05 stress
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The document discusses stress and its effects on the body. It defines stress as a state of tension that can disrupt homeostasis. It describes the body's stress responses, including activation of the sympathetic nervous system and hypothalamus-pituitary-adrenal axis, which increases catecholamines and glucocorticoids respectively. These hormones produce various effects on organ systems and metabolism to help the body adapt to stressors. The document also discusses cellular responses like increased heat shock proteins and acute phase proteins that help protect cells under stress.
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05 stress
- 1. Dept. of PathologyDept. of Pathology Medical CollegeMedical College Hunan Normal UniversityHunan Normal University (( 湖南 范大学医学院病理学教研室师湖南 范大学医学院病理学教研室师 )) 1 Chapter 5Chapter 5 StressStress （ 激）应（ 激）应
- 2. StressStress
- 3. 33 StressStress a.a. IntroductionIntroduction b.b. Stress ResponsesStress Responses c.c. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction d.d. Stress and DiseasesStress and Diseases
- 4. Stress ( 力应 , 应 激） Section 1 Introduction
- 5. What Is Stress? A series ofA series of non-specific systemic adaptation responsesnon-specific systemic adaptation responses ofof the body to anythe body to any strong stimulusstrong stimulus.. A state of tension that can lead to disharmony orA state of tension that can lead to disharmony or disruption of the homeostasis of the body.disruption of the homeostasis of the body.
- 6. SpecificSpecific NecrosisNecrosis AcidosisAcidosis Non-specific ResponsesNon-specific Responses (Stress)(Stress) StimulateStimulateSurgery Trauma Infection Hypoxia Intense light Noise Drugs HR ↑HR ↑ BP ↑BP ↑ Muscle contractionMuscle contraction FearFear AnxietyAnxiety Stressors
- 7. Walter Cannon (1871 ～ 1945 ) —— American Physiologist 1920~1930 “Emergence Reaction” Sympathetic nerve system – the major player of stress response Science ， 78:43-48, 1933 Hans Selye （ 1907~1982 ） —— Canadian Physiologist 1920~1930 “General Adaptation Response” Hypothalamus-pituitary gland-adrenal cortex system – important in stress Nature, 138:32, 1936.
- 8. Alarm ( 警觉 期 ) Resistance ( 抵抗期 ) Rapid, shortRapid, short Sympathetic adrenal medullary system activity ↑Sympathetic adrenal medullary system activity ↑ Adrenal cortex activity ↑Adrenal cortex activity ↑ Sustained Adrenal cortex hormone ↑Sustained Adrenal cortex hormone ↑ Stress-related diseasesStress-related diseases StagesStages CharacteristicsCharacteristics General Adaptation Syndrome （ GAS ） Exhaustion ( 衰竭期 )
- 9. General Adaptation Syndrome （ GAS ） A classical description of Stress.A classical description of Stress. Emphasizes:Emphasizes: the general (systemic) responsesthe general (systemic) responses the non-specificitythe non-specificity Focuses more on the neuroendocrine responses duringFocuses more on the neuroendocrine responses during stress.stress. GASGAS ≠ Stress≠ Stress
- 10. Wu Song Fights the Tiger ( 武松打虎 )
- 15. A stimulus or agent that induces stress.A stimulus or agent that induces stress. StressorsStressors Psychological or socio-culturalPsychological or socio-cultural Intrinsic enrionment of the bodyIntrinsic enrionment of the body Extrinsic factors (Physical, chemical, biological)Extrinsic factors (Physical, chemical, biological) Threat to self-esteem ( 自尊心 ), human relationships, accident, etc. Cold, heat, toxins, drugs, bacteria, etc. Homeostasis, disease, cancer, etc. StressorStressor
- 16. Life Changing Unit (LCU) Disease Frequency Rate (Morbidity) ＞３００ ８６％ １５０～３００ ５０％ ＜１５０ No Psychological Stress vs Disease Development
- 17. EustressEustress (( 良性 激应 )) Preparing for Holidays Preparing for a job interview, presentation, etc. DistressDistress (( 劣性 激应 )) Traffic accidentTraffic accident BurnBurn TumorTumor Dual Effects of Stress
- 18. 2020 StressStress a.a. IntroductionIntroduction b.b. Stress ResponsesStress Responses c.c. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction d.d. Stress and DiseasesStress and Diseases
- 19. Section 2. Stress Responses Neuroendocrine Responses Cellular Responses
- 20. Neuroendocrine Responses to StressNeuroendocrine Responses to Stress Locus ceruleus-norepinephrine (LC-NE) ↑ Catecholamines (NE) ↑ Hypothalamus-pituitary-adrenal cortex (HPA) ↑ ACTH → Glucocorticoids (GCs) ↑ NeuroendocrineResponses
- 21. Medulla Adrenal gland Locus ceruleusLocus ceruleus StressorStressor Norepinephrine (NE)Norepinephrine (NE) The LC-NE SystemThe LC-NE System Sympathetic nerveSympathetic nerve
- 22. The LC-NE System Stressor LC-NELC-NE Central effects Peripheral effectsExcitement, alert, nervousness, anxiety Changes of organ systems NE Sympathetic nerveSympathetic nerve
- 23. Stressor Epinephrine Norepinephrine Cold, Hypoxia 10~20-fold 4~5-fold Shock (hemorrhagic) 50-fold 10-fold Increase of Plasma Catecholamines (CAs) During Stress
- 24. Neuroendocrine Responses to StressNeuroendocrine Responses to Stress Locus ceruleus-norepinephrine (LC-NE) ↑ Catecholamines (NE) ↑ Hypothalamus-pituitary-adrenal cortex (HPA) ↑ NeuroendocrineResponses ACTH → Glucocorticoids (GCs) ↑
- 25. The HPA SystemThe HPA System Stressor Central effects CRH↑ Depression, anxiety, anorexia Peripheral effects GCs↑ ACTH↑ HPA: Hypothalamus-pituitary-adrenal cortex CRH: Corticotropin-releasing hormone ACTH: Adrenocorticotropic hormone GCs: Glucocorticoids (Hypothalamus) (Pituitary gland) (Adrenal cortex)
- 26. LC-NE System Cardiovascular System CAs CRH ACTH GCs HPA System ↑ Sensitivity to CAs Link Between Two Neuroendocrine Systems
- 27. Section 2. Stress Responses Neuroendocrine Responses Cellular Responses
- 28. Cellular Responses to StressCellular Responses to Stress In response to sustained stressors, cells arouse a series ofIn response to sustained stressors, cells arouse a series of intracellular signal transduction and activation of certain genesintracellular signal transduction and activation of certain genes and synthesize some protective proteins, including:and synthesize some protective proteins, including: Heat shock proteins (HSPs)Heat shock proteins (HSPs) Acute phase proteins (APPs)Acute phase proteins (APPs)
- 29. Heat Shock Proteins (HSPs) A group of non-secretory proteins induced or enhancedA group of non-secretory proteins induced or enhanced by heat or other stressors – also calledby heat or other stressors – also called Stress ProteinsStress Proteins.. Heat induced gene expression first observed in 1962. Chromosomes of Drosophila melanogaster Heat Shock Response
- 30. HSP Family HSP110 Small molecule HSP (HSP27, HSP10, etc.) HSP90 HSP70 HSP60 HSP40 Ubiquitin Class Intracellular location Cytoplasm/Nucleus Cytoplasm/ER Cytoplasm/Nucleus/ER/Mito Cytoplasm/Mito Cytoplasm/ER Cytoplasm/ER/Nucleus Cytoplasm/Nucleus
- 31. Biological Properties of HSPs （ 1 ） Non-specificity of induction （ 2 ） Ubiquitous existence （ 3 ） Conservation of structure
- 32. Degradation Folding/Modification Protein (Functional) Translation Poly- peptide mRNA Transcription DNA 5’ 3’ Denature HSP HSPs: “Molecular Chaperones” HSPs help protein:HSPs help protein: FoldingFolding RenaturationRenaturation TranslocationTranslocation DegradationDegradation
- 33. 【【 Acute phase proteins, APPsAcute phase proteins, APPs 】】 A class of proteins whose plasma concentrationsA class of proteins whose plasma concentrations increase (increase (positive acute phase proteinspositive acute phase proteins) during the) during the acute phase response.acute phase response. APPs are secretory proteins.APPs are secretory proteins. 【【 AAcute phase responsecute phase response 】】 A quick non-specific defensive response elicited inA quick non-specific defensive response elicited in response to stress or inflammation –response to stress or inflammation – secretion ofsecretion of proteins to plasmaproteins to plasma.. Acute Phase Proteins
- 34. Name Mol. Wt. (kDa) Peak Time (h) Main Functions Group I: > 1,000-fold increase C-reactive protein 105 6-10 Complement activation Serum amyloid A 160 6-10 Cholesterol clearance Group II: > 2-4-fold increase α1-acid glycoprotein 40 24 Promote fibroblast growth α1- antichymotrypsin 68 10 Inhibit cathepsin G Haptoglobin 100 24 Inhibit cathepsins B, H, L Fibrinogen 340 24 Coagulation, tissue repair Group III: <2-fold increase Ceruloplasmin 151 48-72 Inhibit free radicals Complement C3 180 48-72 Chemotaxis, mast cell degranulation Common Acute Phase Proteins
- 35. 1. Inhibit the activation of proteinases1. Inhibit the activation of proteinases →→ ↓↓ Damage to the tissueDamage to the tissue 2. Prevent the spread of pathogens2. Prevent the spread of pathogens 3. Inhibit the production of free radicals3. Inhibit the production of free radicals - Role of Ceruloplasmin- Role of Ceruloplasmin 4. Clear foreign bodies and necrotic4. Clear foreign bodies and necrotic tissuestissues - Role of CRP- Role of CRP Functions of Acute Phase Proteins - arouse rapid defense mechanism
- 36. C-Reactive Protein, CRP Synthesized by the liver in response to inflammation. Rises within two hours of the onset of inflammation, up to a 50,000-fold. Activates the complement system, promoting phagocytosis by macrophages. - clears necrotic and apoptotic cells and bacteria.
- 37. 4545 StressStress a.a. IntroductionIntroduction b.b. Stress ResponsesStress Responses c.c. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction d.d. Stress and DiseasesStress and Diseases
- 38. ① Stimulate excitability of CNS and keep alert ② Enhance cardiac output (CO) and BP ③ Improve alveolar ventilation and oxygen supply ④ Maintain blood supply to vital organs ⑤ Increase energy supply Compensatory Significance of CAs
- 39. Blood Cardiovascular Respiratory ↑ Viscosity ( 粘滞度 ) ↑Contractibility ↑Heart rate ↑BP (→ Hypertension) Blood redistribution Dilation of bronchi Nervous Excitement, anxiety, anger Digestive Anorexia, gluttony (↑ appetite) Stress ulcer Effects of CAs on Organ Systems
- 40. HormoneHormone EffectEffect ACTH Glucagon Thyroid hormone Parathyroid hormone Calcitonin Renin Erythropoietin Insulin ↑ ↑ ↑ ↑ ↑ ↑ ↑ ↓ Effects of CAs on Hormone Secretion - a positive regulatory mechanism
- 41. ↑↑ Metabolic rateMetabolic rate ↑↑ Breakdown of fatty acids and proteinsBreakdown of fatty acids and proteins →→ Weight loss, weakness,Weight loss, weakness, ↓↓immunityimmunity ↓↓ Synthesis of biomoleculesSynthesis of biomolecules ↑↑ Blood sugarBlood sugar →→ HyperglycemiaHyperglycemia Effects of CAs on MetabolismEffects of CAs on Metabolism
- 42. Glucagon ↑ Insulin ↓ CAs ↑ α cells of pancreas β cells of pancreas Stressor Sugar ↑ Stress Hyperglycemia
- 43. GCs: Promoting Adaptation Anti-insulin – ↑ blood sugar Enhance the effect of CAs → ↑ BP Enhance the metabolic rate of the body Stabilize the lysosome membrane
- 44. GCs: Adverse Effects ↓Immune response ↓ Growth and development ↓ Sex glands ↓ Protein and collagen synthesis
- 45. 5454 StressStress a.a. IntroductionIntroduction b.b. Stress ResponsesStress Responses c.c. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction d.d. Stress and DiseasesStress and Diseases
- 46. Section 4 Stress and Diseases Stress disease Stress-related diseases Stress ulcer Hypertension Coronary heart disease Atherosclerosis Irritable bowel syndrome Depression
- 47. Stress Ulcer Mucosal damage or lesions of the esophagus,Mucosal damage or lesions of the esophagus, stomach or small intestine in stressed patients.stomach or small intestine in stressed patients. Severe trauma patients have a high rate ofSevere trauma patients have a high rate of stress ulcer (80-100%).stress ulcer (80-100%). Differences with digestive ulcer:Differences with digestive ulcer: Disease history (stress)Disease history (stress) No repeated occurrenceNo repeated occurrence Prognosis betterPrognosis better
- 48. Protective Mechanism of Gastric Mucosa
- 49. H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ Ischemia HCO3 - Mucus Blood flow ↓ Stress H+ Diffusion Lumen Ischemia of mucosaIschemia of mucosa – basic mechanism– basic mechanism Diffusion of HDiffusion of H++ from lumen to mucosafrom lumen to mucosa 58 Mechanisms of Stress Ulcer Mucosa
- 50. Section 4 Stress and Diseases Stress disease Stress-related diseases Stress ulcer Hypertension Coronary heart disease Atherosclerosis Irritable bowel syndrome Depression
- 51. StressorStressor Sympathetic nerve activity ↑Sympathetic nerve activity ↑ Catecholamines ↑Catecholamines ↑ VasoconstrictionVasoconstriction HypertensionHypertension ReninRenin Angiotensin ⅡAngiotensin Ⅱ ADSADS Retention of NaRetention of Na++ and Hand H22OO Essential HypertensionEssential Hypertension Stress-related Disease (1) (2) (3)