1. Disorders of potassium Dr Muhammad Rizwan ul Haque Assisstant Professor of Nephrology Shaikh Zayed Postgraduate Medical institute Lahore

2. Potassium Functions Most abundant intracellular cation Regulates heart function Essential for protein and nucleic acid synthesis Important for neuromuscular excitability Maintains resting membrane potential

3. Potassium Metabolism Normal potassium level is 3.5-5.0 mEq/L Poor indicator of total body stores Total body potassium stores are approximately 50 mEq/kg (3500 mEq in a 70-kg person).

4. Serum Potassium Regulation Well-developed systems for sensing potassium by the pancreas and adrenal glands High serum potassium -  insulin – stimulation of sodium potassium pump in muscles -  muscle uptake of potassium  aldosterone- enhancement of distal renal expression of secretory potassium channels (ROMK) –  potassium excretion

5. Serum Potassium Regulation Low potassium states result in insulin resistance, impairing potassium uptake into muscle cells cause decreased aldosterone release leading to decrease renal potassium excretion

6. Potassium Metabolism 88-90 % 2-3 % 9-10% In Renal Failure K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+

7. -35 -60 SA Node Action Potential

8. Threshold Potential Resting Membrane Potential Excitability Potential Normal Cardiac Tissue Excitability - 90 - 60 +20 0

9. Nernst Equation E x = - x log 61 Z XiXoXiXo Resting membrane potential is the combination of equilibrium potential and conductance of various ions Equilibrium Potential

10. Equilibrium Potential Nernst Equation 96-(134+52)=-90 mv

11. Disorders of Potassium Hyperkalemia Intake > Excretion (loss) Transcellular shift Hypokalemia Excretion (loss) > Intake Transcellular shift

12. Renal Excretion of Potassium Renal adaptive mechanisms allow the kidneys to maintain potassium homeostasis until the GFR drops to less than 15-20 mL/min Obligatory renal losses are 10-15 mEq/day.

13. Increased Renal Excretion Aldosterone High distal delivery of sodium (diuretics) High urine flow rate (osmotic diuresis) High serum potassium Delivery of non-absorbable anions to collecting duct. (bicarbonate)

14. Decreased Renal Excretion Aldosterone deficiency or resistance to aldosterone Low distal delivery of sodium Low urine flow rate Low serum potassium Renal failure

15. Trans-cellulr shift Glucoregulatory hormones Insulin enhances potassium entry into cells, Glucagon impairs potassium entry into cells Adrenergic stimuli: Beta-adrenergic stimuli enhance potassium entry into cells Alpha-adrenergic stimuli impair potassium entry into cells pH: Alkalosis enhances potassium entry into cells Acidosis impairs potassium entry into cells

16. Transcellular Potassium Shift Insulin Beta-adrenergic stimuli Alkalemia Blood at higher temp Glucagon Beta blockers Alpha adrnerigic stimulation Tissue destruction Acidemia Acute increase in serum osmolility Blood stored at <4 C o K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ HYPOKALEMIA HYPERKALEMIA

17. Hyperkalemia 5 % in general population 10 % of hospitalized patients

18. Classification of Hyperkalemia 5.5-6.0 mEq/L – Mild Hyperkalemia 6.1-7.0 mEq/L - Moderate 7.0 mEq/L and greater - Severe

19. Mortality Overall mortality rate 14.3%. The risk increasing as the potassium level increases. Serum PotassiumMortality rate 7 meq/l28 % <6.5 meq/l9 %

20. Causes of Hyperkalemia For excessive potassium intake, Eating disorders - exclusively high-potassium foods, such as fruits, dried fruits, juices, and vegetables with little to no sodium Heart healthy diets - Very low–sodium and high- potassium diets Use of potassium supplements in over-the-counter herbal supplements, salt substitutes, or prescribed pharmacologic agents

21. Causes of Hyperkalemia Renal failure Ingestion of drugs that interfere with potassium excretion Potassium-sparing diuretics, Angiotensin-converting enzyme inhibitors, Nonsteroidal anti-inflammatory drugs, Impaired responsiveness of the distal tubule to aldosterone Type IV renal tubular acidosis observed with diabetes mellitus, sickle cell disease. Chronic partial urinary tract obstruction

22. Causes of Hyperkalemia Hyperosmolality Rhabdomyolysis Tumor lysis syndrome Succinylcholine administration, which depolarizes the cell membrane EACA (Epsilon aminocapric acd), arginine and lysine administration Hyperkalemic periodic paralysis Insulin deficiency or insulin resistance (ie, type I or type II diabetes mellitus) Use of beta-adrenergic antagonist therapy (eg, for hypertension or angina

23. Pseudohyperkalemia Prolonged use of tourniquet Hemolysis (in vitro) Delay in processing of blood Severe leukocytosis Severe thrombocytosis

24. Symptoms Nonspecific, related to muscular or cardiac function. Weakness and fatigue. Occasionally, frank muscle paralysis or shortness of breath. May be palpitations or chest pain.

25. Hyperkalemia- Signs Bradycardia due to heart block or tachypnea due to respiratory muscle weakness. Muscle weakness and flaccid paralysis Depressed or absent deep tendon reflexes Muscle tenderness, weakness, suggesting rhabdomyolysis.

26. ECG in Hyperkalemia

27. Threshold Potential Resting Membrane Potential Excitability Potential Normal Cardiac Tissue Excitability - 90 - 60 +20 0

28. Threshold Potential Resting Membrane Potential Excitability Potential Increased Excitability - 60 - 70 - 90

29. Threshold Potential Resting Membrane Potential Excitability Potential Persistent Depolarization in Hyperkalemia

30. Work-up Urinary potassium, serum sodium, urine osmolality Transtubular potassium gradient = (urine K x serum osmolarity)/(serum K x urine osmolarity) TTKG of < 3 - lack of aldosterone effect on collecting tubules – decreased excretion TTKG greater > 7 - an aldosterone effect, - normal excretion 24 hour urinary potassium.

31. Transtubular Potassium Gradient (TTKG) It is a measurement of net K+ secretion by the distal nephron after correcting for changes in urinary osmolality Determine whether hyperkalemia is caused by Aldosterone deficiency/resistance or Nonrenal causes. Clinical correlation and potassium intake should be assessed. TTKG = (Ku/Ks) × (Sosm/Uosm)

32. Transtubular Potassium Gradient

33. Evaluation of Hyperkalemisa

34. Emergently treat K+ Are K sparing medications are being administered Are ECG changes are present

35. Treatment Evaluation for potential toxicities Decreasing potassium intake Increasing potassium uptake into cells Increasing potassium excretion Determining the cause to prevent future episodes

36. Treatment of Hyperkalemia DrugRoute of Admin. OnsetDuration CalciumIV 10 cc 10%1-3 min30 min Insulin- Glucose IV20-30 minutes 2 hours Beta adrenergic20 mg in 4 ml nebulize in 10 m 15-30 min30 min- 3 hrs Ion exchange resins 15 G in 15-30 ml 70% sorbitol 2-6 hrs6-12 hrs DiureticsIV 40-80 mg Furosemide 15 min2-3 hours HemodialysisImmediate Until dialysis completed

37. Threshold Potential Resting Membrane Potential Excitability Potential Normal Cardiac Tissue Excitability – Effect of Calcium - 90 - 60 High Serum Calcium

38. Threshold Potential Resting Membrane Potential Excitability Potential Increased Excitability - 60 - 90 - 30

39. Threshold Potential Resting Membrane Potential Excitability Potential Increased Excitability- Effect of Calcium -60 - 70 -90 -40 30 10 30

40. Hypokalemia

41. Defined as a potassium level less than 3.5 mEq/L. Mild hypokalemia - serum level of 3-3.5 mEq/L. Moderate hypokalemia - serum level of 2.5-3 mEq/L. Severe hypokalemia - level less than 2.5 mEq/L.

42. Symptoms Palpitations Skeletal muscle weakness or cramping Paralysis, paresthesias Constipation Nausea or vomiting Abdominal cramping Polyuria, nocturia, or polydipsia Psychosis, delirium, or hallucinations Depression

43. Signs Signs of ileus Hypotension Ventricular arrhythmias Cardiac arrest Bradycardia or tachycardia Premature atrial or ventricular beats Hypoventilation, respiratory distress Respiratory failure Lethargy or other mental status changes Decreased muscle strength, fasciculations, or tetany Decreased tendon reflexes

44. ECG in Hypokalemia

45. Threshold Potential Resting Membrane Potential Excitability Potential Hyperpolarization in Hypokalemia -120

46. Causes of Hypokalemia Medications: Thiazide and loop diuretics, aminoglycosides, amphotericin B, β 2 - agonists, and adrenal steroids, Chronic laxative abuse GI Vomiting, diarrhea, NG suction

47. Causes of Hypokalemia Renal: Renal tubular acidosis, (type 1, 2) Magnesium deficiency Primary hyperaldosteronism Cushing Syndrome Salt-losing nephropathies Bartter and Gitelman syndromes Therapeutic alkalinization of the urine

48. Causes of Hypokalemia Treatment of megaloblastic anemia with vitamin B 12 and folatemegaloblastic anemia Miscellaneous toxic conditions: Barium intoxication; chloroquine toxicity; glue sniffing due to hippurate accumulation, Tocolytic therapy in pregnant women to treat premature labor Amphotericin B therapy

49. Causes of Hypokalemia Genetics disorders Familial (hypokalemic) periodic paralysis Congenital adrenogenital syndromes Liddle syndrome Bartter and Gitelman syndromes Familial interstitial nephritis Glucocorticoid-remediable aldosteronism

50. Diagnostic Workup of Hypokalemia

52. Treatment of Hypokalemia Potassium replacement How much? What route? How fast ? What salt ?

53. Treatment Asymptomatic mild hypokalemia Oral replacement Moderate to severe (no emergency) Intravenous 40 meq/l 160 meq per day Hypokalemia with cardiac dysarrythmias 20 meq/100 cc /hr under ECG monitoring

54. Treatment of Hypokalemia Metabolic alkalosis Potassium chloride Metabolic acidosis Potassium citrate/acetate Diabetic ketoacidosis (+hyphosphatemia) Potassium phophate

55. Threshold Potential Resting Membrane Potential Excitability Potential Hyperpolarization in Hypokalemia -120

56. Threshold Potential Resting Membrane Potential Excitability Potential Hyperpolarization in Hypokalemia -120 Ca ++ administration

57. Threshold Potential Resting Membrane Potential Excitability Potential Low Serum Potassium & Calcium -120 S. Potassium correction in hypocalcemia Hypocalcemia

58. Threshold Potential Resting Membrane Potential Excitability Potential Low Serum Potassium & Calcium -120 S. Calcium correction in hypokalemia Hypocalcemia