Calcium metabolism or calcium homeostasis is the mechanism by which the body maintains adequate calcium

Calcium

Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 levels. Derangements of this mechanism lead to hypercalcemia or hypocalcemia, both of which 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

Blood plasma

Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

. Approximately 500 mmol of calcium is exchanged between bone and the ECF over a period of twenty-four hours.

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

Serum albumin

Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...

, 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 decrease 0.8 mg/dL in measured serum Ca and thus 0.8 must be added to the measured Calcium to get a corrected Calcium value.

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 decrease 0.02 mmol/L in measured serum Ca and thus 0.02 must be added to the measured value to take this into account and get a corrected calcium.

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

Absorption

About 25 mmol

Mole (unit)

The mole is a unit of measurement used in chemistry to express amounts of a chemical substance, defined as an amount of a substance that contains as many elementary entities as there are atoms in 12 grams of pure carbon-12 , the isotope of carbon with atomic weight 12. This corresponds to a value...

 of calcium enters the body in a normal diet. Of this, about 40% (10 mmol) is absorbed in small intestine

Small intestine

The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...

, and 5 mmol leaves the body in feces, netting 5 mmol of calcium a day.

Calcium is absorbed across the intestinal brush border

Brush border

A brush border is the name for the microvilli-covered surface of simple cuboidal epithelium and simple columnar epithelium cells found in certain locations of the body. Microvilli are approximately 100 nanometers in diameter and their length varies from approximately 100 to 2,000 nanometers in...

 membrane, passing through ion channels such as TRPV6

TRPV6

TRPV6 is a membrane calcium channel which is responsible for the first step in calcium absorption in the intestine. It was first named CAT1, or ECaC2, and has been described in the intestine in several species, including humans. It is located in the apical brush-border membrane of the intestinal...

. Calbindin

Calbindin

Calbindin refers to several calcium-binding proteins. They were originally described as vitamin D-dependent calcium-binding proteins in the intestine and kidney in the chick and mammals...

 is a vitamin D-dependent calcium-binding protein

Vitamin D-dependent calcium-binding protein

Vitamin D-dependent calcium binding proteins were discovered in the cytosolic fractions of chicken intestine, and later in mammalian intestine and kidney, by workers including Robert Wasserman of Cornell University....

 inside intestinal epithelial cells which functions together with TRPV6 and calcium pumps (PMCA1) in the basal membrane to actively transport

Active transport

Active transport is the movement of a substance against its concentration gradient . In all cells, this is usually concerned with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. If the process uses chemical energy, such as from adenosine...

 calcium into the body. The active transport occurs primarily in the duodenum when calcium intake is low, and passive paracellular diffusion occurs in the ileum and jejunum, independent of Vitamin D, when calcium intake is high.

Excretion

The kidney

Kidney

The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

 excretes 250 mmol a day in pro-urine, and resorbs 245 mmol, leading to a net loss in the urine of 5 mmol/d. In addition to this, the kidney processes Vitamin D into calcitriol

Calcitriol

Calcitriol , also called 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3, is the hormonally active form of vitamin D with three hydroxyl groups...

, the active form that is most effective in assisting intestinal absorption. Both processes are stimulated by parathyroid hormone

Parathyroid hormone

Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...

.

The role of bone

Although calcium flow to and from the bone

Bone

Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...

 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

Parathyroid hormone

Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...

. Calcitonin

Calcitonin

Calcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the parafollicular cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium , opposing the effects of parathyroid hormone . Calcitonin has been found...

 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

Meta-analysis

In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...

, the authors found that fifty out of the fifty-two studies that they reviewed showed that calcium intake promoted better bone balance. With a better bone balance, the risk of osteoporosis is lowered.

Potential positive interactions

• Vitamin D
  Vitamin D
  Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
  
   is an important co-factor in the intestinal absorption of calcium, as it increases the number of calcium binding protein
  Calbindin
  Calbindin refers to several calcium-binding proteins. They were originally described as vitamin D-dependent calcium-binding proteins in the intestine and kidney in the chick and mammals...
  
  s, involved in calcium absorption through the apical membrane of enterocyte
  Enterocyte
  Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells found in the small intestines and colon. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase surface area for the digestion and transport of molecules from the intestinal...
  
  s in small intestine
  Small intestine
  The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
  
  . It also promotes re-absorption of calcium in the kidneys.
• Boron
  Boron
  Boron is the chemical element with atomic number 5 and the chemical symbol B. Boron is a metalloid. Because boron is not produced by stellar nucleosynthesis, it is a low-abundance element in both the solar system and the Earth's crust. However, boron is concentrated on Earth by the...
  
  

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."
• Sodium
  Sodium
  Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
  
   binding to calcium
• Phytic acid
  Phytic acid
  Phytic acid is the principal storage form of phosphorus in many plant tissues, especially bran and seeds. Phytate is not digestible to humans or nonruminant animals, however, so it is not a source of either inositol or phosphate if eaten directly...
  
    binding to calcium
• Oxalic acid
  Oxalic acid
  Oxalic acid is an organic compound with the formula H2C2O4. This colourless solid is a dicarboxylic acid. In terms of acid strength, it is about 3,000 times stronger than acetic acid. Oxalic acid is a reducing agent and its conjugate base, known as oxalate , is a chelating agent for metal cations...
  
   binding to calcium
• Caffeine
  Caffeine
  Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
  
   binding to calcium
• Cortisol
  Cortisol
  Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
  
   binding to calcium
• Low pH food and proteins (the latter promotes gastric acid)

Regulatory organs

Primarily calcium is regulated by the actions of 1,25-Dihydroxycholecalciferol, parathyroid hormone (PTH) 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 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. 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

Thyroid

The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...

, 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

Parathyroid hormone

Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...

.

Pathology

Hypocalcemia and hypercalcemia are both serious medical disorders.

Renal osteodystrophy

Renal osteodystrophy

Renal osteodystrophy or chronic kidney disease-mineral and bone disorder is a bone pathology, characterized by bone mineralization deficiency, that is a direct result of the electrolyte and endocrine derangements that accompany chronic kidney disease...

 is a consequence of chronic renal failure

Chronic renal failure

Chronic kidney disease , also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite...

 related to the calcium metabolism.

Osteoporosis

Osteoporosis

Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...

 and osteomalacia

Osteomalacia

Osteomalacia is the softening of the bones caused by defective bone mineralization secondary to inadequate amounts of available phosphorus and calcium, or because of overactive resorption of calcium from the bone as a result of hyperparathyroidism...

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. Data from the four published trials are available. Some forty carcinogenesis studies in rats or mice, reported in the Chemoprev.Database, also support that calcium could prevent intestinal cancer.