Stress应激相关

1、Teaching contentsnOverviewnNeuroendocrine responsenCellular and humoral responsesnEffects of stress on the bodynStress and diseasesnPathophysiological basis of prevention and treatment SurgeryBurnInfectionHypoxiaTraumaNoise Threat to self esteem, relationships with other people.Cold, heat, toxins, d

2、rugs, bacteria.Homeostasis, disease, cancer. that is harmful to our body and induces diseases is termed distress Eustress or positive stress occurs when your level of stress is high enough to motivate you to move into action to get things accomplished. What is eustress?What is distress? Distress or

3、negative stress occurs when your level of stress is either too high or too low and your body and/or mind begin to respond negatively to the stressors. 4.General adaptation syndrome, GAS Alarm stageResistance stageExhaustion stage Changes in functions and metabolism of organs and systemsTeaching cont

4、entsnOverviewnNeuroendocrine responsenCellular and humoral responsesnEffects of stress on the bodynStress and diseasesnPathophysiological basis of prevention and treatmentCortisol Hypothalamus Pituitary Heart Liver Adrenal gland Sympathetic outflowEpinophrineNorepinophrineStress and the bodys respon

5、se:Flight or fight? Emotion of LC) of LC) Rapidly Increasing the levels of resistanceThe levels of CA in blood during stress (times)Stress NE AdreninHypoxia, Anoxia 1020 45hemorrhagic shock 50 10 receptor in pancreasCortisolHSP90 R RHSP90RRRHSP90HSP90RGCGCGREInflammation medium mRNAAnti-inflammation

6、 of GCPVN Pituitary Pituitary Adrenal CortexAdrenal CortexGCCRHACTH Locus ceruleus adrenal medullaAmygdaloid nucleus, hippocampi, limbic system PVNLimbic systemInteregrating informationStressors PituitorySympthetic-adrenal medulla excitementamygdaloid nucleus Adrenal CortexTeaching contentsnOverview

7、nNeuroendocrine responsenCellular and humoral responsesnEffects of stress on the bodynStress and diseasesnPathophysiological basis of prevention and treatment In responses of cellular-molecular level to more stressors (mainly non-psychogenic stressors), cells arouse a series of intracellular signal

8、transduction and activation of correlative gene and synthesize some protective proteins, which mainly are heat shock proteins and acute phase proteins. APP have been defined as one whose plasma concentration increases (positive acute phase proteins) or decreases (negative acute phase proteins) durin

9、g the acute phase responses. Acute phase proteins The acute phase response is a quickly mobilized, non-specific defensive response elicited in response of the host to infection, tissue injury or inflammation, etc., , , Stress HSPEnvironment stressHeat shockFree radicalHeavy metalPathological stateFe

10、verInflammationIschemiaTraumaVirusAntineoplasticGrowth factorDevelopment and differentiationOncogeneOtherHSPHSEHSFHSFFactors inducing HSP productionheat-shock element (HSE) soluble tuberculosis factor (STF) Endoplasmic reticulum stressEndoplasmic Reticulum (ER)/wiki/Unfolded_pr

11、otein_responseER stress Inducers:Thapsigargin (TG);Tunicamycin (Tun);Brefeldin A (BFA)ER StressERResults in the accumulation of unfolded/misfolded proteins which can threaten the cell.CausesDisrupting calcium homeostasisVirusOxidative Stress Altered GlycosylationHow do you deal with stress?CELLER St

12、ressERRESPONSEDEATHSurvivalBiP Activates Kinase PERKNormal ConditionsPERKStress ConditionsBiP is released from PERKBip binds to unfolded/misfolded proteinsPerk dimerizes and becomes phosphorylated.ERBiPPERKBiPCytoplasmIRE 1 IRE 1 BiP, GRP78 (glutamate uptakeregulatory protein)ERPERKIRE 1 eIF2 Nrf2PE

13、RK-eIF2 Pathway eIF2 Normal ConditionseIF2-GTP-tRNA Initiates TranslationeIF2 Stress ConditionsDecreases the amount of total mRNA translation of proteins and reduces workload on stressed ER. It can now selectively translate specific mRNA.eIF2 is phosphorylated preventing the formation of the transla

14、tion complex.PERKERCytoplasmNrf2PERK-Nrf2 PathwayNormal ConditionsNrf2Keap 1Nrf2 is bounded to the cytoskeleton anchor Keap 1 leaving Nrf2 inactiveStress ConditionsNrf2 translocates to nucleus Nrf2 is phosphorylated and dissociates from Keap 1CytoplasmPERKERNucleusNrf2Keap 1Nrf2Keap 1ERPERKIRE 1 eIF

15、2 Nrf2NQO1Decreased protein loadATF 4SURVIVALCHOPDEATHEndoribonuclease, IRE1; Phospho-Extracellular related kinase Teaching contentsnOverviewnNeuroendocrine responsenCellular and humoral responsesnEffects of stress on the bodynStress and diseasesnPathophysiological basis of prevention and treatmentn

16、Central nervous systemnCardiovascular systemnDigestive systemnImmune system nThe blood systemnUrogenital systemEffects of stress on the body Function alteration WBC、Platelet，blood coagulation Teaching contentsnOverviewnNeuroendocrine responsenCellular and humoral responsesnEffects of stress on the b

17、odynStress and diseasesnPathophysiological basis of prevention and treatmentThis patient with no Helicobacter infection got this ulcer during a period of severe somatic stress due to a heart disease. Stress ulcer is the term given to mucosal damage or lesions of the esophagus, sto-mach or duodenum i

18、n critically ill or stress- ed otherwise healthy patients. Mucosa ischemiaMucosa ischemia EmotionNoisesExertionTensionAldosterone (ald) , Teaching contentsnOverviewnNeuroendocrine responsenCellular and humoral responsesnEffects of stress on the bodynStress and diseasesnPathophysiological basis of pr

19、evention and treatmentPathophysiological basis of prevention and treatmentnDeleting stressorsnApplication of glucocordicoidsnNutrientsnTreatmentRemembernOnly a healthy lifestyle can help you in a big waynYou cant smoke, drink, smoke crack, have unprotected sex and say “Oh, but I have a positive outl

20、ook, so I will be just finenHealth psychologists are also interested in promoting health, why people go to the Dr. etc.Multiple Organ Dysfunction SyndromeWorld War OneCirculatory failure, hypovolemic shockWorld War TwoKorean WarPost-traumatic acute renal insufficiencyViet Nam WarPost-traumatic acute

21、 respiratory insufficiencySeventys70s syndrome1991Multiple organ dysfunction syndromeLeft leg open traumaDay 2:Shortness of breath, OliguriaDay 4:T 39.5 WBC (18109/L)R 35 /m, cyanosis, PaO260mmHgUrine 90 beat/min.Respiration rate 20/min or PaCO2 12,000/mm3 or 10% immature cells.above 3820/min12,000/

22、mm3SIRSRenal failureRespiratory failureLeft leg open traumaCase reviewCompensatory Anti-inflammatory Response Syndrome( CARS)An uncontrolled anti-inflammation processAnti-inflammatory signals exceed its normal domain or degree Result in end-organ damage and multi-system failure.【Definition】Immune pa

23、ralysisAnti-inflammatory reactionIL-10, IL-4, TGF-IL-1ra ,LipoxinCell eliminatePro-inflammatory reactionTNF-a, IL-1, IL-6, IFNTXA2, PAFCell activationSIRSCARSMODSUncontrolled inflammatory responseInfection/InjuryControlled inflammatory responseInfection/injury controlledInfection/InjuryHostresponseS

24、IRSCARSMODSUncontrolled inflammatory responseExcessiveAdequateDeathInadequateInfection/injury controlledSummary The restoration of blood flow after transient ischemia may be associated with further reversible or irreversible cell damage, which is called ischemia-reperfusion injury or reperfusion inj

25、ury.Ischemia-reperfusion injuryIn the definition of ischemia-reperfusion injury 3 3 Key points are:Key points are: Ischemia for a long time Reestablishment of blood flow More severe injury Characteristics of ischemia-reperfusion injury: 1. Reversible Irreversible injury2. Having reported in heart, kidney, liver, lung, brain, intestine, skeletal musclesnCalcium paradox nOxygen paradoxnpH paradoxWhich factors are involved in reper