RACHITIS, VITAMIN D RICKETSIA, OSTEOMALACIA

1
RACHITIS, VITAMIN D RICKETSIA, OSTEOMALACIA

• EKA AGUSTIA RINI

2
(No Transcript)
3
(No Transcript)
4
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
5
Risk factors

• Living in northern latitudes (gt30o)
• 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

6
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).

7
Calcium homeostasis - PTH action
-ve feedback
Decreased Ca Clearance
1,25-(OH)2D
Increased Resorption
Increased Ca Absorption
Serum Ca2
8
Vitamin D Metabolism
Calcium absorption ?
9
PTH Response to Hypocalcemia
-ve feedback
PTH ?
1,25-(OH)2D ?
Increase
10
Role of Calcium

• Bone Growth
• Blood Clotting
• Maintenance of trans membrane potential
• Cell replication
• Stimulus-contraction stimulus-contracting
  coupling
• Second messenger process

11
Intestine

• Increases calcium binding protein
• Active transport in the jejunal cells
• Phosphorus ions absorption through specific
  phosphate carrier
• Alkaline phosphatase (AP) synthesis
• ATP-ase sensibility to calcium ions

12
Factors in Calcium Homeostasis

• Ca sensing receptor (CaSR) ?
• membrane protein that binds Ca
• determines the set-point for PTH secretion.
• Parathyroid hormone (PTH)
• 84 amino acid peptide
• ? increases calcium concentration
• ? calcium reabsorption in the kidney
• ? calcium resorption from bone
• ? intestinal calcium absorption via ? renal
  formation 1,25-diOH-D).

13
Factors in Calcium Homeostasis

• Vitamin D (1,25-diOH-D).
• ? absorption / reabsorption of calcium
  (intestines, bone, and kidney).
• Calcitonin.
• 32 amino acid peptide
• Secretion ? if serum calcium ? (antagonist PTH)
• inhibits osteoclast activity ? bone calcium
  resorption ?

14
Calcium metabolism
15
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
16
Pathophysiology of Calcium

• Disorders of homeostatic regulators
• PTH
• vitamin D
• Disorders of the skeleton
• bone metastases
• Disorders of effector organs
• gut - malabsorption
• kidney
• Diet

17

• Breast milk contains 30-50IU/liter, cows 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.

18

• Calcium regulation in the blood is as follows
• Vitamin D2 in the food (exogenous) vitamin D3
  (skin, endogenous) gtliver microsomes
• gt25(OH) D3 gt 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

19

• 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)

20
Physiology of PTH
Bone ? Resorption free Ca2, orthophosphate, Mg, citrate, hydroxyproline,osteocalcin.
GIT ? Calcium absorption indirectly through vit D metabolism
Kidney ? phosphate excretion via proximal tubules Inhibits bicarbonate reabsorption ? metabolic acidosis ? favours calcium ionization ? ? bone resorption dissociation of calcium from plasma protein binding sites
21
Causes of rickets
Vit. D deficiency Lack of adequate sunlight Unsupplemented breast-fed infant. Total parenteral nutrition (TPN)
Ca deficiency Lack of dietary Ca Inadequate Ca in TPN
Phosphat def. Breast-fed infant Inadequate PO4 in TPN
22
Causes of rickets
Vit. D deficiency Lack of adequate sunlight Consumption of diet low in fortified foods Unsupplemented breast-fed infant. Total parenteral nutrition (TPN) UV / increased sunlight exposure Vit D2 Vit D2 for premature Vit D2 in TPN / oral
Ca deficiency Lack of dietary Ca Inadequate Ca in TPN Ca 700 mg/day Ca in prmature / TPN
Phosphat def. Breast-fed infant Inadequate PO4 in TPN
23
CLINICAL MANIFESTATIONS

• Rickets may develop in any age of an infant, more
  frequent at 3-6mo, early in prematures.
• The first signs of hypocalcaemia are CNS changes-
  excitation, restlessness, excessive sweated
  during sleep and feeding, tremors of the chin and
  extremities.

24

• Skin and muscle changes- pallor, occipital
  alopecia, fragile nails and hair, muscular
  hypotony,motor retardation.
• Complications- apnoea, stridor, low calcium level
  with neuromuscular irritability (tetany).
• CNS changes are sometimes interpreted as CNS
  trauma and the administration of the

25
(No Transcript)
26
ACUTE SIGNS

• Have acute and subacute clinical signs
• Craniotabes acute sign of rickets, osteolyses
  detected by pressing firmly over the occipital or
  posterior parietal bones, ping-pong ball
  sensation will be felt. Large anterior
  fontanella, with hyperflexible borders, cranial
  deformation with asymmetric occipital flattening.

27
SUBACUTE SIGNS

• Subacute signs are all the following frontal and
  temporal bossing
• False closure of sutures (increase protein
  matrix), in the X-ray craniostenosis is absent.
• Maxilla in the form of trapezium, abnormal
  dentition.

28

• Late dental evolution, enamel defects in the
  temporary and permanent dentition.
• Enlargement of costo-chondral junctions-rickets
  rosary
• Thorax, sternum deformation, softened lower rib
  cage at the site of attachment of the diaphragm-
  Harrison groove.

29
(No Transcript)
30
Subacute signs

• Spinal column- scoliosis, lordosis, kyphosis.
• Pelvis deformity, entrance is narrowed (add to
  cesarean section in females)
• Extremities- palpated wrist expansion from
  rickets, tibia anterior convexity, bowlegs or
  knock kness legs.
• Deformities of the spine, pelvis and legs result
  in reduced stature, rachitic dwarfism.
• Delayed psychomotor development (heat holding,
  sitting, standing due to hypotonia).

31
LABORATORY DATA

• Serum calcium level (N2.2-2.6mmol/l). At the
  level lt2.0mmol/l convulsions sets in.
• Phosphorus normal (1.5-1.8mmol/l). Normal ratio
  of Ca P 21 in rickets become 31 41.
• Serum 25(OH)D3 (N282.1ng/ml) and
  1,25(OH)2D3(N0.0350.003ng/ml)
• Serum alkaline phosphatase is elevated
  gt500mmol/l.
• Thyrocalcitonin can be appreciated
  (N23.63.3pM/l)
• Serum parathyroid hormone (N5985.0pM/l)
• In urine Aminoaciduria gt1.0mg/kg/day
• Urinary excretion of 35 cyclic AMP
• Decreased calcium excretion (N50-150mg/24h)

32
Radiological findings

• Only in difficult diagnostic cases.
• X-ray of the distal ulna and radius concave
  (cupping) ends normally sharply, Fraying
  rachitic metaphyses and a widened epiphyseal
  plate.
• Osteoporosis of clavicle, costal bones, humerus.
• Greenstick fractures.
• Thinning of the cortex, diaphysis and the cranial
  bones.

33
EVOLUTION

• The evolution is slow with spontaneous healing at
  the age of 2-3 years.
• If treated can be cured in 2-3mo with the
  normalization of the skeletal and the cellular
  system.
• Gibbous, palatal deformity and the narrow pelvis
  may persist.

34
DIFFERENTIAL DIAGNOSIS

1. Osteogenesis imperfecta, chondrodystrophy,
   congenital diseases- CMV, rubella, syphilis.
2. Chronic digestive and malabsorption disorders.
3. Hereditary Fanconis disease, phosphorus
   diabetes, renal tubular acidosis.

35
                                                                                                                                                                                                                                     
Slide 3 of 21
36
Radiology
Thinning of cortex Widening, cuping
metaphyses Decreased bone density
Biochemistry Ca serum low / N ALP
increased PTH increased
37
PROPHILAXIS IN RICKETS

• Specific antenatal prophylactic dose
  administration 500-1000IU/day of vitamin D3
  solution at the 28-th week of pregnancy.
• The total dose administered is 135000-180000IU.
  In term infants prophylactic intake of vitamin
  D2 700IU/d started at 10 days of age during the
  first 2 years of life in premature the dose may
  increase to 1000IU/day.

38
PROPHILAXIS IN RICKETS

• WHO recommendation for rickets prophilaxis in a
  children coming from unfavorable conditions and
  who have difficult access to hospitals is
  200000IU vitamin D2 i/muscular,
• On the 7day, 2, 4, 6 month- total dose 800000IU.
  In case of the necessary prolongation 700IU/day
  till 24mo are given.

39
SPECIFIC TREATMENT IN RICHETS

• The treatment is with vitamin D3 depending on the
  grade.
• In grade I- 2000-4000IU/day for 4-6weeks, totally
  120000-180000IU.
• In grade II- 4000-6000IU/day for 4-6 weeks,
  totally 180000-230000IU.
• In grade III- 8000-12000IU/day for 6-8 weeks,
  totally 400000-700000IU.

40
SPECIFIC TREATMENT IN RICHETS

• Along with vitamin D, calcium is also
  administered (40 mg/kg/day for a term baby,
• 80 mg/kg/day for a premature baby) also indicate
  vitamin BC preparations.
• From the 7-th day of the treatment massage can
  be started. Intramuscular administration
• of ATP solution in case of myotonia 1ml/day is
  preferred.

41
Vit D. def TPN 0,5 ug/kg/day Oral 400-800 IU
daily
Ca deficiency Premature 75-150 mg/dl Oral 200
mg/kg/day IV solution 20 mg/dl
42
RICKETS COMPLICATIONS

1. Rickets tetany in result of low concentration of
   serum calcium (lt2mmol/l), failure of the PTH
   compensation and muscular irritability occur.
2. Hypervitaminosis D

43
HYPERVITAMINOSIS D

• Symptoms develop in hypersensitivity to vitamin D
  children or after1-3mo of high doses intakes of
  vitamin D they include hypotonia, anorexia,
  vomiting, irritability, constipation, polydipsia,
  polyuria, sleep disorder, dehydration. High serum
  level of acetone, nitrogen and
• Cagt2.9mmol/l are found. Increase calcium
  concentration in urine may provoke incontinence,
  renal damage and calcification.