Sodium Reabsorption in the Distal Nephron

  • Key function of the kidneys is to ensure sodium balance:
    Sodium intake = sodium excretion.

Sodium Reabsorption by Segment:

  • 67% of filtered load is reabsorbed in proximal tubule.
  • 25% in thick ascending limb
  • 5% in the early distal tubule
  • 3% in the late distal tubule and collecting duct.
  • Less than 1% of the filtered load is excreted in the urine.

Load-dependent Sodium Reabsorption

  • In the distal segments, ensures that reabsorption rate remains relatively constant despite changes in filtered load.

Thick ascending limb:

  • Sodium reabsorption is linked to potassium and chloride reabsorption.
  • Sodium-potassium ATPase on basolateral membrane pumps sodium out of cell, potassium into it.
  • Drives cotransport of sodium, potassium, and chloride into the cell.
    In presence of ADH, activity of cotransporter is increased;
    In presence of Loop diuretics, chloride-binding site is blocked, cotransport ceases, and sodium is not reabsorbed.
  • Chloride and potassium diffuse out of the cell through the basolateral membrane;
    some potassium “leaks” back into the lumen.
  • Thick ascending limb is impermeable to water.

Early distal tubule:

  • Sodium and chloride reabsorption are linked.
  • Sodium-potassium ATPase creates electrochemical gradient that drives cotransport of sodium and chloride from lumen into cell.
    – Thiazide diuretics block chloride binding site on contransporter, so sodium is not reabsorbed.
  • Chloride exits via simple diffusion.
  • Early distal tubule is impermeable to water.

Late distal tubule and collecting duct:

  • Principal cells link sodium reabsorption to potassium secretion.
  • Sodium-potassium ATPase creates electrochemical gradient that drives sodium diffusion via epithelial sodium channels.
  • Potassium is secreted into lumen.
  • Aldosterone increases sodium reabsorption and potassium secretion.
  • Late distal tubule and collecting duct are only permeable to water in presence of ADH, which increases aquaporin-2 water channels.
  • Water exits cell via aquaporin 3 and 4 water channels.
    – K-sparing diuretics act on late distal tubule and collecting ducts to reduce sodium reabsorption and potassium secretion.

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