Abstract
The volume and tonicity of body fluids are maintained within a narrow normal range by regulation of sodium and water balance. The volume of extracellular fluid is determined by total body sodium content whereas the osmolality and sodium concentration of extracellular fluid are determined by water balance. The kidney balances excretion of sodium and water with their intake and avidly conserves them when intake is restricted. Serum sodium concentration is an indication of the amount of sodium relative to the amount of water in extracellular fluid and provides no direct information about total body sodium content. Patients with hyponatraemia or hypernatraemia may have decreased, normal, or increased total body sodium content. An increased serum sodium concentration implies hyperosmolality whereas a decreased serum sodium concentration usually, but not always, implies hypoosmolality.
Hypernatraemia
Hypertonicity of extracellular fluid and hypernatraemia can be caused by a pure water deficit, loss of hypotonic fluid, or gain of sodium. The main causes of hypertonicity due to pure water deficit are hypodipsia due to neurologic disease and central or nephrogenic diabetes insipidus, which are associated with abnormal renal loss of water. Hypodipsia, hypernatraemia, and hypertonicity due to an abnormal thirst mechanism occur in young female miniature Schnauzers. Clinical signs include anorexia, lethargy, weakness, disorientation, ataxia, and seizures. These dogs can be managed clinically by addition of water to their food, but hypernatraemia and neurologic dysfunction recur whenever water supplementation is discontinued.
Central diabetes insipidus (CDI) is due to a partial or complete lack of vasopressin production and release in the neurohypophysis. It may be idiopathic or result from trauma or neoplasia. Animals with CDI have severe polydipsia and polyuria. Their urine typically is hyposthenuric but urine osmolality may approach 400–500 mOsm/kg in the presence of dehydration. Increased plasma osmolality and hypernatraemia are common, suggesting that affected dogs and cats do not obtain enough water to maintain water balance and are presented in a hypertonic state. Treatment with vasopressin restores medullary hypertonicity and normal urinary concentrating ability. Desmopressin is a structural analog of vasopressin that is available as an nasal spray or injectable solution. Chlorpropamide potentiates the renal tubular effects of small amounts of vasopressin and may be useful in management of animals with partial CDI. Nephrogenic diabetes insipidus (NDI) refers to a group of disorders in which there are structural or functional abnormalities that interfere with the ability of the kidneys to concentrate urine. Thiazide diuretics have been used to treat animals with CDI and NDI. Diuretic administration results in mild dehydration, enhanced proximal renal tubular reabsorption of sodium, decreased delivery of tubular fluid to the distal nephron, and reduced urine output. Restriction of dietary sodium and protein reduces the amount of solute that must be excreted in the urine each day and may further reduce obligatory water loss and polyuria.
Hypotonic fluid losses probably are the most common type encountered in small animal medicine. They may be classified as extrarenal (eg, gastrointestinal, third space, and cutaneous) or renal. Gastrointestinal losses include vomiting, diarrhoea, and small intestinal obstruction whereas third space losses include pancreatitis and peritonitis. Cutaneous losses usually are not clinically important in dogs and cats. Renal losses may result from osmotically- or chemically-induced diuresis or defective urinary concentrating ability due to intrinsic renal disease.
The development of hypertonicity due to excessive salt ingestion is unlikely if the animal in question has an intact thirst mechanism and access to water. Therapeutic administration of hyperosmolar solutions containing large amounts of sodium (eg, hypertonic saline, sodium bicarbonate) during cardiac resuscitation can cause transient hypernatraemia. Administration of sodium phosphate enemas and hyperadrenocorticism also may be associated with mild hypernatraemia.
The clinical signs of hypernatraemia are related to osmotic movement of water out of brain cells. The severity of clinical signs is related more to the rapidity of onset of hypernatraemia than to its magnitude. In dogs and cats, clinical signs of hypernatraemia are observed when the serum sodium concentration exceeds 170 mEq/l and include anorexia, lethargy, vomiting, weakness, disorientation, ataxia, seizures, coma, and death. If hypotonic losses are the cause of hypernatraemia, clinical signs of volume depletion may be observed. If hypernatraemia has developed as a result of gain of sodium, signs of volume overload (eg, pulmonary edema) may be observed, especially in patients with underlying cardiac disease.
The main goals of treatment in patients with hypernatraemia are to replace the water and electrolytes that have been lost and, if necessary, to facilitate renal excretion of excess sodium. The first priority in treatment should be to restore extracellular fluid volume to normal. The next priority is to diagnose and treat the underlying disease responsible for the water and electrolyte deficits. A pure water deficit can be replaced by giving 5% dextrose in water intravenously. The water deficit must be replaced and hypernatraemia corrected slowly over 48–72 h. Hypotonic losses cause more severe extracellular volume contraction than do losses of pure water. As a result, signs of volume depletion are more likely with hypotonic losses, and the original replacement fluid should be isotonic so that extracellular volume repletion proceeds rapidly. The patient with an excess of sodium-containing impermeant solute in the extracellular fluid can be treated by administration of 5% dextrose intravenously. The main disadvantage of this approach is that it will cause further expansion of the extracellular compartment in a patient already suffering from extracellular volume expansion. Administration of a loop diuretic (eg, furosemide) will promote excretion of the existing sodium load and hasten return of extracellular fluid volume to normal. As in the case of pure water deficit, it is essential that fluid administration proceed slowly and that serum sodium concentration be lowered gradually over 48–72 h to avoid neurologic complications.
Hyponatraemia
The first step in the approach to the patient with hyponatraemia is to determine whether or not hypoosmolality of the extracellular fluid actually is present. This can be determined by measurement of plasma osmolality. Evaluation of hyponatraemia then may be approached using the patient's plasma osmolality as a guide.
The occurrence of decreased serum sodium concentration as measured by flame photometry or indirect potentiometry with normal plasma osmolality is called pseudohyponatraemia. Pseudohyponatraemia occurs in conditions associated with hyperlipidaemia or severe hyperproteinaemia and has no specific consequences for the health of the patient. Treatment should be directed at the underlying disorder causing hyperproteinaemia or hyperlipidaemia. Hyponatraemia with hyperosmolality may be caused by hyperglycaemia in diabetes mellitus or mannitol administration.
The total body sodium content and extracellular fluid volume of patients with hyponatraemia and hypoosmolality may be normal, decreased, or increased. The second step in the evaluation of the patient with hyponatraemia therefore is to estimate total body sodium content and extracellular fluid volume status. The history may indicate a source of fluid loss whereas a complete physical examination provides the best evidence of the patient's volume status.
For a patient with volume depletion to develop hyponatraemia, the total body deficit of sodium must exceed that of water. Hyponatraemic patients with volume depletion have lost fluid by renal or non-renal routes. Gastrointestinal, third space, and cutaneous losses constitute the non-renal routes of fluid and salt loss. Fluid and salt loss by the renal route may be due to hypoadrenocorticism, diuretic administration, or renal disease. Hyponatraemia also has been associated with chronic blood loss in dogs.
Hyponatraemia may occur despite the presence of increased total body sodium and expansion of the extracellular fluid compartment in patients with ascites or edema. The pathophysiologic events in these patients impair the excretion of ingested water and exert a dilutional effect on the serum sodium concentration. Hyponatraemia with hypervolaemia is observed in three clinical conditions: congestive heart failure, severe liver disease and nephrotic syndrome.
Hyponatraemia with normovolaemia may occur as a result of primary (psychogenic) polydipsia, clinical conditions characterised by inappropriate secretion of vasopressin, administration of hypotonic fluids or drugs with anti-diuretic effects, and in myxedema coma of severe hypothyroidism. Overt signs of hypervolaemia are not usually present because the majority of retained water is distributed to the intracellular compartment. Apparent psychogenic polydipsia usually occurs in large breed dogs. These dogs have severe polydipsia, polyuria, and hyposthenuria and demonstrate mild plasma hypoosmolality and hyponatraemia. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) refers to vasopressin release in the absence of normal osmotic or non-osmotic stimuli. This syndrome may occur in patients with malignancies, pulmonary disease, or central nervous system disorders. A diagnosis of SIADH must be made by excluding other causes of hyponatraemia. Drugs that stimulate vasopressin release or potentiate its renal effects may lead to hyponatraemia with normovolaemia.
The clinical signs of hyponatraemia are related more to the rapidity of onset than to the severity of the associated plasma hypoosmolality. Reduction in plasma osmolality and influx of water into the central nervous system cause the clinical signs observed in acute hyponatraemia. Clinical signs may be absent in chronic disorders characterised by slower decreases in serum sodium concentration and plasma osmolality. Acute water intoxication is likely only if the patient has some underlying cause of impaired water excretion at the time a water load occurs. Signs may include lethargy, weight gain, vomiting, dyspnea, coma, and seizures.
The two main goals of treatment in hyponatraemia are to manage the underlying disease and, if necessary, to increase serum sodium concentration and plasma osmolality. Severe, symptomatic hyponatraemia of rapid onset is uncommon in clinical veterinary practice. In the more common clinical setting of chronic hyponatraemia, emphasis should be placed on appropriate treatment of the underlying disease. Patients with true volume depletion should receive an infusion of isotonic saline. Sodium is safely administered and the volume deficit also corrected using this approach. Only if hyponatraemia is severe (serum sodium <110–120 mEq/l) and the patient has neurologic signs attributed to hyponatraemia is use of hypertonic saline solutions justified. Water should carefully be restricted to an amount less than urine output in normovolaemic patients with hyponatraemia or drugs causing an antidiuretic effect should be discontinued if possible. In edematous patients, dietary sodium restriction and diuretic therapy should be considered. Hypertonic saline may be administered concurrently with loop diuretics (eg, furosemide) to effect more rapid correction of hyponatraemia in overhydrated symptomatic patients.