Back to NephrologyHyponatremic Encephalopathy
Among all the electrolyte disorders commonly found in general medical practice, hyponatremia appears to be the most common abnormality. Its importance is due to its association with a vast array of signs and symptoms, of which, undobtedly, the neurologic manifestations are the ones that present the highest morbidity and mortality.
Hyponatremia may be observed in a wide spectrum of clinical settings, the most common being: postoperative hyponatremia, renal failure, liver failure, heart failure, nephrotic syndrome and the syndrome of inappropriate secretion of vasopressin (SIADH). In the latter syndrome, the causes may be highly variable, ranging from the inappropriate secretion secondary to structural lesions ( tumors, CNS diseases, lung diseases ) to the one caused by certain drugs (antineoplastic, oral hypoglycemics, diuretics, clofibrate, carbamazepine and morphine-like analgesics). Other causes of the SIADH are chronic illnesses and the aquired immune deficiency syndrome, which courses frequently with hyponatremia.
Neurologic manifestations
Generally observed with plasma sodium levels lower than 130mmol/L, the neurologic manifestations of hyponatremia range from mild symptoms, such as headache, nausea and emesis to those more severe like seizures, coma and respiratory arrest. Psychiatric signs may be observed, the most common of which being a bizarre behavior of recent onset. Other manifestations tend to occur less frequently, but seem to be very characteristic of this entity called “hyponatremic encephalopathy”. These less common ocurrences are bradycardia, hypertension, hypothermia and dilated pupils. Urinary incontinence may occur, although much less frequently. Other signs and symptoms may be observed in protracted hyponatremia such as : weakness (focal or generalized), ataxia, asterixis, Babinski sign and delirium. Psychiatric manifestations in these cases may include depression, cognitive impairment and psychosis.
Although generally accepted as being 130mmol/L or less, the serum sodium level does not always correlate , in a linear fashion, to the presence of symptomatology; making it possible for an individual with sodium levels as low as 115mmol/L to be completely asymptomatic. On the other hand, a patient with a “not so decreased” sodium concentration ( 128mmol/L), may present with coma or even respiratory arrest.
Pathogenesis
The proposed sequence of events that lead to hyponatremic encephalopathy is as follows:
- First, with serum sodium of less than 130mmol/L (usually less than 120mmol/L) there is a progressive shift of water into brain cells. That starts as soon as twenty minutes after the acute reduction in sodium concentration;
- the increased levels of vasopressin (AVP), as often seen in hyponatremic states, causes a movement of water into brain cells, regardless of the presence or not of significant hyponatremia;
- as the brain cells edema is increasing, molecular mechanisms play an important role in the extrusion of sodium from brain cells (active transport), aiming the reduction of the transcellular gradient;
- as the brain swells, mechanical pressure against the nonyielding skull bones leads to decreased cerebral blood flow as well as decreased CSF formation;
- vasopressin and estrogens have an inhibitory effect on the ATP synthesis by the brain cells, resulting in an impaired outward transport of Na+ and K+, and consequently, greater edema. This mechanism might explain the more severe course of the hyponatremic encephalopathy usually seen in child-bearing age women (higher doses of circulating estrogens);
- at this point, unless the hyponatremia is corrected, there’s an important cerebral edema culminating in tentorial herniation of the brain, decreased cerebral blood flow and cerebral ischemia. The herniation may cause respiratory arrest, with an even greater reduction in blood flow, magnifying the ischemia.
Relationship between hypoxic events and hyponatremic encephalopathy
Due to the mechanisms explained above, hyponatremia causes an important reduction in cerebral blood flow as well as a decrease in arterial pO2 (secondary to the depressed ventilation). With an advanced ventilatory depression, respiratory insufficiency ensues, further aggravating the hypoxemia and, due to CO2 retention, increasing the cerebral edema. The occurrence of such hypoxic event is a major factor contributing to permanent brain damage in patients with hyponatremia. The combination of systemic hypoxemia and hyponatremia is much more harmful than the occurrence of either event alone (hypoxia inhibits the adaptive mechanisms of brain cells to hyponatremia). So, the major goal is to prevent such hypoxic episodes from occurring, usually by the correction of the sodium abnormality as soon as detected.
Symptomatic hyponatremia and female preponderance
There are many studies seggesting that the gender and age of the patient are important variables affecting the clinical course and outcome (wether or not permanent brain damage will be present). In those patients with symptomatic hyponatremia (usually less than 128mmol/L) older women and men of any age seem to have a better chance of recovering from the acute episode (after correction of the imbalance) without permanent neurologic damage, whereas menstruant women show a greater chance of either dying or developing permanent neurologic damage.
Treatment of hyponatremia
The treatmaent of symptomatic hyponatremia has been a matter of debate during the last few years. Most of this controversy arises from the fact that neurologic disorders become apparent both in untreated acutely hyponatremic patients and occasionally during the treatment of such hyponatremia. The latter case is best illustrated by the entity called “central pontine myelinolysis” or “osmotic demyelination syndrome”. Recently it has been shown that both terms are innacurate since the lesions found in patients who received correction for hyponatremia are neither confined to the pons nor occurred after an important osmotic imbalance. The syndrome of central pontine myelinolysis is commonly found in alcoholic individuals, and the full blown syndrome is characterized by flaccid quadriplegia, dysphagia and dysartrhia. The mechanisms predisposing to this neurologic complication are not completely understood; some suggest that th4e rate of correction of hyponatremia is implicated in the development of such syndrome, while others consider the magnitude of correction (the absolute change in Na+ concentration over a given period) as the main predisposing factor. Therefore, attention to both the rate and the magnitude of correction are warranted.
The magnitude of correction should not be a matter of concern, since in those patients with symptomatic hyponatremia, it is not necessary to attain hyperatremic or even eunatremic levels, as the symptomatology usually subsides after correction from moderate/severe hyponatremia to only mild hyponatremia (130mmol/L).
Rapid correction (over a 48h-period) is indicated for patients with acute symptomatic hyponatremia. This should be accomplished by the infusion of hypertonic saline aiming to increase the serum Na+ concentration by 0.5 to 1mmol/L/h with the upper limit being an increase of 25 mmol/L in the first 24 or, preferentially, 48 hours. The moment when the infusion of the hypertonic saline should be stopped should be dicteted by the appearence of any one of the following: the patient becomes asymptomatic; the plasma sodium has increased by 25mmol/L; or a serum sodium of 125-130mmol/L is achieved. The use of a loop diuretic should be considered if the possibility of excessive fluid load exists (cardiac failure, renal failure). An adequate formula to calculate the sodium requirements is:
[125 - measured serum Na+] x 0.6 body weight* = required mEq (mmol) of Na+
* = total body water
References :
1) The Kidney - Barry M. Brenner
2) Clinical Disorders of Fluids and Electrolyte Metabolism - Maxwell and Kleeman
3) Fluid, Electrolyte and Acid-Base Disorders - Arieff and DeFronzo
4) Clinical Physiology of Acid-Base and Electrolyte Disorders - Rose
5) Cecil’s Textbook of Medicine - 20th edition
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