1. 3/10/2016concentration&dilution of urine1

2. Renal mechanisms of diluting and concentrating urine  The kidneys excrete excess water by forming dilute urine and conserves water by excreting concentrated urine.  Can excrete urine with an osmolarity as low as 50mOsm/L  Conversely, can excrete urine with concentration of  1200 –1400mOsm/L. 3/10/2016concentration&dilution of urine2

3. Renal mechanisms of diluting and concentrating urine  ADH alters renal excretion of water independent of rate of solute excretion.  ADH secretion  when the solute in the body fluids become too concentrated.  It increases the permeability of late distal tubules and collecting ducts to water. 3/10/2016concentration&dilution of urine3

4. Excretion of dilute urine  When there is a large excess of water in the body the kidneys can excrete as much as 20L/day of dilute urine. Continue to reabsorb solutes while failing to reabsorb large amount of water in distal parts of the nephron.  Glomerular filtrate has osmolarity  that of plasma. 3/10/2016concentration&dilution of urine4

5. Excretion of dilute urine  In proximal tubules, solutes and water are reabsorbed in equal proportions, so that little change in osmolarity occur. 3/10/2016concentration&dilution of urine5

6. Excretion of dilute urine  In the descending loop of Henle water is reabsorbed by osmosis and the tubular fluid reaches equilibrium with surrounding interstitial fluid. 3/10/2016concentration&dilution of urine6

7. Excretion of dilute urine  Ascending limb of loop of Henle is impermeable to water even in presence of large amounts of ADH. 3/10/2016concentration&dilution of urine7

8. Excretion of dilute urine  Active reabsorption of solutes, causing the tubular fluid to become more dilute as it flows into the early distal tubule,  osmolarity decreasing progressively to  100mOsm/L. 3/10/2016concentration&dilution of urine8

9. Excretion of dilute urine  In the distal tubules, cortical collecting duct and medullary duct there is additional reabsorption of NaCl.  In the absence of ADH these segments are also impermeable to water. 3/10/2016concentration&dilution of urine9

10. Excretion of dilute urine  Tubular fluid become even more dilute decreasing its osmolarity to as low as 50 mOsm/L 3/10/2016concentration&dilution of urine10

11. Excretion of concentrated urine  Essential for survival of mammals that live on land.  Fluid intake is required to match with fluid loss.  The ability of the kidney to form a small volume of concentrated urine minimizes the intake required to maintain homeostasis. 3/10/2016concentration&dilution of urine11

12. Excretion of concentration urine  When there is water deficit in the body the kidney forms small volume concentrated urine by continuing to excrete solutes while increasing water reabsorption.  Obligatory urine volume  0.5l/day.  Excretion of concentrated urine requires. High ADH level. Hyperosmotic renal medullary interstitium. 3/10/2016concentration&dilution of urine12

13. 3/10/2016concentration&dilution of urine13 Excretion of concentrated urine NaCl H2OH2O Urea H2OH2O H2OH2O NaCl H2OH2O 300 600 1200 100 300 600 1200 cortex medullar

14. Stimuli for ADH secretion   ECF osmolarity   Blood volume/Arterial pressure  Stimuli to CNS  Drugs, Alcohol inhibits ADH secretion 3/10/2016concentration&dilution of urine14

15. Hyperosmotic renal medullary interstitium  Provide osmotic gradient necessary for water reabsorption to occur ○ in the presence of high levels of ADH  Water moves through the tubular membrane by osmosis ○ into the renal interstitium then by vasa recta back into the blood. 3/10/2016concentration&dilution of urine15

16. Causes of hyperosmotic renal medullary interstitium  Special anatomical arrangements of the loops of Henle and vasa recta. 3/10/2016concentration&dilution of urine16

17. Causes of hyperosmotic renal medullary interstitium  Major factors that contribute to hyperosmolarity of renal medullary interstitium are  Active transport of Na +, and cotransport of K +, Cl - and others out of the thick portion of loop of Henle. Capable of establishing concentration gradient ○ of 200 mOsm/L  Active transport of ions from the collecting duct into the medullary interstitium.  Passive diffusion of urea from inner medullary collecting ducts into the interstitiusm 3/10/2016concentration&dilution of urine17

18. Causes of hyperosmotic renal medullary interstitium  Diffusion of only small amount of water from the medullary collecting ducts into the medullary interstitium. large amount being reabsorbed ○ in late distal tubules and cortical collecting ducts.  Some passive reabsorption of NaCl in the descending loop of Henle. 3/10/2016concentration&dilution of urine18

19. Mechanisms  Active pump of thick ascending limb of loop of Henle establishes 200mOsm/L concentration gradient between the tubular fluid and interstitial fluid. 3/10/2016concentration&dilution of urine19

20. Mechanisms  Tubular fluid in the descending limb of loop of Henle and the interstitial fluid quickly reach osmotic equilibrium.  Hyperosmotic fluid formed in the descending limb flows into ascending limb. 3/10/2016concentration&dilution of urine20

21. Mechanisms  Once this fluid is in the thick segment additional ions are pumped into the interstitium with water remaining behind until osmotic gradient of 200mOm/L ○ is established. 3/10/2016concentration&dilution of urine21

22. Mechanisms  Tubular fluid in the descending loop and hyperosmotic medullary interstitial fluid reaches equilibrium. 3/10/2016concentration&dilution of urine22

23. Mechanisms  These are repeated over and over with the net effect of adding more and more solutes to the medulla in excess of water. 3/10/2016concentration&dilution of urine23

24. Mechanisms  With sufficient time this process multiplies the concentration gradient established by active transport of ions in the thick segment of loop of Henle raising the osmolarity to 1200 – 1400mOm/L  This process Counter current multiplier. 3/10/2016concentration&dilution of urine24

25. Mechanisms  Passive reabsorption of urea from inner medullary collecting ducts contributes  40% of the renal medullary interstitium osmolarity when the kidney is forming maximally concentrated urine. 3/10/2016concentration&dilution of urine25

26. Mechanisms  Very little urea is reabsorbed in the loop of Henle.  Distal tubules and cortical collecting ducts are impermeable to urea even in the presence of high concentration of ADH. 3/10/2016concentration&dilution of urine26

27. Mechanisms  In the presence of high [ADH], Urea] increases rapidly in cortical collecting duct. 3/10/2016concentration&dilution of urine27

28. Mechanisms  As fluid flows into inner medullary collecting ducts further reabsorption of water takes place,  [Urea] increase. 3/10/2016concentration&dilution of urine28

29. Mechanisms  Increased [Urea] causes large amount of urea to diffuse into the interstitium because this segment is highly permeable to urea  ADH increases this permeability even more. 3/10/2016concentration&dilution of urine29

30. Urea cycle  Urea is recycled several times before it is excreted.  Some diffusion of urea into the thin loop of Henle from the medullary interstitium. 3/10/2016concentration&dilution of urine30

31. Maintenance of hyperosmolarity of the renal medulla  Medullary blood flow is low  The vasa recta serves as counter current exchangers, Minimizing wash out of solutes from the medullary interstitium.  Blood enters and leaves the medulla by the way of vasa recta at the boundary of cortex and medulla. 3/10/2016concentration&dilution of urine31

32. Maintenance of hyperosmolarity of the renal medulla  As blood descends into the medulla toward the papillae it becomes progressively more concentrated party by solute ○ entry from the interstitium 3/10/2016concentration&dilution of urine32

33. Maintenance of hyperosmolarity of the renal medulla and party by water diffusing ○ into the interstitium  By the time blood reaches the tips of vasa recta it has conc. of  1200mOm/L. 3/10/2016concentration&dilution of urine33

34. Maintenance of hyperosmolarity of renal medulla  As blood ascends back toward the cortex it become progressively less concentrated water moving into vasa recta ○ solutes diffusing out. 3/10/2016concentration&dilution of urine34

35. Maintenance of hyperosmolarity of renal medulla  Thus although there is large amount of fluid and solute exchange ○ across the vasa recta, there is little ○ net dilution of the concentration ○ of the interstitial fluid at each level of the medulla. 3/10/2016concentration&dilution of urine35

36. 3/10/2016concentration&dilution of urine36 Vasa recta mOsm/L Renal medullary interstitium Renal medullary interstitium H2OH2O H2OH2O H2OH2O 600 800 1000 1200 600 300 solutes 600 800 900 1200 800 300