发热的病因和机制学习培训课件

新冠疫情期间闻“热”丧胆，有你吗？——发热的病因和机制

我们可以在发热的哪些环节实施解热呢?Whichstepoffevercanwecarryoutantipyretictreatmentstodecreasebodytemperature?0102?发热是机体的敌人还是朋友?Isfeveranenemyorafriendtoourbody?发热的机制RegulatorymechanismsinvolvedinthepathogenesisoffeverPyrogenicactivator11发热激活物Releaseofcentralmediators（PGE2,cAMP,Na+/Ga2+↑,AVP,

CRH,etc.）ThermoregulationcenterSet-point↑CutaneousvasoconstrictionHeat

dissipation↓Bodytemperature↑Heatproduction↑

34ThermoregulationeffectorresponseSkeletalmuscletension释放中枢调节介质骨骼肌紧张体温中枢调定点上移皮肤血管收缩调温效应器反应产热增多体温升高散热减少Activationofmonocytes/macrophagesReleaseofEPs(IL-1,IL-6,TNF)2激活单核细胞或巨噬细胞释放内生致热原发热激活物是指能激活人体产内生致热原细胞产生内生致热原的一类物质。Thesubstanceswhichcanactivateendogenouspyrogens(EP)-producingcellsofthehumanbodytoproduceendogenouspyrogens(EP)aretermedpyrogenicactivators.一、发热激活物PyrogenicactivatorInfectivefactors一、发热激活物——外生致热原Pyrogenicactivator—Exogenouspyrogens大肠杆菌(Escherichiacoli)肺炎双球菌(Streptococcuspneumoniae)G-：脂多糖(LPS)内毒素(endotoxin，ET)G+：外毒素(exotoxin)

肽聚糖(peptidoglycan)01白假丝酵母菌(Candidaalbicans)血吸虫(Schistosome)03Exogenouspyrogens流感病毒(Influenzavirus)新冠病毒(COVID-19)02细菌Bacteria病毒Virus真菌、螺旋体、寄生虫Fungi,Spirochetes,Parasitenon-microbialpyreticsubstances01抗原抗体复合物Antigen-antibodycomplexes系统性红斑狼疮(Systemiclupuserythematosus)类风湿(Rheumatoid)一、发热激活物——非微生物致热物质Pyrogenicactivator—non-microbialpyreticsubstances02严重组织损伤Severetissuedamages急性心肌梗死，外伤，重大外科手术Acutemyocardialinfarction,trauma,majorsurgicaloperationsNon-infectivefactors0304类固醇Steroids尿酸盐结晶UratecrystalsPyrogenicactivator1发热激活物Activationofmonocytes/macrophages2ReleaseofEPs激活单核细胞或巨噬细胞释放内生致热原二、内生致热原endogenouspyrogen,EP内生致热源是在发热激活物的作用下，由产EP细胞产生的可以直接引起发热的物质。Epscanbedefinedasanymoleculeswithdirectfever-inducingactivities,whichareproducedendogenouslybyEP-producingcellsuponstimulationbyexogenouspyrogensorendogenouspyrogenicactivators.单核细胞(Monocytes)巨噬细胞(Macrophages)枯否细胞(Kupffercells)淋巴细胞(lymphocytes)神经胶质细胞(Neuroglialcells)肿瘤细胞(Tumorcells)白细胞介素-1(IL-1)肿瘤坏死因子(TNF)干扰素(IFN)白细胞介素-6(IL-6)巨噬细胞炎症蛋白-1(MIP-1)产EP细胞EP种类二、内生致热原endogenouspyrogen，EP发热不是绝对的坏事

Feverisnotabsolutelybad增强机体抗感染能力Enhancetheanti-infectioncapacity引起急性期反应Triggeracutephaseresponse分解代谢旺盛Acceleratetherateofcatabolism引发器官功能紊乱Triggerdysfunctionoforgans导致胎儿发育障碍、脱水和高热惊厥Causesfetaldevelopmentaldisorders,dehydration,febrileseizures药物降温Drugcooling

物理降温Physicalcooling38℃发热的机制RegulatorymechanismsinvolvedinthepathogenesisoffeverPyrogenicactivator11发热激活物Releaseofcentralmediators（PGE2,cAMP,Na+/Ga2+↑,AVP,

CRH,etc.）ThermoregulationcenterSet-point↑CutaneousvasoconstrictionHeat

dissipation↓Bodytemperature↑Heatproduction↑

34ThermoregulationeffectorresponseSkeletalmuscletension释放中枢调节介质骨骼肌紧张体温中枢调定点上移皮肤血管收缩调温效应器反应产热增多体温升高散热减少Activationofmonocytes/macrophagesReleaseofEPs(IL-1,IL-6,TNF)2激活单核细胞或巨噬细胞释放内生致热原三、EP进入体温调节中枢的方式TheroutesforEPsignalsintothethermoregulatorycenter脉络丛(Choroid

plexus)直接通过血脑屏障Directtransportedacrossblood-brainbarrier(BBB)通过迷走神经传入纤维Viastimulationofvagusnerve通过下丘脑终板血管器Viaorganumvasculosumlaminaeterminalis(OVLT)下丘脑终板血管器(OVLT)视交叉(Opticchiasma)毛细血管capillary（1）通过下丘脑终板血管器Viaorganumvasculosumlaminaeterminalis(OVLT)OVLT神经元

OVLTneurons介质mediatorsPOAH神经元POAH

neuronsEPOpticchiasma3rdventricleSuperioropticrecess下丘脑终板血管器(OVLT)视交叉(Opticchiasma)第三脑室视上隐窝视交叉介质mediatorsPOAH神经元POAH

neurons（2）直接通过血脑屏障Directtransportedacrossblood-brainbarrier(BBB)01

血脑屏障的毛细血管床部位存在IL-1,IL-6,TNF的

可饱和转运机制。ThecapillaryendothelialcellsatBBBpossessseveralundefinedtransportersforIL-1,IL-6,andTNF.BBBBloodBrainIL-1、IL-6、TNF（2）直接通过血脑屏障Directtransportedacrossblood-brainbarrier(BBB)02通过脉络丛被动扩散转运入脑，通过脑脊液到达POAH。EPsmayenterintothebrainbypassivediffusionacrossthechoroidplexus,reachingPOAHthroughcerebrospinalfluidcirculation.脉络丛(choroid

plexus)内生致热原可刺激胸、腹腔脏器巨噬细胞周围的迷走神经，通过迷走神经传入纤维将致热信号传入体温调节中枢。EPscanstimulatethevagusnervearoundhepaticmacrophages,andsendtheperipheralpyrogenicsignalintothethermoregulatorycenterthroughtheafferentfibersofthevagusnerve.（3）通过迷走神经传入纤维ViastimulationofvagusnerveHeartBronchioflungsLiverStomachSmallintestinesLargeintestineRectum体温调定点上移ThermoregulationcenterSet-point↑？EPs内生致热源能直接引起调定点上移？CanEPsdirectlyelevatethetemperatureset-point?发热的机制RegulatorymechanismsinvolvedinthepathogenesisoffeverPyrogenicactivator11发热激活物ThermoregulationcenterSet-point↑Releaseofcentralmediators3释放中枢调节介质体温中枢调定点上移Activationofmonocytes/macrophagesReleaseofEPs(IL-1,IL-6,TNF)2激活单核细胞或巨噬细胞释放内生致热原四、中枢发热介质CentralmediatorsoffeverCentralmediatorsoffeverPositiveNegativePGE2AVPCRHα-MSHcAMPlipocortin-1Na+/Ga2+ratioIL-10NO热限Febrileceiling发热时体温上升的高度被限制在一定范围内的现象称为热限。Thephenomenonthattheelevationofbodytemperatureislimitedtoacertainrangeisfebrileceiling.热限Febrileceiling体温升高Bodytemperature↑EP体温正调节中枢Positivethermoregulatorycenter体温负调节中枢Negativethermoregulatorycenter负调节介质Negativemediators42℃41℃Pyrogenicactivator11发热激活物Releaseofcentralmediators（PGE2,cAMP,Na+/Ga2+↑,AVP,

CRH,etc.）ThermoregulationcenterSet-point↑CutaneousvasoconstrictionHeat

dissipation↓Bodytemperature↑Heatproduction↑

34Thermoregula