STROXTUM I\" MAX AXD RKAST 



per litre and of strontium is 40 fig or l^arely 1 acquiv. per litre. Thus, 

 raising the plasma level of strontium one h unci red ff)ld has an insignificant 

 effect on the combined molar concentration of calcium and strontium. 



Furllier evidence in support of this concept of central lack of discrimination 

 at a control centre is obtained from the work of MacDonald et al.'\ who 

 showed that adding calcium carriers to diets reduced the absorption of 

 strontium. If the control centre regulates the absorption of calcium from the 

 gut to amounts necessary for maintaining balance or optimal growth, then 

 by reducing the percentage of calcium al«orbed from diets high in calcium, 

 the percentage of strontium absorbed will be similarly limited if the strontium 

 intake is kept constant (which is in practice practically impossible, as all 

 natural sources of calcium contain strontium), or if the normal calcium to 

 strontium ratio is not markedly disturl:)cd, which is the condition likely to 

 be found experimentally. 



In addition, Wasserman et al.^^ have equilibrated rats on diets of adequate 

 calcium status, but varying by a factor of four in calcium (and therefore 

 probably strontium also). When a state of equilibrium was attained, 

 constant doses of radio-active calcium (Ca*) and strontium (Sr*) tracers were 

 added to each diet. The active isotopes were deposited in bone in such a 

 way that the radio-active strontium was deposited according to its concen- 

 tration in terms of calcium in the diet, that is, the observed ratio of Sr*/Ca* 

 bone to Sr*/Ca* diet was the same in each group. In other words, as far as 

 the master mechanism was concerned, strontium behaved as an analogue 

 of calcium; but individual mechanisms within the body did discriminate 

 between the two. That this result was obtained in virtue of the varying 

 calcium contents of the diet and not of the unmeasured stable strontium 

 contents was shown by a control experiment, in which varying the stable 

 strontium by a factor of four made no difference to the percentage uptake of 

 radio-active tracer strontium. 



The Mechanism of Peripheral Discrimination 

 The discrimination that does occur within various tissues can perhaps be 

 explained on purely physico-chemical grounds. The mechanism whereby 

 ions are actively carried across cells or cell membranes is still uncertain, but 

 it is possible to postulate that chelation plays some part. Nearly all chelating 

 agents so far investigated are more efficient binders of calcium than stron- 

 tium, the ratio of the appropriate constants for calcium and strontium being 

 usually in the region of two. Such a mechanism if common to membranes 

 in the gut, mammary gland and placenta would explain why each apparently 

 discriminates in favour of calcium by a factor of aljout two. The apparently 

 reverse phenomenon in the kidney is explicable in terms of renal physiology. 

 The glomeruli of the kidney merely passively excrete an ultrafiltrate of 

 plasma, 95 per cent or more of the volume of which is reabsorbed by the 

 tubules. The discriminating powers of the kidney lie largely in the tubules 

 and reabsorption of the so-called threshold substances almost certainly 

 favours calcium to strontium as in the other active processes. Harrison's 

 calculations suggest that the human kidney clears plasma of calcium at the 

 rate of 2 ml./min, but of strontium at about 8 ml./min. The clearance of 

 strontium is independent of the plasma levels of strontium within a range of 



120 



