Effects of hypercalcemia on serum concentrations of magnesium, potassium, and phosphate and urinary excretion of electrolytes in horses

Ramiro E. Toribio Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Search for other papers by Ramiro E. Toribio in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Catherine W. Kohn Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Search for other papers by Catherine W. Kohn in
Current site
Google Scholar
PubMed
Close
 VMD
,
Kelly M. Rourke Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Search for other papers by Kelly M. Rourke in
Current site
Google Scholar
PubMed
Close
 BS
,
Andrea L. Levine Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Search for other papers by Andrea L. Levine in
Current site
Google Scholar
PubMed
Close
 BS
, and
Thomas J. Rosol Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Search for other papers by Thomas J. Rosol in
Current site
Google Scholar
PubMed
Close
 DVM, PhD

Abstract

Objective—To determine effects of experimentally induced hypercalcemia on serum concentrations and urinary excretion of electrolytes, especially ionized magnesium (iMg), in healthy horses.

Animals—21 clinically normal mares.

Procedures—Horses were assigned to 5 experimental protocols (1, hypercalcemia induced with calcium gluconate; 2, hypercalcemia induced with calcium chloride; 3, infusion with dextrose solution; 4, infusion with sodium gluconate; and 5, infusion with saline [0.9% NaCl] solution). Hypercalcemia was induced for 2 hours. Dextrose, sodium gluconate, and saline solution were infused for 2 hours. Blood samples were collected to measure serum concentrations of electrolytes, creatinine, parathyroid hormone, and insulin. Urine samples were collected to determine the fractional excretion of ionized calcium (iCa), iMg, sodium, phosphate, potassium, and chloride.

Results—Hypercalcemia induced by administration of calcium gluconate or calcium chloride decreased serum iMg, potassium, and parathyroid hormone concentrations; increased phosphate concentration; and had no effect on sodium, chloride, and insulin concentrations. Hypercalcemia increased urinary excretion of iCa, iMg, sodium, phosphate, potassium, and chloride; increased urine output; and decreased urine osmolality and specific gravity. Dextrose administration increased serum insulin; decreased iMg, potassium, and phosphate concentrations; and decreased urinary excretion of iMg. Sodium gluconate increased the excretion of iCa, sodium, and potassium.

Conclusions and Clinical Relevance—Hypercalcemia resulted in hypomagnesemia, hypokalemia, and hyperphosphatemia; increased urinary excretion of calcium, magnesium, potassium, sodium, phosphate, and chloride; and induced diuresis. This study has clinical implications because hypercalcemia and excessive administration of calcium have the potential to increase urinary excretion of electrolytes, especially iMg, and induce volume depletion.

Abstract

Objective—To determine effects of experimentally induced hypercalcemia on serum concentrations and urinary excretion of electrolytes, especially ionized magnesium (iMg), in healthy horses.

Animals—21 clinically normal mares.

Procedures—Horses were assigned to 5 experimental protocols (1, hypercalcemia induced with calcium gluconate; 2, hypercalcemia induced with calcium chloride; 3, infusion with dextrose solution; 4, infusion with sodium gluconate; and 5, infusion with saline [0.9% NaCl] solution). Hypercalcemia was induced for 2 hours. Dextrose, sodium gluconate, and saline solution were infused for 2 hours. Blood samples were collected to measure serum concentrations of electrolytes, creatinine, parathyroid hormone, and insulin. Urine samples were collected to determine the fractional excretion of ionized calcium (iCa), iMg, sodium, phosphate, potassium, and chloride.

Results—Hypercalcemia induced by administration of calcium gluconate or calcium chloride decreased serum iMg, potassium, and parathyroid hormone concentrations; increased phosphate concentration; and had no effect on sodium, chloride, and insulin concentrations. Hypercalcemia increased urinary excretion of iCa, iMg, sodium, phosphate, potassium, and chloride; increased urine output; and decreased urine osmolality and specific gravity. Dextrose administration increased serum insulin; decreased iMg, potassium, and phosphate concentrations; and decreased urinary excretion of iMg. Sodium gluconate increased the excretion of iCa, sodium, and potassium.

Conclusions and Clinical Relevance—Hypercalcemia resulted in hypomagnesemia, hypokalemia, and hyperphosphatemia; increased urinary excretion of calcium, magnesium, potassium, sodium, phosphate, and chloride; and induced diuresis. This study has clinical implications because hypercalcemia and excessive administration of calcium have the potential to increase urinary excretion of electrolytes, especially iMg, and induce volume depletion.

  • 1

    Brown EM, MacLeod RJ. Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 2001;81:239297.

  • 2

    Barbagallo M, Dominguez LJ, Galioto A, et al. Role of magnesium in insulin action, diabetes and cardio-metabolic syndrome X. Mol Aspects Med 2003;24:3952.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3

    Dai LJ, Ritchie G, Kerstan D, et al. Magnesium transport in the renal distal convoluted tubule. Physiol Rev 2001;81:5184.

  • 4

    Hoenderop JG, Bindels RJ. Epithelial Ca2+ and Mg2+ channels in health and disease. J Am Soc Nephrol 2005;16:1526.

  • 5

    Ward DT, Riccardi D. Renal physiology of the extracellular calcium-sensing receptor. Pflugers Arch 2002;445:169176.

  • 6

    Carlstedt F, Lind L, Rastad J, et al. Parathyroid hormone and ionized calcium levels are related to the severity of illness and survival in critically ill patients. Eur J Clin Invest 1998;28:898903.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7

    Garcia-Lopez JM, Provost PJ, Rush JE, et al. Prevalence and prognostic importance of hypomagnesemia and hypocalcemia in horses that have colic surgery. Am J Vet Res 2001;62:712.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    Johansson AM, Gardner SY, Jones SL, et al. Hypomagnesemia in hospitalized horses. J Vet Intern Med 2003;17:860867.

  • 9

    Toribio RE, Kohn CW, Chew DJ, et al. Comparison of serum parathyroid hormone and ionized calcium and magnesium concentrations and fractional urinary clearance of calcium and phosphorus in healthy horses and horses with enterocolitis. Am J Vet Res 2001;62:938947.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Toribio RE. Disorders of the endocrine system. In:Reed SM, Bayly WM, Sellon DC, ed.Equine internal medicine. 2nd ed.St Louis: Saunders, 2004;12951379.

    • Search Google Scholar
    • Export Citation
  • 11

    Soliman HM, Mercan D, Lobo SS, et al. Development of ionized hypomagnesemia is associated with higher mortality rates. Crit Care Med 2003;31:10821087.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Adami S, Parfitt AM. Calcium-induced natriuresis: physiologic and clinical implications. Calcif Tissue Int 2000;66:425429.

  • 13

    El-Hajj FG, Seifter J, Scott J, et al. Calcium-regulated renal calcium handling in healthy men: relationship to sodium handling. J Clin Endocrinol Metab 1998;83:23662372.

    • Search Google Scholar
    • Export Citation
  • 14

    Gill JR Jr, Bartter FC. On the impairment of renal concentrating ability in prolonged hypercalcemia and hypercalciuria in man. J Clin Invest 1961;40:716722.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Wang W, Kwon TH, Li C, et al. Reduced expression of Na-K-2Cl cotransporter in medullary TAL in vitamin D-induced hypercalcemia in rats. Am J Physiol Renal Physiol 2002;282:F34F44.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Toribio RE, Kohn CW, Capen CC, et al. Parathyroid hormone (PTH) secretion, PTH mRNA and calcium-sensing receptor mRNA expression in equine parathyroid cells, and effects of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha on equine parathyroid cell function. J Mol Endocrinol 2003;31:609620.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Martell AE. Critically selected stability constants of metal complexes. Version 5.0. Gaithersburg, Md: United States Department of Commerce, National Institute of Standards and Technology, Standard Reference Data Program, 1997.

    • Search Google Scholar
    • Export Citation
  • 18

    Joint FAO/WHO Expert Committee on Food Additives. International Programme on Chemical Safety. WHO Food Additives Series 42. Geneva: World Health Organization, 1999. Available at: www.inchem.org/documents/jecfa/jecmono/v042je12.htm. Accessed May 1, 2006.

    • Search Google Scholar
    • Export Citation
  • 19

    Gajatto S. Pharmacological research on sodium gluconate. Arch Farmacol Sper Sci Affin 1939;68:113.

  • 20

    Stetten MR, Stetten D Jr.. The metabolism of gluconic acid. J Biol Chem 1950;187:241252.

  • 21

    Stetten MR, Topper YJ. Pathways from gluconic acid to glucose in vivo. J Biol Chem 1953;203:653664.

  • 22

    Toribio RE, Kohn CW, Sams RA, et al. Hysteresis and calcium set-point for the calcium parathyroid hormone relationship in healthy horses. Gen Comp Endocrinol 2003;130:279288.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Coulston F, Hulme NA, Mielens ZE, et al. Comparison of parenterally administered calcium kinate gluconate with calcium gluconate and calcium chloride. Toxicol Appl Pharmacol 1962;4:492503.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24

    Toribio RE, Kohn CW, Hardy J, et al. Alterations in serum parathyroid hormone and electrolyte concentrations and urinary excretion of electrolytes in horses with induced endotoxemia. J Vet Intern Med 2005;19:223231.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Gabrielsson J, Weiner D. Pharmacodynamic concepts. In:Gabrielsson J, Weiner D, ed.Pharmacokinetic and pharmacodynamic data analysis: concepts and applications. 2nd ed.Stockholm: Swedish Pharmaceutical Press, 1997;172248.

    • Search Google Scholar
    • Export Citation
  • 26

    Carr CW. Competitive binding of calcium and magnesium with serum albumin. Proc Soc Exp Biol Med 1955;89:546549.

  • 27

    Dai LJ, Ritchie G, Bapty BW, et al. Insulin stimulates Mg2+ uptake in mouse distal convoluted tubule cells. Am J Physiol 1999;277:F907F913.

    • Search Google Scholar
    • Export Citation
  • 28

    Brandle M, Pfammatter T, Spinas GA, et al. Assessment of selective arterial calcium stimulation and hepatic venous sampling to localize insulin-secreting tumours. Clin Endocrinol (Oxf) 2001;55:357362.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    McKenzie EC, Valberg SJ, Godden SM, et al. Comparison of volumetric urine collection versus single-sample urine collection in horses consuming diets varying in cation-anion balance. Am J Vet Res 2003;64:284291.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30

    Clausen T. Clinical and therapeutic significance of the Na+, K+ pump. Clin Sci (Lond) 1998;95:317.

  • 31

    Shiber JR, Mattu A. Serum phosphate abnormalities in the emergency department. J Emerg Med 2002;23:395400.

  • 32

    Murer H, Hernando N, Forster I, et al. Proximal tubular phosphate reabsorption: molecular mechanisms. Physiol Rev 2000;80:13731409.

  • 33

    Hausman E. Change in plasma phosphate concentration on infusion of calcium gluconate or Na2EDTA. Proc Soc Exp Biol Med 1970;134:182184.

  • 34

    Hiatt HH, Thompson DD. Some effects of intravenously administered calcium on inorganic phosphate metabolism. J Clin Invest 1957;36:573580.

  • 35

    Chen PS Jr, Neuman WF. Renal excretion of calcium by the dog. Am J Physiol 1955;180:623631.

  • 36

    Forster IC, Traebert M, Jankowski M, et al. Protein kinase C activators induce membrane retrieval of type II Na+-phosphate cotransporters expressed in Xenopus oocytes. J Physiol 1999;517:327340.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37

    Berndt TJ, Knox FG. Proximal tubule site of inhibition of phosphate reabsorption by calcitonin. Am J Physiol 1984;246:F927F930.

  • 38

    Levi M, Molitoris BA, Burke TJ, et al. Effects of vitamin D–induced chronic hypercalcemia on rat renal cortical plasma membranes and mitochondria. Am J Physiol 1987;252:F267F275.

    • Search Google Scholar
    • Export Citation
  • 39

    Sands JM, Naruse M, Baum M, et al. Apical extracellular calcium/ polyvalent cation-sensing receptor regulates vasopressin-elicited water permeability in rat kidney inner medullary collecting duct. J Clin Invest 1997;99:13991405.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40

    Salem M, Kasinski N, Munoz R, et al. Progressive magnesium deficiency increases mortality from endotoxin challenge: protective effects of acute magnesium replacement therapy. Crit Care Med 1995;23:108118.

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement