Hyponatremia Overview

Hyponatremia

• Hyponatremia is a condition where the sodium level in the blood is too low, typically less than 135 mEq/L.
• The most common cause is an excess of water relative to sodium.
• Antidiuretic hormone (ADH) or vasopressin plays a crucial role in regulating water reabsorption in the kidneys.
• ADH levels are appropriately increased when blood volume or blood pressure is low.
• Low blood volume/pressure activates juxtaglomerular (JG) cells in the kidneys, leading to renin release, initiating the renin-angiotensin-aldosterone system (RAAS).
• Angiotensin II stimulates ADH release from the posterior pituitary gland.
• ADH acts on V2 receptors in the collecting ducts of the kidneys, causing water reabsorption.
• This reabsorption increases blood volume and pressure, but can also cause hyponatremia due to sodium dilution.
• High ADH states show high urine osmolality, typically greater than 300 mOsm/kg.
• Inappropriately high ADH levels define Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH).
• SIADH causes hyponatremia without a blood volume or pressure-related stimulus, triggered by various factors including: intracranial disease, pulmonary diseases, medications, and endocrinopathies.
• ADH levels are normally suppressed by high water intake or low solute intake.
• High water intake or low solute intake reduces plasma osmolality, decreasing ADH production.
• Low ADH results in diminished water reabsorption and more dilute urine.
• Urine osmolality is typically less than 300 mOsm/kg in low ADH states.
• Hyponatremia classification is based on the patient's volume status:
  • Hypovolemic hyponatremia: Reduced total body water and sodium, but sodium loss exceeds water loss. This leads to volume depletion and increased ADH activity, further diluting sodium.
  • Euvolemic hyponatremia: Mild increase in total body water compared to sodium content, primarily due to inappropriate ADH secretion, often caused by SIADH.
  • Hypervolemic hyponatremia: Increased total body water and slightly more total body sodium. This usually arises from fluid accumulating in interstitial spaces and cells, causing edema and fluid overload.

Causes of Hyponatremia

• Hypovolemic:
  • Renal: Diuretics (loop and thiazide), low aldosterone (Addison's disease, certain medications like ACE inhibitors and ARBs, renal tubular acidosis type 4, cerebral salt wasting).
  • Extrarenal: Gastrointestinal losses (vomiting, diarrhea, reduced oral intake), skin losses (burns, excessive sweating).
• Euvolemic:
  • SIADH: CNS injury (stroke, TBI), pulmonary diseases (pneumonia, ARDS, COPD), medications (SSRIs, carbamazepine), malignancy (small cell lung cancer), endocrinopathies (adrenal insufficiency, hypothyroidism).
• Hypervolemic:
  • Extrarenal: Congestive heart failure (CHF), cirrhosis.
  • Renal: Chronic kidney disease (CKD) stages 4-5 or on hemodialysis, excess hypotonic fluid administration.

Complications of Hyponatremia

• Cerebral edema: Water shifts from the bloodstream to brain tissue, increasing intracranial pressure (ICP). Clinical manifestations include headache, nausea/vomiting, altered consciousness (lethargy, obtundation, coma), and pupil abnormalities (fixed/dilated). Severe and acute hyponatremia (less than 120 mEq/L) is the most dangerous for cerebral edema risk.
• Osmotic demyelination syndrome (ODS): Rapid sodium correction pulls water too quickly from brain tissue, causing shrinkage and cell death, especially in the pons. Risk factors include severe hyponatremia, specific causes (beer potomania, tea and toast diet), and duration of hyponatremia exceeding 48 hours. Symptoms usually appear 1-2 weeks post-correction. ODS can present as quadriplegia, diplopia (vertical gaze preserved), dysarthria, dysphagia, and impaired consciousness.
• Seizures: Hyponatremia can induce seizures as the cortex becomes inflamed.

Hypernatremia

• Hypernatremia is a condition with elevated sodium levels, usually above 145 mEq/L.
• The main cause involves diminished water reabsorption, a deficiency or ineffective ADH.
• Central diabetes insipidus (DI): ADH production deficiency due to hypothalamus or posterior pituitary issues.
• Nephrogenic diabetes insipidus (DI): ADH receptor defect, hindering water reabsorption despite adequate ADH. Commonly seen with lithium use, hypokalemia, or hypercalcemia.
• Other causes: high aldosterone (primary/secondary), sodium chloride-containing solutions (isotonic/hypertonic saline, bicarbonate, TPN), water losses (renal/extrarenal).

Complications of Hypernatremia

• Dehydration: Water loss leads to dehydration causing hypovolemia (low blood volume -> hypotension, tachycardia, decreased skin turgor), and neurological symptoms (headache, lethargy, seizures, coma).
• Cellular dehydration: Particularly in the brain, resulting in neurological dysfunction.

Diagnosis and Treatment of Sodium Disorders

• Hyponatremia:
  • Evaluation: Serum sodium, serum osmolality, urine osmolality, urine sodium, volume status.
  • Treatment:
    • Severe (less than 120 mEq/L): 3% hypertonic saline IV.
    • Hypovolemic: 0.9% saline IV.
    • Euvolemic: Water restriction, loop diuretics (furosemide), ADH antagonists (tolvaptan).
    • Hypervolemic: Water restriction, loop diuretics.
• Hypernatremia:
  • Evaluation: Serum sodium, urine osmolality.
  • Treatment:
    • Replace free water deficit (calculations based on weight and serum sodium). Mild/moderate: free water orally/NG tube. Severe: D5W IV.
    • Hypovolemic: Hemodynamically unstable: Normal saline or LR IV. Stable: Hypotonic saline (0.45% or 0.25%).
    • Euvolemic: Central DI: Desmopressin (DDAVP). Nephrogenic DI: Thiazide diuretics.
    • Hypervolemic: Loop/thiazide diuretics.
• Monitoring: Careful monitoring crucial to prevent overcorrection and complications (ODS in hyponatremia, cerebral edema in both disorders).
  • Avoid sodium changes of more than 10-12 mEq/L/day in hypernatremia and 6-8 mEq/L/day in hyponatremia.