1. K + Homeostasis

2. The need: ECF K + concentration is critical for the function of excitable cells However, about 98% of is in K + ICF ICF concentration of K + – 120-140 mmol/L ICF volume – twice the ECF volume BUT The kidney has to regulate K + handling based on K + level in ECF Increase in in the body will have a smaller effect on ICF than ECF

3. K + Homeostasis The need: ECF K + concentration needs to be maintained

4. Extracellular & Intracellular K + K+K+ K+K+ Equilibrium between Intracellular and extracellular K + Helps stabilise ECF K +

5. Glomerular Filtration of K +  Freely filtered at the glomerulus

6. Tubular Handling of K + Fate of filtered K + Percentage of filtered load reabsorbed / secreted Variable 60-70 % 20 % Variable

7. K + Reabsorption in the Proximal Tubule K + dependent on Na + reabsorption Na + reabsorption is mostly a constant fraction of filtered load K + reabsorption is also a constant fraction of filtered load Na+ K+ Na+ Tubular Lumen Capillary water K+K+ K+K+ K+K+ K+K+

8. K + Reabsorption in Loop of Henle Thick ascending limb Absorbed with Na+ Percentage absorbed constant Na+ K+ 2Cl- Tubular Lumen Capillary Na+

9. K + Handling in the Distal Tubule Principal cells – regulated by aldosterone  K + is secreted in exchange for Na + at the luminal surface Na + Capillary K+K+ Na+ K+ Na+ Lumen

10. K + Handling in the Distal Tubule Intercalated cells H + is secreted in exchange for K + at the luminal surface K+K+ Capillary H+H+ Lumen

11. K + Handling by Kidney K+ reabsorption / secretion 1. Linked to reabsorption or secretion of other ions  Mostly Na+  H+ to a lesser extent 2. Depends on aldosterone  Secretion is regulated mostly by renin-angiotensin mechanism  Serum K+ also has a direct effect on aldosterone secretion

12. K + Handling by Kidney Regulatory mechanism for Plasma K + 1.Intracellular K + - depends on several factors  dietary K + content  Acid base status  Insulin – increases influx of K + 2. Increased plasma K + stimulates aldosterone secretion However, aldosterone is mainly a Na + regulator K + handling by the kidney is determined more by other factors than plasma K + itself

13. K + Excretion K + excretion by kidney is increased by 1.Aldosterone 2.Alkalosis 3.Increased delivery of Na + to the distal tubule 4.Increased dietary K + 5.Exit of from K + cells – damage to cells, lack of insulin  High K + levels result in increased filtration of K +

14. ICF and ECF K + Equilibrium Factors affecting K + flux between ICF and ECF 1.Acid base status 2.Insulin 3.Sympathetic neurotransmitters 4.Exercise 5.Damage to cell membrane

15. Ca 2+ Handling by the Kidney

16. Glomerular Filtration of Ca 2+ Ca 2+ In blood 1.Free – 55-60%  Ionised  Complexed with organic anions 2.Bound to protein – 40-45% Only the free Ca 2+ is filterable

17. Tubular Handling of Ca 2+ Fate of filtered Ca 2+ Reabsorption only No secretion 8 % 65 % 25 % 2 %

18. Proximal tubular Reabsorption of Ca 2+  Passive  Paracellular  Due to concentration gradient created by Na + reabsorption Na + dependent reabsorption Na+ K+ Na+ Tubular Lumen Capillary water Ca 2+ water

19. Thick Ascending Limb Reabsorption of Ca 2+  Passive  Paracellular  Due to concentration gradient created by Na + reabsorption Na + dependent reabsorption Na+ K+ 2Cl- Tubular Lumen Capillary Na+ Ca 2+

20. Reabsorption of Ca 2+  Approximately 90% of Ca 2+ reabsorption is Na + dependent

21. Distal Tubular Reabsorption of Ca 2+  Active  transcellular  Regulated by parathormone Ca 2 + Tubular Lumen Capillary Na+ Ca 2 +

22. Regulation of Tubular Reabsorption of Ca 2+  Na + reabsorption  Parathormone – sensitive to ionised calcium level in blood  Acid base status – acidosis inhibits reabsorption and alkalosis enhances reabsorption

23. Phosphate Handling by the Kidney

24. Glomerular Filtration of Phosphate Phosphate In blood 1.Free – 90-95% 2.Bound to protein – 5-10% The free phosphate is freely filtered

25. Tubular Handling of Phosphate Fate of filtered phosphate Reabsorption almost entirely in the proximal tubule 85 % 15 %

26. Proximal Tubular Reabsorption of Phosphate  Symport system coupled to Na + reabsorption  Has tubular maximum  Parathormone inhibits reabsorption The phosphate that is excreted in urine performs an important function – buffering secreted H +

27. Magnesium Handling by the Kidney

28. Glomerular Filtration of Magnesium Magnesium in blood 1.Free – 50-60 % 2.Bound to protein – 40-50 % The free magnesium is filtered

29. Tubular Handling of Magnesium Fate of filtered magnesium Highest reabsorption in the thick ascending limb 30 % 5 % 60 % 5 %

30. Tubular Reabsorption of Magnesium  Passive  Mostly paracellular route  Dependent on Na + reabsorption

31. Urate Handling by the Kidney

32. Renal Handling of Urate  Freely filtered at the glomerulus  Proximal tubule  Passively reabsorbed in the early part  Actively secreted in the mid proximal tubule  Passively reabsorbed in the late segment  Secretion is regulated by plasma levels of urate Reabsorption > secretion