H3i: Outline the effect of diuretics on other solutes

  • Diuretics aim to ↑Na+ excretion to ↓ECF
  • By altering renal handling of Na+, this will have a knock-on effect on other solutes

K+ Excretion

  • Diuretic given proximally to the K+ secretory site (DCT, Collecting Duct)
  • By ↑Na+ & H2O loss will ↑tubular flow
  • This will ↑K+ secretion
  • ↓ECF volume will also stimulate Aldosterone, which promotes K+ excretion

HCO3- Excretion

  • CA: ↑HCO3– secretion & inhibition H+ secretion ∴metabolic acidosis
  • Loop + thiazide
    • ↓ECF volume causes subsequent ↑Na+ reabsorption at PCT
    • ↑Na+/H+ antiporter activity causing maximal HCO3– reabsorption at PCT (almost all)
    • ↓ECF volume
    • ↑Aldosterone
    • ↑H+ secretion by Principle Cells
    • Because almost all HCO3– is reabsorbed at PCT
    • H+ secretion to non-HCO3– buffers → which produces NEW HCO3–
    • Overall: METABOLIC ALKALOSIS
  • K+ sparing:
    • Inhibits Na+ reabsorption
    • Creates a -ve lumen voltage
    • ∴↓H+ secretion
    • METABOLIC ACIDOSIS

Ca2+ & Pi Excretion

  • All except K+ sparing alters Ca2+ excretion

PCT

  • Na + H2O loss
  • ↓solvent drag
  • ∴↓Ca2+ reabsorption
  • NB: Ca2+ is less soluble in alkaline urine → ∴predisposes to formation of Ca2+ containing stores

Loops

  • ↑Ca2+ loss by altering voltage
  • Normal LoH voltage is +ve
  • Drives Ca2+ paracellularly to Peritubular caps
  • ∴loss of +ve lumen voltage = loss of Ca2+ reabsorption

Thiazide

  • ↑Ca2+ reabsorption
  • Blocking Na/Cl symporter
  • ↓intrac Na++
  • ↑activity of Ca2+/3Na+ symporter
  • NB: Thiazides sometimes used to Tx Ca2+ stones in patients with high Ca2+ urine