病理生理英文课件.ppt

Stress7-years student刘承武刘承武20121StressStressReviewGeneral response in stressCellular response in stressmetabolic and function changed in stressstress and diseasesOUTLINE231 Basic concepts of stress StressorStressor Classification of stress responseClassification of stress response Significance of stressSignificance of stressStressStress StressStress 4 1Stress External or internal factors body systemic,non-specific adaptive reaction.necrosisnecrosisfesterfesteracidosisacidosisnon-specific reactionDefinite Definite intensity intensity stimulatestimulateoperationburninfectionhypoxiaStrong lightnoiseNo direct association with original factorsStressStressSpecificreactionsanxietydread blood reditributionHR Stress5 2Stressor The stimuli or agents that induce stress.The stimuli or agents that induce stress.Stressor Psychological,sociological factorsInternal factorsExternal factorsWork pressure,life rhythm,interpersonal relationCold,heat,toxins,drugs,bacteria,light.Homeostasis,disease,cancer.StressStress6StressStress78 human organism animal plant?stress emergence reactionHigher organismLower organism9Mimosa10 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 stress3Classification of stress responseStress reactionPhysical stressPhysical,chemicalPsycho-social factorsStressStress11 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 stimulate the body too long,it is harmful,and can lead to stress-induced diseases.Stress122 General response in stressStressstressorsstressorsCellular and Cellular and humoralhumoral response responseAPP,HSP APP,HSP NeuroendocrineNeuroendocrine response response+general general adaptive reactionadaptive reaction CA,GCCA,GC Functional and metabolic changes of Functional and metabolic changes of organs and systemsorgans and systems1314Neuroendocrine responses to stressNeuroendocrine responsesLocus ceruleus-norepinephrine/Sympathetic-adrenal medulla axis（LC-NE）catecholamine(CA)Hypothalamic-pituitary-adrenal cortex system(HPA)activatedglucocorticoid(GC)Stressother hormonal responses to stress15 (1)LC-NE components（central integrating and regulating）ACTHLCMedullaAdrenal gland Physical stimulationCRHGCpalliumLimbic systemParaventricular nucleus（PVN）Social-psycho stressCACortex adrenal glandpituitaryStressEmotional reaction1.Locus ceruleus-Norepinephrine（LC-NE）161）Center Effects Cause emotions:excitement,awake,nervous and anxiety.Essential for initiating the HPA axis.（upward fibers of LC）Stress(2)Basic effects of LC-NE17Stress2）Peripheral Effects Plasma CA（Adr,NE,Dopamine）level rapidly.（downward fibers of LC）(2)Basic effects of LC-NE18StressStress 1 1）metabolismmetabolism stress stress CA A Cell -R-R（+）Glucagon B Cell -R-R（+）insulin blood glucoseinsulin blood glucose glucogen,lipidglucogen,lipid degradation degradation fit the body energy demandsfit the body energy demands energy consumptionenergy consumption,tissue decomposition,tissue decomposition （bad results）prolonged+_(3)Functional and metabolic responses in body 19GLUT2(glucose transport protein)glucoseglucoseinsulinGlucagoncell,pancreascell,pancreas202）cardiovascular system stressCA HR,contractility,COperi-resistanceblood redistribitionkey organs blood supplyprolongedHeart afterload hypertensionunfavorable results21 4）other 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&O222PVN pituitary Cortex of adrenal glandGCCRHACTH 2.Hypothalamic-pituitary-adrenal（HPA）(1)components HPA axis:hypothalamic paraventricular nucleus(PVN)+pituitary gland+adrenal gland cortex.PVN is the central site.StressStressEmotion stress responseamygdala,hippocampi,limbic system LC-NEPeripheral effectorPhysical stress response23PVNLimbic systemIntegrate signalsPhysical stress signalpituitaryADH+(2)Basic effects of stress Effects of CNSStressStressCRH+sympathetic-adrenalMedulla excitedCACA+-endorphin-endorphin-Aldrenal cortexGCACTH24(2)Basic effects of stress StressStress suitable CRH facilitate adaptation excitement,delighted excessive CRH adaptation disturbance anxiety,depression,Effects of peripheral:via GC25 GC:maintain blood pressure and enhance the 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 decomposed immune restrain,infection inhibit tissue regeneration depress sexual gland axis slow growth;behavior change26Question:Whats the mechanisms of elevated blood glucose during stress？vinsulin:islet cell-R activated insulin excretionvGlucagon:CAislet cell-R activated its excretionvGC：the lipid mobilization of CA&glucagon27 Insulin islet cell TRH hypothalamus TSH pituitary 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 StressStress282930314.general adaptation syndrome(GAS)valarm stagevresistance stagevexhaustion stageStressStress32General adaptation syndrome（GAS）Alarm stageResistance 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 resistance CharacteristicSignificanceStressStress33General Adaptation Syndrome34 3 cellular response in stress expressed proteins in CellsAcute phase protein,(APP)Heat shock protein,(HSP)Physical stressor stimulation35 【Negative AP】proteins downregulated during acute phase response:albumin,pre-albumin,Fe+-carrying 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,APP36APP is synthesized in liver.APP is a secretive protein,increased in stress.StressStress(1)Origin of APP37proteinase 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)Classification of APP38depress the activity of protease tissue injury protease suppressive pro.tissue injury the generation of OFR copper-protein activate SOD；OH-.StressStress(3)Function of APP39promotion of the function of phagocyte anti-inflammation CRP+bacteria wall phagocytosis eliminate necrosis tissue CRP(-)platelet phospholipase C inflammatory mediator necrosis tissue eliminate StressStress402.Heat shock protein,HSP【definition】a protein family produced under stress especially in heat environment.41(1)Factors inducing HSP production【HSP biological features】non-specific in induce universal conservative in structureStressStress42(2)basic structure of HSP HSP70 structureATPase motif(highly conservative)Recognising motif（variable）Protease binding siteN-450 aa residual 200 aa residual -CStressStress43HSP：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 injured protein “Molecular chaperone”(3)function and classification44vThe major function of HSP folding translocation renaturation degradation4546(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 HSPStressStress471.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 diabetesStressStress4 metabolic and function changed in stress48（3）lipid metabolism fat mobilization,utilization free fatty acid,ketobody（4）protein metabolism AA provide material for APP,HSP synthesisStressStress492.System and organ changesStressStress （1）CNS HPA axis:suitable excited is helpful for good memory and emotion.HPA:excessive excited or depressive CNS disfunction （awake)50（4）immune system:depression（5）blood system （6）urinogenital system（2）cardiovascular：HR，contractility，CO ，BP。（3）digestive system:appetite，stress ulcerStressStress51 1.Stress ulcer（1）definition （2）manifestations bleeding：stress ulcer：StressStress5 stress and diseases5253 3)pathogenesis （1）stomach mucous 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 repair StressStress54 （2）GC （3）PGs StressStress55 2)genetic susceptibility is activated 3 hypertension 1)RAAS excited EmotionNoiseExertionTensionstressors hypothalamus sympathetic N impulseCAContraction of BVrenin angiotesin Aldo Water and Na retensionArterial pressure hypertensionStressStress56 Child,male,10 years.left arm and lower 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 this 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？58