The Role of Calcium in the Body and Its Homeostasis - Report Example

THE ROLE OF CALCIUM IN THE BODY AND ITS HOMEOSTASIS Introduction Calcium is a chemical element and is a soft grey alkaline metal. Although considereda trace element, it is the most abundant element in the bodies of human beings. Total calcium in body amounts to around 1.5kg. It is a constituent of bones and teeth and the major sources of this important element are milk, fish and eggs. Daily requirement of calcium is 20mg/day. However, this amount varies with age and gender (Cussler et al, 2005). Discussion The first and the second parts of duodenum are the sites where calcium is absorbed. It is absorbed against the concentration gradient and thus requires the breakdown of ATP (Ajibade et al, 2010). It also utilizes a carrier protein aided by calcium dependent ATPase. The absorption of calcium depends on a number of factors, some of which are discussed below; Vitamin D plays an important role in absorption of calcium. The synthesis of a carrier protein for calcium is induced by Calcitriol. This process takes place in the epithelial cells of the intestinal walls which aids the calcium absorption. It promotes bone growth as well. Vitamin D acts on special receptors of tissues to maintain the calcium absorption. About 85% of the body’s calcium is absorbed due to the effect of vitamin D (Lehmann, 2007). A number of other factors also affect the absorption of calcium. Parathyroid hormone increases the calcium transport from the cells of the intestinal lining. It stimulates osteoclasts in the bone to reabsorb bone mineral so that it releases calcium in the blood when the blood calcium level is low. It promotes calcium absorption from the epithelial cells of the intestines. Also it indirectly, influences the kidney to reabsorb calcium to retain it in the body (Qin & Partridge, 2012). Low pH levels in the blood increase the absorption of calcium. The optimum pH for the absorption of calcium is towards the lower side i.e. below value 7 (Linkswiler et al, 2012). Some amino acids also affect calcium absorption. Especially lysine and arginine increase absorption. Among the factors which decrease absorption of calcium, phytic acid, oxalates and higher levels of phosphate are important (Cao et al, 2011). As far as phytic acid is concerned, the fermentation or cooking of cereals which have hexaphosphate of inositol may show the effect of decreased absorption of calcium. It is known to precipitate calcium. Oxalates which are readily available in some green vegetables form insoluble calcium oxalates thus decreasing the absorption of calcium. Similarly, elevated phosphate levels cause the precipitation of calcium as calcium phosphates. The optimum ratio of calcium to phosphorus which allows peak absorptions is 2:1. Transport of calcium and its biochemical properties From every 500mg of calcium taken orally, 400mg is excreted as stool 100mg is excreted in urine. In blood, calcium is present in both extra cellular and intra cellular compartments. The concentration of extracellular calcium is 2.5 mmol/L where as in the intracellular compartment; the concentration of calcium is less than 10umol/L. When calcium enters the body orally, it goes through the gut to be absorbed into the blood stream via the intestines. Most of the calcium is in the form of complex crystals such as calcium phosphate in the body. These crystals are stored in the teeth and bones. 50% of body calcium is ionized calcium and is ready to be utilized by different body functions. The rest of calcium is bound to a blood protein called albumin, which is responsible for the transport of substances that cannot be dissolved in the blood plasma (Heaney, 2010). Of the 25mmol of calcium that is taken orally 10mmol is absorbed in the intestines where as 5mmol is excreted in feaces. The kidney excretes 250mmol of calcium a day in the urine. 99% of the calcium in the body is stored in the bone (Frassetto et al, 2010). After an hour of ingestion of the calcium, the hormone PTH is secreted by the parathyroid gland to regularize the calcium level in the blood. Also the PTH regularizes the conversion of vitamin D from the inactive form to the active form to aid the absorption of calcium. A number of enzymes in the body are activated by the action of calcium. The calcium binding regulatory protein, Calmodulin, is identical to the muscle protein; Troponin C. Calmodulin can bind with 4 calcium ions which cause activation of particular enzymes (Rumi-Masante et al, 2011). It is also part of regulatory kinases. Enzymes like, Adenylcyclase, glycerol-3-phosphate protein kinases, myosin kinases, phosphorylase kinase, pyruvate kinase etc. are activated by Ca++ and mediated by Calmodulin. Calcium is also responsible for the activation of a number of enzymes of the coagulation pathways, pancreatic lipase and rennin (enzyme responsible from milk clotting in stomach). Calcium’s also plays a role in muscle excitation and contraction. Calcium activates ATPase thus increases the reaction of myosin and actin and causes excitation-contraction coupling. The inactive myosin kinase is activated by calcium ions (Sellers et al, 2008). The trigger of muscle contraction is the interaction of calcium with Troponin C. Calcium decreases neuro-muscular irritability. The deficiency of calcium can result in tetany. Calcium is also involved in the transmission of nerve impulse from the pre-synaptic neuron to the post-synaptic neuron. It causes the binding of neurotransmitter containing vesicles to the membrane of the pre-synaptic neuron. A number of other functions of calcium in living organisms have been identified. Calcium together with Calmodulin regulates micro-filament mediated processes like degranulation of secretory vesicles, endocytosis and cell motility. Hormones such as Calcitonin, parathyroid hormone, vasopressin, and insulin are secreted from the endocrine cells by the action of calcium. Calcium along with cyclic AMP acts as second messengers for a variety of different hormones. One example is Glucagon. The permeability of serum through capillary is decreased by calcium. Sometimes referred to as factor-4 in blood coagulation cascade, calcium also plays a role in coagulation pathways. Prothrombin contains gamma carboxy glutamate which is chelated by Ca++ during thrombin formation (Vasudevan et al, 2011). Thus it is highly essential in blood clotting. In myocardium, Ca++ prolongs systole. During contraction, calcium is released from sarcoplasmic reticulum, which is found inside muscle fibers, and if calcium is not released properly, the heart function is very significantly impaired. Calcium can be taken into account because it can bring a decrease in hypertension. However, in extreme cases of hypercalcemia, cardiac arrest can occur during systole. Most of the calcium is used in teeth and bone formation. The storage of calcium takes place in the bones of the body. The living tissue in bone is made up of minerals densely packed into osteoblasts and osteoclasts. Calcium and vitamin D are the most essential bone minerals which give bones its strength. Several epidemiological studies suggest that individuals with high calcium intake are at a lesser risk of colorectal cancer as compared to individuals who have generally low level of calcium intake. Homeostasis of calcium Normal levels of calcium in blood range from 9 to 11mg/dl (Mutnick, 2004). The effective control factors for the maintenance of the levels of calcium in blood are many and a few important ones are discussed here. Vitamin D is hydroxalated in the liver and then further hydroxalation is carried out in the kidney to produce Calcitriol. In the mucosa of intestines, a carrier protein is induced by calcitriol as a result of which the calcium absorption is increased, ultimately resulting in an elevation of calcium level in the blood. The parathyroid gland secretes the parathyroid hormone. The level of ionized calcium provides a negative feedback to control the release of this hormone. The release of this hormone is also mediated by cyclic AMP. The normal PTH level in serum is 10 to 60mg per Liter. PTH binds with a receptor protein on the surface of target cells. This activates adenyl cyclase with consequent increase in the calcium concentration. A kinase is activated and thus enzyme systems are activated. The PTH has three major independent sites of action; kidney where its action causes a decreased excretion of calcium from kidneys, bone where it causes demineralization and intestine where it increases absorption of calcium. All the three levels of action increase calcium level in the blood. PTH also acts on the kidney to stimulate the production of active form of vitamin D. It is produced by exposure of skin to light. This active form of vitamin D acts on the intestines to promote Ca++ absorption. The most rapid effect PTH has is on the bones, whereby it causes the stimulation of osteoblasts which pump Ca++ ions from the fluid surrounding the bone to the extra cellular fluid. This can result in bone resorption. (Zivkovic, 2011) The effect of Calcitonin: It is secreted by clear cells but the secretion is dependent upon stimulation by serum calcium. Calcitonin decreases calcium levels. Osteoclastic activity is reduced whereas osteoblastic activity is increased by the action of calcitonin. Major functions of calcitonin together with PTH include promotion of bone remodeling and bone growth. When calcium levels fall in the blood, PTH secretion increases while inhibition of calcitonin takes place. The result of this change is bone demineralization which causes release of calcium from bones back to blood. When calcium levels are restored, PTH secretion is inhibited while calcitonin’s secretion increases, thereby resulting in storage of calcium in the bones. The effect of Phosphorus: An inverse relationship exists between phosphorus and calcium. The ionic product of calcium and phosphorus is held at 40 in serum. If phosphorus level is increased above the normal value the level of calcium in blood decreases. Thus a change in the dietary intake of any of the two elements can have significant impact on the blood concentration of the other. The effect of serum proteins: In hypoalbuminemia, the total calcium is decreased. About 0.8mg/dl of calcium is reduced with the lowering of each 1g/L of albumin (Myers, 2005). This is because the calcium in blood is transported by the use of albumin. This is the sole transporter of ionic calcium in the blood. The effect of Alkalosis and Acidosis: Alkalosis favors binding of more calcium with proteins. As a consequence, the blood concentration of ionized calcium decreases. Hence total level of calcium may be normal but deficiency will be noticed because of the decrease in the available ionized calcium. Children/Pregnancy: In children the calcium levels are normally high. Even the ionic product of calcium and phosphorus is around 50 where as in adults it is 40. When a woman is pregnant or lactating, the calcium levels in the blood are always in the lower limit because of the additional requirements of the fetus or the child. A regular intake of calcium is thus required to avoid complications to the health of the mother or the baby. Kidney Threshold The mean normal calcium level in blood is 10mg/dl. Elevated levels of calcium in blood (above 10mg/dl) result in excretion of excess calcium in the urine as a result of action of kidneys. This is the reason that when calcium is injected intravenously, most of it is excreted in the urine. Any disorder in the functioning of kidney can therefore have significant effect on the serum calcium levels. Hypercalcemia The term denotes that the blood calcium level is more than 11mg/dl. The major cause is hyperparathyroidism. This may be because of a parathyroid adenoma or an ectopic PTH secreting tumor. Calcium may be precipitated in the urine leading to recurrent bilateral urinary calculi. In multiple myeloma, Paget’s disease and metastatic carcinoma of bone there will be bone resorption and mild hypercalcemia. Increased absorption of calcium from intestine is seen in milk alkali syndrome and vitamin D toxicity. Solid tumors like breast cancer or lung cancer can be the cause of increase in serum calcium. Moreover, when the first signs of hypercalcemia are observed, the parathyroid glands are checked for any abnormality in function. This is because the increase or decrease of calcium in blood is directly related to the functioning of the parathyroid gland. However, other factors also need to be taken into account, like excessive lithium in the body, or vitamin A intoxication or some kind of thiazide use. Renal failure can lead to more calcium being reabsorbed in the kidneys from the urine, making it less concentrated, which can increase the serum calcium by significant amounts. One of the possible outcomes of a persistent hypercalcemia is a bathmotropic effect which is essentially the blockage of the sodium channels in the body. This is because calcium has the tendency to block sodium ion channels. As a result, the nerve impulses are affected. The depolarization of nerve impulse is prolonged because the sodium ions cannot pass through the protein channels. The most common symptoms of this disorder are pains in bone, abdominal pains, vomiting, and renal stones. The psychological effects can be very pressing as well. There is a known increase of the onset of depression in 40% of individuals who suffer from hypercalcemia. The immediate course of treatment for such an increasing calcium concentration in the blood is the excessive intake of fluids to avoid being dehydrated. However, on the other hand, salt intake is also increased. This is because if excessive sodium is taken, the kidney will excrete excessive sodium which will in turn increase the excretion of calcium from the body. The intake of biophosphates can help reduce the effects of hypercalcemic bone resorption. Calcitonin also serves to decrease bone resorption and also increases the amount of calcium which is excreted in the kidneys daily. Severe cases of hypercalcemia can lead to fatal consequences like coma. Hypocalcemia When serum calcium level is below 8.8mg/dl, it is attributed to a deficiency in the blood concentration of calcium also known as hypocalcemia. If serum calcium level is below 8.5mg/dl the person might experience mild tremors. If it is below 7.5 mg/dl it can cause a life threatening condition known as tetany. Tetany may also be due to accidental removal of parathyroid gland or by autoimmune diseases. In tetany, neuro-muscular irritability is increased. Main manifestations are carpopedal spasm and stridulous. Laryngeal spasm can also result which can prove fatal. The main course of treatment is to re-establish the balance of mineral nutrients in the body. An intravenous course of calcium is given accompanied by administration of vitamin D. Serum calcium levels are lowered corresponding with increase in phosphate level. Pseudo-hypoparathyroidism is an X-linked dominant condition. Although PTH levels are normal, there is a lack of end organ response to PTH. This leads to hypocalcemia. Similarly, renal tubular acidosis is an inherited abnormality. The H+ production is deficient in renal tubules. Kidney cannot lower pH below 5 which mean there is an excess urinary loss of Ca++. This can also leads to a decrease in serum calcium levels. Individuals afflicted with Hypoparathyroidism have underactive parathyroid glands. The PTH hormone secreted by this gland regulates calcium and phosphorous in the blood. The occurrence of kidney stones, fragile and brittle bones, excessive urination, abdominal pains and joint pains are few of the symptoms of the onset of hyperparathyroidism. Individual suffering from this disease is put on a high calcium and low phosphorous diet. Often calcium supplements are also prescribed to cope with excessive deficiency. Ongoing research for investigating the co-relation of calcium level and blood pressure show that an increase in calcium level can reduce the chances of hypertension significantly. In fact, a regular dose of calcium supplement for 6 to 8 weeks can result in the lowering of blood pressure especially in pregnancy and preeclampsia, with additional fluid retention and an increase in protein level in the urine (Rolfes, 2012). For individuals with hypercholesterolemia, a dose of 1200 mg calcium a day i.e. a very high dose over a long period of time, together with healthy diet and exercise can help lower the cholesterol level in the blood. Rickets is a disease caused by the deficiency of calcium or vitamin D. There are different types of bone abnormalities that occur in rickets. However, each one of them is associated with poor mineralization of either calcium or phosphate. It is especially prevalent in children. It can be either due to malnutrition or the inability of the body to synthesize vitamin D. The bones become soft and brittle which can cause recurrent fractures. The prevailing symptoms of this disease are bone pain and tenderness, accompanied with muscle weakness. There is an increased risk of bone deformities which can be diagnosed through an X-ray. If the blood tests show a calcium serum level below normal then it is concluded that the calcium is not being properly absorbed from the gut. The most obvious treatment plan is to expose the individual to direct sunlight and to increase calcium intake in diet accompanied with a daily calcium supplement. Osteoporosis is one the leading consequences of the hypocalcemic disorder. The maximum amount of calcium content in bone is reached by the age of 30. After the age of 45, calcium absorption reduces and calcium excretion is increased so there is osteopenia (Vasudevan & Sreekumari, 2012). However, after the age of 60, osteoporosis is seen which results in weakening of bones and increased risk of fractures. The bone is a living tissue which needs to be replaced constantly. In osteoporosis, the ability to absorb calcium in the body is lowered. In women, the loss of bone tissue is more severe. This excessive loss is attributed to a drop in estrogen during menopause. In men, it is attributed to the dropping levels of testosterone. The onset symptoms can be fractures. In rare cases, there is spine pain, which can be caused by fractures in the spine. For the diagnosis, a bone mineral density test is carried out to see the extent of osteoporosis. The obvious treatment is the administration of calcium and vitamin D. A healthy lifestyle change which includes maximum dairy diet is suggested. In women, a regular dose of estrogen is prescribed. For adults, under the age of 50, a regular daily dose of 1000mg is required. A regular exercise to help strengthen the bones and joints is also advised. (Osteoporosis Treatment - Natural Osteoporosis Treatments, 2013) 1000mg of calcium a day during the latter phase of menstruation cycle can help reduce the premenstrual symptoms like cramps, bloating and mood disorders. The drop of the level of estrogen after ovulation can cause the calcium of the bones to be depleted. Thus it becomes all the more essential to take calcium supplements during the menstruation cycle (Freeman, 2010). Conclusion Calcium ion is one of the nature’s amazing gifts to not only the mankind, but also other living beings, as a large number of chemical processes are carried out by this important constituent of our diet. Calcium ion concentration in its right balance in the blood holds a lot of significance as discussed earlier. Thus, it becomes necessary for adults aged above 20 to take regular doses of calcium in the daily diet. Both lower and higher levels contribute to the precipitation of a number of well understood disorders of calcium. It is therefore of paramount importance, that in making diagnosis of various diseases, the role of calcium should always be considered by every clinician. REFERENCES: Top of Form Bottom of Form Top of Form Bottom of Form Top of Form Bottom of Form Top of Form Bottom of Form Top of Form Bottom of Form Ajibade, D., Benn, B. S., & Christakos, S. (2010). Mechanism of action of 1, 25-dihydroxyvitamin D 3 on intestinal calcium absorption and renal calcium transport. Vitamin D, 175-187. Cao, J. J., Johnson, L. K., & Hunt, J. R. (2011). A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting markers of bone resorption or formation in postmenopausal women. The Journal of Nutrition, 141(3), 391-397. Cussler, E. C., Going, S. B., Houtkooper, L. B., Stanford, V. A., Blew, R. M., Flint-Wagner, H. 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