6.

RENAL CONCENTRATION AND

DILUTION OF THE URINE.

Prof. Sherif W. Mansour

Physiology dpt., Mutah School of medicine
2020-2021
A. Regulation of plasma osmolarity
■   is accomplished by varying the amount of water excreted relative to the amount of solute
excreted (i.e., by varying urine osmolarity).
1. Response to water deprivation
2. Response to water intake
B. Production of concentrated urine
■   is also called hyperosmotic urine, in which urine osmolarity > blood osmolarity.
■   is produced when circulating ADH levels are high (e.g., water deprivation, volume
depletion,SIADH).

1. Cortico-papillary osmotic gradient—high ADH

■   is the gradient of osmolarity from the cortex (300 mOsm/L) to the papilla (1200 mOsm/L)
and is composed primarily of NaCl and urea.
■   is established by countercurrent multiplication and urea recycling.
■   is maintained by countercurrent exchange in the vasa recta.
a. Countercurrent multiplication in the loop of Henle
■   depends on NaCl reabsorption in the thick ascending limb and countercurrent flow in
the descending and ascending limbs of the loop of Henle.
■   is augmented by ADH, which stimulates NaCl reabsorption in the thick ascending
limb. Therefore, the presence of ADH increases the size of the corticopapillary
osmotic gradient.
b. Urea recycling from the inner medullary collecting ducts into the medullary interstitial
fluid also is augmented by ADH (by stimulating the UT1 transporter).
c. Vasa recta are the capillaries that supply the loop of Henle. They maintain the cortico-
papillary gradient by serving as osmotic exchangers. Vasa recta blood equilibrates
osmotically with the interstitial fluid of the medulla and papilla.
2. Proximal tubule—high ADH
■   The osmolarity of the glomerular filtrate is identical to that of plasma (300 mOsm/L).
■   2/3 of the filtered H2O is reabsorbed isosmotically (with Na+, Cl-, HCO3-, glucose,
amino acids, and so forth) in the proximal tubule.
■   TF/P osm = 1.0 throughout the proximal tubule because H2O is reabsorbed isosmotically
with solute.
3. Thick ascending limb of the loop of Henle—high ADH,   is called the diluting segment.
■■   reabsorbs NaCl by the Na+–K+–2Cl- cotransporter.
TF: Tubular Fluid P: Plasma.
■   is impermeable to H2O. Therefore, H2O is not reabsorbed with NaCl, and the tubular fluid
becomes dilute.
■   The fluid that leaves the thick ascending limb has an osmolarity of 100 mOsm/L and
TF/Posm < 1.0 as a result of the dilution process.
4. Early distal tubule—high ADH,    is called the cortical diluting segment.
■   Like the thick ascending limb, the early distal tubule reabsorbs NaCl but is impermeable
to water. Consequently, tubular fluid is further diluted.
5. Late distal tubule—high ADH
■   ADH increases the H2O permeability of the principal cells of the late distal tubule.
■   H2O is reabsorbed from the tubule until the osmolarity of distal tubular fluid equals
that of the surrounding interstitial fluid in the renal cortex (300 mOsm/L).
■   TF/Posm = 1.0 at the end of the distal tubule because osmotic equilibration occurs in the
presence of ADH.
6. Collecting ducts—high ADH
■   As in the late distal tubule, ADH increases the H2O permeability of the principal cells of
the collecting ducts.
■   As tubular fluid flows through the collecting ducts, it passes through the corticopapillary
gradient (regions of increasingly higher osmolarity), which was previously established
by countercurrent multiplication and urea recycling.
 I- Countercurrent mechanisms

Types: 1-countercurrent multiplier. 2-countercurrent exchanger.

1- Countercurrent multiplier mechanism.
• It is the mechanism by which the kidney can increase osmotic pressure in the renal medulla
to 1200 mosmol/L (in cortex = 300 mosmol/L).
• Hypertoncity in the renal medulla → shift of water from collecting tubules to renal
interstitium & blood flow of vasa recta → concentrated urine.
Loop of Henle is a countercurrent multiplier:
1- currents of fluids run in opposite direction,
parallel to & near to each other
(descending & ascending limbs).
2- Descending limb is permeable to water
but not to Na+, while the ascending limb
is impermeable to water but permeable to Na+.
3- Thick ascending part of the loop has
sodium pump which need energy derived from ATP.
Steps of countercurrent multiplier mechanism:
The first step:
- Active transport of Na+ from the thick ascending part of Henle’s loop followed by co-
transport of K+, 2Cl- (or other ions like Ca2+ & Mg2+).
- This is not followed by water reabsorption because the whole ascending limb is nearly
impermeable to water.
- This lead to:
a) Medulla become hypertonic.
Fluid passing to DCT become hypotonic.
The second Step:
- Reabsorption of water of the tubular fluid in thin descending part (& from the collecting
tubules) to the hypertonic medulla by osmosis.
- With time, Na+ & other ions remain inside lumen → progressive increasing of their
concentration, till reach their maximum concentration in the fluid at the bottom of the
loop =1200 mosmol/L.
- Also, Na CL passes from medulla to lumen of descending part → increase or multiply
the amount of Na CL delivered to thick part (more Na pump).
The third step:
- Some of NaCL diffuses passively out the thin portion of the ascending loop of Henle to
the interstitium → Marked increase osmolality of medulla.
Then repetition of the first step & so on.
2- Countercurrent exchanger Mechanism:
• It is the function of vasa recta to Maintains the medullary hypertonicity.
• Vasa recta is a U shaped long thin capillary loop that supply the renal medulla & run
adjacent to the Henel’s loop of juxta medullary nephrons.
• It induces absorption of 20% of NaCL & 15% H2O loads inside the vasa recta to
general circulation.
Steps of counter current exchanger mechanism:
- In the descending limb of vasa recta:
1- Both NaCL & urea diffuse from renal medulla to the blood (because of their high
concentration in the medulla).
2- Water pass to the hypertonic medulla (because the hydrostatic pressure in descending
limb is higher than the osmotic pressure of plasma proteins).

- In the ascending limb (the reverse occur)

1- As blood flows up, NaCL & urea diffuse out to the medullary interstitium (because
their high concentration in the vasa recta).
2- While, water is reabsorbed (due to increased concentration of plasma proteins).
This water reabsorption represents the water that leaves the descending loop of Henle &
the collecting tubules.

So, vasa recta keeps the high tonicity of the medulla by 2 mechanisms:
1- Adjust removal of NaCL from medulla by blood flow.
2- Reabsorption of excess water reaching the medulla to the blood.
 II- Urea cycle

• Re-circulation of urea has a role in hyper-osmolality of renal medulla

• The only parts that are permeable to urea are collecting tubules, the lower thin
descending part of Henle’s loop & the thin ascending limb.
• Thick ascending part of loop of Henle, DCT & cortical collecting tubules are all
impermeable to urea.

• Steps:
a- Water reabsorption from the medullary collecting tubules (by the high osmolality of
renal medulla) → marked elevation in urea concentration → diffuses to renal interstitium
(helped by ADH) → increase osmolality in renal medulla.
b- Then, urea enter again to the lumen of the descending & thin ascending parts of Henel’s
loop to re-circulation again and again till it reaches the medullary collecting tubules to
start a new cycle and so on.
• Urea cycle add about 500 mosmol/litre to the renal medulla → important role in urine
concentration (especially with high protein diet as it give large amount of urea).
• Low plasma levels of ADH diminish efficiency of urea to create high osmolality in the
renal medulla.
Thank You