Dr Sankalp Mohan

Senior Resident

Dept of Neurology

Govt Med college,Kota

SODIUM - Hyponatremia

-Hypernatremia

POTASSIUM - HypokalemiaHyperkalemia

CALCIUM - Hypercalcemia Hypocalcemia

MAGNESIUM - Hypomagnesemia Hypermagnesemia

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 osmolalityincreases above a threshold level of 285 mosmol/kg

Thirst and thus water ingestion also are activated at 285 mosmol/kg,

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

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%

Overview

normal

measure lipids, proteins

volume expanded

CHF

Cirrhosis

nephrotic

Volume Depleted

adrenal insuff

extrarenal losses

renal salt wasting

Euvolemic

polydipsia

SIADH

low (<280)

Assess ECF Clinically

High (>>280)

glucose

mannitol, sorbitol, glycine

serum osm (measured)

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

HYPONATREMIAHYPOVOLEMIC

EUVOLEMIC

HYPERVOLEMIC

Hypovolemic Hyponatremia

Hypovolemia causes a marked neurohumoralactivation, increasing circulating levels of AVP

increase in circulating AVP helps preserve blood pressure via vascular and baroreceptor V1A receptors and increases water reabsorption via renal V2 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 mM.

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

Hypervolemic Hyponatremia

proportionately greater increase in total body water, leading to a reduced plasma Na+ concentration

congestive heart failure (CHF), cirrhosis, and nephroticsyndrome

Arterial underfilling

Urine Na+ concentration is typically very low

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

CAUSES OF SIADH

SIADH Diagnosis of Exclusion CRITERIA Laboratory findings : Euvolemic hyponatremia <134 mEq/L, and POsm <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

Low Solute Intake and Hyponatremia –

very low intake of dietary solutes-

Alcoholics –beer potomania

Approach to hyponatremia

Pathogenesis of cerebral Edema

brain needs ∼48h 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

CLINICAL FEATURES Acute or Chronic

incidental

many patients present due to manifestations of other medical comorbidities

Mild – nausea malaise ,lethargy,concentrationdifficulties

DIAGNOSISSTEP 1

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

For hyperglycemic

hyponatremia

- or Add 2.4 mmol/l for every 100 mg/dl glucose

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 ≤30mmol/l suggests low effective arterial blood volume

Patient on diuretics – interpretation difficult

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;

Chronic hyponatremia - plasma Na+ concentration is corrected by >8–10 mM within the first 24 h and/or by >18 mM 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

CHRONIC HYPONATREMIA Fluid restriction

Vassopressin-2 receptor antagonists

Conivaptan and tolvaptan - fda approved

indicated for hypervolemic and euvolemichyponatremia (ie, serum Na level < 125 mEq/L )

Demeclocycline- a 2–3 day delay in onset .Nephrotoxic

Hypernatremia

plasma Na+ concentration to >145 mM

losses of H2O in excess of those of Na+.

or iatrogenic administration of excess Na+

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

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.

APPROACH TO HYPERNATREMIA

Treatment: Hypernatremia replacing the calculated free-water deficit over 48 h.

no more than 10 mM/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),

HYPOKALEMIA

ETIOLOGY

CLINICAL FEATURES Acute onset quadriparesis

Consiousness preserved

Respiratory and Bulbar involvement – rare and mild

Attacks of periodic paralyses

Examination- Proximal > distal muscle weakness,Legsmore than arms,hypotonia, hyporeflexia

In between attacks examination is normal

Progressive Proximal Myopathy develops usually at the age of 50 years

Paralytic Ileus

Associated features – metabolic alkalosis ,polyuria

Approach in general

- To exclude pseudohypokalemia

- Redistribution hypokalemia

- Urine potassium, Acid base status

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

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

HYPERKALEMIA plasma potassium level of 5.5 mM

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

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

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

Calcium abnormalities Calcium stabilizer of electrically exictable tissue

HYPERCALCEMIA

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

DIAGNOSIS IONISED calcium and Albumin levels

Correction - adding 0.2 mM (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

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)2D-mediated hypercalcemia –GLUCOCORTICOIDS – iv Hydrocortisone , oral prednisolone

HYPOCALCEMIA

Clinical Manifestations may be asymptomatic if mild or chronic

Moderate to severe hypocalcemia is associated with paresthesias, usually of the fingers, toes, and circumoralregions – lips tongue

Cramps ,fasciculations ,spasms

Chovstek s sign

Trosseau sign

Severe hypocalcemia can induce seizures- generalised or focal

carpopedal spasm. choreoathetosis

, bronchospasm, laryngospasm

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

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)

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

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

Treatment: Hypomagnesemia Mild, hypomagnesemia -with oral magnesium salts

[MgCl2, MgO, Mg(OH)2] in divided doses totaling 20–30 mmol/d (40–60 meq/d

severe hypomagnesemia -with IV MgCl2, continuous infusion of 50 mmol/d (100 meq Mg2+/d) if renal function is normal. Iv Mgso4 can cause hypocalcemia

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

THANK YOU

REFERENCES Clinical practice guideline on diagnosis and

treatment of hyponatraemia - Eur J Endocrinol March 1, 2014 170G1-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