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.
