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Disorders of calcium and magnesium balance: a physiology-based approach

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Abstract

Disorders of calcium and magnesium balance are physiologically interesting and clinically challenging. In this review, we attempt to bridge the gap between physiology and practice by providing a physiology-based approach to understanding hypocalcemia, hypercalcemia and hypomagnesemia. Calcium and, to a lesser extent, magnesium balance is achieved through a complex interplay between the parathyroid gland, bone, the intestine and the kidney. Our understanding of the molecular physiology of calcium and magnesium balance has grown considerably following the discovery of the calcium-sensing receptor (CaSR) and the main intestinal and renal transporters for calcium and magnesium, namely, the transient receptor potential channels TRPV5, TRPV6 and TRPM6. The regulation of parathyroid hormone (PTH) secretion by CaSR and the subsequent effects of PTH and vitamin D on TRPV5 constitute an increasingly characterized regulatory loop. In contrast, no truly magnesiotropic hormones have been identified, although the recently established interactions between the epidermal growth factor and TRPM6 suggest a possible candidate. Overall, the aim of this review is to illustrate the clinical disorders of calcium and magnesium balance from the perspective of their integrated physiology.

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Authors and Affiliations

  1. Department of Internal Medicine—Nephrology, Erasmus Medical Center, Room H-436, PO Box 2040, 3000 CA, Rotterdam, The Netherlands

    Ewout J. Hoorn & Robert Zietse

Authors
  1. Ewout J. Hoorn
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Correspondence to Ewout J. Hoorn.

Additional information

Correct answers

1.c

2.c

3.a

4.d

5.c

Multiple choice questions (answers are provided following the reference list)

Multiple choice questions (answers are provided following the reference list)

  1. 1.

    Which hormone regulates magnesium balance?

    1. a.

      Parathyroid hormone

    2. b.

      Fibroblast growth factor 23 (FGF23)

    3. c.

      No hormones primarily regulating magnesium balance have been identified

    4. d.

      1,25-dihydroxyvitamin D

  2. 2.

    In which part of the kidney does active magnesium transport take place?

    1. a.

      Proximal tubule

    2. b.

      Thick ascending limb

    3. c.

      Distal convoluted tubule

    4. d.

      Collecting duct

  3. 3.

    A patient with hypocalcemia has a high PTH but normal concentrations of 25-monohydroxyvitamin D and 1,25-dihydroxyvitamin D. Which cause is unlikely?

    1. a.

      Chronic kidney disease stage 2 or 3

    2. b.

      Loss of calcium from the circulation (eg due to binding or chelation)

    3. c.

      Pseudohypoparathyroidism

    4. d.

      Hypomagnesemia

  4. 4.

    Why are hypomagnesemia and hypokalemia often found together?

    1. a.

      Hypomagnesemia causes hypokalemia by stimulating potassium secretion

    2. b.

      Hypokalemia causes hypomagnesemia by stimulating magnesium excretion

    3. c.

      The same factors that cause hypokalemia often also cause hypomagnesemia

    4. d.

      Answers a and c are correct

    5. e.

      Answers b and c are correct

  5. 5.

    Which laboratory parameter can be used to differentiate Bartter syndrome from Gitelman syndrome?

    1. a.

      Serum potassium concentration

    2. b.

      Serum magnesium concentration

    3. c.

      Urinary calcium excretion

    4. d.

      Urinary sodium excretion

Correct answers

  1. 1.

    c

  2. 2.

    c

  3. 3.

    a

  4. 4.

    e

  5. 5.

    c

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Hoorn, E.J., Zietse, R. Disorders of calcium and magnesium balance: a physiology-based approach. Pediatr Nephrol 28, 1195–1206 (2013). https://doi.org/10.1007/s00467-012-2350-2

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