StressChengwuLiu20141StressChengwuLiu1StressReviewGeneralresponseinstressCellularresponseinstressmetabolicandfunctionchangedinstressstressanddiseasesOUTLINE2StressReviewOUTLINE2§1Basicconceptsofstress■Stressor■Classificationofstressresponse■SignificanceofstressStress■Stress

3§1Basicconceptsofstress■Sstress-7-yrs-english-病理生理學雙語課件stress-7-yrs-english-病理生理學雙語課件

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

CA

ACTH,GH,EPO,T3\T4andreninexcretion.Aim：bodyenter“arouse”statetocopewithchangedenvironment.unfavorableresults3）RespiratorysystemStress

RRfaster&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↑:CA

isletαcellβ-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+bacteriawall

phagocytosis↑■eliminatenecrosistissue

CRP(-)plateletphospholipase

C

inflammatorymediator↓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：熱休克轉錄因子；HSE：熱休克元件HSF三聚體stressInjuredproteinprotein

HSPStress47(4)HSPgeneexpressionregula1.Effectsonmetabolism【features】

metabolicrate↑,decomposition↑,synthesis↓

（1）Highmetabolicrate

Severestress

CA、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:excessiveexcitedordepressive

CNSdysfunction

（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