Hyponatremia is defined as a serum sodium concentration of less than 135 mEq/L but can vary to a small extent in different laboratories. Hyponatremia is a common electrolyte abnormality caused by an excess of total body water when compared to total body sodium content. Edelman discovered that serum sodium concentration does not depend on total body sodium but the ratio of total body solutes (e.g., total body sodium and total body potassium) to total body water. Hyponatremia represents an imbalance in this ratio where total body water is more than total body solutes. Total body water (TBW) has two main compartments, extracellular fluid (ECF) accounting for one-third and intracellular fluid (ICF), accounting for the remaining two-thirds. Sodium is the major solute of ECF and potassium for ICF.
The etiology of hyponatremia can be classified based on volume status, the extracellular fluid. As mentioned earlier, sodium is the major solute of extracellular fluid (ECF). Based on the volume of ECF, a patient can be hypovolemic, euvolemic, or hypervolemic.
Physiologic stimuli that cause vasopressin release combined with fluid intake can cause hyponatremia. Hypothyroidism and adrenal insufficiency may contribute to an increased release of vasopressin. Physiologic stimuli for vasopressin release include loss of intravascular volume (hypovolemic hyponatremia) and the loss of effective intravascular volume (hypervolemic hyponatremia).
Causes of hypovolemic hyponatremia (TBW decreases more than a decrease in total body sodium)
Causes of hypervolemic hyponatremia (TBW increases greater than an increase in total body sodium)
Causes of euvolemic hyponatremia (TBW increase with stable total body sodium)
Nonosmotic, pathologic vasopressin release may occur in the setting of normal volume status, as with euvolemic hyponatremia.
Causes of euvolemic hyponatremia include:
Many drugs cause hyponatremia, and the most common include:
Hyponatremia is the most common electrolyte disorder, with a prevalence of 20% to 35% in hospitalized patients. The incidence of hyponatremia is prevalent in critically ill patients in the intensive care unit (ICU) and also postoperative patients. This is more common in elderly patients due to multiple comorbidities, multiple medications, and a lack of access to food and drinks.
Thirst stimulation, antidiuretic hormone (ADH) secretion, and handling of filtered sodium by kidneys maintain serum sodium and osmolality. Normal plasma osmolality is around 275 mOsm/kg to 290 mOsm/kg. To maintain normal osmolality, water intake should be equal to water excretion. Imbalance of water intake and excretion causes hyponatremia or hypernatremia. Water intake is regulated by the thirst mechanism where osmoreceptors in the hypothalamus trigger thirst when body osmolality reaches 295 mOsm/kg. Water excretion is tightly regulated by antidiuretic hormone (ADH), synthesized in the hypothalamus and stored in the posterior pituitary gland. Changes in tonicity lead to either enhancement or suppression of ADH secretion. Increased ADH secretion causes reabsorption of water in the kidney, and suppression causes the opposite effect. Baroreceptors in the carotid sinus can also stimulate ADH secretion, but it is less sensitive than the osmoreceptors. Baroreceptors trigger ADH secretion due to decreased due to effective circulating volume, nausea, pain, stress, and drugs.
Hypertonic hyponatremia (Serum osmolality of greater than 290 mOsm/kg)
Isotonic hyponatremia (Serum osmolality between 275 mOsm/kg and 290 mOsm/kg)
Hypotonic hyponatremia (Serum osmolality of less than 275 mOsm/kg)
Hypotonic hyponatremia represents an excess of free water. This excess free water can be caused by two mechanisms:
There are three mechanisms involved in the inability of kidneys to excrete water:
1. High ADH activity: Three different mechanisms can cause high ADH:
2. Low glomerular filtration rate (GFR): a low glomerular filtration rate would impair the kidney's ability to get rid of water. Typical examples are acute kidney injury (AKI), chronic kidney disease (CKD), and end-stage renal disease (ESRD).
3. Low solute intake: Patients on a regular diet consume 600 mOsm to 900 mOsm of solute per day. Solutes are defined as substances that are freely filtered by the glomeruli but have a relative or absolute difficulty in being reabsorbed by the tubules in relationship to water. The main solutes are urea (which comes from the metabolism of proteins) and electrolytes (e.g., salt). Carbohydrates do not contribute to solute load. In steady-state conditions, solute intake is equal to urine solute load. Therefore, it is expected that these patients also excrete 600 mOsm to 900 mOsm of solute in the urine. Urine volume, and hence water excretion, is dependent on the urine solute load. The more solute one needs to excrete, the larger the urine volume one needs to produce. The less solute one needs to excrete, the smaller the urine volume one needs to produce. Patients who eat a low amount of solute per day (e.g., 200 mOsm/day), on steady-state conditions, will also excrete a low amount of solute in the urine, and therefore they will do it in a smaller volume of urine. This decreased urine volume will limit the capacity of the kidneys to excrete water. Typical examples of this are beer potomania and tea-and-toast diet.
SIADH (Syndrome of inappropriate antidiuretic hormone secretion)
This is a condition where inappropriate secretion of ADH despite normal or increases plasma volume causes impaired water excretion by the kidney leading to hyponatremia. SIADH is a diagnosis of exclusion, as there is no single test to confirm the diagnosis. Patients are hyponatremic and euvolemic.
Causes of SIADH include
Treatment includes fluid restriction and the use of vasopressin 2 receptor inhibitors.
Symptoms depend upon the degree and chronicity of hyponatremia. Patients with mild-to-moderate hyponatremia (greater than 120 mEq/L) or gradual decrease in sodium (greater than 48 hours) have minimal symptoms. Patients with severe hyponatremia (less than 120 mEq/L) or rapid decrease in sodium levels have multiple symptoms.
Symptoms can range from anorexia, nausea and vomiting, fatigue, headache, and muscle cramps to altered mental status, agitation, seizures, and even coma.
Apart from symptoms, a detailed history taking to include a history of pulmonary and CNS disorders, all home medications, and social history (increased beer intake or use of MDM or ecstasy) is very important.
Physical examination includes assessing volume status and neurological status.
Patients with neurological symptoms and signs need to be treated promptly to prevent permanent neurological damage.
The following steps may be performed while evaluating a patient with suspected hyponatremia:
Step 1: Plasma osmolality (275 mOsm to 290 mOsm/kg)
Step 2: Urine osmolality
Step 3: Volume status (ECF status)
Step 4: Urine Sodium concentration
Other tests that might help in differentiating the causes include
Treatment of hyponatremia depends upon the degree of hyponatremia, duration of hyponatremia, the severity of symptoms, and volume status.
Acute symptomatic hyponatremia:
Chronic asymptomatic hyponatremia
Drugs: Selective vasopressin 2 receptor antagonists are being used recently. They increase the excretion of water in the kidneys without effecting sodium, thereby increase serum sodium levels. These medications are used in patients with euvolemic and hypervolemic conditions (except liver failure) if the above measure does not help.
The goal of correction: Correct sodium by no more than 10 mEq/L to 12 mEq/L in any 24 hour period.
Risk factors for osmotic demyelination syndrome (ODS): Hypokalemia, liver disease, malnutrition, alcoholism.
Limits of correction:
True hyponatremia is associated with hypoosmolality. Conditions causing hyperosmolar hyponatremia and iso-osmolar hyponatremia (pseudo-hyponatremia) should be differentiated first.
The differential diagnosis for hypo-osmolar hyponatremia include:
Prognosis in patients with hyponatremia depends on the severity of hyponatremia and the underlying condition causing it. Prognosis is poor in patients with severe hyponatremia, acute hyponatremia, and elderly patients.
If left untreated or inadequately treated, patients with hyponatremia can develop rhabdomyolysis, altered mental status, seizures, and even coma.
Rapid correction of chronic hyponatremia (greater than 10 mEq/L to 12 mEq/L of sodium in 24 hrs) can lead to osmotic demyelination syndrome.
Osmotic demyelination syndrome, formerly known as central pontine myelinolysis is a complication of rapid correction sodium in patients with chronic hyponatremia. In patients with hyponatremia, the brain adapts to a fall in serum sodium level, without developing cerebral edema, in about 48 hours. As a result, patients with chronic hyponatremia are mostly asymptomatic. Once the brain adapts to low serum sodium, the rapid correction of sodium leads to osmotic demyelination syndrome. Clinical manifestations are typically delayed by few days and comprise several irreversible neurological symptoms, including seizures, disorientation, and even coma. "Locked-in" syndrome occurs in severely affected patients. These patients are awake but unable to move or communicate.
It is imperative to consult a nephrologist in a patient with severe hyponatremia or a rapid decrease in sodium or persistent hyponatremia.
Cardiology and gastroenterology consultation might be necessary for patients with congestive heart failure and hepatic failure, respectively.
Patients with hyponatremia should be followed closely at discharge by both the primary care provider and nephrology. Follow up labs are ordered as needed, and patients needing fluid restriction should be educated appropriately.
Hyponatremia is a common electrolyte abnormality. Sodium levels need to be closely monitored, as this could be a life-threatening condition if left untreated. This is even more important in patients with renal disease and those who are on diuretics. Good interprofessional communication between the primary care provider and a nephrologist is needed to keep a close eye on sodium and treat as needed.
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