Hyponatraemia (Hyponatremia) - classification, causes, pathophysiology, treatment

Hyponatremia: A Comprehensive Overview

Key Concepts: Hyponatremia, serum sodium concentration, pseudo hyponatremia, hypervolemic hyponatremia, euvolemic hyponatremia, hypovolemic hyponatremia, osmolality, ADH (antidiuretic hormone), natriuresis, cerebral edema, central pontine myelinolysis.

1. Definition and Prevalence

Hyponatremia is defined as a serum sodium concentration below 130 millimoles per liter (mmol/L). It affects 1-15% of hospitalized patients. While most cases are mild, acute hyponatremia can be life-threatening.

2. The Role of Sodium and Body Fluid Compartments

• Sodium's Importance: Sodium is a critical cation, primarily located in the extracellular fluid (ECF).
• Body Compartments:
  • Intracellular Compartment: Contains approximately 12 mmol/L of sodium. Potassium is the main cation here (155 mmol/L).
  • Extracellular Compartment: Composed of the interstitial and intravascular spaces, containing about 145 mmol/L of sodium.
• Sodium-Potassium Pump: This transporter maintains the high extracellular sodium concentration by exchanging sodium for potassium.
• Water Movement: Water diffuses freely between compartments, including through aquaporin channels.

3. Classification of Hyponatremia by Volume Status

Hyponatremia is classified based on the patient's volume status:

• Hypervolemic Hyponatremia: Low serum sodium with fluid overload (e.g., peripheral edema, pulmonary edema).
• Euvolemic Hyponatremia: Low serum sodium with normal fluid status.
• Hypovolemic Hyponatremia: Low serum sodium with dehydration (e.g., fast heart rate, low blood pressure).

4. Pseudo Hyponatremia (False Low Sodium Readings)

It's crucial to rule out pseudo hyponatremia before diagnosing true hyponatremia. Serum osmolality is key in differentiating.

• Hyperglycemia: High blood glucose draws water into the intravascular space, diluting sodium. Serum osmolality is increased. Insulin binds on to receptors on cell surface to allow expression of glute transporters which facilitates glucose moving inside the cells.
• Mannitol: This osmotic agent draws water into the intravascular space, causing dilution. Used to reduce intracranial pressure. Serum osmolality is increased.
• Hyperlipidemia and Hyperproteinemia: Lipids and proteins interfere with lab analysis, falsely lowering sodium. Serum osmolality is normal.
• TURP (Transurethral Resection of the Prostate): Irrigation with mannitol or glycine can lead to absorption and dilutional hyponatremia. Serum osmolality is normal (possibly due to rapid clearance of mannitol/glycine).

5. Hypervolemic Hyponatremia: Causes and Mechanisms

Characterized by fluid overload and low serum sodium. True hyponatremia with low plasma osmolality.

• Congestive Cardiac Failure (CHF):
  • Reduced arterial blood flow leads to increased thirst and ADH release.
  • ADH causes water retention, diluting sodium.
  • Symptoms: Elevated JVP, lung crackles, peripheral edema.
  • Serum osmolality is low.
  • Urine sodium is usually low (kidneys reabsorbing sodium).
• Liver Cirrhosis:
  • Reduced albumin synthesis leads to water shifting into the interstitial space (edema).
  • Portal hypertension and low albumin decrease arterial volume, stimulating thirst and ADH release.
  • Serum osmolality is low.
  • Urine sodium is usually low.
• Nephrotic Syndrome:
  • Glomerular damage causes albumin loss (hypoalbuminemia).
  • Water shifts out of the intravascular space, stimulating thirst and ADH release.
  • Serum osmolality is low.
  • Urine sodium is usually low.
• Chronic Renal Failure:
  • Decreased glomerular filtration rate (GFR) activates the renin-angiotensin-aldosterone system (RAAS).
  • Aldosterone and ADH increase water and sodium retention, leading to dilution.
  • Serum osmolality is low.
  • Urine sodium is high (nephrons unable to retain sodium).
• Hypothyroidism:
  • Low thyroid levels cause bradycardia and reduced GFR.
  • Reduced cardiac output and GFR stimulate ADH release and RAAS activation.
  • Serum osmolality is low.
  • Urine sodium is high.

6. Euvolemic Hyponatremia: Causes and Mechanisms

Characterized by normal fluid status and low serum sodium.

• Syndrome of Inappropriate ADH Secretion (SIADH):
  • Non-physiological ADH release from the pituitary or ectopic sources.
  • ADH increases aquaporins in kidney collecting ducts, leading to water retention.
  • Fluid overload stimulates ANP and BNP release, inhibiting the RAAS.
  • Reduced aldosterone leads to natriuresis (sodium excretion).
  • Urine sodium is high.
  • Serum osmolality is low.
  • Renal Adaptation: Long-term, kidneys reduce aquaporin expression, leading to diuresis and a euvolemic state.
• Beer Potomania:
  • Chronic alcohol drinkers consume large volumes of beer with poor nutrition.
  • Malnutrition leads to low protein and solute intake.
  • Fluid overload suppresses ADH, causing water excretion.
  • The body tries to retain solutes, resulting in euvolemic hyponatremia.

7. Hypovolemic Hyponatremia: Causes and Mechanisms

Characterized by true volume depletion and low serum sodium.

• Diuretics (Thiazides):
  • Inhibit sodium and chloride reabsorption in the distal convoluted tubule.
  • Cause natriuresis and diuresis, leading to hypovolemia and hyponatremia.
  • ADH is triggered to retain water, but thiazides have no effect on aquaporins.
  • Symptoms: Thirst, dry mucous membranes, reduced skin turgor, tachycardia, hypotension.
  • Urine sodium is increased.
• Vomiting:
  • Loss of water and electrolytes.
  • Loss of stomach acid increases serum pH.
  • Kidneys excrete bicarbonate with sodium to compensate.
  • Urine sodium is increased.
• Diarrhea:
  • Loss of water and electrolytes (sodium, bicarbonate).
  • Bicarbonate loss leads to acidemia.
  • Kidneys secrete hydrogen ions to normalize pH.
• Hypoaldosteronism (e.g., Addison's Disease, Spironolactone):
  • Low aldosterone reduces sodium reabsorption in the kidneys.
  • Increases natriuresis and diuresis.
  • Urine sodium is increased.
• Sweating, Burns, Pancreatitis:
  • Water and sodium loss from the intravascular space.
  • Sweating: Sodium and water loss from sweat glands.
  • Burns: Water and electrolyte loss from soft tissue injury.
  • Pancreatitis: Third spacing of fluid outside the intravascular space.
  • Urine sodium is low (renal system attempts to retain sodium).

8. Clinical Presentation

Symptoms often appear when sodium is below 120 mmol/L.

• General Symptoms: Headaches, lethargy, malaise, nausea, vomiting.
• Fluid Status Changes: Hypervolemic, euvolemic, or hypovolemic signs.
• Rapid Sodium Drop: Can cause rapid fluid shift into cells, leading to cerebral edema and non-cardiogenic pulmonary edema.

9. Diagnosis

• Electrolytes, Urea, Creatinine: To identify hyponatremia (sodium < 130 mmol/L).
• Plasma Osmolality: High in pseudo hyponatremia, low in true hyponatremia.
• Urine Osmolality and Sodium Concentration: To differentiate causes.

10. Management

• Mild Asymptomatic Hyponatremia: Usually requires no treatment.
• Low Sodium, Asymptomatic/Ongoing Hyponatremia:
  • Strict fluid restriction (750 mL - 1.2 L).
  • Slow isotonic saline administration.
• Acute Severe Hyponatremia (Symptomatic):
  • Resuscitation if necessary.
  • Strict fluid restriction.
  • Slow hypertonic saline administration.
• Slow Correction: Plasma sodium should be corrected slowly (maximum 12 mmol/L in 24 hours) to prevent central pontine myelinolysis.

11. Central Pontine Myelinolysis

• Cause: Rapid shift of water from intracellular to extracellular space due to overly rapid sodium correction.
• Mechanism: Brain cells shrink due to water loss.
• Symptoms: Flaccid paralysis, dysarthria, dysphasia.
• Outcome: Significant morbidity and mortality.

12. Conclusion

Hyponatremia is a manifestation of underlying conditions, not a disease itself. Accurate diagnosis and management, including slow correction of sodium levels, are crucial to prevent serious complications.