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Common electrolyte disorder in the inpatient setting

Occurs in 15-30% of hospitalised patients

Defined as serum Na <135mmol/L

Clinically important because


Associated with increased mortality in both the ambulatory and inpatient setting


Confers a poorer prognosis in a range of underlying


diseases including cirrhosis, pulmonary HTN, MI, CKD, hip fractures and PE Rapid correction can cause severe neurological deficits and death

AJM 2013

Regulation of body water

Disturbances in serum Naare generally due to changes in the body’s water balance, not sodium, i.e. changes in plasma osmolality.

↑ osmolality sensed by the osmo-receptors in the hypothalamus thirst & release of ADH ↑ water reabsorption from renal collecting ducts.

Non-osmotic stimuli (hypovolaemia, stress, nausea) can also cause ADH release (even if serum osmolality is normal or low)



(1) Measure plasma osmolality (2) Assess extracellular volume

Classification according to plasma


1. Isotonic hyponatremia (280-285mOsm/kg):

*Pseudohyponatremia ; hyperlipidemia or hyperproteinemia results in low measured Naconcentration (but osmolality is normal)

(rare lab artefact)

2. Hypertonic hyponatremia (>285mOsm/Kg):

excess of another effective osmole (glucose, mannitol/sorbitol) that draws water intravenously

3. Hypotonic hyponatremia (<280mOsm/kg):

most common scenario

true water excess relative to Na(± salt loss).

Serum osmolality and sodium

Serum Osm = 2x [Na+] + glucose + urea (units all in mmol/L)

Corrected Na+ = Measured Na + 0.3 x (serum glucose 5.5) mmol/L

AJM 2013

AJM 2013



(1) Measure plasma osmolality (2) Assess extracellular volume

Volume status

Assess volume status (extracellular fluid volume) Hypotonic hyponatremia has 3 main etiologies:

Hypovolemic both H2O and Na decreased (H2O < Na)

Consider obvious losses from diarrhea, vomiting, dehydration, malnutrition/poor oral intake, diuretics etc

Euvolemic H2O increased and Na stable

Consider SIADH, drugs, thyroid disease, glucocorticoid deficiency

Hypervolemic H2O increased and Na increased (H2O > Na)

Consider CHF, cirrhosis, renal failure

Measurement of urinary Na+ will help in differentiating the above


serum osm (measured) normal low (<280) High (>>280) measure lipids, proteins Assess ECF Clinically
serum osm (measured)
low (<280)
High (>>280)
measure lipids, proteins
Assess ECF Clinically
mannitol, sorbitol, glycine
volume expanded
Volume Depleted
adrenal insuff
extrarenal losses
renal salt wasting

Hypotonic hyponatremia

Hypotonic hyponatremia

85yo man admitted with 3/7 of nausea/vomiting/diarrhoea and headache

Na+ on admission found to be 122, baseline unknown







Aspirin 100mg D Perindopril 10mg D

Atorvastatin 40mg nocte

Panadol Osteo

No focal neurological deficits; clinically dry

CT Brain NAD

Serum osmolality is 266. Urine osmolality is 465. Urine Na+ is 8

Hypovolemic. Serum osmolality is 266. Urine osmolality is 465. Urine Na+ is 8

Hypovolemic. Serum osmolality is 266. Urine osmolality is 465. Urine Na+ is 8


IV N/Saline

72yo woman from nursing home admitted with increasing falls and recent headstrike

Na+ 125


Dementia CCF Recurrent UTIs Ex-heavy smoker


Irbesartan HCT 300/12.5mg D

Aspirin 100mg D Esomeprazole 20mg D Simvastatin 80mg nocte

Clinically euvolemic

CTB: nil acute pathology

CXR: 5cm right hilar mass

Na 125, serum osmolality 270, urine osmolality 122, urine Na+ 55

Euvolemic. Serum osmolality is 270. Urine osmolality is 122. Urine Na+ is 55

Euvolemic. Serum osmolality is 270. Urine osmolality is 122. Urine Na+ is 55


Cease exacerbating drug (ie. HCT)

Fluid restriction

Bronchoscopy and biopsy: bronchogenic carcinoma

Before diagnosis of SIADH must rule out drugs,

hypothyroidism and hypocortisolism (as they can mimic




CNS: neoplasms, bleed, encephalitis/meningitis, sarcoidosis, pituitary surgery, nausea

Drugs: SSRI, carbamazepine, haloperidol, amitriptyline, bromocriptine, MDMA etc

Pulmonary disease: pneumonia, TB, ARDS, malignancy

Ectopic ADH: carcinomas (small cell lung ca), pancreatic or duodenal ca, thymic ca

55F presents to ED following witnessed seizure with confusion and drowsiness

Na+ 108


Chronic ETOH abuse (6L wine/day) Hepatitis C Anxiety and depression


Recently commenced on escitalopram by LMO for depression

CTB: nil acute pathology

Multifactorial hyponatremia

Decreased solute intake in the setting of ETOH abuse (beer potomania, ‘tea and toast’ diet) SIADH secondary to escitalopram


Hyponatremia with neurological symptoms is a medical


Bolus of 100ml to 150ml of 3% hypertonic saline

Monitor hourly serum Na and aim for target Na of


Indications for hypertonic saline:

- Severe symptomatic hyponatremia: seizures, altered conscious state

Rate of Correction

The rate of sodium correction should be 6 to 12 mmol/L in

the first 24hrs and 18mmol/L or less in 48hrs

High risk of osmotic demyelination:

Serum sodium concentration <105mmol/L

Hypokalemia Alcoholism


Advanced liver disease

NEJM 2015

NEJM 2015


Vasopressin receptor antagonists, eg tolvaptan, have been approved for treatment of hypervolemic or euvolemic hyponatremia Blocks action of endogenous ADH thereby increasing water excretion whilst sparing solute loss (unlike traditional diuretics such as frusemide)

JCEM 2013

JCEM 2013


Vaptans not currently on PBS for treatment of hyponatremia in Australia Due to cost and concerns regarding controlling rate of rise of serum Na and hence increased risk of osmotic demyelination

JCEM 2013

Answer C

Answer C



Diabetes Insipidus

Polyuria: > 3 L/d



Diabetes mellitus Hypercalcaemia

Solute diuresis:

Polydipsia: > 3.5 L/d

Volume expansion 2° saline loading

High-protein feeds (urea as osmotic agent)

Diabetes insipidus:

Central (CDI)

Nephrogenic (NDI)

Primary (psychogenic) polydipsia

Diabetes Insipidus DDx

Diabetes Insipidus DDx Central (CDI) • Idiopathic • autoimmune • Neurosurgery, head trauma • Cerebral

Central (CDI)



Neurosurgery, head trauma Cerebral hypoperfusion


Craniopharyngioma, pituitary adenoma, suprasellar

meningioma, pineal gland,



Fe, Sarcoid, Histiocytosis

Nephrogenic (NDI)

Genetic due to defect in vasopressin or aquaporin gene

Tubules not responsive to vasopressin:

- Hypokalemia

- Hypercalcemia (2° to HPT in


- Renal disease: after ATN,

post-obstructive uropathy, RAS, renal transplant, amyloid, Sickle cell anemia

- Sjogren’s syndrome

- Drugs:

Lithium, 20% of chronic users

amphotericin, colchicine

What is appropriate urine concentration?

What is appropriate urine concentration? 1) Complete DI 2) Defective osmoreceptor, normal ADH release to ECFv


Complete DI


Defective osmoreceptor, normal ADH release to ECFv contraction


High-set osmoreceptor: ADH release is sluggish/delayed


ADH release at normal Posm but subnormal in amount

Diabetes Insipidus

Healthy out-patients

DI with intact thirst or access to water

High-normal serum sodium (142-145 mmol/L)

Polydipsia (crave cold fluids)

Polyuria, Nocturia sleep disturbance

1˚ Psychogenic Polydipsia

Low-normal serum sodium (135-137 mmol/L)

Middle-aged women

Psychiatric illness, phenothiazine (dry mouth)

Diabetes Insipidus

Intact thirst & access to water

Hi-normal serum sodium (142-145 mEq/L)

Polydipsia (crave cold fluids)

Polyuria, nocturia sleep disturbance

1° treatment is DDAVP and drink to thirst

Impaired thirst or access to water:


Insufficiently concentrated urine

1° treatment is fixed free water replacement and DDAVP

1˚ Polydipsia

1 ˚ Polydipsia

Water Deprivation Test

Stop water intake for 2-3h prior to coming in

Continue to withhold water & monitor:

Urine volume, U OSM q1h

Serum Na, OSM q2h

If serum osmolality/Na+ do not rise above normal ranges & urine

osmolality reaches 600mOsm/kg 1˚ Polydipsia

If serum osmolality reaches 295-300 mOsm/kg & U OSM doesn’t ↑

Diabetes Insipidus established

Give DDAVP 10 mcg IN and monitor for further 3 hrs

Central DI: U OSM ↑ by 100-800% (complete CDI), ↑ by 15- 50% (partial CDI) with absolute U OSM > 345mOsm/kg

Nephrogenic DI: U OSM ↑ by up to < 9%, sometimes ↑ as high as 45% but absolute U OSM always < isotonic (290 mOsm/kg)