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Chapter 11
SECTION F SUMMARY
Effector Sites for Calcium Homeostasis
I. The effector sites for the regulation of plasma calcium
concentration are bone, the gastrointestinal tract, and the
kidneys.
II. Approximately 99 percent of total-body calcium is contained
in bone as minerals on a collagen matrix. Bone is constantly
remodeled as a result of the interaction of osteoblasts and
osteoclasts, a process that determines bone mass and provides a
means for raising or lowering plasma calcium concentration.
III. Calcium is actively absorbed by the gastrointestinal tract, and
this process is under hormonal control.
IV. The amount of calcium excreted in the urine is the difference
between the amount fi ltered and the amount reabsorbed, the
latter process being under hormonal control.
Hormonal Controls
I. Parathyroid hormone (PTH) increases plasma calcium
concentration by infl uencing all of the effector sites.
a. It stimulates kidney reabsorption of calcium, bone
resorption with release of calcium into the blood, and
formation of the hormone 1,25-dihydroxyvitamin D, which
stimulates calcium absorption by the intestine.
b. It also inhibits the reabsorption of phosphate in the kidneys,
leading to increased excretion of phosphate in the urine.
II. Vitamin D is formed in the skin or ingested and then
undergoes hydroxylations in the liver and kidneys. The kidneys
express the enzyme that catalyzes the production of the
active form, 1,25-dihydroxyvitamin D. This process is greatly
stimulated by parathyroid hormone.
Metabolic Bone Disease
I. Osteomalacia (adults) and rickets (children) is a disease
in which the mineralization of bone is defi
cient—usually due
to inadequate vitamin D intake, absorption, or activation.
II. Osteoporosis is a loss of bone density (loss of matrix and
minerals).
a. Bone resorption exceeds formation.
b. It is most common in postmenopausal (estrogen-defi cient)
women.
c. It can be prevented by exercise, adequate calcium
and vitamin D intake, and medications (such as
bisphosphonates).
Additional Clinical Examples
I. Hypercalcemia (chronically elevated plasma calcium levels)
can occur from several causes.
a. Primary hyperparathyroidism is usually caused by a
benign adenoma, which produces too much PTH.
Increased PTH causes hypercalcemia by increasing bone
resorption of calcium, increasing kidney reabsorption of
calcium, and increasing kidney production of
1,25-(OH)
2
D, which increases calcium absorption in
the intestines.
b. Humoral hypercalcemia of malignancy is often due to the
production of PTH-related peptide (PTHrp) from cancer
cells. PTHrp acts like PTH.
c. Excessive vitamin D intake may also result in
hypercalcemia.
II. Hypocalcemia (chronically decreased plasma calcium levels)
can also be traced to several causes.
a. Low PTH levels from primary hypoparathyroidism
(loss of parathyroid function) lead to hypocalcemia by
decreasing bone resorption of calcium, decreasing urinary
reabsorption of calcium, and decreasing renal production
of 1,25-(OH)
2
D.
b. Pseudohypoparathyroidism is caused by target organ
resistance to the action of PTH.
c. Secondary hyperparathyroidism is caused by vitamin
D defi ciency due to inadequate intake, absorption, or
activation in the kidney (e.g. in kidney disease).
Among these symptoms are tiredness and lethargy with
muscle weakness, as well as nausea and vomiting (due to
effects on the GI tract).
Hypocalcemia can result from a loss of parathyroid
gland function
(
primary hypoparathyroidism
);
one cause
of this is the removal of parathyroid glands that rarely occurs
when a person with thyroid disease has his or her thyroid
gland surgically removed. Because PTH is low, 1,25-(OH)
2
D
production from the kidney is also decreased. Decreases in
both hormones lead to decreases in bone resorption, kidney
calcium reabsorption, and GI calcium absorption. Resistance
to the effects of PTH in target tissue can also lead to the
symptoms of hypoparathyroidism, even though in such cases
PTH levels in the blood tend to be elevated. This condition is
called
pseudohypoparathyroidism
.
Another interesting hypocalcemic state is
secondary
hyperparathyroidism
.
Failure to absorb vitamin D from the
gastrointestinal tract, or decreased kidney 1,25-(OH)
2
D
production, which can occur in kidney disease, can lead to
secondary hyperparathyroidism. The decreased plasma calcium
that results from decreased GI absorption of calcium results
in stimulation of the parathyroid glands. While the increased
parathyroid hormone does act to restore plasma calcium toward
normal, it does so at the expense of signifi cant loss of calcium
from bone and the acceleration of metabolic bone disease.
The symptoms of hypocalcemia are also due to its effects
on excitable tissue. It increases the excitability of nerves and
muscles, which can lead to CNS effects (seizures), muscle
spasms
(
hypocalcemic tetany
),
and nerve excitability. Long-
term treatment of hypoparathyroidism involves giving calcium
and 1,25-(OH)
2
D (calcitriol). Poor absorption is treated
with supplemental dietary calcium and high doses of dietary
vitamin D. If high doses of dietary vitamin D do not overcome
the problem, injections of vitamin D can be administered.
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