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Approach to Hyponatremia

Dr.Anuradha, MD, MNAMS Director, Dept. of Nephrology Mediciti Hospitals Hyderabad

Normal Serum [Na] (135-145 mEq/L) Closely Guarded

ADH (pM) ECFv Thirst

0 130 135 140 145 PNa (mEq/L)

[Na] is a measure of Na relative to water.

Low [Na] reflects abnormality of water metabolism rather than sodium metabolism Kidney is the main culprit. Brain is ultimate victim

ECF and ICF Compartments under Normal Conditions and during States of Hyponatremia.

Adrogu HJ, Madias NE. N Engl J Med 2000;342:1581-1589.

Milionis, H. J. et al. CMAJ 2002;166:1056-1062

Copyright 2002 Canadian Medical Association or its licensors


determine whether the hyponatremia represents a true

hypo-osmolar state Urea is an ineffective osmole effective serum osmolality =

serum osmolality - serum urea (mmol/l)

Plasma Osmolality: Posm = 2 (Na) + glucose + urea Normal = 2 (140) + 5 + 5 = 290 (275-290 mM) Urine Osmolality:

Normal: 400-500 mM

Maximal dilution 50-100 mM (USG 1.002-1.003) Maximal concentration 900-1200 mM (USG 1.030-1.040)

Concentrated Urine: > 500 mM (at least!), USG > 1.017 i.e. UOSM > POSM is not enough to R/O Diabetes Insipidus

Normal or Elevated Effective Serum Osmolality

Pseudohyponatremia ( water content of serum decreased)
hyperparaproteinemia Hypertriglyceridemia

concentrations of other osmoles

Glucose (measured and calculated osm high) Mannitol ( measured osm high, calculated low)

Normal or Elevated Effective Serum Osmolality

Pseudohyponatremia avoided by Ion-selective

electrodes Hyperglycemia : decrease of 1.6 mmol/L in the serum sodium level per increase of 100 mg (5.6 mmol/L) in the glucose level) "standard" correction factor of 1.6 may be too low, especially when glucose levels 22.2 mmol/L. correction factor of 2.4 mmol/L may be a better overall estimate
Am J Med 1999;106:399-403

The kidney has a tremendous capacity to generate free water, about 18 liters a day In true hypoosmolar state, urine osmolality assesses ability of kidneys to excrete water.

Urine Specific Gravity USG

Estimates solute concentration of urine on basis of weight as

compared with an equal volume of distilled water

Normal Posm is 0.8-1.0% heavier than water so PSG = 1.008-1.010

Each in UOSM 30-35 mM USG by 0.1% (0.001) Therefore, USG of 1.010 ~ UOSM 300-350 mM Larger MW urinary OSM (glucose, radiocontrast, carbenicillin) if

present will falsely elevate USG Nothing falsely lowers USG

Mechanism of free water excretion by the kidney

Mechanism of free water excretion by the kidney

Role of the thick ascending limb first nephron segment to generate free water osmolality of fluid leaving TAL 100 mosm/kg/H2O Role of the collecting duct final osmolality of the urine determined by the CD under the influence or the absence of AVP

kidney needs to take two steps to generate hypotonic fluid

There has to be fluid reaching TAL (the diluting

segment) There has to be absence of ADH We can explain all hyponatremia by failure to fulfill one or both conditions.

Urine osmolality


True Hypo-osmolar Hyponatremia With Normal Water Excretion

Primary polydipsia : than 10 to 15 L/d water intake

Extremely reduced solute intake : ability to excrete water reduced by a poor dietary intake
Beer potomania syndrome Anorexics

Reset osmostat syndrome :

water intake reduces the serum osmolality below the new threshold for ADH release Variant of SIADH

Impaired water excretion

Mechanism of Hyponatremia in Adrenal and Thyroid Disorders

Glucocorticoid deficiency
increases water permeability in the collecting tubules Elevated ADH levels

ADH-mediated and intrarenal mechanisms implicated inability to maximally suppress AVP Decreased GFR lowers water delivery to TAL

Hyponatremia in Pregnancy
Downward resetting of serum osmolality Mediated by HCG-induced release of relaxin


Urine Na < 20 mmol/l

Results from hypovolemia or diminished EABV (HF,

Cirrhosis, Nephrotic Syndrome) urine sodium concentration in euvolemic hyponatremia may be less than 20 mmol/L when dietary sodium intake is low

Milionis, H. J. et al. CMAJ 2002;166:1056-1062

Copyright 2002 Canadian Medical Association or its licensors

Normal ECFv (or slightly increased) Hypothyroidism & AI ruled out serum Na/OSM UOSM > 100 mM, UNa > 40 mEq/L Low plasma uric acid (< 238 umol/L)

Fluid Restriction Oral Salt, Hi-protein diet or Urea(30 g/d): promote solute diuresis Lasix 20 mg po od-bid: Loop direct diminishes medullary gradient Demeclocycline 300-600 mg bid (can be nephrotoxic) Lithium (induces NDI) IV salt solution:
Rarely if ever needed (i.e. only if symptomatic with SZ/coma) Solution given must be of greater OSM than UOSM or in long run will just make hyponatremia worse (often IV NS not sufficient)

Intracranial disease Pulmonary disease Chest wall disorder (surgery, VZV) Severe pain or emotional distress Severe N/V Ectopic ADH: Small cell lung cancer Drugs: opiods, carbamazepine, chlorpropamide, cyclophosphamide, cisplatin, vincristine, vinblastine, amitriptylline, SSRI, neuroleptics, bromocriptine, ecstasy (MDMA)

SIADH: Example
UOSM fixed 600 mM due to ADH action 1L NS given: 300 mM (154 mM each of Na and Cl) All sodium will be excreted as renal sodium handling is intact in SIADH. 300 mmoles of osmols given excreted in 500cc urine (300mmoles/500mL = 600 mM) Therefore net gain of 500 cc free water! 1L 3% saline given: 1026 mmoles Excreted in 1.7L to keep UOSM 600 mM Therefore net loss of 700 cc free water! NOT advocating use of any IV NS (0.9% or 3%) in SIADH unless absolutely neccesary (i.e. SZ, coma). Most SIADH hyponatremia is chronic and should be corrected slowly with fluid restriction ONLY.

Hyponatremia with Diuretics

Thiazides more frequent cause than loop diuretics
hypovolemia-stimulated ADH release interference with urine dilution in the cortical diluting segment, an alteration in osmoreceptor sensitivity Alteration in thirst regulation mediated by potassium depletion

Hyponatremia in Renal Failure

Decreased GFR reduces delivery of water to TAL
Dilution capacity fixed Hyponatremia when water intake exceeds this fixed

capacity. When GFR 5 mL/min, only about 1.5 L/24 h can be excreted as water

Metabolic alkalosis
Rare cause of volume depletion associated with urine

sodium > 40 mmol/l filtered load of NaHCO3 exceeds the reabsorptive capacity of the proximal tubule urinary chloride excretion is low (less than 10 to 20 mmol/L)

Milionis, H. J. et al. CMAJ 2002;166:1056-1062

Copyright 2002 Canadian Medical Association or its licensors

Reset Osmostat
25-30% of circumstances which cause SIADH Downward resetting of the threshold for both ADH

release and thirst. Mild asymptomatic hyponatremia (Na 125-135 mEq/L) Distinguish from SIADH by observing response to water load (10-15 mL/kg po or IV) Normal subjects and those with reset osmostat will secrete the entire water load over 4h without any worsening of the hyponatremia Attempts to correct hyponatremia in reset osmostat are not needed and will cause severe thirst

Cerebral Salt Wasting

Cerebral disease (particularly SAH) Mimics SIADH with hyponatremia except primary

defect is salt wasting not water retention. Circulating factor which impairs renal tubular fn.

Atrial natriuretic peptide? Brain natriuretic peptide? Endogenous ouabain?

Plasma urate variable (normal or even lower than

SIADH) Treatment is NS to correct ECFv contraction

SIADH v.s. Cerebral Salt Wasting




Urine volume Serum urate Urine urate

N or

N or N or