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OBJECTIVES

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  • State the normal total plasma calcium concentration and the fraction that is free.

  • Describe the distribution of calcium between bone and extracellular fluid and the role of bone in regulating extracellular calcium.

  • Describe and compare the roles of the gastrointestinal tract and kidneys in calcium balance.

  • Describe and compare bone remodeling and plasma calcium buffering by bone.

  • Describe the role of vitamin D in calcium balance.

  • Describe how the synthesis of the active form of vitamin D (calcitriol) is regulated.

  • Describe the regulation of parathyroid hormone secretion and state the major actions of parathyroid hormone.

  • Describe the renal handling of phosphate.

  • Describe how parathyroid hormone changes renal phosphate excretion.

  • Describe the control of FGF23 production and its actions in the kidney.

  • Describe the major features of magnesium balance.

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OVERVIEW

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Calcium, magnesium, and phosphorus (in the form of phosphate) are major elemental constituents of the body, the majority of all of them being components of bone. Most of the non-bone fractions are compartmentalized in organelles within cells or complexed with cytosolic proteins, and only small fractions of any of these substances are free in the ECF. However, plasma levels of the free form of these ions, even though representing small percentages of total body amounts, are crucial for body function. Deviations lead to serious, even life-threatening pathologies. Calcium and phosphate are usually discussed together because both their physiological roles and mechanisms of regulation are intertwined. All three substances are regulated by cooperative interactions between the kidneys, the GI tract, and bone.

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The Chemistry of Calcium, Magnesium, and Phosphate

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The physiology and regulation of calcium, magnesium, and phosphate are critically dependent on their chemical properties. Calcium and magnesium are both divalent alkali metal cations that play similar roles in some contexts and different roles in others. Their free (non-complexed) concentrations in the ECF are roughly the same (∼1 mM), low enough so that they are not significant components of plasma osmolality. However, being divalent, they are major contributors to the layer of cations that are attracted to negative charges on plasma membranes and large plasma proteins. Alterations in plasma levels of either one of these species have major effects on the behavior of excitable cells because they alter the electric field sensed by voltage-gated channels. In contrast, their intracellular levels are vastly different from each other and these ions perform very different functions. Most intracellular magnesium is complexed with ATP or other negatively charged molecules. The concentration of the free dissolved component is about 0.5 mM, only slightly lower than in the ECF. In contrast, the free intracellular calcium concentration is less than 1000th of magnesium. This difference and their different functional roles within cells are due to nuances of their chemistry.

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As with all inorganic ions, calcium and magnesium are surrounded by hydration shells of water. Calcium is a larger ion and holds its water less ...

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