1、17-years student刘承武刘承武20122ReviewGeneral response in stressstress and diseasesOUTLINE34 5 1Stress External or internal factors body systemic,non-specific adaptive reaction.non-specific reactionoperationburninfectionhypoxiaStrong lightnoiseNo direct association with original factorsSpecificreactionsa
2、nxietydread blood reditributionHR Stress6 2Stressor Psychological,sociological factorsInternal factorsExternal factorsWork pressure,life rhythm,interpersonal relationCold,heat,toxins,drugs,bacteria,light.Homeostasis,disease,cancer.789 human organism animal plant?stress emergence reactionHigher organ
3、ismLower organism10Mimosa11 If the stress is favor of the Fight or Flight under emergency situation,Eustress If the stressors are too strong cause pathology or even death,DistressPsychological stressStress reactionPhysical stressPhysical,chemicalPsycho-social factors12 4Significance of stress|Defens
4、e and damnification are concomitance，they are reciprocal transformation.Defense:stress is a transmutation of organism adaptation,it can increase the bodys readiness,and help the body fight or flight.Damnification:If stress is too strong or stimulate the body too long,it is harmful,and can lead to st
5、ress-induced diseases.Stress13General response in stressGeneral response in stressStress 1415Neuroendocrine responses to stressNeuroendocrine responsesLocus ceruleus-norepinephrine/Sympathetic-adrenal medulla axis（LC-NE）catecholamine(CA)catecholamine(CA)Hypothalamic-pituitary-adrenal cortex system(H
6、PA)activatedglucocorticoidglucocorticoid(GC)(GC)Stressother hormonal responses to stress16 (1)LC-NE components（central integrating and regulating）ACTHLCLCMedullaMedullaAdrenal glandAdrenal gland Physical Physical stimulationstimulationCRHGCpalliumLimbic systemParaventricular nucleus（PVN）Social-psych
7、o stressCACACortex adrenal glandpituitaryStressEmotional reaction1.Locus ceruleus-Norepinephrine（LC-NE）171 1）CenterCenter EffectsEffects Cause emotions:excitement,awake,nervous and anxiety.Essential for initiating the HPA axis.（upward fibers of LC）Stress (2)Basic effects of LC-NE(2)Basic effects of
8、LC-NE18Stress2 2）PeripheralPeripheral EffectsEffects Plasma CA（Adr,NE,Dopamine）level rapidly.（downward fibers of LC）(2)Basic effects of LC-NE(2)Basic effects of LC-NE19 1 1）metabolismmetabolism stress stress CA A Cell -R-R（+）Glucagon B Cell -R-R（+）insulin blood glucoseinsulin blood glucose glucogen,
9、lipidglucogen,lipid degradation degradation fit the body energy demandsfit the body energy demands energy consumptionenergy consumption,tissue decomposition,tissue decomposition （bad resultsbad results）prolonged+_ (3)Functional and metabolic responses in body3)Functional and metabolic responses in b
10、ody 20GLUT2(glucose transport protein)glucoseglucoseinsulinGlucagoncellcell,pancreas,pancreascellcell,pancreas,pancreas212）cardiovascular system stressCA HR,contractility,COperi-resistanceblood redistribitionkey organs blood supplyprolongedHeart afterload hypertensionunfavorableunfavorable results r
11、esults22 4 4）other hormones changesother hormones changes CAACTH,GH,EPO,T3T4 and renin excretion.Aim：body enter“arouse”state to cope with changed environment.unfavorable results3）Respiratory systemStressRR faster&deep O2 carrying tissue O2 supplyRespiratory alkalosis tissue lack blood&O223PVN pituit
12、ary pituitary Cortex of Cortex of adrenal glandadrenal glandGCCRHACTH 2.Hypothalamic-pituitary-adrenal（HPA）(1)components HPA axis:hypothalamic paraventricular nucleus(PVN)+pituitary gland+adrenal gland cortex.PVN is the central site.Emotion stress responseamygdala,hippocampi,limbic system LC-NEPerip
13、heral effectorPhysical stress response24PVNLimbic systemIntegrate signalsPhysical stress signalpituitaryADH(2)Basic effects of stress Effects of CNSCRHsympathetic-adrenalMedulla excited+-endorphin-endorphin-Aldrenal cortexGCACTH25(2)Basic effects of stress suitable suitable CRHCRH facilitatefacilita
14、te adaptationadaptation excitementexcitement,delighteddelighted excessive excessive CRHCRH adaptationadaptation disturbancedisturbance anxietyanxiety,depression,depression,Effects of peripheral:via GC26 GC:maintain blood pressure and enhance the GC:maintain blood pressure and enhance the function of
15、 CA,glucagon in lipid mobilization.function of CA,glucagon in lipid mobilization.defense bad impacts (3)the physiological significance of elevated GC (GC25-37mg/d）Stressblood glucose&energy supply improve cardiovascular function restrain inflammation,tissue injury stabilize lysosome membrane protein
16、 decomposed immune restrain,infection inhibit tissue regeneration depress sexual gland axis slow growth;behavior change27Question:Whats the mechanisms of elevated blood glucose during stress？vinsulin:islet cellinsulin:islet cell-R activated-R activated insulin excretioninsulin excretionvGlucagon:CAG
17、lucagon:CAislet cellislet cell-R activated-R activated its excretion its excretionvGC GC：the lipid mobilization of CA&glucagonthe lipid mobilization of CA&glucagon28 Insulin islet cell TRH hypothalamus TSH pituitary front lobe T3,T4 thyroid gland GhRH hypothalamus name secreting site change-endorphi
18、ne pituitary gland ADH hypothalamus(PVN)growth hormone pituitary gland acute,chronic aldosterone adrenal cortex glucagons islet cells prolactin pituitary gland 3.other hormonal responses to stress 2915.17 Autonomic Activation during a Stress Situation(Part 1)3015.17 Autonomic Activation during a Str
19、ess Situation(Part 2)3115.17 Autonomic Activation during a Stress Situation(Part 3)324.general adaptation syndrome(GAS)valarm stagevresistance stagevexhaustion stage33General adaptation syndrome（GAS）Alarm stageResistance stageExhaustion stageResponse rapidly，short duration.Sympathetic-adrenal medull
20、a excitedArouse,emergency mobilization Sympathetic-adrenal medulla response ，GC increased graduallyAlarm symptoms present again,GC continue；homeostasis brokenDefense deposit is gradually consumed.Exhaustion of resistance CharacteristicSignificance34General Adaptation Syndrome35 3 cellular response i
21、n stress expressed proteins in CellsAcute phase protein,(APP)Heat shock protein,(HSP)Physical stressor stimulation36 【Negative AP】proteins downregulated during acute phase response:albumin,pre-albumin,Fe+-carrying protein.【Acute phase protein】Some proteins expressed during acute phase response.【Acut
22、e phase response】A non-specific reaction occurred shortly after(hours to days)some disorders,especially infective diseases,trauma,inflammation and immune diseases.1.Acute phase protein,APP37APP is synthesized in liver.APP is a secretive protein,increased in stress.(1)Origin of APP38proteinase suppre
23、ssive pro.:1 antichymotrypsin coagulation&plasmin related pro.stress thrombinogen,plasmin,fibrinogen,factor complements transfer pro.（copper-pro.,haptoglobin.etc）other pro.（CRP,1 acid glycoprotein）(2)Classification of APP39depress the activity of protease tissue injury protease suppressive pro.tissu
24、e injury the generation of OFR copper-protein activate SOD；OH-.(3)Function of APP40promotion of the function of phagocyte anti-inflammation CRP+bacteria wall phagocytosis eliminate necrosis tissue CRP(-)platelet phospholipase C inflammatory mediator necrosis tissue eliminate 412.Heat shock protein,H
25、SP【definition】a protein family produced under stress especially in heat environment.42(1)Factors inducing HSP production【HSP biological features】non-specific in induce universal conservative in structure43(2)basic structure of HSP HSP70 structureATPase motif(highly conservative)Recognising motif（var
26、iable）Protease binding siteN-450 aa residual 200 aa residual -C44HSP：HSP110,HSP90,HSP70,HSP60&small HSP.induced HSP induced by various stressors,repair or get rid of injured protein to prevent cells from severe injury.structural HSP structural pro.In cells,help to fold,transfer or degradation new or
27、 injured protein “Molecular chaperone”(3)function and classification45vThe major function of HSP folding translocation renaturation degradation4647(4)HSP gene expression regulationHSPHSFHSEHSF：热休克转录因子；：热休克转录因子；HSE：热休克元件：热休克元件HSF三三聚体聚体stressInjured proteinprotein HSP481.Effects on metabolism【features
28、】metabolic rate,decomposition,synthesis （1）High metabolic rate Severe stress CA、GC decompose BMR thin,weak,resistance（2）glucose metabolism stress insulin；CA,Glucagon,GH,GC stress hige blood sugar of stress diabetes4 metabolic and function changed in stress49（3）lipid metabolism fat mobilization,utili
29、zation free fatty acid,ketobody（4）protein metabolism AA provide material for APP,HSP synthesis502.System and organ changes （1）CNS HPA axis:suitable excited is helpful for good memory and emotion.HPA:excessive excited or depressive CNS disfunction （awake)51（4）immune system:depression（5）blood system （
30、6）urinogenital system（2）cardiovascular：HR，contractility，CO ，BP。（3）digestive system:appetite，stress ulcer52 1.Stress ulcer（1）definition （2）manifestations bleeding：stress ulcer：5 stress and diseases5354 3)pathogenesis （1）stomach mucous membrane ischemia RAAS excited （+）small blood vessel constracted m
31、ucous membrane ischemia HCO3-and mucous mucous cell regenerationMucous barrier broken inter-cellular conjunction injury H+enter mucous membrane H+cannot transfer in time H+accumulated in membrane stress ulcer membrane leak,uneasy to repair 55 （2）GC （3）PGs 56 2)genetic susceptibility is activated 3 h
32、ypertension 1)RAAS excited EmotionNoiseExertionTensionstressors hypothalamus sympathetic N impulseCAContraction of BVrenin angiotesin Aldo Water and Na retensionArterial pressure hypertension57 Child,male,10 years.left arm and lower left limb have been burn for a large area.on admission,T：37.5,HR:12
33、5/min,Bp:135/80mmHg,WBC:1.5109/L,N:0.90.GLU:10mmol/L(normal fasting blood glucose:3.9-6.0mmol/L).After 2-3 days,it is unwell in epigastrium,with dark stools twice,fecal occult blood（+）.questions：1)What is the pathologic status in this patient？2)Why this patient have dark stools？Explain the pathogenesy.3)How about the neuroendocrine system in this patient？58QUESTIONS1Illustrate the significance and disadvantages of CA and GC in stress.2How about the body metabolic changes during stress?3How about the features and mechanism of stress ulcer?4Whats heat shock protein？
