VITAMIN D DISORDERS Flashcards
The most important source of vitamin D…..
Cutaneous synthesis
Natural dietary sources of vitamin D…….
Fish liver oils have a high vitamin D content.
Other good dietary sources include fatty fish and egg yolks.
Most children in industrialized countries receive vitamin D via fortified foods
Breast milk has a low vitamin D content, approximately…..
12-60 IU/L.
7-dehydrochlesterol to vitamin D3 (3-cholecalciferol) by……
Ultraviolet B (UVB) radiation from the sun
25-hydroxlase converts……..
vitamin D into 25-hydroxyvitamin D (25-D),
the most abundant circulating form of vitamin D
25-D is the standard method for determining a patient’s vitamin D status why…….,.
Because there is little regulation of this liver hydroxylation step.
1α-hydroxylase adds a
second hydroxyl group, resulting in 1,25-D
The 1α-hydroxylase is…..regulated by……
Upregulated by PTH and hypophosphatemia and
Inhibited by hyperphosphatemia and 1,25-D
Vitamin D deficiency most frequently occurs in infancy why…….
Because of a combination of poor intake and inadequate cutaneous synthesis
Lab findings in vit D deficiency rickets….
Hypocalcemia : is a variable finding because the elevated PTH acts to increase the serum calcium concentration.
The hypophosphatemia : is caused by PTH-induced renal losses of phosphate, combined with a decrease in intestinal absorption.
The wide variation in 1,25-D levels : (low, normal, or high) is secondary to the upregulation of renal 1α-hydroxylase caused by concomitant hypophosphatemia and hyperparathyroidism
stoss therapy
vitamin D (300,000-600,000 IU) is administered orally (preferred) or intramuscularly as 2-4 doses over 1 day (vitamin D3 is preferred to D2 because of longer half-life of D3).
The alternative strategy……for vit D
The alternative strategy is daily vitamin D with a minimum dose of 2,000 IU/day for a minimum of 3 mo
Indication for calcitriol iv injection in vit D deficiency..
Transient use of IV or oral 1,25-D (calcitriol) is often helpful in reversing hypocalcemia in the acute phase by providing active vitamin D during the delay as supplemental vitamin D is converted to active vitamin D
Calcitriol doses are typically 0.05 µg/kg/day. IV calcium is initially given as an acute bolus for symptomatic hypocalcemia (20 mg/ kg calcium chloride or 100 mg/kg calcium gluconate)
radiologic healing occurring within a few
months
children with severe disease can have……prognosis
permanent deformities and short stature
Congenital Vitamin D Deficiency…….?
Occurs when there is severe maternal vitamin D deficiency during pregnancy
Congenital Vitamin D Deficiency features….
These newborns can have symptomatic hypocalcemia, intrauterine growth retardation, and decreased bone ossification, along with classic rachitic changes
Secondary Vitamin D Deficiency…….
vitamin D deficiency can result from inadequate absorption, decreased hydroxylation in the liver, and increased degradation.
Because vitamin D is fat soluble, its absorption may be decreased in patients with a variety of liver and GI diseases, including cholestatic liver disease, defects in bile acid metabolism, cystic fibrosis and other causes of pancreatic dysfunction, celiac disease, and Crohn disease
Treatment of vitamin D deficiency attributable to malabsorption requires high doses of
vitamin D.
Because of its better absorption, 25-D (25-50 µg/ day or 5-7 µg/kg/day) is superior to vitamin D
Vitamin D–Dependent Rickets, Type 1…..
Children with vitamin D–dependent rickets type 1A,
an autosomal recessive disorder,
have mutations in the gene encoding renal 1α-hydroxylase,
preventing conversion of 25-D into 1,25-D
Children with vitamin D–dependent rickets type 1A laboratory findings……
They have normal levels of 25-D but low levels of 1,25-D
Occasionally, 1,25-D levels are at the lower limit of normal, inappropriately low
given the high PTH and low serum phosphorus levels, both of which should increase the activity of renal 1α-hydroxylase and cause elevated levels of 1,25-D
Vitamin D–dependent rickets type 1B is secondary to…
A mutation in the gene for a 25-hydroxylase
Patients have low levels of 25-D but normal levels of 1,25-D
Vitamin D–dependent rickets type 1A responds to long-term treatment with…………
1,25-D (calcitriol)
Initial doses are 0.25-2 µg/day, and lower doses are used once the rickets has healed
Especially during initial therapy, it is important to ensure adequate intake of calcium
Monitoring in patient treated with calcitriol………
Periodic assessment of urinary calcium excretion, with a target of <4 mg/kg/day
Because: Targeting a low-normal calcium concentration and a high-normal PTH level avoids excessive dosing of calcitriol, which can cause hypercalciuria and nephrocalcinosis
Vitamin D–dependent rickets type 1B may respond to pharmacologic doses of …..
Vitamin D2 (3,000 U/day) as a result of alternative enzymes with 25-hydroxylase activity or residual activity of the mutant protein
Vitamin D–Dependent Rickets, Type 2A…..
Patients with vitamin D–dependent rickets type 2A have 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 …………… in this autosomal recessive disorder VDDR T2A
Levels of 1,25-D are extremely elevated in this autosomal recessive disorder
alopecia areata to alopecia totalis common in which type of VDDR ……
Vitamin D–Dependent Rickets, Type 2A
Vitamin D–dependent rickets type 2B appears to result from…….
overexpression of a hormone response element–binding protein that interferes with the actions of 1,25-D.
Alopecia may be present.
