Question 4

Describe the renal handling of sodium.

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College Answer

A description of filtration and reabsorption, including amounts was required. Better answers
described sodium handling in a logical sequence as it progressed through the nephron including
the percentages reabsorbed in each segment. In addition to the amounts reabsorbed, the
mechanisms of transport across the tubular luminal and basolateral membranes into interstitial
space should have been described.


  • Sodium is freely filtered in the glomerulus.
  • 65% is then reabsorbed in the proximal tubule:
    • The reabsorption is driven by a concentration gradient which is created by the action of basolateral Na+/K+ ATPase
    • Most of the sodium is reabsorbed by the NHE3 sodium-hydrogen exchanger
    • Other transport proteins include SGLT2, phosphate co-transporter Npt2a and multiple organic anion co-transporters
  • None is reabsorbed in the thin descending limb:
    • it is impermeable to sodium
  • Some minimal amount is reabsorbed in the thin ascending limb
    • it is permeable to ions, but not to water
    • Some sodium is reabsorbed passively here
  • 25% is reabsorbed in the thick ascending limb:
    • Most of this is by the frusemide-sensitive NKCC2 co-transporter
  • 5-10% is reabsorbed in the distal convoluted tubule:
    • ​​​​​​​Most of this is by the thiazide-sensitive NCC co-transporter
    • This step is load-sensitive, i.e. reabsorption increases whenever there is increased sodium delivery to this segment
  • 2% is reabsorbed in the collecting duct:
    • Most of this is passive, via the amiloride-sensitive ​​​​​​​ENaC channel
  • Regulation of sodium reabsorption:
    • ​​​​​​​Angiotensin II (increases reabsorption by increasing Na+/K+ ATPase activity in the proximal tubule, and increases NHE3 activity)
    • Aldosterone (increases ENaC activation in the collecting duct and Na+/K+ ATPase activity in the thick ascending limb)
    • Vasopressin (increases expression of ENaC in the collecting duct and NKCC2 in the thick ascending limb)
    • Catecholamines by increasing NKCC2 expression in the thick ascending limb


Weinstein, A. M. "Sodium and chloride transport: proximal nephron." Seldin and Giebisch's The Kidney. Elsevier Inc., 2008. 849-887.1081-1142

Reeves, W. Brian, and Thomas E. Andreoli. "Sodium chloride transport in the loop of Henle, distal convoluted tubule, and collecting duct." Seldin and Giebisch's The Kidney. Elsevier Inc., 2018 1143-1180

Matsubara, Mitsunobu. "Renal sodium handling for body fluid maintenance and blood pressure regulation." Yakugaku Zasshi 124.6 (2004): 301-309.