dr. hossein moravej. bone consists of : a protein matrix: osteoid a mineral phase, principally...
TRANSCRIPT
- Slide 1
- Dr. Hossein Moravej
- Slide 2
- Bone consists of : a protein matrix: osteoid a mineral phase, principally composed of calcium and phosphate: hydroxyapatite
- Slide 3
- Osteomalacia: Inadequate mineralization of bone osteoid; in children or adults Rickets: a disease of growing bone, due to unmineralized matrix at the growth plates.
- Slide 4
- . VITAMIN D PHYSIOLOGY
- Slide 5
- Cutaneous synthesis The most important source of vitamin D Conversion of 7-dehydrochlesterol to vitamin D 3 (3-cholecalciferol) by ultraviolet B radiation from the sun. Covering the skin with clothing or applying sunscreen, also decrease vitamin D synthesis. Children who spend less time outside have reduced vitamin D synthesis.
- Slide 6
- dietary sources Fish liver oils have a high vitamin D content. Other good dietary sources include fatty fish and egg yolks. Vitamin D fortified foods, especially formula Supplemental vitamin D may be vitamin D 2 (which comes from plants or yeast) or vitamin D 3 ; they are biologically equivalent. Breast milk has a low vitamin D content, approximately 1260 IU/L.
- Slide 7
- Metabolism of Vit.D Vitamin D is transported to the liver and converts to 25-hydroxyvitamin D (25-D), the most abundant circulating form of vitamin D. In the kidney, 1-hydroxylase adds a second hydroxyl group, resulting in 1,25- dihydroxyvitamin D (1,25-D). The 1-hydroxylase activity is regulated by PTH, phosphate, and 1,25-D levels.
- Slide 8
- Action of Vit. D On GI: marked increase in calcium absorption, which is highly dependent on 1,25-D. phosphorus absorption, most dietary phosphorus absorption is vitamin Dindependent. On bone, mediating resorption. Suppresses PTH secretion 1,25-D inhibits its own synthesis in the kidney.
- Slide 9
- Etiology of Rickets
- Slide 10
- Slide 11
- Causes of rickets
- Slide 12
- Clinical Manifestations
- Slide 13
- Slide 14
- Slide 15
- The chief complaint in a child with rickets: skeletal deformities difficulty walking due to a combination of deformity and weakness. failure to thrive symptomatic hypocalcemia.
- Slide 16
- Clinical Manifestations Most manifestations of rickets are due to skeletal changes. Craniotabes, occiput or parietal Craniotabes may also be secondary to osteogenesis imperfecta, hydrocephalus, and syphilis. It is a normal finding in many newborns, but disappears within a few months of birth.
- Slide 17
- Clinical Manifestations Thickening of growth plate, causing widening of the wrists and ankles. general softening of the bones that causes them to bend easily when subject to
- Slide 18
- Clinical Manifestations Widening of the costochondral junctions results in a rachitic rosary; along the costochondral junctions
- Slide 19
- Slide 20
- Growth plate widening causes enlargement at the wrists and ankles. Harrison groove: The horizontal depression along the lower anterior chest; occurs due to pulling of the softened ribs by the diaphragm during inspiration
- Slide 21
- Slide 22
- Clinical Manifestations Softening of the ribs also impairs air movement and predisposes patients to atelectasis. The risk of pneumonia is elevated.
- Slide 23
- Clinical Manifestations There is some variation in the clinical presentation of rickets based on the etiology. Changes in the lower extremities tend to be the dominant feature in X-linked hypophosphatemic rickets. Symptoms secondary to hypocalcemia occur only in those forms of rickets associated with decreased serum calcium.
- Slide 24
- Clinical Manifestations Other manifestations: dental caries poor growth delayed walking waddling gait hypocalcemic symptoms.
- Slide 25
- Windswept deformity
- Slide 26
- Wrist enlargement
- Slide 27
- Bowing deformity
- Slide 28
- scoliosis
- Slide 29
- Rib beading (rachitic rosary)
- Slide 30
- Ankle enlargement
- Slide 31
- Bowleg deformity (genu varum)
- Slide 32
- Frontal bossing
- Slide 33
- Knock knee deformity (genu valgum )
- Slide 34
- Radiology Rachitic changes are most easily visualized on posteroanterior radiographs of the wrist: The edge of the metaphysis loses its sharp border, which is described as fraying. The edge of the metaphysis changes from a convex or flat surface to a more concave surface. This is termed cupping.
- Slide 35
- Slide 36
- Slide 37
- Laboratory findings Alk.ph is always elevated, except in zinc def. or protein def. Ph. is always decreased, except in renal failure. Ca. is always normal or decreased
- Slide 38
- Slide 39
- Diagnosis Diagnosis is based on the presence of classic radiographic abnormalities, supported by physical examination and history and laboratory results.
- Slide 40
- Vit.D Deficient Rickets
- Slide 41
- . Vit.D deficient Rickets The most common cause of rickets globally and is prevalent, even in industrialized countries.
- Slide 42
- Vit.D deficient Rickets Etiology: Most commonly occurs in infancy due to a combination of poor intake and inadequate cutaneous synthesis. Transplacental transport of 25-D provides enough vitamin D for the 1st 2 mo of life unless there is severe maternal vitamin D deficiency.
- Slide 43
- Vit.D deficient Rickets Infants who receive formula receive adequate vitamin D, even without cutaneous synthesis. Breast-fed infants, because of the low vitamin D content of breast milk, rely on cutaneous synthesis or vitamin supplements.
- Slide 44
- Laboratory Findings. Hypocalcemia is a variable finding due to elevated PTH. Hypophosphatemia is due to increased PTH and decreased vit.D. Wide variation in 1,25-D levels (low, normal, or high) Some patients have a metabolic acidosis secondary to PTH-induced renal bicarbonate-wasting. There may also be generalized aminoaciduria.
- Slide 45
- Diagnosis and Differential Diagnosis Based on the combination of History of poor vitamin D intake and risk factors for decreased cutaneous synthesis, Radiographic changes consistent with rickets typical laboratory findings
- Slide 46
- Treatment 2 strategies for administration of vitamin D. Stoss therapy, 300,000600,000 IU of vitamin D are administered orally or intramuscularly as 24 doses over 1 day. Alternative is daily, high-dose vitamin D, with doses ranging from 2,0005,000 IU/day over 46 wk. Either strategy should be followed by daily vitamin D intake of 400 IU/day, as a multivitamin. Adequate dietary calcium and phosphorus; by milk, formula, and other dairy products.
- Slide 47
- Treatment Symptomatic hypocalcemia need intravenous calcium acutely, followed by oral calcium supplements, which typically can be tapered over 26 wk in children who receive adequate dietary calcium.
- Slide 48
- Prognosis Excellent response to treatment Radiologic healing within a few months, first finding is Z-P line. Normalization of laboratory test results : Ca and Ph after 5 to 7 days, Alk-ph after a few weeks
- Slide 49
- Prevention Daily multivitamin containing 200400 IU of vitamin D to children who are breast-fed. For other children, the diet should be reviewed to ensure that there is a source of vitamin D.
- Slide 50
- SECONDARY VITAMIN D DEFICIENCY Etiology: inadequate absorption, decreased hydroxylation in the liver, and increased degradation in patients with liver and gastrointestinal diseases
- Slide 51
- SECONDARY VITAMIN D DEFICIENCY phenobarbital, phenytoin, isoniazid and rifampin increase degradation of vitamin D by inducing the P450 system.
- Slide 52
- VITAMIN DDEPENDENT RICKETS, TYPE 1
- Slide 53
- VITAMIN DDEPENDENT RICKETS, TYPE 1. Mutations in the gene encoding renal 1- hydroxylase, preventing conversion of 25-D into 1,25-D. Present during the 1st 2 yr of life
- Slide 54
- Laboratory Findings. Most lab. Findings are similar to Vit. D def. rickets: Hypocalcemia is a variable finding due to elevated PTH. Hypophosphatemia is due to increased PTH and decreased vit.D. Wide variation in 1,25-D levels (low, normal, or high) Some patients have a metabolic acidosis secondary to PTH-induced renal bicarbonate-wasting. There may also be generalized aminoaciduria. But 1,25 D level is decreased.
- Slide 55
- VITAMIN DDEPENDENT RICKETS, TYPE 1 Treatment: Long-term treatment with 1,25-D (calcitriol)
- Slide 56
- VITAMIN DDEPENDENT RICKETS, TYPE 2
- Slide 57
- VITAMIN DDEPENDENT RICKETS, TYPE 2. mutations in the gene encoding the vitamin D receptor, preventing a normal physiologic response to 1,25-D. Levels of 1,25-D are extremely elevated. Present during infancy 5070% of children have alopecia.
- Slide 58
- VITAMIN DDEPENDENT RICKETS, TYPE 2 Treatment Some respond to extremely high doses of vitamin D 2, 25-D, or 1,25-D, due to a partially functional vitamin D receptor.
- Slide 59
- Slide 60
- X-LINKED HYPOPHOSPHATEMIC RICKETS Pathophysiology: Increased urinary phosphate wasting
- Slide 61
- X-LINKED HYPOPHOSPHATEMIC RICKETS Clinical Manifestations: These patients have rickets, but abnormalities of the lower extremities and poor growth are the dominant features.
- Slide 62
- CHRONIC RENAL FAILURE Decreased activity of 1-hydroxylase in the kidney, leading to diminished production of 1,25- D. unlike the other causes of vitamin D deficiency, patients have hyperphosphatemia as a result of decreased renal excretion
- Slide 63
- Clinical Evaluation Initial evaluation should focus on a dietary history, emphasizing intake of vitamin D and calcium. ask about time spent outside, sunscreen use, and clothing.
- Slide 64
- Clinical Evaluation when a neonate or young infant has rachitic findings: Consider maternal risk factors for nutritional vitamin D deficiency, including diet and sun exposure.
- Slide 65
- Clinical Evaluation Take history of anticonvulsants use (phenobarbital and phenytoin), and aluminum- containing antacids.
- Slide 66
- Clinical Evaluation History of liver or intestinal disease, although occasionally, rickets may be the presenting complaint.
- Slide 67
- Clinical Evaluation A history of renal disease (proteinuria, hematuria, urinary tract infections.
- Slide 68
- Clinical Evaluation The family history is critical. Inquire about leg deformities, difficulties with walking, or unexplained short stature because some parents may be unaware of their diagnosis.
- Slide 69
- Clinical Evaluation Physical examination: Observe the child's gait, auscultate the lungs to detect atelectasis or pneumonia, and plot the patient's growth. Alopecia suggests vitamin D dependent rickets type 2.
- Slide 70
- Clinical Evaluation The initial laboratory tests in a child with rickets should include: serum calcium; phosphorus; alkaline phosphatase; parathyroid hormone (PTH); 25- hydroxyvitamin D; 1,25-dihydroxyvitamin D 3 ; creatinine; and electrolytes. Urinalysis is useful for detecting the glycosuria and aminoaciduria.