neurology of electrolyte imbalance

NEUROLOGY OF ELECTROLYTE IMBALANCE

DR. PIYUSH OJHADM RESIDENT

DEPARTMENT OF NEUROLOGYGOVT MEDICAL COLLEGE, KOTA

• SODIUM - Hyponatremia- Hypernatremia

• POTASSIUM - Hypokalemia- Hyperkalemia

• CALCIUM - Hypercalcemia

- Hypocalcemia

• MAGNESIUM - Hypomagnesemia

- Hypermagnesemia

SODIUM

• Major ECF cation (140mEq/L ECF vs 25 mEq/L ICF)

• Total body sodium ~ 5,000 mEq in a normal adult

• 85-90% is extracellular.

• Responsible for > 90% of total osmolality of ECF.

• Daily requirement = 100 mEq or 6 gm of NaCl.

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 water ingestion also are activated at 285

mosmol/kg.

Hyponatremia

Hyponatremia

• Defined as plasma Na+ concentration < 135 mEq/L

• Occurs in approx 2.2% of hospitalised patients.

• Acute severe hyponatremia has a high morbidity and mortality. ( Na level < 105 has >50% mortality)

• Mostly a result of an increase in circulating AVP and/or increased sensitivity to AVP, combined with any intake of free water.(EXCEPTION – hyponatremia due to low solute intake)

• MILD – 130 -135 mEq/L

• MODERATE – 125-129 mEq/L

• PROFOUND - <125

• ACUTE - <48 HRS . CHRONIC > 48 HRS

Hyponatremia

• Depending on Osmolality, hyponatremia is divided into

Pseudo hyponatremia and Hypoosmolar (True )

Hyponatremia.

• Depending on clinical history and volume status,

Hypoosmolar hyponatremia (TRUE hyponatremia ) is

subdivided into –

– Hypovolemic

– Euvolemic

– Hypervolemic.

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 V1A receptors

and increases water reabsorption via renal V2 receptors

• Nonrenal causes –

gastrointestinal (GI) loss (vomiting, diarrhoea, tube

drainage, etc.) and insensible loss (sweating, burns) of

Na+Cl– and water.

urine Na+ concentration is typically <20 mEq/L.

• Renal causes –

Urinary Na concentration is typically > 20 mEq/L.

Deficiency in circulating aldosterone and/or its renal

effects.

Salt-losing nephropathies including reflux nephropathy,

interstitial nephropathies, post-obstructive uropathy,

medullary cystic disease, recovering ATN

Thiazide diuretics

Cerebral salt wasting syndrome – volume depleted state

(as in SAH, traumatic brain injury, encephalitis,

meningitis, craniotomy)

Hypovolemic Hyponatremia

Hypervolemic Hyponatremia

• Proportionately greater increase in total body water

compared to that of Na+, leading to a reduced plasma

Na+ concentration

• Congestive heart failure (CHF), cirrhosis, and nephrotic

syndrome (urinary Na < 20 mEq/L)

• Renal failure (urinary Na > 20 mEq/L)

Euvolemic Hyponatremia

• Moderate to severe hypothyroidism - after the achievement of a euthyroid state

• Psychogenic Polydipsia

• secondary adrenal insufficiency due to pituitary disease

• Syndrome of inappropriate antidiuretic hormone (most common cause)

• SIADH is characterised by high urinary sodium, osmolality and specific gravity, inspite of low serum sodium and hypoosmolality.

• erratic AVP secretion is seen in about a third of patients

Pseudohyponatremia and

Translocational hyponatremia

• Pseudohyponatremia -high concentrations of lipids or proteins in the blood interfere with the accurate measurement of sodium

• Normal osmolality- hyperlipdemia, hyperprotenemia

• High osmolality – hyperglycemia, Mannitol

• Low Solute Intake and Hyponatremia – Very low intake of dietary solutes

Alcoholics –beer potomania

Very low urine osmolality < 100-200 mosmol/kg with a urine

Na+ concentration <10-20mM.

Clinical features of Hyponatremia

• The severity of symptoms depend on severity of

Hyponatremia and rate at which Na concentration is

lowered.

• So acute and severe hyponatremia is symptomatic while

chronic and mild hyponatremia is well tolerated.

Mild Moderate Severe

Anorexia

Headache

Nausea

Vomiting

Lethargy

Personality changes

Muscle cramps

Muscular weakness

Confusion

Ataxia

Drowsiness

Diminished reflexes

Convulsions

Coma

death

Clinical features of Hyponatremia

Diagnosis of Hyponatremia

• History and physical examination is often helpful in

identifying hypovolemic hyponatremia. (diarrhoea,

vomiting, burns, diuretics etc.)

• Severity of hyponatremia often correlates with severity of

underlying condition and is an important prognostic factor.

• Three important diagnostic tests are :-

1. plasma osmolality

2. urinary osmolality

3. urinary Na concentration

• Levels can be repeated to rule out any lab error.

• Blood should always be drawn from a vein that does

not have IV fluids flowing through it.

• MEASURE PLASMA OSMOLARITY –

= 2 X Na + [Glucose(mg/dl)/18] + [BUN(mg/dl)/2.8]

• Hyponatremia is usually associated with low plasma

osmolality. But if it is normal or high, exclude

pseudohyponatremia

• Pseudohyponatremia does not cause brain edema.

Diagnosis of Hyponatremia

• Hyponatremia in edematous patient – consider CHF,

cirrhosis, nephrotic disease or other renal disease.

• In hypovolemic patients, rule out renal or extrarenal

causes.

• Associated hyperkalemia- suggests renal insufficiency or

adrenal insufficiency with hypoaldosteronism.

• Associated hypokalemia and metabolic alkalosis –

suggests vomiting or diurteic therapy.

• Diuretic induced hyponatremia is almost always due

to thiazide diuretics and rare with loop diuertics.

Steps in initial Evaluation of Hyponatremia

• Measure Plasma osmolality

• Low – True Hyponatremia

• Normal or elevated – Pseudohyponatremia

• Measure Urinary Osmolality

• <100 mOsm/kg or sp gravity < 1.003, dilute urine suggest

primary polydipsia with normal water excretion.

• > 100 mOsm/kg, other causes in which water excretion is

impaired

• Urine Na Concentration

• < 15 mEq/L – effective volume depletion eg diarrhoea,

vomiting

• > 20 mEq/L – SIADH or renal salt wasting.

Confirm diagnosis of Hyponatremia

Rule out PseudohyponatremiaNormal or High Osmolality

Hypoosmolality

Assess Renal status Primary renal disease

Impairedrenal function

Assess Volume status

Normal

OEDEMA – CHF, Cirrhosis, Nephrotic Syndrome

VOLUME DEPLETION

Urinary Na excretion (mEq/L)

Urinary Na < 15Diarrhoea, vomiting, burns, pancreatitis

Urinary Na > 20Diuretics, salt losing nephropathy

Normovolemic

Normovolemic

Assess Adrenal & Thyroid function

Adrenal or thyroid insufficiency

Normal

Able to dilute urine in response to water load

SIADH

Dilute Urine

No

Yes

Psychogenic Polydypsia

• Must be individualized considering etiology, rate of

development, severity and clinical signs and symptoms.

• In short,

Treatment of Hyponatremia

HYPONATREMIA

NORMOVOLEMIAOEDEMA HYPOVOLEMIA

salt & water supplementation

No saltFluid restrictionLoop diuretics

Fluid restriction

• Specific treatment :-

– Treatment of the underlying disease like adrenal

insufficiency, hypothyroidism, nephrotic syndrome,

CHF, DM

– Removal of the offending drug like Thiazide diuretics,

chlorpropamide or IV cyclophosphamide

General guidelines for sodium correction

• Chronic Asymptomatic Hyponatremia :-

– The target rate of plasma sodium correction should

be < 10-12 mEq/L on the first day and < 18 mEq/L

over first 2 days.

– As per recent recommendations, the correction rate

should not exceed 8 mEq/L on any day of treatment.

– If the rate of correction is faster or rise in serum Na is

> 25 mEq/48 hrs, there is a high risk of central

pontine myelinosis.


• Acute Hyponatremia with severe Neurological

symptoms :-

– Require rapid correction with hypertonic saline 3% or

1.6% .

– The initial rate of rise of plasma sodium correction

should be < 1.5-2 mEq/L/hr for the first 3 to 4 hours or

until severe neurological symptoms improve

– Besides this initial rapid correction, rise in the plasma

Na concentration should not exceed 10-12 mEq in

first 24 hours.


• Chronic Hyponatremia

• 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

HYPERNATREMIA

HYPERNATREMIA

• Defined as plasma Na concentration > 145mEq/L.

• A less frequent diorder.

• Mortality rates 40-60%

• Mostly due to combined losses of water and electrolytes with losses of H2O in excess of those of Na+.

• Less frequently due to ingestion or iatrogenic administration of excess Na+

ETIOLOGY OF HYPERNATREMIA

1. Excess water loss

a. Insensible loss :

Dermal : heat exposure, severe burns, severe exercise

Respiratory : mechanical ventilation

b. Renal loss : Diabetes inspidus (central or nephrogenic),

excessive diuretics, uncontrolled DM

c. GI losses : Osmotic diarrhoea

2. Water defecit due to imapaired thirst.

Primary hypodypsia, confused or comatose conditions

3. Sodium retention.

excesive IV hypertonic NaCl or NaHCO3

ETIOLOGY

• Elderly individuals with reduced thirst and/or diminshedaccess to fluids are at highest risk.

• renal water loss including 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 or mechanical

• Diarrhea is the most common gastrointestinal cause of hypernatremia

• Nephrogenic DI (NDI) characterized by renal resistance to AVP (Hypercalcemia & Hypokalemia and drugs like Li,Ifosfamide may also lead to NDI)

• Central DI

Clinical Features of Hypernatremia

• Hypernatremia leads to increased osmolality of ECF –

osmotic gradient btwn ECF and ICF – efflux of

intracellular water – cellular shrinkage.

• Symptoms are predominantly Neurologic.

• Altered mental status is the most common manifestation,

ranging from mild confusion and lethargy to deep coma

• Sudden shrinkage of brain cells may lead to

parenchymal or subarachnoid hemorrhages and/or

subdural hematomas – predominantly in children.

Clinical Features of Hypernatremia

• Other features include nausea, muscular weakness,

focal neurological defecit, seizures.

• Osmotic damage to muscle membranes also can lead to

Hypernatremic rhabdomyolysis.

• Chronic hypernatremia are less likely to develop severe

neurologic compromise because of cerebral adaptations.

APPROACH TO HYPERNATREMIA

• Detailed history with focus on thirst, polyuria and/or extrarenal water loss.

• Detailed neurological examination.

• Assessment of ECFV.

• Accurate I/O charting.

• Lab investigations – serum and urine osmolality and urinary electrolytes.

APPROACH TO HYPERNATREMIA

Treatment of Hypernatremia

• Correction of underlying cause.

• To replace the calculated free-water deficit over

48-72 hrs to avoid cerebral edema.(ongoing loss and

insensible loss are to be considered seperately)

Water Defecit = [(plasma Na -140)/140] x 0.6 x body wt (kg)

• No more than 10 mEq/L/day or

• A rare exception is acute hypernatremia (<48hrs)

due to sodium loading.

(can be corrected at rate of 1mM/hr).

Treatment of Hypernatremia

• Goal of treatment is to reduce Na to 145mEq/L.

• Free water orally or through RT.

• Acute hypernatremia is treated vigorously by D-5%

infusion.

• Hypotonic saline solutions (0.45% NS)

•

• Patients with central DI - DDAVP

• NDI due to lithium may reduce their polyuria with

amiloride (2.5–10 mg/d).

POTASSIUM

POTASSIUM

• Major intracellular cation.

• Total body potassium ~ 3,500 mEq (98% intracellular &

2% extracellular )

• Normal serum potassium concentration = 3.5 – 5 mEq/ L

( vs intracellular 150 mEq/L)

• Normal daily potassium requirement = 50-80 mEq/day

HYPOKALEMIA• Potassium levels below 3.5 mEq/L.

• Causes of Hypokalemia :-

1.Poor intake – low dietary intake or potassium free fluids.

2. Non-renal loss (Urinary K excretion <20mEq/day)

vomiting, diarrhoea, excessive sweating, large

nasogastric aspiration

3. Renal loss – (Urinary K excretion >30mEq/day)

diuretics, salt wasting nephropathies, mineralocorticoid

excess, cushing’s syndrome, steroid therapy,

Magnesium deficiency, amhotericin B therapy

4. Redistribution (shift of K into cells)

metabolic alkalosis, insulin, adrenergic agonist

(eg Salbutamol)

CLINICAL FEATURES OF HYPOKALEMIA

• Manifestations are mainly neuromuscular and cardiac.

• Fatigue, myalgias and muscular weakness.

• Smooth muscle weakness- constipation,ileus or urinary retention.

• Acute onset quadriparesis with preserved consciousness

• Respiratory and Bulbar involvement – not common

• 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

ECG CHANGES IN HYPOKALEMIA

• Early changes :

– Flattening or inversion of T waves

– Prominent U waves

– ST segment depresion

– Prolonged QT interval

• Severe potassium depletion :

– Prolonged PR interval

– Decreased voltage

– Widening of QRS complex

– Ventricular arrhythmia

DIAGNOSIS OF ETIOLOGY OF HYPOKALEMIA

A. History – poor dietary intake, abnormal losses,

diuretics, drugs causing transcellular shift

B. Urinary K excretion –

1. Hypokalemia with low renal K excretion (<25 m

Eq/day)

suggests poor oral intake, diarrhoea, excessive

sweating, vomiting or diuretics.

2. Hypokalemia with high urinary K excretion :

a. K wasting with metabolic acidosis with no

hypertension : DKA, proximal and distal RTA,

amphotericin B

b. K wasting with variable pH : renal salt wasting :

recovering ATN, postobstructive diuresis

c. K wasting with metabolic alkalosis with no

hypertension :

- low urinary chloride (<20 mEq/day) : vomiting

- High urinary chloride : Diuretics, Bartter syndrome

d. K wasting with metabolic alkalosis with

hypertension.

Primary and secondary aldosteronism, cushing’s syndrome,

renovascular hypertension, Liddle’s syndrome

DIAGNOSIS OF ETIOLOGY OF HYPOKALEMIA

TREATMENT OF HYPOKALEMIA

• Therapeutic goals :-

1. Prevention of hypokalemia

2. To prevent life threatening complications

(arrhythmia & respiratory failure)

3. To correct K deficeit

4. To minimize ongoing losses

5. To treat underlying etiology


• Normal potassium intake of 60 mEq/day is sufficient to

prevent hypokalemia .

• Patients at risk like on digitalis therapy, DM, cirrhosis

should be given adequate supplementation.

• Roughly 1mEq/L fall in serum potassium = 200-400 mEq

total body potassium.


• WHEN TO TREAT :-

– 3.5 – 4 mEq/L : no potassium supplementation,

increased oral intake of K rich foods, add K sparing

diuretic or decrease dose of diuretic

– 3 – 3.5 mEq/L : treatment in selected high risk

patients (risk of arrhythmia eg. CHF, digitalis therapy,

IHD)

– < 3 mEq/L : needs definitive therapy


• In oliguria / anuria, avoid or supplement K cautiously.

• Failure to increase serum K after sufficient doses and

duration of potassium supplement should raise

possibility of associated Magnesium deficiency.


• Potassium chloride (KCl) is usually the preparationof

choice and will promote correction of hypokalemia as

well as of metabolic alkalosis.

• KCl is available in market as solution containing 20 mEq

potassium per 15 ml solution (1 gm KCl= 13.4 mEq of K).

• KCl tablets are also available as 8 mEq potassium per

tablet.


• Potassium bicarbonate and citrate tend to alkalinize the

patient and would be more appropriate for hypokalemia

associated with chronic diarrhoea or distal RTA.

• Oral potassium preparation may frequently cause GI

irritation so patient is adviced to take KCl solution with

proper dilution in a glass of water, after food.

• Oral potassium supplementation is safer than IV route as

there is minimal risk of hyperkalemia.


• In mild to moderate Hypokalemia (3-3.5 mEq/L), average

dose of KCl is 60-80 mEq/day (20mEq, 3-4 times) along

with treatment of underlying disorder.

• In severe (<2mEq/L) or symptomatic hypkalemia, more

rapid replacement is needed and dose can be increased

to 40 mEq 6 hourly under close ECG monitoring.


• IV potassium supplementation should be reserved for

severe symptomatic hypokalemia (<3mEq/L) or those

cannot ingest oral potassium.

• Continuous ECG monitoring and frequent K level

monitoring is recommended.

• Avoid IV potassium, till urine output is established.

• Don’t give > 10-20 mEq/ hour or > 40 mEq/litre or >240

mEq/day.

• Injection KCl available as : Inj KCl 15%, 10 ml ampoule

• 10 ml of 15 % KCl = 20 mEq of potassium = 1.5 gm KCl


• IV KCl bolus injection are contraindicated as it may lead to sudden hyperkalemia and cardiac arrest.

• KCl should be mixed with isotonic saline while administration.

• As soon as cardiac rhythm stabilises or respiratory muscle strength is restored to normal, IV potassium is discontinued and oral KCl is initiated.

• Potassium rich food : fruit juice, coconut water, banana, dry fruits, chocolate, coffee, salt substitute eg Lona salt.

HYPERKALEMIA

HYPERKALEMIA

• Serum potassium level > 5.5 mEq/L.

• Often asymptomatic until K level is 6.5-7.0 mEq/L.

• Vague muscular weakness is usually the first symptom

of hyperkalemia.

• Muscular weakness with preserved consciousness may

be present beside cardiac manifestation

CAUSES OF HYPERKALEMIA

• Increased intake

• Tissue breakdown – bleeding into soft tissues, hemolysis, catabolic state

• Shift of potassium out of cell – tissue damage (ischemia), severe exercise, metabolic acidosis, uncontrolled DM, aldosterone deficiency, succinylcholine

• Impaired excretion – ARF/CRF, potassium sparing diuretics, ACE inhibitors, heparin, reduced tubular excretion as in Addison disease

• Pseudohyperkalemia – traumatic hemolysis in blood drawing, marked leucocytosis

DIAGNOSIS OF HYPERKALEMIA

• Depends on clinical suspicion, serum K levels and

characteristic ECG changes.

• ECG changes are as follows :-

– 6-7 mEq/L – tall peaked T waves

– 7-8 mEq/L – loss of P waves and widening of QRS

complexes

– 8-10 mEq/L – QRS merges with T waves forming Sine

waves

– > 9 mEq/L – AV dissociation, VT or fibrillation and

cardiac standstill

DIAGNOSIS OF ETIOLOGY OF HYPERKALEMIA

• The urinary K excretion rate or transtubular potassium

gradient (TTKG) is widely used to differentiate renal

(hypoaldosteronism) and extrarenal causes of

hyperkalemia.

• Extrarenal Causes – urinary K excretion > 80 mEq/day

and TTKG >10

• Renal causes – urinary K excretion <20 mEq/day and

TTKG < 3

• Transtubular potassium gradient (TTKG) =

(Uk) / [Uosm/Posm]/Pk

TREATMENT OF HYPERKALEMIA

• Principles of treatment of Hyperkalemia : -

– Antagonism of membrane effects of hyperkalemia: Ca Gluconate

– Potassium movement into cells : insulin & glucose, Inj Sodium Bicarbonate, Beta2 agonist (salbutamol)

– Removal of potassium from the body : loop or thiazide diuretics, cation exchange resin (Keyxalate), peritoneal dialysis or hemodialysis


• CALCIUM GLUCONATE : -

– Available as 10% solution in 10 ml ampoules.

– Usual dose is 10-20 ml infused over 5-10 mins.

– Rapid but short lived effect.

– Dose can be repeated if no change is seen in ECG

after 10 mins

– Prevents cardiotoxicity of hyperkalemia.

– NO EFFECT ON POTASSIUM LEVELS.


• INSULIN & GLUCOSE: -

– Rapid way to lower K levels.

– 25 to 50 gms of glucose together with 10-20 units of

regular insulin is to be given.

– If effective, the plasma potassium concentration will

fall by by 0.5 to 1.5 mEq/L. this effect begins in 15

mins, peaks at 60 mins and may last for

approximately 4-6 hours.


• SODIUM BICARBONATE INFUSION: -

– Shifts K into cells.

– NaHCO3 7.5%, 50-100 ml(45-90 mEq) is given as

bolus IV slowly over 10-20 mins followed by IV

NaHCO3 infusion.

– Onset of its effect is within 5-10 mins and effect lasts

for 1-2 hours.

– Most likely to be useful in severe hyperkalemia with

metabolic acidosis.


• BETA ADRENERGIC AGONISTS: -

– Beta2 agonists such as Salbutamol promote cellular

uptake of potassium and thus decrese level.

– Dose 20 mg in 4 ml of saline by nasal inhalation over

10 minutes, or 0.5 mg by IV infusion.

– Generally becomes effective in 30-60 mins and its

effect persists for 2-4 hrs. it lowers K level by 0.5-

1.5mEq/L.


– Calcium gluconate, glucose insulin , NaHCO3 and

Beta2 agonists are temporary measures. They donot

remove excess potassium from the body.

– Measures to remove potassium from body are

diuretics, cation exchange resins and dialysis.


• CATION EXCHANGE RESINS: -

– Eg Sodium polystyrene sulphonate (Keyxalate) promote

exchange of sodium for potassium in GI tract.

– Each gram binds 1 mEq of potassium and releases 2-3 mEq of

sodium.

– When given orally, usual dose is 25-30 grams mixed with 100ml

20% sorbitol 3-4 times daily.(sorbitol prevents constiaption)

– Can also be given as retention enema consisting 50gm resin and

50 ml of 70% sorbitol mixed in 150ml water every 4-6 hourly.

– Each enema generally lowers levels by 0.5-1 mEq/L within 1-2

hrs and effect lasts for 4-6 hours.

– Adverse effects – anorexia, nausea, vomiting and constipation.

– Should be cautiously used in CHF patients.


• DIALYSIS: -

– Most rapid and effective way of lowering potassium

levels.

– Should be reserved for patients with renal failure and

those with severe life threatening hyperkalemia

unresponsive to conservative measures.

– Peritoneal dialysis also remove potassium but is only

15-20 % as effective as hemodialysis.

CALCIUM

• Essential for bone formation and neuromuscular

function.

• Parathyroid hormone (PTH) and Vitamin D (1,25(OH)2

D-3) are main factors that maintain normal serum ionized

Calcium.

• Normal adult human body contains ~ 1.2 – 1.4 Kg Ca

• So it is most abundant cation in body.

• 99% present in bone.

• Normal range = 9.5-10.5 mg/dl

• 40% is bound to albumin and 50-55% in ionized form

CALCIUM

CALCIUM

• Ionized free form is the physiologically active form (4.8

mg/dl)

• Total serum calcium does not always reflect ionized Ca

level.

• Hypoproteinemia leads to reduced protein bound and

total serum calcium but the ionized Ca remains

unchanged.

• Correction for total serum Ca level in Hypoalbuminemia :

add 1mg/dl to serum Ca level for each 1gm/dl reduction

in serum albumin level below 4 gm/dl.

CAUSES OF HYPERCALCEMIA

• Increased bone turnover :

– Primary and secondary hyperparathyroidism

– Malignancy (lung,breast, kidney, multiple myeloma)

– Thyrotoxicosis

– Lithium therapy

• Increased intestinal absorption

– Vitamin D intoxication

– Milk alkali syndrome

– Granulomatous disease ( i.e. Sarcoidosis)

• Decreased renal excretion

– Familial hypocalciuric hypercalcemia

– Thiazide diuretics

– Acute adrenal insufficiency

CLINICAL FEATURES OF HYPERCALCEMIA

• Secondary to underlying disorders.

• Secondary to Hypercalcemia :

– Mild hypercalcemia is asymptomatic.

– Severe Hypercalcemia may manifest as :

• CNS symptoms : weakness, fatigue, depression,

confusion, stupor or coma.

• GI symptoms : constipation, anorexia, nausea

and vomiting, abdominal pain

• Renal symtoms : polyria, nocturia and calculi

formation.

• Cardiac : more prone to digitalis toxicity

DIAGNOSIS OF HYPERCALCEMIA

• Primary hyperparathyroidism and malignancy account

for 90% of cases.

• History

• Physical examination

• Imaging (eg.Cxray)

TREATMENT OF HYPERCALCEMIA

A. Measures to increase urinary excretion :

– Volume restoration, expansion and saline diuresis

are most useful and effective measures to correct

hypercalcemia.

– 0.9% NaCl corrects dehydration, expands volume

and causes natriuresis and Ca secretion in urine.(4-6

L/day)

– Forced diuresis with Frusemide (20-160 mg IV 8

houly after volume expansion)

– Haemodialysis


B. Measures to inhibit bone resorption :

– Bisphosphonates :Pamidronate is most potent and

widely used in hypercalcemia due to bone

resorption. Dose – 90mg IV over 4 hours, maximal

effect in 2-3 days and effect lasts for few weeks .

– Plicamycin – highly toxic

– Calcitonin – inhibits bone resorption and increases

urinary clcium excretion. Rapid onset of action. So

useful in acute conditions only. Dose 4 IU/kg s/c 12

hourly


C. Measures to decrease intestinal absorption :

– Glucocrticoids : decreases intestinal absorption

and increases urinary excretion. Effective in

hypercalcemia due to vitamin intoxication,

sarcoidosis, and malignancies but donot alter

calcium levels in primary hyperthyroidism or in

normal person.

Dose – 200-300 mg Hydrocortisone IV 6 hrly for 3-5 days

– Oral phosphate : inhibits calcium absorption and

promotes calcium deposition in bone and soft

tissues. Should be used only when serum

phosphorus < 3 mg/dl and normal renal function.


D. Specific treatment :

– Discontinue drug responsible.

– Surgical treatment of hyperparathyroidism

– Specific treatment for malignancy

HYPOCALCEMIA

CAUSES OF HYPOCALCEMIA

• Hypoalbuminemia

• Hypoparathyroidism

– Post surgical

– Hypomagnesemia

– Idiopathic

• Defect in Vitamin D metabolism

– Nutritional, lack of sunlight exposure

– Malabsorption

– Liver disorders, renal failure

– Vitamin D depenedent rickets

• Miscellaneous

– Metabolic or respiratory alkalosis

– Sepsis, toxic shock syndrome, burns, acute pancreatitis,

massive transfusion of citrated blood

CLINICAL FEATURES OF HYPOCALCEMIA

• Vary with degree and rate of onset.

• Due to increased neuromuscular excitability.

• Weakness, circumoral and distal extremity parasthesias,

muscle spasms, carpopedal spasm, tetany and mental

changes such as irritability, depression and psychosis.

• On physical examination, patient may have increased

DTR’s or signs of latent tetany (Chevostek sign,

Trousseau sign)

• ECG – prolonged QT interval.

• Severe hypocalcemia may cause lethargy, confusion,

laryngeal spasm, seizure or reversible heart failure.

• Chronic state due to hypoparathyroidism may cause

catarcts and basal ganglia calcification.

DIAGNOSIS OF HYPOCALCEMIA

• Detailed History

• Physical examination

• Serum albumin

• Serum HCO3.

• Serum Magnesium

• Serum PTH

TREATMENT OF HYPOCALCEMIA

A. Acute management :

• Symptomatic hypocalcemia should be treated as an

emergency with 10% calcium gluconate (90 mg

elemental calcium/10ml) 10-20 ml IV, slowly over 10

mins.

• May also require infusion of 60 ml of calcium

gluconate in 500 ml 5% dextrose (Ca concentration

1mg/ml at rate 0.5-2 mg/kg/hour)

• If IV calcium doesnot relieve tetany, then rule out

(and correct) hypomagnesemia.

• When citrated blood is transfused rapidly,

hypocalcemia can occur. So for every 4 units of

blood, give 10ml of 10% calcium gluconate.

TREATMENT OF HYPOCALCEMIA

A. Long term management :

• Treatment of underlying etiology.

• Calcium supplementation : oral elemental calcium

1 to 3 gm per day. Calcium is best absorbed when

taken between meals.

• Vitamin D supplementation :

• Calcitriol [1,25(OH)2 D3] is the most potent of

vitamin D preparations.

MAGNESIUM

MAGNESIUM

• 4th most common cation of body (after Na, K, and Ca)

• 2nd most common intracellular cation (after K)

• Commonest intracellular divalent cation.

• 60 % of body Mg is in bones

• Normal serum Mg level = 1.4-2.2 mEq/L (1.8-3.0 mg/dl)

• Since clinical effects of Magnesium disorders are

determined primarily by tissue magnesium content,

serum Mg levels have limited diagnostic value.

• Mg plays an important role in neuromuscular function

and maintenance of cardiovascular tone.

CAUSES OF HYPERMAGNESEMIA

• Serum Mg levels > 3 mg/dl.

• Rarely seen in clinical practice if renal function is normal

• Seen in : -

• Renal failure patients, receiving Mg containing antacids,

laxative or IV fluids is the most common cause.

• Treatment of pre-eclampsia with IV Mg sulphate.

• ARF with acute rhabdomyolysis.

• DKA without treatment.

CLINICAL FEATURES OF HYPERMAGNESEMIA

• Neuromuscular manifestations : muscular weakness,

lethargy, loss of DTRs, respiratory depression and

respiratory failure.

• Cardiac manifestations : hypotension due to peripheral

vasodilatation, bradyarrhythmia, and in severe cases

cardiac asystole.

• ECG changes : prolonged PR interval, increased QRS

duration and QT interval, complete heart block

• Hypocalcemia may occur due to hypermagnesemia

induced decreased secretion of PTH and end organ

resistance of PTH.

TREATMENT OF HYPERMAGNESEMIA

1. Eliminate source : stop Mg containing antacids,

laxatives etc

2. 10 % Ca Gluconate, 10-20 ml IV slowly over 10 mins

will effectively correct hypotensionby lowering Mg

levels.

3. If renal function is normal, IV Furosemide after

rehydration with Normal Saline will enhance renal

excretion.

4. Hemodialysis is the treatment of choice in renal failure

patients.

5. Supportive treatment like Artificial respiration in case of

respiratory failure.

HYPOMAGNESEMIA

CAUSES OF HYPOMAGNESEMIA

• Serum Mg levels < 1.5 mEq/L (1.8 mg/dl).

• Symptomatic hypomagnesemia = Mg < 1 mEq/L

• Common causes are :

1. Increased renal excretion : loop diuretics, osmotic

diuretics, hypercalcemia, acute pancreatitis

2. Increased GI losses : malabsorption syndrome,

vomiting or nasogastric aspiration

3. Poor intake : prolonged malnutrition

4. Chronic alcoholism

5. Others : primary aldosteronism, hypoparathyroidism,

drugs like Aminoglycosides, Cisplatin, Amphotericin B

etc.

CLINICAL FEATURES OF HYPOMAGNESEMIA

• Rarely occurs as a single entity. It often causes

hypocalcemia and hypokalemia which contribute the

clinical picture.

• Neuromuscular manifestations : lethargy, confusion,

tremor, fasciculations,ataxia, tetany and seizures.

• Cardiac manifestations : ECG changes : prolonged PR

interval and QT interval.

• Metabolic abnormalities : hypocalcemia, hypokalemia,

TREATMENT OF HYPOMAGNESEMIA

1. Correct underlying etiology and coexisting

hypocalcemia and hypokalemia.

2. Magnesium Sulphate : available as powder as well as

10% or 50% solution.

– 5 ml of 10% or 1 ml of 50% contains 4 mEq magnesium.

– 1 gram MgSO4 = 8.1 mEq of magnesium

3. Mild deficiency (Mg ~ 1.8 mg/dl) needs oral

supplementation of 2gms three times a day without

producing diarrhoea. Mg rich diet include green

vegetables, nuts and legumes, chocolate and fruits

such as banana, grapes and oranges


4. Severe Mg deficiency (Mg level < 1.2 mg/dl) needs

parenteral Mg supplementation.

– 2 gram MgSO4 (4 ml of 50%, 16 mEq) is given

slowly over 10 minutes. Followed by 1 mEq/kg/24 hrs

as slow continuous infusion or IM injection.

– For IV infusion, 10 ml of 50% MgSO4 is added to

500 ml NS which will contain 40 mEq Magnesium.

– Alternatively, 2 gm MgSO4 is given every 6 to 8 hrs

as im injections.


• Caution and monitoring of MgSO4 therapy :

Check DTR every 15 mins. Disappearance of

Patellar reflex is a useful clinical sign to detect onset

of Mg intoxication. If Knee jerk on examination prior

to a repeat dose is absent, no additional Mg should

be given until they return.

Periodic monitoring of Mg levels is essential.

Mg therapy is contraindicated in heart block or in

patients with extreme myocaridal damage.

Maintain urine output at minimum rate of 100 ml

every 4 hours.

THANK YOU

REFERENCES

• Practical guidelines on Fluid therapy 2nd edition

• 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 edition

neurology of electrolyte imbalance

Health & Medicine