Calcitriol

Calcitriol (CAL-sih-TRY-ol) is a form of vitamin D produced by the sequential action of the skin, liver, and kidneys (fig. 7. 15):

1. Epidermal keratinocytes use ultraviolet radiation from sunlight to convert a steroid, 7-dehydrocholesterol, to previtamin D3. Over another 3 days, the warmth of sunlight on the skin further converts this to vitamin D3, and a transport protein carries this to the bloodstream.

2. The liver adds a hydroxyl group to the molecule, converting it to calcidiol [25(OH)D].

3. The kidney then adds another hydroxyl group, converting calcidiol to calcitriol [1, 25(OH)2D], the most active form of vitamin D.

Calcitriol behaves as a hormoneā€”a blood-borne chemical messenger from one organ to another. It is called a vitamin

Figure 7.13 Carpopedal Spasm. Such muscle tetany occurring in the hands and feet can be a sign of hypocalcemia.

28 hyper = above normal + calc = calcium + emia = blood condition

Saladin: Anatomy & Physiology: The Unity of Form and Function, Third Edition

232 Part Two Support and Movement

232 Part Two Support and Movement

Calcitriol Pth Calcitonin

Figure 7.14 Hormonal Control of Calcium Balance. Calcitriol, parathyroid hormone (PTH), and to some extent calcitonin maintain the blood calcium concentration at 9.2 to 10.4 mg/dL. Calcitriol and PTH promote absorption of dietary calcium, reabsorption of calcium by the kidneys, and resorption of calcium from bone. Calcitonin weakly promotes deposition of calcium in bone. These hormones also have certain inhibitory effects on calcium metabolism and effects on phosphate balance (not illustrated).

Figure 7.14 Hormonal Control of Calcium Balance. Calcitriol, parathyroid hormone (PTH), and to some extent calcitonin maintain the blood calcium concentration at 9.2 to 10.4 mg/dL. Calcitriol and PTH promote absorption of dietary calcium, reabsorption of calcium by the kidneys, and resorption of calcium from bone. Calcitonin weakly promotes deposition of calcium in bone. These hormones also have certain inhibitory effects on calcium metabolism and effects on phosphate balance (not illustrated).

only because it is added to the diet, mainly in fortified milk, as a safeguard for people who do not get enough sunlight to initiate its synthesis in the skin.

The principal function of calcitriol is to raise the blood calcium concentration. It does this by three mechanisms:

1. Increasing calcium absorption by the small intestine. (It increases the absorption of phosphate and magnesium ions as well.)

2. Increasing calcium (and phosphate) resorption from the skeleton. Calcitriol binds to osteoblasts, which release another chemical messenger, osteoclast-stimulating factor. This messenger stimulates precursor cells to fuse and form osteoclasts. These new osteoclasts then liberate calcium and phosphate ions from bone.

3. Weakly promoting the reabsorption of calcium ions by the kidneys, so less calcium is lost in the urine.

Although calcitriol promotes bone resorption, it is also necessary for bone deposition. Without it, calcium and phosphate levels in the blood are too low for normal bone deposition. The result is a softness of the bones called rickets in children and osteomalacia29 in adults.

(see fig. 17.8). It is secreted when the blood calcium concentration rises too high, and it lowers the concentration by two principal mechanisms (fig. 7.16a):

1. Osteoclast inhibition. Within 15 minutes after it is secreted, calcitonin reduces osteoclast activity by as much as 70%, so osteoclasts liberate less calcium from the skeleton.

2. Osteoblast stimulation. Within an hour, calcitonin increases the number and activity of osteoblasts, which deposit calcium into the skeleton.

Calcitonin plays an important role in children but has little effect in most adults. The osteoclasts of children are highly active in skeletal remodeling and release 5 g or more of calcium into the blood each day. By inhibiting this activity, calcitonin can significantly lower the blood calcium level in children. In adults, however, the osteoclasts release only about 0.8 g of calcium per day. Calcitonin cannot change adult blood calcium very much by suppressing this minor contribution. Calcitonin deficiency is not known to cause any adult disease. Calcitonin may, however, prevent bone loss in pregnant and lactating women, and it is useful for reducing bone loss in osteoporosis (see insight 7.4 at the end of the chapter).

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