MECHANISMS OF HYPONATREMIA IN SINGAPORE CHILDREN

Abstract

Hyponatremia occurs frequently in sick patients. Its pathogenesis is conventionally explained by excessive sodium loss and/or water excess. However, these standard mechanisms, more often cannot fully account for all the hyponatremia cases. Hence it is important to re-examine the causes of hyponatremia such that more effective treatment can be ensured. A possible alternative mechanism of hyponatremia is sick cell syndrome which causes a shift of sodium ions from the extracellular fluid into the intracellular compartment as a result of impaired sodium pump. This ingress of sodium ions into the cells at the expense of the extracellular fluid can provoke hyponatremia. Previous studies on hyponatremia had often neglected this possibility. In the present investigation of hyponatremia in children, both conventional mechanisms and sick cell hypothesis were taken into consideration. Altogether twenty-six hyponatremia patients and twenty-four normal controls were studied. Their plasma samples were analysed for osmolality, sodium, potassium, glucose and urea concentrations; erythrocytes for intracellular sodium, potassium and ATP concentrations; erythrocyte membranes for Na-K and total ATPase activity; urine samples from hyponatremia patients for sodium concentration and osmolality. From these laboratory data and clinical features of the patients, their mechanisms of hyponatremia were identified. Results indicate that approximately two thirds of the patients had a single cause of hyponatremia while the other one third was due to various combinations of causes. The three main conventional causes were SIADH, dilutional syndromes and extrarenal sodium loss. SIADH was associated with 38.5% of the patients. Dilutional syndromes and extrarenal sodium loss were each associated with 26. 9% of the cases. Another less frequently encountered cause diagnosed was adrenal insufficiency and this was present in 7.7% of the patients. Not all cases of hyponaremia can be explained by these standard mechanisms. The role of sick cell syndrome in causing hyponatremia was assessed from the erythrocyte sodium, potassium, ATP content and Na-K-ATPase activity. 9 hyponatremia cases ( i.e 34.6% of the patients) had increased erythrocyte sodium concentration and Na-K-ratio. Two of these patients had intrinsic cell membrane abnormality such that Na-K-ATPase activity was reduced, causing sodium ions to be accumulated inside the erythrocytes. The other seven cases had hypokalaemia. That hypokalaemia can cause inhibition of Na-K-ATPase activity was confirmed by measuring its activity in mediums containing varying amount of potassium ions. Hence hypokalaemia in these patients was the cause of impairment of sodium pump. The metabolic energy supply to the sodium pump in all these patients had been sufficient as shown by the normal quantity of ATP in erythrocytes. The fact that approximately one third of the patients showed sodium ingress into cells strongly indicates a significant role of sick cell syndrome in the pathogenesis of hyponatremia. The study therefore suggests that besides the commonly accepted mechanisms, sick cell syndrome could be another possible cause of hyponatremia.