Pathogenesis of rickets
Last reviewed: 23.04.2024
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Vitamin D, which enters the body with food, combines with a 2- globulin and enters the liver, where it is converted into a biologically active metabolite, 25-hydroxycholecalciferol (25-OH-D3), (calcidiol) by the action of the enzyme 25-hydroxylase. This metabolite comes from the liver to the kidneys, where under the influence of the enzyme 1 os-hydroxylase from it, two metabolites are synthesized:
- 1,25-dihydroxycholecalciferol [l, 25- (OH) 2- D3 (calcitriol), which is 5-10 times more active than vitamin D. It is a high-speed active compound that plays a key role in regulating calcium absorption in the intestine and delivering it to the organs and fabrics.
- 24,25-dihydroxycholecalciferol [24,25- (OH) 2 -D3, which provides fixation of calcium and phosphate in the bone tissue, inhibits the secretion of parathyroid hormone. This is a long-acting compound that controls the mineralization of the bone with sufficient delivery of calcium to the sites of its formation.
The concentration of calcium in the serum is constant and is 2.25-2.7 mmol / l. Normally, the concentrations of calcium and phosphorus are maintained at a ratio of 2: 1, which is necessary for the proper formation of the skeleton. Calcium in the blood is in 2 forms - ionized and associated with protein.
The absorption of calcium ions carries out the epithelium of the small intestine with the participation of calcium-binding protein, the synthesis of which stimulates the active metabolite of vitamin D-1, 25- (OH) 2 -D 3. It is necessary along with the hormones of the thyroid and parathyroid glands for normal ossification and growth of the skeleton. The lack of vitamin D leads to a decrease in the level of the active metabolite in the blood serum, which disrupts the absorption of calcium ions in the intestine, their reabsorption by the renal tubules, and also reduces the activity of resorption of calcium and phosphorus from the bone, which can lead to hypocalcemia.
A decrease in the level of ionized calcium in the blood plasma leads to stimulation of parathyroid gland receptors, which stimulates the production of parathyroid hormone. The main effect of PTH - activation absorbable bone tissue of osteoclasts and the inhibition of collagen synthesis in osteoblasts. As a result, calcium is absorbed from the bone tissue into the blood (compensating for hypocalcemia) and the formation of an uninoculated bone, which causes the development of osteoporosis, and then osteomalacia. Simultaneously, the parathyroid hormone decreases the reabsorption of phosphates in the tubule of the kidneys, as a result of which phosphorus is excreted in the urine, hyperphosphaturia and hypophosphatemia develop (an earlier sign than hypocalcemia). Reducing the phosphorus in the blood plasma leads to a slowdown in oxidative processes in the body, which is accompanied by the accumulation of under-oxidized metabolites and the development of acidosis. Acidosis also prevents the calcification of bones, supporting the phosphoric-calcium salts in the dissolved state. The main pathological changes in rickets are noted in the metaepiphyseal zones of the bones. They soften, twist, thin. Along with this, an incomplete (uninfected) osteoid tissue proliferates.
Calcitonin is a potent antagonist of parathyroid hormone. It reduces the number and activity of osteoclasts, inhibits bone resorption, provides calcium return to bone tissue and suppresses the secretion of parathyroid hormone. Secretion of calcitonin increases with an increase in the concentration of calcium in the blood and decreases when it decreases.
In the development of rickets, in addition to the disturbance of mineral metabolism, violations of fat and carbohydrate metabolism, in particular, reduction of the formation of citrates from pyruvic acid, are important, as reducing the concentration of citric acid disrupts the transport of calcium into the blood. In addition, the reabsorption of amino acids in kidneys is reduced, aminoaciduria develops, the disturbances in protein metabolism worsen the absorption of calcium and phosphate.
The most significant links in the pathogenesis of rickets are:
- violation of the formation of cholecalciferol in the skin;
- violation of phosphoric-calcium metabolism in the liver, kidneys;
- insufficient intake of vitamin D.
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