Adrenal physiology

Sub-section: Adrenal Section: Endocrine

Adrenal Cortex

• All synthesized from cholesterol

Mineralocorticoid (Zona Glomerulosa)

• Stimulation
  • Mainly Aldosterone
  • Secretion stimulated by Angiotensin II
    • Can also be stimulated by ACTH and blood K+ level
  • Renin-angiotensin-aldosterone axis
    • Responds to Na+ delivery to Distal Tubules
      • Low if hypovolaemic, shock, Renal Artery constriction, hyponatraemia
    • Low Na+ stimulates Renin release (from JGA)
  • Renin
    • Converts angiotensinogen from liver to Angiotensin I
    • Further cleavage by ACE in lungs to Angiotensin II
    • Also stimulated by hyperkalaemia
    • Inhibited by hypokalaemia
  • Angiotensin II
    • Potent vasoconstrictor
    • Stimulates aldosterone release
• Actions
  • Aldosterone actions
    • Regulates circulating fluid volume and electrolyte balance
    • Acts on distal renal tubule
      • ↑ Na+ (and H2O) resorption to ↑ circulating volume
        • At the expense of K+ or H+ (lost in urine)
      • Also causes chloride retention
  • Negative feedback
    • Increased delivery of Na+ to distal tubules inhibits renin release

Glucocorticoid (Zona Fasciculata)

• Stimulation
  • Mainly cortisol and corticosterone
  • Hypothalamus releases Corticotropin-releasing hormone (CRH) in response to stress
    • Stimulates Adrenocorticotropic hormone (ACTH) release from Anterior Pituitary
      • Normally pulsatile fashion, has circadian rhythm
        • Highest levels when waking, lowest early evening
  • ACTH stimulates glucocorticoid secretion
• Actions
  • Broad ranging effects on most organs
    • Generally create catabolic state (stress response)
  • Glucose and protein metabolism
    • Hepatic gluconeogenesis and glycogenolysis ⇒ Hyperglycaemia
    • Glucose uptake in peripheral tissues inhibited, general state of insulin resistance
    • Protein catabolism in muscle
    • Lipolysis in fat (and release of FFA’s)
  • Weak mineralocorticoid effects
  • Stimulates - gut Ca2+ absorption and ⇧ urinary excretion (high levels cause osteoporosis)
  • Potent immunosuppressant and anti-inflammatory effect
  • Important cardiovascular effect
    • Glucocorticoids enhance the effect of catecholamines by sensitizing arterial smooth muscle to beta-adrenergic stimulation

Sex Steroids (Zone Reticularis)

• Weakly androgenic steroids under action of ACTH
• Dehydroepiandrosterone (DHEAS) most important
  • Converted in peripheral tissues to
    • Dihydrotestosterone and Oestradiol via Aromatase system

Medulla

• Catecholamine
  • Synthesis
    • All from Tyrosine, via DOPA
      • Dopamine
        • Dopamine β-hydroxylase
      • Noradrenaline
        • PNMT (only in Adrenal)
      • Adrenaline
        • Sympathetic stimulation releases stored catecholamines
• Actions
  • Exert effects by binding to α- and β-adrenoreceptors
    • α- Higher affinity for noradrenaline
    • β- Higher affinity for adrenaline
  • “Fight or flight”
    • ⇧HR, BP, Cardiac output
    • CNS excitation
    • ⇧ Muscle and CNS perfusion
    • Decrease splanchnic perfusion
    • Metabolic effects – Lipolysis, gluconeogenesis, glycogenolysis
• Clearance
  • Potent, but short acting
    • T1/2 = 1 minute (therefore hard to measure)
    • Noradrenaline and Adrenaline inactivated by Monoamine Oxidase and COMT
      • Breakdown products are
        • Metanephrine and Normetanephrine
          • Can detect these in both plasma and urine
          • Plasma levels of metanephrines much more stable
            • Better diagnostic markers
  • Catecholamine metabolites secreted renally