chapter 37
Mineral Metabolism
in the regulation o f both calcium and phosphorus h om e-
ostasis are the gastrointestinal tract, kidney, and bone.
B ased on p hysiological signals the gastrointestinal tract
regulates absorption, the kidney regulates reabsorption
and excretion, and bone regulates accretion and m obiliza-
tion o f calcium and phosphorus. A bnorm al serum calcium
concentration has deleterious p hysiological effects on di-
verse cellular processes involving m uscular, neurological,
gastrointestinal, and renal system s.
Three form s o f calcium are in equilibrium in serum:
nondiffusible calcium bound prim arily to albumin; dif-
fusible com plexes o f calcium w ith lactate, bicarbonate,
phosphate, sulfate, citrate, and other anions; and diffusible
ion ized calcium (Ca2+). Ionized calcium accounts for ap-
proxim ately h alf o f total serum calcium , and nondiffusible
and com plexed calcium account for 45% and 5% , respec-
tively. Ionized calcium is the p hysiological active form;
its concentration is regulated by the parathyroid gland.
A decrease in serum ionized calcium can cause
(involuntary m uscle contraction) and related neurological
sym ptom s, regardless o f the total serum calcium con cen -
A lthough ionized and protein-bound calcium are in
equilibrium , release from the protein-bound fraction is
slow and changes in plasm a protein (esp ecially album in)
concentration result in parallel changes in total plasm a cal-
cium . A decrease in serum album in o f 1 g/dL results in a
decrease o f about 0.8 m g/dL in total serum calcium . The
equilibrium am ong the three form s o f serum calcium is
affected by changes in blood pH. Thus, at pH
6 .8
sis), about 54% o f serum calcium is in the ionized form ,
w hereas at pH 7 .8 (alkalosis), on ly 38% is ionized.
The m ost accurate and sensitive m ethod o f determ in-
ing ionized calcium concentration is by an ion-specific
electrode. The percentage o f total ionized calcium can be
estim ated from the em pirical equation:
% ionized calcium = 100 —
x album in (g/dL ) + 2
x globulin (g/dL ) + 3]
T his form ula reflects the fact that album in has a greater
affinity for calcium than do other serum proteins.
B esid es being the principal com ponent o f teeth and
for blood coagulation
(Chapter 36), m uscle contraction (Chapter 21), secretion
o f digestive en zym es (Chapter 12), secretion and action o f
m any horm ones (Chapter 30), and other body system s.
C alcium is intim ately involved in transfer o f infor-
m ation and m aterial across m em branes. H orm one bind-
in g to a plasm a m em brane receptor or electrical depo-
larization o f the plasm a m em brane (as in m uscle con -
traction) causes calcium entry into the cell or release
from binding sites on the inner surface o f the m em -
brane. C ytoplasm ic calcium concentration in unstim ulated
cells is about 10
- 7
m ol/L (com pared to 10
- 2
m ol/L in
the extracellular fluid). U pon stim ulation, the cytoplas-
m ic ionic calcium content rises rapidly to about
1 0
-6 -
- 5
m ol/L . If the intracellular concentration in resting
cells is too high or the extracellular concentration is too
low , cellular function is impaired. T he intracellular con -
centration is m aintained by a Ca2+-ATPase located in
the plasm a m em brane. Vitamin D and the other com -
ponents o f the calcium hom eostatic system are respon-
sible for keeping the extracellular calcium at the required
Intracellular ionized calcium acts as a second m essen-
ger, coupling the action o f a horm one or electrical im -
pulse (the first m essenger) on the outside o f the cell to
intracellular events, such as horm one or protein secre-
tion, protein kinase activity, or m uscle contraction. The
effect o f Ca2+ on intracellular processes is often m edi-
ated by a sm all calcium -binding protein, such as troponin
C in m uscle (Chapter 21) or calm odulin in many other
cells (Chapters 15 and 30). Synthesis o f these calcium -
binding proteins is not directly affected by vitam in D or
any o f its m etabolites. M any stim uli that affect perm eabil-
ity to calcium also activate m em brane-bound adenylate cy -
clase and increase the intracellular concentration o f cA M P
(Chapter 30).
A bout 80% o f the phosphate in the body is com bined
with calcium as hydroxyapatite in the skeleton. The re-
m ainder is present in many organic com pounds as phos-
phate esters and anhydrides, e.g., n ucleic acids, nucleoside
triphosphates (particularly ATP), m em brane phospho-
lipids, and sugar-phosphate m etabolites. Phosphate is d is-
tributed fairly equally betw een extracellular and intracel-
lular com partm ents. A typical m ale contains about 670 g
o f phosphorus and a fem ale about 6 3 0 g, or an average
o f about 12 g/kg o f fat-free tissue. Serum inorganic phos-
phorus concentration under fasting conditions in children
is 4 - 6 m g/dL (1 -1 .5 m m ol/L ) and in adults 3 -5 m g/dL
(0 .7 5 -1 .2 5 m m ol/L). T hese values m ay vary considerably
during the day, particularly follow in g m eals. Although
total plasm a concentrations o f calcium and phosphate
are at or near the solubility product for calcium phos-
phate, precipitation does not occur because 45% o f the
calcium and
1 0
% o f the inorganic phosphate are protein-
bound. The rem ainder o f the serum phosphate is present as
H PO 2 - and H
, w ith the relative proportions depen-
dent on pH (at pH 7 .4 0 , [H P 0
“ ]/[H
P O “ ] A 4:1). Inor-
ganic phosphate is a substrate in oxidative phosphorylation
(Chapter 14), in glycogen breakdown (Chapter 15), in for-
m ation o f 1,3-bisphosphoglycerate from glyceraldehyde-
3-phosphate (Chapter 13), in conversion o f nucleosides to
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