1. Stress Response
   1. Starts with the central nervous system and the endocrine system
   2. Corticotropin-releasing hormone (CRH) is released from the hypothalamus
   3. CRH is also peripherally released at inflammatory sites
   4. May be perceived as real threat
   5. Norepinephrine promotes arousal, increased vigilance, increased anxiety, and other protective emotional responses
2. Central Stress Response
   1. Major Stress Hormones
      1. Glucocorticoids from the adrenal cortex in response to adrenocorticotropic hormone (ACTH) from the pituitary gland
   2. Parasympathetic System
      1. Balances the SNS (Opposes Catechloamine) Influences adaptation or maladaptation to stress
   3. Allostasis
      1. Adaptive Physiological response to stress - Chronic or Disregulated long term exaggerated response can lead to disease
         1. Allostatic Load - cumulative (genetic, lifestyle, behavioral)
         2. Allostatic Overload - PNS decreases restraint of SNS prolonging inflammatory response. The brain is influential in determining when overload occures
3. Many immune-related conditions and diseases are associated with stress. Stress and negative emotions increase levels of pro-inflammatory cytokines, providing a possible link among stress, immune function, and disease. Stress-induced immune changes affect immune cell functions.
   1. decreased natural killer cell
      1. Stress-induced immune changes cause
   2. cause impaired B cell function
   3. increased risk for infection
   4. decrease in melatonin
4. Aging and Stress
   1. Excitability changes in the limbic system and hypothalamus
   2. Increased catecholamines, antidiuretic hormone (ADH), ACTH, and cortisol
   3. Decreased testosterone, thyroxine, and other hormones
   4. Alterations of opioid peptides
   5. Immunodepression
   6. Alterations in lipoproteins
   7. Hypercoagulation of the blood
   8. Free radical damage of cells
   9. Development of stress reactions
   10. Lower adaptive reserve and coping mechanisms
5. Neuroendocrine Regulation
   1. Neuroendocrine Regulation
      1. SNS: Is aroused during the stress response Causes the adrenal gland medulla to release catecholamines
      2. Hypothalamic CRH stimulates the pituitary gland to release a variety of hormones
         1. Posterior pituitary gland: Antidiuretic hormone and oxytocin
         2. Anterior pituitary gland: Prolactin, endorphins, growth hormone (GH), and adrenocorticotropic hormone (ACTH), which stimulate the adrenal gland cortex to release cortisol
      3. Catecholamines - Bound to albumin
         1. Mimic sympathetic stimulation
            1. Released from chromaffin cells of the adrenal medulla
            2. Large amounts of norepinephrine Small amounts of epinephrine
            3. Noreprinephrine
            4. Peripherial vasoconstriction - Raises Blood Pressure
            5. Dilates Pupils
            6. Piloerection - hairs stand up
            7. Sweaty arm pits, palms
            8. Epinephrine
            9. Acts on Several organs - Metabolized quickly Metabolic Regulation Decreased insulin = Decreased glucose uptake Promoting Gluconeogenesis and glycogenolysis in Liver
            10. Cardiac action: Increases myocardial contractility (Inotropic effect) Increases Heart rate Vasodilation = Increased venous return = increased cardiac output/blood pressure and oxygenation
      4. Receptor Binding Types
         1. α-adrenergic receptors (α1 and α2)
         2. β-adrenergic receptors (β1 and β2)
         3. Epinephrine: Binds and activates both α- and β-adrenergic receptors Norepinephrine: Binds primarily to α-adrenergic receptors
6. Glucocorticoid
   1. Cortisol activated by ACTH
      1. Stimulates gluconeogenesis
      2. Elevates the blood glucose level
      3. Has a protein anabolic effect in the liver and a catabolic effect in other tissues
      4. Is lipolytic in some areas of the body and lipogenic in others
      5. Is a powerful antiinflammatory or immunosuppressive agent
      6. Causes poor wound healing and an increased susceptibility to infection
      7. Metabolic syndrome and the pathogenesis of obesity
      8. Development of diabetes is secondary to cortisol-induced obesity
      9. Chronic cortisol excess = lipogenesis in the abdomen, trunk, face, resulting in central obesity
   2. Cortisol and the Immune System
      1. T1 helper activity supressed
      2. T2 activity is stimulated
      3. T1 to T2 shift. (T1 decreases and T2 increases)
      4. Systemic responses may decrease innate immunity enhancing adaptive immunity
      5. Local responses can produce pro-inflammatory activities
   3. Cortisol and the Immune System Effects
      1. A patient will have stress and release cortisol
         1. Increases protein synthesis in the liver (Anabolic action)
         2. Promotes gastric secretions
         3. Suppresses immune function and reduces inflammation
         4. Reduces fibroblasts at wound sites and slows wound healing
7. Stress, Personality, Coping,and Illness
   1. A stressor for one person may not be astressor for another
   2. Psychologic distress
      1. General state of unpleasant arousal after life events that result in physiologic, emotional, cognitive, and behavior changes
   3. Coping
      1. Is managing stressful demands and challenges that are appraised as taxing or exceeding the resources of the person.
      2. May be adaptive or maladaptive
8. Stress and the Immune System
9. Prolactin, Oxytocin, Testosterone
   1. Prolactin
      1. Pituitary gland
         1. Anterior pituitary gland
            1. Lactation and breast development
   2. Oxytocin
      1. Hypothalamus Orgasm
         1. Posterior pituitary gland
            1. Released during child-birth and lactation. Has antistress properties. Reduces HPA activity
   3. Testosterone
      1. Testes Adrenal glands
         1. Leydig cells
            1. Regulates libido and male secondary sex characteristics. Decreases after stressful stimuli
10. Somatotropin (Growth Hormone)
    1. Produced by: Anterior Pituitary Mononuclear Phagocytic cells
    2. Functions: Affects protein, lipid, and carbohydrate metabolism. Counters the effects of insulin Enhances immune function
11. Endorphins and Enkephalins
    1. These are proteins in the brain that have pain relieving action
    2. Causing insensitivity to pain increased feeling of excitement, pos well-being, even euphoria (runners high)
12. Hormones of the Female Reproductive System
    1. Cortisol suppresses the release of luteinizing hormone, estradiol, and progesterone
    2. Stress suppresses the hypothalamic gonadotropin-releasing hormone
    3. Estrogen stimulates the HPA axis
    4. Leptin inhibits the HPA axis - maybe decrease food intake
13. Other Hormones
    1. Neuropeptide Y (NPY): Sympathetic neurotransmitter
    2. NPY is a stress mediator
       1. NPY is a growth factor for many cells
          1. implicated in atherosclerosis and tissue remodeling
    3. Other hormones can influence the stress and immune responses
    4. Some may suppress or enhance the immunity response Response is dependent upon the concentration and length of exposure, the target cell, and the specific immune function studied
14. Concepts of Stress
    1. Causes psychologic and physical responses. Defined as interactional/transactional (How we interact, perceive, experience stress). Demand of stress may exceed coping abilities resulting in disturbed thinking, emotions or behaviors that are maladaptive and adversely effect wellness.
    2. Reactive response involves psychologic stressors Anticipatory response anticipates a disruption in homeostasis Conditional response associates a stimulus with danger may cause posttraumatic stress disorder (PTSD) or phobias
       1. Can precipitate disease Cardiac disease Can worsen an existing disease Irritable bowel disease Asthma Autoimmune diseases Human immunodeficiency virus (HIV) progression
       2. PTSD - in response to a memory
15. Historical Background - Dr. Hans Selye
    1. Dr. Selve worked to discover a new sex hormone
    2. Injected ovarian extracts into rats
    3. Dr. Selve witnessed Enlargement of the adrenal cortex Thymic atrophy Development of bleeding ulcers in the stomach and duodenal lining Witnessed these changes with many agents and called these stimuli stressors
    4. Dr Selve termed - GAS - General Adaptation Syndrome
       1. GAS has 3 Stages
          1. Alarm stage - Arousal of body defenses—fight or flight. Triggers hypothalamic-pituitary-adrenal (HPA) axis
          2. Stage of resistance or adaptation. Mobilization that contributes to fight or flight. Begins with the actions of adrenal hormones. Cortisol, epinephrine, and norepinephrine
          3. Stage of exhaustion (Allostatic overload) Breakdown of compensatory mechanisms - May lead to disease Only happens if stress continues without adaptation
16. Psychoneuroimmunologic Mediators (PNI) Of Stress
    1. Defined as: Conscious interactions from the brain, spinal cord, bodies defense
    2. Stressors elicit a response of the Nervous & Endocrine systems (Pain, Trauma, Malnutrition, Excitement, Drugs, Surgery an many others)