Counter current mechanism

Mechanism of production of Diluted & Concentrated Urine

1. Counter-Current Mechanism
Prof. Dr. Rashid Mahmood

2. Counter-
Current
Mechanism
Prof. Dr. Rashid Mahmood
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 2

3. The Body Fluids and
Kidneys
Regulation of
ECF
Osmolarity
and Na+
Concentration
Renal concentration
and dilution of urine
Counter-
Current
Mechanism
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 3

4. Objectives
Goal/Aim:
Describe mechanism of Renal concentration and dilution
of urine
Specific Objectives:
By the end of this session students should be able to
Describe the handling of water by the various portions of the
nephron,
Describe how ADHregulates the excretion of water by the
kidneys.
Describe the handling of Na+by the various portions of the
nephron and the factors that regulate its excretion.
Distinguish among the factors that regulate thirst and cause
the secretion of ADH
Explain the response of the kidneys to changes in the
extracellular fluid volume and concentration.
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 4

5. Lesson Contents
1.Mechanisms that cause the kidneys to
eliminate excess waterby
excreting dilute urine
2.Mechanisms that cause the kidneys to
conserve waterby excreting
concentrated urine
3.Renal feedback mechanisms
that control the ECF sodium
concentration and osmolarity
4.Thirst and salt appetite
mechanismthat determine the
intake of water and salt
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 5

6. Sample questions (Preamble)
1.What is meant by counter-current mechanism?
What are its components? What are the special
characteristics of Loop of Henle that cause
solutes to be trapped in the renal medulla?
2.Discuss the roll of Distal Convoluted tubule and
Collecting Ducts in excreting a Concentrated
Urine.
3.Summarize the urine concentrating mechanism
and changes in osmolarity in different
segments of the renal tubules
4.discuss the roll of ADH in controlling body fluid
osmolarity
5.What are the requirements of excreting
concentrated urine?
6.discuss the roll of osmoreceptors in controlling
urine osmolarity
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 6

7. Sample questions
7.discuss the roll of centers for thirst in controlling urine
osmolarity
8.discuss the roll of salt-appetite mechanism in
controlling urine osmolarity
9.discuss the roll of Angiotensin II and Aldosterone in
controlling ECF osmolarity and Sodium concentration
10.Enumerate the Factors affecting the diluting and
concentrating mechanism. Describe how intracellular
volume is maintained in the Hyperosmotic medulla
11.What is meant by Pressure diuresis and pressure
Natriuresis? Describe their mechanism
12.Name a few Disorders of Urinary Concentrating Ability.
Discuss the roll of centers in the brain in Control of ECF
osmolarity Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 7

8. Regulation of ECF Osmolarity
and Na
+
Concentration
1.Fluid intake
i.Thirst
ii.Salt appetite
2.Renal excretion of WATERand solutes
i.Elimination of excess WATERand solutes
Dilute urine
ii.Conservation ofWATERand solutes
Concentrated urine
iii.Renal feedback control mechanisms
Independent regulation of water excretion:
Counter-current mechanism
Counter-Current Mechanism | © Prof. Dr. Rashid Mahmood
16 July 2021 8

9. Requirements for excreting
concentrated urine
1.High ADH level
2.Hyperosmotic renal medulla
Produced by COUNTERCURRENT
multipliers
i.Active transport of ions
ii.Relatively less absorption of water
iii.Urea and NaCl trapping
Maintained by COUNTERCURRENT
exchangers
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 9

10. Counter-Current
Mechanism
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
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11. Counter-Current Mechanism
•Counter =
Opposite
•Current =
Flow
•Definition:
A counter-current system is a system
in which the inflow runs parallel to
the outflow for some distance.
Parts of Nephron involved:
•Loop of Henle
•Vasa recta
Counter-Current Mechanism | © Prof. Dr. Rashid Mahmood 16 July 2021 11

12. Counter-
Current
Mechanism
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 12

13. Q.1
•Name the two important solutes
required for counter-current
mechanism.
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 13
Urea, NaCl

14. Functional considerations
Purpose
1.Dilute and concentrated urine
Water requirement
2.Constant Osmolarity of plasma
Urine Osmolarity= 50-1400 mOsm/l
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
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15. Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 15

16. Roll of ADH (Anti-Diuretic Hormone)
ADH present: ? % water reabsorbed
99
ADH absent: ? % water reabsorbed
88
Stimulated by ?
↑ osmolarity of body fluids
Inhibited by ?
↓osmolarity of body fluids
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 16

17. Components of Counter Current Mechanism
1
5b
2
3
4
5c
5a
7
6
1 to 5
Nephron
Counter-
Current
Multipliers
6
Medullary
Interstitium
7
Vasa Recta
Counter-
Current
Exchangers
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 17

18. Osmolarity in different segments of Nephron
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
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19. Basic Mechanism
1.Formation of vertical
osmotic gradient(V.O.G.)
Multiplication
×300
2.Maintenance of vertical
osmotic gradient
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 19

20. Q.2
•A person drinks 1.25 Liters of water. After 2
hours, which of the following will significantly
decrease?
A.Urine flow rate
B.Urinary solute excretion
C.Urine Osmolarity
D.Plasma Osmolarity
E.Plasma Sodium
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 20
C

21. Osmolarity
300
300
600
900
1200
NaClUrea
294
294
400
600
600
6
6
200
300
600
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 21

22. Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 22

23. Fundamental Processes
1.Active Transport of Na
+
and co-transport of K
+
and
Cl
-
out of thick ALH
2.Active reabsorption of ions from collecting duct
3.Passive diffusion of Urea from inner medullary
collecting duct
4.Passive absorption of relatively small amounts of
water
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 23

24. Regardless
of ADH
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
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25. Permeability
of different
segments
of nephron
Nephron segmentPermeability Active
transport
of Na+WaterUrea NaCl
Proximal tubule++ + + 2+
Thin Descending
Limb
4+ + ± 0
Thin Ascending
Limb
0 + 4+ 0
Thick Ascending
Limb
0 ± ± 4+
Distal convoluted
tubule
± ± ± 3+
Cortical collecting
tubule
3+ 0 ± 2+
Outer Medullary
collecting tubule
3+ 0 ± 1+
Inner Medullary
collecting tubule
3+ 3+ ± 1+
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 25

26. Q.3
•In what part of the renal tubule, water is
not reabsorbed, and NaCl is mainly
reabsorbed actively?
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 26
Thick Ascending Limb

27. Water Reabsorption and osmolarity
in various parts of nephron
65%
15%
10%
9.3
%
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Dr. Rashid Mahmood
16 July 2021 27

28. Changes in water temperature while
passing through a counter-current set-up
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29. Changes in urine osmolarity while passing through
different parts of counter-current multipliers
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
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30. Mechanism of formation of vertical
and horizontal osmotic gradient
(Horizontal gradient= Single effect)
1.Counter-current flow
2.Active transport of NaCl
3.Water Reabsorption
(Cortex > Medulla)
•PCT and DCT always in cortex
• Little water reabsorbed by Loop of Henle
•main site of action of ADH: DCT and cortical
collecting duct
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 30

31. Q.4
•Name the substance that is reabsorbed by the
renal tubules but it does not enter the general
circulation.
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 31
Urea
Next:RecirculationandtrappingofUrea

32. Mechanism of addition of urea to the inner
medullary gradient (Recirculation and
trappingof Urea)
Urea
transporters
Activated
by ADH
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 32

33. Maintenance of medullary
gradient
•Counter-current exchangers
•Vasa recta
•Medullary blood flow= 1-10 % of renal blood
flow
•Sluggish
•Passive process
•Highly permeable to water and solutes
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 33

34. Maintenance of medullary
gradient
•Equilibrium lag
•Solute wash
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
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35. Equilibrium lag
and
Solute wash
×
×
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Dr. Rashid Mahmood
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36. Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 36

37. Oncotic
pressure
and lag in
equilibrium
favor net
fluid
absorption
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
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38. Q.5
•Name the hormone activates Urea
transporters in Medullary Collecting
Duct.
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 38
ADH

39. Counter-current flow in
other parts of nephron
Cortical part of ascending limb and
segment 3 of proximal tubule (pars recta)
Counter-Current Mechanism |
© Prof. Dr. Rashid Mahmood
16 July 2021 39

40. Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 40

41. Roll of ADH
•Main site of action
•Collecting duct
•Facultative water Reabsorption
•ADH present
0.5% of filtered load is excreted
Urine osmolarity: 1200
•ADH absent
15% of filtered load is excreted
Urine osmolarity: 50
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 41

42. Axial profile of osmolarity of the
tubular fluid
Counter-Current Mechanism | © Prof.
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43. Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
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44. Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 44

45. Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 45

46. Q.6
•Normally maximum Osmolarity of Tubular
Fluid is in
A.Proximal Convoluted Tubule
B.Loop of Henle
C.Distal Convoluted Tubule
D.Cortical Collecting Duct
E.Medullary Collecting Duct
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 46
B

47. Factors affecting the diluting
and concentrating mechanism
1.Length of loop of Henle
2.Percentage of nephrons with long loop
3.Availability of urea
Protein deficiency
4.Rate of flow through the loop of Henle
5.Rate of flow through the collecting duct
6.Rate of through the vasa recta
1.↑BP (Pressure diuresis)
2.Vasodilators
7.Prostaglandins
contd……….
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 47

48. Prostaglandins
Prostaglandins
Effects on renal
vasculature
Effects on thick
ascending limb
Effects on
collecting duct
↑blood flow
through
vasa recta
↓NaCl
Reabsorption
↓urea absorption
In papillary
Collecting duct
↓water absorption
In collecting duct
↓osmolarity of
medullary
gradient
↓urine
osmolarity
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 48

49. Maintenance of intracellular
volume in the medulla
•Organic solutes
–Sorbitol
–Inositol
–Betaine
–Glycerophosphoryl choline
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 49

50. (Pressure diuresis)
•↑GFR
•↑ Pc → ↓Reabsorption
•↑ flow through vasa recta
•↓ Angiotensin → ↓NaCl Reabsorption
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 50

51. Disorders of Urinary
Concentrating Ability
1.Inappropriate secretion of ADH
Central Diabetes Insipidus
2.Inability of nephrons to respond to ADH
Nephrogenic Diabetes Insipidus
3.Impairment of counter-current
mechanism
Infections of kidney
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 51

52. Control of ECF osmolarity by
centers in the brain
1.Osmoreceptor-ADH control feedback
system
2.Cardiovascular reflex stimulation of
ADH
3.Centers for thirst
4.Salt-appetite mechanism
5.Angiotensin-II and Aldosterone
–Little roll
•Simultaneous Reabsorption of water
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 52

53. Q.7
In case of increased arterial Pressure, GFR
does not significantly increase due to
Autoregulatory mechanisms. Then what is
the mechanism for increased urine output
in case of increased arterial pressure?
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 53
1.↑ Pc → ↓Reabsorption
2.↑ flow through vasa recta
3.↓ Angiotensin → ↓NaCl Reabsorption
4.↑GFR (Autoregulatory mechanism are not 100% perfect

54. 1. Osmoreceptor-ADH control
feedback system
Water deficit
↑ECF osmolarity
Stimulation of osmoreceptors
in hypothalamus
ADH secretion by Post. Pituitary
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 54

55. 2. Cardiovascular reflex stimulation
of ADH
1.↓Arterial pressure
2.↓Blood volume
Stimulation of
hypothalamus
ADH secretion by
Post. Pituitary
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 55

56. 3.Thirst Center
•Increased thirst
1.↑ osmolarity
2.↓blood volume
3.↓blood
pressure
4.↑ angiotensin
5.Dryness of
mouth
•Decreased thirst
1.↓osmolarity
2.↑blood volume
3.↑blood
pressure
4.↓angiotensin
5.Gastric
distension
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 56

57. 4. Salt-appetite mechanism
↑salt appetite
1.↓ECF Sodium concentration
2.↓blood volume
3.↓blood pressure
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 57

58. Coordinated Control of ECF osmolarity by centers in the brain
↓blood pressureWater deficit ↓blood volume
↑osmolarity
1.↑ADH
2.↑thirst
↑salt appetite
↓osmolarity
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 58

59. Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 59

60. Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 60

61. Q.8
•Name the THREE main requirements
for excreting concentrated urine
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 61
1.High ADH level
2.Hyperosmotic renal medulla
3.Control of ECF osmolarity
by centers in the brain

62. Requirements for excreting concentrated urine
1.High ADH level
2.Hyperosmotic renal
medulla
A.Produced by
countercurrent
multipliers
i.Active
transport of
ions
ii.Relatively less
absorption of
water
iii.Urea and NaCl
trapping
B.Maintained by
countercurrent
exchangers
3.Control of ECF
osmolarity by
centers in the brain
Summary
Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 62

63. Counter-Current Mechanism | © Prof.
Dr. Rashid Mahmood
16 July 2021 63

64. Thank You
Questions/ comments/Feedback
[email protected]
[email protected]
Counter-Current Mechanism | © Prof. Dr. Rashid Mahmood 16 July 2021 64