Hyponatremia

Hyponatremia — a serum sodium below 135 mEq/L — is the most common electrolyte disorder in hospitalized patients. It is also one of the most misunderstood. The instinct is to think about sodium. The correct frame is water.

In almost every case of true hyponatremia, the body is retaining free water relative to sodium. The sodium is not necessarily low in absolute terms — the water is high. The kidney is either unable to excrete free water normally, or the patient is taking in more free water than the kidney can handle.

The clinical work begins with two questions: Is this true hyponatremia, or is it artifactual? And if it is true, what is the volume status? The answers to those two questions direct every subsequent step.

Before working up hyponatremia, confirm it is real. Pseudohyponatremia is a falsely low sodium caused by extreme hyperlipidemia or hyperproteinemia (as in multiple myeloma). These conditions displace water from the plasma, reducing the fraction of plasma that is aqueous — and since sodium is measured per unit of plasma volume, the reported sodium is falsely low. Plasma osmolality is normal. No treatment is needed.

Hypertonic hyponatremia is a different phenomenon. When plasma osmolality is elevated — from hyperglycemia, mannitol, or contrast agents — water shifts out of cells into the extracellular space, diluting sodium. For every 100 mg/dL rise in glucose above normal, sodium falls by approximately 1.6–2.4 mEq/L. Correcting the glucose corrects the sodium. This is not a water-handling problem.

True hypotonic hyponatremia — low serum sodium with low plasma osmolality — is the clinical entity that requires a full workup. Confirm with a measured plasma osmolality below 275 mOsm/kg before proceeding.

Once true hypotonic hyponatremia is confirmed, volume status is the first and most important branch point. The clinical examination — mucous membranes, skin turgor, heart rate, blood pressure, JVP, edema — combined with the history and urine studies directs the workup.

Hypovolemic hyponatremia occurs when total body sodium is depleted and water is also depleted, but proportionally less. The kidney responds to perceived volume depletion by releasing ADH, which retains free water — worsening the hyponatremia. Causes include vomiting, diarrhea, diuretics, adrenal insufficiency, and third-spacing. The urine sodium is typically low (below 20 mEq/L) as the kidney avidly conserves sodium — unless the cause is diuretics or adrenal insufficiency, in which case urine sodium may be elevated.

Euvolemic hyponatremia is the most common category in hospitalized patients. Total body sodium is normal; the problem is excess free water retention. SIADH is the dominant cause. Hypothyroidism and adrenal insufficiency must be excluded before diagnosing SIADH. The urine sodium is typically above 40 mEq/L and urine osmolality is above 100 mOsm/kg.

Hypervolemic hyponatremia occurs in heart failure, cirrhosis, and nephrotic syndrome. Total body sodium and water are both increased, but water excess is proportionally greater. The effective arterial blood volume is reduced despite total body fluid excess — the kidney responds by retaining sodium and water, worsening the hyponatremia. Urine sodium is typically below 20 mEq/L.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is diagnosed when: serum osmolality is low, urine is inappropriately concentrated (osmolality above 100 mOsm/kg), urine sodium is elevated (above 40 mEq/L), the patient is clinically euvolemic, and adrenal insufficiency and hypothyroidism have been excluded.

The causes of SIADH are broad. Pulmonary disease — pneumonia, COPD exacerbation, lung malignancy, positive pressure ventilation — is a common trigger. CNS disease — stroke, meningitis, encephalitis, traumatic brain injury, subarachnoid hemorrhage — is another. Medications are among the most common causes in clinical practice: SSRIs, SNRIs, carbamazepine, oxcarbazepine, cyclophosphamide, and many others. Pain, nausea, and surgery are also potent ADH stimuli.

Management of SIADH centers on fluid restriction — typically 800–1000 mL per day — and treating the underlying cause. In patients with severe or symptomatic hyponatremia, hypertonic saline is indicated regardless of the underlying cause. Vaptans (tolvaptan, conivaptan) block the V2 receptor and promote free water excretion, but their use requires careful monitoring and is generally reserved for refractory cases.

The rate of sodium correction is the most critical safety principle in hyponatremia management. Correcting chronic hyponatremia too rapidly causes osmotic demyelination syndrome (ODS) — a devastating neurological injury that can cause locked-in syndrome, quadriplegia, and death.

The brain adapts to chronic hyponatremia (present for more than 48 hours) by extruding osmoles — organic solutes that reduce intracellular osmolality and prevent cerebral edema. When sodium is corrected rapidly, the extracellular osmolality rises faster than the brain can restore its intracellular osmoles. The resulting osmotic gradient pulls water out of neurons, causing demyelination.

The safe correction limit is 8–10 mEq/L in any 24-hour period, and no more than 18 mEq/L in 48 hours. Risk is highest in patients with severe hyponatremia (below 120 mEq/L), malnutrition, alcoholism, and liver disease. Sodium should be checked every 2–4 hours during active correction.

Symptomatic hyponatremia — seizures, severe altered mental status, respiratory failure from cerebral edema — is the exception. These patients require immediate treatment with hypertonic saline (3% NaCl) to raise sodium by 1–2 mEq/L per hour until symptoms resolve, then slow correction to stay within the daily limit. The risk of untreated cerebral edema outweighs the risk of ODS in the acute symptomatic setting.