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StressChengwuLiu20141StressChengwuLiu1StressReviewGeneralresponseinstressCellularresponseinstressmetabolicandfunctionchangedinstressstressanddiseasesOUTLINE2StressReviewOUTLINE2§1Basicconceptsofstress■Stressor■Classificationofstressresponse■SignificanceofstressStress■Stress
3§1Basicconceptsofstress■Sstress7yrsenglish病理生理学双语课件stress7yrsenglish病理生理学双语课件
2.Stressor
Thestimulioragentsthatinducestress.Stressor
Psychological,sociologicalfactorsInternalfactorsExternalfactorsWorkpressure,liferhythm,interpersonalrelationCold,heat,toxins,drugs,bacteria,light.Homeostasis,disease,cancer.Stress62.StressorStressorPsyStress7Stress788humanorganismanimal
plant?
stressemergencereactionHigherorganismLowerorganism9humanHigMimosa10Mimosa10■IfthestressisfavoroftheFightorFlightunderemergencysituation,Eustress
■Ifthestressorsaretoostrongcausepathologyorevendeath,
DistressPsychologicalstress3.ClassificationofstressresponseStressreactionPhysicalstressPhysical,chemicalPsycho-socialfactorsStress11■Ifthestressisf
4.SignificanceofstressDefenseanddamnificationareconcomitance,theyarereciprocaltransformation.Defense:stressisatransmutationoforganismadaptation,itcanincreasethebody'sreadiness,andhelpthebodyfightorflight.Damnification:Ifstressistoostrongorstimulatethebodytoolong,itisharmful,andcanleadtostress-induceddiseases.Stress124.SignificanceofstressDefen§2GeneralresponseinstressStressstressorsCellularandhumoralresponseAAP,HSP↑
Neuroendocrineresponse+
generaladaptivereaction
CA,GC↑
Functionalandmetabolicchangesoforgansandsystems13§2GeneralresponseinstressS1414NeuroendocrineresponsestostressNeuroendocrineresponsesLocusceruleus-norepinephrine/Sympathetic-adrenalmedullaaxis(LC-NE)catecholamine(CA)↑Hypothalamic-pituitary-adrenalcortexsystem(HPA)activatedglucocorticoid(GC)↑Stressotherhormonalresponsestostress15Neuroendocrineresponsestost(1)LC-NEcomponents(centralintegratingandregulating)
ACTHLCMedullaAdrenalgland
PhysicalstimulationCRHGCpalliumLimbicsystemParaventricularnucleus(PVN)Social-psychostressCACortexadrenalglandpituitaryStressEmotionalreaction1.Locusceruleus-Norepinephrine(LC-NE)16(1)LC-NEcomponents(central1)Center
Effects
■Causeemotions:excitement,awake,nervousandanxiety.
■EssentialforinitiatingtheHPAaxis.(upwardfibersofLC)Stress
(2)BasiceffectsofLC-NE171)CenterEffectsStress(2)BasStress2)Peripheral
Effects■
PlasmaCA(Adr,NE,Dopamine)level↑rapidly.(downwardfibersofLC)
(2)BasiceffectsofLC-NE18Stress2)PeripheralEffects(2)Stress1)metabolism
stressCA↑Cell-R(+)Glucagon↑
Cell-R(+)
insulin↓bloodglucose↑glucogen,lipiddegradation↑
fitthebodyenergydemands
energyconsumption↑,tissuedecomposition↑
(badresults)prolonged+_
(3)Functionalandmetabolicresponsesinbody
19Stress1)metabolismprolongGLUT2(glucosetransportprotein)←glucose↑glucose↓→insulin↑Glucagon↑
cell,pancreas
cell,pancreas20GLUT2(glucosetransportprote2)cardiovascularsystemstressCA↑HR↑,contractility↑,CO↑peri-resistance↑bloodredistribitionkeyorgansbloodsupplyprolongedHeartafterload↑hypertensionunfavorableresults212)cardiovascularsystemstress
4)otherhormoneschanges
CAACTH,GH,EPO,T3\T4andreninexcretion.Aim:bodyenter“arouse”statetocopewithchangedenvironment.unfavorableresults3)RespiratorysystemStressRRfaster&deepO2carrying↑tissueO2supply↑Respiratoryalkalosistissuelackblood&O2224)otherhormoneschangesAiPVNpituitaryCortexofadrenalglandGC↑CRH↑ACTH↑
2.
Hypothalamic-pituitary-adrenal(HPA)
(1)components
HPAaxis:hypothalamicparaventricularnucleus(PVN)+pituitarygland+adrenalglandcortex.PVNisthecentralsite.
StressEmotionstressresponseamygdala,hippocampi,limbicsystemLC-NEPeripheraleffectorPhysicalstressresponse23PVNpituitaryCortexofadrenaPVNLimbicsystemIntegratesignalsPhysicalstresssignalpituitaryADH↑+
(2)Basiceffectsofstress
■
EffectsofCNSStressCRH↑+sympathetic-adrenalMedullaexcitedCA↑+β-endorphin↑--AldrenalcortexGC↑ACTH↑24PVNLimbicsystemPhysicalstres
(2)Basiceffectsofstress
Stress●suitableCRH↑
facilitateadaptation
excitement,delighted
●excessiveCRH↑
adaptationdisturbance
anxiety,depression,■Effectsofperipheral:viaGC25(2)BasiceffectsofstressSt
GC:maintainbloodpressureandenhancethefunctionofCA,glucagoninlipidmobilization.defensebadimpacts
(3)thephysiologicalsignificanceofelevatedGC(GC↑>25-37mg/d)Stress●↑bloodglucose&energysupply●improvecardiovascularfunction●restraininflammation,↓tissueinjury●stabilizelysosomemembrane●proteindecomposed↑●immunerestrain,infection↑●inhibittissueregeneration●depresssexualglandaxis●slowgrowth;behaviorchange26GC:maintainbloodprQuestion:
What’sthemechanismsofelevatedbloodglucoseduringstress?insulin↓:isletβcellα-Ractivated↓insulinexcretionGlucagon↑:CAisletαcellβ-Ractivated↑itsexcretionGC↑:↑thelipidmobilizationofCA&glucagon27Question:
What’sthemechanismInsulinisletβcell↓TRHhypothalamus↓TSHpituitaryfrontlobe↓T3,T4thyroidgland↓GhRHhypothalamus↓
namesecretingsitechange
-endorphinepituitarygland↑ADHhypothalamus(PVN)↑growthhormonepituitaryglandacute↑,chronic↓aldosteroneadrenalcortex↑glucagonsisletcells↑prolactinpituitarygland↑3.otherhormonalresponsestostress
Stress28Insulin2929303031314.generaladaptationsyndrome(GAS)alarmstageresistancestageexhaustionstageStress324.generaladaptationsyndromeGeneraladaptationsyndrome(GAS)AlarmstageResistancestageExhaustionstageResponserapidly,shortduration.Sympathetic-adrenalmedullaexcitedArouse,emergencymobilizationSympathetic-adrenalmedullaresponse↓
,GCincreasedgraduallyAlarmsymptomspresentagain,
GCcontinue↑;
homeostasisbrokenDefensedepositisgraduallyconsumed.ExhaustionofresistanceCharacteristicSignificanceStress33Generaladaptationsyndrome(GAGeneralAdaptationSyndrome34GeneralAdaptationSyndrome34
§3cellularresponseinstress
expressedproteinsinCellsAcutephaseprotein,(APP)Heatshockprotein,(HSP)Physicalstressorstimulation35§3cellularresponseinstres【NegativeAP】
proteinsdown-regulatedduringacutephaseresponse:albumin,pre-albumin,Fe++-carryingprotein.【Acutephaseprotein】
Someproteinsexpressedduringacutephaseresponse.【Acutephaseresponse】
Anon-specificreactionoccurredshortlyafter(hourstodays)somedisorders,especiallyinfectivediseases,trauma,inflammationandimmunediseases.
1.Acutephaseprotein,APP36【NegativeAP】【■APPissynthesizedinliver.■APPisasecretiveprotein,increasedinstress.Stress
(1)OriginofAPP37■APPissynthesizedinliver.S■proteinasesuppressivepro.
:α1antichymotrypsin↑■coagulation&plasminrelatedpro.
stress
thrombinogen
,plasmin,fibrinogen,factorⅧ↑■complements↑
■transferpro.↑(copper-pro.,haptoglobin.etc)■otherpro.(CRP,α1acidglycoprotein↑)
(2)ClassificationofAPP38■proteinasesuppressivepro.:■depresstheactivityofprotease↓tissueinjury
proteasesuppressivepro.↑
↓tissueinjury■↓thegenerationofOFR
copper-proteinactivateSOD;↓OH-.
Stress(3)FunctionofAPP39■depresstheactivityofprote■promotionofthefunctionofphagocyteanti-inflammationCRP+bacteriawallphagocytosis↑■eliminatenecrosistissue
CRP(-)plateletphospholipase
Cinflammatorymediator↓necrosistissueeliminate↑Stress40Stress402.Heatshockprotein,HSP【definition】
aproteinfamilyproducedunderstressespeciallyinheatenvironment.412.Heatshockprotein,HSP【def(1)FactorsinducingHSPproduction
【HSPbiologicalfeatures】
■non-specificininduce■universal■conservativeinstructureStress42(1)FactorsinducingHSPprodu(2)basicstructureofHSP
■HSP70structureATPasemotif(highlyconservative)
Recognisingmotif(variable)ProteasebindingsiteN-450aaresidual200aaresidual
-CStress43(2)basicstructureofHSP■HSHSP:HSP110,HSP90,HSP70,HSP60
&smallHSP.
■induced
HSPinducedbyvariousstressors,repairorgetridofinjuredproteintopreventcellsfromsevereinjury.■structural
HSPstructuralpro.Incells,helptofold,transferordegradationneworinjuredprotein“Molecularchaperone”
(3)functionandclassification44HSP:HSP110,HSP90,HSP70,HSP6ThemajorfunctionofHSPfoldingtranslocationrenaturationdegradation45ThemajorfunctionofHSP454646(4)HSPgeneexpressionregulationHSPHSFHSEHSF:热休克转录因子;HSE:热休克元件HSF三聚体stressInjuredproteinprotein
HSPStress47(4)HSPgeneexpressionregula1.Effectsonmetabolism【features】
metabolicrate↑,decomposition↑,synthesis↓
(1)Highmetabolicrate
SeverestressCA、GC↑
decompose↑
BMR↑
thin,weak,resistance↓(2)glucosemetabolism
stress
insulin↓;CA,Glucagon,GH,GC↑
stresshigebloodsugarofstressdiabetesStress§4metabolicandfunctionchangedinstress481.Effectsonmetabolism(1)(3)lipidmetabolism
fatmobilization,utilization↑
freefattyacid,ketobody↑(4)proteinmetabolismAA↑providematerialforAPP,HSPsynthesisStress49(3)lipidmetabolism(4)pro2.SystemandorganchangesStress(1)CNS
■HPAaxis:suitableexcitedishelpfulforgoodmemoryandemotion.
■HPA:excessiveexcitedordepressiveCNSdysfunction
(awake)502.SystemandorganchangesStr(4)immunesystem:depression(5)bloodsystem
(2)cardiovascular:HR
↑,contractility↑,CO↑
,BP↑。(3)digestivesystem:appetite↓,stressulcerStress51(4)immunesystem:depression(2
1.Stressulcer(1)definition
(2)manifestations
■bleeding:
■stressulcer:Stress§5stressanddiseases52(2)manifestationsStress
3)pathogenesis
(1)stomachmucousmembraneischemiaRAASexcited(+)
smallbloodvesselconstracted
mucousmembraneischemia
HCO3-andmucous↓mucouscellregeneration↓Mucousbarrierbroken
inter-cellularconjunctioninjuryH+entermucousmembrane
H+cannottransferintime
H+accumulatedinmembrane
stressulcer
membraneleak,uneasytorepair
Stress533)pathogenesisStr(2)GC↑
(3)PGs↓
Stress54(2)GC↑Stress542)geneticsusceptibilityisactivated
3hypertension
1)RAASexcited
EmotionNoiseExertionTensionstressors
hypothalamus
sympatheticNimpulse↑CA↑ContractionofBVrenin↑angiotesinⅡ↑Aldo↑WaterandNaretensionArterialpressure↑hypertensionStress552)geneticsusceptibilityisChild,male,10years.leftarmandlowerleftlimbhavebeenburnforalargearea.onadmission,T:37.5℃,HR:125/min,Bp:135/80mmHg,WBC:1.5×109/L,N:0.90.GLU:10mmol/L(normalfastingbloodglucose:3.9-6.0mmol/L).After2-3days,itisunwellinepigastrium,withdarkstoolstwice,fecaloccultblood(+).
questions:
1)Whatisthepathologicstatusinthispatient?
2)Whythispatienthavedarkstools?Explainthepathogenesy.
3)Howabouttheneuroendocrinesysteminthispatient?56Child,male,10years.leQUESTIONS1.IllustratethesignificanceanddisadvantagesofCAandGCinstress.2.Howaboutthebodymetabolicchangesduringstress?3.Howaboutthefeaturesandmechanismofstressulcer?4.What’sheatshockprotein?57QUESTIONS1.IllustratethesignStressChengwuLiu201458StressChengwuLiu1StressReviewGeneralresponseinstressCellularresponseinstressmetabolicandfunctionchangedinstressstressanddiseasesOUTLINE59StressReviewOUTLINE2§1Basicconceptsofstress■Stressor■Classificationofstressresponse■SignificanceofstressStress■Stress
60§1Basicconceptsofstress■Sstress7yrsenglish病理生理学双语课件stress7yrsenglish病理生理学双语课件
2.Stressor
Thestimulioragentsthatinducestress.Stressor
Psychological,sociologicalfactorsInternalfactorsExternalfactorsWorkpressure,liferhythm,interpersonalrelationCold,heat,toxins,drugs,bacteria,light.Homeostasis,disease,cancer.Stress632.StressorStressorPsyStress64Stress7658humanorganismanimal
plant?
stressemergencereactionHigherorganismLowerorganism66humanHigMimosa67Mimosa10■IfthestressisfavoroftheFightorFlightunderemergencysituation,Eustress
■Ifthestressorsaretoostrongcausepathologyorevendeath,
DistressPsychologicalstress3.ClassificationofstressresponseStressreactionPhysicalstressPhysical,chemicalPsycho-socialfactorsStress68■Ifthestressisf
4.SignificanceofstressDefenseanddamnificationareconcomitance,theyarereciprocaltransformation.Defense:stressisatransmutationoforganismadaptation,itcanincreasethebody'sreadiness,andhelpthebodyfightorflight.Damnification:Ifstressistoostrongorstimulatethebodytoolong,itisharmful,andcanleadtostress-induceddiseases.Stress694.SignificanceofstressDefen§2GeneralresponseinstressStressstressorsCellularandhumoralresponseAAP,HSP↑
Neuroendocrineresponse+
generaladaptivereaction
CA,GC↑
Functionalandmetabolicchangesoforgansandsystems70§2GeneralresponseinstressS7114NeuroendocrineresponsestostressNeuroendocrineresponsesLocusceruleus-norepinephrine/Sympathetic-adrenalmedullaaxis(LC-NE)catecholamine(CA)↑Hypothalamic-pituitary-adrenalcortexsystem(HPA)activatedglucocorticoid(GC)↑Stressotherhormonalresponsestostress72Neuroendocrineresponsestost(1)LC-NEcomponents(centralintegratingandregulating)
ACTHLCMedullaAdrenalgland
PhysicalstimulationCRHGCpalliumLimbicsystemParaventricularnucleus(PVN)Social-psychostressCACortexadrenalglandpituitaryStressEmotionalreaction1.Locusceruleus-Norepinephrine(LC-NE)73(1)LC-NEcomponents(central1)Center
Effects
■Causeemotions:excitement,awake,nervousandanxiety.
■EssentialforinitiatingtheHPAaxis.(upwardfibersofLC)Stress
(2)BasiceffectsofLC-NE741)CenterEffectsStress(2)BasStress2)Peripheral
Effects■
PlasmaCA(Adr,NE,Dopamine)level↑rapidly.(downwardfibersofLC)
(2)BasiceffectsofLC-NE75Stress2)PeripheralEffects(2)Stress1)metabolism
stressCA↑Cell-R(+)Glucagon↑
Cell-R(+)
insulin↓bloodglucose↑glucogen,lipiddegradation↑
fitthebodyenergydemands
energyconsumption↑,tissuedecomposition↑
(badresults)prolonged+_
(3)Functionalandmetabolicresponsesinbody
76Stress1)metabolismprolongGLUT2(glucosetransportprotein)←glucose↑glucose↓→insulin↑Glucagon↑
cell,pancreas
cell,pancreas77GLUT2(glucosetransportprote2)cardiovascularsystemstressCA↑HR↑,contractility↑,CO↑peri-resistance↑bloodredistribitionkeyorgansbloodsupplyprolongedHeartafterload↑hypertensionunfavorableresults782)cardiovascularsystemstress
4)otherhormoneschanges
CAACTH,GH,EPO,T3\T4andreninexcretion.Aim:bodyenter“arouse”statetocopewithchangedenvironment.unfavorableresults3)RespiratorysystemStressRRfaster&deepO2carrying↑tissueO2supply↑Respiratoryalkalosistissuelackblood&O2794)otherhormoneschangesAiPVNpituitaryCortexofadrenalglandGC↑CRH↑ACTH↑
2.
Hypothalamic-pituitary-adrenal(HPA)
(1)components
HPAaxis:hypothalamicparaventricularnucleus(PVN)+pituitarygland+adrenalglandcortex.PVNisthecentralsite.
StressEmotionstressresponseamygdala,hippocampi,limbicsystemLC-NEPeripheraleffectorPhysicalstressresponse80PVNpituitaryCortexofadrenaPVNLimbicsystemIntegratesignalsPhysicalstresssignalpituitaryADH↑+
(2)Basiceffectsofstress
■
EffectsofCNSStressCRH↑+sympathetic-adrenalMedullaexcitedCA↑+β-endorphin↑--AldrenalcortexGC↑ACTH↑81PVNLimbicsystemPhysicalstres
(2)Basiceffectsofstress
Stress●suitableCRH↑
facilitateadaptation
excitement,delighted
●excessiveCRH↑
adaptationdisturbance
anxiety,depression,■Effectsofperipheral:viaGC82(2)BasiceffectsofstressSt
GC:maintainbloodpressureandenhancethefunctionofCA,glucagoninlipidmobilization.defensebadimpacts
(3)thephysiologicalsignificanceofelevatedGC(GC↑>25-37mg/d)Stress●↑bloodglucose&energysupply●improvecardiovascularfunction●restraininflammation,↓tissueinjury●stabilizelysosomemembrane●proteindecomposed↑●immunerestrain,infection↑●inhibittissueregeneration●depresssexualglandaxis●slowgrowth;behaviorchange83GC:maintainbloodprQuestion:
What’sthemechanismsofelevatedbloodglucoseduringstress?insulin↓:isletβcellα-Ractivated↓insulinexcretionGlucagon↑:CAisletαcellβ-Ractivated↑itsexcretionGC↑:↑thelipidmobilizationofCA&glucagon84Question:
What’sthemechanismInsulinisletβcell↓TRHhypothalamus↓TSHpituitaryfrontlobe↓T3,T4thyroidgland↓GhRHhypothalamus↓
namesecretingsitechange
-endorphinepituitarygland↑ADHhypothalamus(PVN)↑growthhormonepituitaryglandacute↑,chronic↓aldosteroneadrenalcortex↑glucagonsisletcells↑prolactinpituitarygland↑3.otherhormonalresponsestostress
Stress85Insulin8629873088314.generaladaptationsyndrome(GAS)alarmstageresistancestageexhaustionstageStress894.generaladaptationsyndromeGeneraladaptationsyndrome(GAS)AlarmstageResistancestageExhaustionstageResponserapidly,shortduration.Sympathetic-adrenalmedullaexcitedArouse,emergencymobilizationSympathetic-adrenalmedullaresponse↓
,GCincreasedgraduallyAlarmsymptomspresentagain,
GCcontinue↑;
homeostasisbrokenDefensedepositisgraduallyconsumed.ExhaustionofresistanceCharacteristicSignificanceStress90Generaladaptationsyndrome(GAGeneralAdaptationSyndrome91GeneralAdaptationSyndrome34
§3cellularresponseinstress
expressedproteinsinCellsAcutephaseprotein,(APP)Heatshockprotein,(HSP)Physicalstressorstimulation92§3cellularresponseinstres【NegativeAP】
proteinsdown-regulatedduringacutephaseresponse:albumin,pre-albumin,Fe++-carryingprotein.【Acutephaseprotein】
Someproteinsexpressedduringacutephaseresponse.【Acutephaseresponse】
Anon-specificreactionoccurredshortlyafter(hourstodays)somedisorders,especiallyinfectivediseases,trauma,inflammationandimmunediseases.
1.Acutephaseprotein,APP93【NegativeAP】【■APPissynthesizedinliver.■APPisasecretiveprotein,increasedinstress.Stress
(1)OriginofAPP94■APPissynthesizedinliver.S■proteinasesuppressivepro.
:α1antichymotrypsin↑■coagulation&plasminrelatedpro.
stress
thrombinogen
,plasmin,fibrinogen,factorⅧ↑■complements↑
■transferpro.↑(copper-pro.,haptoglobin.etc)■otherpro.(CRP,α1acidglycoprotein↑)
(2)ClassificationofAPP95■proteinasesuppressivepro.:■depresstheactivityofprotease↓tissueinjury
proteasesuppressivepro.↑
↓tissueinjury■↓thegenerationofOFR
copper-proteinactivateSOD;↓OH-.
Stress(3)FunctionofAPP96■depresstheactivityofprote■promotionofthefunctionofphagocyteanti-inflammationCRP+bacteriawallphagocytosis↑■eliminatenecrosistissue
CRP(-)plateletphospholipase
Cinflammatorymediator↓necrosistissueeliminate↑Stress97Stress402.Heatshockprotein,HSP【definition】
aproteinfamilyproducedunderstressespeciallyinheatenvironment.982.Heatshockprotein,HSP【def(1)FactorsinducingHSPproduction
【HSPbiologicalfeatures】
■non-specificininduce■universal■conservativeinstructureStress99(1)FactorsinducingHSPprodu(2)basicstructureofHSP
■HSP70structureATPasemotif(highlyconservative)
Recognisingmotif(variable)ProteasebindingsiteN-450aaresidual200aaresidual
-CStress100(2)basicstructureofHSP■HSHSP:HSP110,HSP90,HSP70,HSP60
&smallHSP.
■induced
HSPinducedbyvariousstressors,repairorgetridofinjuredproteintopreventcellsfromsevereinjury.■structural
HSPstructuralpro.Incells,helptofold,transferordegradationneworinjuredprotein“Molecularchaperone”
(3)functionandclassification101HSP:HSP110,HSP90,HSP70,HSP6ThemajorfunctionofHSPfoldingtranslocationrenaturationdegradation102ThemajorfunctionofHSP4510346(4)HSPgeneexpressionregulationHSPHSFHSEHSF:热休克转录因子;HSE:热休克元件HSF三聚体stressInjuredproteinprotein
HSPStress104(4)HSPgeneexpressionregula1.Effectsonmetabolism【features】
metabolicrate↑,decomposition↑,synthesis↓
(1)Highmetabolicrate
SeverestressCA、GC↑
decompose↑
BMR↑
thin,weak,resistance↓(2)glucosemetabolism
stress
insulin↓;CA,Glucagon,GH,GC↑
stresshigebloodsugarofstressdiabetesStress§4metabolicandfunction
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