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aldosterone

aldosterone

introduction

  • A mineralocorticoid secreted from adrenal cortex & rapidly conjugated by liver (and kidney) so T1/2 = 20 minutes

secretion:

stimulated by:

  • ACTH (via cAMP & protein kinase A);
  • angiotensin II (via diacylglycerol & protein kinase C);
    • ⇒ cholesterol → pregnenolone, &,
    • ⇒ corticosterone → aldosterone;
  • incr. plasma [K];
  • decr. plasma [Na];

with stimulation of glucocorticoid secretion:

  • surgery, anxiety, physical trauma, haemorrhage;

without stimulation of glucocorticoid secretion:

  • K/Na changes;
  • constriction of IVC in thorax;
  • standing;
  • sec. hyperaldosteronism: CCF, cirrhosis, nephrosis;

actions:

  • Binds to i/cell. mineralocorticoid receptors, exposing DNA binding domain of receptor which binds to DNA and promotes formation of mRNA's that in turn incr. protein synthesis, esp. Na-K ATPase, thus providing target cells with more Na pumps; This process takes 10-30 minutes;
    • ⇒ incr. reabsorption of Na from urine, sweat, saliva, gastric juice;
    • ⇒ Na retention ⇒ incr. ECFV ⇒ incr. blood volume ⇒ incr. renal perfusion
    • ⇒ inhibition of renin release ⇒ decr. angio II
    • ⇒ decr. aldosterone;
    • ⇒ decr. reabsorption of K from urine, etc; ⇒ K depletion;
  • NB.
    • as water is retained with the osmotically active Na ions, significant hypernatraemia does not occur;
    • if Na intake is restricted, total body Na will not rise;
    • when ECFV passes certain point, Na excretion is usually increased in spite of continued aldosterone action on renal tubules “escape phenomenon” prevents XS ECFV that would cause oedema and this is probably due to incr. ANP.
    • This escape may not occur in certain diseases ⇒ oedema results;
    • XS mineralocorticoid activity may cause prolonged K diuresis, and this K depletion may in turn damage the kidney resulting in loss of concentrating ability and polyuria (hypokalaemic nephropathy).
  • Glucocorticoids also bind the receptors strongly and would have far greater mineralocorticoid activity if the enzyme 11 B-hydroxysteroid dehydrogenase did not metabolise the glucocorticoid to a 11-oxy derivative which does not bind the receptor.
    • Aldosterone is not affected by this enzyme;
    • Licorice contains glycyrrhetinic acid which inhibits this enzyme and ⇒ produces Na retention;
    • This enzyme is not found in heart/brain but mainly in kidney;
aldosterone.txt · Last modified: 2014/04/03 17:06 (external edit)