Hyponatremia

Hyponatremia is a condition characterized by a decrease in the concentration of sodium in the blood serum to less than 135 mmol/l. Normally, a decrease in sodium intake does not lead to the development of hyponatremia, since water excretion also decreases at the same time.

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Causes hyponatremia

In pathology, the causes of hyponatremia are situations related to:

• with renal and extrarenal sodium losses, provided that the electrolyte losses exceed the total intake of it into the body;
• with blood dilution (due to excess water intake in polydipsia or increased production of ADH in the syndrome of disproportionate ADH production);
• with the redistribution of sodium between the extracellular and intracellular sectors, which can occur with hypoxia, long-term use of digitalis and excessive ethanol consumption.

Pathological sodium losses are classified as extrarenal and renal.

The main extrarenal sources of sodium loss are: the gastrointestinal tract (during vomiting, diarrhea, fistulas, pancreatitis, peritonitis), skin (sweat losses due to thermal effects, cystic fibrosis, skin damage due to burns, inflammation), massive bleeding, paracentesis, blood sequestration due to extensive limb trauma, dilation of peripheral vessels. Sodium loss with urine can occur both with unchanged kidneys (use of osmotic diuretics, mineralocorticoid deficiency) and with renal pathology.

The main kidney diseases that lead to sodium loss are chronic renal failure, non-oliguric acute renal failure, the recovery period after oliguric acute renal failure, salt-losing nephropathy: elimination of obstructive nephropathy, nephrocalcinosis, interstitial nephritis, cystic diseases of the renal medulla (nephronophthisis, spongy medullary disease), Bartter syndrome. All of these conditions are characterized by the inability of the renal tubular epithelium to normally reabsorb sodium even under conditions of maximum hormonal stimulation of its reabsorption.

Since total body water content is closely related to ECF volume, hyponatremia must be considered in conjunction with fluid status: hypovolemia, normovolemia, and hypervolemia.

Main causes of hyponatremia

Hyponatremia with hypovolemia (decreased OVO and Na, but the sodium level is reduced relatively more)

Extrarenal losses

• Gastrointestinal: vomiting, diarrhea.
• Sequestration in spaces: pancreatitis, peritonitis, small bowel obstruction, rhabdomyolysis, burns.

Renal losses

• Taking diuretics.
• Mineralocorticoid deficiency.
• Osmotic diuresis (glucose, urea, mannitol).
• Salt wasting nephropathy.

Hyponatremia with normovolemia (increased OVO, Na level close to normal)

• Taking diuretics.
• Glucocorticoid deficiency.
• Hypothyroidism.
• Primary polydipsia.

Conditions that increase ADH release (postoperative opioids, pain, emotional stress).

Syndrome of inappropriate ADH secretion.

Hyponatremia with hypervolemia (decrease in total Na content in the body, relatively greater increase in TBO).

Non-renal disorders.

• Cirrhosis.
• Heart failure.
• Renal disorders.
• Acute renal failure.
• Chronic renal failure.
• Nephrotic syndrome

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Symptoms hyponatremia

Symptoms of hyponatremia include the development of neurological symptoms (from nausea, headache, loss of consciousness to coma and death). The severity of symptoms depends on both the degree of hyponatremia and the rate of its increase. A rapid decrease in intracellular sodium content is complicated by the movement of water into the cell, which can lead to cerebral edema. A serum sodium concentration below 110-115 mmol/l poses a risk to the patient's life and requires intensive treatment.

The main symptoms are those of CNS dysfunction. However, when hyponatremia is accompanied by disturbances in total body sodium content, there may be signs of volume depletion. The severity of symptoms is determined by the degree of hyponatremia, the rate of its development, the cause, the age, and the general condition of the patient. In general, older patients with chronic diseases develop more symptoms than younger, otherwise healthy patients. Symptoms are more severe with rapidly developing hyponatremia. Symptoms usually begin to appear when the effective plasma osmolality falls below 240 mOsm/kg.

Symptoms may be vague and consist primarily of mental status changes, including personality disorder, somnolence, and impaired consciousness. As plasma sodium falls below 115 mEq/L, stupor, neuromuscular hyperexcitability, seizures, coma, and death may occur. In premenopausal women, severe cerebral edema may develop with acute hyponatremia, probably because estrogen and progesterone inhibit Na/K ATPase and reduce the clearance of solutes from brain cells. Possible sequelae include hypothalamic and posterior pituitary infarction and, occasionally, brain stem herniation.

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Forms

The main mechanism of hyponatremia development - loss of sodium or impaired water excretion - determines the hemodynamic variant of hyponatremia: hypovolemic, hypervolemic or isovolemic.

Hypovolemic hyponatremia

Hypovolemic hyponatremia develops in patients with loss of sodium and water through the kidneys, gastrointestinal tract, or due to bleeding or redistribution of blood volume (in pancreatitis, burns, injuries). Clinical manifestations correspond to hypovolemia (hypotension, tachycardia, increasing in a standing position; decreased skin turgor, thirst, low venous pressure). In this situation, hyponatremia develops due to excessive fluid replenishment.

There is a deficit in TBO and total body sodium, although sodium is lost in greater amounts; Na deficiency causes hypovolemia. Hyponatremia occurs when fluid losses that include salt, as in persistent vomiting, severe diarrhea, or fluid sequestration in spaces, are replaced by plain water or intravenous hypotonic solutions. Significant ECF losses may cause a release of ADH, causing renal water retention, which may maintain or worsen hyponatremia. In extrarenal causes of hypovolemia, since the normal renal response to fluid loss is sodium retention, the urine sodium concentration is usually less than 10 mEq/L.

Renal fluid losses leading to hypovolemic hyponatremia may be observed in mineralocorticoid deficiency, diuretic therapy, osmotic diuresis, and salt-wasting nephropathy. Salt-wasting nephropathy includes a wide group of kidney diseases with predominant renal tubular dysfunction. This group includes interstitial nephritis, juvenile nephrophthalmia (Fanconi disease), partial obstruction of the urinary tract, and sometimes polycystic kidney disease. Renal causes of hypovolemic hyponatremia can usually be differentiated from extrarenal causes by taking the medical history. Patients with ongoing renal fluid loss can also be distinguished from those with extrarenal fluid losses by high urinary sodium concentrations (> 20 mEq/L). An exception is observed in metabolic alkalosis (in severe vomiting), when large amounts of HCO3 are excreted in the urine, which requires excretion of Na to maintain neutrality. In metabolic alkalosis, the concentration of CI in the urine allows us to distinguish renal from extrarenal causes of fluid excretion.

Diuretics may also cause hypovolemic hyponatremia. Thiazide diuretics have the most pronounced effect on the excretory capacity of the kidneys, simultaneously increasing sodium excretion. After the volume of the ECF is reduced, ADH is released, leading to water retention and increasing hyponatremia. Concomitant hypokalemia leads to the movement of Na into the cells, stimulating the release of ADH, thus again increasing hyponatremia. This effect of thiazide diuretics may be observed for up to 2 weeks after discontinuation of therapy; however, hyponatremia usually disappears with compensation of the deficit of K and fluid and restriction of water intake until the effect of the drug ceases. Hyponatremia caused by thiazide diuretics is more likely to develop in elderly patients, especially in the presence of impaired renal water excretion. Rarely, severe, life-threatening hyponatremia due to excessive natriuresis and impaired renal dilution capacity develops in these patients within a few weeks of starting thiazide diuretics. Loop diuretics are less likely to cause hyponatremia.

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Hypervolemic hyponatremia

Hypervolemic hyponatremia is characterized by an increase in total body sodium (and hence ECF volume) and TBW, with a relatively large increase in TBW. Various disorders that cause edema, including heart failure and cirrhosis, cause hypervolemic hyponatremia. Rarely, hyponatremia occurs in nephrotic syndrome, although pseudohyponatremia may occur due to the effect of elevated lipids on sodium measurements. In all of these conditions, volume depletion causes release of ADH and angiotensin II. Hyponatremia results from the antidiuretic effect of ADH on the kidneys and direct impairment of renal water excretion by angiotensin II. Decreased SCF and thirst stimulation by angiotensin II also potentiate the development of hyponatremia. Urinary Na excretion is usually less than 10 mEq/L, and urine osmolality is high relative to plasma osmolality.

The main symptom of hypervolemic hyponatremia is edema. Such patients have decreased renal blood flow, decreased SCF, increased proximal sodium reabsorption, and sharply decreased excretion of solute-free water. This type of water-electrolyte disturbances develops in congestive heart failure and severe liver damage. It is considered a poor prognostic sign. Hyponatremia is rarely detected in nephrotic syndrome.

Normovolemic hyponatremia

In normovolemic hyponatremia, the total body sodium content and ECF volume are within normal limits, but the amount of TBW is increased. Primary polydipsia can cause hyponatremia only if water intake exceeds the excretory capacity of the kidneys. Since the kidneys can normally excrete up to 25 liters of urine per day, hyponatremia due to polydipsia occurs with large water intakes or with impaired renal excretory capacity. This condition is mainly observed in patients with psychosis or with a more moderate degree of polydipsia in combination with renal failure. Hyponatremia can also develop as a result of excess fluid intake without sodium retention in the presence of Addison disease, myxedema, nonosmotic secretion of ADH (eg, stress; postoperative state; intake of drugs such as chlorpropamide or tolbutamide, opioids, barbiturates, vincristine, clofibrate, carbamazepine). Postoperative hyponatremia is caused by a combination of nonosmotic release of ADH and excessive administration of hypotonic solutions. Some drugs (eg, cyclophosphamide, NSAIDs, chlorpropamide) potentiate the renal effect of endogenous ADH, while others (eg, oxytocin) have a direct ADH-like effect on the kidney. In all these conditions, inadequate water excretion is observed.

Syndrome of inappropriate secretion of ADH (SIADH) is characterized by excessive release of ADH. It is determined by excretion of sufficiently concentrated urine against the background of plasma hypoosmolality (hyponatremia) without a decrease or increase in fluid volume, emotional stress, pain, intake of diuretics or other drugs that stimulate ADH secretion, with normal cardiac, hepatic, adrenal and thyroid function. SIADH is associated with a large number of different disorders.

Isovolemic hyponatremia develops when the body retains 3-5 liters of water, of which 2/3 is distributed into cells, as a result of which edema does not occur. This variant is observed in the syndrome of disproportionate secretion of ADH, as well as in chronic and acute renal failure.

Hyponatremia in AIDS

Hyponatremia has been found in over 50% of patients hospitalized with AIDS. Possible causative factors include administration of hypotonic solutions, renal dysfunction, release of ADH due to decreased intravascular volume, and use of drugs that impair renal excretion of fluid. Also, adrenal insufficiency due to damage to the adrenal glands by cytomegalovirus infection, mycobacterial infection, and impaired synthesis of glucocorticoids and mineralocorticoids by ketoconazole has been increasingly observed in patients with AIDS. SIADH may be present due to concomitant pulmonary or CNS infections.

Diagnostics hyponatremia

Hyponatremia is diagnosed by measuring serum electrolytes. However, Na levels may be artificially low if severe hyperglycemia increases osmolality. Water moves from the cells into the ECF. Serum sodium concentrations decrease by 1.6 mEq/L for every 100 mg/dL (5.55 mmol/L) increase in plasma glucose above normal. This condition is called carryover hyponatremia because there is no change in TBO or Na. Pseudohyponatremia with normal plasma osmolality may occur in hyperlipidemia or excessive hyperproteinemia because lipids and proteins fill the plasma volume removed for analysis. New methods of measuring plasma electrolytes using ion-selective electrodes have overcome this problem.

Determining the cause of hyponatremia should be comprehensive. Sometimes the medical history suggests a specific cause (eg, significant fluid loss due to vomiting or diarrhea, kidney disease, excessive fluid intake, use of drugs that stimulate the release of ADH or enhance its action).

The patient's volume status, particularly the presence of obvious volume changes, also suggests certain causes. Patients with hypovolemia usually have an obvious source of fluid loss (with subsequent replacement with hypotonic solutions) or an easily identifiable condition (e.g., heart failure, liver disease, or kidney disease). In patients with normal volumes, more laboratory testing is needed to determine the cause.

The severity of the condition determines the urgency of treatment. The sudden appearance of CNS disorders suggests an acute onset of hyponatremia.

Laboratory studies should include determination of osmolality and electrolytes in blood and urine. In normovolemic patients, thyroid and adrenal function should also be assessed. Hypoosmolality in normovolemic patients should result in excretion of large amounts of dilute urine (eg, osmolality < 100 mOsm/kg and specific gravity < 1.003). Low serum sodium and osmolality and abnormally high urine osmolality (120-150 mmol/L) in relation to low serum osmolality suggest volume expansion or volume depletion or syndrome of inappropriate antidiuretic hormone (SIADH). Volume depletion and volume expansion are differentiated clinically. If these conditions are not confirmed, SIADH is suspected. Patients with SIADH are usually normovolemic or mildly hypervolemic. Blood urea nitrogen and creatinine levels are usually within normal limits, and serum uric acid levels are often decreased. Urine sodium levels are usually greater than 30 mmol/L, and fractional excretion of sodium is greater than 1%.

In patients with volume depletion and normal renal function, sodium reabsorption results in urinary sodium levels of less than 20 mmol/L. Urinary sodium levels greater than 20 mmol/L in patients with hypovolemia suggest mineralocorticoid deficiency or salt-wasting nephropathy. Hyperkalemia suggests adrenal insufficiency.

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Treatment hyponatremia

Successful treatment of hyponatremia depends on a preliminary assessment of the hemodynamic variant of the electrolyte disturbance.

If hypovolemic hyponatremia is detected, treatment is aimed at restoring fluid deficit. A 0.9% sodium chloride solution is administered at a calculated rate until the symptoms of hypovolemia disappear. If the cause of hypovolemia is excessive and prolonged use of diuretic drugs, in addition to replenishing fluid volume, 30 to 40 mmol/L of potassium is administered.

In hyponatremia with normal BCC, treatment is carried out depending on the cause of the sodium imbalance. In kidney diseases that lead to sodium loss, the amount of sodium administered should be increased. In the case of using large doses of diuretics, both sodium and potassium levels are corrected. If hyponatremia has arisen as a result of using large amounts of hypoosmolar fluid, it is necessary to limit water intake and correct the sodium content.

In hyponatremia with hyperhydration, water intake is reduced to 500 ml/day, its excretion is stimulated by loop, but not thiazide diuretics; in heart failure, ACE inhibitors are prescribed, peritoneal dialysis and hemodialysis may be necessary. Treatment of hyponatremia with severe clinical symptoms should be carried out gradually and very carefully, since rapid administration of sodium can cause dangerous neurological disorders. The first stage of treatment consists of increasing the sodium content of blood serum to 125-130 mmol/l using hypertonic (3-5%) sodium chloride solutions; at the second stage, the sodium level is slowly corrected with isotonic solutions.

Rapid correction of even mild hyponatremia is associated with the risk of neurological complications. Sodium levels should be corrected no faster than 0.5 mEq/(lh). The increase in sodium levels should not exceed 10 mEq/l during the first 24 hours. The cause of hyponatremia should be treated in parallel.

Mild hyponatremia

In mild asymptomatic hyponatremia (i.e., plasma sodium > 120 mEq/L), progression should be prevented. In diuretic-induced hyponatremia, elimination of the diuretic may be sufficient; some patients require sodium or potassium supplementation. Similarly, if mild hyponatremia is caused by inadequate parenteral fluid intake in a patient with impaired water excretion, discontinuation of hypotonic solutions may be sufficient.

In the presence of hypovolemia, if adrenal function is not impaired, administration of 0.9% saline usually corrects hyponatremia and hypovolemia. If the plasma Na level is less than 120 mEq/L, full correction may not occur due to restoration of intravascular volume; restriction of solute-free water intake to 500-1000 ml/day may be necessary.

In patients with hypervolemia whose hyponatremia is due to renal Na retention (eg, heart failure, cirrhosis, nephrotic syndrome), fluid restriction in combination with treatment of the underlying cause is often effective. In patients with heart failure, correction of refractory hyponatremia may be achieved with a combination of an ACE inhibitor and a loop diuretic. If hyponatremia does not respond to fluid restriction, high doses of a loop diuretic may be used, sometimes in combination with intravenous 0.9% saline. K and other electrolytes lost in the urine must be replaced. If hyponatremia is severe and does not respond to diuretics, intermittent or continuous hemofiltration may be necessary to control ECF volume while hyponatremia is corrected with intravenous 0.9% saline.

In normovolemia, treatment is directed at correcting the underlying cause (eg, hypothyroidism, adrenal insufficiency, diuretics). In the presence of SIADH, strict fluid restriction is necessary (eg, 250-500 ml/day). In addition, a loop diuretic can be combined with intravenous 0.9% saline, as in hypervolemic hyponatremia. Long-term correction depends on the success of treating the underlying cause. If the underlying cause is incurable (eg, metastatic lung cancer) and strict fluid restriction is not possible in a given patient, demeclocycline (300-600 mg every 12 hours) can be used; however, demeclocycline may cause acute renal failure, which is usually reversible after discontinuation of the drug. In studies, selective vasopressin receptor antagonists effectively induce diuresis without significant electrolyte losses in the urine, which may be used in the future to treat resistant hyponatremia.

Severe hyponatremia

Severe hyponatremia (plasma sodium < 109 mEq/L, effective osmolality > 238 mOsm/kg) in asymptomatic patients can be corrected by strict fluid restriction. Treatment is more controversial in the presence of neurologic symptoms (eg, confusion, somnolence, seizures, coma). The rate and extent of correction of hyponatremia are controversial. Many experts recommend increasing plasma sodium levels by no more than 1 mEq/(L h), but in patients with seizures, a rate of up to 2 mEq/(L h) during the first 2-3 hours is recommended. In general, the increase in Na levels should not exceed 10 mEq/L during the first 24 hours. More intensive correction increases the likelihood of developing demyelination of central nervous system fibers.

Hypertonic (3%) solution may be used, but electrolyte levels must be measured frequently (every 4 hours). In patients with seizures or coma, < 100 ml/h may be administered over 4-6 hours in an amount sufficient to raise the serum Na level by 4-6 mEq/L. This amount may be calculated using the formula:

(Desired Change in Na) / OBO, where OBO = 0.6 body weight in kg for men or 0.5 body weight in kg for women.

For example, the amount of Na needed to increase the sodium level from 106 to 112 in a 70 kg man is calculated as follows:

(112 meq/l 106 meq/l) (0.6 l/kg 70 kg) = 252 meq.

Since hypertonic saline contains 513 mEq Na/L, approximately 0.5 L of hypertonic saline is required to raise the sodium level from 106 to 112 mEq/L. Adjustments may be necessary, and plasma sodium levels should be monitored for the first 2 to 3 hours after initiation of therapy. Patients with seizures, coma, or altered mental status require additional treatment, which may include mechanical ventilation and benzodiazepines (eg, lorazepam 1 to 2 mg IV every 5 to 10 minutes as needed) for seizures.

Osmotic demyelination syndrome

Osmotic demyelination syndrome (previously called central pontine myelinolysis) may develop if hyponatremia is corrected too rapidly. Demyelination may involve the pons and other areas of the brain. The disorder is more common in patients with alcoholism, malnutrition, or other chronic diseases. Fringe paralysis, articulation disorders, and dysphagia may develop within days to weeks. The disorder may extend dorsally to involve sensory pathways and result in pseudocoma (a "wandering" syndrome in which the patient can only move the eyes due to generalized motor paralysis). The damage is often permanent. If sodium replacement is too rapid (eg, > 14 mEq/L/8 hours) and neurologic symptoms develop, further increases in plasma sodium levels should be prevented by discontinuing hypertonic solutions. In such cases, hyponatremia induced by the administration of hypotonic solutions may attenuate possible permanent neurological damage.