Hypocalcemia and Hypercalcemia

  • Mark R. Hughes
  • Wadi N. Suki

Abstract

Calcium is the fifth most abundant inorganic element of the body, the principal component of the human skeleton, and a vital participant in normal neuromuscular function, blood coagulation, membrane function, and multiple enzyme reactions. Its transmembrane flux plays a critical role in hormone secretion and metabolic coordination. Exquisitely sensitive homeostatic mechanisms have evolved to monitor and regulate the calcium ion in plasma while allowing an enormous reservoir to exist in bone where it principally serves a mechanical function. The normal adult human has roughly 25 g of total body calcium per kg of lean body mass (about 1–1.5 kg). Ninety-nine percent of it is present in bone as calcium phosphate while only 1% of skeletal calcium is freely exchangeable with the extracellular fluid. Mobilization of extensive amounts of skeletal calcium requires active resorption such as that promoted by vitamin D and parathyroid hormone (PTH). Perhaps the most frequent challenge to calcium homeostasis occurs with dietary calcium deprivation. When this occurs, a triad of efficient systems join to combat any tendency to hypocalcemia (Figure 1). Hormonally-induced bone resorption probably represents the most important mechanism by which sudden deficits in calcium homeostasis are overcome. Reduction in urinary excretion of calcium and increased efficiency of calcium absorption from the gut (in response to calcium deficiency) serve as additional mechanisms for maintaining extracellular fluid calcium; the renal effect is probably more important than previously realized. Renal reabsorption of calcium can rise to essentially 100% but this occurs only if the calcium level drops below 7 mg/dl. If calcium is low but above this level, PTH seems to be the principal effector involved in renal calcium conservation (1–10).

Keywords

Phosphorus Magnesium Adenoma Pancreatitis Prostaglandin 

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References

  1. 1.
    Bringhurst FR, Potts JT: Calcium and phosphate distribution, tumover, and metabolic actions. In: Endocrinology Vol II, DeGroot U (ed) New York, Grune & Stratton, 1979, p 551.Google Scholar
  2. 2.
    Glimcher MJ: Composition, structure and organization of bone and other mineralized tissues and the mechanism of calcification. In: Handbook of Physiology, Sec. 7: Endocrinology, Vol III, Aurbach GD (ed). Washington American Physiological Society, 1976, p25.Google Scholar
  3. 3.
    Sledge CB: Formation and resorption of bone. In: Textbook of Rheumatology, Kelley WN (ed). Philadelphia, Saunders, 1981, p277.Google Scholar
  4. 4.
    Parfitt AM, Kleerekoper M: Clinical disorders of calcium, phosphorus and magnesium metabolism. In: Clinical Disorders of Fluid and Electrolyte Metabolism, Maxwell MH, Kleeman CR (eds). New York, McGraw Hill, 1980, p947.Google Scholar
  5. 5.
    Rasmussen H, Bordier P: The Physiologic and Cellular Basis of Metabolic Bone Disease, Baltimore. Williams & Wilkins, 1974.Google Scholar
  6. 6.
    Borle AB: Parathyroid hormone and cell calcium. In: Calcium, Parathyroid Hormone, and Calcitonins, Talmage RV, Munson PL (eds). Amsterdam, Excerpta Medica, 1972.Google Scholar
  7. 7.
    Habner JF, Potts JT: Biosynthesis of parathyroid hormone. N Eng J Med 299: 580 - 635, 1978.CrossRefGoogle Scholar
  8. 8.
    Coop DH: Parathyroids, calcitonin and control of calcium. Recent Prog Horm Res 20: 59, 1964.Google Scholar
  9. 9.
    Segre GV, d’Amour P, Rosenblatt M, Potts JT: Heterogeneity and metabolism of parathyroid hormone. In: Endocrinology of Calcium Metabolism, Copp DH, Talmage RV (eds). Amsterdam, Excerpta Medica, 1978.Google Scholar
  10. 10.
    Habener JF, Potts JT: Parathyroid physiology and primary hyperparathyroidism. In: Metabolic Bone Disease, Avioli LV, Krane SM (eds). New York Academic Press, Vol II 1978, pi.Google Scholar
  11. 11.
    Wilkinson R: Absorption of calcium, phosphorus, and magnesium. In: Calcium, Phosphate, and Magnesium Metabolism. Nordin BEC (ed), London, churchill Livingstone, 1976.Google Scholar
  12. 12.
    Holick MF: The cutaneous photosynthesis of previtamin D: a unique photoendocrine system. J Inv Dermatol 76: 51, 1981.CrossRefGoogle Scholar
  13. 13.
    Haussler Mr, McCain BS: Basic and clinical concepts related to vitamin D metabolism and action. N Eng J Med 38. 297: 974, 1977.CrossRefGoogle Scholar
  14. 14.
    Hughes MR, Baylink DJ, Jones PG, Haussler MR: Radioligand receptor assay for 25-hydroxyvitamin D2/D3 and 39. 1,25-(OH)2D3: Application to hypervitaminosis D. J Clinical Investigation 58: 61, 1976.CrossRefGoogle Scholar
  15. 15.
    Bell NH: Hypercalcemic and hypocalcemic disorders: Diagnosis and treatment. Nephron 23: 147, 1979.PubMedCrossRefGoogle Scholar
  16. 16.
    Jaun D: Hypocalcemia: Diffemtial diagnosis and mechansims. Arch Intern Med 139: 1166, 1979.CrossRefGoogle Scholar
  17. 17.
    Paterson CR: Hypocalcemia: Differential diagnosis and investigation. Ann Clin Biochem 13: 578, 1976.PubMedGoogle Scholar
  18. 18.
    Slatopolsky E, Rosenbaum R, Mennes P, Klahr S: The hypocalcemia of magnesium depletion. Adv Exp Med Biol 103: 263, 1978.PubMedGoogle Scholar
  19. 19.
    Rastogi S, Arruda JAL: Hypocalcemia: Its clinical manifestations point to the diagnosis. Consultant July, 1983.Google Scholar
  20. 20.
    Mosekilde L, Melson F, Bagger JP, Sorenson NS: Bone changes in hyperthyroidism. Acta Endocrinol 85: 515, 1977.PubMedGoogle Scholar
  21. 21.
    Mosekilde L, Christensen MS: Decreased parathyroid function in hyperthyroidism. Acta Endocrinol 84: 566, 1977.PubMedGoogle Scholar
  22. 22.
    Kaptein EM, Singer FR, Nicoloff JT, Bishop JE, Norman AW: Plasma 1,25-dihydroxy vitamin D is decreased in hyperthyroidism. Clin Res 27: 369A, 1979.Google Scholar
  23. 23.
    Michie W, Duncan T: Mechanisms of hypocalcemia after thyroidectomy for thyrotoxicosis. Lancet 1: 508, 1971.PubMedCrossRefGoogle Scholar
  24. 24.
    Nagant deDeuxchasisnes C: Dissociation of parathyroid hormone bioactivity and immunoreactivity in pseudohypoparathyroidism type 1. J Clin Endocrinol Metab 53: 1105, 1981.CrossRefGoogle Scholar
  25. 25.
    Farfel Z: Defect of receptor-cyclase coupling protein in pseudo hypoparathyroidism. N Eng J Med 303: 237, 1980.CrossRefGoogle Scholar
  26. 26.
    Nordin BEC, Peacock M: Role of the kidney in regulation 50. of plasma calcium. Lancet 2: 1280, 1969.PubMedCrossRefGoogle Scholar
  27. 27.
    Porter RH, Cox BG, Heaney D, Hostetter TH, Stinebaugh BJ, Suki WN: Treatment of hypoparathyroid patients with 51. chlorthalidone. N Eng J Med 298: 577, 1978.CrossRefGoogle Scholar
  28. 28.
    Nagant de Dewxchaisnes C: Hyperparathyroidism. In: Metabolic Bone Disease. Vol 2, Avioli LV, Krane SM (eds). New York, Academic Press, 1978.Google Scholar
  29. 29.
    Myers WPL: Hypercalcemia associated with malignant disease. In: Endocrine and Nonendocrine Hormone-Producing Tumors. Chicago: Year Book Medical, 1973, p 147.Google Scholar
  30. 30.
    Gottlieb S, Rude RK, Sharp CF, Singer FR: Humoral hypercalcemia of malignancy: a syndrome in search of a hormone. Am J Med 73: 751, 1982.CrossRefGoogle Scholar
  31. 31.
    Heath H: Primary hyperparathyroidism: Incidence, morbidity, and potential economic impact in a commimity. N Eng J Med 302: 189, 1980.CrossRefGoogle Scholar
  32. 32.
    Castleman B, Schantz A, Roth SL: Parathyroid hyperplasia in primary hyperparathyroidism — A review of 85 cases. Cancer 38: 1668, 1976.PubMedCrossRefGoogle Scholar
  33. 33.
    Schantz A, Castleman B: Parathyroid carcinoma — A study of 70 cases. Cancer 31: 600, 1973.PubMedCrossRefGoogle Scholar
  34. 34.
    Baxter JD, Bondy PK: Hypercalcemia of thyrotoxicosis. Ann Internal Med 65: 429, 1966.Google Scholar
  35. 35.
    Parfitt AM, Dent CE: Hyperthyroidism and hypercalcemia. Q J Med 39: 171, 1970.PubMedGoogle Scholar
  36. 36.
    Adams PH, Jowsey J, Kelly PJ, et al: Effects of hyperthyroidism on bone and mineral metabolism in man. QJ Med 36: 1, 1976.Google Scholar
  37. 37.
    Shetty KR, Ajlouni K, Rosenfeld PS. Protracted vitamin D intoxication. Arch Internal Med 135: 986, 1975.CrossRefGoogle Scholar
  38. 38.
    Barbour GL. Hypercalcemia in an anephric patient with sarcoidosis. Evidence for extrarenal generation of 1,25 di- hydroxyvitamin D. N Eng J Med 305: 440, 1981.CrossRefGoogle Scholar
  39. 39.
    Suki WN, Hull AR, Rector FC, et al: Mechanism of the effect of thiazide diuretics on calcium and uric acid. Clin Research 15: 78, 1967.Google Scholar
  40. 40.
    Brinkman AS, Massry SG, Cobum JW. Changes in serum and urinary calcium during treatment with hydorchlorthiazide. J ain Invest 51: 945, 1972.CrossRefGoogle Scholar
  41. 41.
    McMillian DE, Freeman RB: The milk alkali syndrome: A study of the acute disorder with comments of the development of the chronic condition. (Medicine 44: 485, 1965.Google Scholar
  42. 42.
    Pederson KO: Hypercalcemia in Addisons disease. Acta Med Scand 181: 691, 1967.CrossRefGoogle Scholar
  43. 43.
    Frame B, Jackson CE, Reynolds WA, Unphrey JE: Hypercalcemia and skeletal effects of chronic hypervitaminosis A. Ann Internal Med 80: 44, 1974.Google Scholar
  44. 44.
    Raisz LH: Comparison of commercially available parathyroid hormone immunoassays in differential diagnosis of hypercalcemia due to primary hyperparathyroidism of malignancy. Ann Int Med 91: 739, 1979.PubMedGoogle Scholar
  45. 45.
    Stewart AF: Biochemical evaluation of patients with cancer-associated hypercalcemia. N Eng J Med 303: 1377, 1980.CrossRefGoogle Scholar
  46. 46.
    Deftos U, Nees RM: Medical management of the hypercalcemia of malignancy. Ann Rev Med 25: 323, 1974.PubMedCrossRefGoogle Scholar
  47. 47.
    Suki Wn, Yium JJ, VonMinden M, Eknoyan G, Martinez- Maldonado M: Acute treatment of hypercalcemia with furosemide. N Eng J Med 283: 836, 1970.CrossRefGoogle Scholar
  48. 48.
    Rodman JS, Sherwood LM: Disorders of mineral metabolism. In: Metabolic Bone Disease, Vol 2, Avioli LV, Krane S, (eds). New York, Academic Press, 1978, p578,.Google Scholar
  49. 49.
    Strauck BS, Ball MF: Hemodialysis in the treatment of severe hypercalcemia. JAMA 235: 1347, 1976.CrossRefGoogle Scholar
  50. 50.
    Nolph KD, Stoh M, Maher JF: Calcium free peritoneal dialysis. Treatment of vitamin D intoxication. Arch Int Med 128: 809, 1971.CrossRefGoogle Scholar
  51. 51.
    Stolz ML, Nolph KD, Maher JF: Factors affecting calcium removal with calcium-free peritoneal dialysis. J Lab Clin Med 78: 389, 1971.Google Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston/ The Hague/ Dordrecht/ Lancaster 1984

Authors and Affiliations

  • Mark R. Hughes
  • Wadi N. Suki

There are no affiliations available

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