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Hyponatremia - Comprehensive Clinical Notes

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Definition & Classification

• Mild: 130-134 mEq/L
• Moderate: 125-129 mEq/L
• Severe: < 125 mEq/L
• Critical/Symptomatic emergency: < 120 mEq/L (or < 115 mEq/L for seizures/coma)

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Pathophysiology

1. Reduced renal free-water excretion - the dominant cause in most clinical settings
   • Actions of ADH (vasopressin) on collecting duct → aquaporin-2 insertion → water reabsorption
   • Low distal delivery of filtrate (reduced GFR, increased proximal tubule NaCl reabsorption)
2. Excessive free-water intake overwhelming renal capacity (e.g., psychogenic polydipsia)

• Osmotic: triggered by plasma osmolality >280 mOsm/kg at the hypothalamic osmostat
• Non-osmotic: hypovolemia, hypotension, nausea, pain, stress (via carotid sinus/left atrial baroreceptors)

• Acute hyponatremia (<48 hrs): brain cells swell → cerebral edema → neurological symptoms
• Chronic hyponatremia (>48 hrs): brain cells export K⁺, organic osmolytes (taurine, myoinositol) → volume normalizes → symptoms diminish
• Rapid correction of chronic hyponatremia → osmotic demyelination syndrome (ODS / central pontine myelinolysis)

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Classification by Osmolality

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Diagnostic Evaluation Chart

Step-by-Step Evaluation

Serum Na⁺ < 135 mEq/L
         │
         ▼
Step 1: Measure PLASMA OSMOLALITY
         │
    ┌────┴────────────────────┐
    ▼                         ▼
>290 mOsm/L            275-290 mOsm/L          <275 mOsm/L
(Hyperosmolar)         (Iso-osmolar)            (Hypo-osmolar)
    │                         │                         │
Hyperglycemia         Pseudohyponatremia         ▼
Mannitol              (Hyperlipidemia,    Step 2: Measure URINE OSMOLALITY
                      Hyperproteinemia,          │
                      Post-TURP)          ┌──────┴──────┐
                                          ▼             ▼
                                     >100 mOsm/L   <100 mOsm/L
                                    (ADH present)  (ADH absent/Max dilute urine)
                                          │         Primary polydipsia
                                          ▼         Beer potomania
                               Step 3: Assess ECF VOLUME STATUS
                                          │
                         ┌────────────────┼──────────────────┐
                         ▼                ▼                   ▼
                    HYPERVOLEMIC      EUVOLEMIC           HYPOVOLEMIC

Key Urine Indices in Evaluation

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Causes (by Volume Status)

1. HYPOVOLEMIC HYPONATREMIA

• Vomiting, diarrhea, GI suction
• Sweating, burns
• Third-spacing: bowel obstruction, pancreatitis, rhabdomyolysis

• Thiazide diuretics (most common drug cause in adults)
• Loop diuretics
• Mineralocorticoid deficiency / Hypoaldosteronism
• Salt-wasting nephropathies (including cerebral salt wasting)
• Osmotic diuresis (glycosuria, urea diuresis)
• Renal tubular acidosis
• Bicarbonaturia (from vomiting-induced alkalosis or proximal RTA)
• Ketonuria

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2. EUVOLEMIC HYPONATREMIA

• Hypo-osmolar hyponatremia
• Urine osmolality > 100 mOsm/kg (inappropriately concentrated)
• Urine Na⁺ > 20-40 mEq/L
• Clinically euvolemic
• Normal thyroid and adrenal function
• No diuretics

• Hypothyroidism - reduced cardiac output → baroreceptor-mediated ADH release
• Adrenal insufficiency (cortisol deficiency) - CRH stimulates ADH; aldosterone deficiency causes Na⁺ loss
• Reset osmostat - osmostat set at lower threshold; urine can be appropriately diluted after water load
• Primary polydipsia - urine Osm < 100 mOsm/kg (maximally dilute); psychiatric illness, medications
• Beer potomania - low dietary solute + high free water; very low urine Osm

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3. HYPERVOLEMIC HYPONATREMIA

• Heart failure - low cardiac output → baroreceptor activation → ADH + RAAS
• Cirrhosis - splanchnic vasodilation → reduced EABV → ADH + RAAS
• Nephrotic syndrome - hypoalbuminemia → reduced oncotic pressure → edema

• Renal failure (acute or chronic) - reduced GFR limits distal delivery

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Clinical Features

Symptoms (severity correlates with rate of fall and degree)

• Acute hyponatremia (developing <48 hrs): symptoms appear at higher Na⁺ levels due to rapid cerebral edema
• Chronic hyponatremia (>48-72 hrs): adapted brain cells - symptoms appear at lower Na⁺ levels
• Special risk: Pre-menopausal women are more vulnerable to cerebral herniation from acute hyponatremia

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Management

General Principles

1. Identify and treat the underlying cause
2. Determine acuity (acute <48 hrs vs. chronic >48 hrs)
3. Assess symptom severity (mild/moderate vs. severe)
4. Correct at a safe rate to avoid ODS

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Rate of Correction (Critical!)

ΔNa⁺ = (Infusate Na⁺ - Serum Na⁺) ÷ (TBW + 1) TBW = 0.6 × lean body weight (men), 0.5 × lean body weight (women)

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Management by Type

A. Hypovolemic Hyponatremia

• Isotonic saline (0.9% NaCl) - replaces volume deficit
• Volume repletion removes the ADH stimulus → spontaneous water excretion
• Risk: Na⁺ can rise rapidly once volume is restored; monitor closely
• If adrenal insufficiency: hydrocortisone replacement

B. Euvolemic Hyponatremia (SIADH)

• Oral salt tablets + loop diuretics (furosemide) - increases solute excretion
• Demeclocycline 600-1200 mg/day - causes nephrogenic DI; onset slow (days); useful in chronic SIADH (avoid in liver disease)
• Urea (30-60 g/day orally) - increases urine solute excretion; effective but unpalatable
• Vaptans (V2-receptor antagonists):
  • Tolvaptan (oral): 15 mg/day → titrate to 30-60 mg if needed - causes selective free water excretion ("aquaresis"); avoid if liver disease; do not initiate in hospital for chronic hyponatremia (rapid correction risk)
  • Conivaptan (IV): approved for euvolemic and hypervolemic hyponatremia in hospital setting
  • Not recommended for >30 days due to hepatotoxicity concerns
• Treat the cause: Chemotherapy for SCLC, stop offending drugs, treat pneumonia/CNS disease

C. Hypervolemic Hyponatremia

• Fluid and Na⁺ restriction (cornerstone)
• Treat underlying condition:
  • Heart failure: ACE inhibitors, diuretics, optimize cardiac function
  • Cirrhosis: Fluid restriction to 1.5 L/day for Na⁺ <130 mEq/L; tolvaptan as bridge to transplant only; avoid in hepatotoxicity risk
  • Renal failure: dialysis when indicated
• Loop diuretics (furosemide) for symptom relief in fluid-overloaded states
• Vaptans: modest short-term benefit in CHF/cirrhosis but no survival benefit

D. Acute Severe/Symptomatic Hyponatremia

• 3% Hypertonic saline - indicated immediately
• Goal: raise Na⁺ by 4-6 mEq/L in first hour to halt cerebral edema
• Infusion rate: ~100 mL of 3% NaCl over 10-20 minutes, repeat up to 3 times if needed (European guidelines)
• Or: 1-2 mL/kg/hr of 3% NaCl
• Once symptoms improve, slow correction to ≤8 mEq/L total in 24 hrs
• Monitor serum Na⁺ every 2-4 hours

• If Na⁺ rises too fast → stop all Na⁺ infusions
• Give D5W or DDAVP (desmopressin 2-4 mcg IV) to re-lower Na⁺
• Can "re-lower" sodium deliberately with free water if overcorrection occurs

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Summary Management Table

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Osmotic Demyelination Syndrome (ODS)

• Previously "central pontine myelinolysis"
• Caused by rapid osmotic shifts shrinking cerebral vascular endothelial cells → blood-brain barrier breakdown → oligodendrocyte damage
• Clinical features: Flaccid paralysis, dysarthria, dysphagia, locked-in syndrome
• Imaging: MRI shows T2 hyperintensity in pons (and extrapontine)
• Prevention: Never exceed 8-10 mEq/L correction in 24 hours in chronic hyponatremia
• Risk factors: Alcoholism, malnutrition, hypokalemia, liver disease, elderly females

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Special Situations

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