Figure 1. Regulation of parathyroid hormone (PTH). This illustration shows the direct (solid lines) and indirect (dashed line)
effects of PTH on bone, kidneys, and intestines. PTH's net effect is to increase serum calcium and decrease serum phosphorus
concentrations.
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PTH mobilizes both calcium and phosphorus from bone, causes the kidneys to retain calcium and excrete phosphate, and indirectly
increases intestinal absorption of calcium and phosphate (Figure 1).1,2,9 PTH has both rapid and long-term effects on bone.7 In acute hypocalcemic situations, the rate of bone breakdown and subsequent calcium release into the blood is increased,
and changes in serum calcium can be noted within minutes.7,9 Initially, calcium salts (about 1% of total body calcium), particularly CaHPO4, serve as a readily exchangeable reservoir of calcium.7,8 If hypocalcemia and elevation in PTH continue for several days to weeks, PTH causes proliferation of osteoclast-mediated
breakdown of existing bone (osteolysis). Osteoclasts, unlike osteoblasts and osteocytes, lack receptors for PTH, so osteoclast
activation is likely indirect through cytokines (e.g. insulin-like growth factor 1, interleukin 6, granulocyte-macrophage stimulating factor) released by activated osteoblasts
and osteocytes.7,9 Osteolysis results in increased serum phosphorus and calcium concentrations.
In normal animals, ionized and complexed calcium (but not protein-bound calcium) passes into the glomerular filtrate.7 Ninety-nine percent of this calcium is eventually reabsorbed.7,13 About 90% of the reabsorption of calcium occurs in the proximal tubules, loop of Henle, and early distal tubules.7 In the thick ascending limb of the loop of Henle, there is marked reabsorption of calcium because of the positive charge
within the lumen of the tubules compared with the surrounding interstitial fluid.7 The reabsorption of the final 9% or 10% of calcium depends on the serum ionized calcium concentration and presence of PTH,
which if present increase the degree of calcium reabsorption in the late distal tubules and early collecting ducts.1,7,9,13 In the proximal tubule, phosphate reabsorption is inhibited by PTH.7,9,13 PTH in the proximal tubule also stimulates the enzyme 1-alpha-hydroxylase, vital in the final conversion of the vitamin
D precursor to its most active form, calcitriol (discussed later).9,11 The net effects of PTH on the kidneys are to decrease the serum phosphorus concentration and increase the serum calcium
concentration.
Calcitonin
Calcitonin's activity further controls the effects of PTH on calcium. Calcitonin, the hormone produced by the parafollicular
cells (also called C cells) of the thyroid gland, antagonizes the actions of PTH, particularly on bone.7 The effects of calcitonin are relatively weak compared with PTH.7
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