HYPERKALEMIA Dr.Sujith S

1. HYPERKALEMIADr.Sujith S

2. Normal Plasma K+ concentration 3.5 - 5mmol/L Major intracellular cation K+ in the ECF <2% of the total body content ICF/ECF=38:1

3. K+ intake-40-120 mmol/day,90% of which is absorbed by the GI tract. Maintenance of steady state Extrarenal adaptive mechanism Urinary excretion

4. Major source of excretion-renal Filtered load of K+ is 20 fold greater than ECF K+ content. 90% of filtered K+ is absorbed by the PCT & loop of Henle K+ Excretion

5. Proximally K+is reabsorbed passively with Na & water. Luminal Na+-K+-2Cl- co transporter- mediates K+uptake in thick ascending limb of loop of Henle. Regulation of renal excretion & total K balance is regulated in the distal nephron

6. K+secretion Two physiological stimuli ?Aldosterone & hyperkalemia. ?K+ conc alone directly affects the K+secretion. ?Increased distal flow rate �increases renal K+loss

7. Ion transport in collecting tubule

8. Serum K+ concentration is determined by ?K+intake ?distribution between the cells & extracellular fluid ?urinary excretion of K+

9. Measurement Urine K+ levels A value above 80 to 100 meq/day ? increased potassium intake Urine K+ excretion

10. Identifies condition that predisposes to hyperkalemia. Asymptomatic Generalised fatigue Paralysis Palpitations Clinical Features

11. Cardiac examination may reveal extrasystoles, pauses. Neurologic examination may reveal diminished deep tendon reflexes or decreased motor strength. In rare cases, muscular paralysis and hypoventilation may be observed. Search for the stigmata of renal failure, such as edema, skin changes, and dialysis sites. Look for signs of trauma that could put the patient at risk for rhabdomyolysis

12. Complete Blood Count Electrolytes BUN S.Creatinine S.Osmolality Urine osmolality Investigations

13. Mild Hyperkalemia(5.5-6.5mmol/L)-Tall peaked T waves with narrow base Moderate hyperkalemia(6.5-8 mmol/L)-Peaked T waves Prolonged PR interval Decreased amplitude of P waves Widening of QRS complex ECG

14. Severe Hyperkalemia- Absence of P waves Intraventricular blocks,BBB, Progressive widening of QRS complex Sine wave pattern ventricular fibrillation,asystole

18. Increased potassium release from cells Pseudohyperkalemia Metabolic acidosis Insulin deficiency, hyperglycemia, and hyperosmolality Increased tissue catabolism �-adrenergic blockade Exercise Other Digitalis overdose Hyperkalemic periodic paralysis Succinylcholine Arginine hydrochloride Reduced urinary potassium excretion Hypoaldosteronism Renal failure Effective circulating volume depletion Hyperkalemic type 4 renal tubular acidosis Selective impairment of potassium excretion Ureterojejunostomy Causes

19. ?Renal Failure ?Decreased distal flow(decreased effective arterial volume) ?Decreased K+secretion a)Impaired Na+ reabsorption 1)Primary hypoaldosteronism:adrenal insufficiency,adrenal enzyme deficiency Causes

20. 2)Secondary Hypoaldosteronism:Hyporeninemia,drugs (ACEI,NSAIDS,Heparin) 3)Resistance to aldosterone: Pseudohypoaldosteronism,tubulointerstitial disease,drugs(K+sparing diuretics,trimethoprim,pentamidine. b)Enhanced Cl-reabsorption 1)Gordon�s syndrome 2)Cyclosporine

21. The severity of Hyperkalemia is determined by ?Symptoms ?Plasma K+ concentration ?Electrocardiographic abnormalities

22. POTASSIUM ADAPTATION due to more rapid potassium excretion in the urine Excess K+ Intake

23. Increase K+ release from cells

24. Elevation in Serum K+ concentration due to movement of K+ out of the cells. Occurs In mechanical trauma during venipuncture Cooling of sample & specimen deterioration In leucocytosis>100000, thrombocytosis>400000 Pseudohyperkalemia

25. Metabolic acidosis Insulin deficiency,hyperglycaemia,hyperosmolarity Beta-adrenergic blockade Exercise Hyperkalemic Periodic Paralysis Other causes

26. In metabolic acidosis, more than one-half of the excess hydrogen ions is buffered in the cells. Electroneutrality is maintained in part by the movement of intracellular K+ into the extracellular fluid. Metabolic acidosis results in a plasma K+ concentration that is elevated in relation to total body stores. On average, the plasma K+ concentration will rise by 0.6 meq/L (range 0.2 to 1.7 meq/L) for every 0.1 unit reduction in extracellular pH. Metabolic Acidosis

27. Insulin promotes K+ entry into cells The ingestion of glucose (which stimulates endogenous insulin secretion) minimizes the rise in the serum K+concentration. Mechanisms of K+ out of cells. ?The loss of water raises the cell K+ concentration, thereby creating a favorable gradient for passive K+ exit. Insulin deficiency,hyperglycaemia,hyperosmolarity

28. Hyperosmolality-induced hyperkalemia ?Administration of hypertonic mannitol�/ development of hypernatremia. Somatostatin-postprandial hypotension cases fall in insulin levels Fasting in dialysis patients lowers insulin levels enough to cause clinically important hyperkalemia and resistance to beta-adrenergic stimulation of K+uptake .

29. ?Trauma (including noncrush trauma) ?Administration of cytotoxic / radiation therapy to patients with lymphoma / leukemia (the tumor lysis syndrome) Tissue Catabolism

30. Mechanisms mediated: ?A delay between K+ exit during depolarization and subsequent reuptake by the Na-K-ATPase pump. ?With severe exercise, there is increased number of open K+ channels in the cell membrane. These channels are inhibited by ATP, an effect that is removed by the exercise-induced decline in ATP levels which removes the inhibitory effect of ATP on these channels . ?The release of K+ during exercise may have a physiologically important role. The local increase in K+ concentration has a vasodilator effect, thereby increasing blood flow and energy delivery to the exercising muscle Exercise

31. Hyperkalemic form of periodic paralysis is an autosomal dominant disorder Episodes of weakness / paralysis are usually precipitated by cold exposure,/rest after exercise, fasting/ the ingestion of small amounts of potassium. The primary abnormality in hyperkalemic periodic paralysis - a point mutation in the gene for the alpha subunit of the skeletal muscle cell sodium channel. Hyperkalemic Periodic Paralysis

32. The degree of potassium secretion is primarily stimulated by three factors: ?An increase in the serum potassium concentration ?A rise in the plasma aldosterone concentration ?Enhanced delivery of sodium and water to the distal secretory site

33. Chronic Hyperkalemia ?Impaired secretion ?Diminished distal solute delivery

34. Decreased K+ Secretion

35. Primary hypoaldosteronism Congenital adrenal hyperplasia Impaired Na+Reabsorption

36. ?Hyporeninemia- Decrement in the angiotensin II production intradrenal defect-decline in aldosterone secretion Causes Diabetic Nephropathy-renal failure Chronic Interstitial Nephritis Features: ?Low plasma renin activity is common in diabetic patients dueto a defect in the conversion of the precursor prorenin to active renin ?the increase in atrial natriuretic peptide release in these patients can suppress both the release of renin and hyperkalemia-induced secretion of aldosterone Secondary Hypoaldosteronism 

37. NSAID(Low PRA & aldosterone) ?Reduce renal secretion & vasodilatory renal prostaglandins ?Impair angiotensin II induced aldosterone secretion. ACEI,ARB ?Angiotensin I----Angiotensin II ?Angiotensin II Receptor ?Inhibits renin activity Drugs

38. Antibiotics ?Trimethoprim & pentamidine--- distal nephron Na reabsorption Heparin has a direct toxic effect on the adrenal zona glomerulosa cells Mediated by reduction in the number and affinity of adrenal angiotensin II receptors . Amiloride & triamterene block the apical Na channels in the principal cell Other.....

39. Pseudohypoaldosteronism Characterised by Resistence to aldosterone

40. Decreased excretion Increased distal flow rate & K+secretion compensate for the decreased renal mass. As GFR falls below10-15ml/min/oliguria ensues-hyperkalemia Other nephropathies Interstitial nephritis Lupus nephritis Sickle cell disease Diabetic nephropathy Renal Failure

41. Characterized by Hyperkalemia Metabolic acidosis Normal GFR Volume expanded with suppressed renin-aldosterone levels as well as refractory to the kaliuretic effect of exogenous mineralocorticoids Due to incresed distal Cl-reabsorption Gordon�s syndrome

42. In cases where urinary potassium excretion is impaired ?TTKG=���[Urine K � (Urine osmolality / Plasma osmolality)] ���Plasma K ?TTKG in normal subjects is 8 to 9 ?Rises to above 11 with a K+ load, indicating increased K+ secretion TTKG

43. A value below 7 and particularly below 5 in a hyperkalemic patient may be due to: Hypoaldosteronism resistence to renal effects of mineralocortricoid

45. Hyperkalemia ?Movement of potassium out of the cells ?Administration of potassium to patients who are unable to excrete potassium in the urine due to 1)Advanced renal failure 2)Volume depletion 3)Hypoaldosteronism of any cause Diagnosis

46. Diagnosis of hypoaldosteronism

47. Drug / presence of a disease that can impair aldosterone release: Nonsteroidal antiinflammatory drug, Angiotensin converting enzyme (ACE) inhibitor Cyclosporine Heparin Acquired immune deficiency syndrome

48. ?It is associated with low PRA (in most but not all cases) ?low serum aldosterone concentration ?normal serum cortisol concentration. Hyporeninemic Hypoaldosteronism

49. low serum aldosterone Low cortisol concentrations, High PRA due to volume depletion and hypotension. Primary adrenal insufficiency

50. Hypoaldosteronism can result from a deficiency of enzymes required for aldosterone synthesis, which may or may not be associated with concurrent abnormalities in cortisol and androgen production, Low serum aldosterone Low cortisol concentrations, High PRA due to volume depletion and hypotension Congenital Adrenal Hyperplasia

51. Congenital isolated hypoaldosteronism is a rare inherited disorder-autosomal Recessive trait,defect in the aldosterone synthase (CYP11B2) Clinical Presentation ?recurrent dehydration ?salt wasting ?failure to thrive

52. These disorders can be differentiated by measurement of plasma renin activity (PRA) and serum aldosterone and cortisol These tests should be performed after the administration of a loop diuretic or three hours in the upright position, which will increase renin and aldosterone release in normals.

53. Determined plasma K+ concentration Muscular weakness ECG changes Fatal hyperkalemia-7.5mmol/L Treatment

54. Severe Hyperkalemia Minimizing membrane potential Shifting K+into the cells Promoting K+ loss

55. Treatment of Hyperkalemia

56. Cause Presence of symptoms & signs The most serious manifestations of hyperkalemia ?muscle weakness or paralysis, ?cardiac conduction abnormalities ?cardiac arrhythmias sinus bradycardia, sinus arrest, slow idioventricular rhythms, ventricular tachycardia, ventricular fibrillation, and asystole. Urgency of therapy

57. Occurs at serum pK concentration>7 Meq/L in chronic hyperkalemia Clinically manifests-in one or more ECG abnormalities with hyperkalemia

58. Continuous cardiac monitoring and serial electrocardiograms are warranted in patients with hyperkalemia on rapidly acting therapies. The serum potassium should be measured at one to two hours after the initiation of therapy. Monitoring

59. Calcium directly antagonizes the membrane actions of hyperkalemia. Hyperkalemia-induced depolarization of the resting membrane potential leads to inactivation of sodium channels and decreased membrane excitability. The effect of intravenous calcium administration begins within minutes, but is relatively short-lived (30 to 60 minutes) The usual dose of calcium gluconate�is 1000 mg (10 mL of a 10 percent solution) infused over two to three minutes, with constant cardiac monitoring. Calcium

60. The dose of either formulation can be repeated after five minutes if the ECG changes persist or recur. Calcium Gluconate�can be given peripherally, ideally through a small needle or catheter in a large vein. Calcium should not�be given in bicarbonate-containing solutions, which can lead to the precipitation of calcium carbonate

61. When hyperkalemia occurs in patients treated with digitalis, calcium should be administered for the same indications as in patients not treated with digitalis (eg, widening of the QRS complex or loss of P waves) Hypercalcemia potentiates the cardiotoxic effects of digitalis A dilute solution can be administered slowly, infusing 10 mL of 10 percent calcium gluconate�in 100 mL of 5 percent dextrose in water over 20 to 30 minutes, to avoid acute hypercalcemia

62. Insulin administration lowers the serum potassium concentration Drives potassium into the cells, primarily by enhancing the activity of the Na-K-ATPase pump in skeletal muscle Insulin should be given alone if the serum glucose is =250 mg/dL (13.9 mmol/L) The serum glucose should be measured one hour after the administration of insulin. Insulin & Glucose

63. One commonly used regimen for administering insulin and glucose is 10 units of regular insulin�in 500 mL of 10 percent dextrose, given over 60 minutes. Another regimen consists of a bolus injection of 10 units of regular insulin, followed immediately by 50 mL of 50 percent dextrose (25 g of glucose).

64. Hypertonic glucose in the absence of insulin may acutely increase the serum potassium concentration by raising the plasma osmolality, which promotes water and potassium movement out of the cells

65. The effect of insulin begins in 10 to 20 minutes, peaks at 30 to 60 minutes, and lasts for four to six hours. In almost all patients, the serum potassium concentration drops by 0.5 to 1.2 meq/L

66. Patients with renal failure are resistant to the glucose lowering effect of insulin, they are not resistant to the hypokalemic effect because Na-K-ATPase activity is still enhanced

67. Impaired renal function ?hypovolemia, ?nonsteroidal antiinflammatory drugs, ?urinary tract obstruction ?inhibitors of the renin-angiotensin-aldosterone system Treatment of Reversible Causes

68. ?Diuretics ?Cation exchange resin ?Dialysis Potassium Removal

69. Loop and thiazide diuretics increase potassium loss in the urine in patients with normal renal function. Diuretics

70. The major available cation exchange resin is sodium polystyrene sulfonate. If a cation exchange resin is given, we prefer the preparation of sodium polystyrene sulfonate�without�sorbitol. In the gut, sodium polystyrene sulfonate�takes up potassium (and calcium and magnesium to lesser degrees) and releases sodium. Each gram of resin may bind as much as 1 meq of potassium and release 1 to 2 meq of sodium. A potential side effect is exacerbation of edema due to sodium retention. � Cation Exchange resin

71. Dosing The oral dose is usually 15 to 30 g, which can be repeated every four to six hours as necessary. Single doses are probably ineffective. Lower doses of sodium polystyrene sulfonate�(5 or 10 g) are generally well tolerated (no nausea or constipation), and can be given one to three times per day to control chronic asymptomatic mild to moderate hyperkalemia in patients with chronic kidney disease, often without the necessity of concurrent laxative therapy

72. 50 g of sodium polystyrene sulfonate is mixed with 150 mL of tap water (not�sorbitol). After a cleansing enema with tap water at body temperature, the resin emulsion should be administered at body temperature through a rubber tube placed at about 20 cm from the rectum with the tip well into the sigmoid colon . The emulsion should be introduced by gravity and flushed with an additional 50 to 100 mL of non-sodium-containing fluid.

73. The emulsion should be kept in the colon for at least 30 to 60 minutes and preferably two to four hours. A cleansing enema (250 to 1000 mL of with tap water at body temperature should follow.

74. Prevention

75. In Chronic Kidney disease ,in stable maintenance haemodialysis patients. ?Low Potassium diet ?Avoid episodes of fasting. ?Avoid, if possible, drugs that raise the serum potassium concentration

76. Patients with chronic kidney disease or heart failure are often treated with RAAS inhibitors. ?Close monitoring of serum K+ concentration and estimated GFR ?The dose of RAAS inhibitors should be reduced with moderate hyperkalemia (serum potassium =5.5 meq/L) and discontinued if the serum potassium rises above 5.5 meq/L.

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