Transcript of Dr. Hossein Moravej. Bone consists of : a protein matrix: osteoid a mineral phase, principally...
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- Dr. Hossein Moravej
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- Bone consists of : a protein matrix: osteoid a mineral phase,
principally composed of calcium and phosphate: hydroxyapatite
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- Osteomalacia: Inadequate mineralization of bone osteoid; in
children or adults Rickets: a disease of growing bone, due to
unmineralized matrix at the growth plates.
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- . VITAMIN D PHYSIOLOGY
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- 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.
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- 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.
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- 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.
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- 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.
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- Etiology of Rickets
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- Causes of rickets
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- Clinical Manifestations
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- 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.
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- 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.
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- 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
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- Clinical Manifestations Widening of the costochondral junctions
results in a rachitic rosary; along the costochondral
junctions
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- 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
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- Clinical Manifestations Softening of the ribs also impairs air
movement and predisposes patients to atelectasis. The risk of
pneumonia is elevated.
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- 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.
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- Clinical Manifestations Other manifestations: dental caries
poor growth delayed walking waddling gait hypocalcemic
symptoms.
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- Windswept deformity
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- Wrist enlargement
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- Bowing deformity
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- scoliosis
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- Rib beading (rachitic rosary)
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- Ankle enlargement
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- Bowleg deformity (genu varum)
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- Frontal bossing
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- Knock knee deformity (genu valgum )
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- 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.
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- 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
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- Diagnosis Diagnosis is based on the presence of classic
radiographic abnormalities, supported by physical examination and
history and laboratory results.
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- Vit.D Deficient Rickets
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- . Vit.D deficient Rickets The most common cause of rickets
globally and is prevalent, even in industrialized countries.
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- 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.
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- 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.
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- 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.
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- 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
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- 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.
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- 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.
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- 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
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- 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.
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- SECONDARY VITAMIN D DEFICIENCY Etiology: inadequate absorption,
decreased hydroxylation in the liver, and increased degradation in
patients with liver and gastrointestinal diseases
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- SECONDARY VITAMIN D DEFICIENCY phenobarbital, phenytoin,
isoniazid and rifampin increase degradation of vitamin D by
inducing the P450 system.
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- VITAMIN DDEPENDENT RICKETS, TYPE 1
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- 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
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- 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.
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- VITAMIN DDEPENDENT RICKETS, TYPE 1 Treatment: Long-term
treatment with 1,25-D (calcitriol)
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- VITAMIN DDEPENDENT RICKETS, TYPE 2
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- 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.
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- 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.
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- X-LINKED HYPOPHOSPHATEMIC RICKETS Pathophysiology: Increased
urinary phosphate wasting
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- X-LINKED HYPOPHOSPHATEMIC RICKETS Clinical Manifestations:
These patients have rickets, but abnormalities of the lower
extremities and poor growth are the dominant features.
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- 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
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- 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.
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- 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.
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- Clinical Evaluation Take history of anticonvulsants use
(phenobarbital and phenytoin), and aluminum- containing
antacids.
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- Clinical Evaluation History of liver or intestinal disease,
although occasionally, rickets may be the presenting
complaint.
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- Clinical Evaluation A history of renal disease (proteinuria,
hematuria, urinary tract infections.
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- 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.
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- 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.
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- 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.