Neurology of electrolyte imbalance

1. Neurology of Electrolyte Imbalance Dr Sankalp Mohan Senior Resident Dept of Neurology Govt Med college,Kota

2. SODIUM -  Hyponatremia          - Hypernatremia   POTASSIUM  - Hypokalemia     Hyperkalemia   CALCIUM -  Hypercalcemia    Hypocalcemia   MAGNESIUM -  Hypomagnesemia    Hypermagnesemia

3. Sodium Disorders Abnormalities in water homeostasis that lead to changes in the relative ratio of Na + to body water Water intake and circulating AVP AVP secretion is stimulated as systemic osmolality increases above a threshold level of 285 mosmol /kg Thirst and thus water ingestion also are activated at 285 mosmol /kg,

4. Hyponatremia DEFINITIONS Defined as sodium concentration < 135 mEq /L MILD – 130 -135 mEq /L MODERATE – 125-129 mEq /L PROFOUND - <125 ACUTE - <48 HRS . CHRONIC > 48 HRS

5. EPIDEMIOLOGY incidence is 0.97% and prevalence is 2.48% in hospitalised Age - more common in elderly persons  Sex - No sex prediliction . Symptoms more in younger women Mortality – Severe hyponatremia –high mortality . less than 105 mEq /L, the mortality is over 50%

6. Overview

7. Pseudohyponatremia and Translocational hyponatremia Pseudohyponatremia -high concentrations of lipids or proteins in the blood interfere with the accurate measurement of sodium Measurement of serum osmolarity ---hypotonic, isotonic or hypertonic, High osmolarity – glucose or hypertonic solutions

8. HYPONATREMIA HYPOVOLEMIC EUVOLEMIC HYPERVOLEMIC

9. Hypovolemic Hyponatremia Hypovolemia causes a marked neurohumoral activation, increasing circulating levels of AVP increase in circulating AVP helps preserve blood pressure via vascular and baroreceptor V 1A receptors and increases water reabsorption via renal V 2 receptors Nonrenal causes – gastrointestinal (GI) loss (vomiting, diarrhea , tube drainage, etc.) and insensible loss (sweating, burns) of Na + - Cl – and water urine Na + concentration is typically <20 m M .

10. Renal causes – deficiency in circulating aldosterone SalT -losing nephropathies include reflux nephropathy, interstitial nephropathies, post-obstructive uropathy , medullary cystic disease, recovering ATN Thiazide diuretics "cerebral salt wasting – volume depleted state most patients with CSW have elevated circulating levels of ADH

11. Hypervolemic Hyponatremia proportionately greater increase in total body water, leading to a reduced plasma Na + concentration congestive heart failure (CHF), cirrhosis, and nephrotic syndrome Arterial underfilling Urine Na + concentration is typically very low

12. Euvolemic Hyponatremia moderate to severe hypothyroidism - after the achievement of a euthyroid state secondary adrenal insufficiency due to pituitary disease , Glucocorticoid syndrome of inappropriate antidiuresis – erratic AVP secretion is seen in about a third of patients

13. CAUSES OF SIADH

14. SIADH   Diagnosis of Exclusion CRITERIA Laboratory findings : Euvolemic hyponatremia  <134 mEq /L, and P Osm  <275 mOsm /kg Urine osmolality >100mOsm/kg of water during hypotonicity [2] Urine sodium concentration >40 mEq /L with normal dietary salt intake Other findings : Clinical euvolemia without edema or ascites Low  blood urea nitrogen  (BUN) Normal serum  creatinine Low  uric acid Normal Acid-Base, K+ balance Normal Adrenal, Thyroid function

15. Low Solute Intake and Hyponatremia – very low intake of dietary solutes- Alcoholics –beer potomania

16. Approach to hyponatremia

17. Pathogenesis of cerebral Edema

18. brain needs ∼48 h to adapt to a hypotonic environment once adaptation is completed, brain cells can again sustain damage if the serum sodium concentration increases too rapidly. breakdown of the myelin sheath insulating individual neurons can result in what is called the osmotic demyelination syndrome

19. CLINICAL FEATURES Acute or Chronic  incidental many patients present due to manifestations of other medical comorbidities Mild – nausea malaise , lethargy,concentration difficulties

20. DIAGNOSIS STEP 1

21. STEP 2 – To Exclude pseudohyponatremia or hypertonic hypernatremia Non hypotonic hypernatremia does not cause brain edema . Psuedohyponatremia – laboratory artefact .use of ion specific electrodes MEASURE SERUM OSMOLARITY – variable Other – judge clinical scenario –like mannitol infusion measure glucose.lipids ,proteins urea and

22. For hyperglycemic hyponatremia - or Add 2.4 mmol /l for every 100 mg/dl glucose

23. Volume status measurement . However not very accurate – low sensitivity and specificity Measurement of urine osmolarity .less than 100 – excess water intake ( polydipsia ) Urine sodium concentration -  urine sodium concentration ≤30  mmol /l suggests low effective arterial blood volume Patient on diuretics – interpretation difficult

24. TREATMENT Hyponatraemia with severe symptoms Prompt infusion of hypertonic saline 3 % or 1.6 % Change in Serum Sodium = (Fluid Sodium - Serum Sodium) / (Total Body Water + 1) Total Body Water = (Wt in kg * % Water )   hyponatremia should be corrected at a rate not exceeding 10  mmol /L/24 h or 0.5  mEq /L/h;

25. Chronic hyponatremia - plasma Na + concentration is corrected by >8–10 m M within the first 24 h and/or by >18 m M within the first 48 h Hypovolemic hyponatremia will respond to intravenous hydration with isotonic normal saline, Hypervolemic hyponatremia due to congestive heart failure often responds to improved therapy of the underlying cardiomyopathy

26. CHRONIC HYPONATREMIA Fluid restriction Vassopressin-2 receptor antagonists Conivaptan and tolvaptan   - fda approved  indicated for hypervolemic and euvolemic hyponatremia ( ie , serum Na level < 125 mEq /L ) Demeclocycline - a 2–3 day delay in onset  . Nephrotoxic

27. Hypernatremia plasma Na + concentration to >145 m M losses of H 2 O in excess of those of Na + . or iatrogenic administration of excess Na +

28. ETIOLOGY Elderly individuals with reduced thirst renal water loss include osmotic diuresis secondary to hyperglycemia , excess urea, postobstructive diuresis , and mannitol Insensible losses of water may increase in the setting of fever, exercise, heat exposure, severe burns, Diarrhea is the most common gastrointestinal cause of hypernatremia Nephrogenic DI (NDI) is characterized by renal resistance to AVP Central DI

29. Clinical Features Altered mental status is the most common manifestation, ranging from mild confusion and lethargy to deep coma parenchymal or subarachnoid hemorrhages and/or subdural hematomas – more in children Osmotic damage to muscle membranes also can lead to hypernatremic rhabdomyolysis chronic hypernatremia are less likely to develop severe neurologic compromise.

30. APPROACH TO HYPERNATREMIA

31. Treatment: Hypernatremia replacing the calculated free-water deficit over 48 h. no more than 10 m M /d free water orally or through RT free water in dextrose-containing IV solutions hypotonic saline solutions (1/4 or 1/2 normal saline); Patients with central DI - ddavp NDI due to lithium may reduce their polyuria with amiloride (2.5–10 mg/d),

32. HYPOKALEMIA

33. ETIOLOGY

34. CLINICAL FEATURES Acute onset quadriparesis Consiousness preserved Respiratory and Bulbar involvement – rare and mild Attacks of periodic paralyses Examination- Proximal > distal muscle weakness,Legs more than arms,hypotonia , hyporeflexia In between attacks examination is normal Progressive Proximal Myopathy develops usually at the age of 50 years

35. Paralytic Ileus Associated features – metabolic alkalosis , polyuria Approach in general To exclude pseudohypokalemia Redistribution hypokalemia Urine potassium, Acid base status

36. INVESTIGATIONS Serum potassium – mean 2.4 . Hypokalemic PP- K normal between attacks ECG changes of Hypokalemia – ST depression,U waves ,decreased T wave amplitude T3,T4,TSH ABG ,Other Electrolytes –Ca ,Po4 CPK may be elevated Electromyography (EMG)- during attack CMAP may be reduced

37. TREATMENT ACUTE TREATMENT – Oral potassium chloride 60 -120 meq incrementally 30 meq orally every 30 min  Iv potassium is reserved for cardiac arrhythmia or airway compromise due or accessory respiratory muscle paralysis. iv dose is usually 20–40 mmol of K + - Cl – per liter ; Very severe – iv line -10-20 meq /hr with iv monitoring Cardiac monitoring recommended

38. HYPERKALEMIA plasma potassium level of 5.5 m M 10% of hospitalized patients . 1 % more than 6 mM Pseudohyperkalemia Redistribution and Hyperkalemia Excess Intake or Tissue Necrosis Hypoaldosteronism and Hyperkalemia Renal Disease and Hyperkalemia Medication-Associated Hyperkalemia

39. CLINICAL FEATURES Cardiac arrhythmias associated with hyperkalemia include sinus bradycardia , sinus arrest, slow idioventricular rhythms, ventricular tachycardia, ventricular fibrillation begins in the legs, thighs, and lower back and spreads to the hands, forearms, and shoulders Respiratory muscles are usually spared

40. TREATMENT Immediate antagonism of the cardiac effects of hyperkalemia - 10 mL of 10% calcium gluconate (3–4 mL of calcium chloride), infused intravenously over 2 to 3 min with cardiac monitoring Rapid reduction in plasma K + concentration by redistribution into cells - 10 units of IV regular insulin followed immediately by 50 mL of 50% dextrose B2 -agonists Intravenous bicarbonate has no role Removal of potassium - SPS 15-30 g/day Diuretics ,dialysis

41. Calcium abnormalities Calcium stabilizer of electrically exictable tissue

42. HYPERCALCEMIA

43. Clinical Manifestations Mild hypercalcemia (up to 11–11.5 mg/ dL ) is usually asymptomatic CNS -vague neuropsychiatric symptoms , including trouble concentrating, personality changes ,proximal muscle fatigue Occasionally symptoms like MND, bradykinetic disorder like parkinsonism OTHER -peptic ulcer disease or nephrolithiasis , and fracture risk severe hypercalcemia (>12–13 mg/ dL ), particularly if it develops acutely, may result in lethargy, stupor, or coma, gastrointestinal symptoms bradycardia , AV block, and short QT interval

44. DIAGNOSIS IONISED calcium and Albumin levels Correction - adding 0.2 m M (0.8 mg/ dL ) to the total calcium level for every decrement in serum albumin of 1.0 g/ dL PTH level .phosphate levels Increased PTh – primary hyperparathyroid .. Decreased pTH with hypercalcemia – malignancy Serum Vit D3 levels – granulomatous disorders

45. TREATMENT MILD / asymptommatic – does not require therapy Severe symptommatic - 4–6 L of intravenous saline may be required over the first 24 h . may be given with loop diuretics Severe hyperparathyrid /malignancy – Zoledronic acid (e.g., 4 mg intravenously over 30 min), pamidronate (e.g., 60–90 mg intravenously over 2–4 h), and etidronate (e.g., 7.5 mg/kg per day for 3–7 consecutive days) 25(OH) 2 D-mediated hypercalcemia – GLUCOCORTICOIDS – iv Hydrocortisone , oral prednisolone

46. HYPOCALCEMIA

47. Clinical Manifestations may be asymptomatic if mild or chronic Moderate to severe hypocalcemia is associated with paresthesias , usually of the fingers, toes, and circumoral regions – lips tongue Cramps , fasciculations ,spasms Chovstek s sign Trosseau sign Severe hypocalcemia can induce seizures- generalised or focal carpopedal spasm. choreoathetosis , bronchospasm , laryngospasm

48. DIAGNOSIS Ionised calcium ,albumin, phosphorus, and magnesium levels. PTH levels and Vit D levels ECG – QT prolongation EEG – generalised /focal slowing or triphasic waves – s/o metabolic encephalopathy

49. TREATMENT Acute, symptomatic hypocalcemia – calcium gluconate , 10 mL 10% wt/ vol (90 mg or 2.2 mmol ) intravenously, diluted in 50 mL of 5% dextrose or 0.9% sodium chloride, given intravenously over 5 min constant intravenous infusion - calcium gluconate or 900 mg of calcium in 1 L of 5% dextrose or 0.9% sodium chloride administered over 24 h Chronic hypocalcemia due to hypoparathyroidism is treated with calcium supplements (1000–1500 mg/ of vitamin D (50,000 U, 2–3 times per week for several months)

50. MAGNESIUM NORMAL mg - of 0.7–1 mmol /L (1.5–2 meq /L ) crucial for normal neuromuscular activity HYPOMAGNESEMIA ETIOLOGY -intestinal malabsorption ; protracted vomiting, diarrhea , or intestinal drainage; defective renal tubular magnesium reabsorption

51. HYPOMAGNESEMIA Symptoms similar to hypocalcemia Hypomagnesemia may cause generalized alterations in neuromuscular function, including tetany , tremor, seizures, muscle weakness, Headache blurred vision ataxia, nystagmus , vertigo, apathy, depression, irritability, delirium, and psychosis ,auditory changes sinus tachycardia, other supraventricular tachycardias , and ventricular arrhythmias prolonged PR or QT intervals, T-wave flattening

52. Treatment: Hypomagnesemia Mild, hypomagnesemia -with oral magnesium salts [MgCl 2 , MgO , Mg(OH) 2 ] in divided doses totaling 20–30 mmol /d (40–60 meq /d severe hypomagnesemia -with IV MgCl 2 , continuous infusion of 50 mmol /d (100 meq Mg 2+ /d) if renal function is normal. Iv Mgso4 can cause hypocalcemia

53. Hypermagnesemia rarely seen in the absence of renal insufficiency CLINICAL FEATURES - vasodilation and neuromuscular blockade >2 mmol /L Hypotension that is refractory to vasopressors respiratory failure, paralysis, and coma, with hypoactive tendon reflexes, at serum magnesium levels >4 mmol /L prolongation of PR, QRS, and QT intervals; heart block TREATMENT - Use of magnesium-free cathartics or enemas , vigorous iv hydration , hemodialysis

54. THANK YOU

55. REFERENCES Clinical practice guideline on diagnosis and treatment of hyponatraemia - Eur J Endocrinol  March 1, 2014  170 G1-G47 New European guidelines management of Hyponatremia 2014 Neurology Clinics – neurology and systemic disease Feb 2010 .vol28 Harrison s principles of internal medicine 18 th