Kidney and acid base physiology : part 3

Distal tubule (DT) and collecting duct (CD)

Distal tubule and the collecting duct are the chief sites of K⁺ secretion. Along with that about 7% of filtered NaCl and about 10-15 % of water (in principal cells only in the presence of ADH hormone) is also absorbed here. As for the details, let us just go through the following points and then compare with the previous two sections:

1.      The key player is Na⁺-Cl^- symporter in the early Distal tubule which moves NaCl inside the cell.

2.      This segment is totally impermeable to water hence its name ‘cortical diluting segment.

3.      Thiazide diuretics also act here and inhibit NaCl transport inside the cell.

4.      Principal cells are involved in the potassium secretion where it reaches a high concentration via Na⁺/K⁺ ATPase.

5.      Na⁺ also gets absorbed here through epithelial sodium channels (ENaC) channel present on the apical surface.

6.      The inward movement of Na results in a relatively low voltage in the lumen as compared to the voltage across the basolateral surface. This lumen negative transepithelial voltage acts as a driving force for K⁺ from blood to the lumen via voltage gated K⁺ channels on the apical surface (which are inhibited by high cytosolic Ca⁺⁺ or H^+.

7.      Sensitivity of the K channels in the principal cells can explain stimulation of K⁺ excretion during metabolic alkalosis or increased bicarbonate excretion.

8.      Intercalated cells have very less Na/K ATPase activity and absolutely no conductance channel on the apical surface for ions; all they possess is gastric parietal type H⁺/K⁺ ATPases which are active constitutively and Colonic type H⁺/K⁺ ATPases which get activated only during dietary NaCl depletion, potassium depletion and acidotic condition.

9.      In the intercalated cells of the CD and late DT, H⁺-ATPase and H⁺/K⁺ ATPase are present on the apical membrane to facilitate the H⁺ ion exit from the cell into the lumen.

10.  The HCO₃^- leave the cell via AE1 (as described previously). Aldosterone increase the H⁺ secretion by stimulating H⁺-ATPase.

11.  Resorption of K⁺ ions occurs only when there is a need for K⁺ conservation. On dietary loading , area of basolateral surface and activity of Na⁺/K⁺ ATPase increases.

12.  Stimulation of K transport by mineralocorticoids

a.       Activate Na/K pump

b.      Increased rate of electrogenic cationic exchange

c.       Hyperpolarisation of cell negative basolateral membrane voltage

13.  There are two types of K⁺ channels on the apical membrane: the secretory type ( with a small conductance and a high open probability; inhibited by increased cytosolic H⁺ and Ca⁺⁺ concentration) and maxi-K⁺ type (large conductance and low open probability; high cytosolic Ca⁺⁺ concentration activate this channel).

14.  Amiloride inhibits K⁺ secretion by reducing the lumen - negative transepithelial voltage by blocking the Na⁺ channels from the luminal side.

15.  Aldosterone penetrates the cell from the interstitial side and combines with the mineralocorticoid receptor MR. This complex enters the nucleus and promotes mRNA synthesis which then directs the synthesis of Aldosterone-induced-proteins (AIP).

16.  The AIPs include Na+ channels and Na/K-ATPase and increase ATP production by mitochondria. All these act to promote sodium absorption and increase K+ and H+ secretion.

17.  Spironolactone binds to MR and prevents aldosterone effects.