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Principles of Biochemistry: White,Handler and Smith, Fourth Edition.Copyright 1968
Thirty years of Sunrises and Sunsets.

MyNote: I am using the older spelling for Hypercalcemia, so I havereplaced the word accordingly. Hypercalcaemia.

Chapter 39, Page 888
Regulation of Plasma Calcium Concentration.

The Calcium of normal human plasma varies from 9 to 11 mg. per 100ml. ( 4.5 to 5.6 meq. per liter ) and exists in two major forms. The concentrationof ionic calcium, the form in which calcium exerts its physiological effects,is 5 to 6 mg. per 100 ml. The second form
is calcium which is not diffusible through semipermeable membranesthrough which ionized calcium can pass. This fraction consists largelyof calcium bound to plasma proteins, particularily albumin. The amountof this fraction is a function of the total protein concentration; plasmalow in protein also exhibits a low total calcium concentration. The extentof calcium binding by protein increases with increasing pH.
Ionic calcium can be determined by a biological assay using thefrog or turtle heart, the activity of which is proportional to the ionizedcalcium concentration of the medium. For clinical purposes, estimationof the ionized calcium is possible from a knowledge of the total calciumand protein concentrations, using the nomogram shown in Fig. 39-1.

Reference: Nomogram showing the relations between total serum calcium,protein, and
ionized calcium concentrations. ( F. C. McLean and A. B. Hastings,American Journal of
Medical Scince, 189, page 601, 1935 )

Maintenance of normal neuromuscular irritability is critically dependentupon the concentration of ionic calcium as one of the factors in the ratio:

[ K+ ] + [ Na+ ]
-----------------------------------
[ Ca++ ] + [ Mg++ ] + [ H+ ]

This relationship is intended only to convey the direction of thechange in irritabilty
resulting from alterations in the concentrations of these ions.A significant decrease in concentration of ionic calcium results in tetany,while an increase may sufficiently impair
function as to lead to respiratory or cardiac failure.

The plasma calcium concentration is homeostatically maintained. Themechanism includes a storage compartment, the skeleton, which may be drawnupon or into which excess may be deposited; the kidneys; excretion throughthe bile and intestine; and two
hormones, parathormone and calcitonin ( Chapter 43 ), the secretionof which is sensitive to the plasma concentration of Ca++.

Serum Phosphate and Ca++ concentrations normallyexhibit a reciprocal relationship;
when phosphate concentration is deminished, [ Ca++ ]is elevated and vice versa, as
would be expected were serum the soluble phase of a saturated solution.However, in
hyperparathyroidism the concentrations of both ions may be elevated,whereas in juvenile rickets both maybe deminished. Thus, a simplesolubility product relationship does not
always obtain, and the concentrations of these ions are under cellularcontrol.

The normal major pathway of calcium excretion is the intestinal tract.Individuals on a calcium-free diet continue to excrete calcium in the feces.The calcium is a constituent
of various digestive secretions, particularly the bile; the amountexcreted depends upon the plasma calcium concentration. Normally, the kidneyexcretes little calcium. On the other hand, chronic hypercalcaemia maybe accompanied by sufficient calciuria to cause formation of renal calculi.In normal individuals 99% of the Ca++ filtered through the glomeruliis reabsorbed, even at artificially elevated plasma concentrations. However,
the fraction reabsorbed decreases in several pathological conditionsin which bone mineral resorption is active.

Bone serves as the store of calcium in the operation of a homeostaticmechanism.
Under circumstances which might otherwise lead to hypercalcaemia,calcium is withdrawn
from the skeleton. Conversely, hypercalcaemia may be prevented bydeposition of
calcium in bone.

Wonderful of the United States Olympic Commitee to reintroduce SKELETON
as an OLYMPIC SPORT for SALT LAKE 2002.

Daring to go head first, were no man has been before.
Any chin burns yet?

regards,

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