After studying this chapter, you should be able to:
Understand the importance of maintaining homeostasis of body calcium and phosphate concentrations.
Describe the body pools of calcium, their rates of turnover, and the organs that play central roles in regulating movement of calcium between stores.
Delineate the mechanisms of calcium and phosphate absorption and excretion.
Identify the major hormones—vitamin D, parathyroid hormone, and calcitonin—and other factors that regulate calcium and phosphate homeostasis, their sites of synthesis, targets of their action, and consequences of dysfunction.
Define the basic anatomy of bone and understand how linear bone growth is arrested after puberty.
Delineate the cell types that regulate bone formation and resorption and their mechanism of action, and discuss diseases that result from abnormalities in bone homeostasis.
Calcium is an essential intracellular signaling molecule and also plays a variety of extracellular functions, thus the control of body calcium concentrations is vitally important. The components of the system that maintains calcium homeostasis include cell types that sense changes in extracellular calcium and release calcium-regulating hormones, and the targets of these hormones, including the kidneys, bones, and intestine, that respond with changes in calcium mobilization, excretion, or uptake. Three hormones are primarily concerned with the regulation of calcium homeostasis. 1,25-Dihydroxycholecalciferol is a steroid hormone formed from vitamin D by successive hydroxylations in the liver and kidneys. Its primary action is to increase calcium absorption from the intestine. Parathyroid hormone (PTH) is secreted by the parathyroid glands. Its main action is to mobilize calcium from bone and increase urinary phosphate excretion. Calcitonin, a calcium-lowering hormone that in mammals is secreted primarily by cells in the thyroid gland, inhibits bone resorption. Although the role of calcitonin seems to be relatively minor, all three hormones probably operate in concert to maintain the constancy of the calcium level in the body fluids. Phosphate homeostasis is likewise critical to normal body function, particularly given its inclusion in adenosine triphosphate (ATP), its role as a biologic buffer, and its role as a modifier of proteins, thereby altering their functions. Many of the systems that regulate calcium homeostasis also contribute to that of phosphate, albeit sometimes in a reciprocal manner, and thus will also be discussed in this chapter.
CALCIUM & PHOSPHORUS BALANCE IN THE BODY
The body of a young adult human contains about 1100 g (27.5 moles) of calcium. Ninety-nine percent of the calcium is in the skeleton. Plasma calcium, normally at a concentration of around 10 mg/dL (5 mEq/L, 2.5 mmol/L), is partly bound to protein and partly diffusible (Table 21–1). The distribution of calcium inside the cells and the role of Ca2+ as a second messenger molecule are discussed in Chapter 2.
TABLE 21–1Distribution (mg/dL) of calcium in normal human plasma.