Calcium (Book)
How is calcium present in foods?
Calcium is present in foods in the form of insoluble salts.
How do magnesium and zinc, which are divalent cations, interact with calcium absorption?
Divalent cations such as magnesium and zinc can interact with calcium to inhibit calcium absorption. This occurs as magnesium and calcium compete with each other for intestinal absorption whenever an excess of either is present within the gastrointestinal tract.
What is paracellular absorption?
Paracellular absorption is the absorption of a molecule in between cells rather than into them.
When does paracellular absorption mainly, or most frequently occur?
Paracellular absorption occurs mainly when higher calcium concentrations are present in the lumen, thus creating a concentration gradient between the lumen and the basolateral side of the enterocyte.
What are two gycosaminoglycans associated with bone and cartilage formation?
Two glycosaminoglycans associated with bone and cartilage formation include hylauronic acid and chondroitin sulfate.
What is the typical range in which blood calcium is often maintained?
Blood calcium is often maintained between 8.5 to 10.5 mg/dL or 2.12 to 2.63 mmol/L.
How does bone mineralization occur during osteoblast activity?
Bone mineralization occurs as osteoblasts secrete the proteins and ground substances and thus become embedded in the current protein and ground substance matrix over time. Minerals such as phosphorous, magnesium, and calcium enter bone fluid from the blood and then attach to bone proteins and ground substances eventually forming the hydroxyapetite matrix.
In addition to caffeine, what other dietary factors decrease Calcium absorption from the diet?
In addition of caffeine, phytic acid or phytate or inositol hexaphosphate, have been found to inhibit calcium absorption, and are typically found in foods such as whole grain breads, seeds, and legumes.
In addition to caffeine and phytic acid, what other dietary factor has been found to decrease or inhibit calcium absorption?
In addition to caffeine and phytic acid, calcium absorption is also found to be inhibited by the presence of oxalic acid which chelates the ionized calcium, has a very low solubility and increases fecal calcium excretion as a result. It is found primarily in vegetables such as spinach, rhubarb, swiss chard, beets, celery, egg plant, greens, okra, squash, currants, strawberries, blackberries, blueberries, gooseberries, nuts such as pecans, peanuts, and some beverages such as ovaltine, cocoa and tea.
what is the tolerable upper intake level of calcium for adults?
In adults, the tolerable upper intake level has been established at 2500 mg/day which then decreases to 2000 mg/day in those over the age of 51.
What is MAARS?
MAARS is short for membrane-associated rapid response steroid-binding protein and is though to be involved in transcaltachia which is initiated by calcitriol binding to the receptors on enterocytes in the brush border cells of the small intestine.
What medications can contribute to a decreased absorption of calcium in foods from the diet?
Medications such as proton pump inhibitors, prevacid, and nexium, which are typically used to treat GERD or gastric ulcers can inhibit calcium absorption as they result in a decreased production of stomach acid available to solubilize calcium salts.
What other non dairy sources of calcium are there?
Other non dairy sources of calcium include vegetables such as kale, turnip, mustard greens, broccoli, cauliflower, as well as legumes, which include tofu and nuts are also able to provide calcium in the diet.
How do osteoblasts act in the process of producing new bone?
Osteoblasts act in producing new bone, after being in contact with calcitriol, PTH, estrogen and other hormones, and acts in producing collagen, and other proteins as well as ground substances, including the bone matrix/extracellular matrix surrounding the bone cells that becomes mineralized over time.
How do osteoclasts function in breaking down bone and releasing calcium into the blood?
Osteoclasts, are large multinucleated cells that attach onto one selected area on the bone surface and start the degradation process. Resorption is thought to begin when two proteins, macrophage colony stimulating factor or M-CSF and receptor activator of nuclear factor k B ligand or RANKL, are produced by osteoblasts. These proteins in turn, bind to RANK receptors on osteoclast precursor cells to stimulate their prolifferation, differentiation, and fusion to produce mature osteoclasts as a result.
What is the difference between osteonectin, osteopontin, osteocalciun, matrix Gla protein?
Osteonectin, a phosphoprotein, is the most abundant and binds both to calcium, and collagen, while osteopontin, binds to both hydroxyapetite, and bone cells, and osteocalcin and matrix Gla protein, function in calcium and hydroxyapatite binding and mineral deposition. Osteocalcin and matrix Gla protein are both dependent on vitamin K for their carboxylation of their glutamic acid residues for functionality. Their synthesis is dependent on the action of calcitriol. Bone sialoprotein promotes hydroxyapetite crystal nucleation as well.
What are some other physical factors effecting the absorption of calcium within the diet?
Other factors affecting the absorption of calcium in the diet include the presence of pregnancy, lactation, growth which increase calcium absorption from the diet.
How does parathyroid hormone act in increasing extracellular fluid calcium concentrations in the body? (Blood plasma/serum)
Parathyroid hormone acts in increasing extracellular fluid calcium concentrations in its interaction with the kidneys and bones. For example, in the kidney, PTH increases the synthesis of calcitriol from 25-OH Vitamin D. Calcitriol then is produced as a result, increases the renal tubular reabsorption of calcium and does this through the synthesis of calbindin D28k, a vitamin D-dependent calcium transporter found in the kidneys. In the bone, PTH interacts with receptors on osteoblasts, which can also involve calitriol as well in its action. The osteoblast then produce two proteins, macrophage colony stimulating factor and receptor activator of nuclear factor k B ligand, or RANKL, which binds to RANK receptors on the osteoclast precursor cells to stimulate their proliferation and differentiation into osteoclasts. The osteoclasts then release proteases and acids that degrade bone, and promote the release of calcium from the bone into the blood as a result.
What factors have been shown to increase urinary calcium excretion?
Protein, caffeine, and sodium have been shown to increase urinary calcium excretion yet while high intakes of protein may increase urinary calcium excretion, it is thought that the protein's ability to enhance calcium absorption and inhibit calcium secretion into the GI tract cancel out its promotion of urinary calcium losses. Urinary sodium and calcium excretion are linked in the proximal renal tubule as they both share a common resorption mechansim. Thus sodium consumption of 500 mg per day can increase calcium excretion by 10 mg per day accordingly. Loss of calcium endogenously ranges from 45 to 100 mg/day.
What is TRPV6? What type of pathway is it involved in with regard to calcium absorption?
TRPV6 refers to transient receptor potential vitamin-D dependent membrane channel protein receptor vanilloid 6 which is involved in the transport of Calcium from the lumen of the SI, across the enterocyte's brush border membrane then across the cytosol of the enterocyte into the blood plasma of the patient. Other factors involved include calbindin D9k, and Vitamin D-dependent calcium-ATP ase pump on the luminal side of th enterocyte which acts in releasing the calcium then into the blood plasma.
What is the recommended daily allowance for calcium in the diet?
The RDA for calcium is 1000 mg/day for adult men and women age 19 to 70, while for females age 51 and older as well as males age 71 and older, the RDA for calcium is increased to 1200 mg/day.
What are the best sources of calcium found in the diet?
The best food sources of calcium include dairy products, especially milk, cheese, yogurt and selected sea foods such as salmon, sardines, clams, and oysters.
What percentage of calcium constitute the bone and teeth?
The bone and teeth constitute roughly 99% of the body's available calcium.
What is the daily value for calcium?
The daily value for calcium is 1000 mg/day.
What is the final minor pathway contributing to calcium absorption, where does it occur?
The final minor pathway contributing to calcium absorption occurs in the large intestine where bacteria may release calcium that is bound to some fermentable fibers such as pectins, where about 4 to 10% of a person's dietary calcium is absorbed each day.
Where is the main transport system of calcium located in the small intestine?
The main transport system for calcium operates primarily in the duodenum and proximal jejunum. It is saturable at low to moderate calcium intakes.
What is the most abundant divalent cation in the body?
The most abundant divalent cation in the body is calcium
What acts in regulating the process of osteoclast activity?
To regulate the process of the dissolving of bone, osteoclasts thus produce osteprotegerin, a protein that binds to RANKL to prevent it form binding to receptors on osteoclastic cells thus osteoprotegerin inhibits osteoclast differentiation and activity as a result.
How does transcaltachia occur? How is it effected by calcitriol?
Transcaltachia occurs within minutes of calcitriol binding to the receptors on an enterocyte's basolateral membrane A Vitamin D-binding protein receptor called membrane -associated rapid response steroid-binding protein (MARRS) is though to be involved in transcaltachia.
What two systems contribute in a minor capacity to calcium absorption in the small intestines?
Two other systems which contribute to calcium absorption in the small intestine are vesicular transport and transcaltachia.
In addition, how do unabsorbed dietary fatty acids inhibit calcium absorption from the diet?
Unabsorbed dietary fatty acids, which can occur in the occurrence of steatorrhea, can interfere with calcium absorption by forming insoluble calcium soaps in the lumen of the small intestine which cannot be absorbed and are thus excreted in the feces. Thus, steatorrhea, and inadequate calcium absorption are a higher risk for those with fat malabsorptive conditions such as IBS, and disorders affecting the pancreas such as pancreatitis and cystic fibrosis.
What is Vesicular transport? What does it involve?
Vesicular transport involves endocytosis of calcium across the intestinal cell's brush border membrane after which the calcium is sequestered into vesicles. These vesicles merge with lysosomes to facilitate the release of calicum into the cell cytosol.
Major minerals are required in adults for more than what amount per day?
major minerals are required in the body more than 100 mg per day
What is calbindin D28k? Where is it produced? What does it effect?
Calbindin D28k is a vitamin D-dependent calcium transporter found in the kidneys. It acts in increasing the renal tubular reabsorption of calcium back into the blood within the kidney's filtering process.
What is calbindin D9k?
Calbindin D9k is a Vitmain D-dependent cytosolic binding protein that shuttles the calcium across the cell cytosol in the active,carrier mediated uptake of calcium that is saturable.
How does calcitonin act in normilizing blood calcium values?
Calcitonin syntesized in the parafollicular cells of the thyroid gland functions in opposition to PTH and calcitriol to lower serum calcium concentrations should they rise above the upper end of the normal range which is above 10.5 mg/dL. Calcitonin suppresses PTH production, and inhibits the activity of osteoclasts to prevent further mobilization of Ca2+ out of the bones and into the blood supply.
How does the hormone, calcitriol act in improving or increasing calcium absorption within the small intestine?
Calcitriol acts in improving calcium absorption in the lumen of the small intestines mainly by interacting with nuclear Vitamin D receptors to induce the transcription of the gene that codes for calbindin D9k which functions as a calcium-binding protein to promote calcium transport through the cytosol of the enterocyte. Calcitriol also enhances calcium absorption at the brush border membrane by increasing calcium ATPase pumps as well. The vitamin also appears to facilitate paracellular absorption by promoting the synthesis of specific claudin proteins. Thus, the net effect of these actions by PTH and calcitriol is to increae serum calcium concentrations up into the normal range.
How does calcitriol increase the rate of absorption of calcium?
Calcitriol's action on the enterocytes of the brush border of the small intestine through active and passive diffusion increases the absorption of calcium by about 10% in its action.
What form of calcium supplement available is favorable for those with limited gastric acid production?
Calcium citrate is most beneficial for those with limited gastric acid, and can also be digested without food.
What parts of the body are most effected by development of a calcium deficiency?
Calcium deficiency most profoundly affects bone and muscles whereas rickets occurs in children and osteomalacia in adults along with a decreased Vitamin D intake. Low levels of free Ca2+ in the blood may result in tetany, a condition characterized by intermittent muscle contractions that fail to relax muscles of the arms and legs. Muscle pain, cramps, or spasms as well as numbness or tingling in the hands and feet are also common signs of tetany as well as convulsions which may occur. In addition to osteoporosis, calcium deficiency increases a person's risk for the development of hypertension, colon cancer, type 2 diabetes, and obesity.
Who are primarily at higher risk for the development of calcium deficiency?
Calcium deficiency occurs at higher rates in patients with fat malabsorption, immobilization, decreased GI transit time, and long-term use of thiazide diuretics.
How is calcium absorbed in the cells of the small intestine via active carrier mediated diffusion?
Calcium is absorbed from the lumen of the GI tract across the enterocyte's brush border membrane, then across the cytosol of the enterocyte and into the plasma using this system requires: a vitamin D-dependent membrane channel protein called transient receptor potential vanilloid (V)6, also known as TPV6 but also called calcium transporter 1 or Ca T1. Also required for Ca absorption across the enterocyte's brush border is the Vitamin-D dependent cytosolic binding protein called calbindin D9k that shuttles the calcium across the cell cytosol, and Vitamin D-dependent calcium-ATP-ase. pump on the luminal side of the enterocyte which causes a release of Ca into the membrane of the enterocyte on the brush border of the GI tract.
How is calcium absorbed in the small intestine?
Calcium is absorbed within the small intestine by using two main transport systems, including saturable, carrier mediated active transport, as well as diffusion.
How is calcium mainly excreted from the body?
Calcium is excreted from the body mainly in the urine and feces although up to 182 mg may be lost daily through the skin as well in conditions of extreme sweating. Of the calcium that is filtered in the kidneys, most is reabsorbed by the kidneys such that urinary calcium losses range from 100 to 240 mg per day with an average of roughly 170 mg/day typically. Most of the filtered calcium is reabsorbed passively in the proximal tubule. In the ascending loop of henle calium sensing receptors respond to serum calcium concentrations and adjust active reabsorption accordingly while Transient receptor potential calcium channel vanilloid or TRPV 5 and calbindin D28k regulate active calcium absorption within the distal tubule region.
In what main forms is calcium transported in the blood?
Calcium is mainly transported in the blood in three forms, including some calcium that is bound mainly to proteins such as albumin and prealbumin in the blood, which accounts for 40% of calcium present in the blood. Other forms include calcium that has been complexed with sulfate, phosphate, or citrate in the blood. The final way in which calcium has been found to be transported in the blood is in its free or ionized form.
What percentage of the body's mineral mass and body weight does calcium represent?
Calcium represents at least 40% of the body's mineral mass and 1.5 to 2.0% of the person's body weight.
How and where are calcium salts solubilized?
Calcium salts are solubilized or made soluble in the stomach by the stomach acid as it dissolves the calcium salts. It does so in roughly 1 hr.
What are claudins, how does Vitamin D intake affect them? How are they involved in calcium absorption?
Claudins are selected transmembrane proteins which are essential for paracellular intestinal calcium absorption. Vitamin D enhances the expression of genes that code for claudins.
What are some factors influencing absorption of calcium from foods and supplements in the diet?
Factors which influence calcium absorption from foods include a diet low in calcium (<400 mg/day). This is because a drop in blood calcium levels causes an increase in activity of parathyroid hormone which acts to produce calcitriol from the kidneys which act on enterocytes in the small intestine to increase the saturable, carrier-mediated active transport mechanism as well as the passive, paracellular method of calcium absorption through the increase in activity and production of claudins.
What essential body processes is free ionized calcium an essential component in?
Free ionized calcium is essential for blood clotting, in which the calcium is needed in the clot formation, as well as skeletal muscle contraction, as well as visceral smooth muscle contractions, membrane permeability, ion channels of nerotransmitters, and in various binding proteins such as calmodulin which is a cytosolic calcium-binding protein operative in most body calls. Calmodulin interacts with a variety of enzymes such as calcineurin, myosin light-chain kinase, phosphorylase kinase, and calcium calmodulion kinases.
What mediates the process of paracellular absorption in the small intestine?
Increases in concentration of intracellular calcium ions are thought to mediate the process through a series of reactions to ultimately open the junctions between cells to facilitate calcium absorption in the lumen. Vitamin D has also been shown to enhance the expression of genes that code for selected trans-membrane proteins, called claudins, which have been shown to be essential for paracellular intestinal calcium absorption. Fructose oligosaccharides, inulin, and other non-digestible saccharides also have been shown to enhance paracellular calcium absorption in the small intestines.
What is the difference between the amount of calcium absorption of infants and children and adults?
Infants and children absorb up to twice the amount of calcium than adults and typically absorb roughly 60% of their calcium from the diet.
What nutrients have been found to inhibit or enhance calcium absorption from the diet?
Ingestion of large amounts of calcium with a phosphorous-containing meal inhibits phosphorus absorption, while calcium intake from dietary sources and supplements has been found to decrease primarily non-heme iron absorption.
How is the main transport system in the duodenum and the jejunum regulated?
It is regulated by calcitriol, the active form of Vitamin D.
How much calcium do milk and/or yoghurt provide?
Milk and yoghurt provide 200 to 400 mg of Ca per cup or 8 fl oz.
What dietary components have also seen a decrease in absorption of calcium from the diet?
Several dietary components diminish calcium absorption or promote its secretion from the blood back into the GI Tract, the ingestion of caffeine leads to an increased secretion of calcium in the gut, thus leading to higher levels of endogenous fecal calcium losses as a result.
What are some of the main proteins found in bone?
Some of the main proteins found in bone include osteonectin, osteopontin, and osteocalcin and matrix Gla protein, as well as bone sialoprotein.
What are some signs and symptoms of hypercalcemia and systemic alkalosis?
Some signs and symptoms of hypercalcemia and systemic alkalosis include lethargy, anorexia, nausea, vomiting and heart arrhythmias.
Which foods contain oxalic acid and are poor sources of calcium?
Soom sources of oxalic acid include spinach rhubarb and swiss chard.
What is the overall average percentage of calcium absorption of adults from the diet?
The overall percentage of calcium absorbed from foods in the diet is roughly 25 to 30% of the calcium found in foods as a whole.
What percentage of calcium absorption accounts for active, carrier mediated transport in the duodenum and proximal jejunum?
The percentage of absorption of calcium accounted for by saturable, carrier mediated active transport is roughly 60% of calcium intakes up to 400- 500 mg/meal.
What is the second major route for calcium absorption?
The second major route for calcium absorption is paracellular diffusion. This route is passive and non-saturable and is a non-regulated process, that is very concentration dependent and occurs throughout the small intestine but mostly within the jejunum and ileum.
What are some other roles of calcium in the body?
The small amount of calcium, roughly 1% of total body calcium, that is not associated with bone is found btoh intracellularly, within organelles such as the mitochondria, the endoplasmic reticulum or sarcoplasmic reticulum in muscle, the nucleus, and vesicles and extracellularly in the blood plasma, of which roughly 50% is found to be ionized as well.
What is involved in extracellular calcium concentration regulation?
The three main hormones involved in calcium homeostasis in the blood serum/plasma are PTH, calcitriol, and calcitonin all of which act to maintain normalized blood serum calcium levels.
What factors have been shown to decrease absorption of calcium in the diet?
With aging and with deficiencies of estrogen, calcium absorption has been found to diminish from 30% to 15-20% due to a decreased calcitriol production and its diminished effects on TRPV6 channels as a result.