FORMATION OF CONCENTRATED URINE HUMAN RENAL PHYSIOLOGY

1. Formation Of
Concentrated Urine
By
Dr. Nusrat Tariq
Associate Professor of Physiology
M.MIDC

2. countercurrent
system

4. Kidneys Conserve Water by
Excreting Concentrated Urine

5. The Basic Requirements For Forming A
Concentrated Urine :
(1) A high level of ADH
(2) Development and maintenance of
Hyperosmotic Renal Medullary
Interstitium

6. (1) A high level of ADH
?

7. (1) A high level of ADH:
increases the permeability of
the distal tubules and collecting
ducts to water

8. (2)Development and maintenance of
Hyperosmotic Renal Medullary
Interstitium by:
a)- countercurrent system
b)- urea recycling

9. a)countercurrent system
• 1. Countercurrent multiplier
• 2. Countercurrent exchanger

10. 1- Countercurrent multiplier:
• formed by loop of Henle , which deposits
NaCl in the deeper regions of the kidney
• establishes the medullary osmotic gradient
2- Countercurrent exchanger:
• formed by vasa recta.
• helps maintain the gradient

11. a)- Countercurrent System
1-Countercurrent Multiplication
The process for establishing the osmotic
gradient:
• Step 1
• Step 2
• Step 3
• Step 4

12. Step 1 is the single effect.
NaCl is reabsorbed out of the ascending limb and
deposited in the surrounding interstitial fluid
Interstitial fluid osmolarity increases to 400 mOsm/L.
The fluid in the ascending limb is diluted to 200
mOsm/L.
Fluid in the descending limb equilibrates with the
interstitial fluid, and its osmolarity also becomes 400
mOsm/L.

13. .

14. Step 2 is the flow of fluid.
New fluid with an osmolarity of 300 mOsm/L
enters the descending limb from P.T and an
equal volume of fluid is displaced from the
ascending limb.
As a result the high osmolarity fluid in the
descending limb (400 mOsm/L) is "pushed
down" toward the bend of the loop of Henle.
Even at this early stage, the medullary osmotic
gradient is beginning to develop.

15. .

16. Step 3 is the single effect again.
NaCl is reabsorbed out of the ascending limb
and deposited in interstitial fluid, and water
remains behind in the ascending limb.
The osmolarity of the interstitial fluid and
descending limb fluid increases, adding to the
gradient that was established in the previous
steps. The osmolarity of the fluid of the
ascending limb decreases further

17. .

18. Step 4 is the flow of fluid again.
New fluid with an osmolarity of 300 mOsm/L
enters the descending limb from the proximal
tubule, which displaces fluid from the
ascending limb.
As a result the high osmolarity fluid in the
descending limb is pushed down toward the
bend of the loop of Henle. The gradient of
osmolarity is now larger than it was in step 2.

19. .

20. 2-countercurrent exchange
The vasa recta are freely permeable to
small solutes and water.
 Blood flow through the vasa recta is
slow, and solutes and water can move in
and out, allowing for efficient
countercurrent exchange.

21. 2-countercurrent exchange
Blood entering the descending limb of vasa recta has
an osmolarity of 300 mOsm/L. As this blood flows
down the descending limb, it is exposed to interstitial
fluid with increasingly higher osmolarity .
NaCl and urea, diffuse into the descending limb and
water diffuses out, allowing blood in the descending
limb of the vasa recta to equilibrate osmotically with
the surrounding interstitial fluid.

22. .

23. At the bend of the vasa recta, the blood has an
osmolarity equal to that of interstitial fluid at the tip
of the papilla, 1200 mOsm/L.
 In the ascending limb, the opposite events occur.
As blood flows up the ascending limb, it is exposed
to interstitial fluid with decreasing osmolarity. Small
solutes diffuse out of the ascending limb and water
diffuses in, and the blood in the ascending limb of
the vasa recta equilibrates with the surrounding
interstitial fluid.

24. .

25. b)Urea Recycling
Urea recycling from the inner
medullary collecting ducts is
the second process that
contributes to the
establishment of the
corticopapillary osmotic
gradient.

26. b)Urea Recycling
The diffusion of urea is greatly
facilitated by specific urea
transporters:
UT-A1 and UT-A3.
UT-A3, is activated by ADH

27. b)Urea Recycling
In the cortical and outer medullary collecting ducts,
ADH increases water permeability, but it does not
increase urea permeability. As a result, water is
reabsorbed but urea remains behind in the tubular
fluid.
• This differential effect of ADH on water and urea
permeability in cortical and outer medullary
collecting ducts causes the urea concentration of
tubular fluid to increase.

28. b)Urea Recycling
In the inner medullary collecting ducts, ADH
increases both water and urea permeability
In the presence of ADH, the inner medullary
collecting ducts are permeable to urea, and urea
diffuses down its concentration gradient into the
interstitial fluid.
• Urea that would have otherwise been excreted is
recycled into the inner medulla, where it is added
to the medullary osmotic gradient.

29. Urea Recycling

30. Steps Involved in Production of Hyperosmotic Urine :
1. The osmolarity of glomerular filtrate is identical to that of blood, 300 mOsm/L, because
water and small solutes are freely filtered and water is always reabsorbed in exact
proportion to solute; that is, the process is isosmotic.
2. In the thick ascending limb of the loop of Henle, NaCl is reabsorbed via the Na+-K+-2Cl-
cotransporter. The cells of this segment are impermeable to water . As solute is
reabsorbed, water is left behind, and the tubular fluid is diluted. The osmolarity of tubular
fluid leaving this segment is 100 mOsm/L. Thus, the thick ascending limb is a diluting
segment.
3. In the early distal tubule, NaCl is reabsorbed by an Na+-Cl- cotransporter. Like the thick
ascending limb, cells of the early distal tubule are impermeable to water, and water
reabsorption cannot follow solute reabsorption. Here, the osmolarity of tubular fluid
becomes even more dilute, as low as 80 mOsm/L. Thus, the early distal tubule also is called
the cortical diluting segment (cortical because the distal tubule is located in the cortex,
rather than in the medulla where the thick ascending limb is found).

31. .
4- In the late distal tubule, the principal cells are permeable to water in the presence of
ADH. The fluid entering the late distal tubule is quite dilute, 80 mOsm/L. Since the cells
are now permeable to water, water flows out of the tubular fluid by osmosis. Water
reabsorption will continue until the tubular fluid equilibrates osmotically with the
surrounding interstitial fluid. The tubular fluid leaving the distal tubule is equilibrated
with the interstitial fluid of the cortex, and it has an osmolarity of 300 mOsm/L.
5- In the collecting ducts, The principal cells of the collecting ducts are permeable to
water in the presence of ADH. As tubular fluid flows down the collecting ducts, it is
exposed to interstitial fluid with increasingly higher osmolarity (i.e., the Medullary
osmotic gradient). Water will be reabsorbed until the tubular fluid equilibrates
osmotically with surrounding interstitial fluid. The final urine will reach the osmolarity
present at the tip of the papilla, 1200 mOsm/L.

33. Summary of Tubule Characteristics—Urine
Concentration

34. Regulation of ADH Secretion

35. Disorders of Urinary Concentrating Ability
The inability of the kidneys to concentrate or dilute the
urine appropriately can occur with one or more of
the following abnormalities:
1. Inappropriate secretion of ADH. Too little ADH
secretion “Central” Diabetes Insipidus.
2. Impairment of the countercurrent mechanism. A
hyperosmotic medullary interstitium is required for
maximal urine concentrating ability. No matter how
much ADH is present, maximal urine concentration is
limited by the degree of hyperosmolarity of the
medullary interstitium.

36. obligatory urine volume
• A normal 70-kilogram human must excrete about 600
milliosmoles of solute each day.
• The human kidney can produce a maximal urine
concentration of 1200 to 1400 mOsm/L, four to five
times the osmolarity of plasma.
• If maximal urine concentrating ability is 1200 mOsm/L,
the minimal volume of urine that must be excreted,called
the obligatory urine volume, can be calculated as:
• 600 mOsm/ day÷ 1200 mOsm L = 0.5 L day

37. Rapid dehydration that occurs in shipwreck victims
who drink seawater.
• Sodium chloride concentration in the oceans averages about 3.0 to 3.5 per cent, with an
osmolarity between about 1000 and 1200 mOsm/L.
• Drinking 1 liter of seawater with a concentration of 1200 mOsm/L would provide a total sodium
chloride intake of 1200 milliosmoles.
• If maximal urine concentrating ability is 1200 mOsm/L, the amount of urine volume needed to
excrete 1200 milliosmoles would be 1200 milliosmoles divided by 1200 mOsm/L, or 1.0 liter.
• The kidney must also excrete other solutes, especially urea, which contribute about 600 mOsm/L
• The maximum concentration of sodium chloride that can be excreted by the kidneys is about 600
mOsm/L.
• Thus, for every liter of seawater drunk, 2 liters of urine volume would be required to rid the body
of 1200 milliosmoles of sodium chloride.
• This would result in a net fluid loss of 1 liter for every liter of seawater drunk, explaining the rapid
dehydration that occurs in shipwreck victims who drink seawater

38. .

39. .