Calcium metabolism

Calcium

Calcium metabolism or calcium homeostasis is the mechanism by which the body maintains adequate calcium levels. Derangements of this mechanism lead to hypercalcemia or hypocalcemia, which both can have important consequences for health.

Calcium location and quantity

Calcium is the most abundant mineral in the human body. The average adult body contains in total approximately 1 kg, 99% in the skeleton in the form of calcium phosphate salts. The extracellular fluid (ECF) contains approximately 22.5 mmol, of which about 9 mmol is in the serum. Approximately 500 mmol of calcium is exchanged between bone and the ECF over a period of twenty-four hours.^[1]

Normal ranges

The serum level of calcium is closely regulated with a normal total calcium of 2.2-2.6 mmol/L (9-10.5 mg/dL) and a normal ionized calcium of 1.1-1.4 mmol/L (4.5-5.6 mg/dL). The amount of total calcium varies with the level of serum albumin, a protein to which calcium is bound. The biologic effect of calcium is determined by the amount of ionized calcium, rather than the total calcium. Ionized calcium does not vary with the albumin level, and therefore it is useful to measure the ionized calcium level when the serum albumin is not within normal ranges, or when a calcium disorder is suspected despite a normal total calcium level.

Corrected calcium level

One can derive a corrected calcium level when the albumin is abnormal. This is to make up for the change in total calcium due to the change in albumin-bound calcium, and gives an estimate of what the calcium level would be if the albumin were within normal ranges.

Corrected calcium (mg/dL) = measured total Ca (mg/dL) + 0.8 (4.0 - serum albumin [g/dL]), where 4.0 represents the average albumin level in g/dL.

in other words, each 1 g/dL decrease of albumin will raise 0.8 mg/dL in serum Ca

Or: Corrected calcium (mmol/L) = measured total Ca (mmol/L) + 0.02 (40 - serum albumin [g/L]), where 40 represents the average albumin level in g/L

in other words, each 1 g/L decrease of albumin, will raise 0.02 mmol/L in serum Ca

When there is hypoalbuminemia (a lower than normal albumin), the corrected calcium level is higher than the total calcium.

Effector organs

Sources

About 25 mmol of calcium enters the body in a normal diet. It can be lower if the diet is low in milk and dairy products, or other calcium-containing foods (such as some kind of fish, or calcium-rich water; the calcium of leafy green vegetables is poorly absorbed).^{[citation needed]} Of this, about 40% (10 mmol) is absorbed in gut, and 5 mmol leaves the body in feces, netting 5 mmol of calcium a day.

Excretion

The kidney excretes 250 mmol a day in pro-urine, and resorbs 245 mmol, leading to a net loss in the urine of 5 mmol/l. In addition to this, the kidney processes Vitamin D into calcitriol, the active form that is most effective in assisting intestinal absorption. Both processes are stimulated by parathyroid hormone.

The role of bone

Although calcium flow to and from the bone is neutral, about 5 mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Calcium release from bone is regulated by parathyroid hormone. Calcitonin stimulates incorporation of calcium in bone, although this process is largely independent of calcitonin.

Low calcium intake may also be a risk factor in the development of osteoporosis. In one meta-analysis, the authors found that only two out of the 52 studies that they reviewed showed that calcium intake did not promote better bone balance.^[2] With a better bone balance, the risk of osteoporosis is lowered.

Interaction with other chemicals

Potential positive interactions

• Vitamin D is an important co-factor in the intestinal absorption of calcium, as it increases the number of calcium binding proteins, involved in calcium absorption through the apical membrane of enterocytes in small intestine. It also promotes re-absorption of calcium in the kidneys.
• Boron

Potential negative interactions

• "Unesterified long-chain saturated fatty acids, i.e. palmitic acid, have a melting point above body temperature and, with sufficient calcium in the intestinal lumen, form insoluble calcium soaps."^[3]
• Sodium^{[citation needed]}
• Phytic acid^{[citation needed]}
• Oxalic acid^{[citation needed]}
• Caffeine^{[citation needed]}
• Cortisol^[4]
• Low pH food and proteins (the latter promotes gastric acid)

Regulatory organs

Primarily calcium is regulated by the actions of 1,25-OH-vitamin D3, parathyroid hormone and calcitonin and direct exchange with the bone matrix. Plasma calcium levels are regulated by hormonal and non-hormonal mechanisms. After ingestion of substantial amounts of calcium, for example in a glass of milk, the short term control that prevents calcium spiking in the serum is absorption by the bone matrix. After about an hour, PTH will be released and not peak for about 8 hours.^[5] The PTH is, over time, a very potent regulator of plasma calcium, and controls the conversion of vitamin D into its active form in the kidney. The parathyroid glands are located behind the thyroid, and produce parathyroid hormone in response to low calcium levels.

The parafollicular cells of the thyroid produce calcitonin in response to high calcium levels, but its significance is much smaller than that of PTH.

Pathology

Hypocalcemia and hypercalcemia are both serious medical disorders.

Renal osteodystrophy is a consequence of chronic renal failure related to the calcium metabolism.

Osteoporosis and osteomalacia have been linked to calcium metabolism disorders.

Research into cancer prevention

The role that calcium might have in reducing the rates of colorectal cancer has been the subject of many studies. However, given its modest efficacy, there is no current medical recommendation to use calcium for cancer reduction. Several epidemiological studies suggest that people with high calcium intake have a reduced risk of colorectal cancer. These observations have been confirmed by experimental studies in volunteers and in rodents. One large scale clinical trial shows that 1.2 g calcium each day reduces, modestly, intestinal polyps recurrence in volunteers.^[6] Data from the four published trials are available.^[7] Some forty carcinogenesis studies in rats or mice, reported in the Chemoprev.Database, also support that calcium could prevent intestinal cancer.^[8]

See also

• Disorders of calcium metabolism
• Calcium in biology

References

External links

• Physiology at MCG 5/5ch6/5ch6line