potasium disorNNNNNNNNNNNders [Autosaved].pptx

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1. Potassium disorders with Ca ++ Prepared by :-DR ABDIRISAK JACDA Moderator:- DR CHALA Abdirisak jacda 1 AU-HRU 18 April 2024

2. Content Potassium metabolism Hypokalemia Causes Diagnosis Treatment principles Hyperkalemia Causes Diagnosis Treatment principles calcium disorders summary References 18 April 2024 Abdirisak jacda 2

3. Question: Which electrolyte imbalance is common among hospitalized patients? a. Hyponatremia b. Hypokalemia c. Hypocalcemia d. Hyperkalemia Jameson, J.L., Fauci , A., Kasper, D., Hauser, S., Longo, D. & Loscalzo , J. . Harrison's Principles of Internal Medicine 21th Edition. 18 April 2024 Abdirisak jacda 3

4. Question: Which electrolyte imbalance is common among hospitalized patients? a. Hyponatremia – 22% b. Hypokalemia – 20% c. Hypocalcemia--variable d. Hyperkalemia – 10% 18 April 2024 Abdirisak jacda 4

5. 18 April 2024 Abdirisak jacda 5 Scenario: 32y/M; presented with bilateral lower extremity weakness after a sumptuous meal during fiesta; Non diabetic Na = 136, K=2.9 , Ca =2.4, Mg =1.2 Calculate Potassium Deficit

6. Potassium Deficit: 222 mEqs Correct in 24-48 hours KCl 40mEqs per A. NS 1L + 40 mEqs KCl to run for 8 hourly Repeat for 3 cycles = 120 mEqs B. KCl tablets 2 tablets 3x daily (1 tablet ~ 10mEqs) = 60 mEqs C. 2 Banana per meal ( 1 serving ~12 meqs ) = 48 mEqs 228 mEqs Repeat S. Potassium every 6 hours until it is corrected If symptoms improve oral maintainence for 2-3 days of 20-40mEqs BID/TID will be enough Scenario: 18 April 2024 Abdirisak jacda 6

7. Potassium Disoders plasma concenteration 3.5 - 5.5 mmol /L In a healthy individual at steady state , the entire daily intake of potassium is excreted , ~90% in the urine and 10% in the stool >98% of total-body potassium is intracellular, chiefly in muscle Crucial for normal neuromuscular function Less than 1% of adults with normal renal function not receiving medicines develop hypokalemia or hyperkalemia and 50% those who took drug like Diuretics 18 April 2024 Abdirisak jacda 7

8. Daily intake—40-120mmol Potassium ingestion=potassium excretion After K load: 1. Redistribution into cells 2. Renal elimination During K restriction 1. Redistribution out of cells 2. Renal conservation 18 April 2024 Abdirisak jacda 8

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10. Hypokalemia serum concentration < 3.5 mmol/L occurs in up to 20% of hospitalized patients Associated with a tenfold increase in in-hospital mortality , due to adverse effects on cardiac rhythm, blood pressure, and cardiovascular morbidity. Mild 3.0 mmol/L-3.4 mmol/L Moderate 2.5mmol/L-3.0 mmol/L Severe < 2.5 mmol/L or symptomatic with ecg manifestation of any level < 3.5 mmol/L 18 April 2024 Abdirisak jacda 10

11. Hypokalemia cont.. one of four causes: Pseudohypokalemia is artifactual decreament of serum [K] due to phelebotomy , hyperleukocytosis ,thrombocytosis Redistribution , shift of [K] from ECF to ICF mediated by mainly mediated by hormones insulin aldosterone, B- adrenegic stimulation and rarely, hypokalemic periodic paralysis Extrarenal potassium loss due to excessive sweating or chronic diarrhea ,Vomiting or nasogastric suction renal potassium loss. The most common cause of hypokalemia , which typically results from drugs, endogenous hormone production, or rarely, intrinsic renal defects, Magnesium depletion, Bicarbonaturia 18 April 2024 Abdirisak jacda 11

12. 18 April 2024 Abdirisak jacda 12 Common endocrine diseases Cushing Hyperaldosteronism

13. Clinical Manifestations in most cases, hypokalemia is asymptomatic Hypokalemia alters the resting membrane potential, which can impair normal functioning of almost every cell in the body Symptoms generally do not become manifest until the serum potassium is below 3.0  mEq /L , unless the serum potassium falls rapidly or the patient has a potentiating factor, such as a predisposition to arrhythmia due to the use of digitalis Symptoms usually resolve with correction of the hypokalemia 18 April 2024 Abdirisak jacda 13

14. Muscular Rhabdomyolysis lead to muscle cramps myoglobinuria   Severe muscle weakness involvement of gastrointestinal muscles, resulting in paralytic ileus 18 April 2024 Abdirisak jacda 14

15. Cardiovascular A variety of arrhythmias may be seen in patients with hypokalemia including ventricular tachycardia or fibrillation  Abnormalities in the ECG are the major manifestation of hypokalemia, and can be present in 50% of cases With hypokalemia, the EKG may again be a better measure of serious toxicity than the serum potassium level The risk of arrhythmia from hypokalemia is highest in older patients, patients with organic heart disease, and patients on  digoxin  or antiarrhythmic drugs 18 April 2024 Abdirisak jacda 15

16. Common ECG manifestation Several changes can be seen, occurring in no particular order: ST-segment depression Flattening of the T wave with prolongation of the QT interval also seen in drugs hypocalcemia or hypomagnesemia Appearance of a U wave also seen in digitals and LVH 18 April 2024 Abdirisak jacda 16

17. Renal abnormalities Prolonged hypokalemia can cause multiple structural and functional changes in the kidney including : ●Impaired concentrating ability ● Reduced medullary blood flow and increased renal vascular resistance may predispose to hypertension ●Increased ammonia production ●Increased bicarbonate reabsorption ●Altered sodium reabsorption ● Hypokalemic nephropathy ●Elevation in blood pressure??? 18 April 2024 Abdirisak jacda 17

18. Glucose intolerance/ Hormonal Hypokalemia impairs insulin release and induces insulin resistance, resulting in worsened glucose control in diabetic patients. The insulin resistance that usually occurs with thiazide diuretic therapy is caused by endothelial dysfunction mediated by thiazide-induced hypokalemia and hyperuricemia 18 April 2024 Abdirisak jacda 18

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20. Treatment The goals of therapy To prevent or treat life-threatening complications (arrhythmias, paralysis, rhabdomyolysis, and diaphragmatic weakness), To replace the potassium deficit safely To diagnose and correct the underlying cause 18 April 2024 Abdirisak jacda 20

21. Estimation of the potassium deficit In different studies, the serum potassium concentration fell by approximately 0.27  mEq /L  for every 100 mEq reduction in total body potassium stores In chronic hypokalemia, a potassium deficit of 200 to 400 mEq is required to lower the serum potassium concentration by 1  mEq /L  this estimation  does not apply  is diabetic ketoacidosis or nonketotic hyperglycemia, and in redistributive causes of hypokalemia 18 April 2024 Abdirisak jacda 21

22. ROUTE Potassium replacement is the mainstay of therapy in hypokalemia Mild —oral route KCL ,KHCO3, K-Citrate, K- gluconate Severe or symptomatic —IV route Avoid dextrose solution???? concomitant Mg 2+ deficiency should always be corrected with oral or intravenous repletion depending on severity of mg deficit 18 April 2024 Abdirisak jacda 22

23. RATE OF REPLACEMENT The maximum rate of intravenous potassium replacement is usually set at 10-20 mEq /hr But dose rates of 40 mEq /hour may be necessary (e.g., serum K+ <1.5 mEq /L or serious arrhythmias ), and dose rates as high as 100 mEq /hour have been used safely only through central line Why 18 April 2024 Abdirisak jacda 23

24. Hyperkalemia serum pottassium level > 5.5mmol/L occurring in up to 10% of hospitalized patients severe hyperkalemia (>6.0 mM ) occurs in ~1%, with a significantly increased risk of mortality distinctly unusual in healthy individuals with normal renal function not being treated with drugs that alter renal K+ handling, with less than 1% of normal healthy adults developing hyperkalemia 18 April 2024 Abdirisak jacda 24

25. Etiology Hyperkalemia can result from Pseudohyperkalemia Potassium redistribution from intracellular to extracellular space, Imbalances between potassium intake and renal potassium excretion 18 April 2024 Abdirisak jacda 25

26. Pseudohyperkalemia Artifactual increase in serum K+ due to the release of K+ during or after venipuncture diagnosed by showing that the serum [K+] is more than 0.3 mmol /l higher than in a simultaneous sample excessive muscle activity during venipuncture (fist clenching, etc.) a marked increase in cellular elements (thrombocytosis, leukocytosis, and/or erythrocytosis ) 18 April 2024 Abdirisak jacda 26

27. Redistribution Hyperkalemia may be observed in cases of severe hyperglycemia (due to effects of osmolarity ), in association with severe nonorganic acidosis, rarely with β2-adrenoceptor blockers, ACE inhibitors, ARBs, and MR blockers. Patients who have received mannitol may also develop hyperosmolarity induced hyperkalemia 18 April 2024 Abdirisak jacda 27

28. Excess intake Excessive potassium ingestion generally does not lead to hyperkalemia unless other contributing factors are present As many as 4% of patients receiving potassium supplements develop hyperkalemia However, if renal potassium excretion is impaired , for example, by drugs ,or stage 4 and 5 CKD excessive potassium intake can produce hyperkalemia 18 April 2024 Abdirisak jacda 28

29. Impaired renal secretion Factors that affect renal potassium excretion are classified into those due to reduced nephron number AKI or CKD (decreased GFR or functioning nephron) those due to intrinsic impairment of renal potassium handling Drugs that inhibit RAAS 18 April 2024 Abdirisak jacda 29

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31. Clinical feature may be asymptomatic but still life-threatening. The most prominent effect of hyperkalemia is alteration of cardiac conduction also affects muscle contraction. Skeletal muscle cells are particularly sensitive to hyperkalemia , causing weakness (“rubbery” or “spaghetti” legs). With severe hyperkalemia , respiratory failure may occur from paralysis of the diaphragm. 18 April 2024 Abdirisak jacda 31

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33. Treatment Therapies for ACUTE hyperkalemia are divided into those that minimize the cardiac effects of hyperkalemia ; Calcium gluconate/chloride decrease in plasma potassium those that induce potassium uptake by cells resulting in a decrease in serum potassium insulin with 40% dextrose B- agonist Removal of potassium from the body Cat ion resin exchange Diuretics Dialysis 18 April 2024 Abdirisak jacda 33

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35. Chronic Treatment dietary modification use of diuretics treatment of chronic metabolic acidosis reversal of factors that can cause hyperkalemia ( eg,NSAIDS , hypovolemia ) In some instances, drugs that inhibit the RAAS are reduced or discontinued Synthetic mineralocorticoid therapy, such as fludrocortisone 18 April 2024 Abdirisak jacda 35

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38. Calcium disorders Ca has critical role in normal cellular function and signaling, regulating diverse physiologic processes Such as neuromuscular signaling, cardiac contractility, hormone secretion, and blood coagulation Thus, extracellular calcium concentrations are maintained within an exquisitely narrow range ( 8.9-10.1mg/dl) 38 18 April 2024 Abdirisak jacda

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40. This narrow range is maintained by PTH Calcitriol Vitamin D Plus 3 organs GI Renal skin 40 18 April 2024 Abdirisak jacda

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42. Hypercalcemia Is defined as total serum calcium is above 10.5 mg/dl Mild : 10.5-12mg/dl Moderate :12-14mg/dl Severe : >14mg/dl Pseudohypercalcemia vs true hypercalcemia serum calcium increase by 0.8-1 mg/dl for 1 g/dl albumin increment Simple correction may be incorrect in advanced CKD 42 18 April 2024 Abdirisak jacda

43. Etiology Main are – Malignancies - Hyperparathyroidism - Renal disease Malignancies Elevated bone resorption is the most common causes Solid tumors followed by hematologic malignancies Direct invasion vs paraneoplastic process( PTHrp ) 43 18 April 2024 Abdirisak jacda

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45. Clinical Manifestations Depends on severity and rate of development In general the first symptoms are increasing fatigue and muscle weakness, inability to concentrate ,nervousness and depression Subsequently GI symptoms may occur nephrogenic DI , renal salt wasting syndrome , nephrolithiasisis and occasionally n ephrocalcinosis (medulla >cortex) 45 18 April 2024 Abdirisak jacda

46. Con.. With long-standing hyperparathyroidism, patients may present with bone pain or pathologic fractures Neuropsychiatric manifestations ( coma is rare) Elevated BP (usually due to association) ECG may show short QT interval and coving ST-waves 46 18 April 2024 Abdirisak jacda

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48. Diagnostic Approach The first step in the diagnostic is to differentiate from pseudohypercalcemia 45% of calcium is bound principally to albumin. It is generally preferable to measure total calcium* and albumin to "correct" the serum calcium. Serum calcium is increased by 0.8 mg/dl for every 1 g/dl serum albumin increment 48 18 April 2024 Abdirisak jacda

49. Diagnostic Approach A detailed history may provide important clues for etiologies The history should include medication use, previous neck surgery, and systemic symptoms suggestive of Sarcoidosis or lymphoma Once true hypercalcemia is established, the second step is to determine serum PTH level Increases in PTH are often accompanied by hypophosphatemia In addition, serum creatinine should be measured ; Hypercalcemia may impair renal function, renal clearance of PTH may be altered 49 18 April 2024 Abdirisak jacda

50. Diagnostic Approach If the PTH level is increased (or "inappropriately normal") in the setting of elevated calcium and low phosphorus, the diagnosis is almost always primary hyperparathyroidism A suppressed PTH level in the face of hypercalcemia is consistent with non-parathyroid-mediated hypercalcemia , most often due to underlying malignancy Although a tumor that causes hypercalcemia is generally overt, a PTHrP level may be needed to establish the diagnosis of hypercalcemia of malignancy Serum 1,25(OH) 2 D levels are increased in granulomatous disorders 50 18 April 2024 Abdirisak jacda

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52. Treatment of Hypercalcaemia Goals of treatment are 1. lowering the serum calcium concentration Inhibiting bone resorption , Increasing urinary calcium excretion, or Decreasing intestinal calcium absorption 2. treating underlying disease Optimal choice varies with cause & severity of hypercalcemia 52 18 April 2024 Abdirisak jacda

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54. Treatment Based On Severity Asymptomatic or mildly symptomatic hypercalcemia (<12 mg/ dL ) Do not require immediate treatment Avoid factors that can aggravate hypercalcemia Thiazide diuretics Lithium carbonate therapy, Volume depletion, Prolonged bed rest or inactivity, High calcium diet (>1000 mg/day) 54 18 April 2024 Abdirisak jacda

55. Treatment…… Asymptomatic or mildly symptomatic individuals with chronic moderate hypercalcemia (12 - 14 mg/ dL  ) May not require immediate therapy An acute rise to these levels may cause gastrointestinal side effects, muscle ache and changes in sensorium, Treatment as for severe hypercalcemia 55 18 April 2024 Abdirisak jacda

56. Treatment…… Severe (calcium >14 mg/ dL  [3.5  mmol /L]) or symptomatic hypercalcemia 1. Saline hydration Restores GFR Promotes natriuresis and calciuresis 500 to 1 000 mL of 0.9% N/S over the 1 st hour ,then 250 to 500 mL/h thereafter depending on the state of volume contraction to maintain the urine output at 100 -150 mL/hour Concomitant use of loop diuretics Should not be routine in renal insufficiency or heart failure 56 18 April 2024 Abdirisak jacda

57. Treatment…… 2. Calcitonin 4 IU/kg  im or SC BID; can be increased up to 6 to 8 IU/kg QID Increase renal calcium excretion Decrease bone resorption via interference with osteoclast function Safe and relatively nontoxic Relatively weak agent but it works rapidly, lowering the serum calcium concentration by a maximum of 1 to 2 mg/ dL  (0.3 to 0.5  mmol /L) beginning within 4 to 6 hours Efficacy is limited to the first 48 hours( tachyphylaxis ),b/c of receptor down regulation Co- administration of glucocorticoids Most beneficial  when combined with hydration and bisphosphonates 57 18 April 2024 Abdirisak jacda

58. Treatment…… 3.Bisphosphonates Pamidronate : 60 to 90 mg in 250 mL of saline over 1 to 4 hours   Zoledronic acid: 4-mg intravenous infusion over 1 5-30 minutes More potent, with a similar safety profile to pamidronate   Ibandronate,clordronate,etidronate 58 18 April 2024 Abdirisak jacda

59. Treatment…… 4. Glucocorticoids Potentiation of calcitonin's effects Effective only in the management of hypercalcemia due to Lymphoproliferativ disease Vitamin D toxicity Disseminated granulomatous disease Reduce serum calcium concentrations within two to five days by decreasing calcitriol production by macrophages 59 18 April 2024 Abdirisak jacda

60. Treatment…… 5. Dialysis Generally reserved for those with severe hypercalcemia Severe malignancy-associated hypercalcemia and renal insufficiency or heart failure , in whom hydration cannot be safely administered Persistent hypercalcemia despite maximal saline and diuresis As a tool to bridge the interval until more definitive therapy ( eg , bisphosphonates) can achieve its maximal effect 6. Denosumab is a RANK ligand inhibitorthat inhibits osteoclast formation (120 mg sc on days 1, 8, 15, 29 and then every 4 weeks) for hypercalcemia refractory to bisphosphonates 60 18 April 2024 Abdirisak jacda

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62. Hypocalcemia Calcium level < 8.5mg/dl Chronic hypocalcaemia is less common than hypercalcemia Acute hypocalcaemia is relatively more common especially in critically ill patients due to several factors PTH is important for minute to minute regulation of serum calcium 62 18 April 2024 Abdirisak jacda

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64. Approach to Patient Hx Family hx - CaSR mutation, pseudohypoparathydoism Neck surgery Dietary habit, sun exposure, use of sun screens and sun blocks Transfusions, drugs Underlying disease, renal, liver, high grade malignancy P/E Latent signs of tetany Invest Ca , Mg, K+, PTH, PO4 Vit D, metabolites RFT, ALP 64 18 April 2024 Abdirisak jacda

65. Clinical Manifestation Neuromuscular Symptoms Numbness and tingling in fingertips, toes and perioral areas Muscle cramps and spasms Tetany , laryngospasm and bronchospasm Neuropsychiatric Seizures Raised ICP emotional instability, anxiety, depression and psychosis CVS Prolonged QT Hypotension Underlying disease specific manifestations Hypoparathyodism , vit.D def , genetic problems 65 18 April 2024 Abdirisak jacda

66. Hypocalcemia : Signs 66 18 April 2024 Abdirisak jacda

67. Hypocalcemia : Signs Trousseau sign: (very uncomfortable and painful) More specific than Chvostek's sign A blood pressure cuff is inflated to a pressure above the patients systolic level Pressure is continued for three minutes Carpopedal spasm: * flexion at the wrist * flexion at the MP joints * extension of the IP joints * adduction thumbs/fingers 67 18 April 2024 Abdirisak jacda

68. Diagnostic Approach Serum calcium, albumin, phosphorus, and magnesium levels. PTH level Low  Hypoparathyroidism / Mg Deficiency Elevated – Vit D related hypocalcemia , PTH-R, CKD, acute conditions and drugs Vit D level Serum 25-hydroxyvitamin D levels,  Nutritional def Serum 1,25(OH) 2 D levels  In the setting of renal insufficiency or suspected vitamin D resistance 68 18 April 2024 Abdirisak jacda

69. Diagnostic Summary 69 18 April 2024 Abdirisak jacda

70. Treatment of Hypocalcaemia Depends on: Severity of the hypocalcaemia, Rapidity with which it develops, and Accompanying complications (e.g., seizures, laryngospasm) 70 18 April 2024 Abdirisak jacda

71. Indications for IV Treatment Acute symptomatic Carpopedal spasm Seizure Tetany Acute hypocalcemia <7.5 mg/dl Post parathyroidectomy ….hungry bone syndrome Prolonged QT interval IV preparations Calcium gluconate : 1gm/10ml=90 mg of elemental calcium Calcium chloride:1gm/10ml= 270mg of elemental calcium 71 18 April 2024 Abdirisak jacda

72. Acute Symptomatic Hypocalcaemia Calcium gluconate , 10 mL 10% wt/ vol (90 mg) IV, diluted in 50 ml of 5% dextrose or 0.9% NaCl , over 10-20 mins Maintenace = 10 ampules of calcium gluconate or 900 mg of calcium in 1 L of 5% dextrose or 0.9% NaCl over 24 h NB Calcium solutions must be diluted. If not venous irritation Solutions should not contain bicarbonate or phosphate: forms insoluble salts If these solutions are needed, use other IV lines In hypercatabolic states: avoid calcium unless symptomatic, until hyperphosphatemia is treated ….dialysis 72 18 April 2024 Abdirisak jacda

73. Cause Directed Therapy—Chronic Chronic hypocalcemia due to hypoparathyroidism 1000–1500 mg/day elemental Ca in divided doses Calcium carbonate: 1gm contains 400 mg of ele . Calcium Calcium citrate: 1gm=211 mg of calcium Vitamin D 2 or D 3 25,000–100,000U daily or Calcitriol [1,25(OH) 2 D, 0.25–2 μg /d] Recombinant PTH, analogs CKD/CLD– Vit D metabolites( calcitriol , calcidol , dihydrotachysterol ) Vit D deficiency- should be supplemented 50,000 IU of vit D2 or D3 weekly for 6-8 weeks 73 18 April 2024 Abdirisak jacda

74. Treat Hypomagnesaemia Magnesium is required for PTH release May also be required for effects on target organs Mechanisms: End-organ unresponsiveness to PTH Impaired release of PTH Impaired formation of 1,25-vitamin D3 Supplements Magnesium sulphate :2gm of 10% solution infused over 10-20 mins ….then maintenance 1gm in 100ml of NS / hr 74 18 April 2024 Abdirisak jacda

75. References UpToDate 2024 Comprehensive clinical nephrology 7 th edition Harrison 21 st edition 18 April 2024 Abdirisak jacda 75