1. Water Homeostasis concentration and dilution of urine

2. Water Homeostasis Changes in water excretion is based mainly on OSMOLALTY OF ECF The objective of modulation of water excretion is to maintain the osmolality of ECF The primary aim of changes in water excretion is NOT the maintenance of ECF volume

3. Water Homeostasis In the kidney: Water excretion is increased by producing urine with low osmolality – dilute urine Water excretion is in decreased by producing urine with high osmolality – concentrated urine

4. Tubular Fluid Osmolality iso-osmolar hyper-osmolar Hyposmolar

5. Tubular Fluid Osmolality Hyposmolar Hyperosmolar ADH LowADH High Dilute UrineConcentrated Urine

6. Tubular Fluid Osmolality Until tubular fluid reaches the late distal tubule, the changes in osmolality of tubular fluid are the same, irrespective of the osmolality of ECF The modulation of water excretion based on the osmolality of ECF occurs in distal tubule and COLLECTING DUCT (mainly medullary part)

7. Tubular Fluid Osmolality Hyposmolar Hyperosmolar ADH LowADH High Dilute UrineConcentrated Urine

8. Regulation of ADH Secretion Hyperosmolar ADH High High ECF osmolality Stimulation of osmoreceptors in anterior hypothalamus High ICF osmolality Increased ADH secretion from posterior pituitary Increased water reabsorption in collecting duct Stimulation of thirst Concentrated Urine

9. Regulation of ADH Secretion Hyperosmolar ADH High Low blood volume Low blood pressure Increased ADH secretion from posterior pituitary Increased water reabsorption Angiotensin II Concentrated Urine

10. Regulation of ADH Secretion Low ECF osmolality Hyposmolar ADH Low Inhibition of osmoreceptors in anterior hypothalamus Low ICF osmolality Decreased ADH secretion from posterior pituitary Decreased water reabsorption in collecting duct Inhibition of thirst Dilute Urine

11. Regulation of ADH Secretion Hyposmolar ADH Low High blood volume High blood pressure Decreased of ADH secretion from posterior pituitary Decreased water reabsorption Dilute Urine

12. Actions of ADH Main action of ADH

13. Actions of ADH Actions in the kidney tubule 1.Increase permeability of late distal tubule and collecting duct (both cortical and medullary) to water 2.Increase the activity of the Na+K+2Cl- transporter in the thick ascending limb 3.Increase permeability of the medullary collecting duct to urea

14. Water Reabsorption in CD  Water moves by osmosis  In the presence of ADH water can move across the tubular cells  Water will move from tubule to the outside only if the outside osmolality is higher  Thus to concentrate urine the medullary interstitium must have a high osmolality water HyperosmolarADH High

15. Establishing High Medullary Osmolality water 20 0 C

16. Establishing High Medullary Osmolality water 20 0 C30 0 C Maximum temperature that can be achieved is 30 0 C

17. Establishing High Medullary Osmolality water 20 0 C30 0 C

18. Establishing High Medullary Osmolality water 20 0 C 25 0 C 30 0 C

19. Establishing High Medullary Osmolality water 20 0 C 35 0 C 25 0 C

20. Establishing High Medullary Osmolality water 20 0 C 30 0 C

21. Establishing High Medullary Osmolality A higher maximum temperature can be achieved A counter current multiplier system water 20 0 C 30 0 C 40 0 C Point of highest temperature

22. Counter Current Multiplier “Counter current”  Flow in the two limbs opposite directions  Transfer from outgoing to incoming limb “Multiplier”  Achieves a higher level than otherwise possible

23. Osmotic Gradient in the Medulla Loop of Henle is a counter current multiplier It creates an osmotic gradient in the medulla

24. Role of Vasa Recta Renal medulla, like any other tissue needs a blood supply In any tissue plasma and interstitial tissues participate in a fluid exchange through the capillary wall.

25. Role of Vasa Recta 300 400 600 800 1000 cortex medulla 400 600 800 1000 300

26. Role of Vasa Recta 400 600 800 1000 cortex medulla 400 600 800 1000 300 400 600 800 1000 300 Counter Current Exchanger Helps maintain the osmotic gradient

27. Role of Vasa Recta Vasa recta descend from the cortex, supply the medulla and ascend again to the cortex They act as counter current exchangers

28. Urine Osmolality Range of urine osmolality 50 – 1400 mOsm/L (compare with normal plasma osmolality 285-295) ? normal urine osmolality ? appropriate urine osmolality Linked to plasma osmolality High plasma osmolality - High urine osmolality Low plasma osmolality - Low urine osmolality

29. Free Water Clearance Plasma Urine (output per minute) same osmolality KIDNEY In this situation: solute and water are excreted in same proportion as in plasma

30. Free Water Clearance Plasma Urine (output per minute) urine lower osmolality than plasma KIDNEY

31. Free Water Clearance Plasma OR Free Water Clearance Water that is in excess of the volume of urine if it were to be isotonic Free water clearance has a positive value when urine is dilute

32. Free Water Clearance Plasma Urine (output per minute) urine higher osmolality than plasma KIDNEY

33. Free Water Clearance Plasma OR Free water clearance has a negative value when urine is concentrated

34. Diabetes Insipidus Production of large volume of urine because of non-absorption of water in the collecting duct  Diabetes Insipidus “diabetes” – large volume of urine “insipidus” – as opposed to “mellitus” 1.Deficiency of ADH – central/pituitary diabetes insipidus 2.Defect in ADH receptors – nephrogenic diabetes insipidus High plasma osmolality Low urine osmolality

35. Inappropriate Secretion of ADH Excessive secretion of ADH when there is no necessity  Results in reabsorption of water even when there is no need Low plasma osmolality High urine osmolality

36. Urea Recycling in the Kidney Fate of filtered urea 1.Reabsorbed in PT – removed by blood flow 2.Reabsorbed in MCD – enters the medullary interstitium 3.Secreted into DL – as medullary concentration is high 1 2 3

37. Urea Recycling in the Kidney Handling of urea by the tubule 1.Passive reabsorption by diffusion in the proximal tubule 2.Facilitated diffusion in medullary collecting duct, enhanced by ADH 3.Entry into descending loop of Henle from the medullary interstitial fluid Helps in the countercurrent multiplier system