Stress Response and Adaptation

Stress 101 - Defining the Pressure

• Stress: A state of threatened homeostasis; body's physiological & psychological response to demands (stressors).
• Stressors: Stimuli eliciting stress response.
  • Types:
    • Physical (e.g., trauma, infection, surgery, extreme temperatures)
    • Physiological (e.g., hypoglycemia, hypoxia, pain)
    • Psychological/Emotional (e.g., fear, anxiety, grief, exams)
    • Social (e.g., conflict, isolation)
  • Eustress (beneficial, motivating) vs. Distress (harmful, overwhelming).
• General Adaptation Syndrome (GAS) - Hans Selye: Classic model of stress response.

⭐ Hans Selye's General Adaptation Syndrome (GAS) outlines three predictable stages the body uses to respond to stressors: 1. Alarm Reaction, 2. Stage of Resistance, and 3. Stage of Exhaustion. Chronic stress can lead to "diseases of adaptation."

Hormonal Havoc - The Stress Axes

Two primary neuroendocrine axes orchestrate the body's response to perceived threats or challenges:

• Sympathetic-Adrenal-Medullary (SAM) Axis:

  • Trigger: Acute stressors (e.g., immediate danger).
  • Pathway: Sympathetic nerves → Adrenal Medulla.
  • Key Mediators: Epinephrine (Adrenaline), Norepinephrine (Noradrenaline).
  • Response: Rapid "fight-or-flight"; ↑HR, ↑BP, ↑glucose, ↑alertness.
  • Onset: Seconds. Duration: Short-lived.

• Hypothalamic-Pituitary-Adrenal (HPA) Axis:

  • Trigger: Sustained/chronic stressors (e.g., exams, illness).
  • Pathway: Hypothalamus (CRH) → Pituitary (ACTH) → Adrenal Cortex.
  • Key Mediator: Cortisol (glucocorticoid).
  • Response: Slower, sustained adaptation; ↑glucose, ↑lipolysis, ↑proteolysis, anti-inflammatory (initial), immunosuppressive (chronic).
  • Onset: Minutes to hours. Duration: Prolonged.
  • Regulation: Negative feedback by cortisol on hypothalamus & pituitary.

⭐ SAM axis: Rapid onset (seconds), short duration; primarily neural. HPA axis: Slower onset (minutes-hours), longer duration; primarily hormonal.

Body Under Siege - Systemic Impact

• Cardiovascular: ↑BP, atherosclerosis, arrhythmias, ↑CVD risk.
• Immune System: Initial activation → chronic suppression/dysregulation. ↑Infections, impaired wound healing, ↑inflammation.
• Metabolic: Insulin resistance (→ T2DM), dyslipidemia, central obesity, metabolic syndrome.
• CNS:
  • Anxiety, depression, cognitive impairment (memory, concentration).
  • Sleep disturbances.
• Endocrine: HPA axis dysregulation (altered cortisol rhythm), thyroid dysfunction, ↓gonadal function.
• Gastrointestinal: ↑IBS & PUD risk, altered gut motility & permeability.
• Musculoskeletal: Muscle tension, chronic pain, ↑osteoporosis risk (cortisol).
• Cellular: ↑Oxidative stress, telomere shortening (accelerated aging).

⭐ Chronic stress leads to hippocampal atrophy, impacting learning and memory.

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Bouncing Back - Adaptation & Allostasis

• Adaptation: Long-term structural/functional adjustments to chronic stress (e.g., myocardial hypertrophy in chronic hypertension).
• Allostasis: Achieving stability through change; active physiological process for acute stress.
  • Mediators: Cortisol, catecholamines, cytokines.
  • Maintains internal milieu despite external demands.
• Allostatic Load:

  ⭐ Allostatic Load: The cumulative physiological burden or "wear and tear" from chronic stress and/or dysregulated stress responses. High allostatic load is a key predictor of disease risk.

• Allostatic Overload: Pathological state from prolonged/excessive allostatic load.
  • Leads to ↑ risk of Cardiovascular Disease (CVD), metabolic syndrome, immunosuppression.
  • Four types: (1) Repeated hits (multiple stressors); (2) Lack of adaptation (same stressor); (3) Prolonged response (no shut-off); (4) Inadequate response (compensatory hyperactivity).

High‑Yield Points - ⚡ Biggest Takeaways

• HPA axis (CRH, ACTH, Cortisol) is central to chronic stress.
• Sympathetic nervous system (Adrenaline, Noradrenaline) mediates acute stress ("fight or flight").
• Cortisol has permissive effects on catecholamines; ↑gluconeogenesis, proteolysis, lipolysis.
• Chronic stress can lead to immunosuppression, muscle wasting, and insulin resistance.
• Allostasis is achieving stability via change; allostatic load is wear and tear from chronic stress.
• General Adaptation Syndrome (GAS) stages: Alarm, Resistance, Exhaustion (Selye).