Chapter: Modern Pharmacology with Clinical Applications: Parathyroid Hormone, Calcitonin, Vitamin D

Calcium Homeostasis

Calcium is the principal extracellular electrolyte regu-lated by PTH, calcitonin, and D3.

CALCIUM HOMEOSTASIS

 

Calcium is the principal extracellular electrolyte regu-lated by PTH, calcitonin, and D3. Extracellular calcium is a critical component of signal transduction across the plasma membrane, which regulates a wide spectrum of physiological events including muscle contraction, se-cretion of neurotransmitters and hormones, and the action of growth factors, cytokines, and protein hormones. Intracellular calcium is an important cofactor in many enzymatic reactions. Plasma calcium exists in three forms: ionized (50%), protein bound (46%), and com-plexed to organic ions (4%). Total plasma calcium con-centration is normally tightly maintained within the range of 4.5 to 5.7 mEq/L, primarily by the actions of PTH and D3, which regulate bone resorption and cal-cium absorption from the intestine and kidney. The calcium-lowering actions of calcitonin may regulate postprandial plasma calcium deposition into bone and prevent hypercalcemia.

 

The regulation of serum calcium concentration is a complex process that requires the coordinated re-sponses of these three hormones and their target tis-sues. The model shown in Figure 66.1 consists of three wings depicting overlapping feedback loops that repre-sent the interrelationship between bone (wing 1), intes-tine (wing 2), and kidney (wing 3) in modulating calcium homeostasis. The left side of the model (A loops) describes events that increase blood calcium in response to hypocalcemia, whereas the right side (B loops) de-scribes events that decrease blood calcium in response to hypercalcemia.


 

Hypocalcemia directly increases PTH synthesis and release and inhibits calcitonin release. PTH in turn re-stores plasma calcium by initially stimulating transport of free or labile calcium from bone into the blood. PTH also increases renal 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) production, which is the most active form of D3. 1,25-(OH)2D3 induces enterocyte differenti-ation in the intestine, which in turn results in increased absorption of calcium. Finally, during long periods of hypocalcemia, PTH can mobilize more stable calcium deep in the hydroxyapatite of bone by activating deep osteoclasts.

 

Hypercalcemia, in contrast, results in calcitonin syn-thesis and release, while PTH release and formation of 1,25-(OH)2D2 are inhibited. Calcitonin inhibits bone re-sorption directly by reducing osteocyte activity. Calcitonin also induces an initial phosphate diuresis, followed by increased renal calcium, sodium, and phos-phate excretion.

 

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Modern Pharmacology with Clinical Applications: Parathyroid Hormone, Calcitonin, Vitamin D : Calcium Homeostasis |


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