CNTF)
• Oncostatin M
• Cardiotropin–1
• Leukemic inhibitory factor (LIF)

MECHANISM FEVER

• These cytokine factors are released into general circulation where they migrate to thecircumventricular organs of the brain due to easier absorption caused by the blood-brain  barrier 's reduced filtration action there. The cytokine factors then bind withendothelialreceptorson vessel walls, or interact with localmicroglial cells. When these cytokine factors bind, thearachidonic acid pathway is then activated.
• Exogenous One model for the mechanism of fever caused by exogenous pyrogens includes LPS,which is a cell wall component of gram-negative bacteria.An immunological protein calledlipopolysaccharide-binding protein(LBP) binds to LPS. The LBP–LPS complexthen binds to theCD14 receptor of a nearby macrophage.This binding results in the synthesis and release of various
• endogenouscytokinefactors, such as interleukin 1 (IL-1), interleukin 6 (IL-6), and the tumor necrosis factor-alpha. In other words, exogenousfactors cause release of endogenous factors, which, in turn, activate the arachidonic acid pathway.
• PGE2 release comes from the arachidonic acidpathway. This pathway (as it relates to fever), is mediated by theenzymes  phospholipase A2(PLA2),cyclooxygenase-2(COX- 2), and prostaglandin E2 synthase.These enzymes ultimately mediate the synthesis and release of PGE2.PGE2 is the ultimate mediator of the febrile response.
• The set-point temperature of the body will remain elevated until PGE2 is no longer present. PGE2 acts on neurons in the preoptic area (POA) through the prostaglandin E receptor 3 (EP3). EP3-expressing neurons in the POA innervate thedorsomedial hypothalamus(DMH), the rostralraphe   pallidus nucleus in themedulla oblongata(rRPa) and the  paraventricular nucleus(PVN) of thehypothalamus. Fever signals sent to the DMH and rRPa lead to stimulation of thesympatheticoutput system, which evokes non-shivering thermogenesis to produce bodyheat and skin vasoconstriction to decrease heat loss from the body surface. It is presumedthat the innervation from the POA to the PVN mediates the neuroendocrine effects of fever through the pathway involving pituitary glandand variousendocrine organs.
• The set-point temperature of the body will remain elevated until PGE2 is no longer present.
• PGE2 acts on neurons in the preoptic area (POA) through the prostaglandin E receptor 3 (EP3).
• EP3-expressing neurons in the POA innervate thedorsomedial hypothalamus(DMH), the rostralraphe   pallidus nucleus in themedulla oblongata(rRPa) and the  paraventricular nucleus(PVN) of thehypothalamus. 

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