Question 10(p.2)

College Answer

Candidates were essentially expected to describe the fate of sodium as t passes through the
kidney from filtration at the glomerulus to ending up in the urine. Essentially, most Na+ is
reabsorbed at the proximal tubule (65%), reabsorption being down an electrochemical
gradient (inside cell negative and low Na+ concentration) which is maintained by active
Na+/K+ ATPase activity at the basolateral membrane. Then Loop of Henle reabsorbs a
further 15% of filtered Na+. At descending limb – no Na+ reabsorption. At ascending limb,
thick segment – active process as per proximal tubule, but mostly coupled to K+ and Cl- and
paracellular diffusion through tight junctions. Finally the distal convoluted tubule and
collecting ducts, a further almost 20% reabsorbed – leaving < 1%
Factors influencing loss are
- aldosterone = stimulates Na+ reabsorption at the collecting tubules
- intra renal factors such as interstitial pressure which is lowered during
hypovolaemia and reduced renal perfusion, thus promoting Na+ reabsorption
gradient
- sympathetic nervous system – influences interstitial pressure and increases renin
production
- angiotensin II – stimulates reabsorption at proximal tubule
- Atrial Naturetic Peptide/Factor – inhibits Na+ reabsorption
- Others – dopamine, cortisol, insulin => increase Na+ reabsorption, but minor
factors

Reference – Textbook of medical Physiology, Guyton, Chp 28

Discussion

• 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
  • Increased renal sodium delivery, which increases reabsorption in the DCT

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.