DISORDERS OF WATER AND ELECTROLYTE BALANCE DR. ALI ABDUL-RAHMAN YOUNIS

Water and electrolyte distribution In a typical adult male, total body water (TBW) is approximately 60% of body weight (somewhat more for infants and less for women). For an average individual, TBW is about 40L.Approximately 25 L is located inside cells (the intracellular fluid or ICF), while the remaining 15 L is in the extracellular fluid (ECF) compartment . Most of the ECF (approximately 12 L) is interstitial fluid, which is within the tissues but outside cells, whereas the remainder (about 3 L) is in the plasma compartment.

Water and electrolyte distribution The dominant cation in the ICF is potassium, while the dominant cation in the ECF is sodium. Phosphates and negatively charged proteins constitute the major intracellular anions, while chloride and, to a lesser extent, bicarbonate dominate the ECF anions. An important difference between the plasma and interstitial compartments of the ECF is that only plasma contains significant concentrations of protein.

Osmolality the concentration of a solution in terms of osmoles of  solutes per kilogram of solvent. serum osmolality a measure of the number of dissolved particles per unit of water in serum. In a solution, the fewer theparticles of solute in proportion to the number of units of water (solvent), the less concentrated the solution. A low serumosmolality means a higher than usual amount of water in relation to the amount of particles dissolved in it, andaccompanies overhydration, or edema.

Presenting problems in disorders of sodium balance When the balance of sodium intake and excretion is disturbed, any tendency for plasma sodium concentration to change is usually corrected by the osmotic mechanisms controlling water balance . As a result, disorders in sodium balance present chiefly as alterations in the ECF volume, resulting in hypovolaemia or oedema, rather than as an alteration in plasma sodium concentration.

Sodium depletion

Clinical assessment The diagnosis of hypovolaemia is based on characteristic symptoms and signs in the context of a relevant precipitating illness. Supportive evidence may be obtained from the clinical biochemistry laboratory. Although plasma sodium concentration may not be reduced if salt and water are lost in equal proportions, a number of other parameters are altered during appropriate renal, hormonal and haemodynamic responses to hypovolaemia. During the early stages of hypovolaemia, GFR is maintained while urinary flow rate is reduced as a consequence of activation of sodium- and water-retaining mechanisms in the nephron.

Clinical assessment Thus, plasma creatinine, which reflects GFR, may be relatively normal, but the plasma urea concentration is typically elevated, since urea excretion is affected by both GFR and urine flow rate. Plasma uric acid may also rise, reflecting activation of compensatory proximal tubular reabsorption. With avid retention of sodium and water, the urine osmolality increases while the urine sodium concentration falls. Under these circumstances, sodium excretion may fall to less than 0.1% of the filtered sodium load.

Management Management of sodium and water depletion has two main components: • treat the cause where possible, to stop ongoing salt and water losses. • replace the salt and water deficits, and provide ongoing maintenance requirements, usually by intravenous fluid replacement when depletion is severe.

Intravenous fluid therapy The choice of fluid and the rate of administration depend on the clinical circumstances, as assessed at the bedside and from laboratory data . In the absence of normal oral intake (as in a fasting or post-operative patient in hospital), maintenance quantities of fluid, sodium and potassium should be provided. If any deficits or continuing pathological losses are identified, additional fluid and electrolytes will be required. In prolonged periods of fasting (more than a few days), attention also needs to be given to providing sufficient caloric and nutritional intake to prevent excessive catabolism of body energy stores .

Intravenous fluid therapy If fluid containing neither sodium nor protein is given, it will distribute in the body fluid compartments in proportion to the normal distribution of total body water. Thus, giving 1 L of 5% dextrose will contribute relatively little (approximately 3/40 of the infused volume) towards expansion of the plasma volume. This makes 5% dextrose ineffective at restoring the circulation and perfusion of vital organs. Intravenous infusion of an isotonic (normal) saline solution, on the other hand, results in more effective expansion of the extracellular fluid, although a minority of the infused volume (some 3/15) will contribute to plasma volume.

Intravenous fluid therapy Carrying this reasoning further, it might be expected that a solution containing plasma proteins would be largely retained within the plasma, thus maximally expanding the circulating fluid volume and improving tissue perfusion. However, recent clinical studies have not shown any overall advantage of infusions containing albumin in the treatment of acute hypovolaemia . Resuscitation fluids containing synthetic colloids such as carbohydrate polymers should not be used in the acute resuscitation of volume-depleted patients since they offer no benefit over crystalloids and are associated with increased mortality.

Management The management of ECF volume overload involves a number of components: • specific treatment directed at the underlying cause, such as ACE inhibitors in heart failure and corticosteroids in minimal change nephropathy • restriction of dietary sodium (to 50–80 mmol/day) to match the diminished excretory capacity • treatment with diuretics.

Presenting problems in disorders of water balance

Hyponatraemia Hyponatraemia (plasma Na <135 mmol/L) is a common electrolyte abnormality, which is often asymptomatic but which can also be associated with profound disturbances of cerebral function, manifesting as anorexia, nausea, vomiting, confusion, lethargy, seizures and coma. The likelihood of symptoms occurring is related more to the speed at which electrolyte abnormalities develop rather than their severity. When plasma osmolality falls rapidly, water flows into cerebral cells, which become swollen and ischaemic.

Hyponatraemia However, when hyponatraemia develops gradually, cerebral neurons have time to respond by reducing intracellular osmolality, through excreting potassium and reducing synthesis of intracellular organic osmolytes . The osmotic gradient favoring water movement into the cells is thus reduced and symptoms are avoided

Aetiology The causes of hyponatraemia are best categorised according to any associated changes in the ECF volume . In all cases, there is retention of water relative to sodium, and it is clinical examination rather than the biochemical results that gives a clue to the underlying cause. Artefactual causes of hyponatraemia should also be considered. severe hyperlipidaemia or hyperproteinaemia, when the aqueous fraction of the plasma specimen is reduced because of the volume occupied by the macromolecules (although this artefact is dependent on the assay technology). Transient hyponatraemia may also occur due to osmotic shifts of water out of cells during hyperosmolar states caused by acute hyperglycaemia or by mannitol infusion.

Investigations Plasma and urine electrolytes and osmolality are usually the only tests required to classify the hyponatraemia. Doubt about clinical signs of ECF volume may be resolved with measurement of plasma renin activity. Measurement of ADH is not generally helpful in distinguishing between these categories of hyponatraemia. This is because ADH is activated both in hypovol-aemic states and in most chronic hypervolaemic states, as the impaired circulation in those disorders activates ADH release through non-osmotic mechanisms.

Investigations The only disorders in which ADH is suppressed are primary polydipsia and iatrogenic water intoxication, where the hypoosmolar state inhibits ADH release from the pituitary.

Management The treatment of hyponatraemia is critically dependent on its rate of development, severity and underlying cause. If hyponatraemia has developed rapidly (over hours to days), and there are signs of cerebral oedema such as obtundation or convulsions, sodium levels should be restored to normal rapidly by infusion of hypertonic (3%) sodium chloride. A common approach is to give an initial bolus of 100 mL, which may be repeated once or twice over the initial hours of observation, depending on the neurological response and rise in plasma sodium.

Management On the other hand, rapid correction of hyponatraemia that has developed slowly (over weeks to months) can be hazardous, since brain cells adapt to slowly developing hypoosmolality by reducing the intracellular osmolality, thus maintaining normal cell volume . Under these conditions, an abrupt increase in extracellular osmolality can lead to water shifting out of neurons, abruptly reducing their volume and causing them to detach from their myelin sheaths. The resulting ‘myelinolysis’ can produce permanent structural and functional damage to mid-brain structures, and is generally fatal. The rate of correction of the plasma Na concentration in chronic asymptomatic hyponatraemia should not exceed 10 mmol/L/day, and an even slower rate is generally safer.

Management The underlying cause should be treated. For hypovolaemic patients, this involves controlling the source of sodium loss, and administering intravenous saline if clinically warranted. Patients with dilutional hyponatraemia generally respond to fluid restriction in the range of 600–1000 mL/day, accompanied where possible by withdrawal of the precipitating stimulus (such as drugs causing SIADH). If the response of plasma sodium is inadequate, treatment with demeclocycline (600–900 mg/day) may be of value by enhancing water excretion, through its inhibitory effect on responsiveness to ADH in the collecting duct.

Management Hypervolaemic patients with hyponatraemia need treatment of the underlying condition, accompanied by cautious use of diuretics in conjunction with strict fluid restriction. Potassium-sparing diuretics may be particularly useful in this context where there is significant secondary hyperaldosteronism.

Hypernatraemia Aetiology and clinical assessment hypernatraemia (plasma Na >148 mmol/L) reflects inadequate concentration of the urine in the face of restricted water intake. This can be due to failure to generate an adequate medullary concentration gradient (low GFR states, loop diuretic therapy), but more commonly it is due to failure of the ADH system, either because of pituitary damage (central or ‘cranial’ diabetes insipidus) or because the collecting duct cells are unable to respond to circulating ADH (nephrogenic dia-betes insipidus).

Aetiology and clinical assessment Patients with hypernatraemia generally have reduced cerebral function, either as a primary problem or as a consequence of the hypernatraemia itself, which results in dehydration of neurons and brain shrinkage. In the presence of an intact thirst mechanism and preserved capacity to obtain and ingest water, hypernatraemia may not progress very far. If adequate water is not obtained, dizziness, confusion, weakness and ultimately coma and death can result.

Management Treatment of hypernatraemia depends on both the rate of development and the underlying cause. If there is reason to think that the condition has developed rapidly, neuronal shrinkage may be acute and relatively rapid correction may be attempted. This can be achieved by infusing an appropriate volume of intravenous fluid (isotonic 5% dextrose or hypotonic 0.45% saline) at an initial rate of 50–70 mL/hour. However, in older, insti-tutionalised patients it is more likely that the disorder has developed slowly, and extreme caution should be exercised in lowering plasma sodium to avoid the risk of cerebral oedema. Where possible, the underlying cause should also be addressed

THANKS