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Calcium Function, Sources, Absorption, Deficiency, and Management in Human Body

Calcium is the most abundant cation in the body and powerful homeostatic mechanisms control circulating ionized calcium levels. Ninety-eight percent of body calcium is found in the skeleton which is in equilibrium with the extracellular concentration of calcium. Approximately 1% to 2% of body calcium exists in the extracellular fluid for physiological functions like blood coagulation, cellular communication, exocytosis, endocytosis, muscle contraction, and neuromuscular transmission. Calcium affects the intracellular processes through its calcium-binding regulatory protein, calmodulin.

The WHO’s dietary guidelines for calcium differ between countries, with higher intakes usually recommended in places with higher fracture prevalence. Between 20% and 30% of the calcium in the diet is absorbed, depending on vitamin D status and food source. Calcium requirements depend on phosphorus intakes, with an optimum molar ratio (Calcium: Phosphorus) of 1: 1. Excessive phosphorus intakes (e.g. 1–1.5 g/day) with Calcium: Phosphorus of 1: 3 have been shown to cause hypocalcaemia and secondary hyperparathyroidism.

Function

Ionized calcium in the plasma has many vital functions including formation of bones and teeth, coagulation of blood, contraction of muscles, cardiac action, milk production, relay of electrical and chemical messages that arrive at a cell's surface membrane to the biochemical machinery within the cell, keeping the membranes of cells intact and in the metabolism of enzymes and hormones. It also plays a crucial role in the transformation of light to electrical impulses in the retina. In short, the calcium ion controls many life processes ranging from muscle contraction to cell division.

Sources

Calcium is readily available from many sources. The best natural sources are milk and milk products, (e.g. Cheese, curd, skimmed milk, and buttermilk), eggs and fish. A liter of cow's milk provides about 1200 mg of calcium, and human milk about 300 mg. Calcium occurs in milk as calcium caseinogenate which is readily assimilated by the body. The cheapest dietary sources are green leafy vegetables, cereals, and millets. The limiting factor in the complete absorption of calcium from green leafy vegetables (e.g., spinach) is the presence of oxalic acid with which calcium forms an insoluble compound, calcium oxalate which interferes with the absorption of calcium. Most cereals are generous providers of calcium. Rice is very deficient in calcium. The bioavailability of calcium from cereals is poor because of the presence of phytic acid which forms an insoluble compound with calcium, calcium phytate. An additional source of calcium is drinking water which may provide up to 200 mg/day.

Absorption

The intestine serves as a Long-term homeostatic mechanism for calcium. Although the major source of calcium is dietary, less than 15% of dietary calcium is absorbed in ileum and jejunum by means of active transport and facilitated diffusion. Most of the filtered calcium is reabsorbed in the proximal tubule (70%), ascending loop of Henle (20%), and distal tubule and collecting duct (5-10%). Factors that promote calcium reabsorption include parathyroid hormones (PTH), calcitonin, vitamin D, thiazide diuretics, and volume depletion. Volume expansion increases sodium intake and diuretics like mannitol and furosemide promote calcium excretion. Calcium is controlled primarily by major regulatory hormones, PTH, calcitonin, and vitamin D. Additionally thyroid hormones, growth hormone, adrenal and gonadal steroids also have minor influences on calcium metabolism.

Role of the calcium-sensing receptor

The calcium-sensing receptor is a G protein-coupled receptor, which allows the parathyroid chief cells, the thyroidal C cells, and the ascending limb of the loop of Henle (renal tubular epithelial cells) to respond to changes in the extracellular calcium concentration. The ability of the calcium-sensing receptor to sense the serum calcium is essential for the appropriate regulation of PTH secretion by the parathyroid glands and for the regulation of passive Paracellular calcium absorption in the loop of Henle. Calcitonin secretion and renal tubular calcium reabsorption are directly regulated by the action of calcium ion on its receptor. Ionized calcium acts through calcitonin, to inhibit its release from bones. A decrease in extracellular calcium concentration, stimulates the calcium-sensing receptor in parathyroid glands, resulting in an increase in PTH secretion. PTH increases distal renal tubular reabsorption of calcium within minutes and stimulates osteoclast activity, with the release of calcium from the skeleton within 1-2 hours. More prolonged PTH elevation stimulates 1a-hydroxylase activity in the proximal tubular cells, which leads to 1, 25-dihydroxyvitamin D production. In the kidney, vitamin D and PTH stimulate the activity of the epithelial calcium channel and the calcium-binding protein to increase active transcellular calcium absorption in the distal convoluted tubule. These mechanisms help to maintain normal levels of serum calcium.

Plasma calcium exists in three different forms

50% as biologically active ionized form, 45% bound to plasma proteins (mainly albumin), and 5% complexes to phosphate and citrate. In the absence of alkalosis or acidosis, the proportion of albumin-bound calcium remains relatively constant. Metabolic acidosis leads to increased ionized calcium from reduced protein binding and alkalosis has the opposite effect. Plasma calcium is tightly regulated despite its large movements across the gut, bone, kidney, and cells in the normal range of 9-11 mg/ dl. Because calcium binds to albumin and only the unbound (free or ionized) calcium is biologically active, the serum level must be adjusted for abnormal albumin levels. For every 1 g/ dl drop in serum albumin below 4 g/dl, measured serum calcium decreases by 0.8 mg/dl.

Deficiency

Hypocalcaemia is defined as serum calcium less than 8 mg/ dl or ionized calcium below 4 mg/ dl.  Hypocalcaemia manifests as central nervous system irritability and poor muscular contractility. Newborns present with nonspecific symptoms such as lethargy, poor feeding, jitteriness, vomiting, abdominal distension, and seizures. Children may develop seizures, twitching, cramps, and rarely laryngospasm. Tetany and signs of nerve irritability may manifest as muscular twitching, carpopedal spasm, and stridor. Latent tetany can be diagnosed clinically by clinical maneuvers such as Chvostek sign (twitching of the orbicular.is oculi and mouth elicited by tapping the facial nerve anterior to the external auditory meatus).

Management

Tetany, laryngospasm, and seizures must be treated immediately with 2 ml/kg of 10% calcium gluconate, administered intravenous slowly under cardiac monitoring. Calcium gluconate 10% (100 mg/ml) intravenous solution contains 9.8 mg/ml (0.45 mEq/ml) elemental calcium; calcium chloride 10% (100 mg/ml) contains 27 mg/ml (1.4 mEq/ mL) {milli-equivalents per milliliter (mEq/ml), which also equals equivalents per liter (eq/l)}. Initially, IV calcium boluses are given every 6 hr. Thereafter, oral calcium supplementation is provided at 40-80 mg I kg Ida y. Oral calcium therapy is used in asymptomatic patients and as a follow-up to intravenous (IV) calcium therapy. Intravenous infusion with calcium-containing solutions can cause severe tissue necrosis; therefore, the integrity of the intravenous site should be ascertained before administering calcium through a peripheral vein. Rapid infusion of calcium-containing solutions through arterial lines can cause arterial spasm and if administered via an umbilical artery catheter, intestinal necrosis. Magnesium administration is necessary to correct any hypomagnesaemia because hypocalcaemia does not respond until the low magnesium level is corrected. In patients with concurrent acidemia, hypocalcaemia should be corrected first. Acidemia increases the ionized calcium levels by displacing calcium from albumin. Calcium carbonate is an oral supplement providing 40% elemental calcium.

Published : Jan 16 2022
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