1. Addis Ababa UniversityCollege of Health ScienceDepartment of Medical Physiology Presentation on Potassium Homeostasis and its Renal Handling By Girmay F 10/8/2011 1

3. Hypokalemia7. References 10/8/2011 2 Potassium homeostasis and its renal handling

4. 1.Objectives At the end of this presentation students will able to:- Mention the major physiological role of potassium. Explain the main mechanisms of potassium homeostasis. Elaborate renal handling of potassium. Identify factors that affect potassium excretion. List the homeostatic disturbance of potassium. 10/8/2011 Potassium homeostasis and its renal handling 3

5. 2.Introduction The total body stores are approximately 50 to 55 meq/kg. The main intracellular cation. 98% located ICF,150 meq/L. 2% located ECF,4meq/L. 90% readily exchangeable 10% non exchangeable Amount ingested = up to 100meq/d = 2.5 gm/d 92% urinary excretion 8% GIT excretion 10/8/2011 4 Potassium homeostasis and its renal handling

6. Introduction ..cont’d 10/8/2011 5 Potassium homeostasis and its renal handling

8. Neuromuscular excitability

9. Cardiac pacemaker rhythmicity10/8/2011 6 Potassium homeostasis and its renal handling

11. Acid base imbalance

12. Changes in osmolarity

13. Exercise

14. Cell lysis10/8/2011 7 Potassium homeostasis and its renal handling

15. 4.1 Hormonal control of K+ homeostasis Insulin and beta 2agonsists shifts K+ to the cell, by increase the activity of Na+,K+-ATPase, the 1Na+-1K+-2Cl- symporter, and the Na+-Cl- symporter. Aldosterone acting on uptake of K+ into cells and altering urinary K+ excretion. Stimulation of α-adrenoceptors releases K+ from cells, especially in the liver. insulin and epinephrine act within a few minutes, aldosterone requires about an hour to stimulate uptake of K+ into cells. 10/8/2011 8 Potassium homeostasis and its renal handling

16. 10/8/2011 9 Potassium homeostasis and its renal handling

17. 10 Hormonal control of K+ homeostasis

20. …………Cont’d Physiological: Keep Plasma [K+] Constant Epinephrine Insulin Aldosterone Pathophysiological: Displace Plasma [K+] from Normal Acid-base balance Plasma osmolality Cell lysis Exercise Drugs That Induce Hyperkalemia Dietary K+ supplements ACE inhibitors K+-sparing diuretics Heparin 10/8/2011 12 Potassium homeostasis and its renal handling

21. 5.Renal handling of potassium The PCT reabsorbs about 67% of the filtered K+ under most conditions by K+-H+ exchanger and K+-Cl- symport. 20% of the filtered K+ is reabsorbed by the TALH. The distal tubule and collecting duct are able to reabsorb or secrete K+. 10/8/2011 Potassium homeostasis and its renal handling 13

22. ……….cont’d The rate of K+ reabsorption or secretion by the distal tubule and collecting duct depends on a variety of hormones and factors. Most of the daily variations in potassium excretion is caused by changes in potassium secretion in the distal and cortical collecting tubules. 10/8/2011 Potassium homeostasis and its renal handling 14

23. ……………cont’d 10/8/2011 Potassium homeostasis and its renal handling 15

25. ……..cont’d 10/8/2011 Potassium homeostasis and its renal handling 17

26. ………….Cont’d Intercalated cells reabsorb K+ via an H+,K+-ATPase transport mechanism located in the apical membrane . This transporter mediates uptake of K+ in exchange for H+. This phenomena only occur during low potassium dietary intake. 10/8/2011 Potassium homeostasis and its renal handling 18

27. 5.2 REGULATION OF K+ SECRETION .. 1.Dietary K+ A diet high in K+ increases K+ secretion .a diet low in K+ decreases K+ secretions. 2. Aldosterone Increases K+ secretion. Hyperaldosteronism increases K+ secretion and causes hypokalemia . Hypoaldestronism decreases K+ secretion and causes hyperkalemia MOA 10/8/2011 Potassium homeostasis and its renal handling 19

28. …………….cont’d 10/8/2011 Potassium homeostasis and its renal handling 20

29. …..cont’d 3.Acid–Base Acidosis decreases K+ secretion. Alkalosis increases K+ secretion Metabolic acidosis may either inhibit or stimulate excretion of K+ . 10/8/2011 Potassium homeostasis and its renal handling 21

30. ………….cont’d 10/8/2011 Potassium homeostasis and its renal handling 22

31. ………….Cont’d 4.Flow of Tubular Fluid A rise in the flow of tubular fluid (e.g., with diuretic treatment, ECF volume expansion) stimulates secretion of K+ within minutes. A fall (e.g., ECF volume contraction caused by hemorrhage, severe vomiting, or diarrhea) reduces secretion of K+ by the distal tubule and collecting duct. MOA 10/8/2011 Potassium homeostasis and its renal handling 23

32. ………….Cont’d 10/8/2011 Potassium homeostasis and its renal handling 24

33. 10/8/2011 Potassium homeostasis and its renal handling 25 ……………..Cont’d

34. 6.Clinical correlations 10/8/2011 Potassium homeostasis and its renal handling 26 1.Hyperkalemia plasma concentration of K+ > 5.5 mEq / L Causes a. Reduced excretion- acute renal failure -potassium –sparing diuretics. b. Increased intake or release . -potassium supplements - Rhabdomyolysis -Hemolytic sates

36. Beta blockers ,cell destruction

37. Insulin deficiency

38. Addison’s disease

39. Cell lysis 10/8/2011 Potassium homeostasis and its renal handling 27

41. prolong the PR interval, depress the ST segment

42. Lengthen the QRS interval of the ECG.

44. 30 ……………cont’d Decreased intake of K+ Increased K+ loss Diuretics Metabolic alkalosis Trauma and stress Conn’s diseases Redistribution between ICF and ECF.

45. 31 ………….Cont’d Clinical manifestation Neuromuscular disorders Weakness, flaccid paralysis, respiratory arrest, constipation Dysrhythmias Cardiac arrest Prolongs the QT interval, inverts the T wave, and lowers the ST segment of the ECG.

46. 7.References Berne and levy physiology, sixth edition Bruce M.Koeppen, Bruce A. Stanton Guyton and Hall Textbook of Medical Physiology, 12th Edition. Human physiology: The Basis of Medicine, 3rd Edition. Institutional websites 10/8/2011 Potassium homeostasis and its renal handling 32

47. THANK YOU