DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1276
10
9
2.5
Intestine:
800 mg intake
Bone:
8
7
protein bound
40%
2.0
300 mg
300 mg
SECTION V
Total calcium
mg/dl
6
5
4
3
2
complexed
10%
ionized
50%
1.5
1.0
0.5
mM
Diffusible calcium
300 mg absorbed
150 mg endogenous loss
Kidney:
9000 mg filtered
8850 mg reabsorbed
HORMONES AND HORMONE ANTAGONISTS
1
0
0.0
Figure 44–1. Pools of calcium in serum. Concentrations are
expressed as mg/dL on the left-hand axis and as mM on the right.
The total serum calcium concentration is 10 mg/dL or 2.5 mM,
divided into three pools: protein-bound (40%), complexed with
small anions (10%), and ionized calcium (50%). The complexed
and ionized pools represent the diffusable forms of calcium.
The total plasma calcium concentration can be
interpreted only by correcting for the concentration of
plasma proteins. A change of plasma albumin concentration
of 1.0 g/dL from the normal value of 4.0 g/dL
can be expected to alter total calcium concentration by
~0.8 mg/dL.
The extracellular Ca 2+ concentration is tightly
controlled by hormones that affect calcium entry at the
intestine and its exit at the kidney; when needed, these
same hormones regulate withdrawal from the large
skeletal reservoir.
Calcium Stores. The skeleton contains 99% of total body calcium
in a crystalline form resembling the mineral hydroxyapatite
[Ca 10
(PO 4
) 6
(OH) 2
]; other ions, including Na + , K + , Mg 2+ , and F - , also
are present in the crystal lattice. The steady-state content of calcium in
bone reflects the net effect of bone resorption and bone formation, coupled
with aspects of bone remodeling. In addition, a labile pool of bone
Ca 2+ exchanges readily with interstitial fluid. This exchange is modulated
by hormones, vitamins, drugs, and other factors that directly alter
bone turnover or that influence the Ca 2+ level in interstitial fluid.
Calcium Absorption and Excretion. In the U.S., ~75% of dietary calcium
is obtained from milk and dairy products. The adequate intake
value for calcium is 1300 mg/day in adolescents and 1000 mg/day
in adults. After age 50, the adequate intake is 1200 mg/day. This contrasts
with median intakes of calcium for boys and girls ≥9 years of
age of 865 and 625 mg, respectively, and a median daily calcium
intake of 517 mg for women >50 years of age.
650 mg fecal loss
150 mg excreted
Figure 44–2. Schematic representation of the whole body daily
turnover of calcium. (Adapted with permission from Yanagawa
N, Lee DBN. Renal handling of calcium and phosphorus. In:
Disorders of Bone and Mineral Metabolism (Coe FL, Favus MJ,
eds.), Raven Press, New York, 1992, pp. 3–40.)
Figure 44–2 illustrates the components of whole-body daily
calcium turnover. Ca 2+ enters the body only through the intestine.
Active vitamin D–dependent transport occurs in the proximal duodenum,
whereas facilitated diffusion throughout the small intestine
accounts for most total Ca 2+ uptake. This uptake is counterbalanced
by an obligatory daily intestinal calcium loss of ~150 mg/day that
reflects the calcium content of mucosal and biliary secretions and in
sloughed intestinal cells.
The efficiency of intestinal Ca 2+ absorption is inversely related
to calcium intake. Thus, a diet low in calcium leads to a compensatory
increase in fractional absorption owing partly to activation of
vitamin D. In older persons, this response is considerably less robust.
Disease states associated with steatorrhea, diarrhea, or chronic malabsorption
promote fecal loss of calcium, whereas drugs such as glucocorticoids
and phenytoin depress intestinal Ca 2+ transport.
Urinary Ca 2+ excretion is the net difference between the quantity
filtered at the glomerulus and the amount reabsorbed. About 9 g of Ca 2+
are filtered each day. Tubular reabsorption is very efficient, with >98%
of filtered Ca 2+ returned to the circulation. The efficiency of reabsorption
is highly regulated by parathyroid hormone (PTH) but also is influenced
by filtered Na + , the presence of nonreabsorbed anions, and diuretic
agents (Chapter 25). Sodium intake, and therefore sodium excretion, is
directly related to urinary calcium excretion. Diuretics that act on the
ascending limb of the loop of Henle (e.g., furosemide) increase calcium
excretion. By contrast, thiazide diuretics uncouple the relationship
between Na + and Ca 2+ excretion, increasing sodium excretion but diminishing
calcium excretion (Friedman and Bushinsky, 1999). Urine Ca 2+
excretion is a direct function of dietary protein intake, presumably owing
to the effect of sulfur-containing amino acids on renal tubular function.