Treatment of Hypervitaminosis D

Materials for practical classes for 4-years student

Rickets

Rickets - is a disease of children of the 1st years with disorders of bone production and deficiency of their mineralization. Rickets is a disease of growing organism, which appears as a result of polyhypovitaminosis with primary insufficiency of vitamin D, that leads to disturbances in metabolism of phosphorus and calcium and processes of ossification with changes of organs and systems function.

Rickets is a disease of children of first two years. Its diagnostics is based on clinical manifestations involving nervous, osseous, muscular systems and laboratory and instrumental investigations. Case history reveals etiology and factors, which favour the development of disease.

Etiology. There are the following predisposal factors for appearance of rickets:

1. Deficiency of UV irradiation and staying out-doors, because 90% of endogenously created vit D₃ in organism is synthesized in skin under influence of sun beams. It is necessary to take into account that because of pollution of atmosphere of big cities, only minimal quantity of sun beams having antirachitic activity reaches the earth.

2. Food factors. Increase of frequency and severity of rickets was confirmed in groups of children receiving:

a) non-adapted mixtures (to which vit D is not added);

b) milk feeding only for a long time (1L of woman's milk contains 40-70 IU of vit D, cow's milk - 5-40 IU), late prescription of additional food (1 g of egg's yolk contains 140-390 IU of vit D);

c) vegetarian additional food predominantly (vegetables, porridges) without sufficient quantity of animal proteins and fats.

It is necessary to pay attention that not deficiency of vit D in food is a cause of rickets, but feeding not providing optimal conditions for entering of P and Ca from food and for proteins, lipids, microelements, other vitamins metabolism.

In particular, there is a lot of phytin acid in cereals which binds Ca in intestine, and lignin as well which provides the same effect upon vit D and its metabolites. A great quantity of vegetables and cow milk nowdays contain plenty of phosphates (because of wide use of phosphate fertilizers), that inhibits absorption of Ca.

3. Perinatal factors. Prematurity predispose to rickets because the most intensive income of Ca and P from mother to fetus takes place during last months of pregnancy, so a baby born earlier than 30 weeks of gestation very often has osteopenia- more low content of mineral substances in bone. At the same time they are need in greater quantity of Ca and P in food because of greater rate of postnatal growth comparatively with mature children. Besides, prematurity, as well as placental insufficiency, is combined with much more low reserve in organism and more low level of vit D and its metabolites in cord blood.

4. Insufficient motor activity because of not only perinatal encephalopathies, but absence of physical culture also: as blood flow of long bones is increased during muscular activity.

5. Dysbacteriosis with diarrhea.

6. Anticonvulsive prolonged therapy, which leads to speeding up metabolism of active forms of vit D.

7. Syndromes of malabsorption, chronic diseases of liver and kidney, which lead to disorders of formation of active forms of vit D.

8. Hereditary anomalies of metabolism of vit D, Ca and P.

9. Ecological factors. Excess of strontium, zinc and other metals in soil, water, food leads to partial substitution of Ca by these substances.

10. Pigmentation of skin decreases intensity of creation of chotecalciferol in skin.

Pathogenesis.The main pathogenetic factors are deficiency of vit D and its active metabolites in a period of most intensive organism's growth.

Endogenous vit D₃ (cholecalciferol) is synthesized in skin from 7-dihydrocholesterin under influence of ultraviolet rays. More than 60 its metabolites are created in organism later, but nowadays only 2 of them are considered to influence actively upon metabolism of Ca and P - 1,25-dihydrocholecalciferol and 24,25-dihydrocholecalciferol. Both of them are created in kidneys, and intermediate metabolit (25-hydrocholecalciferol) - in liver. The main effects of active metabolites of vit D₃ are stimulation of absorption of Ca and P in intestine and stimulation of bone's mineralization. They activate synthesis of Ca-bounding proteins and increase activity of adenilatcyclase; that's why we consider vit D₃ to be hormone.

Hypocalcemia leads to increased function of parathyroid glands. Parathormone decreases (and vit D increases) reabsorption of phosphates in kidney tubules, stimulates absorption of Ca in intestine, resorbtion of Ca from bone and thus - liquidates hypocalcemia.

Insufficiency of vit D provokes aminoaciduria, leads to disorder of structure of organic matrix of bone (collagen), Disorder of ossification is seen in epiphysis, in metaphysis we see excessive growth of osteoid tissue.

Classification of Rickets

Clinical manifestations. Osseous changes of rickets can be recognized after several months of vitamin D deficiency. In breast-fed infants whose mothers have osteomalacia rickets may develop within 2 mo. Florid rickets appears toward the end of the 1st and during the 2-nd year of life. Later in childhood, manifest vitamin D deficient rickets is rare.

One of the early signs of rickets, craniotabes, is due to thinning of the outer table of the skull and detected by pressing firmly over the occiput or posterior parietal bones. A ping-pong-ball sensation will be felt. Craniotabes near the suture lines is a normal variant. Low-birthweight infants are particularly susceptible to the early development of rickets and to craniotabes. Palpable enlargement of the costochondral junctions (the "rachitic rosary") and thickening of the wrists and ankles are other early evidences of osseous changes. Increased sweating, particularly around the head, may also be present.

Head. Craniotabes may disappear before the end of the 1st year, although the rachitic process continues. The softness of the skull may result in flattening and, at times, permanent asymmetry of the head. The anterior fontanel is larger than normal; its closure may be delayed until after the 2nd year of life. The central pans of the parietal and frontal bones are often thickened, forming prominences or bosses, which give the head aboxlike appearance (caput quadratum). The head may be larger than normal and may remain so throughout life. Eruption of the temporary teeth may be delayed, and there may be defects of the enamel and extensive caries. The permanent teeth that are calcifying may also be affected; the permanent incisors, canines, and first molars usually show enamel defects.

Thorax. Enlargement of the costochondral junctions may become prominent; the beading of the ribs is not only palpable but also visible. The sides of the thorax become flattened, and the longitudinal grooves develop posterior to the rosary. The sternum with its adjacent cartilage appears to be projected forward producing the so-called pigeon breast deformity. Along the lower border of the chest develops a horizontal depression, Harrison's groove which corresponds with the costal insertions of the diaphragm. There may be a variety of other thoracic deformities, including those of the shoulder girdle.

Spinal Column. Slight to moderate degrees of lateral curvature (scoliosis) are common, and a kyphosis may appear in the dorsolumbar region of rachitic children when sitting. Lordosis of the lumbar region may be seen in the erect position.

Pelvis. In children with lordosis there is frequently a concomitant deformity of the pelvis, which is also retarded in growth. The pelvic entrance is narrowed by a forward projection of the promontory the exit, by a forward displacement of the caudal part of the sacrum and the coccyx. In the female, these changes, if they become permanent, add to the hazards of childbirth and may necessitate cesarean section.

Extremities. As the rachitic process continues, the epiphyseal enlargement at the wrists and ankles becomes more noticeable. The enlarged epiphyses can be seen or palpated but are not distinct in roentgenograms because they consist of cartilage and uncalcified osteoid tissue. Bending of the softened shafts of the femur, tibia, and fibula results in bow-legs or knock-knees; the femur and the tibia may also acquire an anterior convexity. Coxa vara is sometimes the result of rickets. Greenstick fractures occur in the long bones; often there are no clinical symptoms.

Deformities of the spine, pelvis, and legs result in reduced stature, rachitic dwarfism.

Ligaments. Relaxation of ligaments helps to produce deformities and partly accounts for knock-knees, overextension of the knee joints, weak ankles, kyphosis, and scoliosis.

Muscles. The muscles are poorly developed and lack tone. As a result, children with moderately severe rickets are late in standing and walking. Potbelly depends to a large extent on weakness of the abdominal muscles; weakness of the gastric and intestinal walls may contribute.

Diagnostic criteria

/. Clinical:

a) syndrome of affection of nervous system is observed in 100% of cases and is revealed at initial period of disease as excitability, interrupted sleep, sweating, and quick persistent red dermographism. At the height of disease flaccidity, lag of motor development or rarely nervous-psychical retardation (only in graveforms of disease);

b) syndrome of lesion of osseous system is revealed in100% of cases. There are the following symptoms:

- symptoms of osteomalacia which manifest in form of softening of the big fontanel's edges, craniotabes, softening of ribs (Harrison's groove), kyphosis, bandy and baker's legs;

- symptoms of hyperplasia of osteoid tissue - increase of frontal and occipital tubers, costohondral prominence ("rachitic rosary"), bracelets on the upper and lower extremities, threads of pearls on finger's phalanges;

- symptoms of hypoplasia of osseous tissue - tardy closing of fontanels, delayed dental eruption, in severe cases - lag of growth of tubular bones in length. In acute course of rickets symptoms of osteomalacia prevail, in subacute - symptoms of hyperplasia of osteoid tissue;

c) muscular hypotonia is seen in 98,8% of patients. Its development leads to delay of statical abilities;

d) changes of internal organs: cardio-vascular system, respiratory tract, digestive tract and so on, increase of liver and spleen.

//. Laboratory:

e) common blood analysis - hypochromic anemia;

f) biochemical analyses of blood:

- increase of alkaline phosphatase at the initial period of disease;

- hypophosphatemia of a slight degree at the initial period of disease but marked at its height (normal level of phosphorus in blood - 0,97-1,62 mmol/l);

- hypocalcemia of moderate or high degree at the height of disease (normal level of calcium in blood is 2,25-2,75 mmol/l);

g) X-ray: disorders of periostal and enchondral ossification in the bone's growth zone are revealed. Bone becomes low contrasted, cortical stratum becomes thinner, zones of enlightenment appear (Loozer's zones). Strip of preliminary calcification disappears (preparatory zone), the edge becomes illegible, loosened. Growth zone dilates, becomes fungus-like or glass-like. Epiphyseal nucleus appears lately.

Differential diagnosis: Vit D-dependent rickets of I type: defect of 25-hydroxyvitamin D-l-hydroxylase in kidney lays in its basis. Laboratory signs are following: hypocalcemia, hypophosphatemia, high levels of parathormone in blood, increased activity of alkaline phosphatase, aminoaciduria, gllucosuria. Usual doses of vit D are ineffective.

Vit D-dependent rickets of II type: almost the same, but total alopecia and retarded growth are present; level of 1,25 (OH)₂ D₃ is normal, but hypocalcemia and hypophosphatemia are preserved.

Phosphat-diabetes: defect is not quite clear, but it concerns reabsorption of phosphates in renal tubules and decreased activity of convertion of 25 (OH) D₃ in 1,25 (OH)₂ D₃. There are O-shaped legs; hypophosphatemia may be revealed by chance from the 1^st month of life, signs of hypocalcemia, hyperplasia of osteoid tissue, myopathy are absent, level of blood Ca is normal or slightly decreased, parathormone in blood is normal, alkaline phosphatase elevated a little bit.

Hypophosphatasia. the length of tubular bones is diminished, there are disorders of ossification of all skeletal bones; activity of alkaline phosphatase in blood is very low. Hypercalcemia, nephrocalcinosis, renal insufficiency may be seen.

Differential diagnosisis also made with congenital fragility of the bones, Down's disease, chondrodystrophy, hypothyrosis, phosphatic diabetes, syndrome of De Toni-Debre-Fanconi, renal tubular acidosis.

Treatment. Common measures in rickets treatment irrespective of it form are the following:

- adequate feeding, regimen and walks;

- massage and curative physical training;

- complex of vitamins A,B,C with microelements.

In initial stage of rickets 1,500-2000 IU of vit D₂ is enough (total dose 100-120 000 IU) during 30-40 days. In moderate and severe rickets it's necessary to prescribe 3-5 000 IU/d (200-400 000 ID) during 30-40 days. Criterion of finishing the treatment is normalization of laboratory findings.

Dose of calcifediol (25(OH)D₃) and calcitriol (1,25(OH)₂D₃) are 10 and 1 mcg/d correspondently during two 10 days courses with 2 weeks' interval between them. After the course of treatment it's necessary to give preventive dose (500 IU/d). UV irradiation is effective. Prescription of citrates is of great use.

In endogenic cases of deficient rickets doubled doses may be used. As a rule active metabolites of vit D are prescribed.

If hypocalcemia is seen the initial dose of vit D must be doubled. Besides, calcium must be given (orally, parenterally, or electrophoresis).

Prevention of Rickets

Prevention may be antenatal and postnatal, specific and non-specific.

Prenatal prevention of rickets is carried out by obstetricians. Specific prevention is not indicated in women older than 35 years, because of excessive Ca deposits in placenta and fetal hypoxia, atherosclerosis in women.

Postnatal specific prevention with vit D is provided by doses 500 IU/d, that is the physiological necessity of a child's organism. Oily solutions of vit D (ergocalciferol) are used more often. Use of total 2-5 daily doses in one intake (correspondingly every 2-5 days). In summer the vitamin is not given. Premature infants need the administration of vit D from 2 weeks by doses 1000-1500 IU/d. Prophylactic course of vitamin D may be interrupted by UV irradiation. Specific prevention isn't carried out in the children receiving formula feeding.

Specific postnatal prevention we begin from 2^nd week with 500 IU of vit D all year round + vit C 0.03 g + B, B₂ - 0,001 g, B₅ 0.003 g 2 weeks in a month. It is possible to alternate vit D with UV irradiation, after course of which it is not necessary to give vit D 3-4 weeks. Once in 2-3 weeks it is necessary to provide test of Sulkowitz; if it is positive, vit D must be abolished.

Non-specific prevention signifies rational feeding, individual care, sufficient stay outdoors, gymnastics, massage.

Hypervitaminosis D

Hypervitaminosis D is a disease, which is stipulated by the toxic action of vitamin D and is characterized with intoxication of different degree, affection of organs and systems and development of hypercalcemia.

Diagnostic criteria

/. Clinical:

1. Syndrome of toxicosis:

Toxicosis of 1 degree - decrease of appetite, irritability, disorders of sleep, delay of weight increase, subfebrile temperature.

Toxicosis of 2 degree - pallor of skin, vomits, decreases of weight, functional disorders of internal organs and systems.

Toxicosis of 3 degree - anorexia, persistent vomits, dehydration, considerable loss of weight, complications such as pneumonia, pyelonephritis, myocarditis, and pancreatitis.

2. Syndrome of functional disorders of nervous system: flaccidity, apathy, alternating with excitability, irritability, drowsiness, hyperesthesia, sweating, meningism, encephalitic reactions, depression of consciousness, convulsions.

3. Cardio-vascular syndrome:

tachycardia, muffled cardiac sounds, systolic murmur, cyanosis, dyspnea, enlargement of liver, edemas. ECG disorders - dilation of QRS-complex, lengthening of PQ interval, smoothing of T-wave, diphase T-wave in lead V₄.

4. Gastro-intestinal syndrome:

decrease of appetite up to anorexia, vomit, persistent constipation, rarely diarrhea, enlargement of liver and spleen.

5. Renal syndrome:

dysuric symptoms, polyuria, probably oliguria up to anuria, azotemia.

6. Changes in osseous system:

consolidation of the skull bones, early closure of big fontanel, craniostenosis.

//. Laboratory:

- blood: leucocytosis, elevated ESR;

- biochemical changes: hypercalcemia, hypophosphatemia, hypomagnesemia, hypokalemia, elevated levels of citrates and cholesterin;

- urine: increase of calcium, Sulkowitch?s test is positive;

- stool: neutral fat;

- acid-base equilibrium - metabolic acidosis.

Classification of Hypervitaminosis D

Treatment of Hypervitaminosis D

This depends upon the severity of general condition. Intensive detoxicative therapy includes: i.v. injections of 5% albumin, 5% solution of glucose with Ringer?s solution, cocarboxylase, vit C, prednisolone, vit E, furosemid (1 mg/kg 3 times/d), thyreocalcitonin (75-150 U i.m. every day), 3% solution of ammonium chloride (teaspoonful 3 times a day), almagel, Trilon B 50 mg/kg 2-3 times/d.

It is necessary to exclude food with high concentration of calcium (milk, curds).

Tetany

Tetany is a disease stipulated by the disturbances of mineral metabolism, hypofunction of parathyroid glands and manifesting with elevated excitability of nervous-muscular apparatus and development of clonotonic convulsions.

Diagnostic criteria

/. Anamnestic data:

Wrong formula feeding, abuse of cow milk, goats and flour meals, insufficient stay at the fresh air, absence of rickets? prevention are revealed in the case history.

//. Clinical signs:

Tetany develops in children suffering from rickets. As a rule, children younger than 2-3 years may be ill both with rickets and tetany.

Clinically we can distinguish latent and manifest tetany.

Symptoms of latent tetany:

a) Chvostec?s symptom - symptom of facial nerve, tapping on the place of outlet of facial nerve causes spastic contraction of mimic facial muscles;

b) Weis?s symptom - irritation of the place of outlet of trigeminal nerve (near the external acoustic meatus) leads to contraction of mimicry muscles;

c) Trousseau?s symptom - squeezing of nerve-vascular bundle on the shoulder causes spastic contraction of hand?s muscles - "obstetrician?s hand";

d) Lust?s symptom - peroneal symptom, tapping lower the head of the fibula causes dorsal flexion and opening of feet?s fingers;

e) Maslov?s symptom - prick on the heel causes apnoe instead of quickening of breathing;

f) Erb?s symptom - closing of cathode on the muscle leads to its spasm while strength of the current is less than 5 mA.

Symptoms of manifest tetany:

a) laryngospasm - convulsive spasm of true glottis during inspiration accompanied by "cock-cry" and development of cyanosis attack;

b) carpo-pedal spasm - tonic convulsions of extremities? muscles;

c) general tonic convulsions of body?s muscles, mimic muscles (epileptoid convulsions) with unconsciousness;

d) expiratory apnoe - stop of respiration on expiration with development of attack of general cyanosis.

Convulsive spasm of a heart muscle leading to child?s death is possible.

///. Laboratory diagnostics:

Hypocalcemia (to 1,2-1,5 mmol/l), quantity of inorganic phosphorus is relatively elevated. Alcalosis is seen in some children.

Differential diagnosis isconducted with hyperthermic convulsions, complicated pneumonia, meningitis, viral diseases, and epilepsy.

Date: 2016-06-12; view: 7