Hyponatremia

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

[1], [2], [3], [4], [5],

Causes of the hyponatremia

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

• with renal and adrenal losses of sodium, provided that the loss of electrolyte exceeds the total intake of it into the body;
• with blood dilution (due to excess water intake for 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 during hypoxia, prolonged use of digitalis and excessive consumption of ethanol.

Pathological losses of sodium are classified as extra-renal (extrarenal) and renal (renal).

The main extra-renal sources of sodium loss: gastrointestinal tract (with vomiting, diarrhea, fistulas, pancreatitis, peritonitis), skin (heat loss afterwards, cystic fibrosis, skin damage due to burns, inflammation), massive bleeding, paracentesis, blood sequestration due to extensive injuries of limbs , the expansion of peripheral vessels. Loss of sodium in the urine can occur as with unchanged kidneys (the use of osmotic diuretics, a deficiency of mineralocorticoids), and with renal pathology.

The main kidney diseases leading to loss of sodium are chronic renal failure, neoligic acute renal failure, recovery period after oliguric acute renal failure, salt-losing nephropathies: elimination of obstructive nephropathy, nephrocalcinosis, interstitial nephritis, cystic kidney disease (nephronophytosis, spongy medullary disease) , Bartter's syndrome. For all these conditions, the inability of the epithelium of the renal tubules to normally reabsorb sodium is characteristic even under conditions of maximum hormonal stimulation of its reabsorption.

 Since the total water content in the body is closely related to the volume of ECG, hyponatremia should be considered together with the status of the fluid: hypovolemia, normovolemia and hypervolemia.

The main causes of hyponatremia

Hyponatremia with hypovolemia (decrease in OBO and Na, however, the sodium level is lowered relatively more)

Out-of-site loss

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

Kidney loss

• Reception of diuretics.
• Deficiency of mineralocorticoids.
• Osmotic diuresis (glucose, urea, mannitol).
• Soltering nephropathy.

Hyponatremia with normovolemia (increase in OBO, close to normal Na level)

• Reception of diuretics.
• Deficiency of glucocorticoids.
• Hypothyroidism.
• Primary polydipsia.

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

Syndrome of inadequate secretion of ADH.

Hyponatremia with hypervolemia (decrease in the total Na content in the body, a relatively larger increase in PSB).

Non-adrenal disorders.

• Cirrhosis.
• Heart failure.
• Renal impairment.
• Acute kidney failure.
• Chronic renal failure.
• Nephrotic syndrome

[6], [7], [8], [9], [10]

Symptoms of the hyponatremia

Symptoms of hyponatremia are the development of neurological symptoms (from nausea, headache, loss of consciousness to coma and death). The severity of symptoms depends both on the degree of hyponatremia, and on the rates of its growth. Rapid reduction in intracellular sodium is complicated by the movement of water inside the cell, which can lead to  edema of the brain. The concentration of sodium in the serum below 110-115 mmol / l represents a risk to the life of the patient and requires intensive treatment.

The main symptoms include manifestations of central nervous system dysfunction. However, in the case when hyponatremia is accompanied by violations of the total sodium content in the body, there may be signs of a change in the volume of the fluid. The severity of symptoms is determined by the degree of hyponatremia, the rate of its development, the cause, age and general condition of the patient. In general, elderly patients with chronic diseases develop more symptoms than younger patients in otherwise healthy patients. Symptoms are more severe with rapidly developing hyponatraemia. Symptoms usually begin to manifest with a decrease in effective plasma osmolality of less than 240 mOsm / kg.

Symptomatics can be fuzzy and consist mainly of changes in mental status, including personality disorder, drowsiness and impaired consciousness. With a decrease in sodium in the plasma below 115 meq / l, stupor, excessive neuromuscular excitability, convulsions, coma and death can develop. In women in the premenopausal period with acute hyponatremia, severe cerebral edema may develop, probably because estrogen and progesterone inhibit Na / K ATPase and reduce the removal of solutes from brain cells. Possible consequences include a heart attack of the hypothalamus and the posterior part of the pituitary gland, as well as sometimes the formation of a herniated brain stem.

[11], [12], [13], [14]

Forms

The main mechanism for the development of hyponatremia - loss of sodium or disruption of water allocation - 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 (with pancreatitis, burns, trauma). Clinical manifestations correspond to hypovolemia (hypotension, tachycardia, increasing in standing position, decreased skin turgor, thirst, low venous pressure). In this situation, hyponatremia develops as a result of excess fluid replenishment.

There is a shortage of OBO and the total sodium content in the body, although sodium is lost significantly more; deficiency of Na causes hypovolemia. Hyponatremia is observed in the case when the loss of fluid, the input of which is lost and the salt, like with continuing vomiting, severe diarrhea, sequestration of fluid in the spaces, are compensated by the intake of pure water or intravenous injection of hypotonic solutions. Significant ECG losses can cause the release of ADH, which causes kidney water retention, which can maintain or worsen hyponatraemia. With extrarenal causes of hypovolemia, since the normal reaction of the kidneys to loss of fluid is sodium retention, the concentration of sodium in the urine is usually less than 10 meq / l.

Renal fluid loss leading to hypovolemic hyponatremia can occur with a deficiency of mineralocorticoids, diuretic therapy, osmotic diuresis, and salt-losing nephropathy. Soltering nephropathy includes a wide group of kidney diseases with predominant dysfunction of the renal tubules. This group includes interstitial nephritis, juvenile nephroptosis (Fanconi's disease), partial obstruction of the urinary tract and sometimes polycystic kidney disease. The kidney causes of hypovolemic hyponatremia can usually be differentiated from extrarenals in the collection of anamnesis. It is also possible to distinguish patients with ongoing renal fluid loss from patients with extrarenal fluid loss at a high concentration of sodium in the urine (> 20 meq / L). An exception is observed in metabolic alkalosis (with severe vomiting), when large amounts of HCO3 are excreted in the urine, which requires the excretion of Na to maintain neutrality. In metabolic alkalosis, the concentration of CI in the urine makes it possible to distinguish the kidney causes of excretion of the fluid from the extrarenal ones.

Diuretics can also cause hypovolemic hyponatraemia. Thiazide diuretics have the most pronounced effect on the excretory capacity of the kidneys, while simultaneously increasing the excretion of sodium. After ECG volume decreases, ADH is released, leading to water retention and hyponatremia. Concomitant hypokalemia leads to the movement of Na inside the cells, stimulates the release of ADH, thus reinforcing hyponatremia. This effect of thiazide diuretics can occur up to 2 weeks after discontinuation of therapy; but hyponatremia usually disappears when the deficiency of K and liquid is compensated and the water intake is limited until the drug stops. Hyponatremia caused by thiazide diuretics is more likely to develop in older patients, especially if there are abnormalities in the excretion of water by the kidneys. It is rare for such patients to develop severe, life-threatening hyponatremia within a few weeks after the onset of thiazide diuretics, caused by excessive natriuresis and impaired dilution capacity of the kidneys. Loop diuretics rarely cause the development of hyponatremia.

[15], [16], [17], [18]

Hypervolaemic hyponatremia

Hypervolaemic hyponatremia is characterized by an increase in the total sodium content in the body (hence, the volume of EWC) and OBO, with a relatively large increase in OBO. Various disorders that cause the appearance of edema, including heart failure and cirrhosis, lead to the development of hypervolemic hyponatremia. Rarely, hyponatremia develops with nephrotic syndrome, although pseudohyponatremia may be observed due to the effect of elevated lipid levels on sodium measurement. With all these conditions, a decrease in the volume of circulating blood leads to the release of ADH and angiotensin II. Hyponatremia occurs due to the antidiuretic effect of ADH on the kidneys and direct disturbance of renal excretion of water by angiotensin II. Reduction of GFR and stimulation of thirst with angiotensin II also potentiate the development of hyponatremia. Urine excretion in the urine is usually less than 10 meq / L, urine osmolality is high relative to the osmolality of the plasma.

The main sign of hypervolemic hyponatremia is swelling. In such patients, renal blood flow was reduced, GFR was reduced, proximal reabsorption of sodium was increased and the excretion of osmotically free water was sharply reduced. This variant of water-electrolyte disorders develops with congestive heart failure and severe liver damage. He is considered a bad prognostic sign. In a nephrotic syndrome, hyponatremia is rarely seen.

Normovolemic hyponatremia

With normovolemic hyponatremia, the total sodium content in the body and the volume of ECG are within the normal range, however, the amount of OBO is increased. Primary polydipsia can cause hyponatraemia only if water intake exceeds the excretory capacity of the kidneys. Since normal kidneys can excret up to 25 liters of urine a day, hyponatremia due to polydipsia is observed when taking large amounts of water or when the excretory capacity of the kidneys is compromised. Basically, this condition is observed in patients with psychosis, or at a more moderate degree of polydipsia in combination with renal insufficiency. Hyponatremia can also develop as a result of excessive fluid intake without sodium retention in the presence of Adison's disease, myxedema, neosmotic secretion of ADH (eg stress, postoperative conditions, taking drugs such as chlorpropamide or tolbutamide, opioids, barbiturates, vincristine, clofibrate, carbamazepine). Postoperative hyponatremia is observed due to a combination of neosmotic ejection 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 kidneys. For all these states, insufficient water excretion is observed.

Syndrome of inadequate secretion of ADH (SNSADG) is characterized by excessive release of ADH. It is determined by deducing sufficiently concentrated urine on the background of hypoosmolality of the plasma (hyponatremia) without decreasing or increasing the volume of fluid, emotional stress, pain, diuretics or other drugs stimulating ADH secretion in normal cardiac, hepatic, adrenal and thyroid functions. SNSSADG is associated with a large number of various violations.

Isovolemic hyponatremia develops with a delay in the body of 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

More than 50% of patients hospitalized with AIDS diagnosed hyponatremia. Possible causative factors include the introduction of hypotonic solutions, impaired renal function, the release of ADH due to a decrease in intravascular volume, the use of drugs that disrupt renal fluid excretion. Also, in patients with AIDS, adrenal insufficiency has recently been observed more often as a result of adrenal damage with cytomegalovirus infection, mycobacterial infection, disruption of the synthesis of glucocorticoids and mineralocorticoids by ketoconazole. There may be SSSADG in connection with concomitant lung infections or CNS.

Diagnostics of the hyponatremia

Diagnosis of hyponatremia is to determine the level of serum electrolytes. However, the Na level can be artificially lowered if severe hyperglycemia increases osmolality. Water passes from the cells to the EWC. The concentration of sodium in the serum is reduced by 1.6 meq / l for every 100 mg / dL (5.55 mmol / L) of plasma glucose elevation above normal. This condition is called portable hyponatremia, since there is no change in the amount of OBO or Na. Pseudohyponatremia with normal plasma osmolality can be observed in case of hyperlipidemia or excessive hyperproteinemia, since lipids and proteins fill the volume of plasma taken for analysis. New methods for measuring the level of plasma electrolytes using ion-selective electrodes have overcome this problem.

The definition of the cause of hyponatremia should be complex. Sometimes an anamnesis suggests a certain cause (for example, a significant loss of fluid due to vomiting or diarrhea, kidney disease, excessive fluid intake, taking drugs that stimulate the release of ADH or enhance its effect).

The condition of the patient's BCC, especially the presence of an apparent change in volume, also suggests certain causes. In patients with hypovolemia, the source of fluid loss is usually obvious (with subsequent compensation for hypotonic solutions) or there is an easily detectable condition (eg, heart failure, liver or kidney disease). In patients with normal fluid volume, more laboratory tests are needed to determine the cause.

The severity of the development of the condition determines the urgency of treatment. The sudden appearance of violations from the central nervous system suggests an acute onset of hyponatremia.

The number of laboratory tests should include the determination of osmolality and electrolytes of blood and urine. Patients with normovolemia also need to determine the function of the thyroid and adrenal glands. Hypoosmolality in patients with normovolemia should result in the excretion of a large amount of diluted urine (eg, osmolality <100 mOsm / kg and density <1.003). Low levels of sodium and osmolality of blood serum, as well as an excessively high level of urine osmolality (120-150 mmol / l) in relation to low serum osmolality suggest an increase or decrease in fluid volume or ADH (inadequate production) syndrome. The decrease and increase in the volume of fluid is differentiated clinically. If these statuses are not confirmed, it is assumed that SNSADG. In patients with SSSADG, usually there is normovolemia or mild hypervolemia. Nitrogen levels of blood urea and creatinine are usually within normal limits, serum uric acid levels are often reduced. The level of sodium in urine is usually more than 30 mmol / l, fractional sodium excretion is more than 1%.

In patients with a decrease in fluid volume with normal renal function, sodium reabsorption results in a sodium level in the urine of less than 20 mmol / l. The level of sodium in the urine of more than 20 mmol / l in patients with hypovolemia indicates a deficiency of mineralocorticoids or solitary nephropathy. Hyperkalemia indicates adrenal insufficiency.

[19], [20], [21], [22], [23], [24]

Treatment of the hyponatremia

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

When hypovolemic hyponatremia is detected, treatment is aimed at restoring fluid deficiency. Enter 0.9% solution of sodium chloride with the calculated rate until the disappearance of symptoms of hypovolemia. If excessive and prolonged use of diuretic drugs is the cause of hypovolemia, in addition to replenishing the volume of fluid, 30 to 40 mmol / L of potassium are injected.

When hyponatremia with normal bcc treatment is carried out depending on the cause that caused a violation of sodium balance. In diseases of the kidneys leading to loss of sodium, you should increase the amount of sodium administered. In the case of using large doses of diuretics, a correction is made for both sodium and potassium levels. If hyponatremia occurs as a result of the use of large amounts of hypoosmolar fluid, it is necessary to limit the administration of water and correct the sodium content.

With hyponatremia with hyperhydration, water intake is reduced to 500 ml / day, stimulates its elimination by loop, but not by thiazide diuretics; when heart failure is prescribed ACE inhibitors, there may be a need for the use of peritoneal dialysis and hemodialysis. Treatment of hyponatremia with severe clinical symptoms should be done gradually and very carefully, since the rapid administration of sodium can cause dangerous neurological disorders. The first stage of treatment is to increase the sodium content of blood serum to 125-130 mmol / l with the use of hypertonic (3-5%) solutions of sodium chloride; at the second stage, the sodium level is adjusted slowly with isotonic solutions.

Rapid correction of even mild hyponatremia is associated with a risk of neurological complications. Correction of the sodium level should occur no faster than 0.5 meq / (lxh). The increase in the sodium level should not exceed 10 meq / l during the first 24 hours. In parallel, the cause of hyponatremia should be treated.

Mild hyponatremia

With mild asymptomatic hyponatremia (ie, sodium level in the plasma> 120 meq / L), it is necessary to prevent its progression. With hyponatremia caused by taking diuretics, there may be enough elimination of the diuretic; some patients require the administration of sodium or K. Similarly, if mild hyponatremia is caused by inadequate parenteral fluid administration in a patient with impaired water excretion, it may be sufficient to stop the administration of hypotonic solutions.

In the presence of hypovolemia, if the function of the adrenal glands is not disturbed, the introduction of 0.9% saline usually corrects hyponatremia and hypovolemia. If the Na level in the plasma is less than 120 meq / l, a full correction may not occur due to the restoration of the intravascular volume; it may be necessary to limit the intake of osmotically free water to 500-1000 ml per day.

In patients with hypervolemia, in which hyponatremia is associated with renal Na delay (eg, in heart failure, cirrhosis, nephrotic syndrome), it is often effective to limit fluid intake in combination with the treatment of the underlying cause. In patients with heart failure, the correction of refractory hyponatremia can be achieved by the combination of an ACE inhibitor with a loop diuretic. If hyponatremia does not respond to the restriction of fluid intake, it is possible to use high doses of loop diuretic, sometimes in combination with intravenous administration of 0.9% saline. It is necessary to compensate K and other electrolytes, lost with urine. If hyponatremia is severe and not corrected by taking diuretics, intermittent or constant hemofiltration may be necessary to control the volume of EWC, while correction of hyponatremia is performed by intravenous administration of 0.9% saline.

With normovolemia, treatment is aimed at correcting the cause (eg, hypothyroidism, adrenal insufficiency, diuretic use). In the presence of SNSSADG, a strict restriction of the liquid (for example, 250-500 ml per day) is necessary. In addition, a combination of a loop diuretic with intravenous administration of 0.9% saline, as with hypervolemic hyponatremia, is possible. Long-term correction depends on the success of the treatment of the underlying cause. In case of non-curability of the main cause (for example, metastatic lung cancer) and the impossibility of strict fluid restriction in this patient, it is possible to use demeclocycline (300-600 mg every 12 hours); However, the use of demeclocicin can cause acute renal failure, which is usually reversible after discontinuation of the drug. In studies, selective antagonists of vasopressin receptors effectively cause diuresis without significant loss of electrolytes in the urine, which in the future can be used for the treatment of resistant hyponatremia.

Severe hyponatremia

Severe hyponatremia (plasma sodium level <109 meq / L, effective osmolality> 238 mOsm / kg) in asymptomatic patients can be corrected by strict restriction of fluid intake. Treatment is more controversial in the presence of neurological symptoms (for example, confusion, drowsiness, convulsions, coma). Controversial points are the speed and degree of correction of hyponatremia. Many experts recommend increasing the sodium level in the plasma to not more than 1 meq / (lh), but in patients with convulsions a speed of up to 2 meq / (l h) is recommended during the first 2-3 hours. In general, the increase in the Na level should not exceed 10 meq / l during the first day. A more intensive correction increases the probability of demyelinating the fibers of the central nervous system.

A hypertonic (3%) solution can be used, but under the condition of frequent (every 4 hours) electrolyte level determination. In patients with convulsions or in a coma, <100 ml / h for 4-6 hours may be administered in an amount sufficient to increase the serum Na level by 4-6 meq / l. This amount can be calculated by the formula:

(Desired change in Na level) / OBO, where OBO = 0.6 body weight in kg in men or 0.5 body weight in kg in women.
 
For example, the amount of Na needed to raise the sodium level from 106 to 112 in a man weighing 70 kg is calculated as follows:

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

Since 513 meq Na / l is contained in the hypertonic solution, approximately 0.5 liters of hypertonic solution is needed to increase the sodium level from 106 to 112 meq / L. Changes may be required, in connection with which it is necessary to monitor the level of sodium in the plasma from the first 2-3 hours from the start of therapy. Patients with convulsions, in a coma, in case of mental disorders, need additional treatment, which may include artificial ventilation and benzodiazepines (eg lorazepam 1-2 mg intravenously every 5-10 minutes as needed) with convulsions.

Syndrome of osmotic demyelination

The syndrome of osmotic demyelination (formerly called central bridge myelinolysis) can develop with too rapid correction of hyponatremia. Demyelination can affect the bridge and other areas of the brain. The defeat is more often observed in patients with alcoholism, with malnutrition or other chronic diseases. Within a few days or weeks, peripheral paralysis, articulation disorders and dysphagia may develop. The lesion can spread in the dorsal direction with the involvement of sensitive pathways and lead to the development of a pseudocoma ("environment" syndrome, in which the patient, due to generalized motor paralysis, can only make eyeball movements). Often damage is permanent. If the sodium level is compensated too quickly (for example,> 14 meq / l / 8 hours) and neurological symptoms develop, it is necessary to prevent a further increase in the sodium level in the plasma by stopping the administration of hypertonic solutions. In such cases, hyponatremia, induced by the introduction of hypotonic solutions, can weaken a possible permanent neurologic lesion.