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RACHITIS, VITAMIN D
RICKETSIA, OSTEOMALACIA
RICKETS
Disorder of mineralization of
the bone matrix / osteoid in
growing bone
Involved : growth plate
Newly trabecular formed
Cortical bone
Osteomalacia
After cessation of growth
Involves only a bone, not the growth plate
Risk factors
Living in northern latitudes (>30o);
Dark skinned children;
Decreased exposure to sunlight
Maternal vitamin D deficiency;
Diets low in calcium, phosphorus and vit. D
Prolonged parenteral nutrition in infancy with
an inadequate supply of intravenous calcium
and phosphate;
Intestinal malabsorption
Defective production of
1,25(OH)2D3
Hereditary type I vitamin D-resistant (or
dependent) rickets (mutation which abolishes
activity of renal hydroxylase);
Familial (X-linked ) hypophosphataemic rickets –
renal tubular defect in phosphate transport;
Chronic renal disease;
Fanconi syndrome (renal loss of phosphate)
Target organ resistance to 1,25(OH)2D3-
hereditary vitamin D-dependent rickets type II
(due to mutations in vitamin D receptor gene).
Calcium homeostasis - PTH action
-ve feedback
PTH
Decreased 1,25-(OH)2D
Ca Clearance
Increased
Resorption
Increased
Ca Absorption
Serum
Ca2+
Vitamin D Metabolism
VitD3 25-OH-D3
7 Dehydrocholesterol VitD3 (cholecalciferol) (calcidiol)
Skin
Calcium absorption
1,25-(OH)2-D3 25-OH-D3
(calcitriol) (calcidiol)
Resorption
PTH Response to Hypocalcemia
-ve feedback Ca2+
Plasma
PTH
Ca2+
Increase
Plasma
1,25-(OH)2D H2PO4-
Renal Excretion
Ca2+
Renal Excretion
Ca2+
GIT absorption
Resorption
Role of Calcium
Bone Growth
Blood Clotting
Maintenance of trans membrane potential
Cell replication
Stimulus-contraction & stimulus-contracting coupling
Second messenger process
Intestine:
25 Mol (99%)
Gut
Kidney
13 mmol/d
300 mmol/day
2.20 mmol/L
(30mmol)
3 mmol/d
290 mmol/day
Plasma/ICF
10 mmol/day
15 mmol/day
Calcium Distribution in
Plasma
Ionised Calcium
~1.0 mmol/L
Total Calcium
~2.0 mmol/L
Bound Calcium
~0.95 mmol/L
Complexed Calcium
~0.05 mmol/L
Pathophysiology of Calcium
Disorders of homeostatic regulators
PTH
vitamin D
Disorders of the skeleton
bone metastases
Disorders of effector organs
gut - malabsorption
kidney
Diet
Breast milk contains 30-50IU/liter, cow’s
milk 20-30IU/l, egg yolk contains 20-
50IU/10gr.
80% of the vitamin D is absorbed in the
small intestine in the present of normal
biliary secretion.
Vitamin D reaches the blood through
thoracic duct along with chilomicrons.
Calcium regulation in the blood is as follows:
Vitamin D2 in the food (exogenous) + vitamin D3
(skin, endogenous) =>liver microsomes
=>25(OH) D3 => Mitochondrial kidney tubules
membrane activated 3 forms:
24,25 (OH)2 D3; 1,24,25 (OH)2 D3; 1,25 (OH)2 D3
!!! last more active.
In placental macrophage of pregnancy women
are present 1,25(OH)2 D3
Serum calcium : narrow physiological
range
Result of complex interaction process
vitamin D, parathyroid hormone (PTH),
and the calcium sensing receptor.
Serum calcium
50% free (ionized)
40% protein bound (80% albumin & 20%
globulin)
10% complexed (phosphate, citrate,
bicarbonate, lactate)
Physiology of PTH
1. Osteogenesis imperfecta,
chondrodystrophy, congenital diseases-
CMV, rubella, syphilis.
2. Chronic digestive and malabsorption
disorders.
3. Hereditary Fanconi’s disease, phosphorus
diabetes, renal tubular acidosis.
Slide 3 of 21
Radiology
Thinning of cortex
Widening, cuping metaphyses
Decreased bone density
Biochemistry
Ca serum : low / N
ALP increased
PTH increased
PROPHILAXIS IN RICKETS
Ca deficiency;
Premature: 75-150 mg/dl
Oral :200 mg/kg/day
IV : solution 20 mg/dl
RICKETS COMPLICATIONS