MINISTRY OF PUBLIC HEALTH OF UKRAINE BUKOVINIAN STATE MEDICAL UNIVERSITY Approval on methodological meeting of the department of pathophisiology Protocol № Chief of department of the pathophysiology, professor Yu.Ye.Rohovyy “___” ___________ 2008 year. Methodological Instruction to Practical Lesson Мodule 2 : PATHOPHYSIOLOGY OF THE ORGANS AND SYSTEMS. Contenting module 7. Pathophysiology of endocrine and nerve systems. Theme 20: STRESS SYNDROME Chernivtsi – 2008 1.Actuality of the theme. The term "stress" indicates nonspecific reaction of the organism arising under the influence of any strong effects stressors ami accompanying by reconstruction of the organism protective systems Selye noticed that despite the variety of stressors (trauma, infection, overcooling, intoxication, narcosis, muscular loading, strong emotions, etc.), they all lead to the same types of changes in the thymus, adrenal glands, lymphatic nodes, blood composition and metabolism. While experimenting on rats, he observed the typical triad, which included hypertrophy of the cortical substance of the adrenal glands, involution of the thymic-lymphatic apparatus ami hemorrhagic ulcers on the mucous membrane of the stomach and duodenum. 2.Length of the employment – 2 hours. 3. Aim: 1. To khow three successive stages in the development of the GAS: (1) the alarm stage, (2) the stage of resistance or adaptation, and (3) the stage of exhaustion. 2.To be able: To analyse the development of the stress reactions. To perform practical work: To analyse the mechanisms of the interactions of the nervous, endocrine, and immune systems in the stress response. 4. Basic level. The name of the previous disciplines 1. histology 2. biochemistry 3. physiology The receiving of the skills General structure of the neuroendocrine system. Type of the endocrine glands. Feedback mechanism of the anterior lobe of the pituitary. The hypothalamicohypophyseal portal system. Functional interrelation between hypothalamus, hypophysis and adrenal gland. Structure and function of the vegetative nervous system. 5. The advices for students. 1. Describe Selyes historic general adaptation syndrome; cite its stages. While attempting to discover a new sex hormone, Selye injected crude ovarian extracts into rats. Repeatedly, he found the following triad of structural changes: (1) enlargement of the cortex of the adrenal gland, (2) atrophy of the thymus gland and other lymphoid structure, and (3) development of bleeding ulcers of the stomach and duodenal lining. Selye discovered that this triad of manifestation was not specific for his ovarian extract but also occurred after he exposed the rats to other noxious stimuli such as cold, surgical injury, and restrain. Selye concluded that this triad or syndrome of manifestation represented a nonspecific response to noxious stimuli. Because many diverse agents caused the same syndrome, Selye suggested that it be called the general adaptation syndrome (GAS). Selye later defined three successive stages in the development of the GAS: (1) the alarm stage, (2) the stage of resistance or adaptation, and (3) the stage of exhaustion. The nonspecific physiologic response identified by Selye consists of interaction among the sympathetic branch of the autonomic nervous system and two glands, the pituitary gland and the adrenal gland. The alarm phase of the GAS begins when a stressor triggers the actions of the pituitary gland and the sympathetic nervous system. The resistance or adaptation phase begins with the actions of cortisol, norepinephrine, and epinephrine. Exhaustion occurs if stress continues and adaptation is not successful. 2. How does stress reactions develop? STRESSORS HYPOTHALAMUS CRF Anterior pituitary ACTH Adrenal cortex Increase of sodium and water retention, increase blood volume Cortisol Increased tissue protein, catabolism, hyperglycemia anti-inflammatory effects, decreases immune response Sympathetic system and adrenal medulla Aldosterone Increase cardiac output, blood pressure elevation, hyperglycemia (fight or flight) Posterior pituitary Increased ADH secretion Water retention increase blood volume 3. Summarize the major interactions of the nervous, endocrine, and immune systems in the stress response. CRF may by a primary mediator of many stress-induced alterations to immune functions because of its role as an initiator of biologic brain response to stress.It activates the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS). However, direct suppressive effects of CRF have also been reported on two immune cell types processing CRF receptors, namely the monocyte-macrophage and CD4 (T helper) lymphocyte. The production of CRF is initiated by high level of IL-1 by activation of macrophages and monocytes are inhibited by circulating glucocorticoids. The stimulation of CRF production in the hypothalamus by IL-1 demonstrates immune-induced regulation of the CNS and the cytokines (TNF and IFN). The T cell growth factor IL-2 can increase pituitary ACTH as well.The following flow chart summarizes interaction of the three systems: 4. Stress-related Diseases. Cardiovascular: Coronary artery disease, hypertension, stroke, arrhythmia. Muscles: Tension headaches, backache Connective tissues: Rheumatoid arthritis Pulmonary: Asthma. Immune: Immunosuppression, deficiency, autoimmunity Gastrointestinal: Ulcer, irritable bowel syndrome, diarrhea, nausea and vomiting, ulcerative colitis Integumetary: Eczema, neurodermatitis, acne Endocrine: Diabetes mellitus, amenorrhea Central nervous: Fatigue and lethargy, type A behavior, overeating, depression, insomnia. 5.1. Content of the theme. Describe Selyes historic general adaptation syndrome; cite its stages. How does stress reactions develop? Summarize the major interactions of the nervous, endocrine, and immune systems in the stress response. Stress-related Diseases. 5.2. Control questions of the theme: 1. Describe Selyes historic general adaptation syndrome ; cite its stages. 2. How does stress reactions develop? 3. Summarize the major interactions of the nervous, endocrine, and immune systems in the stress response. 4. Stress-related Diseases. 5.3. Practice Examination. I. Circle the correct answer or for each question. 1. Which is not a characteristic of Selyes stress syndrome A. Adrenal atrophy B. Shrinkage of the thymus C. Bleeding gastrointestinal ulcers D. Shrinkage of lymphatic organs 2. Which characterizes the alarm stage A.Increased lymphocytes B. Increased sympathetic activity C. Increased parasympathetic activity D. Increased eosinophils 3. Glucocorticoids would be highest during the stage of: A. Exhaustion. B. Alarm. C. Resistance. 4. Which is a correct sequence for Selyes hypothesis for stress A. Increased ACTH secretion, alarm B. Increased ACTH in the blood, hypertrophy of the adrenal cortex C. Stimulation of the sympathetic centers, alarm D. Increased secretion of epinephrine, increased ACTH in the blood 5. Corticotropin-releasing factor (CRF) is released by the: A. Adrenal medulla. B. Adrenal cortex. C. Anterior pituitary D.Hypothalamus. 6. Stress may by defined as any factor that: A. Stimulates the posterior pituitary. B. Stimulates the anterior pituitary. C.Stimulates the hypothalamus to release CRF. D. Stimulated the hypothalamus to release ADH. 7. Which is not true A. Stressors are always injurious, unpleasant, or painful stimuli. B. Stressors are extreme stimuli. C. The emotions of fear, anxiety, and grief can act as stressors. D.Stressors differ in different individuals and in one individual are different. 8. What determines which stimuli are stressors? A. Heredity B. Past experience C. Diet D. All of the above are correct 9. Which is not true A. Generally, psychological stress is independent of the physiological stress. B.Physiological stress is usually accompanied by some degree of psychological stress. C. Identical psychological stressors do not induce identical physiological responses. D. For any one individual,adaptive responses are selective and counteract specific body changes 10. The production of cortisol in response to stress can be initiated by: A. Hypothalamus, anterior pituitary, adrenal cortex. B. Hypothalamus, posterior pituitary, cortex. C. Hypothalamus, sympathetic nerve fibers, adrenal cortex. D.Hypothalamus, sympathetic nerve fibers, adrenal medulla. 11. Cortisol: A. Affects protein catabolism. B. Decreases blood sugar. C.Increases immune response. D. Increases allergic reactions. 12. Which would not occur in response to stress A. Increased systolic blood pressure B. Increased epinephrine C. Constriction of the pupils D. Increased adrenocorticoids 13. Which of the following would be less useful to assess stress A. Total blood cholesterol B. Eosinophils count C. Lymphocyte count D.Adrenocorticoids levels 14. In response to stress, the adrenal cortex secretes: A. Norepinephrine. B. Norepinephrine and cortisol. C. Cortisol and aldosterone. D. Norepinephrine and aldosterone. 15. Severe stress results in all except: A. An overactive immune system. B. Increased heart rate. C. A rise in epinephrine levels. D. Changes in breathing patterns. II. Matching the term with its definition 16. Corticoids 17. Stressors 18. Stress response 19. Exhaustion stage A. Sympathetic activity returns to normal B. Glucocorticoids return to normal C. Secreted by adrenal cortex in response to stress D. Selye’s changes seen in stress E. Stimulates the release of CRF F. High resistance to stressor G. Bodily changes initiated by stress H. Impaired immune response I. Triggers sympathetic nervous 20. Alarm stage Matching the cytokine with its activity: 21. IL-1 22. IL-2 23. NPY 24. IFN 25. Endorphin A. Secreted by the anteriorpituitary B. Stimulates the perceptions of pain C.Produced by macrophages, stimulates release of CRF D. Augments actions of catecholamines E. Increases ACTH levels F. May inhibit CRF secretion G.Released from mast cells, vasoactive Literature: 1.Gozhenko A.I., Makulkin R.F., Gurcalova I.P. at al. General and clinical pathophysiology/ Workbook for medical students and practitioners.-Odessa, 2001.P.248-254. 2.Gozhenko A.I., Gurcalova I.P. General and clinical pathophysiology/ Study guide for medical students and practitioners.-Odessa, 2003.- P.303-317. 3.Robbins Pathologic basis of disease.-6th ed./Ramzi S.Cotnar, Vinay Kumar, Tucker Collins.-Philadelphia, London, Toronto, Montreal, Sydney, Tokyo.-1999.