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Close concepts: tetany, hypoparathyrosis, deficit of vitamin D
The hypocalcemia is characterized by concentration of serumal calcium below norm - 8,5-10,5 mg/dl (2,1-2,5 mmol/l). Implementation in clinical practice of routine biochemical research promoted improvement of diagnosis of disturbances of a metabolism of calcium, especially asymptomatic hypercalcemia. In spite of the fact that in general the hypocalcemia occurs at ambulatories less often, with malignant new growths and diseases of kidneys it can occur at patients more often than a hypercalcemia.
Normal serumal concentration of calcium is maintained within 2,2 — 2,6 mmol/l, however a little less than a half from the general calcium makes calcium, ionized, or untied with protein. The ionized calcium which is physiologically active fraction takes part in a number of various metabolic processes. Level of the general calcium of blood serum is broken as a result of considerable changes of serumal concentration of proteins, especially albumine. The easy way of correction of results of definition of calcium in blood consists in increase in the received concentration of calcium by 0,25 mmol/l at decrease concerning standard of serumal concentration of albumine by each 10 g/l. Deep disturbances of binding of calcium protein happen under the influence of changes rn blood: increase rn leads to increase in binding and, therefore, reduction of content of the ionized calcium. This law explains emergence of symptoms of a hypocalcemia at a hyper ventilating respiratory alkalosis.
The homeostasis of calcium depends on interaction of parathyroid hormone (PTG) and vitamin D with specific target organs: intestines, bones and kidneys. First of all PTG leads to increase in a reabsorption of calcium in kidneys and to absorption by his bone tissue, but, besides, strengthens transformation 25 D3 hydroxyvitamins in 1,25 D3 dihydroxyvitamin (calcitriol). Calcitriol increases active absorption of calcium in intestines and, besides, it is necessary for ensuring impact of PTG on a calcium exchange in bones.
Thus, hypocalcemia symptoms usually are result of decrease of the activity of parathyroid hormone or vitamin D.
Basic reasons of a hypocalcemia are given in the table
Treatment by radioiodine drugs
Dee Gheorghe's syndrome
Deficit of vitamin D
Disturbance of absorption in intestines
Treatment by anticonvulsant drugs
Chronic renal failure
Inborn deficit of vitamin D
Resistance of target organs to vitamin D
Cancer (osteoplastic metastasises)
Hypocalcemia of newborns
The hypoparathyrosis is defined as the state caused by reduction of secretion or peripheral effect of parathormone. Reduction of formation of parathormone causes direct decrease in a reabsorption of calcium in kidneys and the mediated reduction of its absorption in intestines which is carried out due to education reduction 1,25 D3 dihydroxyvitamins. Operative measures in a neck are the most common cause of deficit of PTG. Removal or damage of a parathyroid can be result of a thyroidectomy, parathyroidectomy and radical operation on bodies of a neck. The Posleoperationny hypocalcemia quite often arises even for lack of removal of considerable part of fabric of a parathyroid, apparently, as a result of the ischemia developing as a result of a section of nearby fabrics. The postoperative hypoparathyrosis usually has passing character and exists within several days or weeks. The syndrome of "a hungry bone" represents one of forms of a passing hypoparathyrosis which often arises after removal of adenoma of a parathyroid or after a thyroidectomy concerning a hyperthyroidism.
The deficit of PTG arising for no apparent reason is called an idiopathic hypoparathyrosis; this syndrome covers diverse group of disturbances which have family or sporadic character. On the basis of detection of antibodies to fabric of a parathyroid and autoimmune character of associated diseases, including addisonovy illness, primary hypothyroidism, diabetes mellitus, primary hypogonadism and pernicious anemia, the autoimmune mechanism of an idiopathic hypoparathyrosis was proved. Such patients can have candidiasis of skin and mucous, a vitiligo and focal baldness. Other form of an idiopathic hypoparathyrosis represents the state which is arising sporadic at adult age and not having signs of autoimmune disorders; its etiology is unknown, however at pathoanatomical research the parathyroid replacement of tissue fatty or fibrous tissue usually is found.
Destruction of epithelial bodies can arise also at other states resulting in deficit of PTG. According to messages, the radiation injury as a result of treatment of a hyperthyroidism drugs of a radioiodine leads to the expressed hypoparathyrosis in exclusively exceptional cases. Infiltration of parathyroid fabric iron with the subsequent development of a hypoparathyrosis can arise at primary and secondary forms of hemochromatosis. Infiltration of parathyroids a metastatic tumor represents the frequent phenomenon, especially at a breast cancer, however destruction of gland has to have subtotal character in order that the hypocalcemia developed. Disturbances of embryonic development can lead to an underdevelopment thymic and parathyroids, or to Dee Gheorghe's syndrome.
According to the author's description of Albright (1942), psevdogilolaratireoz represents rare "the inborn disease which is characterized by a hypoparathyrosis and specific organ disturbances. The concept of a psevdogipaparatireoe was expanded and \carry group of the diseases which are characterized by lack of reaction of target organs on to it now (Influence of parathyroid hormone.
At a classical pseudohypoparathyroidism of the I type there is a defect of the hormonal receptors connecting intracellular tsAMF, or disturbance of development of tsAMF that leads to, nonsensitivities of tissues of bones and kidneys to influence of PTG, decrease in content of calcium in blood, and also to decrease in effect of the exogenous PTG directed to increase in content in urine of phosphorus and tsAMF. Most of patients has characteristic organ symptoms, including a korotkopalost, low-tallness, a round face and "pseudo-union" of a neck. The term psevdopsevdogipopartireoz is used for the characteristic of patients at whom the specified somatic symptoms are observed for lack of the biochemical disturbances characteristic of a pseudohypoparathyroidism. At the I type also other disturbances, including a hypothyroidism, deficit of prolactin, a diabetes mellitus, and also lack of reaction to arginine, vazopressiya and a glucagon are described that can demonstrate the general disturbances of a metabolism of tsAMF.
Recently very rare form of a pseudohypoparathyroidism (the II type) was described. At this state the hypocalcemia and normal increase of content in tsAMF urine in response to exogenous receipt of PTG at restriction of its fosfaturichesky effect is found in patients. Characteristic organ disturbances are absent. As too small number of patients was inspected, remains not clear, are available ly metabolic differences of this disturbance from the I type of a pseudohypoparathyroidism. Opioana patients in whom the hormone differing on the structure from normal, therefore, was found they had similarity to patients with a pseudohypoparathyroidism. However they noted normal reaction to introduction of exogenous PTG. This syndrome received the name of a pseudo-idiopathic hypoparathyrosis.
DEFICIT OF MAGNESIUM
The hypocalcemia quite often arises at a hypomagnesiemia which cause can be an alcoholism, disturbances of absorption in a digestive tract or the nephropathy proceeding with magnesium loss. Refer treatment to other reasons of a hypomagnesiemia the diuretics and aminoglycosides strengthening release of magnesium with urine, long parenteral food and inborn defects of absorption of magnesium in intestines. The hypomagnesiemia leads to blockade of secretion of PTG and nonsensitivity to parathormone of kidneys and bones. Intravenous administration of magnesium sulfate leads to immediate release of PTG and the subsequent increase of serumal concentration of calcium.
To understand mechanisms of disturbance of a metabolism of vitamin D which lead to a hypocalcemia it is necessary to make the short overview of stages of biosynthesis of vitamin D. Vitamin D is formed in epidermis under the influence of ultraviolet rays or soaked up in intestines from food sources, first of all firm dairy products and animals (especially fish) fats. Then in a liver it is exposed to transformation in 25-gidrokeivitamin D3 (25-OHD3). This connection is the main circulating vitamin D form, however it possesses low metabolic activity. 25-OHD3 is exposed to a hydroxylation in kidneys and turns into 1,25 D3 dihydroxyvitamin (1,25(OH)2O3), or calcitriol, the most strong or metabolic active form of vitamin D. Calcitriol stimulates intestinal transport of calcium and its mobilization from bones.
Therefore, the hypocalcemia can result from deficit of consumption or absorption of vitamin D, disturbance of process of transformation of vitamin D into l, 25(OH)2D3 or a hyposensitivity of target organs to vitamin D, Food deficit of vitamin D in Russia meets now seldom. The gastrectomy and 1 switching off of a stomach cause disturbances of absorption and can result in deficit of vitamin D. Chronic pancreatitis, operations with switching off of sites of intestines can reduce absorption of vitamin D and increase losses 25-OHD3. Disturbances of absorption of vitamin D and reduction of education 25-OHD3 can arise at diseases of a liver and bilious ways.
Prolonged treatment by anticonvulsant drugs can lead to considerable disturbances of a metabolism of vitamin I) and calcium. These drugs increase activity of liver microsomal enzymes that leads to lowering of the level 25-OHD3 and to formation of less active metabolites (vitamin D. Besides, anticonvulsant drugs can interfere with impact of vitamin D on intestines and bones. The clinical picture is characterized by a hypocalcemia, a hypophosphatemia, increase of level of a serumal alkaline phosphatase, emergence of rickets or osteomalacy.
The hypocalcemia at a chronic renal failure also results from disturbance of synthesis and effect of vitamin D. Reduction of the functioning tissue of a kidney leads to decrease in synthesis of l, 25(OH)2D3. In addition, formation of less active metabolites of vitamin D which at the receptor level can compete with 1,25(OH)2D3 increases. Decrease in level 25-OHO3 at patients with uraemia results also from a hyponutrient, reduction of stay on the sun, and also disturbance of activity of liver microsomal enzymes. The hyperphosphatemia which leads to a hypocalcemia due to reduction of formation of l, 25(OH)2D3 and deposits of phosphatic and calcium complexes in soft tissues is characteristic of patients with a chronic renal failure.
Inborn insufficiency in kidneys of the enzyme of a hydroxylase necessary for formation of l, 25(OH)2D3, leads to a syndrome of inborn dependence on vitamin D. This state is shown at early children's age by a gipokaltsiyemichesky tetany, a hypophosphatemia, increase of level of a serumal alkaline phosphatase and rickets. As successful treatment requires use of high doses of vitamin D, it is considered that peripheral resistance to vitamin D is the cornerstone of a pathogeny of this state. Nevertheless treatment of this state physiological doses of vitamin l, 25(OH)2D3 demonstrates that it insufficient activity of a renal hydroxylase is the reason. In recent years there were messages on family and sporadic forms of resistance of target organs to action of l, 25(OH)2D3.
Hyperphosphatemia. Acute increase of serumal concentration of phosphorus can lead to a hypocalcemia due to formation of extra bone deposits of calcium or suppression of a resorption of bones. This increase of level of a fosfatemiya can result from intravenous administration of phosphorus and use of phosphorus enemas, and also at the massive killing caused by chemotherapy, burns or rabdomiolizy.
Acute pancreatitis. This disease is the well-known reason of a hypocalcemia. Decrease in concentration of calcium is connected with sedimentation of compounds of calcium with the fatty acids forming "soaps" in a bed of a pancreas and other sites of a necrosis of fatty tissue. However some researchers consider that this concept completely does not explain the observed calcium losses. Among other mechanisms causing a hypocalcemia — glucagon hypersecretion, a hyper calcitoninemia and resistance of peripheral bodies to action of PTG. The last researches demonstrate that the steady hypocalcemia at acute pancreatitis can be caused by relative insufficiency of parathyroids.
Medicines. Many medicines can cause a hypocalcemia. Phosphates, anticonvulsant drugs, diuretics, antibiotics of group of aminoglycosides and antineoplastic drugs were mentioned earlier. Use of alkalis reduces amount of the ionized calcium and can cause hypocalcemia symptoms. Besides, EDTA, a calcitonin, mntramntsin and diphosphonates can cause a hypocalcemia. Transfusions of high doses of a citrated blood can lead to formation of calcic complexes and a hypocalcemia. At newborns the short-term hypocalcemia often arises at prematurity, respiratory a distress syndrome and in the presence at mother of diabetes. In these cases some decrease in the PTG level can be observed. The short-term hypocalcemia at newborns within the first week of life can arise when feeding by the cow's milk or mixes containing a large amount of phosphorus.
Osteoblastic metastasises. The hypocalcemia at cancer patients usually arises in connection with osteoblastic metastasises. The most characteristic types of cancer are the metastasizing prostate cancer, a mammary gland and lungs. Osteoblastic metastasises absorb calcium, leading to development of negative balance. Besides, emergence of a hypocalcemia can be promoted by a hypoparathyrosis, a hyperphosphatemia, a hypomagnesiemia and disturbances of a homeostasis of vitamin D. The hypocalcemia can occur at cancer patients also often, as well as the hypercalcemia, and at untimely diagnosis to bring to life-threatening the patient to gipokaltsiyemichesky crisis.