Calcium
metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...
is the movement and regulation of
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...
ions (Ca
2+) ''in'' (via the
gut) and ''out'' (via the gut and
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
s) of the body, and ''between'' body compartments: the
blood plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the int ...
, the
extracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
and
intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
fluids, and
bone
A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
. Bone acts as a calcium storage center for deposits and withdrawals as needed by the blood via continual
bone remodeling.
An important aspect of calcium metabolism is
plasma calcium homeostasis
In biology, homeostasis ( British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
, the regulation of calcium ions in the
blood plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the int ...
within
narrow limits.
The level of the calcium in plasma is regulated by the hormones
parathyroid hormone (PTH) and
calcitonin
Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...
. PTH is released by the
chief cells of the
parathyroid glands
Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes par ...
when the plasma calcium level falls below the normal range in order to raise it; calcitonin is released by the
parafollicular cells of the
thyroid gland
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
when the plasma level of calcium is above the normal range in order to lower it.
Body compartment content
Calcium is the most abundant mineral in the
human body
The human body is the structure of a human being. It is composed of many different types of cells that together create tissues and subsequently organ systems. They ensure homeostasis and the viability of the human body.
It comprises a hea ...
.
The average adult body contains in total approximately 1 kg, 99% in the skeleton in the form of
calcium phosphate
The term calcium phosphate refers to a family of materials and minerals containing calcium ions (Ca2+) together with inorganic phosphate anions. Some so-called calcium phosphates contain oxide and hydroxide as well. Calcium phosphates are whi ...
salts.
The extracellular fluid (ECF) contains approximately 22 mmol, of which about 9 mmol is in the
plasma.
Approximately 10 mmol of calcium is exchanged between bone and the ECF over a period of twenty-four hours.
Blood concentration
The concentration of calcium ions inside cells (in the
intracellular fluid) is more than 7,000 times lower than in the blood plasma (i.e. at <0.0002 mmol/L, compared with 1.4 mmol/L in the plasma)
Normal plasma levels
The plasma ''total calcium'' concentration is in the range of 2.2–2.6 mmol/L (9–10.5 mg/dL), and the normal ''ionized calcium'' is 1.3–1.5 mmol/L (4.5–5.6 mg/dL).
The amount of total calcium in the blood varies with the level of
plasma albumin, the most abundant protein in plasma, and therefore the main carrier of protein-bound calcium in the blood. The biologic effect of calcium is, however, determined by the amount of ''ionized calcium'', rather than the total calcium. It is therefore the plasma
ionized
Ionization, or Ionisation is the process by which an atom or a molecule acquires a negative or positive charge by gaining or losing electrons, often in conjunction with other chemical changes. The resulting electrically charged atom or molecule ...
calcium level which is
tightly regulated to remain within very narrow limits by homeostatic
negative feedback
Negative feedback (or balancing feedback) occurs when some function of the output of a system, process, or mechanism is fed back in a manner that tends to reduce the fluctuations in the output, whether caused by changes in the input or by othe ...
systems.
Between 35 and 50% of the calcium in plasma is protein-bound, and 5–10% is in the form of complexes with organic acids and phosphates. The remainder (50–60%) is ionized. The ionized calcium can be determined directly by
colorimetry
Colorimetry is "the science and technology used to quantify and describe physically the human color perception".
It is similar to spectrophotometry, but is distinguished by its interest in reducing spectra to the physical correlates of color ...
, or it can be read off from
nomograms, though the usefulness of the latter is limited when the pH and protein content of the plasma deviate widely from the normal.
Function
Calcium has several main functions in the body.
Bound to serum proteins
It readily binds to proteins, particularly those with amino acids whose side chains terminate in carboxyl (-COOH) groups (e.g. glutamate residues). When such binding occurs the electrical charges on the protein chain change, causing the protein's tertiary structure (i.e. 3-dimensional form) to change. Good examples of this are several of the
clotting factors in the blood plasma, which are functionless in the absence of calcium ions, but become fully functional on the addition of the correct concentration of calcium salts.
Voltage gated sodium channels
The
voltage gated sodium ion channels in the cell membranes of nerves and muscle are particularly sensitive to the calcium ion concentration in the plasma.
Relatively small decreases in the plasma ionized calcium levels (
hypocalcemia
Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L) while levels less than 2.1 mm ...
) cause these channels to leak sodium into the nerve cells or axons, making them hyper-excitable (
positive bathmotropic effect), thus causing spontaneous muscle spasms (
tetany
Tetany or tetanic seizure is a medical sign consisting of the involuntary contraction of muscles, which may be caused by disorders that increase the action potential frequency of muscle cells or the nerves that innervate them.
Muscle cramps cau ...
) and
paraesthesia (the sensation of "pins and needles") of the extremities and round the mouth.
When the plasma ionized calcium rises above normal (
hypercalcemia
Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcem ...
) more calcium is bound to these sodium channels having a negative bathmotropic effect on them, causing lethargy, muscle weakness, anorexia, constipation and labile emotions.
Intracellular signalling
Because the intracellular calcium ion concentration is extremely low (see above) the entry of minute quantities of calcium ions from the endoplasmic reticulum or from the extracellular fluids, cause rapid, very marked, and readily reversible changes in the relative concentration of these ions in the
cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
. This can therefore serve as a very effective intracellular signal (or "
second messenger
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first m ...
") in a variety of circumstances, including
muscle contraction
Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such a ...
, the release of hormones (e.g.
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism ...
from the beta cells in the
pancreatic islets) or neurotransmitters (e.g.
acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...
from pre-synaptic terminals of nerves) and other functions.
Bone
Calcium acts structurally as
supporting material in bones as
calcium hydroxyapatite (Ca
10(PO
4)
6(OH)
2).
Muscle
In
skeletal
A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...
and
heart muscle, calcium ions, released from the
sarcoplasmic reticulum
The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are ke ...
(the
endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ...
of
striated muscles
Striations means a series of ridges, furrows or linear marks, and is used in several ways:
* Glacial striation
* Striation (fatigue), in material
* Striation (geology), a ''striation'' as a result of a geological fault
* Striation Valley, in Anta ...
), bind to the
troponin C
Troponin C is a protein which is part of the troponin complex. It contains four calcium-binding EF hands, although different isoforms may have fewer than four functional calcium-binding subdomains. It is a component of thin filaments, along wi ...
protein present on the
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...
-containing thin filaments of the
myofibril
A myofibril (also known as a muscle fibril or sarcostyle) is a basic rod-like organelle of a muscle cell. Skeletal muscles are composed of long, tubular cells known as muscle fibers, and these cells contain many chains of myofibrils. Each myofi ...
s. The troponin's
3D structure changes as a result, causing the
tropomyosin
Tropomyosin is a two-stranded alpha-helical, coiled coil protein found in actin-based cytoskeletons.
Tropomyosin and the actin skeleton
All organisms contain organelles that provide physical integrity to their cells. These type of organelles ...
to which it is attached to be rolled away from the
myosin
Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility.
The first myosin (M ...
-binding sites on the
actin molecules that form the back-bone of the thin filaments.
Myosin
Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility.
The first myosin (M ...
can then bind to the exposed myosin-binding sites on the thin filament, to undergo a repeating series of conformational changes called the
cross-bridge cycle, for which
ATP provides the energy. During the cycle, each myosin protein ‘paddles’ along the thin actin filament, repeatedly binding to myosin-binding sites along the actin filament, ratcheting and letting go. In effect, the thick filament moves or slides along the thin filament, resulting in
muscle contraction
Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such a ...
. This process is known as the
sliding filament model
Sliding may refer to:
* Sliding (dance), also floating or gliding, a group of footwork-oriented dance techniques
* Slide (baseball), an attempt by a baseball runner to avoid getting tagged out
*Sliding (motion)
Sliding is a type of frictional mo ...
of muscle contraction.
Sources
Not all the calcium in the diet can be readily absorbed from the gut. The calcium that is most readily absorbed is found in dairy products (72%), vegetables (7%), grains (5%), legumes (4%), fruit (3%), protein (3%). The calcium contained in vegetable matter is often complexed with
phytates
Phytic acid is a six-fold dihydrogenphosphate ester of inositol (specifically, of the ''myo'' isomer), also called inositol hexakisphosphate (IP6) or inositol polyphosphate. At physiological pH, the phosphates are partially ionized, resulting in ...
,
oxalates,
citrate
Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the ...
and other organic acids, such as the long-chained fatty acids (e.g.
palmitic acid
Palmitic acid (hexadecanoic acid in IUPAC nomenclature) is a fatty acid with a 16-carbon chain. It is the most common saturated fatty acid found in animals, plants and microorganisms.Gunstone, F. D., John L. Harwood, and Albert J. Dijkstra. The ...
), with which calcium binds to form insoluble calcium soaps.
Bone storage
Calcium flow to and from the
bone
A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
may be positive, negative, or neutral. When it is neutral, about 5–10 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 in conjunction with
calcitriol
Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the ...
manufactured in the kidney under the influence of PTH.
Calcitonin
Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...
(a hormone secreted by the thyroid gland when plasma ionized calcium levels are high or rising; not to be confused with "calcitriol" which is manufactured in the kidney) stimulates incorporation of calcium into bone.
Intestinal absorption
The normal adult diet contains about 25
mmol of calcium per day. Only about 5 mmol of this is absorbed into the body per day (see below).
[Barrett KE, Barman SM, Boitano S, Brooks H, "Chapter 23. Hormonal Control of Calcium & Phosphate Metabolism & the Physiology of Bone" (Chapter). Barrett KE, Barman SM, Boitano S, Brooks H: Ganong's Review of Medical Physiology, 23e: http://www.accessmedicine.com/content.aspx?aID=5244785 .]
Calcium is absorbed across the intestinal epithelial cell's
brush border
A brush border (striated border or brush border membrane) is the microvilli-covered surface of simple cuboidal and simple columnar epithelium found in different parts of the body. Microvilli are approximately 100 nanometers in diameter and thei ...
membrane. The TRPV6 channel was proposed to be the major player in intestinal Ca
2+ uptake.
However, ''Trpv6'' KO mice didn't display significant reduction of serum calcium levels and showed only slightly reduced
or even unchanged intestinal Ca
2+ absorption, indicating that other absorption pathways must exist. Recently,
TRPM7 was linked to intestinal calcium uptake. The authors could show that intestinal deletion of
TRPM7 results in strongly reduced calcium levels in serum and bones, and intensively increased levels of
calcitriol
Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the ...
and
PTH, indicating that
TRPM7 is essential for the intestinal bulk uptake of calcium. After the cellular uptake, calcium is immediately bound to
calbindin
Calbindins are three different calcium-binding proteins: calbindin, calretinin and S100G. They were originally described as vitamin D-dependent calcium-binding proteins in the intestine and kidney in the chick and mammals. They are now classi ...
, a
vitamin D-dependent calcium-binding protein. Calbindin transfers the calcium directly into the epithelial cell's
endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ...
, through which the calcium is transferred to the
basal membrane on the opposite side of the cell, without entering its
cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
or intracellular fluid. From there calcium pumps (
PMCA1)
actively transport calcium into the body. Active transport of calcium occurs primarily in the
duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine m ...
portion of the intestine when calcium intake is low; and through passive
paracellular transport
Paracellular transport refers to the transfer of substances across an epithelium by passing through the intercellular space ''between'' the cells. It is in contrast to transcellular transport, where the substances travel ''through'' the cell, pass ...
in the
jejunum
The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialised for the absorption by enterocytes of small nutrient molecules which have been previou ...
and
ileum
The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine m ...
parts when calcium intake is high, independently of Vitamin D level.
The active absorption of calcium from the gut is regulated by the
calcitriol
Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the ...
(or 1,25 dihydroxycholecalciferol, or 1,25 dihydroxyvitamin D
3) concentration in the blood. Calcitriol is a cholesterol derivative. Under the influence of ultraviolet light on the skin, cholesterol is converted to previtamin D
3 which spontaneously isomerizes to vitamin D
3 (or cholecalciferol). It is then converted from cholecalciferol to calcifediol in the liver. Under the influence of
parathyroid hormone, the
kidneys
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...
convert calcifediol into the active hormone calcitriol, which acts on the epithelial cells (
enterocyte
Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase i ...
s) lining the small intestine to increase the rate of absorption of calcium from the intestinal contents. In short the cycle is following:
:
Cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell memb ...
Previtamin D3 Vitamin D3 Calcifediol Calcitriol
Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the ...
Low PTH levels in the blood (which occur under physiological conditions when the plasma ionized calcium levels are high) inhibit the conversion of cholecalciferol into calcitriol, which in turn inhibits calcium absorption from the gut. The opposite happens when the plasma ionized calcium levels are low: parathyroid hormone is secreted into the blood and the kidneys convert more calcifediol into the active calcitriol, increasing calcium absorption from the gut.
[Stryer L. ''Biochemistry'' (Fourth Edition). Chapter 27 "Vitamin D is derived from cholesterol by the ring-splitting action of light". New York, W.H. Freeman and Company.]
Reabsorption
Intestine
Since about 15 mmol of calcium is excreted into the intestine via the bile per day,
the total amount of calcium that reaches the duodenum and jejunum each day is about 40 mmol (25 mmol from the diet plus 15 mmol from the bile), of which, on average, 20 mmol is absorbed (back) into the blood. The net result is that about 5 mmol more calcium is absorbed from the gut than is excreted into it via the bile. If there is no active bone building (as in childhood), or increased need for calcium during pregnancy and lactation, the 5 mmol calcium that is absorbed from the gut makes up for urinary losses that are only partially regulated.
Kidneys
The
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
s filter 250 mmol of calcium ions a day in pro-urine (or
glomerular filtrate
In renal physiology, ultrafiltration occurs at the barrier between the blood and the filtrate in the glomerular capsule (Bowman's capsule) in the kidneys. As in nonbiological examples of ultrafiltration, pressure (in this case blood pressure) a ...
), and resorbs 245 mmol, leading to a net average loss in the urine of about 5 mmol/d. The quantity of calcium ions excreted in the urine per day is partially under the influence of the plasma
parathyroid hormone (PTH) level - high levels of PTH decreasing the rate of calcium ion excretion, and low levels increasing it.
[The main determinant of the amount of calcium excreted into the urine per day is the plasma ionized calcium concentration. The plasma parathyroid hormone (PTH) concentration only increases or decreases the amount of calcium excreted at any ''given plasma ionized calcium concentration''. Thus, in primary ]hyperparathyroidism
Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparathyroidism) or as response to external stimuli (secondary hyperparathyroidism) ...
the quantity of calcium excreted in the urine per day is ''increased'' despite the high levels of PTH in the blood. This is because hyperparathyroidism results in hypercalcemia
Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcem ...
, which increases the urinary calcium concentration ( hypercalcuria) despite the modestly increased rate of calcium re-absorption from the renal tubules caused by PTH's effect on those tubules. Kidney stones
Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a calculus (medicine), solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the ...
are therefore often a first indication of hyperparathyroidism, especially since the hypercalcuria is accompanied by an increase in urinary phosphate excretion (a direct result of the high plasma PTH levels). Together the calcium and phosphate tend to precipitate out as water-insoluble salts, which readily form solid “stones”. However, parathyroid hormone has a greater effect on the quantity of
phosphate ions (HPO
42−) excreted in the urine.
Phosphates form insoluble salts in combination with calcium ions. High concentrations of HPO
42− in the plasma, therefore, lower the ionized calcium level in the extra-cellular fluids. Thus, the excretion of more phosphate than calcium ions in the urine raises the plasma ionized calcium level, even though the total calcium concentration might be lowered.
The kidney influences the plasma ionized calcium concentration in yet another manner. It processes
vitamin D
Vitamin D is a group of Lipophilicity, fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group ar ...
3 into
calcitriol
Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the ...
, the active form that is most effective in promoting the intestinal absorption of calcium. This conversion of vitamin D
3 into calcitriol, is also promoted by high plasma parathyroid hormone levels.
Excretion
Intestine
Most excretion of excess calcium is via the bile and feces, because the plasma calcitriol levels (which ultimately depend on the plasma calcium levels) regulate how much of the biliary calcium is reabsorbed from the intestinal contents.
Kidneys
Urinary excretion of calcium is normally about 5 mmol (200 mg) /day. This is less in comparison to what is excreted via the feces (15 mmol/day).
Regulation
The plasma ionized calcium concentration is regulated within narrow limits (1.3–1.5 mmol/L). This is achieved by both the
parafollicular cells of the thyroid gland, and the
parathyroid glands
Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes par ...
constantly sensing (i.e. measuring) the concentration of calcium ions in the blood flowing through them.
High plasma level
When the concentration of calcium rises, the parafollicular cells of the thyroid gland increase their secretion of
calcitonin
Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...
, a polypeptide hormone, into the blood. At the same time, the parathyroid glands reduce the secretion of parathyroid hormone (PTH), also a polypeptide hormone, into the blood. The resulting high levels of calcitonin in the blood stimulate
osteoblast
Osteoblasts (from the Greek language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...
s in bone to remove calcium from blood plasma and deposit it as bone.
The reduced levels of PTH inhibit removal of calcium from the skeleton. The low levels of PTH have several other effects: there is increased loss of calcium in the urine, but more importantly, the loss of phosphate ions through urine is inhibited. Phosphate ions will therefore be retained in the plasma where they form insoluble salts with calcium ions, thereby removing them from the ionized calcium pool in the blood. The low levels of PTH also inhibit the formation of
calcitriol
Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the ...
(not to be confused with
calcitonin
Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...
) from cholecalciferol (vitamin D
3) by the kidneys.
The reduction in the blood calcitriol concentration acts (comparatively slowly) on the epithelial cells (
enterocytes
Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase i ...
) of the duodenum, inhibiting their ability to absorb calcium from the intestinal contents.
[Guyton A (1976). ‘’Medical Physiology’’. p.1062; New York, Saunders and Co.] The low calcitriol levels also act on bone causing the
osteoclast
An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...
s to release fewer calcium ions into the blood plasma.
Low plasma level
When the plasma ionized calcium level is low or falls the opposite happens. Calcitonin secretion is inhibited and PTH secretion is stimulated, resulting in calcium being removed from bone to rapidly correct the plasma calcium level. The high plasma PTH levels inhibit calcium loss via the urine while stimulating the excretion of phosphate ions via that route. They also stimulate the kidneys to manufacture calcitriol (a steroid hormone), which enhances the ability of the cells lining the gut to absorb calcium from the intestinal contents into the blood, by stimulating the production of
calbindin
Calbindins are three different calcium-binding proteins: calbindin, calretinin and S100G. They were originally described as vitamin D-dependent calcium-binding proteins in the intestine and kidney in the chick and mammals. They are now classi ...
in these cells. The PTH stimulated production of calcitriol also causes calcium to be released from bone into the blood, by the release of
RANKL
Receptor activator of nuclear factor kappa- ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiati ...
(a
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...
, or
local hormone
''B))''
Local hormones are a large group of signaling molecules that do not circulate within the blood. Local hormones are produced by nerve and gland cells and bind to either neighboring cells or the same type of cell that prod ...
) from the
osteoblast
Osteoblasts (from the Greek language, Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cell (biology), cells with a single Cell nucleus, nucleus that synthesize bone. However, in the p ...
s which increases the bone resorptive activity by the osteoclasts. These are, however, relatively slow processes
Thus fast short term regulation of the plasma ionized calcium level primarily involves rapid movements of calcium into or out of the skeleton. Long term regulation is achieved by regulating the amount of calcium absorbed from the gut or lost via the feces.
Disorders
Hypocalcemia
Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L) while levels less than 2.1 mm ...
(low blood calcium) and
hypercalcemia
Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcem ...
(high blood calcium) are both serious medical disorders.
Osteoporosis
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone a ...
,
osteomalacia and
rickets
Rickets is a condition that results in weak or soft bones in children, and is caused by either dietary deficiency or genetic causes. Symptoms include bowed legs, stunted growth, bone pain, large forehead, and trouble sleeping. Complications ma ...
are bone disorders linked to calcium metabolism disorders and effects of
vitamin D
Vitamin D is a group of Lipophilicity, fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group ar ...
.
Renal osteodystrophy is a consequence of
chronic kidney failure
Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, v ...
related to the calcium metabolism.
A diet adequately rich in calcium may reduce calcium loss from bone with advancing (post-
menopausal) age.
A low dietary calcium intake may be a risk factor in the development of
osteoporosis
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone a ...
in later life; and a diet with sustained adequate amounts of calcium may reduce the risk of osteoporosis.
Research
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.
See also
*
European Calcium Society
The European Calcium Society is a non-profit society that aims to develop relationships between different generations of scientists in Europe working in the field of calcium signaling and the proteins involved in the Calcium Toolkit.
Origin
...
Footnotes
References
External links
Calciumat Lab Tests Online
*
{{DEFAULTSORT:Calcium Metabolism
Physiology
Calcium
Human homeostasis
Endocrine system