Divalent ion metabolism in patients with acute renal failure: Studies on the mechanism of hypocalcemia

The effect of hypermagnesemia, produced by MgCl(2) infusion, on the activity of parathyroid glands, as assessed by changes in levels of serum calcium (S(Ca)) and in the fraction of filtered phosphate excreted (C(P)/C(Cr)), was studied in 11 intact and 4 thyroparathyroidectomized (T-PTX) dogs. To exclude the effect of diurnal variation in C(P)/C(Cr) on the results, studies were initiated in both morning and afternoon hours and each study with MgCl(2) infusion was paired with a control experiment in the same dog not receiving MgCl(2). During MgCl(2) infusion, serum phosphorus rose progressively. Despite this rise, the levels of C(P)/C(Cr) fell in all experiments and were significantly different from values observed at the same time of the day in the paired control experiments. The concentrations of total S(Ca) fell by 1.0-2.4 mg/100 ml with a proportional decrease in the levels of the diffusible and ionized fractions. The pattern of the fall in C(P)/C(Cr) during MgCl(2) resembled that observed after CaCl(2) infusion (seven dogs) and that which acutely followed thyroparathyroidectomy (seven dogs). When parathyroid extract was given to dogs receiving MgCl(2) infusion both C(P)/C(Cr) and S(Ca) rose, and MgCl(2) infusion did not affect C(P)/C(Cr) and S(Ca) in T-PTX dogs. These results indicate that hypermagnesemia suppresses the activity of the parathyroid glands, probably, by inhibiting production and (or) release of the hormone, without interfering with end-organ response. An increase in serum magnesium of 1.7-2.0 mg/100 ml was capable of producing the suppressive effect. Evaluation of the effect of simultaneous modest hypocalcemia and hypermagnesemia suggests that a decrease in the level of serum calcium is more potent than an increase in the concentration of serum magnesium in the regulation of parathyroid activity.

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Evidence for suppression of parathyroid gland activity by hypermagnesemia

This article will review the methods currently available to the clinician and research worker for measuring the concentration of ionized calcium in various body fluids including whole blood, serum, plasma, urine, cerebrospinal fluid, milk, and synovial fluid. The methods to be reviewed are based on procedures involving bioluminescence, colorimetry and ion-selective electrodes. Emphasis will be given to the precision and, wherever possible, accuracy of each technique. Possible sources of error and interfering agents will be identified. Attention will be given to the recommended conditions for measuring ionized calcium in each body fluid. An assessment will be made of the theoretical and practical importance of measuring ionized calcium rather than total calcium and of its value in clinical medicine.

Ionized calcium in body fluids.

This article will review the methods currently employed for measuring the concentrations of total and ionized calcium in serum or plasma. As far as total calcium is concerned, various techniques such as atomic absorption spectrometry, spectrophotometry, fluorometry, complexometric titration, and flame photometry will be described and compared. Particular emphasis will be given to the accuracy and precision of each technique. Possible sources of error and interfering agents will be identified and the various procedures for the taking and handling of blood samples evaluated. Inter-laboratory variation in the measurement of calcium will be studied. An assessment will be made of a new reference method for measuring total calcium in serum using isotope-dilution mass spectrometry. The usefulness of the total calcium measurement in clinical medicine will be briefly discussed. Within the last decade the refinement of spectrophotometric techniques and the improvements in ion-selective electrode technology have revolutionized the measurement of ionized calcium in serum, such that it may now be possible to replace total calcium measurements with ionized calcium measurements on a routine basis. The various techniques currently in use for measuring ionized calcium will be described and evaluated. Particular attention will be paid to the preparation of standards, the procedures for taking blood samples, and the handling of the samples prior to and during measurement. An assessment of the relative value of measuring total and ionized calcium will be presented.

Calcium measurements in serum and plasma--total and ionized.

1.

The composition of the hemolymph of the crayfish Orconectes limosus was analysed with respect to seasonal variations of its constituents and to the influence of moulting, sex, size and injury. Freezing point depression, sodium, potassium, calcium, magnesium, chloride, acid-soluble phosphate, total phosphorus, lactic acid, copper, protein, non-protein nitrogen, urea, acid-soluble glucose and hexose, number of blood cells and pH were analysed for a 14 months period using 450 animals.




2.

Protein is the most important buffer substance in the hemolymph. Only 18% of the buffer capacity is removed by dialysis. The hemolymph contains about 0.5% copper-free protein. The copper content of crayfish hemocyanin was 0.176 mg copper per g protein. Ultrafiltration experiments showed that sodium, potassium, chloride, glucose and urea pass freely into the filtrate. About one third of the amounts of total phosphorus, non-protein nitrogen and acid-soluble hexose are retained. 18% of both calcium and magnesium appear to be bound by protein.




3.

Most of the constituents analysed showed the same annual pattern of variation: the greatest concentrations were found during the winter months, followed by a sharp decline in the spring, a recovery to medium summer levels before the beginning of the moulting period and a subsequent rise to higher winter values. The amplitude of variation was about ±10% around the mean for the freezing point depression, chloride and sodium, but larger for most other parameters. From the close correspondence between changes in freezing point depression and temperature of the ambient water it was deduced that temperature is a major factor in determining the overall concentration of the hemolymph.




4.

Changes in hemolymph composition in connection with moulting were studied in June and July using 160 animals. During premoult the concentrations of all constituents rise above the intermoult level (about 10% in the case of the inorganic ions). With ecdysis there is a sharp decline in concentrations. Sodium, chloride and potassium decrease by 30% to about 80% of the intermoult values. Total phosphorus, magnesium, non-protein nitrogen and protein reach intermoult levels, while glucose and acid-soluble phosphate decline much farther. Calcium values remain above the intermoult level for about one week following moult. Urea is exceptional as its concentration rises from late premoult through ecdysis and postmoult. The amount of water taken up during the moulting process is calculated to be equivalent to at least 12% of the body weight.




5.

Sexual variation in hemolymph composition seems to be very limited. Females have higher glucose and protein levels and smaller freezing point depressions during winter and higher calcium concentrations during the summer months than males.




6.

Correlation analysis revealed that larger animals tend to have higher potassium values, lower freezing point depressions and lower levels of most of the organic constituents than smaller ones. There is no significant correlation between size and sodium, chloride, calcium or magnesium concentrations.




7.

The changes in hemolymph composition which occured with oviposition and after injury were qualitatively similar to those observed after ecdysis, although the decline of concentrations was less evident.




8.

Van Harreveld's saline seems to be a suitable physiological solution for the animal under consideration. However, suggestions have been made to replace the original bicarbonate buffer by an organic buffer system.

J. Ettori

Papers

A determination of ionized calcium in serum by two- wavelength spectrophotometry of a metal indicator.