1. RENAL SYSTEM PHYSIOLOGY
Dr Shahab Shaikh PhD, MD
Lecture – 7: Concentration and Dilution of Urine
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College of Medicine
Al Maarefa Colleges of Science & Technology

2. OBJECTIVES
Describe the factors that determine the ability of loop of Henle to creat osmotic medullary gradient
Identify countercurrent multiplier and countercurrent exchange systems in concentrating and diluting urine
Explain changes in osmolarity of tubular fluid in the various segments of the loop of Henle when concentrated urine is being produced.
Describe the role of ADH on the ability of the kidney to produce either a dilute or a concentrated urine.

3. Urine Formation
Three Basic Mechanisms (Renal Processes) of Urine Formation include:
Glomerular filtration - GF
Tubular reabsorption - TR
Tubular secretion - TS

4. Urine Formation
“The composition of the blood (internal environment) is determined not by what the mouth ingest but by what the kidney keep.”

5. Urine Formation
Kidneys maintain water homeostasis by adjusting the volume of urine produced.
The ability of the kidney to concentrate or dilute urine is an important function in regulating Extracellular volume (ECV), Extracellular Fluid osmolarity.
The kidney can excrete dilute urine with an osmolarity as low as 30 to 50mosm/liter or concentrated urine with osmolarity as high as about 1200 to 1400mosm/liter.
Kidneys can vary Urine Osmolarity between mosm/kg and urine volume between L/day.

6. Urine Formation
This function of concentrating or diluting the urine is determined in kidneys by the amount of water reabsorption in the renal tubules.
Water reabsorption is obligatory in the proximal(65%) tubules and Loop of Henle(15%).
Thus the final adjustment of the urine volume and osmolarity depends on the extent of water reabsorption in the Collecting Ducts.
Water reabsorption from the collecting ducts depends on:
The blood level of Antidiuretic Hormone (ADH).
The Medullary interstitium (MI) hypertonicity

7. Urine Concentration
The basic requirements for forming a concentrated (or diluted) urine is:
Secretion of antidiuretic hormone (ADH):
Regulates the permeability of the distal tubules and collecting ducts to water.
High ADH causes high reabsorption of water  Concentrated Urine.
High osmolarity of the renal medullary interstitial fluid:
Provides the osmotic gradient necessary for water reabsorption to occur in the presence of high level of ADH.

8. Urine Concentration Counter Current Mechanism:
Provides the osmotic gradient necessary for water reabsorption by creating and maintaining high osmolarity of the renal medullary interstitial fluid.
Is a function of Juxta-medullary nephrons.
Consists of …
Counter Current Multiplier system
Creates the high osmolarity of the renal medullary interstitial fluid
Counter Current Exchanger system
Maintains the high osmolarity of the renal medullary interstitial fluid

9. Counter Current Multiplication
Creates the hyperosmotic Medullary Interstitium by solute deposition in medullary interstitium.
NaCl reabsorbed from the thick ascending limb of loop of Henle is deposited in medullary interstitium.
Active transport of NaCl along thick ascending loop results in the movement of water from the descending limb increasing the osmolarity of descending limb fluid.
Urea reabsorbed from collecting duct (ADH) to medullary interstitium also contribute to medullary hyperosmolarity.

10. Countercurrent Multiplication

11. Countercurrent Multiplication

12. Countercurrent Multiplication

13. Countercurrent Multiplication

14. Countercurrent Multiplication

15. COUNTERCURRENT MULTIPLICATION
BENEFITS:
It establishes a vertical osmotic gradient in the medullary interstitial fluid. This gradient, in turn, is used by the collecting ducts to concentrate the tubular fluid so that a urine more concentrated than normal body fluids can be excreted.
Second, the fact that the fluid is hypotonic as it enters the distal parts of the tubule enables the kidneys to excrete a urine more dilute than normal body fluids.

16. COUNTERCURRENT EXCHANGER
It helps to maintain the Hyperosmolarity of medulla while providing blood to renal medulla.
Occurs by the Vasa Recta supplying the long loop of Henle of Juxtaglomerular nephrons.
As the blood passes through the descending part of Vasa Recta it looses water and gain solutes due to increasing osmolarity in medullary interstitium.
Reverse happens when the blood returns back through the ascending part of vasa recta.
Thus Hyperosmolarity of medulla remains undisturbed.

17. Role of Vasopressin(ADH)
In the distal tubule and collecting duct water reabsorption is variable based on the secretion of ADH.
Osmotic gradient already exists between the tubules and interstitium in the renal medulla created by the countercurrent mechanism.
When ADH is secreted in blood, it increases the permeability of the tubule cells to water by increasing the Aquaporin-2 water channel proteins for the transport of water into interstitium by osmosis. Thus Concentrating Urine.
During a water deficit, the secretion of vasopressin increases. This increases water reabsorption.
During an excess of water, the secretion of vasopressin decreases. Less water is reabsorbed. More is eliminated making urine dilute.

18. Vasopressin: Mechanism of action

19. Vasopressin: Water Regulation

20. The Urea Recirculation

21. The Concentration of Urine
Regulation of H2O reabsorption in response to H2O deficit

22. Regulation of H2O reabsorption in response to H2O excess
The Dilution of Urine
Regulation of H2O reabsorption in response to H2O excess

23. Clinical Aspect
Diuresis is condition in which urine production by the kidneys is increased
Osmotic diuresis is due to filtration of excessive osmotically active substances in renal tubules. Eg. Diabetes Mellitus, Mannitol
Syndrome of Inappropriate Antidiuretic Hormone secretion or SIADH is characterized by excessive release of antidiuretic hormone from the posterior pituitary gland or another source resulting in water retention and dilutional hyponatremia.
Diabetes Insipidus is a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine due to either a problem with the production of ADH (Central D.I) or decreased kidney's response to ADH (Nephrogenic D.I).

24. References Human physiology by Lauralee Sherwood, 8th edition
Text Book Of Physiology by Guyton & Hall, 11th edition
Review of Medical Physiology by Ganong. 24th edition

25. THANK YOU