A healthy patient who drinks a lot of water does not become hyponatremic. The excess of water in the blood is sensed by the brain osmoreceptors, and ADH (or vasopressin) is suppressed and the kidneys pass dilute urine getting rid of excessive water. It is the body’s defence against hypotonic hyponatremia. That is the reason tourists can be seen carrying bottles of mineral water with them and despite drinking frequently do not keel over with hyponatremia. In unacclimatized people coming to a tropical country in summer when temperatures are much higher than they have experienced in the past, who drink only water, with no electrolytes, heat exhaustion and heat cramps develop as they sweat off the electrolytes. They require sweetened drinks with a pinch of salt in them as well as physical cooling. Salty lemonade or lassi (Turkish ayran) are useful drinks. However in certain psychiatric disorders polydipsia may cause hyponatremia.
Hyponatraemia is the most common electrolyte disorder in hospitalised patients, seen in 15–30% of inpatients in the ER and ITC. It is defined as plasma sodium < 135 mmol/L. It is mainly a state of relative excess of body water associated with disordered vasopressin release. It causes significant morbidity and mortality depending on the acuity of onset and other comorbidities.
Hyponatraemia is often asymptomatic when it is mild or if it develops gradually. Acute hyponatraemia can be significantly symptomatic depending on the rapidity of the fall in sodium. How are you going to recognise that there is hyponatremia and whether it is acute in onset or chronic? If the clinical situation has arisen within the last 48 hours then it is acute otherwise the condition is chronic. The symptoms of acute mild to moderate hyponatraemia vary from nausea, headache, irritability and inability to concentrate to confusion and agitation. Severe, rapid-onset hyponatraemia causes vomiting, seizures, obtundation and coma leading to cardiorespiratory arrest.
Chronic hyponatraemia can be asymptomatic and is difficult to pick up. An unsteadiness generally and gait disturbance and recurrent falls especially in the elderly should make one suspect a low sodium. As the brain has had a chance to adapt to hyponatremia fits and convulsion are less likely to occur.
Perhaps the most common cause of hyponatremia seen in the ER is in a patient with DKA (diabetic ketoacidosis). In hyperglycaemic hyponatraemia there is a shift of water from the intracellular compartment to the intravascular space due to the osmotic effect of glucose, which causes a translocational hyponatraemia. The effective osmolality is maintained during treatment when free water returns to the intracellular compartment, thereby leading to an improvement in hyponatraemia, as may be seen in the management of DKA.
Recent evidence shows an association of hyponatraemia with osteoporosis and increased incidence of fractures. This is more relevant in the elderly population and should be considered when they present with confusion or falls.
Remember that although sodium readily permeates cell membrane the tight junctions in the brain capillaries become a barrier which prevents rapid movement or allows no movement of sodium for the above reasons. The fall in serum tonicity in patients with hypotonic hyponatremia promotes water movement into the brain and, if the hyponatremia is acute and severe, can lead to cerebral edema and neurologic symptoms. In response to hyponatremia, the brain makes adaptations that lower the cerebral volume toward normal and reduce the likelihood of these complications. However it takes the brain 2 days or so to return to normal hence the likelihood of recurrent symptoms. Correcting hyponatremia too quickly also damages the brain. Herniation of the brain and central pontine necrosis or ODS (osmotic demyelination syndrome) are likely to occur.
Who is going to get ODS?
- Patients who have had their hyponatremia corrected too quickly.
- Patients with severe liver disease and moderate hyponatremia, whose sodium levels increase after liver transplantation.
- Patients with diabetes insipidus who have developed a moderate degree of hyponatremia as a complication of desmopressin therapy and then have the desmopressin discontinued. Their sodium level may then increase quite rapidly as a result of a water diuresis.
- Patients with
- very low sodium,
- chronic alcoholism,
- chronic liver disease are particularly vulnerable to this disastrous complication.
Pathophysiology of sodium disorders
Are plasma tonicity and hyperosmolality the same or equivalent measurement? Plasma osmolality varies between 275 to 290 mosm/l. Tonicity is determined by molecules that do not move across cell membranes with the same alacrity as water like sodium which because of its large quantity acts as the surrogate for other electrolytes.. Other molecules add to the osmolality i.e. sugar, urea, glycine. ethanol but as they cross the cell membranes readily they do not add to the tonicity. During the management it not essential to measure the osmolality.
The severity (degree) of hyponatremia — Although a variety of definitions have been used. The UptoDate database uses the following:
- Severe hyponatremia – A serum sodium concentration of <120 mEq/L is “severe hyponatremia.” Complications of untreated hyponatremia and complications from overcorrection of hyponatremia are most common among patients with severe hyponatremia.
- Moderate hyponatremia – A serum sodium concentration of 120 to 129 mEq/L.
- Mild hyponatremia – A serum sodium concentration of 130 to 134 mEq/L.
Sodium permeates systemic capillary membranes freely, along with water, to maintain equal concentrations in the plasma and interstitial fluid in most tissues in the peripheral circulation. The blood–brain barrier, in the form of tight endothelial capillaries, prevents this free transit of sodium in the cerebral circulation. This results in free water movement between brain cells and plasma, driven by abnormal sodium levels. Plasma hypertonicity, therefore, leads to shrinkage of brain cells, and hypotonicity can cause cellular swelling.
The symptoms of sodium disorders are the consequences of these changes in the brain. Rapid sodium changes can lead to permanent, severe and even lethal injury to the brain cells, as they do not have time to adapt. The adaptive process that regulates cell volume in the brain may take up to 48 hours, and includes compensatory displacement of interstitial fluid into the cerebrospinal fluid (CSF) (and thereafter into systemic circulation), and volume regulatory decrease where astrocytes protect neurons from osmotic stress by extrusion of potassium and intracellular osmolyte buffers such as glutamate, thereby preventing cellular oedema.
Hyponatraemia is termed acute if it develops within 48 hours and chronic if it develops beyond this window. Acute hyponatraemia causes severe symptoms but rapid normalisation of chronic hyponatraemia is also dangerous, as replenishing lost osmolytes by astrocytes takes at least a week.
The principles of rapid correction of acute hyponatraemia and slow correction of chronic hyponatraemia are based on this physiological understanding of osmolyte transfer.
The treatment of hyponatremia can be in the context of low, normal or excess extracellular fluid volume.
Causes of hyponatraemia
- Increased extracellular fluid (ECF) volume: cardiac, hepatic and renal failure (including nephrotic syndrome), polydipsia
- Normal ECF volume: hypothyroidism, secondary adrenal insufficiency, syndrome of inappropriate antidiuretic hormone (SIADH).
- Translocation hyponatremia as in hyperglycaemia, hyperproteinaemia (IVIG, monoclonal gammopathy) and hyperlipidaemia (triglycerides, cholesterol).
- Low ECF volume,
- renal sodium loss: salt losing nephropathy, adrenal insufficiency, renal tubular acidosis, cerebral salt wasting, diuretics,
- extrarenal sodium loss: gastrointestinal, burns, pancreatitis, fistula, sweat,
- miscellaneous: (non-hypotonic) hyperglycaemia, hypertriglyceridemia, hyperproteinemia, mannitol, glycine (solution used in irrigating post-operatively as in hysterectomy or transurethral resection of the prostate).
Acute hyponatraemia may develop following pre-colonoscopy bowel preparation, prostate resection, endoscopic uterine surgery, postoperative hypotonic fluid administration, exercise including marathon runners, binge drinking or drugs.
Drug-induced hyponatraemia is mostly due to inappropriate antidiuretic hormone (ADH) (vasopressin) secretion. The common drugs implicated are selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), phenothiazines, desmopressin, carbamazepine, opiates and proton pump inhibitors (PPIs). This list is not exhaustive and it is appropriate to consult the product literature if in doubt. Diuretics like thiazides can cause hyponatraemia through SIADH as well as through hypovolaemia.
A thorough history and physical examination looking for the fluid volume status will help immensely with the management. The rapidity of onset of hyponatraemia and the manifesting symptoms will be essential to guide the management.