HYPOKALEMIA APPROACH TO TO FIND CAUSE .pptx

HYPOKALEMIA APPROACH

1. HYPOKALEMIA

2. Hypokalemia , usually defined as plasma K+ of less than 3.5 mmol/L, is a common electrolyte disorder that is present in a number of disease states. When faced with a patient with hypokalemia , THE FIRST STEP IS TO DETERMINE WETHER AN EMERGENCY IS PRESENT. Most serious emergency due to hypokalemia Cardiac arrythmia .(not directly correlated with plasma K+) Muscle weakness. (direct correlation with K+ level) Life threatening entity.

3. SYNOPSIS OF K+ PHYSIOLOGY MOVEMENT OF K+ ACROSS CELL MEMBRANES

4. SYNOPSIS OF K+ PHYSIOLOGY MOVEMENT OF K+ ACROSS CELL MEMBRANES

5. SYNOPSIS OF K+ PHYSIOLOGY MOVEMENT OF K+ ACROSS CELL MEMBRANES An acute shift of K+ into cells occur when insulin is given in DKA. Explains why a high carb load is a risk factor for development of an acute attack in patients with HypoPP . In patients with ( hypokalemia + metabolic acidosis), it is adviced to raise K+ above 3 mEq before giving HCO3. Any adrenergic surge ( AMI, Pancreatitis, SAH, TBI, Alcohol withdrawal etc) can cause hypokalemia . Patients who receive large dose of beta-agonists. Caution is merited for patients early in the course of therapy for pernicious anemia with vitamin B12 and also in cachectic patients who are treated with parenteral nutrition

6. SYNOPSIS OF K+ PHYSIOLOGY MOVEMENT OF K+ ACROSS CELL MEMBRANES REGULATION OF RENAL EXRETION OF K+

7. SYNOPSIS OF K+ PHYSIOLOGY MOVEMENT OF K+ ACROSS CELL MEMBRANES REGULATION OF RENAL EXRETION OF K+

8. INCREASED MINERALOCORTICOID ACTIVITY INCREASED DISTAL DELIVERY OF SODIUM AND WATER

9. CORTISOL (active form) 11b-HSDH CORTISONE (inactive form)

10. CORTISOL (active form) 11b-HSDH CORTISONE (inactive form) 11b-HSDH is lacking 11b-HSDH in inhibited 11b-HSDH action is overwhelmed

11. ETIOLOGIES OF HYPOKALEMIA

12. ETIOLOGIES OF HYPOKALEMIA DECREASED POTASSIUM INTAKE INCREASED ENTRY INTO CELL (TRANSCELLULAR SHIFT) INCREASED POTTASSIUM LOSS GIT KIDNEY SWEAT

13. DECREASED POTASSIUM INTAKE Normal potassium intake is 40 – 120 mEq per day. Our kidney is able to lower the potassium excretion in the presence of lower intake. Thus, decreased intake alone rarely causes significant hypokalemia . However, a low potassium intake can contribute to the severity potassium depletion when another cause of hypokalemia is superimposed.

14. INCREASED ENTRY INTO CELLS (TRANSCELLULAR SHIFT) INCREASED AVIALABILITY OF INSULIN Exogenous Endogenous ELEVATED BETA-ADRENERGIC ACTIVITY Endogenous stress conditions (AMI, AP. SAH, TBI, AWS) Exogenous ELEVATED EXTRACELLULAR pH Metabolic or respiratory alkalosis. Common causes together (close friends) HYPOKALEMIC PERIODIC PARALYSIS Precipitated by exercise, high carb meal PARADOXICAL HYPOKALEMIA AFTER REPELTION Cause is unknown INCREASED RED CELL PRODUCTION Vitamin B12/folate administration in megaloblastic anemia GM-CSF administration in neutropenia.

15. INCREASED ENTRY INTO CELLS (TRANSCELLULAR SHIFT) INCREASED AVIALABILITY OF INSULIN Exogenous Endogenous ELEVATED BETA-ADRENERGIC ACTIVITY Endogenous stress conditions (AMI, AP. SAH, TBI, AWS) Exogenous ELEVATED EXTRACELLULAR pH Metabolic or respiratory alkalosis. Common causes together (close friends) HYPOKALEMIC PERIODIC PARALYSIS Precipitated by exercise, high carb meal PARADOXICAL HYPOKALEMIA AFTER REPELTION Cause is unknown INCREASED RED CELL PRODUCTION Vitamin B12/folate administration in megaloblastic anemia GM-CSF administration in neutropenia. HYPOTHERMIA Accidental or induced BARIUM INTOXICATION Ingestion of contaminated food or suicidal. Blocks the potassium movement out of cells CESIUM INTOXICATION CHLOROQUINE INTOXICATION Potassium movement into the cell May go below 2 mEq ANTIPSYCHOTIC DRUGS Risperidone and quetiapine

16. INCREASED GASTROINTESTINAL LOSS UPPER GI LOSS The concentration of potassium in gastric secretions is very low. Therefore, hypokalemia in this setting is primarily due to increased urinary losses. Is usually associated with metabolic alkalosis LOWER GI LOSS Potassium in lower gi secretions is very high. Typically associated with bicarbonate wasting and hyperchloremic metabolic acidosis. Usually occur when the losses occur over prolonged period ( persistent diarhea , villous adenoma, VIPoma)

17. INCREASED GASTROINTESTINAL LOSS UPPER GI LOSS The concentration of potassium in gastric secretions is very low. Therefore, hypokalemia in this setting is primarily due to increased urinary losses. Is usually associated with metabolic alkalosis LOWER GI LOSS Potassium in lower gi secretions is very high. Typically associated with bicarbonate wasting and hyperchloremic metabolic acidosis. Usually occur when the losses occur over prolonged period ( persistent diarhea , villous adenoma, VIPoma)

18. INCREASED GASTROINTESTINAL LOSS UPPER GI LOSS The concentration of potassium in gastric secretions is very low. Therefore, hypokalemia in this setting is primarily due to increased urinary losses. Is usually associated with metabolic alkalosis LOWER GI LOSS Potassium in lower gi secretions is very high. Typically associated with bicarbonate wasting and hyperchloremic metabolic acidosis. Usually occur when the losses occur over prolonged period ( persistent diarhea , villous adenoma, VIPoma) Other rare causes: Bowel cleansing with both sodium phosphate/PEG based preparations Acute colonic pseudo-obstruction (Ogilvie’s syndrome) Ingestion of clay (geophagia)

19. INCEASED URINARY LOSS Major causes of urinary potassium wasting Diuretic use Increased mineralocorticoid activity Nonreabsorbable anions Loss of gastric secretions

20. INCEASED URINARY LOSS Major causes of urinary potassium wasting Diuretic use Increased mineralocorticoid activity Nonreabsorbable anions Loss of gastric secretions Less common causes of urinary potassium wasting Polyuria Renal tubular acidosis Hypomagnesemia Amphotericin B Salt-wasting nephropathies Liddle’s syndrome Barrter & Gitelman syndromes Low calorie diets

21. INCEASED URINARY LOSS Major causes of urinary potassium wasting Diuretic use Increased mineralocorticoid activity Nonreabsorbable anions Loss of gastric secretions All type of diuretics that acts proximal to potassium secreting site - can cause hypokalemia. Causing urinary potassium excretion. Dose dependent. Thaizide diuretics >>> loop diuretics (due to differential calcium excretion)

22. INCEASED URINARY LOSS Major causes of urinary potassium wasting Diuretic use Increased mineralocorticoid activity Nonreabsorbable anions Loss of gastric secretions Primary hyperaldosterism ( conn’s syndrome) Secondary hyperaldosteronism Apparent mineralocorticoid excess Cushing’s syndrome CAH ( defects in either steroid 11 β- hydroxylase or steroid 17 α- hydroxylase

23. INCEASED URINARY LOSS Major causes of urinary potassium wasting Diuretic use Increased mineralocorticoid activity Non- reabsorbable anions Loss of gastric secretions When sodium is presented to distal tubule with relatively large quantities of non-absorbable anions Bicarbonate – vomiting/RTA-2 BHB – DKA Hippurate – toluene use(glue sniffing) Penicillin derivatives in patients receiving high-dose penicillin therapy Effect is more prominent in presence of volume depletion

24. INCEASED URINARY LOSS Less common causes of urinary potassium wasting Polyuria Renal tubular acidosis Hypomagnesemia Amphotericin B Salt-wasting nephropathies Liddle’s syndrome Barrter & Gitelman syndromes Low calorie diets If UO is over 5-10 L/day. Obilgatory loss Primary polydipsia Central diabetes insipidus

25. INCEASED URINARY LOSS Less common causes of urinary potassium wasting Polyuria Renal tubular acidosis Hypomagnesemia Amphotericin B Salt-wasting nephropathies Liddle’s syndrome Barrter & Gitelman syndromes Low calorie diets Potassium wasting occur in both type 1 and type 2 RTA Masked by tendency of acidemia leading to potassium movement out of cells. Correction of the acidemia may uncover the true state of potassium balance.

26. INCEASED URINARY LOSS Less common causes of urinary potassium wasting Polyuria Renal tubular acidosis Hypomagnesemia Amphotericin B Salt-wasting nephropathies Liddle’s syndrome Barrter & Gitelman syndromes Low calorie diets Present in up to 40% of patients with hypokalemia . Diuretic therapy + vomiting + diarrhea + tubular toxins (gentamicin & ifosfamide ) Hypomagnesemia can itself cause hypokalemia (unknown) Hypokalemia is often cannot be corrected until the magnesium deficit is reversed

27. INCEASED URINARY LOSS Less common causes of urinary potassium wasting Polyuria Renal tubular acidosis Hypomagnesemia Amphotericin B Salt-wasting nephropathies Liddle’s syndrome Barrter & Gitelman syndromes Low calorie diets 50% of patients treated with AmB . Interacts with membrane sterols, leading to an increase in membrane permeability There can also be concurrent distal-RTA

28. INCEASED URINARY LOSS Less common causes of urinary potassium wasting Polyuria Renal tubular acidosis Hypomagnesemia Amphotericin B Salt-wasting nephropathies Liddle’s syndrome Bartter & Gitelman syndromes Low calorie diets Gain of function of mutation in ENaC. Mimicks hyperaldosteronism Hypokalemia + hypertension + metabolic alkalosis. Autosomal dominant.

29. INCEASED URINARY LOSS Less common causes of urinary potassium wasting Polyuria Renal tubular acidosis Hypomagnesemia Amphotericin B Salt-wasting nephropathies Liddle’s syndrome Bartter & Gitelman syndromes Low calorie diets

30. MANIFESTATION OF HYPOKALEMIA

31. MANIFESTATION OF HYPOKALEMIA Proportionate to the degree of hypokalemia . Usually when K+ < 3.0 mEq /L Predisposition may worsen the symptoms

32. MANIFESTATION OF HYPOKALEMIA Muscle weakness Cardiac arrythmias Kidney abnormalities Glucose intolerance.

33. MUSCLE WEAKNESS Occurs when K+ is below 2.5mEq/L or above if its sudden in onset. Weakness usually begins in lower extremeties , progresses to the trunk and upper extremeties .(ASCENDING) Severe potassium depletion can cause muscle cramps, rhabdomyolysis, and myoglobinuria. Respiratory muscle weakness can become severe enough to need mechanical ventilation. Involvement of GI muscles, can results in ileus.

34. CARDIAC ARRHYTHMIA Hypokalemia is associated with variety of arrythmias: PACs, PVCs, sinus bradycardia, junctional tachycardia, AV block, VT/VF. Hypokalemia produces characteristic changes in ECG, usually associated with K+ value <2.7 mEq /L. Basis of ECG abnormalities is DELAYED VENTRICULAR REPOLARISATION. Presence of concomitant risk factors like, coronary ischemia, digitalis, increased beta adrenergic activity, and magnesium deficiency, can promote arrhythmias

35. EFFECTS OF DELAYED REPOLARISATION T WAVE Progressive diminution in amplitude, may eventually disappear. A remnant of T wave may be visible as a slight irregularity U WAVE Progressive increase in amplitude & maintains its rounded appearance. May get superimposed on T – TU complex. ST SEGMENT ST depression is seen in all leads which may be horizontal or concave upwards Prominent U waves combined with ST segment depression & flattened T waves (roller coaster effect) QT INTERVAL U wave may be mistaken for a T wave leading to an incorrect diagnosis of prolonged QT (QU) interval. Actual QT interval may be unchanged P wave Increase in amplitude/duration PSEUDO P PULMONALE PR INTERVAL 1 st degree AV block is common 2 nd degree AV block can also occur

36. HYPOKALEMIA INDUCED KIDNEY DYSFUNCTION Impaired urinary concentrating abilities Intracellular acidosis Increased ammonia production Increased bicarbonate reabsorption Altered sodium reabsorption Hypokalemic nephropathy Occurs especially if persistent. Most of these are reversible with repletion.

37. EVALUATION OF PATIENT WITH HYPOKALEMIA

38. HISTORY PHYSICAL EXAMINATION LABORATORY EVALUATION

39. HISTORY PHYSICAL EXAMINATION LABORATORY EVALUATION Medications (diuretics, laxatives, antibiotics) Diet and dietary habits ( licorice ) Symptoms of specific diseases (periodic weakness, diarrhea ) Blood pressure Volume status Signs of specific disorders Routine blood & urine tests Urinary K+ excretion Acid base status

40. Assessement of urinary potassium excretion 24-hour urine potassium Best method. Excretion of >30 mEq /day in presence of hypokalemia indicate inappropriate renal loss. Sometimes becomes impractical because potassium repletion is urgently needed. Excretion of <15 mEq /day in presence of hypokalemia is indicative of an extrarenal cause of potassium loss. Urine potassium – to – creatinine ratio (KCR Since creatinine is excreted at a near-constant rate, the urine KCR corrects for variations in urine volume. The urine KCR < 13mEq/g of creatinine (1.5 mEq /mmol of creatinine) is s/o extrarenal loss. Value above this is s/o excessive renal loss.

41. TTKG – TRANSTUBULAR K+ GRADIENT It estimates the ratio of potassium in the lumen of CCD to that in the peritubular capillaries. Normal TTKG in subjects on normal diet is 8 – 9. With extrarenal loss it should be <2 (3) In hypokalmia TTKG > 4 is s/o renal potassium wasting.

42. TREATMENT OF HYPOKALEMIA PREVENT/TREAT LIFE THREATENING COMPLICATIONS TO REPLACE THE POTASSIUM DEFICIT TO DIAGNOSE & CORRECT THE UNDERLYING CAUSE

43. TREATMENT OF HYPOKALEMIA PREVENT/TREAT LIFE THREATENING COMPLICATIONS TO REPLACE THE POTASSIUM DEFICIT TO DIAGNOSE & CORRECT THE UNDERLYING CAUSE THE URGENCY OF THERAPY DEPENDS UPON SEVERITY OF HYPOKALEMIA COMORBIDITIES RATE OF DECLINE

44. General issues HYPOMAGNESEMIA: Due to concurrent loss or the primary abnormality. Such patients are refractory to potassium replacement alone. Therefore, magnesium is to be measured in all patients and should be treated if deficient. REDISTRIBUTION HYPOKALEMIA Potential complication is hyperkalemia as the initial process causing redistribution resolves or is corrected. Such patients can develop fatal hyperkalemic arrhythmia. The risk is particularly high in patients with HypoPP and TPP (40-60%) INCREASED SYMPATHETIC TONE Administration of propranalol , should be considered. Greatest experience with hypokalemic thyrotoxic periodic paralysis, but can also be considered in head injury, theophylline toxicity. No risk of rebound of hyperkalemia

45. TOTAL BODY POTASSIUM DEFICIT It is difficult to predict accurately the total body potassium deficit on the basis of serum potassium. However this estimation helps in preventing development of hyperkalemia due to excessive supplementation. The deficit varies widely and directly with severity of hypokalemia . Rough rule of thumb is FOR EACH 100 mEq FALL IN TOTAL BODY POTASSIUM, THE SERUM POTASSIUM FALLS BY 0.27 mEq /L.

46. POTASSSIUM PREPERATIONS POTASSIUM CHLORIDE : preferred in majority of patients. Patients with hypokalemia and metabolic alkalosis are often chloride depleted. Raises the serum potassium at much faster rate compared to other forms. Available as crystalline form (salt substitutes), slow release tablets, liquid, IV injection. POTASSIUM BICARBONATE : Preferred in patients with hypokalemia and metabolic acidosis. Like RTA, diarrhea. POTASSIUM PHOSPHATE : Should be considered only in the rarely seen patients with hypokalemia and hypophosphatemia. Like type 2 RTA a/w Fanconi syndrome and phosphate wasting.

47. TREATMENT OF MILD-MODERATE HYPOKALEMIA

48. TREATMENT OF MILD-MODERATE HYPOKALEMIA 3.0 – 3.4 mEq /L Usually produce no symptoms Be very careful in Organic heart disease Digitalis/ AADs Liver cirrhosis

49. TREATMENT OF MILD-MODERATE HYPOKALEMIA 3.0 – 3.4 mEq /L Usually produce no symptoms Be very careful in Organic heart disease Digitalis/ AADs Liver cirrhosis PATIENTS WITH GI LOSS: Potassium chloride if metabolic alkalosis (vomiting) Potassium bicarbonate if metabolic acidosis ( diarrhea ) 10 – 20 mEq of potassium BD – QID (20 – 80 mEq per day)

50. TREATMENT OF MILD-MODERATE HYPOKALEMIA 3.0 – 3.4 mEq /L Usually produce no symptoms Be very careful in Organic heart disease Digitalis/ AADs Liver cirrhosis PATIENTS WITH GI LOSS: Potassium chloride if metabolic alkalosis (vomiting) Potassium bicarbonate if metabolic acidosis ( diarrhea ) 10 – 20 mEq of potassium BD – QID (20 – 80 mEq per day) RENAL POTASSIUM WASTING: Potassium supplements at usual doses produce only modest response (diuretic therapy, PA) Most administered potassium tend to be excreted in urine. Thus, potassium sparing diuretic is likely to be more effective Amiloride >>> spironolactone. Spironolactone >>>> amiloride.

51. SEVERE OR SYMPTOMATIC HYPOKALEMIA Potassium repletion is most easily accomplished orally but can be given intravenously. The serum potassium concentration can transiently rise by as much 1 – 1.5 mEq /L after an oral dose of 40 – 60 mEq . The serum potassium will then fall back toward baseline over a few hours. Intravenous potassium repletion is recommended in Severe hypokalemia Symptomatic hypokalemia In whom oral therpy cannot be given or non-tolerable.

52. SEVERE OR SYMPTOMATIC HYPOKALEMIA Potassium repletion is most easily accomplished orally but can be given intravenously. The serum potassium concentration can transiently rise by as much 1 – 1.5 mEq /L after an oral dose of 40 – 60 mEq . The serum potassium will then fall back toward baseline over a few hours. Intravenous potassium repletion is recommended in Severe hypokalemia Symptomatic hypokalemia In whom oral therpy cannot be given or non-tolerable. REMEMBER: HYPERKALEMIA IS MORE DANGEROUS THAN HYPOKALEMIA

53. IV POTASSIUM REPLETION Adverse effects: Pain & phlebitis: During parenteral infusion of potassium into a peripheral vein. This primarily occurs at rates above 10 mEq /hour, can be seen at lower rates. Pain occurs, either the infusion rate or, preferably, the potassium concentration should be reduced. Hyperkalemia : Rapid infusion of 40 – 60 mEq of potassium can result in severe hyperkalemia . Inverdent administration of large amount of potassium in short period of time, expected to occur when infusion pump is not used.

54. IV POTASSIUM REPLETION Recommended approach: For GI loss : recommended maximum rate of potassium administration is 10 – 20 mEq /hour. However, initial rates high as 40 mEq /hr have been used for life-threatening hypokalemia . Such large doses should be infused into a large central vein or into multiple peripheral veins. In any 1000mL non-dextrose fluid, suggested maximum of 60mEq of potassium In any 100mL of non-dextrose fluid, suggested maximum of 20mEq of potassium

55. DON’T GIVE > 10 – 20 mEq per hour > 40 mEq per litre > 240 mEq per day

56. Potassium replacement: Initial serum K+ below 3.3 -------- IV potassium 20-40 mEq /hr should be given. If patient has marked hypokalemia , they might require aggressive potassium replacement (40mEq/hr). Initial serum K+ 3.3 – 5.3 ------- IV potassium 20-30 mEq is added to each litre of iv replacement fluid. Adjust the potassium replacement to maintain level in the range of 4-5. Initial serum K+ above 5.3 ------ potassium replacement should be delayed until its concentration has fallen below this level. Even with this replacement, it may result in dramatic fall in serum potassium once insulin administration starts, due to rapid distribution Be careful in patients with associated renal dysfunction, may lead to fatal hyperkalemia

57. FEW CASE SCENARIOS………..