Untitled Quiz

Cortisol

• Cortisol is secreted by the adrenal cortex and is a significant component of the stress response
• Influences protein synthesis and catabolism
  • Increases protein synthesis in the liver
  • Promotes catabolism in the muscles
• Works synergistically with glucagon and epinephrine
• Promotes lipolysis (breakdown of fatty acids) in the extremities
  • Acute stage - Promotes the breakdown of fatty acids for energy
  • Long-term - Redistributes fat, promotes lipogenesis in the face, and trunk
    • Cushingoid signs - Fat pad at the back of the neck (buffalo hump), moon face, or increased abdominal fat
• May be linked to increased autoimmune responses
• Linked to decreased levels of IL-1, 2, 6, and TNF-a which helps limit damage
• Causes a T-helper 2 (Th2) shift, increasing immunity
  • Th1 - Promotes cell-mediated immunity (immune system directly attacks infected cells)
  • Th2 - Increases humoral immunity (antibody production and defense against pathogens)
  • A balance of Th1 & Th2 is required to prevent immune dysfunction
• Cortisol suppresses Th1, decreasing cellular immunity
• Cortisol promotes Th2, increasing humoral immunity and anti-inflammatory response
  • This is called the T-helper 2 shift

Addison Disease

• Characterized by low cortisol and mineralocorticoid secretion
• Reduced cortisol levels limit required hormonal effects

Cushing Syndrome/Disease

• Characterized by excessive cortisol secretion
• May be caused by excessive corticosteroid medication
• Symptoms include: hyperglycemia (steroid diabetes), hypertension edema, poor wound healing (risk for infection), and Cushingoid signs

Zona Reticularis

• Innermost layer of the adrenal cortex
• Produces gonadocorticoids, primarily DHEA (dehydroepiandrosterone)
• DHEA is a weak androgen that regulates male/female traits
• DHEA and its sulphated form (DHEA-Sulphate) are converted to testosterone (males) or estrogen (females)
• Excess DHEA can lead to increased virilisation (male traits in females) or hirsutism (facial hair in women)
  • Common in PCOS (Polycystic Ovarian Syndrome)

Hypothalamic-Pituitary-Adrenal Axis (HPA)

• The HPA is the physiological response to stress
• No matter the stimuli or stressor, the response is always the same
• Exogenous stressors: e.g. Heart disease - A person may not have the cardiac reserve to cope with catecholamine surge during stress
• The stress response involves:
  • Hypothalamus - Stimulates the locus ceruleus, activating the sympathetic nervous system (SNS)
  • Adrenal Medulla - Releases catecholamines
    • β-1 receptor - Increases heart rate (HR) and contractility, and dilates bronchioles (mainly binds epinephrine)
    • α-1 receptor - Increases total peripheral resistance (TPR) (mainly binds norepinephrine)
  • Adrenal Cortex - Releases cortisol and aldosterone

Chronic Stress Feedback

• Function
  • Negative feedback systems become blunted and desensitized, losing responsiveness to increased cortisol levels
  • Increased cortisol causes the hypothalamus to secrete more CRF (corticotropin-releasing factor)
  • Increased cortisol causes the anterior pituitary to secrete more ACTH (adrenocorticotropic hormone)
  • Corticoid effects are greater than catecholamine effects
• Consequences
  • Neural and hormonal pathways become dysfunctional with prolonged activation, leading to overactivation of the HPA axis
  • Loss of muscle mass due to gluconeogenesis and protein catabolism
  • Nitrogen depletion due to muscle catabolism
  • Increased nitrogen excretion in urine
  • Immune suppression through decreased T-cells and thymic atrophy
  • Hyperglycemia
  • Cardiovascular wear and tear due to constant catecholamine release
• Impact:
  • Symptoms: Hypertension, renal and vascular disease, sustained hyperglycemia
  • Example: Controlled diabetes are harder to manage in hospital settings due to the stress response