Skeletal Sodium: A Missing Element in Hypertension and Salt Excretion

Abstract

SKELETAL SODIUM: A MISSING ELEMENT IN HYPERTENSION AND SALT EXCRETION* A. R. MICHELLE The concept of a "kidney ofaccumulation" [1] is not generally applied to mammals except, perhaps, in heavy metal poisoning. Invertebrates, however, frequently deal with excess mineral by accumulating it in their exoskeleton in a form which is relatively insoluble and, therefore, physiologically inert. The present hypothesis proposes that the mammalian skeleton also has a role in excretion, failure of which contributes to disturbances of sodium balance and exacerbates some forms ofhypertension . Exclusion of this factor creates problems in relating such disturbances to salt intake. Bone contains approximately half the body sodium but debate has mainly concerned its importance as a sodium reservoir. With ions which are actively extruded from cells, however (e.g., sodium or calcium), the skeleton provides the only plausible way of sequestering any excess which temporarily cannot be excreted by the kidney. The striking ability of the kidney to excrete sodium dominates renal physiology but it has mainly been demonstrated in relation to transient infused loads, as Levinsky has noted [2]. Even so the upper limit of extracellular volume in man does not appear to be constant [3]. With chronic salt loads it is often difficult to account for the disposition of the sodium even when the problems of unmeasured losses are considered [4, 5]. Thus, in studies of normotensive humans, those on high salt intake showed an increase of exchangeable sodium (compared with controls) 20 percent beyond that accounted for by increased extracellular volume [6]. Bone water provides a sizeable pool of exchangeable sodium distinct from the sodium sequestered in the crystalline structure [7] and can readily accommodate such excess salt. On normal sodium intakes the renal response to dietary restriction is much slower than when body sodium is *This essay was selected for honorable mention in the first Perspectives Writing Award contest for authors 35 years old or younger. tNephrology section, Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637. I am indebted to the organisers of the 1975 Gordon Conference on Food and Nutrition for providing the environment which stimulated these speculations. Perspectives in Biology and Medicine · Autumn 1976 37 depleted [8] suggesting that a temporary excess can be stored prior to excretion. It is proposed that the skeleton acts as a kidney of accumulation for sodium, that high salt intake during skeletal growth creates a hazard for the future hypertensive, and that factors causing skeletal demineralization cause both a steady sodium load, even in salt restricted individuals, and an impairment of the ability to sequester excess sodium. Skeletal Sodium Deposition Infants and young animals fail to excrete sodium loads as promptly as adults [9]. Although this is usually attributed to renal immaturity, it could also reflect easier sodium incorporation into bone during active skeletal growth. Dahl [10] found that a brief period of high salt intake following weaning had a particularly potent effect on the subsequent development of hypertension. This period corresponds with a time of extremely rapid mineral uptake by bone [11] and it is proposed that the resulting high sodium levels [12] eventually prejudice the ability to sequester excess salt. Dahl also observed an ameliorating effect of potassium intake [13], although the daily intakes of sodium and potassium per body weight seem improbably high (equivalent to total body content). Nevertheless it is clear that skeletal potassium is high, especially in young animals [14], that bone sodium and potassium tend to show reciprocal changes, and that potassium loads might therefore protect against excessive skeletal sodium accumulation. The practical implication is that during skeletal growth excess salt intake should be avoided. Skeletal Sodium Mobilisation During sodium depletion, and particularly during acidosis, skeletal sodium is mobilised [15, 16]. Thus during renal failure the patient may be subjected to an endogenous salt load. Endogenous salt loading could also contribute to the enhanced extracellular fluid space and glomerular filtration rate which characterise normal pregnancy [17]; the ability to excrete exogenous salt loads is actually better during pregnancy [18]. Despite this, some degree of oedema is almost a normal feature of pregnancy in humans and animals. It is suggested that this reflects mobilisation of skeletal calcium and sodium. Thus as...