The total and diffusible calcium of serum and the calcium of cerebrospinal fluid in human cases of hypocalcaemia and hypercalcaemia

Abstract

CASES of hypocalcaemia may be divided into three groups. Firstly, there are the various types of low-calcium tetany. Secondly, there are cases of hypocalcaemia associated with low serum-protein, in which no symptoms of tetany occur; this condition may be present in nephrosis, chronic nephritis with oedema, kala-azar and some other conditions. Thirdly, there are cases of chronic nephritis with uraemia, in which the inorganic phosphorus of the serum is increased, and in which the serum-proteins may be normal or only moderately reduced; in some instances neuromuscular irritability and carpopedal spasm occur in addition to uraemic manifestations. One would expect that in tetany a low [Ca++] would be the significant change. The ionic calcium may or may not account for the whole of the diffusible calcium of serum, but it must be included in the diffusible fraction. It would also be expected that when the serum-calcium falls in response to a rise in the inorganic phosphate, the diffusible fraction would be primarily affected, though the change in the diffusible fraction would lead to a secondary change in the protein-bound fraction as a result of the disturbance of equilibrium. On the other hand, where the serum-calcium falls as a result of a fall in the serumprotein, one would expect the protein-bound fraction to be reduced and the diffusible fraction normal, and the absence of tetany would thus be explained. Now those authors who have used the concentration of calcium in the cerebrospinal fluid as a measure of the diffusible calcium of the serum have arrived at results which are inconsistent with the above views, for it has been shown that when the serum-calcium falls in tetany, the calcium of the cerebrospinal fluid is relatively little changed. Authors who have determined the diffusible calcium of the serum by ultrafiltration or dialysis have arrived at variable results, but, on the whole, work done on ultrafiltration of human sera has shown that the diffusible calcium is decreased in tetany and normal in cases of hypocalcaemia with low serum-protein. The view that the calcium of cerebrospinal fluid is equal to the diffusible calcium of serum has been attacked, but as yet only a few comparisons between the cerebrospinal fluid and the serum ultrafiltrate have been made in cases where the total serum-calcium is abnormal. At the outset of the present work the intention was to make comparisons between the calcium of serum and of cerebrospinal fluid in conditions where the

A Note on the Metabolic Criteria of Hyperparathyroidism

“…The literature yields twenty-three instances of hypercalcemia in multiple myeloma where serum proteins were simultaneously determined. In fourteen of these, hyperproteinemia was observed (19,22,24,27,28,33,37) in four hypoproteinemia obtained (10,13,18,19) and in five the total serum proteins were normal (10,19,23,29,39). Only four reports of the condition of the parathyroid glands at autopsy have been found in a series of over thirty case reports of multiple myeloma with hypercalcemia.…”

“…Herbert's (22) filtration studies with serum containing comparably elevated concentrations of protein and calcium (Patient A Ho) indicate that both diffusible and non-diffusible fractions of the serum calcium share in the total increase. In Case 3 the terminal elevation of serum calcium was not accompanied by any increase in the serum proteins; nevertheless both protein-bound and filtrable calcium were increased proportionately.…”

The Ultrafiltrable Calcium of Human Serum. Ii. Variations in Disease States and Under Experimental Conditions1

“…It was pointed out that virtually all previous workers had failed to control both the pH and the temperature during their ultrafiltration procedures. Our data indicated that these variables had a considerable effect on the ultrafiltrability of serum calcium, thus offering an explanation for the lack of agreement, particularly among the early workers (2), in the study of normal and abnormal sera. Only the recent data of Hopkins,Connor,and Howard (3) show reasonable consistency for specific disease states.…”

“…No evidence of bone involvement with cancer was apparent clinically, by X-ray or balance study. 2 The higher values for ultrafiltrable calcium in the studies of Hopkins, Connor, and Howard (3) probably resulted because these authors carried out their ultrafiltration procedures at room temperature instead of 370 C. 87 …”

Calcium metabolism and mental disorder

“…Nor does acute infusion of calcium solutions into normal men (Nordin & Fraser, 1956), or of ethylene diamine tetra-acetate to complex the calcium and reduce the effective plasma level (Fourman et al 1963) provoke EEG change or evident mental abnormality. Furthermore, it has long been known (Herbert, 1933), and frequently confirmed, that the calcium content of lumbar cerebrospinal fluid remains remarkably constant in spite of big changes in plasma calcium in parathyroid disease. There is a paradox here: clinically, exposure to high calcium disturbs the brain, but physiologically a bloodbrain barrier guards the brain against calcium change (Wallach et al 1964).…”