Sodium Reabsorption in the Proximal Nephron

  • Sodium reabsorption in the proximal nephron tubule is coupledwith reabsorption of other key solutes and water, and with secretion of hydrogen.
  • Sodium reabsorption maintains sodium balance, so that sodium intake equals sodium excretion.
    – This is one of the most important functions of the kidney because:
    As the major cation of the extracellular fluid, the amount of sodium determines extracellular fluid volume (because water follows osmotic gradients), and extracellular fluid volume determines plasma volume, blood volume, and blood pressure, which are critical physiological determinants.
  • Two-thirds of sodium reabsorption occurs within the proximal tubule, which comprises both early and late segments.

Early proximal tubule:

  • Sodium reabsorption is linked to reabsorption of nutrients, inorganic and organic acids, and the secretion of hydrogen.
  • Transport occurs via two pathways:
    – The transcellular pathway, which transports substances through tubule cells;
    – The paracellular pathway, which moves substances through “leaky” tight junctions between tubule cells.
  • Sodium-potassium ATPase (aka, pump) actively pumps sodium out of the tubule cell, and brings potassium into it.
    – This exchange creates the electrochemical gradient that drives secondary transport of sodium and other solutes across the luminal membrane and into the tubule cell.
  • Luminal membrane cotransporters couple movement of sodium into the cell with movement of other solutes, including:
    – Glucose
    – Amino acids
    – Inorganic and organic acids.
  • These solutes move out of the cell via facilitated diffusion.
  • As a general rule, water follows sodium:
    – Transcellularly, it passes through aquaporin 1 channelslocated on the luminal and basolateral membranes;
    – Paracellularly, it passes between the tight junctions of tubule cells.
  • Countertransporter exchanges sodium for hydrogen, which it secretes into the tubular lumen.
  • Reactions within the cell produce bicarbonate, which is reabsorbed via facilitated diffusion.

Late Proximal Tubule:

  • Sodium and chloride reabsorption are linked in the late proximal tubule.
    – To understand why this is so, consider that most other solutes were reabsorbed within the early proximal tubule; chloride is not, and, therefore, remains in the tubule fluid as it enters the late proximal tubule.
  • Sodium-potassium pump creates gradient that drives luminal membrane counter transporters:
    – One moves sodium into the cell and hydrogen into the lumen.
    – The other moves chloride into the cell and formate into the lumen (formate ions are metabolic byproducts).
  • Chloride then passes through the basolateral membrane down its concentration gradient via simple diffusion.
  • Both sodium and chloride pass through “leaky” tight junctions between the tubule cells; this is another example of the paracellular pathway.

Glomerulotubular balance

  • Maintains a nearly constant rate of sodium reabsorption, despite changes in GFR.
  • In response to changes in GFR, the proximal tubule alters the total amount of sodium it reabsorbs so that the rate of sodium reabsorption is held at ~67%.
  • However, glomerulotubular balance changes in response to changes in extracellular fluid volume:
    – When ECF volume contracts, total sodium and water reabsorption is increased; this reflects the body’s attempt to increase ECF volume.
    – When ECF volume expands, total sodium and water reabsorption is decreased; excess sodium and water are excreted in the urine in attempt to decrease ECF volume.

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