应激与器官多功能障碍概要课件

1、Stress and Stress-related DiseasesJianzhong Sheng MD PhDStressTeaching contentsOverviewNeuroendocrine responseCellular and humoral responsesEffects of stress on the bodyStress and diseasesPathophysiological basis of prevention and treatmentBasic concepts of stress Stress Stressor Classification of s

2、tress response Significance of stressStress 1Stress Stress is defined as a state of tension that can lead to disharmony or threaten the homeostasis of body.StimulatingSpecific responsesNecrosisPyogenesis AcidosisNonspecific responsesAnxiety DreadBlood re-distributionHeart rate increasesStressSurgery

3、BurnInfectionHypoxiaTraumaNoiseNo relation with the characteristics of the stimuliStress 2Stressor The stimuli or agents that induce stress are termed stressor.Stressor Psychological or social factorsIntrinsic factorsExternal factors（Physical, chemical, biological）Threat to self esteem, relationship

4、s with other people.Cold, heat, toxins, drugs, bacteria.Homeostasis, disease, cancer.Stress 4Significance of stress Stress that is healthy, or gives one a feeling of fulfillment or other positive feelings is termed eustress. (Fight or flight response) Stress that is harmful to our body and induces d

5、iseases is termed distress.Psychological stress 3Classification of stress responseStress responsePhysical stressPhysical, chemicalPsychological or socio-culturalStress Eustress or positive stress occurs when your level of stress is high enough to motivate you to move into action to get things accomp

6、lished. What is eustress?What is distress? Distress or 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 Stress is also called general adaptation syndrome (GAS) Ala

7、rm stageResistance stageExhaustion stageThe body is prepared for fighting against the threats or challenges on homeostasis.The ACTH-glucocorticoids take the major role in this stage. The increased catecholamines fall down soon.The resources are depleted and the signs of “wear and tear” or systemic d

8、amage appears.Organisms become increasingly vulnerable to health problem.The resources are depletedCharacteristicSignificanceStressResponse is quick and short. The sympathetic-adrenal medulla axis catecholamines Bodys responses in the stress StressStressorsCell,Humors HSP Neuro-endocrineCA, GC Chang

9、es in functions and metabolism of organs and systemsTeaching contentsOverviewNeuroendocrine responseCellular and humoral responsesEffects of stress on the bodyStress and diseasesPathophysiological basis of prevention and treatment 1. Neuroendocrine Responses to Stress）Neuroendocrine ResponsesLocus C

10、eruleus (LC)-norepinephrine (NE) sympathetic/Adrenal Medulla AxisCatecholaminesHPA excitementGlucocorticoidsStressRest hormonal responses to stressACTHadrenocorticotropic hormone LC The central integrating site for the automomic nervous system response to stressorsAdrenal Medulla StressorCRHGCCerebr

11、al cortexLimbic systemParaventricular nucleus of the hypothalamus （PVN）Social Psychological StressCatecholaminesAdrenal cortexPituitaryStressEmotion Locus ceruleus - Norepinephrine （LC-NE）1. LC-NEsympathetic/Adrenal Medulla Axis 2. Effects of CNS (Afferent pathways of LC) Inducing exitement, alertne

12、ss, anxiety, etc. The PVN activation initiates the HPA axis for more profound stress responses.Stress 3. Effects of peripheral (Efferent pathways of LC) Rapidly Increasing the levels of CA, Ad, NE and dopamine 4. The effects of CA at high level on the body （Functional and metabolic responses of body

13、） StressCardiovascular SystemStress CA Heart rate , Cardiac contractility , Cardiac outputPeripheral resistance Blood supply redistribution Blood supply in some important organs Respiration System Stress Respiratory rate , Inspiration , Blood carrying O2 , O2 supply StressThe levels of CA in blood d

14、uring stress (times)Stress NE AdreninHypoxia, Anoxia 1020 45hemorrhagic shock 50 10Metabolism Stress CA receptor in A cell (+) Glucagon receptor in B cell (+) Insulin Blood glucose glycogenolysis, lipoclasis Matching the demand of energy in tissues pancreasCortisolHSP90 R RHSP90RRRHSP90HSP90RGCGCGRE

15、Inflammation medium mRNAAnti-inflammation of GCDisadvantage to the body Stress The changes of other hormones CA ACTH, GH, T3/T4, renin secretionConsistent constriction of viscera blood vessels Erosion and hemorrhage in gastrointestinal mucosaVasoconstraction and Heart rate Heart Load HypertensionOve

16、r-exhaustion of the energy in the bodyCA Thrombin formation peripheral sensors (The body stress responses)PVN Pituitary Adrenal CortexGCCRHACTH Hypothalamic-pituitary-adrenal（HPA） 1.Essence of cell HPA axis including PVN, Pituitary and Adrenal Cortex. PVN is the central site in this system. Stress L

17、ocus ceruleus adrenal medullaEmotional stressAmygdaloid nucleus, hippocampi, limbic system 2. Effects of CNS PVNLimbic systemInteregrating informationStressorsCRHADHantidiuretic hormone StressSuitable CRH Adaptation ExcitementHappymemory Over CRH Adaptation anxiety, dumps, inappetence PituitoryACTHS

18、ympthetic-adrenal medulla excitementCA-endorphineamygdaloid nucleus Adrenal CortexGC3. Peripheral effectsStress Proteolysis, gluconeogenesis Effects of CA, Glucagon Sensitivity of cardiovascular system to CA (Permitting) Stabling lysoomeAnti-inflammation Advantage 4. Physiological significance of GC

19、 GC25-37mg/d）Immune Infection Growing slowly Inhibiting sexual gland axis and thyroid Dystropy Over proteolysis negative nitrogen balance Disadvantage Hormone Secreted from Change -Endorphine) Pituitary etc ADH Hypothalamus (ventricular nuclear) Growth hormone Adrenal pituitary Acute, Chronic Ald（Al

20、dehyde) Adrenal cortex Glucagons Cell in pancreatic islet Prolactin adrenal pituitary Insulin Cell in pancreatic islet TRH Hypothalamus TSH Pituitary T3、T4 Thyroid gland GhRH Hypothalamus Rest hormonal responses to stress StressTeaching contentsOverviewNeuroendocrine responseCellular and humoral res

21、ponsesEffects of stress on the bodyStress and diseasesPathophysiological basis of prevention and treatmentStress responses of cellsCell-humour responses to stress In responses of cellular-molecular level to more stressors (mainly non-psychogenic stressors), cells arouse a series of intracellular sig

22、nal transduction and activation of correlative gene and synthesize some protective proteins, which mainly are heat shock proteins and acute phase proteins. Stress 【Acute phase proteins, APP】 APP have been defined as one whose plasma concentration increases (positive acute phase proteins) or decrease

23、s (negative acute phase proteins) during the acute phase responses. 【Acute phase response】（APR）。 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 2Effects of

24、APP1AntitrypsinFibrinogen Stress thrombinogen, profibrinolysin, fibrinogen, factor Complement C3 transport protein （haptoglobin, transferrin ）1. Origin of APPAPP are mainly produced by liver. Ventricular endothelial cells, monocytes and fibroblasts can produce small amount of APP.Hepatocytes synthes

25、ize APP when being stimulated by IL-1、TNF- and IL-6 Stress3. Function of APPInhibiting proteinase activity and decreasing tissue injuryStressOther: Serum amyloid protein A restorationof injured cellsInhibiting free radical productionBlocking pathogene spread Cleaning foreign matters and necrotic tis

26、sue; Promoting phagocyte functions Non-specific inducers Existing in most of cellsConservative structures 1. Biological characteristics of HSP Heat shock protein，HSP 【Concept of HSP】 Heat shock proteins are a family of stress proteins whose synthesis is upregulated in response to a variety of enviro

27、nmental insults such as “heat stress”.Stress2. Funcation and classification of HSPClassification with MW HSP110、HSP90、HSP70、HSP60 and Small MW HSP etc. Environment stressHeat shockFree radicalHeavy metalPathological stateFeverInflammationIschemiaTraumaVirusAntineoplasticGrowth factorDevelopment and

28、differentiationOncogeneOtherHSPHSEHSFHSFFactors inducing HSP productionheat-shock element (HSE) inducible HSPFunctions: Repairing or removing injured proteins; Repairing pre-ribosomal RNA; Protecting cells; Promoting tolerance of cells to stressors.Structural HSPFunctions: Folding and translocation

29、of new synthesized proteins. Also called “Molecular chaperone”。 Classification with biological functionStress3 Basic structure and function of HSP Basic structure of HSP70ATPase (High reservation region) Alterable region Proteinase sensitity siteN- 450 AA residues 200 AA residues -CN-terminal：Having

30、 ATPase activity;C-terminal： Being alterable. Combining with injured proteins and recovering their correct folding (needing ATP to supply energy. Stress The function of HSP Repairing the damaged proteins ，maintain the normal function of cells, increasing the torlerance of cells to stressor. (induced

31、 HSP70)Regulating Na+-K+-ATP activity。Combining with monomer of STF, inhibiting the formation of HSTF trimer，inhibiting HSP production. Stresssoluble tuberculosis factor (STF) Teaching contentsOverviewNeuroendocrine responseCellular and humoral responsesEffects of stress on the bodyStress and diseas

32、esPathophysiological basis of prevention and treatmentCentral nervous systemCardiovascular systemDigestive systemImmune system The blood systemUrogenital systemEffects of stress on the body Function alterationStressChange in glycometabolism Stress insulin, CA, glucagon, GH, GC Glycogenolysis Stress

33、diabetesHigh metabolism rate Sever stress CA, GC catabolism loss of weight, weak, immune1. Effects on metabolism【Characteristics】 Metabolism rate, dialysis , synthesis Changes in lipid metabolism Changes in protein metabolism Stress2. Changes in different systems Change of CNS LC-NE axis activated i

34、nducing excitement, anxiety, angry. HPA axis suitable excitement helpful to good emotion and study. HPA axis over excitement or less inducing function problems of CNS, (dumps, anorexia, suicide) Change of cardiovascular system Change of gastrointestinal Change of immunity Acute stress responseStress

35、 WBC, activity，APs GC、CA Immune StressPsychological stress Lonely life, dumps, death of relatives Immune Diseases Change of blood Acute stress peripheral bloodWBC、Platelet，blood coagulationAdvantage：anti-infection, anti-injury, anti-bleedingdisadvantage：promoting formation of thrombus and DIC (Disse

36、minated intravascular coagulation) Stress Change of kidney and procreation Na+ discharge specific gravity of urine Paramenia, amenorrhea, latex Teaching contentsOverviewNeuroendocrine responseCellular and humoral responsesEffects of stress on the bodyStress and diseasesPathophysiological basis of pr

37、evention and treatmentStress and disease Stress ulcer 1Concept StressThis 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 in criti

38、cally ill or stress- ed otherwise healthy patients. 2Mechanisms of digestive ulcer Mucosa ischemia Sympathetic-adrenal medulla (+) Vasoconstiction in stomach, duodenum Mucosa ischemia HCO3- , mucus Mucosa regeneration Gastric mucosa barrier damaged H+ enters mucosa Entered H+ removing H+ accumulation in mucosa (Stress ulcer)Stress Increased the production and secretion of glucocorti