Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The rare disease that we will be learning about today is:

Hyponatremia

What is Hyponatremia?

• Hyponatremia is a electrolyte abnormality in which there is an excess of body water relative to body sodium​
• Often defined as serum sodium concentration < 135 mEq/L​
• In the United States, the estimated prevalence of hyponatremia ranges from 3.16 million to 6.07 million persons.​
  • By this definition, hyponatremia is not considered rare.
  • Approximately 1% of patients were classified as having acute and symptomatic hyponatremia, 4% acute and asymptomatic, 15%–20% chronic and symptomatic, and 75–80% chronic and asymptomatic​
  • The direct costs of treating hyponatremia in the U.S. on an annual basis were estimated to range between $1.6 billion and $3.6 billion​
  • 24% of hospitalized patients with heart failure present with hyponatremia​
• Typically a complication of other medical illnesses​
• Severe hyponatremia (<125 mEq/L) has a high mortality rate. In patients whose serum sodium level falls below 105 mEq/L the mortality is over 50%​
• Treatment varies depending on the severity of hyponatremia
• The condition is classified in three different forms:
  • Hypovolemic – When sodium loss exceeds fluid loss
    • Generally, patients have a clear source of fluid loss​
  • Euvolemic – Serum sodium is normal, but total body water is higher than normal
    • Lab tests are often necessary to identify the cause
  • Hypervolemic – The increase in total body water is greater than the increase in sodium
    • Generally linked to kidney disease, heart failure, or cirrhosis

How Do You Get It?

• Most common in old people, those that require tube feeding, and hospital patients
• Black people have a reduced risk
• Most cases of hyponatremia are caused by decreased renal excretion of water, secondary to persistent action of vasopressin [ADH (antidiuretic hormone)] or the use of medications that interfere with urinary dilution​
• The clinical disorders leading to hyponatremia share a reduction in arterial blood volume, resulting in persistent ADH activity despite hypo-osmolar plasma
• Inappropriately elevated plasma levels of vasopressin (ADH) increase water reabsorption and retention, which will disproportionately expand the plasma volume, thus resulting in dilutional hyponatremia.​​
• Hyponatremia can be caused by a variety of other diseases and conditions such as:
  • Heart failure*
    • Patients with heart failure are at risk for hypervolemic hyponatremia as a result of excess sodium and water retention, promoted by increased vasopressin levels and compromised glomerular filtration​
    • Reduced cardiac output in heart failure stimulates the release of vasopressin, resulting in elevated levels of circulating vasopressin​
    • Because vasopressin reduces the excretion of free water, elevated levels of vasopressin can contribute to the development of hyponatremia in heart failure patients​
    • Reduced cardiac output and decreased renal perfusion activates the renin-angiotensin-aldosterone system in heart failure patients​
    • The excess of angiotensin II in heart failure causes the following which further exacerbates dilutional hyponatremia: systemic and arteriolar vasoconstriction; increase in aldosterone concentration; increased thirst​
    • In heart failure, water and sodium retention occur in response to aldosterone​​
  • Syndrome of Inappropriate Antidiuretic Hormone (SIADH)*
    • Hyponatremia in SIADH (syndrome of inappropriate antidiuretic hormone secretion) is a result of an excess of water and not a deficiency of sodium​
    • In SIADH impaired water excretion is caused by the inability to suppress the secretion of antidiuretic hormone (ADH)​
    • If water intake exceeds the reduced urine output, the ensuing water retention leads to the development of hyponatremia​
    • ​Hyponatremia in SIADH is marked by water retention secondary to an increase in serum vasopressin and urinary sodium excretion​
    • SIADH accounts for 60% of all types of chronic hyponatremia and is the most common etiology of hyponatremia in hospitalized patients​
    • SIADH is caused by:
      • Cancer, typically small cell lung cancer or head and neck cancer
      • Nonmalignant lung disease
      • Medications such as antipsychotic drugs, anticancer agents, antidepressants, anticonvulsants, narcotics, sulfonylureas, and angiotensin-converting enzyme inhibitors
      • CNS disease or damage – hydrocephalus, trauma, infections
  • Diuretic use​
  • Chronic, severe vomiting or diarrhea​
  • Liver disease​
  • Renal disease​
  • Drinking large amounts of water during endurance sports​
  • Dehydration​
  • Hormonal changes​

What Are The Symptoms?

• Mild hyponatremia may not cause any symptoms, but when they appear they may include:
  • Nausea and vomiting​
  • Headache​
  • Confusion​
  • Loss of energy and fatigue​
  • Restlessness and irritability​
  • Muscle weakness, spasms, or cramps​
  • Seizures​
  • Coma​
  • Seizures​
  • Hallucinations​
  • Acute psychosis​
  • Disorientation
  • Depressed reflexes
• The severity of neurologic symptoms correlates with the rate and degree of the drop in serum sodium. ​

How Is It Treated?

• Physicians should first decide if immediate treatment is required and then decide the most appropriate method of correcting the hyponatremia
• ​Treatment depends on the cause of the hyponatremia, rate of onset of hyponatremia, patient symptoms, and the volume status of the patient​
• In patients with chronic hyponatremia, overzealous and rapid correction should be avoided because it can lead to osmotic demyelination  or death​
• Health Care Team may include: Emergency medicine physicians, oncologists, cardiologists, nephrologists, critical care specialists​
• Some of the methods used to treat include: Demeclocycline, Fluid Restriction, Hypertonic Saline, Isotonic Saline, Lithium, Loop Diuretics, Urea, Vasopressin Receptor Antagonists (Vaptans)​
• Treatment for acute hyponatremia (less than 48 hours)
  • Hypertonic saline (3% NaCl) infusion until an increase of 4-6 mmol/L in serum sodium concentration is achieved​
• Treatment for symptomatic chronic hyponatremia (48 hours or more)
  • 3% NaCl is recommended with or without vasopressin receptor antagonists​
  • Initial administration of 3% NaCl therapy is needed to raise the serum sodium by 4-6 mmol above baseline.​
• Treatment for mild chronic hyponatremia with low symptoms
  • Fluid restriction if the urine to serum electrolyte ratio is less than 0.5​
  • Salt tablets and if necessary, a loop diuretic​
  • Initiation of a vasopressin antagonist without fluid restriction​
• Non-drug treatments may be recommended for mild or asymptomatic cases. Some examples include:
  • Discontinuation of all possible offending drugs​
  • Fluid restriction (less than 1 to 1.5 L per day)​
  • High-sodium diet (Dependent on the cause)​
• Prognosis depends on the underlying cause​
• Hyponatremia among patients with cancer is associated with extended hospital stays and higher mortality rates​
• Correction of hyponatremia that is too rapid may cause permanent neurologic impairment​
• Establishment of cause and appropriate treatment improves outcomes​

Where Can I Learn More???

• Check out our cornerstone on this disease here.