LITERATURE REVIEW
It is important to get the right amount of calcium [at least 1000mg a day] in our food because the body loses calcium every day. Foods rich in calcium include dairy products (milk, cheese), eggs, fish, green vegetables, and fruit.
2.1.0: REASONS FOR SERUM CALCIUM TEST
Most people who have low or high levels of calcium do not have any symptoms. (Marr and Miiler, 2004).
Calcium levels need to be very high or low to cause symptoms. Therefore a blood calcium test may be done as:
To check for problems with the parathyroid glands or kidneys, certain types of cancers and bone problems, inflammation of the pancreas (Pancreatities), and kidney stones. Abnormal results on an electrocardiogram (EKG) test may be caused by high or low calcium level.
To see if symptoms may be caused by a very high calcium level in the blood. Such symptoms may include weakness, lack of energy; nausea and vomiting, constipation, urinating a lot, stomach pains, bone pains.
To see if symptoms may be caused by a very low calcium level in blood. Such symptoms may include muscle cramps and twitching, tingling in the fingers and around the mouth, muscle spasms, confusion, or depression.
Part of a routine blood test.
It could also be done to check certain medical conditions, such as bone disorder, endocrine disorder, blood clotting problems, kidney disease and irregular heart beat.
A blood calcium test cannot be used to check for a lack of calcium in our diet or for the loss of calcium from the bones (osteoporosis), (Dudin, etal 1997).
The body can have normal calcium level even if our diet does not have enough calcium in it. Other tests, such as bone mineral density, check the amount of calcium in the bones.
2.2.0: TECHNIQUES FOR SERUM CALCIUM MEASUREMENT
Calcium is the most abundant mineral elements in the body. About 98% of the 1200g of calcium in the adult is in form of hydroxyapatite in the skeleton. Hydroxyapatite is a lattice like crystal composed of calcium, phosphorus and hydroxide. The remaining calcium is in the extra cellular fluid (50%) and in the various tissue especially skeletal muscles. Calcium is maintained within a fairly narrow range from 8.5 to 10.5mg/dl (4.3 to 5.3meg /l or 2.2 to 2.7mmol/l). Normal values and reference range may vary among laboratories as much as 0.5mg/dl.
The measurement of serum calcium is fraught with possible errors. Several means of contamination might lead to false elevation of calcium level, (Mohn, 2002). Falsely low levels are less common, so if several measurements are obtained, the lowest is usually the most accurate.
Nevertheless, falsely high or low values may be obtained in patients with liver or renal failure or in patients with lipemic or hemolyzed specimens venous occlusion of the arm during venipunctures may increase the total concentration of serum calcium by up to 0.3mmol/l. This results from an increase in plasma protein concentration caused by homodynamic changes. Another source of error is posture, if the patient stands up from a supine position, there may be an increase of 0.05 to 0.20mmol/l in the serum calcium.
Still another possible source of error is hemolysis. Some method of measuring calcium is affected by high level of hemoglobin and red cells may take up calcium after prolonged contact. If an error is suspected and the measurement is to be redone, the blood should be drawn following an overnight fast because the daily intake of calcium concentration as much as 0.15mmol/l. calcium ions activates some enzymes such as succinate dehydrogenase and adenosine triphosphatase. Calcium is absorbed in the upper small intestine with an active absorption process taking place in the ileum. Increase levels of vitamin D are essential for calcium absorption. All the calcium of food is present in the serum unlike phosphorus which is present mainly in the cells as organic phosphate with only a small amounts being in the serum as inorganic phosphate.
Calcium is present in two distinct forms: the non diffusible protein bound and diffusible fraction, (Zarrow, etal 2001).
The diffusible fraction is either complexes to citrate and phosphate or ionized. A significant decrease in this ionized fraction, regardless of the total serum calcium level, results in tetany. There appears to be a reciprocal relationship between calcium and phosphorus.
Still other variation in the level of serum calcium needs to be mentioned. Exercise just before venipuncture tends to increase serum calcium level, so the person should be rested for at least 15 minutes prior to sampling. Men tends have higher serum calcium level by 0.02 to 0.o4mmol/l during summer versus winter.
2.3:0: FACTORS THAT DETERMINES SERUM CALCIUM LEVEL
The calcium homeostatic system depends on several important factors which include:
Parathyroid hormone (PTH)
Vitamin D.
Phosphate.
Magnesium.
Parathyroid hormone serves as a receptor arm to correct alterations in the steady state level of serum calcium. A small fall in ionized calcium will quickly lead to a rise in parathyroid hormone secretion. The result of this increase in parathyroid hormone is a rapid release of calcium from bone. This requires the active form of vitamin D, 1, 25- dihydroxycholecaciferol (1, 25 DHCC), but is not dependent on bone turn over or an increase in the number of osteoclast. This effect of parathyroid hormone most probably is mediated via the transport of calcium from the bone extra cellular fluid (ECF).
Parathyroid hormones also maintain the steady state level of serum calcium by its action on the kidney. It increases the tubular reabsorption of calcium and magnesium and decreases the tubular reabsorption of phosphate, sodium, bicarbonate, potassium, and amino acids. Parathyroid hormone activates the adenylate cyclase system by binding with the receptor sites in the renal cortex. It thus leads to an increase in cyclic adenosine monophosphate.
Vitamin D increases the concentration of serum calcium level by several mechanisms. As mentioned above, it potentiates the effect of parathyroid hormone in bone. Vitamin D also increases the intestinal absorption of calcium, as well as bone and tubular reabsorption of calcium.
The serum phosphorus level also plays a role in the maintenance of a steady state concentration of serum calcium. While there is no exact solubility product for calcium and phosphorus, a rise in the serum phosphate usually leads to a fall in the serum calcium level, (Stroev, etal 1990). Some of this decrement may be caused by enhanced formation of CaHPO4 complexes in the serum. A fall in the serum phosphate level will conversely lead to an increase in the serum ionized and bone extra cellular fluid calcium. Some of the mechanisms that contribute to the drop of calcium includes: hypercalceamia and hyperparathyroidism induced by phosphate depletion.
Alterations of serum magnesium within the normal range (1.5 to 2.5meg/l) do not appear to affect the concentration of serum calcium. But hypomagnesaemia tends to suppress parathyroid hormone secretion and may lead to mild hypocalcaemia. With a fall in serum magnesium below a concentration of 1.0meg/l, parathyroid hormone secretion is suppressed and resistance to the action of parathyroid hormone on target organs develops.
2.4:0: VALUES OF SERUM CALCIUM FRACTIONS
All calcium in the body is technically ionized; the term usually applies to the free ionic fraction that is physiologically active in the blood.
Below shows the values of the serum calcium fractions.
Fig 1:
Fraction
Milligrams per deciliter (mg/dl)
Percent (%)
Ionized (free ions)
4.40
44
Total diffusible
5.60
56
Protein- bound
4.60
46
Complexes
1.00
10
Total
10.00
100
The figure above shows the values of serum calcium fraction
The portion of total calcium that forms ion couplets with anions such as bicarbonate and or citrate is known as complexed calcium. Together, the ionized and complexed calcium constitutes the diffusible fraction of calcium. This portion may also be called the ulterafilterable calcium, since it passes through biological membrane, (Dacie, and Lewis, 1999). This is unlike protein bound calcium, which is not diffusible. About 90% of the protein bound calcium is linked albumin with the remaining 10% bound to a variety of globulins. There are 12 binding sites on each normal condition. Therefore, when an excess of calcium in the blood occurs, each of the three calcium fraction of (i.e. ionized, complexed, protein bound ) increases in the same ratio, resulting in a constant proportion of ultra filterable calcium.
The ability of protein to bind calcium acts as a buffer that alters the effect of an acute load of calcium on the concentration of ionized calcium by about 50%. Still another consequence of the large number of unfilled binding sites for calcium is that competition by magnesium does not have a significant effect on the ionized calcium concentration. The most vital parameter affecting protein binding of calcium is PH. An alkaline PH leads to an increase in binding and hence a decrease in the fraction of ionized calcium. The reason for this is two folds:
Competition between H+ and Ea++ for binding sites
Alteration in configuration of the albumin molecule.
2.5.0: EFFECT OF ABNORMALITIES IN THE SERUM CALCIUM LEVELS
An increase in the serum calcium levels may lead to the following:
Hyperparathyroidism; parathyroid hormone maintains serum calcium levels by mobilizing calcium from the bones.
Multiple myeloma and neuloplastic disease of the bone.
Hypervitaminosis; also a disease in the serum calcium level may results in the following:
Pancreatities; due to the formation of the calcium soaps.
Hypothyroidism
Steatorrhea; due to decreased absorption.
Nephritis, about 50% of calcium is bound to proteins so that decrease in serum proteins will lead to low serum calcium.
2.6.0: BIOLOGICAL FUNCTION OF INORGANIC IONS
Relatively large amounts of acid, sulphuric acid and phosphoric acid are produced from the numerous metabolic processes that takes place in the body. An average person of 70kg will dispose daily the equivalent of 360 liters of 0.1N acid as a non volatile acid through the kidneys, (Lorke, 1999).
This product of metabolism are transported to excretory organs (lungs and kidneys) via the extra cellular fluid without producing any appreciable changes in the body PH. this is accomplished by the combined functions of the buffer systems of the body, the respiratory system and the renal mechanism, (Sharma, and Makarowa 2000). These three systems are also of great important in maintaining the normal composition of cations and anions of the body.
Electrolytes are classified as either anions or cations, depending upon whether they move in an electric field towards the anode or the cathode. That is, whether they have a negative or positive charge, they are essential components of all living matters and are Ca2+, K+, Cl-, HCO3-, HPO4- and Mg2+ as well as the trace elements of Fe3+, Fe2+, CU+, CU2+, I- and Zn2+. The major electrolytes occur primarily as free ions, while the trace elements occur primarily in some special combination with proteins.
The dietary requirements of electrolytes vary widely. Some, like calcium and potassium, are continuously excreted and must be consumed regularly in order to prevent deficiency. Excessive consumption leads to corresponding increased excretion, mainly in the urine, (Haussler, etal 2004). Abnormal loss of electrolytes, which occurs through excessive perspiration, vomiting or diarrhea is readily assessed and can be corrected by administration of salt. The function of electrolytes in the body is many. Most metabolic processes are dependent or affected by electrolytes, (Mallette, etal 1999). They are involved in the maintenance of osmotic pressure and hydration of the various body fluid compartments, maintenance of proper body PH, regulation of proper function of the heart and other muscles, involvement in oxidation reduction (electron transfer) reactions, and participation as an essential part or co-factor of enzymes.
2.7.0: CLINICAL SIGNIFICANCE OF SERUM CALCIUM:
2.7.1 CAUSES OF HYPOCALCAEMIA: There are many factors which could trigger the hypocalcaemia and they are included:
Parathyroid hormone deficiency.
Vitamin D deficiency
Cholecalciferol deficiency (e.g. Sunlight, dietary, insufficiency, gutmalabsorption )
Transient (e.g. hypomagnesaemia)
25- Hydroxycholecalciferol deficiency (e.g. impaired hepatic hydroxylation, hepatobiliary disease, nephritic syndrome, anticonvulsant therapy).
Also a transient hypocalcaemia could be as a result of the following factors:
Intravascular redistribution (e.g. massive transfusion with acid blood).
Sudden increase in net deposition in bone.
Decrease bone resumption (e.g. mithramyan calcitonin)
Failure to increase bone re-absorption in response to calcium depletion (e.g. medullar carcinoma of thyroid)
Increased soft tissue deposition (rhabdomyolysis, Pancreatities, hyperphosphatemia).
2.8.0: CAUSES OF HYPERCALCEMIA
Hyperparathyroidism
Metastatic disease of the bone
Humoral hypercalceamia
Excess of vitamin A
Excess of vitamin D
Proliferative disorders
Leukemia
Thiazide diuretics etc.
The important of normal serum calcium concentration can best be appreciated by a clinical manifestation of hypocalcaemia and hypercalceamia. Hypercalceamia is usually associated with soft tissue calcification, nephropathy, anorexia, nausea electrocardiographic disturbances and a spectrum of neurological changes from headache to serious disorder, (Nordin, 2007). Increase neural excitability is a fairy common manifestation of hypocalcaemia. The patients usually describe tingling of the tip of the fingers and around the mouth. If unabated, these symptoms progress in severity and extend to the limbs and face. The patient may also describe numbness over these areas that may be accompanied by pain and carpal spasm.
Hypocalcaemia may increase central as well as peripheral, neural excitability and two types of convulsive seizures may result. First, the patient may suffer from a seizure disorder similar to a patient without hypocalcaemia. Such as Jacksonian or grand Mali
Secondly, systemic tetany may progress to prolonged tonic spasms, which are also referred to as cerebral tetany.
A fall in serum calcium level will delay ventricular repolarization. This may progress and produce 2:1 heart block.
Chronic hypocalcaemia may also leads to less than adequate cardiac performance associated with a reduction in blood pressure, (McLean, etal, 1995).
Several defects of the ectodemer are often seen in patients with chronic hypocalcaemia cataracts are the most common feature.
These results from alteration of local sodium pump eventually les degeneration and the development of dystrophic calcifications.
Defect in the development enamel of teeth may occur if the hypocalcaemia precedes the maturation of the respective tooth. Hair and nails may also affected by chronic hypocalcaemia both may become dry and brittle; their growth may even be stunted. Still more unusual effects of hypocalcaemia may rarely occur, (Maxwell, and Kleeman, 2006).
These include disturbances of blood coagulation, intestine malabsorption, defective bone mineralization (when associated with vitamin D deficiency).
The manifestations and then the clinical significance of hypercalceamia consist of some effects which include:
Soft tissue calcification.
Tubulointerstitial renal disease
Anorexia and nausea.
Three sites of soft tissue calcification occur with hypercalceamia even in the absence of serum phosphate elevations, (parfitt, and Kleerekoper, 2001).
An acute brain syndrome is the most common side effect of moderate to severe hypercalceamia. And symptoms such as depression, chronic recurrent headache, and memory impairment are often associated with chronic hypercalceamia of a mild to degree, (Benabe, etal, 2001). More pronounced elevations of calcium usually lead to a spectrum of symptoms ranging from mental confusion or delirium to stupor and coma.
2.9.1: EFFECTOR ORGANS/ SOURCES.
About 25mmol of calcium enters the body in a normal diet. It can be lower, if the diet is low in milk and dairy products, or other calcium containing foods such as some kind of fish or calcium rich water, (the calcium of leafy green vegetables is poorly absorbed), in all these, about 40% (10mmol) is absorbed in gut, and (5mole) leaves the body in feaces, therefore, netting 5mmolof calcium a day, (Bron, etal, 2004).
2.9.2: EXCRETION
The kidney excretes 250mmol a day in pro-urine, and reabsorbs 245mmol, leading to a net loss in the urine of 5mmol. In addition to this, the kidney processes vitamin D into calcitrol, the active form that is most effective in assigning intestinal absorption. Both processes are stimulated by parathyroid hormone.
2.9.3: THE ROLES OF BONE.
Although calcium flow to and from the bone is neutral, about 5mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Calcium releases from bone is regulated by parathyroid hormone. Calcitonine stimulates incorporation of calcium in bone, although this process is largely independent of calcitonin (Marshall, 1995). Low calcium intake may also be a risk factor in the development of osteoporosis. In one meta-analysis, the authors found that they reviewed showed that calcium intake did not promote better bone balance. With a better bone balance, the risk of osteoporosis is lowered.
2.9.4.0: INTERACTION OF CALCIUM WITH OTHER CHEMICALS
This interaction may occur in two ways:
potential positive interaction
potential negative interaction
The potential positive interaction:
Vitamin D: this is an important co-factor in the intestinal absorption of calcium, as it increase the number of calcium binding proteins, involved in calcium absorption through the apical membrane of entrecotes in small intestine, (Heaney, 2000). It also promotes reabsorption of calcium in the kidney.
Potential negative interaction: unspecified long chain saturated fatty acids, i.e. politic acid, have a melting point above body temperature and with sufficient calcium in the intestinal lumen, form insoluble calcium soaps, (Robertson, etal 1986).
cortical
Physic acid
Caffeine
Sodium.
2.9.5.0: REGURATORY ORGANS
Primarily calcium is regulated by the actions of 1, 25-OH-vitamin D3, parathyroid hormone and calcitonin and direct exchange with the bone matrix. Plasma calcium levels are regulated by hormonal and non hormonal mechanism, (Medical physiology; Guyton, 1998). After ingestion of substantial amounts of calcium for e.g. in a glass of milk, the short term control that prevents calcium spiking in the serum is absorbed by the bone matrix. After about an hour, parathyroid hormone will be released and not peak for about 8hours. The parathyroid hormone is overtime, a very potent regulator of plasma calcium and controls the conversion of vitamin D into its active form in the kidney, (Lopez 2001). The parathyroid glands are located behind the thyroid and produces parathyroid hormone in response to the calcium level. The Para follicular cells of the thyroid produces calcitonin in response to high calcium levels, but its significance is much smaller than that of parathyroid hormone.