Electrolyte Disturbances

1. Electrolyte Disturbances

2. Introduction • Main electrolytes in the blood • sodium, potassium, calcium, magnesium, chloride, phosphate, and carbonate • Most commonly, problems occur when the level of sodium, potassium, or calcium is abnormal • Levels can become high or low • Often, electrolyte levels change when water levels in the body change

3. Hypokalemia • Most common electrolyte abnormality • Definition < 3.6 mmol/L • Most between 3.0 and 2.5 mmol/L • >20% hospitalized patients (No comparable data available for outpatients) • Hypokalemia has been found in 20-40% of those patients treated with diuretics

4. Hypokalemia • Often asymptomatic and well-tolerated in otherwise healthy individuals • Can be life-threatening when severe • May  the risks of morbidity and mortality in patients with cv disease, even when mild or moderate  As a result, when identified it is important to determine any underlying etiologies and treat appropriately

5. Regulation of Potassium Balance • Total body stores (intracellular and extracellular fluid) are closely regulated by key hormones • Insulin • β-adrenergic catecholamines • Aldosterone • Thyroid hormone • Normal: High ratio of intracellular to extracellular potassium • Both insulin and β- adrenergic catecholamine  cellular potassium uptake by stimulating cell membrane Na+/K+-ATPase

6. Regulation of Potassium Balance • Insulin: feedback system • ↑↑ K+ stimulates insulin • ↓↓ K+ inhibits insulin • β-adrenergic: no feedback system • β blockade ↑↑ serum K+ • β agonist ↓↓ serum K+ • Thyroid Hormone: + synthesis of Na+/K+ ATPase • Aldosterone: • ?? affects on the transcellular distribution of potassium • major regulator of body stores of potassium via its effects on the excretion of potassium by the kidney

7. Regulation of Potassium Balance

8. Clinical Manifestations of Hypokalemia • Often asymptomatic, usually when mild (3-3.5 mmol/L) • Nonspecific symptoms with more severe hypokalemia • generalized weakness; lassitude; constipation • Serum K+ < 2.5 mmol/L muscle necrosis • Serum K+ <2.0 mmol/L ascending paralysis and impairment of respiratory function • Symptoms usually correlate with rapidity of  serum K+

9. Hypokalemia and Cardiac Manifestations • In patients without underlying heart disease, abnormalities in cardiac conduction is very rare, even when the serum potassium <3.0 mmol/L •  risk of development of a cardiac arrhythmia (even with mild to moderate hypokalemia) • heart failure, cardiac ischemia, and/or LVH • Hypokalemia  the arrhythmogenic potential of digoxin

10. Etiology of Hypokalemia • Two main mechanisms: • Abnormal losses • Increased renal potassium loss • Excess potassium loss in stools • Transcellular potassium shift • Drugsare the most common cause

11. Drug Induced Hypokalemia • Transcellular Potassium Shift • Β2-Adrenergic Drugs • Increase Renal Potassium Loss • Diuretics • Mineralocorticoid/Glucocorticoid Effects • Antibiotics • Excess Potassium Loss in Stool

12. Β2-Adrenergic Drugs • Bronchodilators • a standard dose of nebulized albuterol ↓serum K by 0.2 to 0.4 mmol/L • second dose within one hour ↓ K by 1 mmol/L • Decongestants • Tocolytic Agents • ↓ serum K to as low as 2.5 mmol/L after 4-6 hours of IV administration

13. Drug-Induced HypokalemiaTranscellular Shifts • Xanthines • Theophylline • Severe hypokalemia with acute theophylline toxicity • Caffeine • Verapamil intoxication • Chloroquin intoxication • Inhibits potassium from exiting cells • Insulin • Moves potassium into cells • Transient hypokalemia • Intentional overdose of insulin; treatment of DKA

14. Thiazide and Loop Diuretics • Most common cause of hypokalemia • Block Cl-associated Na+ reabsorption ↑delivery of Na+ to collecting tubules↑ Na+ reabsorption  ↑ K+ secretion • Direct relation with dose •  response of hypokalemia with more dietary Na+ intake

15. Diuretics • Furosemide or Bumetanide with Metolazone  Moderate-Severe Hypokalemia • Associated mild to moderate alkalosis • Acetazolamide promote K+ reabsorption • Interferes with H+ linked sodium reabsorption metabolic acidosis

16. Drugs with Mineralocorticoid or Glucocorticoid Effects • Fludrocortisone • Oral mineralocorticoid • promotes renal K+ excretion • If used inappropriately can lead to K+ wasting • Prednisone and Hydrocortisone • Glucocorticoids • indirectly  K+ secretion via effect on filtration rate and distal sodium delivery • ↓ by0.2 to 0.4 mmol/L

17. Other drugs causing renal wasting of potassium • High dose antibiotics •  Na+ delivery to nephrons • PCN, Naficillin, Ampicillin, Carbenicillin • Drugs assoiciated with Mg depletion • Aminoglycosides • Cisplantin • Foscarnet • Amphotericin B

18. Non-Drug Causes of Hypokalemia • Transcellular shifts • Inadequate dietary intake • Abnormal losses of potassium • Looses in stool • Loss through the kidney

19. Hyperthyroidism Severe <3.0 mmol/L  sudden onset of severe muscle weakness and paralysis 2 to 8% of patients with hyperthyroidism in Asian countries Familial Hypokalemic Periodic Paralysis autosomal dominant Mutations of gene encoding the dihydropyridine receptor Sudden attacks of muscle paralysis, K+ < 2.5 mmol/L Provoked by high intake of CHO, sodium, or by exertion Subside < 24 hours Non-Drug Causes Due to Transcellular Shifts

20. Delirium tremens Abrupt ↓ serum K+ by 1mmol/L Β2-adrenergic stimulation Barium compounds Block exit of K+ from cells Vomiting and diarrhea Muscle weakness, paralysis, rhabdomyolysis Severe pernicious anemia Treatment with vitamin B12 rapid uptake of K+ by new cells formed Transfusion with frozen washed red cells Non-Drug Causes Due to Transcellular Shifts

21. Non-Drug Causes Due to Inadequate Dietary Intake •  potassium intake by <1gram/day (25 mmol/day) • Renal excretion of potassium fails to decrease promptly • With starvation or near-starvation depletes body K+ stores compensated by tissue breakdown that releases K+

22. Non-Drug Causes Due to Abnormal Losses of Potassium • Stool losses • Renal losses • Metabolic Alkalosis • Chloride sensitive: vomiting, nasogastric drainage • Chloride insensitive: hyperaldosteronism, Cushing’s syndrome • Genetic abnormalities: Liddle’s syndrome, 11β-hydroxysteroid dehyrogenase deficiency, Bartter’s syndrome, Gitelmans’s syndrome • Metabolic Acidosis • Type I or classic distal renal tubular acidosis • Type II or proximal renal tubular acidosis

23. Treatment of Hypokalemia • Potassium replacement • Note, that supplemental potassium administration is the most common cause of severe hyperkalemia in hospitalized patients • Greatest risk with IV replacement • If given, rate should be no more than 20 mmol/hour and monitor cardiac rhythm • PO administration safer because enters circulation slower

24. Treatment of Hypokalemia • On average, serum potassium  by 0.3 mmol/L for each 100 mmol reduction in total body stores • A portion of administered potassium is always excreted, even in presence of serious potassium depletion

25. Treatment of Hypokalemia • Three salts available • Potassium chloride • Potassium phosphate • Potassium bicarbonate • KCl most often used because of its unique effectiveness with the most common cause of potassium depletion • Liquid or tablet form of KCl available • Initially, 1 mcg of KCL  serum K+ by 0.1 mmol/L

26. Treatment of Hypokalemia • Typically, 40 to 100 mmol of supplemental K+ each day to maintain wnl serum K+ with daily use of diuretics • Hypokalemia persists in patients taking diuretics despite aggressive potassium replacement in 10% of patients • May add a 2nd diuretic that inhibits K+ excretion • Amiloride, triamterene, or spironolactone

27. Hyperkalemia • Diagnosed in up 8% of hospitalized patients • Primary cause of morbidity and death is potassium's effect on cardiac function • Mortality rate can be as high as 67% if severe hyperkalemia is not treated rapidly • Hyperkalemia is defined as a potassium level >5.5 mEq/L 5.5 - 6.0 mEq/L Mild 6.1 - 7.0 mEq/L Moderate 7.0 mEq/L and greater Severe

28. Causes of Hyperkalemia •  or impaired K+ excretion • acute or chronic renal failure (most common) • K+ sparing diuretics, urinary obstruction, sickle cell disease, Addison disease, and SLE • Additions of potassium into extracellular space • K supplements, rhabdomyolysis, hemolysis • Transmembrane shifts • acidosis and medication effects (eg, acute digitalis toxicity, BB, succinylcholine) • Factitious or pseudohyperkalemia • improper blood collection, lab error, leukocytosis, and thrombocytosis

29. Clinical Manifestation • Hyperkalemia frequently discovered as an incidental laboratory finding • However may experience: • Generalized fatigue • Weakness • Paresthesias • Paralysis • Palpitations • EKG findings • Early: peaked T waves, shortened QT interval, and ST segment depression • Later: bundle branch block, resulting in widened QRS, increases in the PR interval, and decreased amplitude of the P wave

30. Hyperkalemia

31. Approach to Hyperkalemia • Is this a true measurement? • Look at prior measurements • Repeat stat • Is patient symptomatic or have underlying reason to explain for the ↑↑ K+? • Renal insufficiency • Medications (BBlockers, K+sparing diuretics, K+ supplements, digitalis) • EKG findings?

32. Approach to Hyperkalemia • ABC’s • IV access and cardiac monitor • EKG • Discontinue any potassium-sparing drugs or dietary potassium • If the hyperkalemia is severe (>7.0 mEq/L) or the patient is symptomatic begin treatment, do not wait for tests • Individualize treatment based upon the patient's presentation, potassium level, and EKG

33. Treatment of Hyperkalemia • Calcium gluconate • Stabilizes cell membrane • 2 amps IV; onset few minutes • Insulin • Drives K into cells • 10 units regular + 1-2 amps D5W; onset 15-30min • Bicarbonate • Drives K into cells in exchange for H • 1-3 amps IV; onset 15-30 minutes • Kayexlate • Exchanges Na for K in GI tract • 30-90 grams po/pr; onset 1-2 hours • Diuretics • Furosemide ≥ 40 mg IV; onset 30 minutes • Hemodialysis

34. Sodium and Water Homeostasis • Disorders of sodium are generally due to changes in total body water, not body sodium • Two key hormones: • Antidiuretic hormone (ADH) • Primary hormone regulator of sodium concentration • Aldosterone • Primary hormone regulator of total body sodium (and therefore volume)

35. Antidiuretic Hormone (ADH) • Stimuli for secretion: hyperosmolality, ↓↓ effective arterial volume (EAV) • Action: open water channels in collecting ducts  passive water reabsorption into medulla • Urine osmolality- indirect assay of ADH activity • Uosm range 60 mOsm/L (no ADH activity) to 1200 mOsm/L (max ADH activity) • ↑↑ ADH = Syndrome of inappropriate ADH (SIADH) • ↓↓ ADH = Central diabetes insipidus

36. Aldosterone • Stimuli for secretion: • hypovolemia (via renin and angiotensin II) • hyperkalemia • Action: isoosmotic reabsorption of sodium in exchange for potassium or H+ • ↑↑ aldosterone = Conn’s Syndrome ( HTN, hypokalemia, metabolic alkalosis) • ↓↓ aldosterone = hypovolemia, hyperkalemia, metabolic acidosis

37. Hyponatremia • A common clinical problem and frequently develops in hospitalized patients • Although morbidity varies widely in severity, serious complications can arise form the disorder itself as well as from errors in management • Defined as the excess of water relative to sodium • A  serum sodium concentration <136 mmol/L

38. Approach to Hyponatremia • FIRST, determine tonicity • Isotonic • Rare laboratory artifact due to hyperlipidemia or hyperproteinemia check lipid panel and/or lft’s • Hypertonic • Excessive presence of other effective osmole • Glucose, mannitol, or glycine • For each 100 mg/dL rise in glucose above 100 mg/dL the Na ↓ 1.6 mEq/L • Hypotonic • True excess of water relative to sodium

39. Approach to Hyponatremia • NEXT, if true excess of water relative to sodium, in other words, hypotonic hyponatremia, determine volume status • Hypovolemic • Euvolemic • Hypervolemic • Vital signs, orthostatics, JVP, skin tugor, mucous membranes, peripheral edema, BUN, Cr, uric acid

40. Hypotonic Hyponatremia • Three categories: • Hypovolemic Hypotonic Hyponatremia • Euvolemic Hypotonic Hyponatremia • Hypervolemic Hypotonic Hyponatremia

41. Hypovolemic Hypotonic Hyponatremia • Primary Na loss secondary H20 gain • Determine renal vs. extrarenal losses • UNa > 20 mEq/L = renal losses • Diuretics • Hypoaldosteronism • Salt-wasting nephropathy • UNa < 10 mEq/L = extrarenal losses • GI losses • Third-spacing • Insensible losses

42. Hypervolemic Hypotonic Hyponatremia • Determine if there is a ↓ EAV or advanced renal failure • UNa < 10 mEq/L = ↓ EAV • CHF (↓ CO) • Cirrhosis (ascites) • Nephrotic Syndrome (hypoalbuminemia edema) • UNa > 20 mEq/L = advanced renal failure

43. Euvolemic Hypotonic Hyponatremia • Primary H2O gain • Determine whether SIADH or ADH suppression • Uosm>100 = SIADH • Uosm <100 = psychogenic polydipsia • >12- 20 L/day • Uosm variable = ADH physiology reset to regulate lower serum Na concentration

44. Etiology of SIADH • Endocrine • Hypothyroidism, Adrenal Insufficiency • Pulmonary • Pneumonia, Asthma, COPD, pneumothorax • CNS • Trauma, infection, hemorrhage, hydrocephalus, CVA, demyelinating diseases, acute psychosis • Malignancy • Small cell lung cancer, intracranial tumors • Drugs • Thiazides, antidepressants, antipsychotics • Others: Post-operative state, pain, nausea

45. Approach to Hypotonic Hyponatremia

46. Clinical Manifestation of Hyponatremia • Severity of symptoms related to how rapid and to what degree the hyponatremia develops • Often with Na+ >125 asymptomatic or may have nonspecific symptoms • Headache, nausea, vomiting, muscle cramps, lethargy, restlessness, disorientation, depressed reflexes • More severe or rapidly developed hyponatremia • Seizures, coma, permanent brain damage, respiratory arrest, brain-stem herniation, and possibly death

47. Management of Hyponatremia • The optimal treatment of hypotonic hyponatremia requires balancing the risks of hypotonicity against those of therapy • The presence of symptoms and their severity largely determine the pace of correction • Too rapid correction  ↑ serum osmolality in setting of low brain osmolality  rapid water egress  acute brain dehydration  central pontine myelinosis

48. Management of Hyponatremia • No consensus about the optimal treatment of symptomatic hyponatremia • Most reported cases of osmotic dymyelination occurred after corrections of only 9 to 10 mmol/L in 24 hours or 19 mmol/L in 48 hours • Targeted rate of correction that does not exceed 8 mmol/L on any day of treatment • The initial rate of correction can still be 1 to 2 mmol/L/hour x several hours in patients with severe symptoms

49. Management of Hyponatremia • Hypovolemic Hyponatremia • Volume replacement, often with 0.9%NaCl • Hypervolemic Hyponatremia • Sodium (1-3 g/day) and water (1.0-1.5 L/day) restriction • SIADH • Free water restriction • If chronic demeclocycline • If neurologic emergency loop diuretic + hypertonic saline

50. Calculating fluid replacement In cases of hypovolemic or severe SIADH with neurological manifestations . . . • Calculate Na+ deficit: NA deficit= 0.6 x ideal body weight x (140 – measured Na) (x 0.85 for women) • Choose appropriate infusate • Calculate # liters of chosen saline required • Calculate rate of infusion, keeping in mind the danger of correcting too fast and at the same time the consequences of the untreated hypotonicity