BASIC PHARMACOLOGY
Calcium
and phosphate, the major mineral constituents of bone, are also two of the most
important minerals for general cellular function. Accordingly, the body has
evolved complex mechanisms to carefully maintain calcium and phosphate
homeostasis (Figure 42–1). Approximately 98% of the 1–2 kg of calcium and 85%
of the 1 kg of phosphorus in the human adult are found in bone, the principal
reservoir for these minerals. This reservoir is dynamic, with con-stant
remodeling of bone and ready exchange of bone mineral with that in the
extracellular fluid. Bone also serves as the princi-pal structural support for
the body and provides the space for hematopoiesis. This relationship is more
than fortuitous as ele-ments of the bone marrow affect skeletal processes just
as skeletal elements affect hematopoeitic processes. Abnormalities in bone
mineral homeostasis can lead to a wide variety of cellular dysfunc-tions (eg,
tetany, coma, muscle weakness), and to disturbances in structural support of
the body (eg, osteoporosis with fractures) and loss of hematopoietic capacity (eg,
infantile osteopetrosis).
Calcium and phosphate enter the body from the intestine. The average American diet provides 600–1000 mg of calcium per day, of which approximately 100–250 mg is absorbed. This amount represents net absorption, because both absorption (principally in the duodenum and upper jejunum) and secretion (principally in the ileum) occur. The quantity of phosphorus in the American diet is about the same as that of calcium. However, the efficiency of absorption (principally in the jejunum) is greater, ranging from 70% to 90%, depending on intake. In the steady state, renal excre-tion of calcium and phosphate balances intestinal absorption. In general, over 98% of filtered calcium and 85% of filtered phosphate is reabsorbed by the kidney. The movement of calcium and phos-phate across the intestinal and renal epithelia is closely regulated. Dysfunction of the intestine (eg, nontropical sprue) or kidney (eg, chronic renal failure) can disrupt bone mineral homeostasis.
Three hormones serve as
the principal regulators of calcium and phosphate homeostasis: parathyroid hormone (PTH),fibroblast growth
factor 23 (FGF23), and vitamin D (Figure
42–2). Vitamin D is a prohormone rather than a true
PTH stimulates the production
of the active metabolite of vitamin D, 1,25-dihydroxyvitamin D (1,25[OH]2D),
in the kidney. Other tissues also produce 1,25(OH)2D; the control of
this production differs from that in the kidney, as will be discussed
subsequently. The complex interplay among PTH, FGF23, and 1,25(OH)2D
is discussed in detail later. To summarize briefly: 1,25(OH)2D
suppresses the production of PTH as does calcium, whereas phosphate stimulates
PTH secretion. 1,25(OH)2D stim-ulates the intestinal absorption of
calcium and phosphate. 1,25(OH)2D and PTH promote both bone
formation and resorp-tion in part by stimulating the proliferation and
differentiation of osteoblasts and osteoclasts. Both PTH and 1,25(OH)2D
enhance renal retention of calcium, but PTH promotes renal phosphate excretion,
whereas 1,25(OH)2D promotes renal reabsorption of phosphate. FGF23
is a recently discovered hormone produced primarily by bone that stimulates
renal phosphate excretion and inhibits renal production of 1,25(OH)2D.
1,25(OH)2D and phosphate in turn stimulate the production of FGF23.
Other hormones—calcitonin,
prolactin, growth hormone, insu-lin, thyroid hormone, glucocorticoids, and sex
steroids—influence calcium and phosphate homeostasis under certain physiologic
cir-cumstances and can be considered secondary regulators. Deficiency or excess
of these secondary regulators within a physiologic range does not produce the
disturbance of calcium and phosphate homeostasis that is observed in situations
of deficiency or excess of PTH, FGF23, and vitamin D. However, certain of these
secondary regulators—especially calcitonin, glucocorticoids, and estrogens— are
useful therapeutically and discussed in subsequent sections.
In addition to these
hormonal regulators, calcium and phos-phate themselves, other ions such as
sodium and fluoride, and a variety of drugs (bisphosphonates, plicamycin, and
diuretics) also alter calcium and phosphate homeostasis.
Related Topics
Privacy Policy, Terms and Conditions, DMCA Policy and Compliant
Copyright © 2018-2024 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.