- 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.