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  1. STRESS AND STRESS-RELATED DISEASES Pathophysiology Department, Tongji Medical College, HUST

  2. Contents • Concepts: general adaptation syndrome, stress, stressor • Mechanism-stress response • Neuroendocrine: LC-NE/sympathetic, HPA • Humoral and cellular: APP, HSP • Functional metabolic alteration • Stress-related diseases: stress ulcer • Prevention and treatment principle • Case discussion

  3. Hans Selye (1907-1982)

  4. General Adaptation Syndrome (GAS) Specific symptoms Different diseases Non-specific symptoms A serial of non-specific signs and symptoms caused by various strong stimulus.

  5. General Principle of Stress Stimulus Disturbance of homeostasis Adaptative response Homeostasis Diseases or symptoms A general adaptative response in order to cope with the altered homeostasis.

  6. Stages of GAS Stimulus Alarm reaction Adaptation Exhaustion Diseases Relaxation

  7. Stress Definition Non-specificresponse of the body to any demand made upon it.

  8. Stressor Any stimuli that elicit the stress response External Internal Psycho-social Physical Psychological Short-term (acute) Long-term (chronic) Stressors: noise, danger, infection on-going highly pressured work, long-term relationship problems, loneliness, and persistent financial worries.

  9. Importance of Stress Without stress, there would be no life Pleasant stress (eustress) wellness Unpleasant stress (distress) disease

  10. Focus of Stress Mechanism Stimulus Disturbance of homeostasis Alarm reaction Adaptative response Diseases or symptoms

  11. Stress Responses Neuroendocrine • Humeral • Cellular

  12. Neuroendocrine Response • Locus ceruleus-norepinephrine (LC/NE) /sympathetic-adrenal medulla axis • Hypothalamic-pituitary-adrenal (HPA) axis

  13. Release of Catecholamines Dopamine Norepinephrine Epinephrine (adrenaline)

  14. Role of Catecholamine Central: Arousal , vigilance and memory (Alarm stage) Peripheral: Heart Blood redistribution Respiratory rate Gastrointestinal activity Insulin Glucagons

  15. CNS Response amygdala emotional response Catecholamines hippocampus long-term memory short-term memory, concentration, and rational thought the front of the brain

  16. Diencephalons

  17. Hormones Released Corticotrophin-releasing hormone (CRH) Adrenocorticotropic hormone (ACTH) Glucocorticoid hormones (cortisol and cortisone) Others (growth hormones, thyroid hormone, reproductive hormones (Large surgical operation, long term effect)

  18. Role of Glucocorticoid Blood glucose↑ Protection Lysosome GC Other hormones Cardiovascular system Immune system↓

  19. Interaction of LC and HPA Amygdala Hippocampus Locus ceruleus Paraventricular nucleus Spinal cord Adrenal cortex

  20. Humoral Response Acute phase protein C-reactive protein Serum amyloid A Ceruloplasmin (chelating protein) (Severe burn injury)

  21. Complement activation Superoxide reduction APP Bind phosphocholine Cytokine secretion

  22. Cellular Response Heat shock protein e.g., HSP70 Chaperone protein: folding, assembly, translocation, degradation

  23. Structure of HSP

  24. Electron micrograph of HSP70 in scrapie infected cell A, Endosome-lysosome related multivesicular dense body; B, HSP70 specific glod particles; C, HSP70 specific particles in the cytoplasm.

  25. Regulation of HSP expression

  26. Understanding Stress Mechanism at Cellular and Molecular levels Stimulus Intracellular protein (e.g., HSP) Release of hormones (e.g., GC) or neurotransmitters (e.g., NA) Neuroendocrine response

  27. Functional and Metabolic Alteration

  28. Memory, Concentration, and Learning Effect of Acute Stress on Memory. Subjects taking cortisone performed significantly worse on memorization tests than those taking the placebo did. Effect of Chronic Stress on Memory. Prolonged exposure to cortisol to shrinkage in the hippocampus, the center of memory.

  29. Heart rate and blood pressure increase; Blood flow may increase 300% to 400%; Breathing becomes rapid and takes in more oxygen;Dryness and difficulty in talking; Spasms of the throat muscles, difficult to swallow; Cool, clammy, sweaty skin; Scalp tightens, hair stand up; Digestive activity shuts down (appetite, ulcer, diarrhea); Genito-urinary system: disturbance of hormone.

  30. Stress Immune system Neuroendocrine system CRH TNF-a IL-1 IL-6 CRH-R1 b-endorphine ACTH

  31. Stress and Disease

  32. Stress Ulcer Mucosal damage or lesion of the stomach or duodenum in critical illness or severely stressed situation. Gastrointestinal mucosal ischemia Counter-diffusion of gastric hydrogen ion to mucosa

  33. Psychological Effects of Stress In one study, two-thirds of subjects who experienced a stressful situation had nearly six times the risk of developing depression within that month. Some evidence suggests that repeated release of stress hormone disrupts normal levels of serotoninwhichis critical for feelings of well-being.

  34. Post-Traumatic Stress Disorder Symptoms Posttraumatic Stress Disorder is a psychiatric disorder that can occur following the experience or witnessing of life-threatening events such as military combat, natural disasters, terrorist incidents, serious accidents, or violent personal assaults like rape. People who suffer from PTSD often relive the experience through nightmares and flashbacks, have difficulty sleeping, and feel detached or estranged, and these symptoms can be severe enough and last long enough to significantly impair the person's daily life.

  35. Other Gastrointestinal Problems (Irritable bowel syndrome, Crohn's disease or ulcerative colitis) Heart Disease (Essential hypertension, coronary artery disease, arrhythmias) Immune Disorders (Rheumatoid arthritis, multiple sclerosis)

  36. Sexual and Reproductive Dysfunction Sexual Function Premenstrual Syndrome Fertility, miscarriage, etc.

  37. Case Presentation A 32-year-old man was severely burned (78% of skin surface, II degree) by gasoline. On the second day, the patient vomited about 200 ml of coffer-colored bloody juice. a Endoscopic examination revealed scattered erosions (2 mm in diameter) throughout the stomach. A bigger ulcer was oozing . Bleeding was stopped by endoscopic hemostasis.

  38. Principle of Treatment and Prevention Treatingstress is a very important component in a medical regimen. Some evidence exists that stress management programs may reduce the risk of heart events (eg, heart attack) by up to 75% in people with heart disease.

  39. "Fight for your highest attainable aim; but never put up resistance in vain."  "Fight for your highest attainable aim; but never put up resistance in vain."  Hans Selye

  40. General Guidelines Rule One - Find your own purpose in life, that fits your own personal stress level.  Rule Two - Control your emotional level by recognizing situations as being either life- threatening or non-life-threatening.  Rule Three - Collect the goodwill and appreciation of others. 

  41. Thank you