Hyponatremia

Presenter: Dr Arun Karmakar

Moderator : Prof. N. Sharatkumar
Introduction
Defined as a serum [Na] below 135 mmol/L.

Most common disorder of electrolytes encountered in

clinical practice, occurring in 22% of hospitalized

patients.
Important clinically because:

1) acute severe hyponatremia can cause substantial

morbidity and mortality;

2) adverse outcomes are higher in hyponatremic

patients with a wide range of underlying diseases;

3) overly rapid correction of chronic hyponatremia can

cause severe neurological deficits and death.

ETIOLOGIES AND PATHOPHYSIOLOGIES OF
HYPOTONIC HYPONATREMIAS
Hypovolemic Hyponatremia(↓H2O, ↓↓Na+)
Gastrointestinal and Third-Space
Sequestered Losses
Vomiting or
Diarrhoea
Burns
Peritonitis
Bowel lumen ileus

Loss water & free water or hypotonic

Na+, Cl -- fluid intake

Vasopressin
due to volume
contraction
Hypovolemic
hyponatremia
 Diuretic therapy

Thiazide
Loop diuretics
diuretics

In TALH
DCT Blocks sodium
reabsorption

interfering with urinary interferes with the

dilution rather than with generation of a hypertonic
urinary concentration medullary interstitium

Limits free water More free water excretion,

excretion inspite of vasopressin
 Cerebral Salt Wasting
syndrome
 Is a syndrome described following SAH, head injury, or

neurosurgical procedures, as well in other settings.

 Primary defect is salt wasting from the kidneys(?role of

BNP) with subsequent volume contraction, which

stimulates vasopressin release.

 Uncommon.
Mineralocorticoid (Aldosterone) Deficiency

Characterized by hyponatremia with ECF volume

contraction (provides the nonosmotic stimulus for

vasopressin release).

Urine [Na+] above 20 mmol/l, and high serum K+.

Euvolemic Hyponatremia(↑H2O, ←→Na+)
SIADH (Syndrome of Inappropriate ADH Secretion)

 A defect in osmoregulation causes vasopressin to be

inappropriately stimulated, leading to urinary concentration.

 MCC of euvolumic hyponatremia

 Excess vasopressin: CNS disturbances such as hemorrhage,

tumors, infections, and trauma.

 Ectopic vasopressin: Small cell lung cancers, cancer of the

duodenum and pancreas, and olfactory neuroblastoma.

 Idiopathic: seen in elderly(10%).
Criteria for Diagnosing SIADH
Decreased effective osmolality of the extracellular fluid.

Inappropriate urinary concentration (Uosm >100 mOsmol/kg

H2O) with normal renal function) at some level of plasma hypo-

osmolality.
Clinical euvolemia.

Elevated urinary sodium excretion (>20 mmol/L) while on

normal salt and water intake.

Absence of other potential causes of euvolemic hypo-osmolality

Normal renal function and absence of diuretic use, particularly

thiazide diuretics.
Supporting diagnostic criteria for SIADH
 Serum uric acid <4 mg/dL

 Blood urea nitrogen <10 mg/dL

 Fractional sodium excretion >1%; fractional urea

excretion >55%
 Failure to improve or worsening of hyponatremia after

0.9% saline infusion

 Improvement of hyponatremia with fluid restriction
 Severe Psychogenic
Posterior pituitary hypothyroidism
polydipsia
(myxedema coma)
glucocor

─
ticoids

↓CO *↑Thirst perception,

Vasopressin
*Acute psychosis
secondary to
↓GFR, schizophrenia, Anxiety
↑vasopressin
*Often on SSRI’s,

*CT or MRI to r/o CNS

sarcoidosis and
craniopharyngioma.
 Postoperative
Exercise-Associated
hyponatremia
Hyponatremia(EAH)
• Long-distance marathon runners.
increased risk:
• BMI below 20 kg/m2,
• Running time exceeding 4 hours
• Excessive infusion of free • Consumption of fluids every mile
water (5% dextrose) and
• ↑Vasopressin due to pain

↑vasopressin
 Drugs Causing Hyponatremia

Vasopressin analogues Drugs that potentiate renal action of

vasopressin

Desmopressin Cyclophosphamide
Oxytocin NSAIDs
Acetaminophen

Drugs that enhance vasopressin release Drugs that cause hyponatremia by

unknown mechanisms

Clofibrate Haloperidol
Carbamazepine Amitryptyline
Vincristine Fluoxetine
Nicotine Fluphenazine
Narcotics IVIG
SSRI Methylmethamphetamine (MDMA)
ifosfamide
Hypervolemic Hyponatremia (↑↑H O, ↑Na )
2
+
Failure
↓MAP, ↓CO

Reduced effective
intravascular volume

↑vasopressin RAAS ↑Norepinephrine

(non osmotic baroreceptor
stimulation)

↑Thirst ↓GFR
 Cirrhosis
In pts of advanced cirrhosis

↑extracellular volume (ascites, edema).

↑ plasma volume (splanchnic venous dilation)

↑plasma renin,
↑ norepinephrine,
↑ vasopressin

↓GFR, ↑free water retention

Dilutional hyponatremia
 Advanced Chronic kidney disease

•Urine output is relatively fixed and water intake in

excess of urine output and insensible losses will cause

hyponatremia.

•Edema usually develops when the Na+ ingested exceeds

the kidneys capacity to excrete.

Clinical Manifestations of Hyponatremia
Acute Hyponatremia – <48 hours

chronic hyponatremia - > 48 hours

STEP 1 – Serum Osmolality
Serum Osmolality: lab value or calculation – in
mosm/kg
=(2 x Na+) + (glucose/18) + (BUN/2.8)

Hypertonic - >295
hyperglycemia, mannitol, glycerol
Isotonic - 280-295
pseudo-hyponatremia from elevated lipids or protein
Hypotonic - <280
excess fluid intake, low solute intake, renal disease, SIADH,
hypothyroidism, adrenal insufficiency, CHF, cirrhosis, etc.
STEP 2 –Volume Status
 2ndassess volume status (extracellular fluid volume)
 Hypotonic hyponatremia has 3 main etiologies:
Hypovolemic – both water and Na decreased (H20 < Na)
Consider obvious losses from diarrhea, vomiting,
dehydration, malnutrition, etc
Euvolemic – water increased and Na stable
Consider SIADH, thyroid disease, primary polydipsia
Hypervolemic – water increased and Na increased (H2O > Na)
Consider obvious CHF, cirrhosis, renal failure
STEP 3 – Urine Studies
For euvolemic hyponatremia, check urine osmolality
Urine osmolality <100 - excess water intake
 Primary polydipsia, tap water enemas, post-TURP
Urine osmolality >100 - impaired renal concentration
 SIADH, hypothyroidism, cortisol deficiency

Check urine sodium & calculate FeNa %

Low urine sodium (<20) and low FeNa (<1%) implies the
kidneys are appropriately reabsorbing sodium
High urine sodium (>20) and high FeNa (>1%) implies the
kidneys are not functioning properly
Treatment
 When considering the treatment of patients with
hyponatremia, five issues must be addressed:

• Risk of osmotic demyelination

• Appropriate rate of correction to minimize this risk

•
• Optimal method of raising the plasma sodium
concentration
• Estimation of the sodium deficit if sodium is to be
given
• Management of the patient in whom overly rapid
correction has occurred
General principles of treatment
 .Primarily determined by the severity of symptoms and
the cause of the hyponatremia

• Symptomatic hyponatremia (seizures, or coma)

o likely to occur with an acute case and marked
reduction in the plasma sodium concentration
o Aggressive therapy is required.
o Chronic but significant hyponatremia
where less severe neurologic symptoms occur
fatigue, nausea, dizziness, gait disturbances,
confusion, lethargy, and muscle cramps
These symptoms typically do not mandate
aggressive therapy
Methods of Sodium Correction
• Water restriction

• primary therapy for hyponatremia in edematous states,

SIADH, primary polydipsia, and advanced renal failure.
• Sodium chloride administration

• usually as isotonic saline or increased dietary salt

given to patients with true volume depletion, adrenal
insufficiency, and in some cases of SIADH.
• contraindicated in edematous patients (eg, heart
failure, cirrhosis, renal failure) since it will lead to
exacerbation of the edema
• Hypertonic saline is generally recommended only for
patients with symptomatic or severe hyponatremia.
• The increase in plasma Na+ concentration can be highly

unpredictable during treatment with hypertonic saline due

to rapid changes in the underlying physiology.

• Patient should be monitored carefully for changes in

neurologic and pulmonary status, and serum electrolytes

should be checked frequently, every 2 - 4 hours.
 Treatment of symptomatic acute hyponatremia

Goal:
 Urgent correction by 1-2 mmol/hr upto 4-6 mmol/L, to

prevent brain herniation and neurological damage from

cerebral ischemia.
Upper limit for correction,10-12 mmol/L in any 24hour

period; 18 mmol/L in any 48-hour period.

 how much fluids to give?
 Total body water = weight x 0.6 for men / 0.5 for woman

• One liter of NS contains: 154 mmol/L of Na+ Cl−

• One liter of 3% saline contains:513 mmol/L of Na+ Cl−

Example: An 60-kg man is having seizure .His s.Na is 110
mmol /L.
Means of correction:
 Given the acuity, the patient should be given hypertonic saline,
which has 513 mmol of Na per liter.
 {513 - 110} /{60 x 0.6 +1}= 10 mmol/L
 One liter of this fluid would increase Na by 10 mmol/L.
Dose of hypertonic saline at 200 mL/hr until symptoms
improve. Maximum 1 litre of 3% NS should be given in 24
hour.
 Treatment of chronic hyponatremia(Avoiding
ODS)
Goal:
 Minimum correction of serum [Na] by 4-8 mmol/L per

day, with a lower goal of 4-6 mmol/L per day if the risk of
ODS is high.

Limits not to exceed:

• 8-10 mmol/L in any 24-hour period.

Treatment of hypovolemic hyponatremia

 Diuretic related- Discontinuation of thiazides and

correction of volume deficits.

 Mineralocorticoid deficiency- Volume repletion with

isotonic saline, Fludrocortisone chronically for

mineralocorticoid replacement.
 Treatment of euvolemic hyponatremia

SIADH - For most cases of mild-to moderate SIADH, fluid

restriction represents the cheapest and least toxic therapy. (fluid

restriction 500 mL/d below the 24-hour urine volume.

 Failure to water restriction

- Vaptans

- Democlocycline 150- 300 mg PO tid or qid

-Fludrocortisone 0.05-0.2 mg bid

 Glucocorticoid Deficiency-glucocorticoid replacement

at either maintenance or stress doses, depending on

the degree of intercurrent illness.

 Severe Hypothyroidism-thyroid hormone replacement at

standard weight-based doses; several days may be needed

to normalize the serum [Na].

Treatment of hypovolemic hyponatremia

Heart Failure-for patients with mild to moderate

symptoms, begin with fluid restriction (1 L/d total) and, if

signs of volume overload are present, administer loop

diuretics.

If the serum [Na] does not correct to the desired level, lift the

fluid restriction and start either conivaptan or tolvaptan.


Cirrhosis-Severe daily fluid restriction,
Vaptans an alternative choice if fluid restriction has failed to maintain

a serum [Na] 130 mmol/L; however, tolvaptan use should be

restricted to cases where the potential clinical benefit outweighs the

risk of worsened liver function, such as in patients with end-stage

liver disease and severe hyponatremia who are awaiting imminent

liver transplantation.
 CKD-Restricting fluid intake. Aquaretics (vaptans)

can be employed{not be expected to cause a

clinically significant aquaresis with severe renal

impairment (ie, serum creatinine >2.5 mg/dL)}.

 Role of VAPTANS
 Vaptans have long been anticipated as a more effective

method to treat hyponatremia by virtue of their unique effect

to selectively increase solute-free water excretion by the
kidneys.
 Although not C/I with decreased renal function, these

agents generally will not be effective if S.Cr is >2.5mg%.

 Conivaptan Tolvaptan Lixivaptan
Receptor V1a/V2 antagonist V2 antagonist V2 antagonist
Route i.v Oral Oral
Urine volume ↑ ↑ ↑

Urine ↓ ↓ ↓
osmolality
Sodium ↔ ↔ ↔ at low dose,
excretion/d ↑at high dose
Status FDA approved FDA & EMA approved Phase 3
completed
Dosage 20mg over 30min f/b cont 15mg on D1, then titrate to -
inf 20-40mg/d 30-60mg/d

Duration of Max 4days (interaction with ≤30days(risk of hepatic -

treatment CYP3A4) injury)

Side effects Headache, thirst, Drymouth, thirst, dizziness, -

hypokalemia hypotension

Indications Euvolumic and Euvolumic and hypervolumic -

hypervolumic hyponatremia hyponatremia
Osmotic demyelination syndrome
 ODS occurs if chronic hyponatremia is corrected too

rapidly.

Present in a stereotypical biphasic pattern (initially

improve neurologically with correction of hyponatremia,

but then, one to several days later, new, progressive, and

sometimes permanent neurological deficits emerge).

• Patients can present para- or quadraparesis, dysphagia,
dysarthria, diplopia, a "locked-in syndrome," and/or loss of
consciousness.

• Most commonly affected area is pons.

• Other regions of the brain affected in ODS: (in order of

frequency) cerebellum, lateral geniculate body, thalamus,
putamen, and cerebral cortex or subcortex.
• As these lesions may not appear until 2 weeks after development, a diagnosis
of myelinolysis should not be excluded if the imaging is initially normal.
 Managing excessive correction of chronic hyponatremia

Starting serum [Na] ≥120 mmol/L: Intervention unnecessary.

Starting serum [Na] <120 mmol/L:
Withhold the next dose of vaptan if the correction is >8

mmol/L;
 Consider therapeutic re-lowering of serum [Na] if
correction exceeds therapeutic limits;
Consider administration of high-dose glucocorticoids (eg,

dexamethasone, 4 mg every 6 hrs) for 24-48hrs following

the excessive correction.
Re-lowering serum [Na]:
 Administer desmopressin to prevent further water losses:

2-4 mg every 8 hours parenterally;

 Replace water orally or as 5% dextrose in water

intravenously: 3 mL/kg/h;
 Recheck serum [Na] hourly and continue therapy infusion

until serum [Na] is reduced to goal

 Approach to a case of hyponatremia
Access serum osmolality Pseudohyponatremia/osmotic related
Normal/high
low

Hypotonic hyponatremia/true
hyponatremia

Access renal Impaired renal Primary renal disease

status function
Normal
Edema – CHF, cirrhosis, nephrotic syndrome
Access volume
Ur, Na + <20 = diarrhoea,
status
vomiting, burns, pancreatitis
Volume depletion
Ur, Na + >20 = diuretics, salt
Normal volume losing nephropathy

Adrenal & thyroid Adrenal & thyroid insufficiency

function
Normal
YES Dilute urine Psychogenic polydipsia
Access Urine
osmolality(Able to
dilute urine) NO
>100 mOsmol/kg H2O SIADH
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