Stress and Disease Chapter 10 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2 Stress  A person experiences stress when a demand exceeds a person’s coping abilities, resulting in reactions such as disturbances of cognition, emotion, and behavior that can adversely affect well-being

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Dr. Hans Selye  Worked to discover a new sex hormone  Injected ovarian extracts into rats  Witnessed:  Enlargement of the adrenal cortex  Thymic atrophy  Development of bleeding ulcers in the stomach and duodenal lining  Dr. Selye witnessed these changes with many agents. He called these stimuli “stressors.”

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 General Adaptation Syndrome (a Nonspecific Response)  Selye termed this general response the general adaptation syndrome (GAS)  Three stages  Alarm stage Arousal of body defenses Arousal of body defenses  Stage of resistance or adaptation Mobilization contributes to fight or flight Mobilization contributes to fight or flight  Stage of exhaustion Progressive breakdown of compensatory mechanisms Progressive breakdown of compensatory mechanisms

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 5 GAS Activation  Alarm stage  Stressor triggers the hypothalamic-pituitary- adrenal (HPA) axis Activates sympathetic nervous system Activates sympathetic nervous system  Resistance stage  Begins with the actions of adrenal hormones Cortisol, epinephrine, norepinephrine Cortisol, epinephrine, norepinephrine  Exhaustion stage  Occurs only if stress continues and adaptation is not successful Onset of disease Onset of disease

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 Psychologic Mediators  Reactive response  To psychologic stressors  Anticipatory response  Anticipating a disruption in homeostasis  Conditional response  Associating a stimuli with danger  Posttraumatic stress disorder (PTSD)

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Stressors  Anything that demands a response in order to maintain homeostasis  Noxious Pain, cold, trauma, hunger, electric shock Pain, cold, trauma, hunger, electric shock  Not noxious Life events (wedding) Life events (wedding) Excitement Excitement

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Stress and Disease  Can precipitate disease  Cardiac  Can worsen existing disease  Irritable bowel disease  Asthma  Autoimmune diseases  HIV progression

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Psychoneuroimmunologic Mediators  Interactions of consciousness, the brain and spinal cord, and the body’s defense mechanisms  Corticotropin-releasing hormone (CRH) is released from the hypothalamus  CRH also released peripherally at inflammatory sites  Immune modulation by psychosocial stressors leads directly to health outcomes

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Stress Response (Neural Recognition)

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 Central Stress Response  Catecholamines  Released from chromaffin cells of the adrenal medulla Large amounts of epinephrine; small amounts of norepinephrine Large amounts of epinephrine; small amounts of norepinephrine  α-adrenergic receptors α 1 and α 2 α 1 and α 2  β-adrenergic receptors β 1 and β 2 β 1 and β 2  Mimic direct sympathetic stimulation

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 Central Stress Response  Cortisol (hydrocortisone)  Activated by adrenocorticotropic hormone (ACTH)  Stimulates gluconeogenesis  Elevates the blood glucose level  Protein anabolic effect in the liver; catabolic effect in other tissues  Lipolytic in some areas of the body, lipogenic in others  Powerful anti-inflammatory or immunosuppressive agent

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Emerging Research  Glucocorticoids, insulin, inflammation  Link to obesity  Link to Type 2 diabetes

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Stress and Immunity  T helper 1 to T helper 2 shift (Th1 to Th2)  Decrease in cellular immunity  Increase in humoral immunity

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Central Stress Response

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Psychoneuroimmunology  Interaction of factors  Psychologic  Neurologic  Immunologic

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 17 Stress-Induced Hormone Alterations  Female reproductive system  Cortisol exerts inhibiting effects by suppressing the release of luteinizing hormone, estradiol, and progesterone  Stress suppresses hypothalamic gonadotropin- releasing hormone  Estrogen stimulates the HPA axis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Stress-Induced Hormone Alterations  Endorphins and enkephalins  Proteins found in the brain that have pain-relieving capabilities  In a number of conditions, individuals not only experience insensitivity to pain but also increased feelings of excitement, positive well-being, and euphoria

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Stress-Induced Hormone Alterations  Growth hormone (somatotropin)  Produced by anterior pituitary, lymphocytes, and mononuclear phagocytic cells  Affects protein, lipid, and carbohydrate metabolism and counters the effects of insulin  Enhances immune function

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 20 Stress-Induced Hormone Alterations  Prolactin  Released from the anterior pituitary  Needed for lactation and breast development  Prolactin levels in the plasma increase as a result of stressful stimuli  Oxytocin  Produced by the hypothalamus  Produced during orgasm in both sexes  May promote reduced anxiety

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Stress-Induced Hormone Alterations  Testosterone  Secreted by Leydig cells  Regulates male secondary sex characteristics and libido  Testosterone levels decrease due to stressful stimuli

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Stress, Personality, Coping, and Illness  A stressor for one person may not be a stressor for another  Psychologic distress  General state of unpleasant arousal after life events that manifests as physiologic, emotional, cognitive, and behavior changes  Coping  Managing stressful demands and challenges that are appraised as taxing or exceeding the resources of the person  Link to coronary heart disease

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Stress, Personality, Coping, and Illness

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 24 Aging and Stress  Stress-age syndrome  Excitability changes in the limbic system and hypothalamus  Increased catecholamines, ADH, ACTH, and cortisol  Decreased testosterone, thyroxine, and other hormones  Alterations of opioid peptides  Immunodepression  Alterations in lipoproteins  Hypercoagulation of the blood  Free radical damage of cells