Increased phosphate excretion in urine
Introduction
Introduction Vitamin D rickets, mainly due to the renal hypertonic tubules, have a barrier to the transport mechanism of phosphorus, increased urinary excretion of phosphate, decreased phytate and affect bone calcification, patients with short stature, treatment with vitamin D is ineffective.
Cause
Cause
1. Vitamin D deficiency: Vitamin D deficiency is the main cause of this disease. There are two ways to source Vit D. One is homology. It is converted into cholecalciferol (cholec) by 7-dehydrocholesterol stored in the basal layer of the skin by ultraviolet rays with a wavelength of 296-310 m in sunlight. Alciferol) is vitamin D3 (VitD3). Another way is exogenous, that is, the food intake contains VitD, such as liver containing 15 ~ 50IU / kg1, milk 3 ~ 40IU / L, egg yolk 25IU /. However, the amount of VitD in these foods is very small, which is not enough for the body. The ergosterol forms a vitamin D2 (calcified alcohol, Calciferol) after being irradiated with ultraviolet rays. Both VD2 and VD3 can be artificially synthesized to have the same effect on humans.
2. Insufficient UV exposure is also a major cause of VitD deficiency, especially in the North. Ultraviolet light is applied to the skin to obtain enough VitD3. China has a vast territory, different natural conditions in the north and south, especially in the sunshine, the length of sunshine is long, the incidence of rickets is low, the sunshine time in the north is short, and the incidence is high. However, ultraviolet rays in sunlight are easily blocked or absorbed by dust, smoke, clothing and ordinary glass. At present, China's industrial development is fast, and there are many urban buildings. In some places, it also brings air pollution. High-rise buildings, light barriers, and living in the home can all affect the ultraviolet radiation.
3. Other factors
(1) If the growth is too fast, more VitD is required. Therefore, children with fast growth are prone to rickets. Premature infants have insufficient calcium and phosphorus reserves, and grow faster after birth. If they lack VitD, they are prone to rickets.
(2) Insufficient calcium or phosphorus content in food or inappropriate proportion may also lead to rickets. For example, the proportion of calcium and phosphorus in human milk is suitable, the ratio is 2:1, easy to absorb; while milk contains more calcium and phosphorus, but the phosphorus is too high and the absorption is poor, so the incidence of rickets in milk-fed children is higher than that of human milk. Children are high.
(3) Excessive cereals contain a lot of phytic acid, which can combine with calcium and phosphorus in the small intestine to form insoluble phytochemical calcium, which is not easy to absorb.
(4) Chronic respiratory infections, gastrointestinal diseases and liver, pancreas and kidney diseases can affect the metabolism of VD and calcium and phosphorus.
(5) Acid and alkalinity are not suitable, and can also affect the absorption of calcium and phosphorus by the intestine. Generally, when the intestinal pH is low, calcium and phosphorus are absorbed more. Calcium and phosphorus metabolism and bone development VitD deficiency affects calcium and phosphorus absorption, which can cause abnormal metabolism of calcium and phosphorus. Calcium and phosphorus metabolism In addition to VitD, there are other factors involved in the body, interacting and linking to exert positive and negative feedback of calcium and phosphorus metabolism to maintain normal calcium, phosphorus metabolism and bone development. Among them are the participation of parathyroid hormone, calcitonin, chondrocytes, osteoblasts and stromal cells. In addition, growth hormone, male and female hormones, thyroxine, glucocorticoids, etc. also have an effect on calcium and phosphorus metabolism.
The relevant factors are briefly described below.
1. The effect of vitamin D on calcium and phosphorus metabolism
VitD, absorbed through the skin or through the digestive tract, is stored in plasma, liver, fat and muscle. VitD is inactive after being absorbed, and it needs to undergo secondary hydroxylation in the body to exert a hormone-like biological effect.
First, VitD is transported to the liver, and the action of the 25-hydroxylase system of the hepatocyte endoplasmic reticulum and microsomes turns VitD3 into a 25-hydroxylase system, which turns VitD3 into 25-hydroxycholine. Alcohol (25-(OH)D3). The latter has an inhibitory effect on the negative feedback of 25-hydroxylase activity to modulate the concentration of 25-(OH)D3 in the blood. 25-(OH)D3 is transported to the kidney, and the 1,25-hydroxyl group is produced by the action of the 25-(OH)D3-1-hydroxylase system (1-hydroxylase) in the mitochondria of the proximal tubule epithelial cells. Cholecalciferol (1,25-(OH)D3). The latter has a negative feedback inhibition effect on the 1-hydroxylase active material, 1,25-(OH)D3 activity is very strong, the effect on calcium and phosphorus metabolism is higher than 25(OH)D3200 times, and the formation of bone salt The effect is 100 times higher.
Active VitD is affected by the concentration of calcium and phosphorus. Low calcium and phosphorus can stimulate the activity of 1-hydroxylase, which accelerates the formation of 1,25-(OH)D3. On the contrary, high blood calcium and phosphorus can inhibit 1- Hydroxylase activity. High blood calcium and phosphorus can also promote the conversion of 25-(OH)D3 to 24-25-(OH)D3, which loses VitD activity or has minimal effect. The role of 1,25-(OH)D3:
1 It can promote the absorption of calcium and phosphorus in the small intestinal mucosa. 1,25-(OH)D3 can bind to the specific receptor of target cells of 1,25-(OH)D3 in the small intestinal mucosa, and then form the VD-binding protein calcium, which is transported from the mucosal side of the epithelium to the serosal membrane. The capillary is absorbed into the blood.
21,25-(OH)D3 can promote the absorption of calcium and phosphorus by the glomerular proximal tubules to increase the concentration of blood calcium and phosphorus.
31,25-(OH)D3 can promote the differentiation of undifferentiated mesenchymal cells into osteoclasts, promote bone resorption, dissolve bone salts in old bone, and increase blood calcium and phosphorus concentrations. 41,25-(OH)D3 can directly stimulate osteoblasts and promote calcium deposition. It can be seen that when liver and kidney dysfunction, it will affect the VD hydroxylation process, which is also the cause of hepatic and renal rickets.
2, the role of parathyroid hormone (PTH)
The secretion of 1PTH depends on the blood calcium concentration. When the blood calcium is lower than normal, the PTH increases, and when the blood calcium is high, the PTH secretion changes. Hypercalcemia can change the target organ adenylate cyclase, which reduces the formation of cyclic adenosine monophosphate (c-AMP). In the case of hypocalcemia, the opposite is true, which can increase c-AMP. PTH acts on the adenylate enzyme system of the target cells, which increases the intracellular c-AMP and promotes the migration of calcium ions into the cytoplasm. The increase in cytosolic ionized calcium increases the calcium pump of the cell membrane, shifting calcium ions out of the cell and increasing blood calcium levels.
The effect of 2PTH on bone: When PTH is increased, the ability to stimulate undifferentiated mesenchymal cells to differentiate into osteoclasts is enhanced, thereby increasing bone resorption and increasing blood calcium and phosphorus concentrations. PTH inhibits osteogenesis and plays an antagonistic role with 1,25-(OH)D3.
The effect of 3PTH on the kidney: PTH acts on the renal tubules, promotes the absorption of calcium, and allows calcium ions to enter the bloodstream through the calcium pump on the serosal surface. PTH inhibits the reabsorption of phosphorus by the renal tubules, promotes the increase of urinary phosphorus, and antagonizes with 1,25-(OH)D3. Another effect of PTH is to make 25-(OH)D3 a 1,25-(OH)D3 velocity recall.
4PTH promotes absorption of intestinal calcium, which is caused by an increase in the concentration of 125-(OH)D3, but it is also believed that PTH has a direct effect on intestinal calcium absorption.
3. Calcitonin (CT): derived from parathyroid and thyroid follicular cells ("C" cells). Calcitonin is affected by blood calcium concentration; the normal value of CT in blood is below 72±7 ng/L. When blood calcium rises, it can promote CT rise, and vice versa.
1CT on bone: it can control the formation of osteoclasts, inhibit bone resorption, prevent bone salt dissolution and bone matrix decomposition. CT can promote the transformation of broken muscle cells into osteoblasts and strengthen the effect of calcium. The calcitonin biological effects of juvenile animals are active.
The effect of 2CT on sputum: inhibit the absorption of calcium and phosphorus by renal proximal tubules, and increase urinary calcium and urinary phosphorus excretion. The effect of 3CT on the intestine: inhibits the absorption of calcium by the digestive tract, and CT also inhibits the absorption of sodium, potassium and phosphorus in the intestinal tract.
VitD, PTH and CT have synergistic and antagonistic effects on calcium and phosphorus metabolism in the intestine, bone and kidney. And there is obvious mutual feedback between them, thus maintaining the normal metabolism of calcium and phosphorus in the body and the normal development of bone.
4. Normal development of bone: There are two forms of normal bone development, one is cartilage osteogenesis and the other is membranous osteogenesis. The former is mainly performed at the long bone end, which makes the bone longer; the latter is performed in the cortical bone and the flat bone, which makes the bone thicker or thicker and widened.
The developmental age of the epiphyseal cartilage is the proliferation of differentiated chondrocytes from the bone end of the bone to the bone. Chondrocytes develop from autologous bone nucleus to metaphyseal cartilage, and their differentiation can be divided into:
1 germinal cell layer, small and small undivided squamous cells, 2 proliferating chondrocyte layer, is formed by the division of germinal cells, the cells are flat, closely arranged into a column, and the columnar cartilage matrix increases.
3 The osteogenic chondrocyte layer, whose cell volume gradually increases, is arranged in a square shape.
4 hypertrophic chondrocyte layer, its cell volume is more hypertrophic, mature, arranged neatly columnar. The calcium, phosphorus, etc. input from the metaphyseal vessels begin to deposit in the matrix of the 3, 4-layer hypertrophic chondrocytes, which in turn degrades the chondrocytes.
5 Degraded layer, the final stage of cell degradation. Cell necrosis and dissolution are the final stages of cell degradation. The cells are necrotic, the tubes are arranged neatly and densely, which is the temporary calcium meridian seen on the X-ray film. The capillaries are visible in the calcified tube, and the osteogenesis cells are arranged around the blood vessels.
6 osteogenic area is the new bone cancellous area. Osteoblasts cling to the calcified wall, secreting bone matrix, followed by calcium deposition, osteoblasts are also embedded, forming initial trabecular bone, and then reconstructed into mature trabecular bone and longitudinal arrangement to form metaphyseal osteoporosis quality.
It has been suggested that there is a matrix vesicles in bone tissue derived from chondrocytes and osteoblasts. Because of its presence in the matrix, it is the name of the matrix blisters. The matrix vesicles have a membrane with a diameter of about 30-300 nm, and the bubbles are rich in alkaline phosphatase, ATPase and pyrophosphatase (some people think that these enzymes are the same). In the hypertrophic chondrocyte layer, under the action of phosphatase on the biofilm of the matrix vesicle, the action of small intracellular pyrophosphate bone salt crystallizes, while pyrophosphatase can decompose pyrophosphate and further be rich in alkali in the vesicle The phosphoric acid further decomposes other phosphates to become inorganic phosphorus. This increases the local calcium and phosphorus concentrations and forms bone salt crystals in the matrix vesicles. This crystal protrudes from the vesicle membrane of the matrix and extends outward to precipitate the bone salt. Further, apatite is formed, that is, a mast cell layer forming a metaphyseal chondrocyte and a calcified part of a bone matrix synthesized by osteoblasts - a temporary calcification zone.
Pediatric growth time bone development, that is, the growth of chondrocytes, the temporary calcification zone is constantly moving forward, the bone pine is constantly remodeled, so that the long bones continue to grow. Bone softening (2/3 in normal children's bones as inorganic matter, 1/3 as organic matter, the proportion of the two bones in the rickets) is opposite, and the calcified bone-like tissue proliferation replaces the normal temporary calcification line, making the bone The length development is significantly changed by the significant obstacles, forming a dwarf state.
Examine
an examination
Related inspection
Urine routine renal function test
Alkaline phosphatase increased earlier in the course of rickets, and recovered at the latest. The level of 25(OH)D3 or 1,25(OH)2D3 in serum was measured, and its value was only zero in typical rickets, and it was also significantly decreased in subclinical rickets, and it was significantly increased after vitamin D treatment, which was sensitive and reliable biochemistry. index.
X-ray changes were evident in long bones with faster bone development, especially at the distal end of the radius and the proximal humerus.
Diagnosis
Differential diagnosis
There are more urinary porphyrins in the urine: it is caused by porphyria. Porphyria is a disorder of porphyrin metabolism disorder characterized by increased excretion of porphyrin and porphyrin precursors in urine and feces. Porphyria is a congenital disease that is mainly caused by a lack of various enzymes involved in heme synthesis and has a family history.
Increased urinary estrogen: Determination of estrogen in urine: There are three main types of estrogen in the urine, namely estrone, estradiol and estriol. Estrogen has different normal values in different stages of menstrual cycle in women of childbearing age. In the first 7 days of menstrual cycle, estrogen levels are very low, and then rise with the development of follicles, reaching a peak on the 13th day, called ovulation peak. After a sudden decline, it gradually rose, and reached the peak on the 21st day, called the peak of the corpus luteum. Later, it will drop to menstrual cramps. Functional uterine bleeding estrogen levels are maintained below normal levels. The level of estrogen in uterine amenorrhea is normal, but the ovarian function is defective or the congenital ovary is not developed and causes amenorrhea. The estrogen level is low, but there is no periodic change. The pituitary or subthalamic amenorrhea, the estrogen level is generally lower. .
Persistent sodium excretion in the urine: belongs to the antidiuretic hormone abnormal syndrome (SIADH), which means that when the plasma osmotic concentration and blood sodium are normal or low, the vasopressin is still secreted, resulting in a decrease in free water clearance, water retention, and low A syndrome of a series of clinical manifestations such as sodiumemia, hypotonic blood pressure, and the like. In addition to the primary disease manifestations, SIADH children are parallel with the degree of hyponatremia. When serum sodium is above 120mmol/L, the clinical symptoms are asymptomatic. When the blood sodium drops below 120mmol/L, there may be loss of appetite and nausea. Symptoms such as vomiting, when the urine sodium content is high, blood sodium is lower than 110mmol / L, neuropsychiatric symptoms, even convulsions, coma until death, when blood sodium is lower than 95 ~ 109mmol / L, for 3 days can cause irreversible Brain Injury.
Increased histamine excretion in the urine: Histamine is a reactive amine compound with a chemical formula of C5H9N3 and a molecular weight of 111. As a chemical conductive substance in the body, it can affect the reaction of many cells, including allergies, inflammatory reactions, gastric acid secretion, etc. It can also affect the nerve conduction in the brain, which can cause sleep and other effects. The metabolites after taking H1 receptor antagonists (ie, antihistamines) are excreted in the kidneys for a few to several tens of hours, and the urine excretion accounts for a large part. This leads to an increase in histamine excretion in the urine.
Alkaline phosphatase increased earlier in the course of rickets, and recovered at the latest.
The level of 25(OH)D3 or 1,25(OH)2D3 in serum was measured, and its value was only zero in typical rickets, and it was also significantly decreased in subclinical rickets, and it was significantly increased after vitamin D treatment, which was sensitive and reliable biochemistry. index. X-ray changes were evident in long bones with faster bone development, especially at the distal end of the radius and the proximal humerus.
