Coupon Accepted Successfully!


Sodium Reabsorption

It occurs in all parts of the tubule except the thin descending part.

It is active reabsorption except in thin ascending portion (where it is passive).

The various mechanisms in different parts of the tubule are:




Na – Amino acids

Na – Citrate / PO4 / SO4 / Lactate


Cl- driven Na+ transport


No reabsorption


Passive (no transportation)


Na+- K+ - 2Cl-; Na-H


Na+ - Cl-


P cell (ENaC)


(P cell = principal cell; ENaC = Epithelial sodium channel)

(Aldosterone acts on collecting duct to increase Na+ reabsorption. It does this by increasing the number of open EnaCs and also by increasing the number of Na+ - K+ ATPase)

Other points

Out of the total filtered load of Na+, 99.4% is reabsorbed 65% in PCT; 25% in Henle; 10% in DCT/CT. Na+ reabsorption is increased by aldosterone (which acts on collecting duct) and by angiotensin II (which acts on PCT) Most of the sodium is reabsorbed along with Cl Natriuresis is caused by PGE2, IL-1, ANP, ouabain, Endothelin.


  1. Glucose is reabsorbed by secondary active transport.SGLT-1,2
  2. All the glucose is reabsorbed in PCT.The
  3. TmG (tubular maximum for glucose i.e. the maximum rate of absorption of glucose by the tubule) is 375 mg/min in males and 300mg/min in females.
  4. Given that the TmG is 375mg/min in males, by calculation, the renal threshold for glucose in blood would be
  5. 300mg/dL.
  6. The actual value of renal Threshold is much less than this; it is 200mg/dL in arterial and 180mg/dL in venous blood.
  7. This deviation in the renal threshold (from the calculated predicted value) in called splay.
  8. The reason for splay is heterogeneity of nephrons (i.e. not all nephrons have TmG of 375 mg/min); further, not all nephrons are maximally active simultaneously.  


Water reabsorption is passive, following the osmotic gradient. The total glomerular filtered load is approximately 180L/day. Out of this, the amount of urine output can vary from 500mL (osmolality of 1400 mosm/L) to 23.3 Litres (osmolality of 30 mosm/L). Water reabsorption is facilitated by water channels (aquaporins) There are various types of aquaporins:




Aquaporin 1

Luminal membrane of PCT

Aquaporin 2

Luminal membrane of CD

Aquaporin 3

Basolateral membrane of CD

Aquaporin 4


Aquaporin 5

Salivary, lacrimal, respiratory system

The % of water reabsorption in the various segments is as follows

1.  PCT 60-70%           
2.  Loop of Henle 15%

3.  Distal Tubule 20%

a.  DCT 5%

b.  CT 15%


Cortical CT 10%

Medullary CT 4.7%


Permeability and Transport in Various Segments of the Nephron.








Active Transport of Na+

Loop of Henle





Thin descending limb





Thin ascending limb





Thick ascending limb





Distal convoluted tubule





Collecting tubule





Cortical portion





Outer medullary portion





Inner medullary portion






The tonicity of tubular fluid at various segments


1.  At the end of PCT :Isotonic


2.  As it goes down the descending limb :Hypertonic


3.  As it goes up the ascending limb:It first, isotonic, then hypotonic.


4.  At the top of ascending limb, it is hypotonic (The ascending limb is called the diluting segment) The permeability characteristics of the tubular


Segments to water is as follows: 







Thin Descending Limb

Highly permeable



Thin ascending limb

Not permeable

Highly permeable


Thick ascending limb (TAL)

Not permeable



[However, TAL has Na+ - K+ - Cl- cotransporter]



The DCT is relatively impermeable to water (Therefore, there is continued dilution of the tubular fluid as it goes along the DCT)


6.  Collecting Duct It becomes permeable to water in the presence of ADH; ADH inserts aquaporin 2 channels in the luminal membrane of collecting duct cells.

Counter Current Mechanism

There are 2 counter current mechanisms in kidney

Counter current multiplier, in loop of Henle (Produces osmolality gradient of medulla 1200 mosm/L)


2.  Counter current exchanger, in vasa recta (Maintains medullary osmolality gradient by selectively reabsorbing water only.


The counter current mechanism depends on the gradient of osmolality in the medullary interstitium. The medullary interstitial gradient depends on


1.  Active transport of Na+ at thick ascending limb (by Na+ - K+ - 2Cl- Co- transporter)


2.  Passive movement of Na+/Cl- out of thin ascending limb without water


3.  (Refer to the permeability characteristics of the tubule)


4.  Permeability of thin descending limb to water


5.  Urea, also contributes


The inner medullary collect duct is significantly permeable to urea; ADH increase this permeability)


The longer the loop of Henle, the greater can be the medullary interstitial osmotic gradient created; thus, the concentration ability is determined by the length of the loop of Henle.

Once the interstitial osmotic gradient is established by the counter current multiplier, it is maintained by the counter current exchange mechanism of the vasa recta; without the counter current exchange mechanism, all the good work of the counter current multiplier will soon be lost. The counter current multiplier mechanism is active whereas the counter current exchange mechanism is passive

Once the medullary interstitial osmotic gradient is established, water can move from the collecting in the presence of ADH

Note that in the cortical collecting duct segment, the urine can at best be concentrated up to isotonicity only; as it moves down the medulla collecting duct, the urine can be concentrated up to the maximum limit determine a by the maximum gradient existing in the medullary interstitium.



Difference between Water and Osmotic diuresis

Water diuresis

Osmotic diuresis

This is by inhibition of ADH

This is by osmosis

Absorption in PCT is normal

Absorption in PCT is decreased

Maximum limit of diuresis is 16ml/min

No such limit


1.  Active reabsorption in PCT; secreted in DCT. K+ secretion is decreased when the amount of Na+ reaching the DCT is small.


2.  K+ secretion is also decreased when the H+ secretion is increased


3.  (In DCT, Na+ is reabsorbed and K+ and H+ compete for their secretion for the amount of Na+ reabsorbed)


4.  K+ is the only electrolyte that is reabsorbed as well as secreted.


5.  65% of the K+ is reabsorbed in PCT, 25% in loop and < 10% reaches the distal rephron

For K+ and H+, remember the terms ‘hypokalemia i.e. alkalosis and hyperkalemic acidosis’.

Hydrogen Secretion

Occurs in PCT, DCT and CD



i. Na+ - H+ exchanger

ii. For each H+ that is secreted, effectively 1 Na+ and 1 HCO3- is reabsorbed.

 iii. (The handling of the secreted H+ in PCT is by carbonic anhydrase)


The secreted H+ in PCT does not acidity the urine; it only helps in the reabsorption of Na+ and HCO3-.

Since the secreted H+ in the PCT is quick by handled, the secretion of H+ in, PCT can be called a high-capacity, low- gradient system. i.e. the capacity is high but the acidification is not there.




  1. ATP – driven proton (H+) pump
  2. H+ - K+ ATPase
The secreted H+ here helps to acidify the urine. Since the secreted H+ is not as quickly handled (recall that there is no carbonic anhydrase in the luminal membrane of DCT), the limit of H+ secretion is reached quickly. Therefore, the H+ secretion here can be called a low-capacity, high-gradient system. i.e. the capacity is low but the acidification is significant.

Clearance :
Clearance for a substance ‘A’ is         

  • Definition: defined as that volume of plasma that is required to contain that much amount of the substance A which is present in one minute’s urine. Its unit is mL/min
  • Formula

It is given by the formula:


P= Where,

C = clearance

U = concentration of the substance in the urine

V = urine flow

P = concentration of the substance in the plasma




  If renal clearance is more than GFR.

  If renal clearance is less than GFR. 

  If renal clearance is same as GFR. 



Tubular secretion

Tubular reabsorption

No secretion & no reabsorption


1.  Filtered Load = Glomerular Filtration Rate x Plasma Concentration,


2.  Tm: no Tm for urea chloride water as passively reabsorbed.


3.  Clearance of Inulin gives GFR (125ml/min)

Extraction Ratio

1.  The fraction of a substance removed from the blood flowing through the kidney or other organ; it is calculated from the formula (RA—RV)/RA, where A and V, respectively, are the concentrations of the substance in Renal artery and vein respectively. For instance, para aminohippuric acid (PAH) is almost completely excreted in the final urine, and thus almost none is found in the venous return (RV ~ 0). Therefore, the extraction ration of PAH ~1. This is why PAH is used in PAH clearance to estimate renal plasma flow.


2.  Clearance of paramino hippuric acid (PAH) gives renal plasma flow (625 ml/min)


3.  Since the extraction ratio of PAH is 0.9 (90%), the value obtained is effective renal plasma flow (ERPF)



Other Points

Clearance is just a mathematical (theoretical) concept eg. Clearance of glucose is normally zero because there is no glucose in the urine. It does not mean that there is no glucose in blood !


Graph showing the effect of increasing plasma concentration on clearance.


1.  For a substance that is reabsorbed its Clearance is less than GFR and on increasing its plasma conc. above renal threshold its Clearance starts increasing. It can become as high as GFR itself but not more than that as they as always reabsorbed eg Glucose.


2.  Whereas for any substance that is secreted it has a Clearance more than GFR and on increasing its plasma conc. its Clearance starts decreasing. It can become as low as GFR again but not less than that.eg PAH Clearance.


3.  Whereas a substance that as no secretion no reabsorption i.e. GFR= Clearance, increasing the plasma conc. Doesn’t affect Clearance at all it remains same as GFR.

Free Water Clearance (CH2O)

This is the difference between actual urine output and the urine output calculated based on clearance of osmoles


CH20 =  V - Uosm X V       where V = actual urine output



(If the value is positive, the urine is hypotonic; if the value is negative, the urine is hypertomic)

Urinary Buffers

Help in acid secretion    

Type of buffer



Bicarbonate(noninducible buffer)


In PCT, it is mostly bicarbonate buffer

Phosphate (noninducible buffer)



Ammonia (inducible buffer)


Both PCT & DCT

Ammonia buffer system: The principal reaction producing NH4+ in cells is conversion of glutamine to glutamate. This reaction is catalyzed by the enzyme glutaminase, which is abundant in renal tubular cells. pK' of this buffer system is 9.0. In chronic acidosis, the amount of NH4+ excreted at any given urine pH also increases, because more NH3 enters the tubular urine. The effect of this adaptation of NH3 secretion, is a further removal of H+ from the tubular fluid and consequently a further enhancement of H+ secretion.


2.  Limiting pH of urine = 4.5

Factors affecting acid secretion


a.  Intracellular PCO2 When PCO2 in high, acid secretion is increased

b.  K+ depletion This increases acid secretion

Hypokalemia tends to cause alkalosis and vice versa.
Hyperkalemia tends to cause acidosis and vice versa.
a. If carbonic anhydrase is inhibited, acid secretion is decreased
b. Aldosterone: This increases Na+ reabsorption and increases K+ and H+ secretion



3.  Titratable Acid :- This is measured by the amount of alkali to be added to urine to make the pH 7.4. Titratable acid mainly reflects the buffering by phosphate buffer. pH of filterate doesnot change till DCT


a.  Net acid excretion: Titratable acid + NH4 excreted – HCO3- excreted.

b.  Net HCO3- gain: Same formula as for net acid excretion.

Test Your Skills Now!
Take a Quiz now
Reviewer Name