DISTAL TUBULAR

FUNCTION

Prof Harbindar Jeet Singh

Faculty of Medicine
Universiti Teknologi MARA
Objectives of this lecture

Distal tubular handling of NaCl

Calcium and magnesium

Potassium

Phosphate
The distal tubule is composed of three morphologically distinct
segments

1. Thick ascending limb of the loop of Henle (pars recta)

2. Macula densa

3. Distal convoluted tubule (pars convoluta)

The thick ascending limb can be divided into

iii) a medullary segment

v) a cortical segment
Transport of NaCl in the TAL

The thick ascending limb is involved in the transport of NaCl

from the lumen to the surrounding interstitium

Its epithelium is impermeable to water

It reabsorbs about 30 % of the NaCl filtered at the glomerulus

The reabsorption of NaCl is mediated by an Na+-K+-2Cl-

cotransport mechanism
This can be inhibited by loop diuretics like furosemide and
bumetanide

Vasopressin (ADH) strongly upregulates this co-transporter

in the thick ascending limb

The energy for this reabsorptive process is provided by the

Na+-K+-ATPase that is located in the basolateral plasma

Na+ exits the cell at the basolateral membrane via the

Na+-K+-ATPase, Cl- exits via the K+/Cl- co-transporter
Calcium handling by the TALH

About 15-20% of the filtered load of

Ca 2+ is reabsorbed in the TAL

About half of calcium reabsorption in

TALH is passive and the other half
is active.

The passive transport is via the

paracellular route, driven by the
positive lumen PD created by the
active reabsorption of
NaCl and the luminal membrane
recycling of K+.

The active component is transcellular.

Calcium enters via ECaC passively and
then extruded actively either through
Ca pump or Na+/Ca 2+ exchange and
active sodium extrusion
PTH increases Ca 2+reabsorption in the
TALH.
It increases the paracellular permeability
to calcium via an effect on claudin-16,
and perhaps also the some active
component of calcium transport.
Magnesium handling by the TALH
The TAL is the major site for magnesium reabsorption, accounting for 60-70%
of magnesium reabsorption

Like calcium, the mechanism of reabsorption of Mg 2+in the TALH is paracellular

and passive, involving a specific tight junction protein called paracellin-1/Claudin-
16. The driving force for paracellular magnesium reabsorption is the positive
lumen PD
Loop diuretics, like furosemide, which inhibit the Na+-K+-2Cl-co-transporter,
and prevent the establishment of the lumen positive PD inhibit Ca 2+ and Mg 2+
reabsorption
Lumen PTH enhances the reabsorption of
Mg 2+ by increasing NaCl
reabsorption generating a
trans-epithelial PD, and increasing
the passive permeability of TALH
to paracellular transport
Potassium handling in the TAL

There is net K+ reabsorption in the TAL, where about 25% of

the filtered load is reabsorbed.

Reabsorption is both passive via paracellular route because of

lumen-positive voltage, and transcellular route involving secondary
active Na+-K+-Cl cotransport (NKCC2).

Inhibited by loop diuretics like furosemide

The medullary TAL, which has a high basolateral-to-apical K+

permeability ratio exhibits net K+ reabsorption

The corticol TAL, which has a low basolateral-to-apical K+ permeability

ratio exhibits net K+ secretion
Tubular function (Distal Convoluted tubule - DCT)

The DCT begins beyond the macula densa and extends to the collecting duct

Reabsorption of NaCl is present in the DCT mainly via the transcellular route
involving the thiazide sensitive Na+/Cl cotransporter and the basolateral
Na+-K+-ATPase.

The Na+/Cl- co-transporter is up-regulated by aldosterone.

In the CCT Na+ reabsorption is mainly transcellular and mediated by the

principal cell.

About 5% of the filtered load is handled at the DCT and CCT.

Sodium crosses the apical membrane of the principal cell via the ENaC,
which is blocked by amiloride.

The medullary CT only reabsorbs about 3 % of the filtered load.

The late distal tubule (CNT) together with the initial collecting tubule (ICT)
has the greatest capacity for K+ secretion

The ICT and the CCT have approximately 70% principal cells (which secrete K+) and
30% intercalated cells (some of which reabsorb K+)

The secretion of potassium is a two-stage process

• Uptake by the cell from the interstitium by Na+-K+-ATPase at the basolateral

surface

a) Passive diffusion of potassium from the cell to the tubular

lumen

The luminal or apical membrane of the principal cells is highly permeable to K+

K+ secretion is sodium chloride dependent, and is inhibited by thiazide diuretics

In cases of potassium depletion, there is net reabsorption of K+ in

the late distal tubule. It occurs through the α intercalated cells.

The capacity for K+ secretion diminishes in the MCD. If anything there might be
some K+ reabsorption in the MCD
Mechanism of potassium secretion in the distal tubule

a) Uptake by the cell

from the interstitium
by Na+-K+-ATPase

a) Passive diffusion of
potassium from the
cell to the tubular
lumen
Renal tubular handling of potassium
A number of factors influence distal tubule K+ secretion
• Increased ECF K+ conc
a) by stimulation of Na+-K+-ATPase
b) increased aldosterone secretion

ii) NaCl delivery to the distal tubule

Increase NaCl delivery increases K+ secretion and reduced

delivery decreases K+ secretion by the distal tubule

iii) Effect of distal tubular flow rate increases K+ secretion

As might occur in increased ECFV or diuretic use

For a given increment in flow, distal secretion is greater
when K+ is high then when it is moderate
When K+ intake is low, flow has little effect on secretion
Potassium excretion as a function of plasma concentration

Intake
K+ secretion as function of distal tubular flow

Diet
• Aldosterone

Aldosterone stimulates active reabsorption of Na+ by the

principal cells, which is mediated through Na+-K+-ATPase
at the basolateral surface
Aldosterone increases the permeability of the luminal
membrane for potassium

i) Acute acidosis decreases potassium secretion, whereas

alkalosis increase potassium secretion

Acidification leads to complete cessation of channel activity.

conductance of both K+ and Na+ decreases

Chronic acidosis leads to an increase in K+ secretion

vi) Role of anions in potassium secretion

Infusion of sodium bicarbonate stimulates K+ excretion

K+ secretion rises sharply in the presence of poorly permeable
anions such as sulphate

vii) Effect of diuretics

Diuretics affect K+ excretion in several ways

a) Directly acting on the transport mechanism

e.g. carbonic anhydrase inhibitors stimulate secretion in
the distal tubule
b) Kaliopenic diuretics such as , spironolactone, amiloride,
triamterene inhibit K+ secretion
a) Furosemide and loop diuretics are powerful inhibitors of
Na+/K+/2Cl- co-transport mechanism in the TAL.
This collapses the positive luminal PD difference thereby
increasing potassium leakage.
The increased flow to the distal region also further
contributes to the increased secretion

i) Circadian fluctuations
K+ excretion by the kidney is lowest in the early morning
(5-6 am) and rises to peak in the late afternoon (4-6 pm)

This diurnal rhythm is independent of food intake or

activity.
i) Other hormones

a) Vasopressin
Vasopressin stimulates Na+ reabsorption and K+ secretion
in the distal tubule
The rise in Na+ reabsorption is triggered by activation of
basolateral V2 receptors, which increase apical membrane
Na+ conductance that is dependent on cAMP and PKA.
Concomittant depolarisation of the apical membrane
stimulates K+ secretion
Vasopressin also increases the activity of the
low-conductance K+ channels in the apical membrane
a) Insulin
Insulin reduces K+ excretion by the kidney independently
of changes in plasma K+ conc and aldosterone

It is possible that this action is associated with a reduction in

Na+ reabsorption secondary to the inhibition of apical sodium
channels by insulin

a) Glucocorticoids
Glucocorticoids stimulate K+ excretion by increased flow
and distal sodium delivery
Calcium and magnesium handling by the distal tubule

Approximately 10-15% of filtered calcium is reabsorbed in the distal tubule

As the PD is lumen negative and the calcium concentration is below that of

plasma, Ca 2+ absorption is therefore active in this segment

Calcium enters apically through ECaC, diffuses

across the cytosol bound to calbindin-D28K and
exits basolaterally through a calcium pump, or a
sodium-calcium exchanger

The DCT is the primary site for PTH action, stimulating Ca 2+ reabsorption via
c’AMP

The distal convoluted reabsorbs about 5-10% of the filtered load of magnesium.
Phosphate reabsorption

Approximately 10% of the filtered load of phosphate might be

reabsorbed in the DCT and the CCT.

This might only be evident during instances of phosphate deficiency.

THANK YOU
Potassium transport along the nephron