Human Physiology, 14th edition (2016)

Regulation of Metabolism 695

mineralization by increasing the tendency of these two ions to

precipitate as hydroxyapatite crystals in the bone matrix.

1,25-dihydroxyvitamin D 3 is also formed as an autocrine/

paracrine regulator by the skin, breast, colon, prostate, and some of

the cells of the immune system. These convert 25-hydroxyvitamin

D 3 (from the liver) into the active regulator, which remains within

the tissues or organ that produces it. As an autocrine or paracrine

regulator within these tissues and organs, 1,25-dihydroxyvitamin

D 3 promotes cell differentiation and inhibits cell proliferation

(thereby protecting against cancer), and aids the function of the

immune system (helping to defend against infections).

hormone results in an increase in production of 1,25-dihydroxyvi-

tamin D 3. Low blood calcium can thus be corrected by the effects

of increased parathyroid hormone and 1,25-dihydroxyvitamin D 3

( fig. 19.22 ).

It is possible for plasma calcium levels to fall while phosphate

levels remain normal. In this case, the increased secretion of para-

thyroid hormone and the production of 1,25- dihydroxyvitamin D 3

that result could abnormally raise phosphate levels while acting to

restore normal calcium levels. This is prevented by the inhibition

of phosphate reabsorption in the kidneys by parathyroid hormone,

so that more phosphate is excreted in the urine ( fig.  19.22 ). By

inhibiting phosphate carriers in the plasma membrane of the cells

facing the lumen of the proximal tubule, parathyroid hormone can

raise blood calcium levels without excessively raising blood phos-

phate concentrations.

The secretion of calcitonin is stimulated by high plasma

calcium levels and acts to lower blood calcium by (1) inhib-

iting the activity of osteoclasts, thus reducing bone resorp-

tion, and (2) stimulating the urinary excretion of calcium

and phosphate by inhibiting their reabsorption in the kidneys

( fig. 19.23 ). As previously mentioned, this mechanism is not

physiologically significant in humans, but it does have medi-

cal significance in the use of high doses of calcitonin to treat

osteoporosis and the excessive osteoclast activity in Paget’s

disease of bone.

CLINICAL APPLICATION

Osteomalacia is a softening of bones due to lack of suf-

ficient calcium phosphate deposition in the bone matrix.

In children, osteomalacia is called rickets. This is usually

due to a vitamin D deficiency, producing insufficient intes-

tinal absorption of calcium and phosphate, which gener-

ally results from inadequate skin production of vitamin D

coupled with inadequate dietary intake. Crohn’s syndrome

and celiac disease can cause insufficient intestinal absorp-

tion of vitamin D, and other diseases (including cancer and

liver disease) can produce osteomalacia by different mech-

anisms. Hyperparathyroidism, usually due to an adenoma

of the parathyroid gland producing excessive parathyroid

hormone, can cause a bone softening known as osteitis

fibrosa cystica. This condition is characterized by exces-

sive mobilization of calcium from bone, resulting in hyper-

calcemia and the tendency to form kidney stones.

Figure 19.22 Homeostasis of plasma Ca^2 1

concentrations. A negative feedback loop returns low blood

Ca^2 1 concentrations to normal without simultaneously raising

blood phosphate levels above normal.

Sensor

Integrating center

Effector

Stimulates

reabsorption

of Ca2+

Inhibits

reabsorption

of PO 4

1,25-Dihydroxyvitamin D 3

Stimulates

intestinal

absorption of

Ca2+ and PO 4

Bone

Stimulates

dissolution of

CaPO 4 crystals

Decreased

plasma

Ca2+ Negative

feedback

Parathyroids

PTH

Kidneys

Increased

plasma

Ca2+

−

3− 3−

Clinical Investigation CLUES

Marty took vitamin D capsules as a dietary supplement.

• How is vitamin D formed in the body, and how does
  it influence the skeletal system?


• Is it possible for a man of Marty’s age to develop
  osteoporosis?


• What is osteomalacia, and how does it relate to the
  physician’s statement that taking vitamin D might
  help prevent bone loss?

Negative Feedback Control of

Calcium and Phosphate Balance

The secretion of parathyroid hormone is controlled by the plasma

calcium concentrations. Its secretion is stimulated by low calcium

concentrations and inhibited by high calcium concentrations.

Since parathyroid hormone stimulates the final hydroxylation step

in the formation of 1,25-dihydroxyvitamin D 3 , a rise in parathyroid

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