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

Abstract

The total serum calcium is composed of two major fractions: the non-diffusible or protein bound calcium, and the diffusible or ultrafiltrable calcium. The latter, containing predominantly ionic calcium, theoretically traverses capillary membranes in vivo and participates in metabolic processes at the cellular level.In a previous publication, a new simple method for the ultrafiltration of human serum was described (1). It was found that in normal adults, between 60 and 70 per cent of the calcium present in serum was ultrafiltrable. These findings were compared with the variable values reported by other authors for the normal percentage of ultrafiltrable calcium. 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. They used the Lavietes mercury-pressure ultrafiltration apparatus, controlled pH, and carried out the ultrafiltration procedure at room temperature.Utilizing the controlled technique previously described (1) METHODSPatients on the general medical wards of the Strong Memorial Hospital with abnormal total serum calcium values were selected for the study of the distribution of serum calcium in disease states. A definite diagnosis was established clinically in all cases. Blood was collected by venipuncture in the non-fasting state and serum ultrafiltered the same day. Another patient, who was being studied on the metabolism ward of the Department of Medicine, served as the subject for the detailed investigation of the effect of experimentally induced conditions on the ultrafiltrability of serum calcium. He was a 75 year old white man with chronic lymphatic leukemia and an annular carcinoma of the rectosigmoid. In spite of the two malignant processes, he appeared well nourished (body weight, 63 Kg.) and was generally asymptomatic but did have slight hypoproteinemia. 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

Some Effects of Magnesium Loading upon Renal Excretion of Magnesium and Certain Other Electrolytes1

“…the amount of magnesium bound to proteins rose proportionately to the total serum concentration of magnesium. They found the same to be true for calcium, as did Terepka, Toribara and Dewey (18). Thus, binding sites are available and Copeland and Sunderman (9) found that magnesium proteinate acts as a dissociated salt, following the mass action law with a calculated pK of 1.77.…”

Calcium Flux During Hemodialysis

“…Quench correction was calculated by the channel ratio technique, and all counts were converted to disintegrations per minute (dpm) per cm3. Ultra filtrable calcium was calculated as 60% of the total plasma calcium, based on previous studies in this and other laboratories that the ultrafiltrable calcium re mains relatively constant at values approximating this percentage if plasma protein concentration is normal [12][13][14][15][16][17][18]. (Plasma protein concentration was estimated in all samples by refractometry and was found to be normal.)…”

Renal Tubular Transport of Calcium

“…The ultrafilterability of calcium across glomerular capillaries is similarly reduced with hypercalcemia, as confirmed by sampling the glomerular filtrate in Munich-Wistar rats (96). Hypocalcemia is usually associated with a decline in ultrafilterability (133,209). Changes in serum protein concentration are accompanied by parallel changes in total serum calcium concentration so that the ultrafilterable fraction remains constant (132,162) except in severe hypoproteinemia, when it becomes elevated (101,209).…”

“…The ultrafilterable and ionized fractions of plasma calcium can be altered by several factors, including changes in total calcium concentration, blood pH, plasma protein concentration, and concentrations of complexing anions. Increases in total serum calcium concentration are usually paralleled by increases in the concentration of the ultrafilterable component up to a total conentration of -4 mM (65,127,133,209). At higher total calcium concentrations, the ultrafilterable fraction declines so that its rise does not match that for total calcium concentration.…”

“…Hypocalcemia is usually associated with a decline in ultrafilterability (133,209). Changes in serum protein concentration are accompanied by parallel changes in total serum calcium concentration so that the ultrafilterable fraction remains constant (132,162) except in severe hypoproteinemia, when it becomes elevated (101,209). Importantly, the free ionized calcium concentration varies inversely with blood pH such that acidemia causes an increase and alkalemia causes a decrease in ionized calcium concentration (101,132,162,186).…”