1. Chapter 8 Stress and Disease

2. Historical Walter Cannon – 1914 Stress – physiologic & psychologic state Hans Selye – 1946 Stress – biologic phenomenon 1970’s Lifestyle / emotions - ↓ immune function

3. Stress Demand exceeds copying abilities Results in disturbance of cognition, emotion, and behavior – may adversely affect well being

5. General Adaptation Syndrome Dr. Hans Selye Ovarian extracts into rats Structural changes ↑ adrenal glands Atrophy of thymus and lymphoid structures Bleeding ulcers – stomach & duodenum Stressor – “nonspecific response”

6. General Adaptation Syndrome (GAS) Three stages 1. Alarm - CNS aroused – “fight or flight” (SNS) - Trigger – hypothalamic – pituitary – adrenal (HPA) axis 2. Resistance or adaptation - Mobilization to fight or flight - Begins with the adrenal glands, NE & E 3. Exhaustion - Breakdown of compensation - Continuous stress - Disease

9. Psychologic Mediators (GAS) Emotional Psychologic Social influences

10. Stress Response Neuroendocrine regulation Corticotropin releasing hormone (CRH) hypothalamus → Pituitary ADH Prolactin, growth hormone, ACTH SNS → NE – adrenergic nerves (catecholamines) → E + NE – adrenal medulla (blood)

12. Catecholamines Adrenal, medulla Epinephrine – rapidly metabolized SNS – NE Alpha – adrenergic receptors (alpha 1, alpha 2 ) beta – adrenergic receptors (beta 1, beta 2 ) “mimics direct sympathetic stimulation”

13. Cortisol Hydrocortisone (Cortisol) Activated by ACTH Stimulates gluconeogenesis (aa/ffa) ↑ blood glucose level Powerful anti-inflammatory & immunosuppressant

14. Cortisol and the Immune System Glucocorticoids and catecholamines ↓ cellular immunity (Tc, NK cells, activated macrophages) ↑ humoral immunity (B-lymphocytes, eosinophils, mast cells) “cytokines form Th cells – Th 2 shift (humoral)

15. Stress Response

16. Other Hormones Endorphins – brain/immune cell ↓ pain when activates endorphin receptors ↓ blood pressure rise with hemorrhage Growth hormone – pituitary/lymphs, mononuclear cell ↑ enhances immune function ↓ with chronic stress

17. Other Hormones Prolactin – pituitary / extrapituitary sites Lactation and breast development ↑ in plasma with stress Oxytocin – hypothalamus Childbirth, lactation Produced with orgasm May promote ↓ anxiety

18. Sex Steroids Testosterone – Leydig cells – testes Male 2° sex characteristic and libido Levels ↓ with stress Exhibits immunosuppressive activities

19. Psychoneuroimmunologic Regulation “interaction between consciousness (psycho), brain and spinal cord (neuro) and the body’s defense (immunology)” Chronic inflammatory process CV, osteoporosis, arthritis, type 2 diabetes, COPD, aging and some cancers Related to proinflammatory cytokines Stress → ↓ T cell cytotoxicity and B cell function