HTHSCI 2PF3 Stress & Adaptation PDF

STRESS AND ADAPTATION Learning Outcomes: Potential Causes of the Stress Response What Occurs During these events Implications of Short-Term and Long-Term Consequences Research in the Area Clinical Implications STRESS RESPONSE "A state manifested by a specific syndrome...

STRESS AND ADAPTATION Learning Outcomes: Potential Causes of the Stress Response What Occurs During these events Implications of Short-Term and Long-Term Consequences Research in the Area Clinical Implications STRESS RESPONSE "A state manifested by a specific syndrome of the body, developed in response to any stimuli that made an intense systemic demand on it" "A person experiences stress when a demand exceeds a person's coping abilities, resulting in reactions such as disturbances of cognition, emotion, and behaviour that can adversely affect well-being" "Stress is the spice of life" — stimulus for achievement or suffering WHAT IS STRESS 3 Components of Stress 1. Stressor: Stimuli + perception leads to response Eustressor- Positive Distressor- Negative (e.g. Conversing with patient while knowing your preceptor will judge you) Neutral- No effect (e.g. Conversing with patient) 2. Stress Response Also leads to hormonal responses 3. Pathophysiological Sequelae External Stimuli- External demands that trigger reactions (3 categorizations) 1. Quantity- negative consequences due to accumulation stressors (positive or negative) in a short period of time E.g. Holmes and Rahe Stress Scale (measures stress & risk of illness); i.e. new job, declining health of relative, moving 2. Quality- Major changes affect large number of people (e.g. war, economic depression) Major changes that affect a few people (e.g. bereavement, divorce) Daily hassles that affect normal people (e.g. complaining of daily stressors) 3. Duration- subtypes aren't mutually exclusive, can occur together Acute (e.g. job interview) Sequential (e.g. changes that follow divorce) Chronic - intermittent (e.g. periodic arguments with spouse) Chronic (e.g. permanent disability) Individual Judgement o Stress is an individual's conscious appraisal that a disturbance has occurred, challenging one's ability to cope o Stress is a demand-resource imbalance o We are not passive victims of stressful forces, we're capable of change o Lazarus & Folkman's Transactional Model of Stress Management PHYSIOLOGICAL RESPONSE Physiological response is an example of the mind, body connection, psycho-neuro-endocrine responses that involves 3 key areas 1. Perception/Emotion o frustration, anger, or fear can lead to emotional release  o Depression, anxiety, excitement as a response to life or anticipatory events can lead to physiological mediated stress response 2. Hormones o Glucocorticoid- mainly cortisol o Mineralocorticoid- primary aldosterone o Catecholamines- epinephrine, norepinephrine, dopamine 3. Consequences o Short & long-term o Autonomic nervous system implications o Hormonal affects o And more THE ADRENAL GLANDS Location: two small retroperitoneal organs on top of each kidney Function: produce hormones to regulate metabolism, immune system, stress response, etc Adrenal Cortex o 80-90% of the adrenal gland o 3 Divisions: Zona Glomerulosa, Zona Fasciculata, Zona Reticularis Adrenal Medulla o Made of chromaffin cells (pheochromocytes) o Pheochromocytoma: neuroendocrine tumour that secretes excessive catecholamines o Rich blood and nerve supply o Epinephrine secreted 10x more potent than norepinephrine, for heart & metabolic activities o Minor source of norepinephrine o Links to autonomic sympathetic nervous system (fight or flight) Zona Glumerulosa — Outermost Layer Mineralocorticoid hormone production – Primarily Aldosterone Touch, fibrous capsule enclosed in fat for protection Aldosterone- o Regulate Na and K secretion and retention o Key in the renin-angiotensin-aldosterone pathway for volume & BP control o Role with pH balance by facilitating excretion of hydrogen ions Excess Aldosterone (Aldosteronism)- related to neoplasms, high sodium, decreased potassium o S/S: hypertension & edema  o Decreased Potassium S/S: muscle weakness, paralysis Decreased Aldosterone- decreased sodium & increased potassium o S/S: hypotension, dehydration, potential weight loss Zona Fasciculata — Middle Layer Glucocorticoid hormone production – Primarily Cortisol Cortisol, cortisone, and corticosterone Cortisol (hydrocortisone)- o Major stress hormone essential for survival o Released with ACTH stimulation (secreted by pituitary gland when body is stressed) o Increased cortisol causes negative feedback (signal to reduce ACTH causes lower cortisol) o Key Roles- Hyperglycemia- Increases blood glucose by decreasing peripheral uptake and promoting gluconeogenesis Decreases insulin sensitivity E.g. Controlled diabetes are harder to control in the hospital setting due to the stress response Protein Synthesis & Catabolism- Increases protein synthesis in the liver & promotes catabolism in the muscles Acts synergistically with glucagon & epinephrine, overall affect is greater than sum of the individual hormones Lipolysis- Cortisol promotes lipolysis (breakdown of fatty acids) in the extremities Acute stage- cortisol promotes breakdown of fatty acids for energy source use Long-term- body redistributes fat or promotes lipogenesis in face & trunk areas Cushingoid Signs- fat pad at back of neck or buffalo hump, moon face, or increased visual abdominal fat Anti-Inflammatory- May be linked to increased autoimmune responses Increased cortisol linked to decreased IL-1, 2, 6, and TNF-a (this aids to limit damage) Immunosuppression- Cortisol causes T-helper 2 (Th2) shift & increases immunity Th1- promotes cell-mediated immunity (immune system directly attacks infected cell) Th2- increases humoral immunity (antibody production & defense against pathogens) Need balance of Th1 & Th2 to prevent immune dysfunction Cortisol supresses Th1 causing decreased cellular immunity Cortisol promotes Th2 causing increased humoral immunity & anti-inflammatory response This activity is called T-helper 2 shift Addison Disease- Adrenal insufficiency o Insufficient cortisol secretion often in conjunction with too little mineralocorticoid o Decreased cortisol limits the required hormonal effects Cushing Syndrome/Disease- Excess cortisol o Adrena cortex secretes too much cortisol or caused by excessive corticosteroid medication o S/S: hyperglycemia (steroid diabetes), hypertension edema, poor wound healing (risk for infection), cushingoid signs) Zona Reticularis — Innermost Layer o Gonadocorticoid hormone production – Primarily DHEA (dehydroepiandrosterone) o Weak androgen that regulates male/female traits o DHEA & DHEA-Sulphate converted to testosterone (males) or estrogen (females) o Excess DHEA-  increased virilisation (male traits in females) or hirsutism (facial hair in women) Common in PCOS (polycystic ovarian syndrome) PHYSIOLOGICAL RESPONSE: HYPOTHALAMIC-PITUITARY-ADRENAL AXIS (HPA) No matter the stimuli/stressor, response is always the same Exogenous Stressors- E.g. cold, trauma, noise, pain, medical treatment Endogenous Stressors- E.g. fear, excitement, anxiety Stressors activate the limbic system & parts of the cerebral cortex & then the hypothalamus HYPOTHALAMUS Homeostasis controls, autonomic control centre, endocrine system controls Releases corticotropin releasing hormone/factor (CRH/CRF) o Stimulates sympathetic nervous system by the locus ceruleus o Stimulates the anterior pituitary o Stimulates the posterior pituitary (lesser extent) Anterior Pituitary Gland CRF release stimulates this gland to release ACTH ACTH releases cortisol from the zona fasciculate in the adrenal cortex (adrenal glands) Cortisol- Stress hormone essential for general adaptation to stress o Crucial in cardiovascular, metabolic, and immunological balances o 90-95% bound to cortisol-binding globulin o Small amount bound to albumin o Bounding protects cortisol being cleared by liver, but must be unbound to be physiologically active Also alters hormones such as beta endorphins, prolactin, & growth hormone in response to hypothalamic stimulation o Increased beta endorphins- reduce pain sensations (endogenous opioids for body) o Prolactin release- some research suggests there is a link to increasing B-cell differentiation by IL- 2  o Increased growth hormones or somatotropin- affects protein, lipid, & carb metabolism and counters insulin effects Locus Ceruleus Located in brain stem Integrating centre for autonomic nervous system Stress causes hypothalamus to stimulate locus ceruleus o Norepinephrine is synthesized here o Norepinephrine travels via afferent pathways back to hypothalamus, limbic system, hippocampal area, & cerebral cortex Sympathetic nervous system (SNS) activation causes release of epinephrine & norepinephrine from chromaffin cells & adrenal medulla o These catecholamines increase physical activity & rapid ATP production o SNS dominates over parasympathetic nervous system & other stimulation o Catecholamines prepare for fight/flight & return to homeostasis after threat is gone Epinephrine- o Increases glucose availability via glucogenesis & glycogenolysis o Limits uptake of peripheral glucose o Limits pancreas production of insulin, causing transient hyperglycemia o Causes bronchodilation (role of epi-pens) o Promotes lipolysis (breakdown of stored fats to provide immediate energy source) o Increases contractibility as a positive inotropy (increases amount of blood pumped) o Increases HR as chronotropic affect (impacts cardiac output) Norepinephrine- o Promotes arousal, vigilance, anxiety o Increases sweat glands (i.e. palms and arm pits) o Triggers piloerection (goosebumps) o Increases CV arterial smooth muscle constriction (increases BP) Posterior Pituitary Gland Hypothalamus has minor role of stimulating posterior pituitary to release anti-diuretic hormone (ADH)  o This is in conjunction with the ANS & release of hormones from the anterior pituitary gland o Facilitates sodium & water retention o Works with the ANS, catecholamines, & cortisol During Low Stress Period- o Anterior pituitary release of ACTH has little/no effect on mineralocorticoid released from adrenal cortex During High Stress Period- o Increased CRF result in increased ACTH blood level, increasing aldosterone secretion o The aldosterone released is likely due to the interaction between renin-angiotensin + ADH working with the ANS & cortisol The Stress Response Breakdown Stress → ANS activation to maintain homeostasis → SNS stimulates hypothalamus / pituitary gland → release of CRF → CRF activates pituitary gland → release of ACTH to adrenal glands → adrenal cortex releases cortisol & adrenal medulla releases catecholamines → catecholamines put body on high alert HPA Axis Overview Minor role for stimulation of posterior pituitary to impact release of ADH (anti-diuretic hormone) o In conjunction with ANS & release of hormones from anterior pituitary o Facilitates sodium & water retention o Works with ANS catecholamines & cortisol ACTH Release o Released by anterior pituitary o If person is NOT under stress- ACTH has no effect on mineralocorticoids (e.g. aldosterone) o If person is HIGH stress- increased CRF causes increased ACTH leading to increased aldosterone secretion Aldosterone release due to interaction between renin-angiotensin + ADH working with the ANS & cortisol ACUTE STRESS FEEDBACK Function- o Occurs at level of hypothalamus in the anterior pituitary gland o Negative feedback system occurs with activation of hypothalamus, which decreases further synthesis & release of more cortisol o Increased cortisol inhibits hypothalamus from releasing more CRF o Increased cortisol inhibits anterior pituitary from releasing more ACTH o Catecholamine effects > Corticoid effects Person readily feels effects of epinephrine & norepinephrine Benefits- o Fight or Flight Activation- Increased arousal, alertness, vigilance, cognitive functioning & focused attention facilitates rapid processing of info during a threatening period  o Hypermetabolic state (from lipolysis, gluconeogenesis, & glycogenolysis) provides body with increased nutrients for healing & energy Impact- o Healthy people can experience pounding headache, cold moist skin, stiff neck o Unhealthy people can experience worse stress responses E.g. heart disease- person may not have the cardiac reserve to cope with catecholamine surge during stress The Stress Response Involves: o Hypothalamus- stimulates locus ceruleus activating SNS o Adrenal Medulla- releases catecholamines B-1 receptor- increases HR, contractility, bronchioles Mostly binds epinephrine) A-1 receptor- increases TPR Mostly binds norepinephrine Adrenal cortex- releases cortisol & aldosterone CHRONIC STRESS FEEDBACK Function- o Negative feedback system is blunted/desensitized & no longer responsive to increased cortisol o Increased cortisol causes hypothalamus to secrete more CRF o Increased cortisol causes anterior pituitary to secrete more ACTH o Corticoid effects > Catecholamine effects Consequences- o Neural & hormonal connections become dysfunctional with prolonged activation, leading to overactivation of this system o Loss of muscle mass due to gluconeogenesis & protein catabolism o nitrogen depletion due to muscle catabolism o Increased nitrogen excreted in urine o Immune suppression due to decreased T-cells & thymic atrophy o Hyperglycemia o *Cardiovascular wear/tear due to constant catecholamine release Impact- o S/S: hypertension, renal & vascular disease, sustained hyperglycemia o E.g. person in emotional & abusive relationship for 20+ years develops impaired glucose tolerance, despite lack of family hx and normal BMI & BP After leaving relationship, energy levels improve, glucose returns to normal, & metabolic rate decreases (now has to be more careful with food intake) MEASUREMENTS OF STRESS RESPONSE Blood (Serum) Tests- o Hyperglycemia- blood test measures blood sugar levels o Adrenal Function Tests- hormone levels (aldosterone, cortisol, ACTH) o Cortisol- blood serum levels Diurnal Rhythm: cortisol levels naturally fluctuate throughout day & peak in the morning Collect sample in morning to get accurate baseline o Dexamethasone Suppression Test- blood samples to measure cortisol response after administering dexamethasone (checks if neg feedback is activated from hypothalamus to cortisol secretion) Measures how well negative feedback system suppresses ACTH Dexamethasone: glucocorticoid drug o ACTH Administration- administering ACTH helps assess adrenal cortex response o Glucagon Challenge- to glucose levels rise? If no, problem with liver o Serum Catecholamines- measures stress hormones (short half-life can complicate results)  o Insulin Tolerance Test (ITT)- hypoglycemic stress test; blood test before & after administering insulin to measure hormonal responses Gold standard for HPA Axis Assessment Determines sensitivity of insulin receptors Intentionally lowering blood glucose levels below 2.2 mmol/L using insulin to assess serum cortisol & growth hormone levels/response to see how body responds to stress Urine Tests- o Cortisol- 24-hr urine collection to assess cortisol metabolites o Urinary Nitrogen Measurement- reflects protein breakdown from urine sample Protein breakdown increases during stress Saliva Test- o Cortisol- slate evening salivary cortisol test used as screening o Oral Glucose Tolerance Test- detect insulin resistance, diagnose DM Other- o Cardiovascular Reactivity- BP & pulse measurements o Psychosocial Measurements- assess anxiety, fear, mood, coping, support (self-reporting) ADAPTATION— ADRENAL CORTICOID RESPONSE Trier social stress test (TSST) Purpose: induce large & consistent endocrine & cardiovascular response and moderate to high seductive stress to assess the adrenal corticoid response o Looked at public speaking responses to stress over 5 days in 20 healthy males Method: o Participants were brought into a room where they were met with 3 people with a video camera and tape recorder. They were asked to speak into a mic & take on the role of a job applicant. o Given 10 mins to prepare for a speech & 5 mins to deliver the speech  o Questions were asked after & then they were asked to perform a mental arithmetic task out loud (e.g. subtract 13 from 1022 continuously), and had to restart with every failure until 20 min mark o Participants then rested for 30-70 mins o Stress Measurement: HR, cortisol level (blood or saliva), serum ACTH, prolactin, & growth hormone Results: o Cortisol increase- peaked 30 mins after the tasks were completed, with gradual decline but still well above baseline ~1hr later o Coping/adaptation strategies- less cortisol was produced with each day & each day showed less of a range in results, although each day was a different job interview & subtraction task STRESS AND HEALING CONSEQUENCES CHRONIC STRESS IS LINKED TO: Decreased immune responses to vaccines o Higher stress levels linked to longer serum conversion time after vaccines Increased susceptibility to infections o Increased cortisol depresses Natural Killer (NK) cells o NK cells are important first line defences for detecting cancer o Increased cortisol associated with immune dysregulation & increased mortality o Chronic stress leads to down regulation of systemic pro-inflammatory responses, meaning body is not as responsive to inflammatory stimuli o Chronic stress can impair angiogenesis (formation of new blood vessels) because cortisol inhibits vascular endothelial growth factor (needed to form need blood vessels) Slow wound healing o Increased cortisol linked to depressed adaptive immune response which is likely to identify pathogens, causing longer wound healing RESEARCH EXAMPLES Caregivers- chronically stressed caregivers took 24% longer to heal a cutaneous wound than control Students- Biopsies revealed that wounds produced before an exam took 40% longer to heal than wounds made during a holiday Couples- Couples with consistently higher levels of hostile behaviour towards one another healed at 60% rate than low hostile couples STRESS AND THE BRAIN CONSEQUENCES Hippocampus: important for verbal & contextual memory o Sensitive to effects of glucocorticoids, especially cortisol- sustained stress damages this area HIGH LEVELS OF CORTISOL IMPAIR HIPPOCAMPAL FUNCTION VIA Neuronal atrophy and destruction o Long-term exposure to adrenal steroids cause dysregulation of HPA axis o Excess cortisol in hippocampus cause atrophy of dendrites of the pyramidal neurons, leading to short-term memory difficulties Decreased short-term memory o High cortisol prevents brain from laying pathways for new memory & accessing existing memories Decreased accuracy of contextual memories & impaired reliability o Reversible if stressor is short-term but continued exposure can supress hippocampal neurogenesis or promote apoptosis Impaired ability to recognize threat of situation CLINICAL IMPLICATIONS Sleep Disturbances- o Insomnia or sedation Muscle & Joint- o Back, shoulder, & neck pain  o Muscle tension & clenched jaw o Headaches Gastrointestinal- o Upset stomach o Reflux, gas, heartburn o Irritable bowel o Ulcer (due to increased gastric acid production & loss of stomach lining) o Constipation o Diarrhea o Weight gain or loss o Eating disorders Cardiovascular- o Hypertension o Arrythmia (irregular heart beat) o Palpitations o Chest pain o Asthma Skin- o Eczema, psoriasis o Ticks o Itching, hives, acne o Sweaty palms/hands Reproductive- o Loss of DHEA (hormone) causes decreased estrogen or testosterone Irregular menstrual cycle, etc o Suppression of gonadotropin releasing hormone (important in release of FSH & LH) Poor Wound Healing Emotional Symptoms- o Nervousness, anxiety, phobias o Depression, moodiness o Butterflies o Irritability, frustration, overreaction o Memory problems o Feeling out of control (leads to addiction) o Substance abuse o E.g. increased arguments, isolation from social activities, conflict with coworkers, frequent job change, road rage, domestic workplace violence, etc MAIN IMPLICATION- o Impact on Health Teaching- pt with multiple stressors may struggle coping with information; nurses should encourage family members who are less detached from the emotional side of stressors to accompany the patient to get a clear picture of what's going on Stress-Related Diseases Central Nervous System o Neuropsychological manifestations o Fatigue, insomnia, loss of motivation o Anxiety, depression, addiction o Overeating Cardiovascular System o Heart rate, arrhythmias o Stroke, heart failure, coronary artery disease  o Hypertension Gastrointestinal System o Crohn's disease (chronic IBD, inflammation & damage to digestive system) o Heartburn, GERD o Gastritis, ulcer o Malabsorption (impaired nutrient absorption) Musculoskeletal System o Tension headache (dull, sensation of tight band around head) o Backache o Inflammation disease of connective tissue (autoimmune diseases) o Arthritis (joint pain, swelling, etc), muscle wasting (chronic inflammation, atrophy) o Osteoporosis (weak bones & susceptibility to fractures) Integumentary System (largest organ; hair, nail, sweat & oil glands) o Eczema (inflammation, redness, itching, dry patchy skin) o Psoriasis (autoimmune disease; overproduction of skin cells; thick scaly patches) o Dermatitis (inflammation; redness, itching, skin rash) o Acne, alopecia (hair loss, bald patches, etc) o Poor wound healing Endocrine System o Hyperglycemia o Diabetes mellitus o Amenorrhea o Cushing disease, Addison disease Respiratory System o Respiratory rate o Hypersensitivity reactions (e.g. asthma) o Exacerbations of COPD Immune System o Immunodeficiency o Immunosuppression o Autoimmune diseases Genitourinary System (reproductive & urinary organs) o Diuresis (increased urine production) o Irritable bladder (uncontrollable, frequent urges to pee) o Renal failure (kidney unable to filter waste from bloodstream) o Impotence (erectile dysfunction) o Menstrual irregularities CLINICAL INTERVENTIONS Eliminate the Stressor(s)- o Most ideal intervention, but not always possible o E.g. antibiotic to attack infection, eliminate noise for patient, promote sleep hygiene, etc Management of Stress Response- o Positive coping mechanisms E.g. promote positive attitude/lifestyle, ensure exercise, adequate rest, healthy diet, etc o Negative coping mechanisms E.g. watch for substance abuse (drugs, alcohol, tobacco, caffeine, overeating, denial, etc) o Prevention or reduction of stress Use methods such as coping, relaxation, and management E.g. watch glucose levels, give insulin, monitor potassium, maintain blood volume, maintain nutrition E.g. decrease environmental stressors & pain control  Blocking the Stress Response- o E.g. distancing or making light of situation, self-control, seeking support, etc o E.g. accepting responsibility, recognizing you brought the problem on yourself Other Non-Pharmacological Treatments- o Relaxation (e.g. controlled breathing exercises, progressive relaxation, meditation, yoga) o Guided imagery (i.e. visualizing a tranquil scene with or without progressive relaxation) o Exercise (decreased cortisol secretion & increases endorphins) o Music therapy o Massage therapy o Biofeedback RESEARCH Sports Fans & Stress- regardless of a win or loss, big games were associated with 3x higher cardiac emergencies Women & Chronic Stress- higher chronic stress had decreased primary breast cancer due to repression of estrogen o However, women with breast cancer with longer survival rate (19+ months longer) if involved in support groups o Good pain control post op oncology surgery had decreased rate of metastasis o Caregivers for dementia patients are 6x more likely to develop dementia themselves, especially men Consider- many issues with the above research o Research is hard to conduct due to individual perception o What's stressful to one person isn't necessarily stressful to someone else o As nurses, we must assess patient stress levels & coping strategies Scenario 26 yr old Sandra, newly widowed mother with 2 children (Jimmy; 2 weeks ago via C-section, and Susie age 4). Sandra is looking for a babysitter but unsure if she can afford it. her mother-in-law will only help with children a couple of hours on the weekends but Sandra admits she is not always reliable CLINICAL PRESENTATION Bloodwork: hyperglycemia, hypernatremia, hypokalemia o Linked to catecholamines & cortisol as they promote gluconeogenesis & decreased insulin release from pancreas o Increase in sodium & decrease in potassium linked to aldosterone secretion with or without ADH impact Neurological: cognitive symptoms (short term memory problems), emotional systems (agitation), physical symptoms (headache), behavioural symptoms (isolation) Cardiovascular: increased HR, BP, palpitations Abdominal: heartburn, weight loss or gain, poor wound healing POST TRAUMATIC STRESS DISORDER PTSD: mental health condition triggered by experiencing a significant physical, emotional, or psychological traumatic event S/S: intrusions, avoidance, negative cognitions & mood, arousal Feature General Stress Post Traumatic Stress Disorder Response (PTSD) Cortisol Levels Elevated Low/Normal Cortisol Receptor Decreased Increased Sensitivity Negative Feedback Blunted Enhanced TAKE HOME MESSAGES 1. Cortisol inhibits hippocampal function o Impacts patient teaching 2. Many patients' clinical manifestations can be attributed to stress o Biological, psychological, behavioural, disease state 3. Stress affects management of disease & disorders o i.e. diabetes, CAD, autoimmunity 4. Stress response can kill o Eliminate stressors o Develop coping strategies o Change perspective on stress Learning Outcomes: Potential Causes of the Stress Response What Occurs During these Events Implications of Short-Term and Long-Term Consequences Research in the Area Clinical Implications STRESS RESPONSE "A state manifested by a specific syndrome of the body, developed in response to any stimuli that made an intense systemic demand on it" "A person experiences stress when a demand exceeds a person's coping abilities, resulting in reactions such as disturbances of cognition, emotion, and behaviour that can adversely affect well-being" "Stress is the spice of life" — stimulus for achievement or suffering WHAT IS STRESS 3 Components of Stress 1. Stressor: Stimuli + perception leads to response Eustressor- Positive Distressor- Negative (e.g. Conversing with patient while knowing your preceptor will judge you) Neutral- No effect (e.g. Conversing with patient) 2. Stress Response Also leads to hormonal responses 3. Pathophysiological Sequelae External Stimuli- External demands that trigger reactions (3 categorizations)  1. Quantity- negative consequences due to accumulation stressors (positive or negative) in a short period of time E.g. Holmes and Rahe Stress Scale (measures stress & risk of illness); i.e. new job, declining health of relative, moving 2. Quality- Major changes affect large number of people (e.g. war, economic depression) Major changes that affect a few people (e.g. bereavement, divorce) Daily hassles that affect normal people (e.g. complaining of daily stressors) 3. Duration- subtypes aren't mutually exclusive, can occur together Acute (e.g. job interview) Sequential (e.g. changes that follow divorce) Chronic - intermittent (e.g. periodic arguments with spouse) Chronic (e.g. permanent disability) Individual Judgement o Stress is an individual's conscious appraisal that a disturbance has occurred, challenging one's ability to cope o Stress is a demand-resource imbalance o We are not passive victims of stressful forces, we're capable of change o Lazarus & Folkman's Transactional Model of Stress Management PHYSIOLOGICAL RESPONSE Physiological response is an example of the mind, body connection, psycho-neuro-endocrine responses that involves 3 key areas 1. Perception/Emotion o frustration, anger, or fear can lead to emotional release o Depression, anxiety, excitement as a response to life or anticipatory events can lead to physiological mediated stress response 2. Hormones o Glucocorticoid- mainly cortisol o Mineralocorticoid- primary aldosterone o Catecholamines- epinephrine, norepinephrine, dopamine 3. Consequences o Short & long-term o Autonomic nervous system implications o Hormonal affects o And more THE ADRENAL GLANDS Location: two small retroperitoneal organs on top of each kidney Function: produce hormones to regulate metabolism, immune system, stress response, etc Adrenal Cortex o 80-90% of the adrenal gland o 3 Divisions: Zona Glomerulosa, Zona Fasciculata, Zona Reticularis Adrenal Medulla o Made of chromaffin cells (pheochromocytes) o Pheochromocytoma: neuroendocrine tumour that secretes excessive catecholamines o Rich blood and nerve supply o Epinephrine secreted 10x more potent than norepinephrine, for heart & metabolic activities o Minor source of norepinephrine o Links to autonomic sympathetic nervous system (fight or flight) Zona Glumerulosa — Outermost Layer Mineralocorticoid hormone production – Primarily Aldosterone Touch, fibrous capsule enclosed in fat for protection Aldosterone- o Regulate Na and K secretion and retention o Key in the renin-angiotensin-aldosterone pathway for volume & BP control o Role with pH balance by facilitating excretion of hydrogen ions Excess Aldosterone (Aldosteronism)- related to neoplasms, high sodium, decreased potassium o S/S: hypertension & edema o Decreased Potassium S/S: muscle weakness, paralysis Decreased Aldosterone- decreased sodium & increased potassium o S/S: hypotension, dehydration, potential weight loss Zona Fasciculata — Middle Layer Glucocorticoid hormone production – Primarily Cortisol Cortisol, cortisone, and corticosterone Cortisol (hydrocortisone)- o Major stress hormone essential for survival o Released with ACTH stimulation (secreted by pituitary gland when body is stressed) o Increased cortisol causes negative feedback (signal to reduce ACTH causes lower cortisol) o Key Roles- Hyperglycemia- Increases blood glucose by decreasing peripheral uptake and promoting gluconeogenesis Decreases insulin sensitivity E.g. Controlled diabetes are harder to control in the hospital setting due to the stress response Protein Synthesis & Catabolism- Increases protein synthesis in the liver & promotes catabolism in the muscles Acts synergistically with glucagon & epinephrine, overall affect is greater than sum of the individual hormones Lipolysis- Cortisol promotes lipolysis (breakdown of fatty acids) in the extremities Acute stage- cortisol promotes breakdown of fatty acids for energy source use Long-term- body redistributes fat or promotes lipogenesis in face & trunk areas  Cushingoid Signs- fat pad at back of neck or buffalo hump, moon face, or increased visual abdominal fat Anti-Inflammatory- May be linked to increased autoimmune responses Increased cortisol linked to decreased IL-1, 2, 6, and TNF-a (this aids to limit damage) Immunosuppression- Cortisol causes T-helper 2 (Th2) shift & increases immunity Th1- promotes cell-mediated immunity (immune system directly attacks infected cell) Th2- increases humoral immunity (antibody production & defense against pathogens) Need balance of Th1 & Th2 to prevent immune dysfunction Cortisol supresses Th1 causing decreased cellular immunity Cortisol promotes Th2 causing increased humoral immunity & anti-inflammatory response This activity is called T-helper 2 shift Addison Disease- Adrenal insufficiency o Insufficient cortisol secretion often in conjunction with too little mineralocorticoid o Decreased cortisol limits the required hormonal effects Cushing Syndrome/Disease- Excess cortisol o Adrena cortex secretes too much cortisol or caused by excessive corticosteroid medication o S/S: hyperglycemia (steroid diabetes), hypertension edema, poor wound healing (risk for infection), cushingoid signs) Zona Reticularis — Innermost Layer o Gonadocorticoid hormone production – Primarily DHEA (dehydroepiandrosterone) o Weak androgen that regulates male/female traits o DHEA & DHEA-Sulphate converted to testosterone (males) or estrogen (females) o Excess DHEA- increased virilisation (male traits in females) or hirsutism (facial hair in women) Common in PCOS (polycystic ovarian syndrome)  PHYSIOLOGICAL RESPONSE: HYPOTHALAMIC-PITUITARY-ADRENAL AXIS (HPA) No matter the stimuli/stressor, response is always the same Exogenous Stressors- E.g. cold, trauma, noise, pain, medical treatment Endogenous Stressors- E.g. fear, excitement, anxiety Stressors activate the limbic system & parts of the cerebral cortex & then the hypothalamus HYPOTHALAMUS Homeostasis controls, autonomic control centre, endocrine system controls Releases corticotropin releasing hormone/factor (CRH/CRF) o Stimulates sympathetic nervous system by the locus ceruleus o Stimulates the anterior pituitary o Stimulates the posterior pituitary (lesser extent) Anterior Pituitary Gland CRF release stimulates this gland to release ACTH ACTH releases cortisol from the zona fasciculate in the adrenal cortex (adrenal glands) Cortisol- Stress hormone essential for general adaptation to stress o Crucial in cardiovascular, metabolic, and immunological balances o 90-95% bound to cortisol-binding globulin o Small amount bound to albumin o Bounding protects cortisol being cleared by liver, but must be unbound to be physiologically active Also alters hormones such as beta endorphins, prolactin, & growth hormone in response to hypothalamic stimulation o Increased beta endorphins- reduce pain sensations (endogenous opioids for body) o Prolactin release- some research suggests there is a link to increasing B-cell differentiation by IL- 2  o Increased growth hormones or somatotropin- affects protein, lipid, & carb metabolism and counters insulin effects Locus Ceruleus Located in brain stem Integrating centre for autonomic nervous system Stress causes hypothalamus to stimulate locus ceruleus o Norepinephrine is synthesized here o Norepinephrine travels via afferent pathways back to hypothalamus, limbic system, hippocampal area, & cerebral cortex Sympathetic nervous system (SNS) activation causes release of epinephrine & norepinephrine from chromaffin cells & adrenal medulla o These catecholamines increase physical activity & rapid ATP production o SNS dominates over parasympathetic nervous system & other stimulation o Catecholamines prepare for fight/flight & return to homeostasis after threat is gone Epinephrine- o Increases glucose availability via glucogenesis & glycogenolysis o Limits uptake of peripheral glucose o Limits pancreas production of insulin, causing transient hyperglycemia o Causes bronchodilation (role of epi-pens) o Promotes lipolysis (breakdown of stored fats to provide immediate energy source) o Increases contractibility as a positive inotropy (increases amount of blood pumped) o Increases HR as chronotropic affect (impacts cardiac output) Norepinephrine- o Promotes arousal, vigilance, anxiety o Increases sweat glands (i.e. palms and arm pits) o Triggers piloerection (goosebumps) o Increases CV arterial smooth muscle constriction (increases BP) Posterior Pituitary Gland Hypothalamus has minor role of stimulating posterior pituitary to release anti-diuretic hormone (ADH) o This is in conjunction with the ANS & release of hormones from the anterior pituitary gland o Facilitates sodium & water retention o Works with the ANS, catecholamines, & cortisol During Low Stress Period- o Anterior pituitary release of ACTH has little/no effect on mineralocorticoid released from adrenal cortex During High Stress Period- o Increased CRF result in increased ACTH blood level, increasing aldosterone secretion o The aldosterone released is likely due to the interaction between renin-angiotensin + ADH working with the ANS & cortisol The Stress Response Breakdown Stress → ANS activation to maintain homeostasis → SNS stimulates hypothalamus / pituitary gland → release of CRF → CRF activates pituitary gland → release of ACTH to adrenal glands → adrenal cortex releases cortisol & adrenal medulla releases catecholamines → catecholamines put body on high alert HPA Axis Overview Minor role for stimulation of posterior pituitary to impact release of ADH (anti-diuretic hormone) o In conjunction with ANS & release of hormones from anterior pituitary o Facilitates sodium & water retention o Works with ANS catecholamines & cortisol ACTH Release o Released by anterior pituitary o If person is NOT under stress- ACTH has no effect on mineralocorticoids (e.g. aldosterone) o If person is HIGH stress- increased CRF causes increased ACTH leading to increased aldosterone secretion Aldosterone release due to interaction between renin-angiotensin + ADH working with the ANS & cortisol ACUTE STRESS FEEDBACK Function- o Occurs at level of hypothalamus in the anterior pituitary gland o Negative feedback system occurs with activation of hypothalamus, which decreases further synthesis & release of more cortisol o Increased cortisol inhibits hypothalamus from releasing more CRF o Increased cortisol inhibits anterior pituitary from releasing more ACTH o Catecholamine effects > Corticoid effects Person readily feels effects of epinephrine & norepinephrine Benefits-  o Fight or Flight Activation- Increased arousal, alertness, vigilance, cognitive functioning & focused attention facilitates rapid processing of info during a threatening period o Hypermetabolic state (from lipolysis, gluconeogenesis, & glycogenolysis) provides body with increased nutrients for healing & energy Impact- o Healthy people can experience pounding headache, cold moist skin, stiff neck o Unhealthy people can experience worse stress responses E.g. heart disease- person may not have the cardiac reserve to cope with catecholamine surge during stress The Stress Response Involves: o Hypothalamus- stimulates locus ceruleus activating SNS o Adrenal Medulla- releases catecholamines B-1 receptor- increases HR, contractility, bronchioles Mostly binds epinephrine) A-1 receptor- increases TPR Mostly binds norepinephrine Adrenal cortex- releases cortisol & aldosterone CHRONIC STRESS FEEDBACK Function- o Negative feedback system is blunted/desensitized & no longer responsive to increased cortisol o Increased cortisol causes hypothalamus to secrete more CRF o Increased cortisol causes anterior pituitary to secrete more ACTH o Corticoid effects > Catecholamine effects Consequences- o Neural & hormonal connections become dysfunctional with prolonged activation, leading to overactivation of this system o Loss of muscle mass due to gluconeogenesis & protein catabolism o nitrogen depletion due to muscle catabolism o Increased nitrogen excreted in urine o Immune suppression due to decreased T-cells & thymic atrophy o Hyperglycemia o *Cardiovascular wear/tear due to constant catecholamine release Impact- o S/S: hypertension, renal & vascular disease, sustained hyperglycemia o E.g. person in emotional & abusive relationship for 20+ years develops impaired glucose tolerance, despite lack of family hx and normal BMI & BP After leaving relationship, energy levels improve, glucose returns to normal, & metabolic rate decreases (now has to be more careful with food intake) MEASUREMENTS OF STRESS RESPONSE Blood (Serum) Tests- o Hyperglycemia- blood test measures blood sugar levels o Adrenal Function Tests- hormone levels (aldosterone, cortisol, ACTH) o Cortisol- blood serum levels Diurnal Rhythm: cortisol levels naturally fluctuate throughout day & peak in the morning Collect sample in morning to get accurate baseline o Dexamethasone Suppression Test- blood samples to measure cortisol response after administering dexamethasone (checks if neg feedback is activated from hypothalamus to cortisol secretion) Measures how well negative feedback system suppresses ACTH Dexamethasone: glucocorticoid drug o ACTH Administration- administering ACTH helps assess adrenal cortex response  o Glucagon Challenge- to glucose levels rise? If no, problem with liver o Serum Catecholamines- measures stress hormones (short half-life can complicate results) o Insulin Tolerance Test (ITT)- hypoglycemic stress test; blood test before & after administering insulin to measure hormonal responses Gold standard for HPA Axis Assessment Determines sensitivity of insulin receptors Intentionally lowering blood glucose levels below 2.2 mmol/L using insulin to assess serum cortisol & growth hormone levels/response to see how body responds to stress Urine Tests- o Cortisol- 24-hr urine collection to assess cortisol metabolites o Urinary Nitrogen Measurement- reflects protein breakdown from urine sample Protein breakdown increases during stress Saliva Test- o Cortisol- slate evening salivary cortisol test used as screening o Oral Glucose Tolerance Test- detect insulin resistance, diagnose DM Other- o Cardiovascular Reactivity- BP & pulse measurements o Psychosocial Measurements- assess anxiety, fear, mood, coping, support (self-reporting) ADAPTATION— ADRENAL CORTICOID RESPONSE Trier social stress test (TSST) Purpose: induce large & consistent endocrine & cardiovascular response and moderate to high seductive stress to assess the adrenal corticoid response o Looked at public speaking responses to stress over 5 days in 20 healthy males Method:  o Participants were brought into a room where they were met with 3 people with a video camera and tape recorder. They were asked to speak into a mic & take on the role of a job applicant. o Given 10 mins to prepare for a speech & 5 mins to deliver the speech o Questions were asked after & then they were asked to perform a mental arithmetic task out loud (e.g. subtract 13 from 1022 continuously), and had to restart with every failure until 20 min mark o Participants then rested for 30-70 mins o Stress Measurement: HR, cortisol level (blood or saliva), serum ACTH, prolactin, & growth hormone Results: o Cortisol increase- peaked 30 mins after the tasks were completed, with gradual decline but still well above baseline ~1hr later o Coping/adaptation strategies- less cortisol was produced with each day & each day showed less of a range in results, although each day was a different job interview & subtraction task STRESS AND HEALING CONSEQUENCES CHRONIC STRESS IS LINKED TO: Decreased immune responses to vaccines o Higher stress levels linked to longer serum conversion time after vaccines Increased susceptibility to infections o Increased cortisol depresses Natural Killer (NK) cells o NK cells are important first line defences for detecting cancer o Increased cortisol associated with immune dysregulation & increased mortality o Chronic stress leads to down regulation of systemic pro-inflammatory responses, meaning body is not as responsive to inflammatory stimuli o Chronic stress can impair angiogenesis (formation of new blood vessels) because cortisol inhibits vascular endothelial growth factor (needed to form need blood vessels) Slow wound healing o Increased cortisol linked to depressed adaptive immune response which is likely to identify pathogens, causing longer wound healing RESEARCH EXAMPLES Caregivers- chronically stressed caregivers took 24% longer to heal a cutaneous wound than control Students- Biopsies revealed that wounds produced before an exam took 40% longer to heal than wounds made during a holiday Couples- Couples with consistently higher levels of hostile behaviour towards one another healed at 60% rate than low hostile couples STRESS AND THE BRAIN CONSEQUENCES Hippocampus: important for verbal & contextual memory o Sensitive to effects of glucocorticoids, especially cortisol- sustained stress damages this area HIGH LEVELS OF CORTISOL IMPAIR HIPPOCAMPAL FUNCTION VIA Neuronal atrophy and destruction o Long-term exposure to adrenal steroids cause dysregulation of HPA axis o Excess cortisol in hippocampus cause atrophy of dendrites of the pyramidal neurons, leading to short-term memory difficulties Decreased short-term memory o High cortisol prevents brain from laying pathways for new memory & accessing existing memories Decreased accuracy of contextual memories & impaired reliability o Reversible if stressor is short-term but continued exposure can supress hippocampal neurogenesis or promote apoptosis Impaired ability to recognize threat of situation CLINICAL IMPLICATIONS Sleep Disturbances-  o Insomnia or sedation Muscle & Joint- o Back, shoulder, & neck pain o Muscle tension & clenched jaw o Headaches Gastrointestinal- o Upset stomach o Reflux, gas, heartburn o Irritable bowel o Ulcer (due to increased gastric acid production & loss of stomach lining) o Constipation o Diarrhea o Weight gain or loss o Eating disorders Cardiovascular- o Hypertension o Arrythmia (irregular heart beat) o Palpitations o Chest pain o Asthma Skin- o Eczema, psoriasis o Ticks o Itching, hives, acne o Sweaty palms/hands Reproductive- o Loss of DHEA (hormone) causes decreased estrogen or testosterone Irregular menstrual cycle, etc o Suppression of gonadotropin releasing hormone (important in release of FSH & LH) Poor Wound Healing Emotional Symptoms- o Nervousness, anxiety, phobias o Depression, moodiness o Butterflies o Irritability, frustration, overreaction o Memory problems o Feeling out of control (leads to addiction) o Substance abuse o E.g. increased arguments, isolation from social activities, conflict with coworkers, frequent job change, road rage, domestic workplace violence, etc MAIN IMPLICATION- o Impact on Health Teaching- pt with multiple stressors may struggle coping with information; nurses should encourage family members who are less detached from the emotional side of stressors to accompany the patient to get a clear picture of what's going on Stress-Related Diseases Central Nervous System o Neuropsychological manifestations o Fatigue, insomnia, loss of motivation o Anxiety, depression, addiction o Overeating  Cardiovascular System o Heart rate, arrhythmias o Stroke, heart failure, coronary artery disease o Hypertension Gastrointestinal System o Crohn's disease (chronic IBD, inflammation & damage to digestive system) o Heartburn, GERD o Gastritis, ulcer o Malabsorption (impaired nutrient absorption) Musculoskeletal System o Tension headache (dull, sensation of tight band around head) o Backache o Inflammation disease of connective tissue (autoimmune diseases) o Arthritis (joint pain, swelling, etc), muscle wasting (chronic inflammation, atrophy) o Osteoporosis (weak bones & susceptibility to fractures) Integumentary System (largest organ; hair, nail, sweat & oil glands) o Eczema (inflammation, redness, itching, dry patchy skin) o Psoriasis (autoimmune disease; overproduction of skin cells; thick scaly patches) o Dermatitis (inflammation; redness, itching, skin rash) o Acne, alopecia (hair loss, bald patches, etc) o Poor wound healing Endocrine System o Hyperglycemia o Diabetes mellitus o Amenorrhea o Cushing disease, Addison disease Respiratory System o Respiratory rate o Hypersensitivity reactions (e.g. asthma) o Exacerbations of COPD Immune System o Immunodeficiency o Immunosuppression o Autoimmune diseases Genitourinary System (reproductive & urinary organs) o Diuresis (increased urine production) o Irritable bladder (uncontrollable, frequent urges to pee) o Renal failure (kidney unable to filter waste from bloodstream) o Impotence (erectile dysfunction) o Menstrual irregularities CLINICAL INTERVENTIONS Eliminate the Stressor(s)- o Most ideal intervention, but not always possible o E.g. antibiotic to attack infection, eliminate noise for patient, promote sleep hygiene, etc Management of Stress Response- o Positive coping mechanisms E.g. promote positive attitude/lifestyle, ensure exercise, adequate rest, healthy diet, etc o Negative coping mechanisms E.g. watch for substance abuse (drugs, alcohol, tobacco, caffeine, overeating, denial, etc) o Prevention or reduction of stress Use methods such as coping, relaxation, and management  E.g. watch glucose levels, give insulin, monitor potassium, maintain blood volume, maintain nutrition E.g. decrease environmental stressors & pain control Blocking the Stress Response- o E.g. distancing or making light of situation, self-control, seeking support, etc o E.g. accepting responsibility, recognizing you brought the problem on yourself Other Non-Pharmacological Treatments- o Relaxation (e.g. controlled breathing exercises, progressive relaxation, meditation, yoga) o Guided imagery (i.e. visualizing a tranquil scene with or without progressive relaxation) o Exercise (decreased cortisol secretion & increases endorphins) o Music therapy o Massage therapy o Biofeedback RESEARCH Sports Fans & Stress- regardless of a win or loss, big games were associated with 3x higher cardiac emergencies Women & Chronic Stress- higher chronic stress had decreased primary breast cancer due to repression of estrogen o However, women with breast cancer with longer survival rate (19+ months longer) if involved in support groups o Good pain control post op oncology surgery had decreased rate of metastasis o Caregivers for dementia patients are 6x more likely to develop dementia themselves, especially men Consider- many issues with the above research o Research is hard to conduct due to individual perception o What's stressful to one person isn't necessarily stressful to someone else o As nurses, we must assess patient stress levels & coping strategies Scenario 26 yr old Sandra, newly widowed mother with 2 children (Jimmy; 2 weeks ago via C-section, and Susie age 4). Sandra is looking for a babysitter but unsure if she can afford it. her mother-in-law will only help with children a couple of hours on the weekends but Sandra admits she is not always reliable CLINICAL PRESENTATION Bloodwork: hyperglycemia, hypernatremia, hypokalemia o Linked to catecholamines & cortisol as they promote gluconeogenesis & decreased insulin release from pancreas o Increase in sodium & decrease in potassium linked to aldosterone secretion with or without ADH impact  Neurological: cognitive symptoms (short term memory problems), emotional systems (agitation), physical symptoms (headache), behavioural symptoms (isolation) Cardiovascular: increased HR, BP, palpitations Abdominal: heartburn, weight loss or gain, poor wound healing POST TRAUMATIC STRESS DISORDER PTSD: mental health condition triggered by experiencing a significant physical, emotional, or psychological traumatic event S/S: intrusions, avoidance, negative cognitions & mood, arousal Feature General Stress Post Traumatic Stress Disorder Response (PTSD) Cortisol Levels Elevated Low/Normal Cortisol Receptor Decreased Increased Sensitivity Negative Feedback Blunted Enhanced TAKE HOME MESSAGES 1. Cortisol inhibits hippocampal function o Impacts patient teaching 2. Many patients' clinical manifestations can be attributed to stress o Biological, psychological, behavioural, disease state 3. Stress affects management of disease & disorders o i.e. diabetes, CAD, autoimmunity 4. Stress response can kill o Eliminate stressors o Develop coping strategies o Change perspective on stress