Hyponatremia, defined as a serum sodium concentration below 135 mmol/L, is the most common electrolyte disorder encountered in clinical practice. It ranges from asymptomatic presentations to life-threatening emergencies and often reflects a complex interplay between sodium and water homeostasis. A thorough understanding of its classification, diagnostic approach, and management is essential for healthcare professionals across all levels of care.
This guide below provides a structured, evidence-based overview of hyponatremia, incorporating both volume status and osmolality-based classification systems.
Classification of Hyponatremia
Hyponatremia can be classified by two primary axes:
- Volume Status: Hypovolemic, Euvolemic, and Hypervolemic
- Serum Osmolality: Hypotonic, Isotonic (Pseudohyponatremia), and Hypertonic
1. Hypotonic Hyponatremia (True Hyponatremia) This is the most common and clinically significant type, defined by serum osmolality <275 mOsm/kg. It reflects a true excess of water relative to sodium and is further divided based on volume status:
Common Causes:
- Hypovolemic: Diuretics, vomiting, diarrhea, salt-wasting nephropathy, adrenal insufficiency
- Euvolemic: SIADH, hypothyroidism, secondary adrenal insufficiency, primary polydipsia, low solute intake
- Hypervolemic: CHF, cirrhosis, nephrotic syndrome, chronic kidney disease
Diagnostic Approach:
- Confirm low serum osmolality (<275 mOsm/kg)
- Assess volume status (physical exam, orthostatic vitals, mucous membranes, weight changes)
- Measure urine osmolality and sodium:
- Urine osmolality >100 mOsm/kg: impaired free water clearance
- Urine sodium <20 mmol/L: extrarenal losses
- Urine sodium >30 mmol/L: renal losses or SIADH
- Evaluate thyroid and adrenal function (TSH, cortisol)
Management:
- Hypovolemic: Isotonic saline (0.9% NaCl), stop diuretics, treat underlying cause
- Euvolemic: Fluid restriction (<1–1.5 L/day), treat SIADH, consider vaptans, urea, loop diuretics, correct endocrine disorders
- Hypervolemic: Fluid and sodium restriction, loop diuretics, optimize CHF/cirrhosis/CKD management, consider vaptans
- Severe symptoms (e.g., seizures, AMS): Administer 3% hypertonic saline, raise sodium by 4–6 mmol/L, avoid >10 mmol/L increase in 24 hrs, monitor closely to prevent ODS
2. Isotonic Hyponatremia (Pseudohyponatremia)
This type presents with a low measured sodium but normal serum osmolality (275–295 mOsm/kg), often due to lab artifact. There is no true hypo-osmolality.
Common Causes:
- Hyperlipidemia (chylomicronemia, severe hypertriglyceridemia)
- Paraproteinemia (e.g., multiple myeloma)
- Use of indirect ion-selective electrode methods
Diagnostic Approach:
- Confirm serum osmolality is normal
- Suspect artifact in asymptomatic patients with high lipids/proteins
- Confirm with direct ion-selective electrode measurement
Management:
- No treatment needed for sodium
- Avoid unnecessary fluid restriction or hypertonic saline
- Treat underlying disorder (e.g., lipid management, plasma cell disorder)
3. Hypertonic Hyponatremia
This type results from the presence of osmotically active substances in the serum (e.g., glucose), drawing water into the extracellular space and diluting serum sodium. Serum osmolality is >295 mOsm/kg.
Common Causes:
- Hyperglycemia (DKA, HHS)
- Mannitol infusion
- Glycine absorption (TURP, hysteroscopy)
- High-dose IVIG in sugar-based carriers
- Radiocontrast agents
Diagnostic Approach:
- Confirm serum osmolality >295 mOsm/kg
- Identify and quantify the osmotic agent
- For hyperglycemia, calculate corrected sodium:
- Na_corrected = Measured Na + [1.6 x (glucose – 100) / 100]
Management:
- Treat underlying osmotic disturbance (e.g., insulin and fluids for hyperglycemia)
- Discontinue or reduce exposure to mannitol/glycine
- Do not administer hypertonic saline
- Monitor serum sodium during correction
General Diagnostic Strategy for Hyponatremia
- Measure serum osmolality to determine true hypotonicity
- Assess volume status clinically and through labs
- Check urine sodium and osmolality
- Evaluate endocrine function (TSH, cortisol)
- Consider contributing comorbidities (CHF, cirrhosis, CKD)
Summary of Management Strategies
- Hypovolemic Hyponatremia: Restore volume with isotonic saline, treat cause
- Euvolemic Hyponatremia: Fluid restriction, treat SIADH or endocrine disorders, consider pharmacologic agents (vaptans)
- Hypervolemic Hyponatremia: Fluid/sodium restriction, loop diuretics, treat underlying organ dysfunction
- Severe/Symptomatic Cases: Use hypertonic saline with caution; monitor closely to avoid ODS
- Isotonic and Hypertonic Types: Do not treat with fluids or sodium; address the underlying metabolic derangement
Conclusion
Hyponatremia is a multifaceted and potentially life-threatening condition. A methodical, evidence-based diagnostic and therapeutic approach—rooted in understanding osmolality and volume status—ensures effective and safe patient care. Recognizing when and how to use isotonic, hypotonic, or hypertonic solutions is key to successful management. Interdisciplinary collaboration, especially with nephrology and endocrinology, enhances outcomes and reduces complications.
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