Renal handling of potassium ions

My presentation

1. RENAL HANDLING OF POTASSIUM IONS PRESENTOR Dr. K. AMUDHA LAKSHMI M.B.B.S.,D.O.,M.D

2. INTRODUCTION HISTORY PHYSIOLOGICAL ROLES OF POTASSIUM RENAL HANDLING OF POTASSIUM POTASSIUM HOMEOSTASIS CLINICAL CORELATIONS SUMMARY REFERENCES

3. INTRODUCTION Potassium is one of the most abundant cations in the body. Principal intracellular cation . The total body stores are approximately 50 to 55 mEq /kg 98% located ICF,140 mEq /L 2%located ECF,4.2 mEq /L

4. 90% readily exchangable 10% non exchangable Amount ingested =up to 100 mEq /d=2.5 gm/d 92%urinary excretion 8%GIT excretion Sources- banana, oranges, pineapples, potatoes, beans, chicken, liver & tender coconut water.

5. HISTORY CARL LUDWIG (1816-1895) German Physician and Physiologist Theory of Renal secretion

6. SIR HUMPHRY DAVY First isolated potassium ion in 1807 First metal isolated by electrolysis.

7. RABINOWITZ AND COLLEAGUES Proposed potassium homeostasis, three decades ago.

8. PHYSIOLOGICAL ROLES OF POTASSIUM ROLES OF INTRACELLULAR K + Maintains Intracellular osmotic pressure Cellular volume maintenance Intracellular pH regulation Optimal activity of enzyme pyruvate kinase of glycolysis . DNA/protein synthesis Cell growth

9. ROLES OF TRANSCELLULAR K + Resting cell membrane potential Transmission of nerve impulse Muscle contraction Cardiac pacemaker rhythmicity Regulation of acid base balance and water balance in the cells.

10. RENAL HANDLING OF POTASSIUM GLOMERULUS : Filtration occurs freely across glomerular capillaries and potassium is not bound to plasma proteins. TF/PK + in Bowman’s space is 1.00

11. PCT : 7% reabsorbed by beek flow or solvet drag 65% reabsorbed by paracellular transport via Na + K + - ATPase . Diffusion of K + along the concentration gradient. Exit from basolateral membrane and entry into cells occurs by conductive K + channel, K + - Cl - cotransporter and Na + K + - ATPase pump.

12. TAL : 27% of the filtered K + is reabsorbed by the Thick ascending loop of Henle by Na + K + Cl - pump -active transport mechanism Paracellular passive reabsorbtion occurs by voltage gradient through NKCC2 .

13. DT & CD: The distal tubule and collecting duct are able to reabsorb or secrete K + Intercalated cells are involved in reabsorption of K + Principal cells are involved in secretion of K + 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.

14. Intercalated cells reabsorb K + via an H + K + - ATP ase transport mechanism located in the apical membrane. This transport mediates uptake of K + in exchange for H + . This phenomenon only occur during low potassium dietary intake . POTASSIUM REABSORPTION IN DT & CD

15. K + SECRETION BY PRINCIPAL CELLS Secretion from blood into the tubule lumen is a two step process: Uptake of K + from blood across the basolateral membrane by Na + K + - ATPase and Diffusion of K + from the cell into tubular fluid via K + channels by electrical & chemical gradient.

16. Three major factors that control the rate of K + secretion by the distal tubule and the collecting duct The activity of Na + K + - ATP ase The driving force (electrochemical gradient) for movement of K + across the apical membrane The permeability of the apical membrane to K + By the presence of ROMK (Renal outer medullary potassium)channels and high conductance BK (big potassium) channels.

17. REGULATION OF K + SECRETION DIETARY K + A diet high in K + increases K + secretion by Stimulation of Na + K + - ATP ase Increasing Permeability of apical membrane to K + Increasing Aldosterone secretion Increasing Flow rate of tubular fluid A diet low in K + decreases K + secretion Opposite to the above effects Stimulating intercalated cells to reabsorb K + by the H + K + - ATP ase

18. RELATION BETWEEN PLASMA POTASSIUM AND POTASSIUM SECRETION

19. ALDOSTERONE Its secretion increased by hyperkalemia & angiotensin II Its secretion is decreased by hypokalemia & ANP Acute increase in aldosterone does not increase K + secretion because: Increased Sodium and water reabsorption , ,decreases tubular flow, decreases K + secretion

20. Chronic rise in Aldosterone increases K + secretion by Increasing amount of Na + K + -ATP ase in principal cells. Making Transepithelial potential difference(TEPD) more lumen negative by increasing more sodium reabsorption by ENaC . Increasing permeability of apical membrane to K + Hyperaldosteronism increases K + secretion and causes hypokalemia eg.Primary aldosteronism Hypoaldosteronism decreases K + secretion and causes hyperkalemia eg.Addison’s disease

21. RELATION BETWEEN POTASSIUM INTAKE,PLASMA POTASSIUM CONCENTRATION AND ALDOSTERONE SYSTEM

22. RELATION BETWEEN PLASMA POTASSIUM CONCENTRATION,POTASSIUM EXCRETION AND ALDOSTERONE

23. RELATION BETWEEN PLASMA POTASSIUM CONCENTRATION AND ALSOSTERONE

24. BASIC FEEDBACK MECHANISM BY ALSODTERONE

25. ACID BASE Acidosis decreases K + secretion Alkalosis increases K + secretion Metabolic acidosis may either inhibit or stimulate excretion of K +

26. FLOW OF TUBULAR FLUID A rise in the flow of tubular fluid ( eg with diuretic treatment ,ECF volume expansion) stimulates secretion of K + within minutes A fall ( eg : ECF volume contraction caused by haemorrhage, severe vomiting or diarrhoea) reduces secretion of K + by the distal convoluted tubule and collecting duct

27. Increase in tubular flow increases K + secretion by Change in electrochemical driving force for K + across the apical membrane Stimulation of K + uptake across basolateral membrane by increasing the Na + K + - ATPase . activity. Increase in tubular flow is directly proportional to dietary intake of K + Thiazide and loop diuretics increase K + secretion by increasing tubular flow rate.

28. RELATION BETWEEN POTASSIUM INTAKE, POTASSIUM SECRETION AND TUBULAR FLOW RATE

29. SODIUM INTAKE: Unchanged potassium excretion. Beneficial effect seen when diet high in potassium and low in sodium content when taken. Yanomamo tribe living in amazon of brazil,sodium intake-10-20 mmol /day Potassium intake-200 mmol /day No Hypertension & Cardiovascular diseases.

30. GLUCOCORTICOIDS: Increases K + secretion by increasing GFR & tubular flow ADH: It has both inhibitory effect(decreasing tubular flow) & stimulatory effect (increasing electrochemical driving force for K + ). Urinary excretion of K + is maintained constant.

31. CAUSES OF INCREASED DISTAL K + SECRETION High K + diet Hyperaldosteronism Alkalosis Thiazide diuretics Loop diuretics Luminal anions CAUSES OF DECREASED DISTAL K + SECRETION Low K + diet Hypoaldosteronism Acidosis K + sparing diuretics

32. POTASSIUM HOMEOSTASIS Wide fluctuations in dietary intake of potassium,its concentration is maintained by Internal balance(ICF & ECF K + distribution) External balance(renal excretion of K + ) INTERNAL BALANCE Physiological and pathological conditions can influence this process Hormones like insulin, catecholomines , aldosterone Acid base imbalance Changes in osmolarity Exercise Cell lysis

33. EXTERNAL BALANCE Maintenance of constant body potassium i.e renal excretion matches dietary intake. Potassium excretion by kidneys takes 6 hours . Its a slow process

34. HORMONAL CONTROL OF K+ HOMEOSTASIS Insulin and beta 2 agonists shifts K+ to the cell, by increase the activity of Na + K + -ATP ase , the 1Na + -1K + -2Cl - symporter , and the Na + - Cl – symporter Role of insulin infusion(with glucose to prevent hypoglycemia ) in correcting hyperkalemia . Aldosterone acting on uptake of K + into cells and altering urinary K + excretion.

35. Stimulation of α - adrenoceptors release K + from cells, especially in the liver. Produces local hyperkalemia in muscle causing local vasodilatation & activation of glycogenolysis . Stimulation of β 2 receptors causes potassium uptake into the cells, lowers plasma potassium during acute stress.eg myocardial ischaemia Insulin and epinephrine act within a few minutes , aldosterone requires about 1 hour to stimulate uptake of K + into cells.

36. MISCELLANEOUS FACTORS ACID BASE IMBALANCE Metabolic acidosis by inorganis acids increases the plasma [K + ] Metabolic acidosis by organic acids does not produce hyperkalemia . Metabolic alkalosis decreases the plasma [K + ] PLASMA OSMOLARITY Hyperosmolarity associated with hyperkalemia Hypoosmolarity results in hypokalemia . CELL LYSIS Crush injury, Tumor lysis syndrome, Rhabdomyolysis associated with destruction of cells and release of K + to ECF

37. EXERCISE Vigorous exercise, plasma [K + ] may increase by 2.0 mEq /L Reversed after taking rest. Patients with disturbed T tubule architecture of muscles, certain endocrine disorders, renal failure, on beta blockers for hypertension can get significant hyperkalemia on exercise.

38. DRUGS THAT INDUCE HYPERKALEMIA Dietary K + suppplements ACE Inhibitors K + sparing diuretics Heparin Prostaglandin suppressing drugs Risk for drug induced hyperkalemia are Elderly individuals Diabetics Renal insufficiency

39. CLINICAL CORRELATIONS HYPERKALEMIA Plasma concentration of K + >5.5 mEq /L CAUSES Reduced excretion- acute renal failure Potassium sparing diuretics Increased potassium intake or release potassium supplements Rhabdomyolysis Hemolytic states

40. Transcellular shifts of potassium Acidosis Beta blockers Cell destruction Insulin deficiency Addison’s disease Cell lysis

41. CLINICAL MANIFESTATIONS Early- hyperactive muscles, paresthesia Late-muscle weakness, flaccid paralysis Dysrhythmias Bradycardia, heart block ,cardiac arrest

42. CHANGES IN ECG PATTERN Appearance of tall, thin T waves Prolonged PR interval ST segment depression Lengthen the QRS interval As plasma [K + ] approaches 10 mEq /L, the P wave disappears ,the QRS interval broadens, the ECG appears as a sine wave and the ventricles fibrillate

43. HYPOKALEMIA Serum K + <3.5 mEq /L CAUSES Diabetes Insulin therapy Ketoacidosis – H + replaces K + ,which is lost in urine β -adrenergic drugs or epinephrine Decreased intake of K +

44. Increased K + loss by Diuretics Metabolic alkalosis Trauma and stress Conn’s diseases Redistribution between ICF & ECF

45. CLINICAL MANIFESTATIONS Neuromuscular disorders Weakness , flaccid paralysis, respiratory arrest constipation Dysarrythmias Cardiac arrest

46. ECG CHANGES : Prolongs the QT interval Inverts the T wave and lowers the ST segment

47. DIURETICS LOOP DIURETICS -TAL Eg:furosemide,ethacrynic acid,bumetanide THIAZIDE DIURETICS -EDT Eg:chlorothiazide,hydrochlorothiazide CARBONIC ANHYDRASE INHIBITORS -PT Eg:acetazolamide POTASSIUM SPARING DIURETICS -LDT Eg:spironolactone,triamterene,amiloride OSMOTIC DIURETICS -PT Eg:mannitol,isosorbide

48. SUMMARY

49. REFERENCES Guyton and Hall- Text Book of Medical Physiology-13 th International edition. Ganong ‘s Review of Medical Physiology 26 th edition. Text book of medical Physiology- Indhu Khurana 2 nd edition Comprehensive Text Book of Medical Physiology- G.K. Pal 2 nd edition Berne & Levy -Text book of Medical Physiology 1 st edition Boron -Text book of Medical Physiology 3 rd edition Sharada Subramaniam - Text book of Medical Physiology 7 th edition Chatterjee - Textbook of human physiology- 13 th edition