• 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.