The Physiology Of Calcium 1021 Calcium Metabolism6

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Ca is an essential nutrient. It is absorbed in the intestine, it is used to build bones, and, to a lesser extent, teeth. It maintains plasma and extra- and intracellular pools, and it is excreted via the feces, the urine, and to some extent from the skin and the hair (Figure 10.1).

Calcitonin

Parathyroid hormone Calcitriol

Parathyroid hormone Calcitri

Urinary calcium

FIGURE 10.1 Schematic representation of Ca homeostasis in the human body.

Bone

Calcitonin

Bone

Parathyroid hormone Calcitriol

Small intestine

Calcitonin

Parathyroid hormone Calcitri

Large intestine

Kidney

Urinary calcium

FIGURE 10.1 Schematic representation of Ca homeostasis in the human body.

The mineralized tissues contain 99.9% of all body Ca, and the remaining 0.1% is found in plasma and extracellular fluids, as well as inside all types of eucaryotic cells. In plasma, total Ca consists of 3 fractions (i.e., about 45% as protein-bound; about 10% as citrate, phosphate, and bicarbonate salts; about 45% as free Ca ions). The normal plasma concentrations of total and ionized Ca are 2.3-2.5 and 1.1-1.3 mM, respectively. The Ca in plasma, extracellular fluids, and cells plays major roles in modulating the activity of a wide range of enzymes and transport or regulatory proteins, especially in mediating vascular contraction and vasodilatation, muscle contraction, nerve transmission, and glandular secretion.7 The physiology of Ca is under close homeostatic control with processes such as absorption, excretion and secretion, and storage in bone being involved in maintaining the concentration of ionized Ca in the plasma within a tightly regulated range. This tight regulation of plasma Ca concentration is achieved through a complex physiological system comprising the interaction of the calcitropic hormones such as the parathyroid hormone, 1,25 dihydroxycholecalciferol (or 1,25 dihydroxy-vitamin D3), and calcitonin, with specific target tissues (kidney, bone, and intestine) that serve to increase or to decrease the entry of Ca into the extracellular space. The secretion of these hormones is governed wholly, or in part, by the plasma concentration of ionized Ca, thus forming a negative feedback system. Parathyroid hormone and 1,25 dihydroxy-cholecalciferol are secreted when plasma Ca is low, while calcitonin is secreted when plasma Ca is high.

The Ca pools in the body are in balance when absorption equates with losses. During growth, more Ca is added to the pools than is lost, and the balance is positive; in adult life absorption and losses are equal; with increasing age, losses are not anymore compensated for by absorption, and the balance progressively becomes negative.

Two main absorption processes exist in the intestine, namely an active and a passive (or simple diffusion) absorption process. The active transport is essentially localized to the upper duodenum but a small part also takes place in the colon. It operates already at low Ca concentration, and it is mediated via the metabolic product of vitamin D (i.e., 1,25-dihydroxycholecalciferol) which stimulates the synthesis of a calcium-binding protein (Ca-binding proteins) that carries the Ca across the gut wall. The passive absorption which involves paracellular as well as transcellular moves through and between the mucosal cells, occurs in all parts of the gut, but mainly in the large bowel. It accounts for most Ca absorption when Ca intake is adequate or high8 and helps salvage Ca that has escaped absorption in the small intestine. It is controlled by osmolarity in the gut lumen and in the extracellular fluids, but also by the intraluminal pH, by the presence of specific compounds (e.g., SCFAs), by the concentration of Ca in the gut lumen, and eventually by the presence of a Ca carrier protein, namely calbindin. It is independent of age or vitamin D intake. The passive intestinal paracellular Ca flux can increase if the space between cells, i.e., between the tight and gap junctions increases.9 The colonic component of Ca absorption (±10%) is independent of the efficiency of the small intestinal absorption, and thus it is proportionately larger in low as compared to high small intestinal absorbers.10 It is also influenced by the metabolic activity of the colonic flora that controls Ca speciation and solubility on the one hand and mucosal transport pathway on the other hand.11

Total Ca absorption efficiency adapts to physiological conditions (higher during growth and adolescence and pregnancy but lower after 50 years of age) as well as to intake (greater at low levels of Ca intake). Usually approximately 30-35% of Ca in food is absorbed but it can be higher or lower, depending on food composition but also probably on genetic factors.

The fecal Ca pool represents the biggest proportion of excreted Ca. It is composed of the nonabsorbed dietary Ca plus the endogenous Ca that is secreted in the gastrointestinal tract (from saliva, pancreas, bile, or intestinal mucosa). Once Ca has reached the bloodstream, the main excretion route is the urine (plus very small losses through hair and skin, and in sweat) but the kidney reabsorbs 98-99% of all Ca that it filters. The amount of Ca excreted in the urine varies considerably with age (reduced excretion in old age), sex (men excrete more than women, who excrete more after than before menopause) but also with dietary habits (high with high intakes of sodium and protein but low with high intakes of phosphorus).

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