Ganong's Review of Medical Physiology, 23rd Edition

364
SECTION IV
Endocrine & Reproductive Physiology

CALCIUM & PHOSPHORUS

METABOLISM

CALCIUM

The body of a young adult human contains about 1100 g (27.5
mol) of calcium. Ninety-nine percent of the calcium is in the
skeleton. Plasma calcium, normally at a concentration of
around 10 mg/dL (5 mEq/L, 2.5 mmol/L), is partly bound to
protein and partly diffusible (Table 23–1). The distribution of
calcium inside cells is discussed in Chapter 2.
It is the free, ionized calcium in the body fluids that is a
vital second messenger (see Chapter 2) and is necessary for
blood coagulation, muscle contraction, and nerve function. A
decrease in extracellular Ca
2+
exerts a net excitatory effect on
nerve and muscle cells in vivo (see Chapters 4 and 5). The
result is
hypocalcemic tetany,
which is characterized by
extensive spasms of skeletal muscle, involving especially the
muscles of the extremities and the larynx. Laryngospasm can
become so severe that the airway is obstructed and fatal
asphyxia is produced. Ca
2+
also plays an important role in
blood clotting (see Chapter 32), but in vivo, fatal tetany would
occur before compromising the clotting reaction.
Because the extent of Ca
2+
binding by plasma proteins is
proportional to the plasma protein level, it is important to
know the plasma protein level when evaluating the total
plasma calcium. Other electrolytes and pH also affect the free
Ca
2+
level. Thus, for example, symptoms of tetany appear at
higher total calcium levels if the patient hyperventilates,
thereby increasing plasma pH. Plasma proteins are more ion-
ized when the pH is high, providing more protein anion to
bind with Ca
2+
.
The calcium in bone is of two types: a readily exchangeable
reservoir and a much larger pool of stable calcium that is only

slowly exchangeable. Two independent but interacting

homeostatic systems affect the calcium in bone. One is the

system that regulates plasma Ca

2+

, providing for the move-

ment of about 500 mmol of Ca

2+

per day into and out of the

readily exchangeable pool in the bone (Figure 23–1). The

other system involves bone remodeling by the constant inter-

play of bone resorption and deposition (see following text).

However, the Ca

2+

interchange between plasma and this sta-

ble pool of bone calcium is only about 7.5 mmol/d.

Ca

2+

is transported across the brush border of intestinal epi-

thelial cells via channels known as transient receptor potential

vanilloid type 6 (TRPV6) and binds to an intracellular protein

known as calbindin-D

9k

. Calbindin sequesters the absorbed
calcium so that it does not disturb epithelial signaling pro-
cesses that involve calcium. The absorbed Ca
2+
is thereby
delivered to the basolateral membrane of the epithelial cell,
from where it can be transported into the bloodstream by
either a sodium/calcium exchanger (NCX1) or a calcium-
dependent ATPase. Nevertheless, it should be noted that

TABLE 23 –1

Distribution (mmol/L)

of calcium in normal human plasma.

Total diffusible 1 .3 4

Ionized (Ca

2+

) 1.18

Complexed to HCO

3

• , citrate, etc 0.16
  Total nondiffusible (protein-bound) 1. 16
  Bound to albumin 0.92
  Bound to globulin 0.24
  Total plasma calcium 2.50

FIGURE 23–1
Calcium metabolism in an adult human.
A typical daily intake of 25 mmol Ca
2+
(1000 mg) moves through many body
compartments.

Diet

25 mmol

GI

tract

Feces

22.5 mmol

Absorption

15 mmol

Secretion

12.5 mmol

Reabsorption

247.5 mmol

ECF

35 mmol

Glomerular

filtrate

250 mmol

Urine

2.5 mmol

Rapid

exchange

Accretion

500 mmol

7.5 mmol

Reabsorption

7.5 mmol

Bone

Exchangeable

100 mmol

Stable

27,200 mmol