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General and ionized calcium in the blood
Medical expert of the article
Determination of the level of ionized calcium
The level of ionized calcium can be determined by standard laboratory tests, usually with sufficient accuracy. Acidosis increases the level of ionized calcium by reducing binding to proteins, while alkalosis reduces the level of ionized calcium. With hypoalbuminemia, the plasma level of calcium is usually reduced, which reflects a low level of calcium bound to proteins, while the level of ionized calcium can be normal. The total plasma calcium level is reduced or increased by 0.8 mg / dl (0.2 mmol / L) for every 1 g / dl for reducing or increasing the level of albumin. Thus, the albumin level of 2 g / dL (normally 4.0 g / dl) reduces the detectable plasma calcium level by 1.6 mg / dl. Also, an increase in the level of plasma proteins, which is observed with multiple myeloma, can increase the overall level of plasma calcium.
The physiological significance of calcium
Calcium is necessary for normal muscle contraction, nerve impulse, hormone release and blood clotting. Also, calcium promotes the regulation of many enzymes.
Maintenance of calcium stores in the body depends on the intake of calcium from food, the absorption of calcium from the digestive tract and renal calcium excretion. With a balanced diet, calcium intake is about 1000 mg every day. About 200 mg per day is lost with bile and other secrets of the gastrointestinal tract. Depending on the concentration of circulating vitamin D, especially 1,25 dihydroxycholecalciferol, which is formed in the kidney from an inactive form, approximately 200-400 mg of calcium is absorbed into the intestine every day. The remaining 800-1000 mg appear in the feces. Calcium balance is maintained by renal calcium excretion, which averages 200 mg per day.
The extracellular and intracellular calcium concentrations are regulated by bi-directional calcium transport through cell membranes and intracellular organelles, such as the endoplasmic reticulum, the sarcoplasmic reticulum of muscle cells and mitochondria. Cytosolic ionized calcium is maintained at a micromolar level (less than 1/1000 plasma concentrations). Ionized calcium acts as an intracellular secondary messenger; participates in the reduction of skeletal muscles, the excitation and contraction of cardiac and smooth muscle tissue, the activation of protein kinase, and the phosphorylation of enzymes. Calcium is also involved in the action of other intracellular messengers, such as cyclic adenosine monophosphate (cAMP) and inositol 1,4,5-triphosphate, and thus participates in the transmission of a cellular response to numerous hormones, including epinephrine, glucagon, ADG (vasopressin), secretin and cholecystokinin.
Despite the important intracellular role, almost 99% of the total calcium content in the body is in bones, mainly in the composition of hydroxyapatite crystals. About 1% of calcium bones is freely exchanged with EKZH and, therefore, can participate in buffer changes in the balance of calcium. Normally, the level of calcium in the plasma is 8.8-10.4 mg / dl (2.2-2.6 mmol / l). About 40% of total blood calcium is associated with plasma proteins, mostly with albumin. The remaining 60% include ionized calcium plus a calcium complex with phosphate and citrate. The total calcium (i.e., protein-bound, within the complexes and ionized) is usually determined by clinical laboratory measurement. Ideally, the definition of ionized or free calcium is necessary, since it is a physiologically active form in plasma; but such a determination due to technical difficulties is usually carried out only in patients with suspected significant disruption of calcium binding by proteins. Ionized calcium is usually considered equal to about 50% of the total calcium in the plasma.
The physiological significance of calcium is to reduce the ability of tissue colloids to bind water, reduce the permeability of tissue membranes, participate in the construction of the skeleton and the system of hemostasis, as well as in neuromuscular activity. It has the ability to accumulate in places of tissue damage by various pathological processes. Approximately 99% of the calcium is in the bones, the rest is mostly in the extracellular fluid (almost exclusively in the blood serum). Approximately half of the serum calcium circulates in the ionized (free) form, the other half in the complex, mainly with albumin (40%) and in the form of salts - phosphates, citrate (9%). The change in serum albumin, especially hypoalbuminemia, affects the total calcium concentration, without affecting the clinically more important indicator - the concentration of ionized calcium. It is possible to calculate the "corrected" total calcium concentration in the serum with hypoalbuminemia according to the formula:
Ca (corrected) = Ca (measured) + 0.02 × (40-albumin).
Calcium, fixed in bone tissue, is in interaction with the ions of blood serum. Acting as a buffer system, the deposited calcium prevents fluctuations in its serum content in large ranges.
Metabolism of calcium
Calcium metabolism regulates parathyroid hormone (PTH), calcitonin and vitamin D derivatives. Parathyroid hormone increases the concentration of calcium in the blood serum, enhancing its leaching out of the bones, reabsorption in the kidneys and stimulating the conversion of vitamin D into active metabolite calcitriol. Parathyroid hormone also increases the excretion of phosphate by the kidneys. The level of calcium in the blood regulates the secretion of parathyroid hormone by the mechanism of negative feedback: hypocalcemia stimulates, and hypercalcemia inhibits the release of parathyroid hormone. Calcitonin is a physiological antagonist of parathyroid hormone, it stimulates the excretion of calcium by the kidneys. Metabolites of vitamin D stimulate the absorption of calcium and phosphate in the intestine.
The calcium content in the blood serum changes with dysfunction of parathyroid and thyroid gland, neoplasms of different localization, especially when metastasizing to the bone, with renal failure. Secondary involvement of calcium in the pathological process takes place in the pathology of the gastrointestinal tract. Often hypo- and hypercalcemia may be the primary manifestation of the pathological process.
Regulation of calcium metabolism
Metabolism of calcium and phosphate (PO) are interrelated. Regulation of the balance of calcium and phosphate is determined by circulating levels of parathyroid hormone (PTH), vitamin D and to a lesser extent calcitonin. Concentrations of calcium and inorganic PO are associated with their ability to participate in the chemical reaction with the formation of СаРО. The product of the concentration of calcium and PO (in meq / liter) is normally 60; when the product exceeds 70, the precipitation of CaPO crystals in soft tissues is likely. Precipitation in the vascular tissue contributes to the development of arteriosclerosis.
PTH is produced by parathyroid glands. It has various functions, but probably the most important thing is preventing hypocalcemia. Parathyroid cells respond to a decrease in calcium concentration in the plasma, in response to it, the release of PTH into the circulation. PTH increases the concentration of calcium in the plasma for minutes by increasing renal and intestinal calcium absorption, and by mobilizing calcium and RO from bone (bone resorption). Renal calcium excretion in general is similar to sodium excretion and is regulated by practically the same factors that control sodium transport in the proximal tubules. However, PTH increases the reabsorption of calcium in the distal sections of the nephron, regardless of sodium. PTH also reduces renal reabsorption of RO and thus increases renal RO loss. Renal loss of RO prevents the increase in the product of Ca and RO binding in the plasma, as the level of calcium rises in response to PTH.
PTH also increases the level of calcium in the plasma by converting vitamin D into the most active form (1,25-dihydroxycholecalciferol). This form of vitamin D increases the percentage of calcium absorbed in the intestine. Despite the increased absorption of calcium, increased secretion of PTH usually leads to further bone resorption by suppressing the osteoblastic function and stimulating the activity of osteoclasts. PTH and vitamin D are important regulators of bone growth and remodeling.
The research of parathyroid function includes determination of the level of circulating PTH by radioimmunity and measurement of total or nephrogenic excretion of cAMP in the urine. The determination of cAMP in the urine is rare, and accurate analyzes on PTH are widespread. The best are assays for intact PTH molecules.
Calcitonin is secreted by the parafollicular cells of the thyroid gland (Scrolls). Calcitonin reduces the concentration of calcium in the plasma by increasing the uptake of calcium by cells, renal excretion and bone formation. The effects of calcitonin on bone metabolism are much weaker than the effects of PTH or vitamin D.