STRESS

Objectives

  • Define stress and its impact on homeostasis/allostasis.

  • Describe the General Adaptation Syndrome.

  • Describe the role of cortisol throughout General Adaptation Syndrome.

  • List disease states that can be caused by stress.

  • Identify the appropriate use of exogenous adrenal replacement.

Homeostasis

  • Definition: Homeostasis refers to the body's ability to maintain a stable internal environment.
      - Components:
        - Homeo: same
        - Stasis: stable

  • Ideal 'set-point': The stable internal environment where balance is achieved, such as:
      - pH
      - Temperature
      - Blood Pressure

Allostasis

  • Definition: Allostasis refers to the process of achieving stability through change.
      - Components:
        - Allo: variable or different
        - Stasis: stable

  • Function: Addresses the need to alter "set-points" based on specific situations, such as:
      - Anticipation of increased demand (e.g., increased respiratory rate with vigorous exercise).

  • Involvement: Alters multiple physiological variables to match demands.

What is Stress?

  • Definition: Stress can be both physical or psychological.
      - Types of Stress:
        - Eustress: Positive reaction to stress that can promote growth (e.g., getting into nursing school).
        - Distress: Negative reaction to stress.

  • Stressor: The actual force exerted that causes stress.

Adaptive Ability

  • Understanding Coping Mechanisms: These mechanisms help individuals respond to stress.
      - Influencing Factors:
        - Genetics
        - Culture
        - Prior experiences/Environment
        - Pre-existing health status
      - Allostatic State: The ability to manage stress effectively.

General Adaptation Syndrome (GAS)

  • Definition: A typical response by the body regardless of the stressor involved.

  • Phases:
      - Alarm: Initial state of arousal and body's first defense mechanism.
      - Resistance: Time-limited phase where the body tries to cope with stress.
      - Exhaustion: When stressor is not relieved, leading to depletion of resources.

Alarm Phase

  • Description: The body's initial reaction to stress.

  • Fight or Flight Response:
      - Mediated by: Sympathetic Nervous System (SNS) and Hypothalamic-Pituitary-Adrenal (HPA) axis.
      - Process:
        - Hypothalamus activates the SNS.
        - Adrenal medulla releases norepinephrine and epinephrine into the bloodstream.
        - Activation of adrenal-cortical system through Corticotropin-Releasing Factor (CRF).
        - Anterior pituitary gland secretes ACTH (Adrenocorticotropic Hormone).
        - ACTH triggers adrenal cortex to release approximately 30 hormones.

Parasympathetic vs. Sympathetic Nervous System Responses

  • Parasympathetic Activation:
      - Stimulates saliva flow.
      - Constricts pupils.
      - Slows heartbeat.
      - Stimulates digestion.

  • Sympathetic Activation:
      - Dilates pupils.
      - Accelerates heartbeat.
      - Inhibits digestion (peristalsis and secretion).
      - Converts glycogen to glucose.
      - Inhibits bladder contraction.

HPA Axis and Hormonal Responses

  • HPA Axis Components:
      - Corticotropin-Releasing Hormone (CRH) from hypothalamus.
      - Adrenocorticotropic Hormone (ACTH) from anterior pituitary.
      - Cortisol from adrenal cortex.
      - Feedback Mechanism: Negative feedback to regulate hormone levels.

  • Hormone Functions:
      - Glucocorticoids (Cortisol):
        - Increases cardiac output and blood pressure.
        - Decreases gonadal hormones (luteinizing hormone, estradiol, progesterone, testosterone).
        - Increases amino acids.
        - Causes atrophy of lymph tissues.
        - Limited increase in WBC response.
      - Mineralocorticoids (Aldosterone):
        - Absorb Na+ and excrete K+ (and H+).
        - Water follows Na+ which affects fluid balance.

Catecholamines and Glucocorticoids

  • Interrelationship:
      - Glucocorticoids promote the synthesis of epinephrine.
      - Both play a role in brain function and memory development, which is critical for survival under stress.

Resistance Phase

  • Characterization:
      - Time-limited; hormonal and catecholamine levels remain elevated until stressor is removed.
      - Parasympathetic Nervous System takes over, promoting relaxation and counteracting stress effects.

Relaxation Response

  • Physiological Changes:
      - Heart rate slows.
      - Blood pressure lowers.
      - Blood lactate levels reduce.
      - Immune system improves.
      - Sense of well-being increases.
      - Sleep quality improves.
      - Normal libido and digestion are restored.

Stress Response vs. Relaxation Response Effects

  • Stress Response Effects:
      - Increased heart rate and blood pressure.
      - Higher cholesterol levels.
      - Reduced immune system efficiency.
      - Increased anxiety and depression.
      - Decreased libido and effective digestion.

Exhaustion Phase

  • Consequences of Chronic Stress:
      - Stressor is not relieved, leading to:
        - Hypertrophy of adrenal cortex.
        - Atrophy of lymphatic tissues.
        - Bleeding ulcers (stomach and duodenum).
        - Depletion of energy stores and inability to adapt.

  • Implications:
      - Negative impact on physical and mental well-being.
      - Immunosuppression due to elevated cortisol.
      - Decreased WBC responsiveness and T-cell levels.
      - Excessive catecholamine release.

Stress and Disease

  • Stress-Induced Conditions:
      - Coronary artery disease.
      - Hypertension.
      - Stroke.
      - Tension headaches.
      - Autoimmune diseases like rheumatoid arthritis, irritable bowel syndrome.
      - Ulcers and sexual dysfunction.
      - Type 2 diabetes mellitus.

Cortisol’s Role in the Body

  • Metabolic Functions:
      - Carbohydrate and Glucose Metabolism:
        - Opposes insulin effects, supplying glucose to the brain through gluconeogenesis.
        - Decreased peripheral glucose utilization and inhibited glucose uptake by muscles and adipose tissue, while promoting storage as glycogen.
      - Protein Metabolism:
        - Has both anabolic (build up) and catabolic (break down) effects, influencing muscle and fat distributions in the body.

Adrenal Insufficiency: Glucocorticoids

  • Context: Can arise from excessive stress, trauma, or sepsis, potentially leading to death. Various implications include:
      - Cardiovascular issues:
        - Increased capillary permeability.
        - Decreased ability of vasoconstriction leading to hypotension.
      - Cerebral effects:
        - Depression, lethargy, irritability, and rare psychosis.
      - General symptoms:
        - Hypotension and hypoglycemia as major health risks.

Adrenal Insufficiency: Mineralocorticoids

  • Consequences:
      - Hyponatremia and hyperkalemia.
      - Cellular dehydration and reduced extracellular fluid volume.
      - Potential renal failure.

Acute Adrenal Insufficiency

  • Results: Can lead to:
      - Hypotension.
      - Dehydration.
      - Weakness and lethargy.
      - Gastrointestinal symptoms including vomiting and diarrhea.

  • Causes:
      - Adrenal or pituitary failure, failure to increase steroid dosages during stress, or abrupt withdrawal of steroids.

Replacement Steroids

  • Usage Context: Indicated for actual or pseudo-insufficiency. These steroids have anti-inflammatory properties and must be utilized at the lowest effective dose.

Specific Steroids and Dosing Strategies

  • Glucocorticoids:
      - Hydrocortisone:
        - Doses: 15-25 mg/day orally; parenteral administration: 50-100 mg IV every 80 minutes.
      - Prednisone:
        - Typical daily dose: 5-10 mg.
      - Dexamethasone:
        - Dose range: 0.25-0.75 mg daily.

Adverse Effects of Glucocorticoids

  • Side Effects/Adverse Reactions:
      - Adrenal insufficiency.
      - Increased risk of infections.
      - Cushingoid effects like fat redistribution and muscle wasting.
      - Weight gain, impaired wound healing, glucose intolerance among others.

  • Teaching Points:
      - Necessity to taper doses and avoid abrupt cessation of steroids.

Mineralocorticoids

  • Fludrocortisone (Florinef):
      - Sole mineralocorticoid replacement, may be necessary with glucocorticoid replacement in cases of salt wasting due to the inability to maintain sodium levels, leading to elevated potassium even with adequate renal function.