McCance 11 -M 10.2 - Understanding Stress: Types, Impact, and History

• Modern society is full of stress due to the work ethic and the pressure to remain connected.
• Stressful experiences include daily hassles, major life events, social isolation, and socioeconomic status.
• Stress begins when the brain perceives a stimulus as stressful, which promotes adaptational and survival-related physiologic responses.
• If the psychologic perception of environmental demand exceeds adaptive capacity, stress may lead to negative health outcomes.
• Acute stress is considered immunoenhancing (protective), while chronic stress is immunosuppressive (destructive).
• Chronic inflammation is driven by the increased expression of genes that promote inflammation and decreased expression of genes that promote antiviral responses, contributing to diseases and mortality.

Historical Context

• Walter B. Cannon used the term "stress" to encompass physiologic and psychologic ideas.
• Hans Selye discovered the biologic syndrome of stress, the general adaptation syndrome (GAS).
• The structural changes that occur: enlargement of the adrenal cortex, atrophy of the thymus gland, and development of bleeding ulcers.
• Selye identified stressors as noxious stimuli like cold, surgical injury, and restraint.
• The GAS includes the alarm stage, resistance stage or adaptation and the stage of exhaustion.

Stages of GAS

• Alarm stage: CNS is aroused, and defenses are mobilized.
• Resistance stage: mobilization contributes to "fight or flight."
• Exhaustion stage: continuous stress causes breakdown of compensatory mechanisms and homeostasis.
• Exhaustion marks the onset of diseases.
• Stress activates the hypothalamus and sympathetic nervous system.
• The adaptation phase involves the hormones cortisol, norepinephrine, and epinephrine.
• Exhaustion involves allostatic overload and causes impairment of the immune response, heart failure, and kidney failure, leading to death.

Stress: Holistic Perspective

• The perspective that combines molecular biology, immunology, neurology, endocrinology, and behavioral science.
• This perspective involves biochemical relationships of the central nervous system (CNS), autonomic nervous system (ANS), the hypothalamic-pituitary-adrenal (HPA) axis, and the immune system.

Concepts of Stress

• Research has demonstrated the sensitivity of the CNS and endocrine system to psychologic influences, including emotion.
• Activation of the adrenal cortex occurs in response to psychologic stressors.

Discovery of GAS

• Mason demonstrated that the GAS depended on the psychologic factors surrounding the stressors and the degree of the discomfort or unpleasantness.
• Stress is defined as a transactional or interactional concept, arising when a person relates to situations in certain ways.

Reactive and Anticipatory Stress

• A person experiences stress when a demand exceeds their coping abilities, disturbing cognition, emotion, and behaviour.
• Reactive response: physiologic response derived from psychologic stressors
• Anticipatory response: physiologic responses develop in anticipation of disruption of homeostasis
• Anticipatory responses are generated either by species-specific, innate programs or by experience-dependent memory programs.

Conditional Response

• One learns to associate specific stimuli with danger, producing a physiologic stress response.
• Strong memory programs under certain circumstances can lead to phobias or posttraumatic stress disorder (PTSD).
• PTSD is defined by flashback memories, sleep disturbances, depression, and other symptoms that compromise normal activities..
• Allostasis, as opposed to homeostasis, proposes that physiologic systems are dynamic and capable of changing set-points after exposure to stress.
• Allostatic load is the individualized cumulative effects of stressors on people's lives and influences their physiologic responses.
• Contributors to allostatic load: vulnerable physiologic/genetic makeup, lifestyle, daily stressful encounters, and extraordinary events.

Brain Function

• The brain is a key player in deciding what is stressful and determining toxic allostatic overload.
• Brain responses to acute and chronic stress include structural remodeling of the hippocampus, amygdala, and prefrontal cortex, which can alter behavioral and physiologic responses.
• Molecules necessary for brain remodeling: brain-derived neurotrophic factor (BDNF), tissue plasminogen activator (tPA), corticotropin releasing hormone (CRH), Lipocalin-2, and endocannabinoids (eCBs).
• An imbalance of neural circuitry affecting cognition, decision-making, anxiety, and mood can disrupt behavioral states.
• Key mediators and biomarkers of allostatic overload: the glucocorticoid cortisol, catecholamines, and proinflammatory cytokines.
• Sleep deprivation has damaging effects like elevated evening cortisol level, elevated insulin and blood glucose levels, increased blood pressure, and proinflammatory cytokines.

Psychosocial Work Environment

• Figure 11.5 summarises psychosocial hazards that may affect both psychological and physical health through stress and risks for work-related stress.

Psychoneuroimmunologic (PNI) Mediators of Stress

• The field encompasses the consciousness, the brain and spinal cord, and the body's defenses.
• Assumes that all immune-mediated diseases result from interrelationships among psychosocial, emotional, genetic, and behavioral factors with the neurologic, endocrine, and immune systems.
• The immune system is sensitive to changes in CNS and endocrine functioning that accompany psychologic states.
• Stressors can elicit the stress response through the nervous and endocrine systems.
• Hormones released by stress influence many metabolic systems and corresponding physiologic events.
• Psychosocial stressors or interventions modulate the immune system to impact health outcomes.
• The link between psychosocial stressors and health outcomes include infectious disease and wound healing.
• Psychologic distress is associated with increased mortality and increased risk of death from cardiovascular disease, external causes, and cancer.
• Job insecurity increases the odds of reporting poor health, high job demands raise the odds of having a diagnosed illness, and long work hours increase mortality.

Initiating Stress

• Perception of stress initiates a series of events in the CNS and peripheral nervous systems.
• The brain elicits an anticipatory response that activates the limbic system, responsible for motivation, emotions, and cognition, as well as an endocrine stress response.
• The sympathetic adrenal medullary system releases catecholamines (norepinephrine and epinephrine), and the HPA system culminates in cortisol secretion.
• Activation of stress systems redirects adaptive energy to the CNS and peripheral body sites to cope with stress.
• Walter Cannon recognized that stress or threat triggers the sympathetic nervous system to rapidly prepare the body for the fight-or-flight response.
• This adaptive activation involves increased blood flow, elevated metabolism, and pupil dilation.
• Catecholamine secretion from the adrenal medulla into the circulatory system facilitates physiologic effects; influence of the brain had been unclear.
• Areas of the frontal lobe and somatosensory cortex, are involved in visceromotor and skeletomotor output.
• The cortical pathway coordinates the body's motor system to cope with stress and metabolism through adrenal medulla catecholamine secretion.
• The medial prefrontal cortex regulates cognitive and emotional processing.
• Failure to assess or cope with a stressful situation may lead to uncontrolled emotional states and heightened activation of the sympathetic nervous system.

Sympathetic Nervous System

• Stress activates the sympathetic nervous system (SNS) to stimulate the release of catecholamines (epinephrine and norepinephrine) from the adrenal medulla into the bloodstream and nerve endings.
• The adrenal medulla innervates chromaffin cells that produce catecholamines.
• Adrenergic effector molecules have multiple effects on gene expression and cellular function in various systems.
• Acute fight-or-flight responses increase heart rate by activating B₁-adrenergic receptors, redistribute blood by activating vascular a₁- and B2-adrenergic receptors, increase respiratory rate by activating bronchial a₁- and B2-adrenergic receptors, mobilize energy by activating receptors in adipose tissue and the liver
• Immune cells are mobilized into circulation by activating B2-adrenergic receptors on leukocytes.
• Epinephrine is rapidly transported and acts on several organs but is metabolized quickly (short-acting); causes transient hyperglycemia by activating enzymes whose actions promote glucose formation and glycogen breakdown in the liver.
• Norepinephrine has a greater influence on cardiac action and is the principal catecholamine involved in metabolic regulation. It enhances myocardial contractility, and increases venous return to the heart for cardiac output and blood pressure.
• Catecholamines modify the numbers of cells of the immune system circulating in the blood, increasing lymphocytes while reducing the responsiveness of T and B lymphocytes.
• Catecholamines also increase proinflammatory cytokine production.
• Glucocorticoids can inhibit proinflammatory production.

Parasympathetic System

• Balances the sympathetic nervous system and influences adaptation to stressful events.
• Parasympathetic system has antiinflammatory effects and opposes sympathetic responses, slowing the heart rate.
• Uses technique heart rate variability to evaluate the relative balance of the parasympathetic and sympathetic nervous systems.

Neuroendocrine Regulation

• It has been found that the PVN of the hypothalamus secretes corticotropin-releasing hormone (CRH), which binds to specific receptors on anterior pituitary cells that, in turn, produce adrenocorticotropic hormone (ACTH).
• After binding to receptors on the adrenal glands, the glucocorticoid hormones (primarily cortisol) are released.
• Cortisol sends a negative feedback signal to the pituitary and hypothalamus to terminate the HPA stress response and enhances immunity during acute stress and suppresses immunity during chronic stress.
• Cortisol reaches all tissues including the brain and reaches numerous glucocorticoid receptors and influences a large proportion of the human genome.
• Cortisol mobilizes substances needed for cellular metabolism, stimulating gluconeogenesis or formation of glucose from noncarbohydrate sources.
• In addition the hormone enhances the elevation of blood glucose level promoted by other hormones.
• Cortisol has an anabolic e