Abstract
Conclusion
1. Contrary to the prevailing view, hyperproteinemia (hypcrglobulinemia) is not “a cause of” or “responsible for” hypercalcemia; it does not lead to abstraction of calcium from the bones either directly, or indirectly lq upsetting the mass law relation 3 in the. blood. In hyperproteinemia, even in the absence of hyperphosphatemia, there is no proportionality between total serum protein and serum calcium levels, and no inference as to the calcium content of the blood can be drawn from the total protein content.
2 Where hypercalcemia does occur in conjunction with hyperproteinemia, as in some cases of multiple myeloma, the calcium increase may well be due, not to hyperproteinemia, but to the complication of co-existent bone destruction by neoplastic tissue; like the hypercalcemia occurring occasionally with metastatic osteolytic carcinoma, in which serum protein levels are normal or low. 6 , 9 The influx of Ca++ caused by bone destruction leads to an increase in protein-bound as well as in ionized calcium, with reëstablishment at higher levels of an equilibrium between these 2 fractions predictable by mass law considerations. 10 The absolute increase in the protein-bound calcium fraction, therefore, appears to be a result and not a cause of the hypercalcemia; the ratio diffusible Ca:total Ca remaining reasonably constant whether the serum protein is increased (multiple myeloma) or normal (hyperparathyroidism).
3. An inlcreased protein content of the serum is not essential to hold in solution such high calcium concentrations as occur in disease. Loeb and Nichols 11 showed that the calcium bound per gram protein is a function of the calcium concentration, the protein normally present in serum binding more calcium at increased than at normal calcium levels. This occurs, presumably, in hyperparathyroidism. In multiple myeloma with both hypercalcemia and hyperproteinemia, it seems not unlikely that most of the increase in calcium bound to protein is calcium bound by albumin; and little, if any, calcium is bound by the euglobulin increment responsible for the hyperproteinemia.
4. The discrepant relation of protein to calcium in hyperproteinemia is only a special case of the discrepant relation of protein to total base in hyperproteinemia. As was pointed out elsewhere, 5 the assumption that all of the serum globulin fraction in hyperglobulinemia binds as much base as the factor ‘B globulin’ in general use 12 icalls for, leads to the result that the sum of total determined acids appears to exceed the total base.
Methods. Serum calcium, inorganic phosphorus, total proteins and protein fractions were determined by methods described elsewhere. 5 The diffusible calcium fraction was estimated by ultrafiltration of 10-15 cc. serum samples through collodion sacs in a Simms apparatus 13 ; positive pressures of 40-50 mm. Hg. were applied, the serum being maintained under normal CO tensions, We are indebted to Dr. H. S. Simms and Mr. A. Stolman for their help.
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