APPROACH

APPROACH TO A PATIENT OF HYPONATREMIA-DR MAHENDRA M MASKE

Introduction Hyponatremia-Most common abnormality15-30% of hospitalized pntsIndependent predictor of mortalityAcute 50 %; Chronic- 10-20%Challenge among physicians > CAUSEBasically a water imbalance.

Total Body Water- 60 % of body weight in Male- 50% of body weight in Female Fat holds less water, obese will have proportionately less body water.

Electrolyte Composition

Plasma Osmolality { mOsm/kg }

Normal Plasma Osmolarity > 275-295 mOsm/kg

Effective OsmolalityEffective Osmolality { mOsm/Kg }= 2 x Na + Glucose18Determine by those solutes which does not permeate cell membrane & act to hold water within ECF.Lipid soluble substances like Urea can cross cell membrane, does not contribute to Osmotic pressure gradient b/w ECF & ICF.

SODIUM 11Na23Na major ECF cation { 140 mEq/l ECF vs 25 mEq/l intracellular}Total body Na > 5000mEq 85-90% Na extra-cellularResponsible for > 90% total osmolarity of ECF.Maintain ECF volume & hence Blood pressure.Daily requirement > 100 mEq i.e. 6 gm salt.1 gm of NaCl contains 17.1 mEq of Na.fromLatin :natrium

HyponatremiaPlasma Na+ concentration associated with normal or increased tonicity.

Isotonic hyponatremia expansion of extracellular fluid with isotonic fluids that do not contain Na there is no transcellular shift of water but the [Na+] decreasesEx- hypertriglyceridemia hyperproteinemia( as in Multiple Myeloma)rise in plasma lipids of 4.6 g/L or plasma protein concentrations greater than 10 g/dL will decrease the sodium concentration by approximately 1 mEq/L.

Hypertonic hyponatremia Seen when there is increase in effective osmoles in the extracellular fluidShift of water from the cells to the ECF and thus causing translocational hyponatremiaEx- hyperglycaemia in DM {plasma Na+ falls by 2 mEq/l for every 100-mg/dL increase in Glucose b/w 200-400 mg/dl; and by 4 mEq/l at Glucose > 400mg/dl}hypertonic mannitol

Hypotonic HyponatremiaHypotonic hyponatremia is the most common form of hyponatremiaHypotonic hyponatremia occurs by two mechanisms1) impaired renal water excretion 2) excess water intakeHypotonic hyponatremia can be classified as hypovolemic, euvolemic and hypervolemic on the basis of ECF volume as assessed clinically by changes in blood pressure and heart rate, edema, jugular venous distension, skin turgor, mucous membranes.

Hypovolemic HyponatremiaTotal body waterTotal body Na

Conditions with UNa > 20The renal causes of hypovolemic hyponatremia inappropriate loss of Na+-Cl in the urine volume depletion and an increase in circulating AVP; Mineralocorticoid deficiency

Hyperkalemia hyponatremia hypotensive and/or hypovolemic patient with high urine Na+ concentration (much >20 mM)

Salt-losing nephropathies -sodium intake is reduced due to impaired renal tubular function reflux nephropathy interstitial nephropathiespost-obstructive uropathy medullary cystic disease the recovery phase of acute tubular necrosis.

Diuretics ExcessThiazides Loop diuretics > blunting the countercurrent mechanism {Water diuresis > Natriuresis}

Osmotic diuresisExcretion of osmotically active nonreabsorbable or poorly reabsorbable soluteglycosuria, ketonuria (e.g., in starvation or in diabetic or alcoholic ketoacidosis), and bicarbonaturia (e.g., in renal tubular acidosis or metabolic alkalosis, in which the associated bicarbonaturia leads to loss of Na.

Cerebral salt wastingRare cause of hypovolemic hyponatremia, hyponatremia clinical hypovolemia inappropriate natriuresisIntracranial disease SAH, trauma, craniotomy, encephalitis and meningitis.Release of BNP {brain natriuretic peptide} in cerebral dysfunction D/D syndrome of inappropriate antidiuresis (SIAD) Cerebral salt wasting typically responds to aggressive Na+-Cl repletion.

Conditions with Una < 20Nonrenal causes of hypovolemic hyponatremiagastrointestinal (GI) loss vomiting, diarrhoea, tube drainage, etc.Third space loss of fluids. Ex- pancreatitis, burnsa rapid increase in plasma Na+ concentration in response to intravenous normal saline.saline induces a water diuresis in this setting, as circulating AVP levels decreases.

Euvolemic HyponatremiaHyponatremia with normal ECF volume is seen inSyndrome of inappropriate antidiuresis (SIAD) Endocrine deficiency -hypothyroidism -adrenal insufficiency

SIADSyndrome of inappropriate antidiuresis (SIAD)SIAD more accurate termADH is inappropriately elevated in SIAD by a variety of mechanismsenhanced and unregulated ADH secretion (by tumor or hypothalamus) elevated secretion of ADH in basal state and in response to hypertonicity Reset osmostatActivating mutation of the V2 receptor permitting reabsorption of water in absence of ADH.Natriuresis (increases ANP) in presence of water retention leads to inappropriately concentrated urine.

Diagnostic Criteria for SIADH:plasma sodium concentration 20mEq/Lpatient clinically euvolaemicabsence of clinical or biochemical features of adrenal and thyroid dysfunction

Serum uric acid is often low ( ADH release.Isolated glucocorticoid deficiency -through corticotropin releasing factor mediated release of ADH.Correction of these hormonal deficits corrects for the water excretion defect and hyponatremia.

Hypervolemic HyponatremiaCausative disorders can be separated by the effect on urine Na+ concentrationUNa > 20-Acute renal failure (ARF)-Chronic renal failure (CRF)UNa < 20-congestive heart failure-nephrotic syndrome-hepatic cirrhosisLow intraarterial fillingMovement of water from the vascular to the interstitial space due to hypoalbuminemiaActivation of the neurohormonal compensatory mechanisms

Exercise induced hyponatremia Marathon runners Females and with low body weight. Excessive drinking of hypotonic solutions (>1.5 l/hour of water or hypotonic sport drinks) and Inappropriate secretion of ADH due to muscle derived interleukin-6.

Primary polydipsia (compulsive water drinking 10-15 liter/day) psychiatric patients -schizophrenia. central defect in thirst regulationexcessive secretion or renal action of ADH and Antipsychotic drugs by anticholinergic action.

Low Solute IntakeA low dietary solute intake (tea-toast diet, extreme vegetarian diets.) as in debilitated residents in nursing homes or chronic alcohol ingestion (beer potomania) causes hyponatremia by decreasing the ability of the kidney to excrete water. Water intake above this renal and insensible water loss will cause hyponatremiaBeer is very low in protein and salt content, containing only 12 millimole per liter of Na+.Associated with low urine osmolality,