RICKETS

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
 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)
Role of Calcium

 Bone Growth
 Blood Clotting
 Maintenance of trans membrane potential
 Cell replication
 Stimulus-contraction & stimulus-contracting
coupling
 Second messenger process
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).
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)
 inhibitsosteoclast activity  bone calcium
resorption 
 Calcium metabolism
25 mmol/day Skeleton

25 Mol (99%)
Gut

Kidney

13 mmol/d 300 mmol/day

2.20 mmol/L
(30mmol)
3 mmol/d 290 mmol/day

Plasma/ICF

15 mmol/day 10 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
 Physiology of PTH

 Resorption: free Ca2+, orthophosphate, Mg,

Bone citrate, hydroxyproline,osteocalcin.

 Calcium absorption indirectly through vit D

GIT metabolism

 phosphate excretion via proximal tubules

Inhibits bicarbonate reabsorption  metabolic
Kidney acidosis  favours calcium ionization   bone
resorption & dissociation of calcium from plasma
protein binding sites
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 
 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
 Causes of rickets
Vit. D Lack of adequate sunlight UV / increased sunlight
exposure
deficiency Consumption of diet low in Vit D2
fortified foods
Unsupplemented breast-fed Vit D2 for premature
infant.
Total parenteral nutrition Vit D2 in TPN / oral
(TPN)
Ca Lack of dietary Ca Ca 700 mg/day
deficiency Inadequate Ca in TPN Ca in prmature / TPN

Phosphat Breast-fed infant

def. Inadequate PO4 in TPN
 Hypocalcemia

-ve feedback
PTH

Decreased 1,25-(OH)2D
Ca Clearance
Urine Ca increased
Increased
Resorption
Demineralization
Increased
Ca Absorption

Serum
Ca2+
increased
Slide 3 of 21
 Radiology
Thinning of cortex
Widening, cuping metaphyses
Decreased bone density

Biochemistry
Ca serum : low / N
ALP increased
PTH increased
Treatment
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