Fever病理生理學(xué)-課件

FEVERChengwuLiu20151PPT課件OutlinesIntroduction1Etiology&Pathogenesis2AlterlationsofMetabolismandFunction4Stage&Manifestation3

PreventionandTreatment52PPT課件Part1Introduction1.normalbodytemperatureanditsregulationnormalbodytemperature:(37℃)

axillarytemperature:36~37.4℃

sublingualtemperature:36.7~37.7℃

rectaltemperature:36.9~37.9℃

3PPT課件Part1Introductionthermoregulatorycenter

seniorcenter:

preoptic

anteriorhypothalamus(POAH)

secondarycenter:medullaspinalcord

1.normalbodytemperatureanditsregulation4PPT課件Part1Introduction1.normalbodytemperatureandthermoregulationtheprocessofthermoregulation

T>37℃T<37℃constanttemperaturePOAH37℃temperaturereceptorafferentnerve

efferentnervethermogenesisthermolysis

efferentnerve5PPT課件Fig.ConditionsofelevationinbodytemperatureTheelevationofBodytemperaturePhysiologicalelevationofbodytemperaturePathologicalelevationofbodytemperatureStressStrenuousexerciseBeforemenstruationFeverHyperthermia

Part1Introduction1.normalbodytemperatureandthermoregulation6PPT課件Part1Introduction2.FeverandHyperthermiafever—

thehypothalamicsetpointisresetatahightemperaturebypyrogen,resultinbodytemperaturebeinghigherthan0.5℃.

hyperthermia—

thebodytemperatureishigherthan0.5℃,butthehypothalamicsetpointhadnotbeenchanged.7PPT課件Part1IntroductionThecomparisonsoffeverandhyperthermiaitemsFeverhyperthermiaetiologypyrogennopyrogenmechanismsetpointturnedtosetpointnochange

ahighlevelordamnificationTreachahighlevel,febrileceilingeffectTriseaveryhighlevel,deadlinesstreatmenteliminatethepyrogensphysicalcooling

alcoholbath

2.FeverandHyperthermia8PPT課件

physiologicalelevatedfever(regulatory)temperatureusually〈42℃

pathological

heperthermia

may〉42℃42℃:ceilingtemperature,feverlimitation9PPT課件Part2Etiology&Pathogenesis1.pyrogenicactivator

pyrogenicactivatorexogenouspyrogenproductsofbodybacteriumvirusesfungispirochetesplasmodiumAb-Agsteroid10PPT課件(1)exogenouspyrogenPart2Etiology&Pathogenesis1.pyrogenicactivator①bacterium

A.gram-positivebacterium:staphylococci,streptococcus,

etc.

(exotoxin)

B.gram-negativebacterium:colibacillus,gonococci,etc.

(endotoxin,ET)

11PPT課件Thestructureoflipopolysaccharide12PPT課件Part2Etiology&PathogenesisThecharactersofETa.ThevenenouscomponentisthelipidAoflipopolysaccharide

b.Molecularweight

is1000～2000KD,difficulttocross

thebloodbrainbarrier(BBB).c.Strongstability,resistacidandheat,inactivatedby160℃for2hours.d.Nospeciesspecificity.1.pyrogenicactivator13PPT課件Part2Etiology&PathogenesisThecharactersofETe.latentperiod:20~30min.f.Pyrogenicdoseis0.1~1.0μg(100~1000ng).g.toleration.h.TheresponsivesiteisEPproducingcells.i.Function:activateEP-producingcellstoproduceandreleaseendogenouspyrogen(EP).

1.pyrogenicactivator14PPT課件(1)exogenouspyrogenPart2Etiology&Pathogenesis①bacterium②viruses:influenzavirus,SARSvirus,measlesvirus,etc.③fungi:

candida

albicans

④spirochetes:

leptospira,⑤plasmodium

1.pyrogenicactivator15PPT課件16PPT課件differentmicroorganismhasdifferentpyrogenicactivatorandproducesdifferentEP,leadingtodifferentfevertypeExamples:Flutuberculosis(TB)Malaria17PPT課件4039383736Ccontinuedfever

1234567891011121314151617daySalmonellatyphimurium.

Pneumonia稽留熱18PPT課件4039383736remittentfeverCSepsis,severetuberculosis(TB),rheumaticfever

1234567891011121314151617day弛張熱19PPT課件4039383736intermittentfeverCmalaria1234567891011121314151617day間歇熱20PPT課件4039383736undulantfeverCBrucelladisease1234567891011121314151617day波狀熱21PPT課件4039383736irregularfeverTB,rheumaticfeverC1234567891011121314151617day不規(guī)則熱22PPT課件(1)categoryofEPPart2Etiology&Pathogenesis2.endogenouspyrogen(EP)IL-1

monocyte/macrophage/endotheliocyte

IL-6

monocyte/fibrocyte/endotheliocyteTNFmacrophage/lymphocyte

IFNWBC/monocyteMIP-1macrophage23PPT課件(2)ThecharactersofEPPart2Etiology&Pathogenesis

a.Thecomponentisproteinb.Lightmolecularweight

,easytocrosstheBBB.c.Poorstability,Thermolabile.d.speciesspecificity.2.endogenouspyrogen(EP)24PPT課件(2)ThecharactersofEPPart2Etiology&Pathogenesis

e.latentperiodabout15min.f.Pyrogenicdoseis30~50ng.g.Notoleration.h.TheresponsivesiteisPOAH.i.Function:up-regulatethesetpointofthermostatcenter.

2.endogenouspyrogen(EP)25PPT課件Comparisonbetweenpyrogenicactivator(ET)andendogenouspyrogens

ET

EPIL-1TNFIFNMIP-1originG-,BM,tumorCM,

LCWBC,MNMN

componentsLPSglycopro.Pro.glycopro.HCP

Moleculewt5~9000kd12~1817~2515~17?Heatresistant+--+--Heattype2peaks2peakssmalldose,1peak1peak1peakbigdose,2peaks（dose-depends）MN:monocytesHCP:Heparin-combiningpro.EP:cytokines,inflammatorymediators26PPT課件(3)ProductionandreleaseofEPPart2Etiology&Pathogenesis

LPSLBPsCD14receptorSignaltransductionGeneexpressionEP:LI-1、TNF、LI-6、INFmonocytemacrophageendotheliocyteLymphocytefibrocyteWBCetc.2.endogenouspyrogen(EP)27PPT課件(1)ThethermoregulationcenterPart2Etiology&Pathogenesis3.Mechanismsofsetpointelevation

thepositiveregulatorycenter:

preopticanteriorhypothalamus,POAHthenegativeregulatorycenter：medialamygdaloid

nucleus,MANventralseptal

area,VSA28PPT課件(2)PathwaysofEPsignaltransductiontothethermoregulationcenterPart2Etiology&Pathogenesis3.Mechanismsofsetpointelevation

BodytemperaturePOAHMAN/VSAsetpoint？EP-producingcellsPyrogenicactivatorEP29PPT課件(2)PathwaysofEPsignaltransductiontothethermoregulationcenterPart2Etiology&Pathogenesis

ViaOrganum

Vasculosum

Laminae

Terminalis,OVLTViaStimulationofVagusDirectEntrythroughBlood-BrainBarrier3.Mechanismsofsetpointelevation30PPT課件Part2Etiology&Pathogenesis

EPmacrophageSupraopticrecessopticchiasma

OVLTmacrophageCapillaryPOAHNeuronPOAHNeuron31PPT課件(3)ThemediatorsofcentralsystemPart2Etiology&Pathogenesis

thepositiveregulatorymediators:thenegativeregulatorymediators:3.Mechanismsofsetpointelevation32PPT課件(3)ThemediatorsofcentralsystemPart2Etiology&Pathogenesis

EPthepositiveregulatorymediatorsthenegativeregulatorymediatorsPOAHMAN,VSACentralbodytemperature+-3.Mechanismsofsetpointelevation33PPT課件(3)ThemediatorsofcentralsystemPart2Etiology&Pathogenesis

1)thepositiveregulatorymediators:①ProstaglandinE(PGE):a.InjectPGEintocerebralventriclescaninduceafebrileresponse.b.DuringEPinducedfever,thePGElevelsincerebrospinalfluidincreasesignificantly.c.InjectPGEinhibitor,thePGElevelsincerebrospinalfluid

decrease.3.Mechanismsofsetpointelevation34PPT課件(3)ThemediatorsofcentralsystemPart2Etiology&Pathogenesis

1)thepositiveregulatorymediators:②Na+/Ca2+ratio,cAMP:InjectNa+incerebralventricles

Na+/Ca2+↑T↑c(diǎn)AMP↑InjectCa2+incerebralventricles

Na+/Ca2+↓T↓cAMP↓3.Mechanismsofsetpointelevation35PPT課件(3)ThemediatorsofcentralsystemPart2Etiology&Pathogenesis

1)thepositiveregulatorymediators:③CRH:IL-1IL-6

CRH↑T↑3.Mechanismsofsetpointelevation36PPT課件(3)ThemediatorsofcentralsystemPart2Etiology&Pathogenesis

1)thepositiveregulatorymediators:④NO:NO

POAH,OVLTT↑Browfattinessmetabolize

↑

Inhibitethenegaviteregulatorymediatorsrelease3.Mechanismsofsetpointelevation37PPT課件(3)ThemediatorsofcentralsystemPart2Etiology&Pathogenesis

2)thenegativeregulatorymediators:①

argininevasopressin(AVP)②alpha-melanocytestimulatinghormones(-MSH)③annexinA1,orcalllipocortin-1(LP-1)3.Mechanismsofsetpointelevation精氨酸加壓素（AVP)：由視上核、室旁核的大細(xì)胞神經(jīng)元合成。在下丘腦腹隔區(qū)的神經(jīng)纖維和神經(jīng)終端中都證實(shí)有AVP的存在，參與抗發(fā)熱。具極強(qiáng)的解熱作用，其解熱作用比醋氨酚(撲熱息痛)大25000倍。38PPT課件(4)ThemechanismsofsetpointelevationcausedbyEPPart2Etiology&PathogenesispyrogenicactivatorEP-producingcellsEP↑Heat-production↑Heat-loss↓Bodytemperature↑

(OVLT？)POAHVSA,MANHypothalamicsetpoint↑3.Mechanismsofsetpointelevation39PPT課件Character:heat-production↑,heat-loss↓heat-production>heat-lossbodytemperature↑Part3Stages&Manifestations1.Thefervescencestage

Manifestation:chill,paleskin,goosefleshThefervescencestagesetpointsetpoint↑40PPT課件Character:heat-production↑,heat-loss↑heat-productionbalancesheat-lossbodytemperature↑Part3Stages&Manifestations2.Thepersistentfebrilestage

Manifestation:feelsneithercoldnorhot,xerosiscutis

,thirstThepersistentfebrilestagesetpointsetpoint↑41PPT課件Character:heat-production↓,heat-loss↑heat-production<heat-lossbodytemperaturedeclinetonormalPart3Stages&Manifestations3.Thedefervesccencestage

Manifestation:hidrosis,disturbanceofwaterandelectrolyteThedefervescencestagesetpointsetpoint↑42PPT課件Character:catabolism↑Part4Alterlationsofmetabolismandfunction1.Metabolism

(1)glycometabolism:

glucosecatabolism↑,

glucogen↓

lacticacid↑

(2)lipometabolism:

lipolysis↑,fattiness↓

acetonebody↑,

ketoacidosis43PPT課件Character:catabolism↑Part4Alterlationsofmetabolismandfunction1.Metabolism

(3)Proteinmetabolism:

proteincatabolism↑,negativenitrogenbalance(4)water,electrolyteandvitaminemetabolism:

The