Hyponatremia - Differential Diagnosis

Algorithm for Evaluation of Hyponatremia (Na < 135 mmol/L)

1. Confirm true hyponatremia
   • Repeat serum sodium to exclude lab error.
   • Measure Serum Osmolality (S Osm):
     • S Osm > 295 mOsm/kg → Hypertonic hyponatremia (hyperglycemia, mannitol, etc.).
     • S Osm 280–295 mOsm/kg → Isotonic (pseudo-) hyponatremia (severe hyperlipidemia/proteinemia).
     • S Osm < 280 mOsm/kg → Hypotonic (true) hyponatremia — continue below.
2. Assess acuity & symptoms (seizure, coma, severe confusion). If present, begin hypertonic saline while continuing evaluation (see treatment table).
3. Estimate volume status by history & exam:
   • Hypovolemic — orthostasis, tachycardia, dry mucous membranes.
   • Euvolemic — no edema, normal skin turgor.
   • Hypervolemic — edema, ascites, pulmonary rales.
4. Check Urine Osmolality (U Osm)
   • U Osm < 100 mOsm/kg → Primary polydipsia, “beer potomania,” low-solute diet.
   • U Osm ≥ 100 mOsm/kg → proceed to urine sodium.
5. Check Spot Urine Sodium (U Na)
   • Hypovolemic
     • U Na < 20 mmol/L → Extrarenal Na⁺ loss (GI, skin, third spacing).
     • U Na > 40 mmol/L → Renal Na⁺ loss (diuretics, mineralocorticoid deficiency, salt-wasting nephropathy).
   • Euvolemic (U Na > 40 mmol/L, U Osm > 100)
     • SIADH (CNS, pulmonary, malignancy, drugs)
     • Glucocorticoid deficiency (Addison’s)
     • Hypothyroidism
     • Reset osmostat, post-surgery, endurance exercise
   • Hypervolemic
     • U Na < 20 mmol/L → CHF, cirrhosis, nephrotic syndrome.
     • U Na > 40 mmol/L → Advanced renal failure (GFR < 15 mL/min).

Key Lab Patterns & Differential Diagnosis

Volume Status	Urine Osm (mOsm/kg)	Urine Na (mmol/L)	Likely Etiologies
Hypovolemic	> 100	< 20	Extrarenal loss: vomiting, diarrhea, burns, pancreatitis / third-spacing
	> 100	> 40	Renal loss: diuretics, adrenal insufficiency, salt-wasting nephropathy
Euvolemic	> 100	> 40	SIADH, hypothyroidism, glucocorticoid deficiency, SSRIs, carbamazepine
Hypervolemic	> 100	< 20	CHF, cirrhosis, nephrotic syndrome
	> 100	> 40	Renal failure (late CKD/ESRD)
Any	< 100	Variable	Primary polydipsia, beer potomania, low-solute diet

Treatment of Hyponatremia

General rule: Correct Na⁺ no faster than 8–10 mmol/L in 24 h (≤ 18 mmol/L in 48 h) to prevent osmotic demyelination. Monitor serum Na every 2–4 h during active therapy.

Etiology / Category	First-Line Therapy	Adjuncts & Pearls
Severe symptomatic (seizure, coma)	100 mL 3% NaCl IV over 10 min; repeat ×2 if needed (goal +4–6 mmol/L Na)	Continuous neuro monitoring; then infusion 0.5–1 mL/kg/h
Hypertonic (hyperglycemia)	Insulin + IV fluids	Na rises ~1.6–2.4 mmol/L per 100 mg/dL glucose corrected
Isotonic (pseudo-)	Treat hyperlipidemia / paraproteinemia	No Na therapy; use direct ISE for accurate sodium
Hypovolemic — extrarenal	0.9% NaCl IV (1–2 L then maintenance)	Replace K+; stop GI losses
Hypovolemic — renal (diuretics, adrenal)	0.9% NaCl IV; stop diuretic	If adrenal insufficiency: hydrocortisone 100 mg IV q8 h
Euvolemic — SIADH	Fluid restriction ≤ 800–1000 mL/day	+ Salt tabs & loop diuretic; consider urea, demeclocycline, or tolvaptan
Euvolemic — endocrine (hypothyroid / adrenal)	Hormone replacement	Re-check Na after correction
Hypervolemic — CHF, cirrhosis, nephrotic	Fluid & Na restriction + loop diuretic	± Tolvaptan; optimize heart / liver / renal therapy
Hypervolemic — renal failure	Dialysis (IHD or CRRT)	Customize dialysate Na to avoid rapid shifts
Primary polydipsia / beer potomania	Fluid restriction; ↑ dietary solute (protein, salt)	Monitor for rapid Na rise once restriction begins

Disclaimer: For educational use by healthcare professionals. Management should be individualized; seek specialist input for complex cases.