1、1Chengwu LiuChengwu Liu201420142ReviewGeneral response in stressstress and diseasesOUTLINE3 6 2Stressor Psychological,sociological factorsInternal factorsExternal factorsWork pressure,life rhythm,interpersonal relationCold,heat,toxins,drugs,bacteria,light.Homeostasis,disease,cancer.789 human organis
2、m animal plant?stress emergence reactionHigher organismLower 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,chemicalPs
3、ycho-social factors12 4Significance of stress|Defense 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 stimulat
4、e the body too long,it is harmful,and can lead to stress-induced diseases.Stress13General response in stressGeneral response in stressStress 1415Neuroendocrine responses to stressNeuroendocrine responsesLocus ceruleus-norepinephrine/Sympathetic-adrenal medulla axis（LC-NE）catecholamine(CA)catecholami
5、ne(CA)Hypothalamic-pituitary-adrenal cortex system(HPA)activatedglucocorticoid(GC)glucocorticoid(GC)Stressother hormonal responses to stress16 (1)LC-NE components（central integrating and regulating）ACTHLCLCMedullaMedullaAdrenal glandAdrenal gland Physical Physical stimulationstimulationCRHGCGCpalliu
6、mLimbic systemParaventricular nucleus（PVNPVN）Social-psycho stressCACACortexCortex adrenal gland adrenal glandpituitarypituitaryStressEmotional reaction1.Locus ceruleus-Norepinephrine（LC-NE）171 1）CenterCenter EffectsEffects Cause emotions:excitement,awake,nervous and anxiety.Essential for initiating
7、the HPA axis.（upward fibers of LC）Stress (2)Basic effects of LC-NE(2)Basic effects of 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 Cel
8、l -R-R（+）Glucagon Cell -R-R（+）insulin blood glucoseinsulin blood glucose glucogen,lipid degradation glucogen,lipid degradation fit the body energy demandsfit the body energy demands energy consumptionenergy consumption,tissue decomposition,tissue decomposition （bad resultsbad results）prolonged+_ (3)
9、Functional and metabolic responses in body3)Functional and metabolic responses in body 20GLUT2(glucose transport protein)glucoseglucoseinsulinGlucagon cell,pancreascell,pancreas cell,pancreascell,pancreas212）cardiovascular system stressCA HR,contractility,COperi-resistanceblood redistribitionkey org
10、ans blood supplyprolongedHeart afterload hypertensionunfavorable resultsunfavorable results22 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&de
11、ep O2 carrying tissue O2 supplyRespiratory alkalosis tissue lack blood&O223PVN pituitary 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
12、 the central site.Emotion stress responseamygdala,hippocampi,limbic system LC-NEPeripheral effectorPhysical stress response24PVNLimbic systemIntegrate signalsPhysical stress signalpituitaryADH(2)Basic effects of stress Effects of CNSCRHsympathetic-adrenalMedulla excited+-endorphin-endorphin-Aldrenal
13、 cortexGCACTH25(2)Basic effects of stress suitable suitable CRHCRH facilitate adaptationfacilitate adaptation excitement,delightedexcitement,delighted excessive excessive CRHCRH adaptation disturbanceadaptation disturbance anxiety,anxiety,depression,depression,Effects of peripheral:via GC26 GC:GC:ma
14、intain blood pressure and enhance the maintain blood pressure and enhance the function of 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 cardio
15、vascular function restrain inflammation,tissue injury stabilize lysosome membrane protein 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 cell-
16、R activated insulin:islet cell-R activated insulin excretioninsulin excretionvGlucagon:CAGlucagon:CAislet cell-R activatedislet cell-R activated its excretion its excretionvGC GC：the lipid mobilization of CA&glucagonthe lipid mobilization of CA&glucagon28 Insulin islet cell TRH hypothalamus TSH pitu
17、itary front lobe T3,T4 thyroid gland GhRH hypothalamus name secreting site change-endorphine 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 Auton
18、omic Activation during a Stress Situation(Part 1)3015.17 Autonomic Activation during a Stress 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 stage
19、Resistance stageExhaustion stageResponse rapidly，short duration.Sympathetic-adrenal medulla excitedArouse,emergency mobilization Sympathetic-adrenal medulla response ，GC increased graduallyAlarm symptoms present again,GC continue；homeostasis brokenDefense deposit is gradually consumed.Exhaustion of
20、resistance CharacteristicSignificance34General Adaptation Syndrome35 3 cellular response in stress expressed proteins in CellsAcute phase protein,(APP)Heat shock protein,(HSP)Physical stressor stimulation36 【Negative AP】proteins down-regulated during acute phase response:albumin,pre-albumin,Fe+-carr
21、ying protein.【Acute phase protein】Some proteins expressed during acute phase response.【Acute 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
22、in liver.APP is a secretive protein,increased in stress.(1)Origin of APP38proteinase suppressive 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)Classific
23、ation of APP39depress the activity of protease tissue injury protease suppressive pro.tissue 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(-)platel
24、et phospholipase C inflammatory mediator necrosis tissue eliminate 412.Heat shock protein,HSP【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)b
25、asic structure of HSP HSP70 structureATPase motif(highly conservative)Recognising motif（variable）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 sever
26、e injury.structural HSP structural pro.In cells,help to fold,transfer or degradation new or 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
27、；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】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 dia
28、betes4 metabolic and function changed in stress49（3）lipid metabolism fat mobilization,utilization 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
29、excited or depressive CNS dysfunction （awake)51（4）immune system:depression（5）blood 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 diseases53 3)pathogenesis （1）stomach mucous
30、 membrane ischemia RAAS excited （+）small blood vessel constracted mucous 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
31、repair 54 （2）GC （3）PGs 55 2)genetic susceptibility is activated 3 hypertension 1)RAAS excited EmotionNoiseExertionTensionstressors hypothalamus sympathetic N impulseCAContraction of BVrenin angiotesin Aldo Water and Na retensionArterial pressure hypertension56 Child,male,10 years.left arm and lower
32、left limb have been burn for a large area.on admission,T：37.5,HR:125/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 thi
33、s patient？2)Why this patient have dark stools？Explain the pathogenesy.3)How about the neuroendocrine system in this patient？57QUESTIONS1Illustrate 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？
