This document provides an overview of calcium metabolism and rickets. It discusses the roles of calcium, parathyroid hormone, vitamin D, and other factors in maintaining calcium homeostasis. Regarding rickets, it describes the causes as vitamin D deficiency, low calcium or phosphorus intake, or renal losses. Symptoms include bone deformities, growth retardation, and hypocalcemia. Treatment involves high-dose vitamin D and calcium supplementation. With nutritional deficiencies, prognosis is generally excellent with resolution of symptoms and bone healing with treatment.

1. PRESENTED BY : KUMAR AMIT
MODERATED BY : DR.K.C.PATRA
HOD AND PROF
DEPT.OF PEDIATRICS

2. CALCIUM METABOLISM

3. INTRODUCTION
 CALCIUM IS THE FIFTH MOST ABUNDANT
ELEMENT IN THE EARTH’S CRUST.
 CALCIUM DERIVES ITS NAME FROM CALCIS
MEANING “LIME”
 IN HUMAN BODY NINETY NINE PERCENT OF
CALCIUM FOUND IN SKELETON AND ABOUT ONE
PERCENT IS IN ECF FOR PHYSIOLOGICAL
FUNCTIONS.

4. FUNCTION OF CALCIUM
 FORMATION OF SKELETON
 BLOOD COAGULATION
 CELLULAR COMMUNICATION
 EXOCYTOSIS AND ENDOCYTOSIS
 MUSCULAR CONTRACTION AND RELAXATION
 NEUROMUSCULAR COMMUNICATION

6. PHYSIOLOGY
 IN BLOOD,
TOTAL CALCIUM CONCENTRATION IS NORMALLY -
8.5-10.5mg/dl

8.  BECAUSE CALCIUM BINDS TO ALBUMIN AND
ONLY THE UNBOUND CALCIUM IS
BIOLOGICALLY ACTIVE ,THE SERUM LEVEL
MUST BE ADJUSTED AS FOLLOWS
CORRECTED Ca2 = [4-plasma albumin in
g/dl]*0.8 + measured serum calcium

9. Factors affecting calcium
concentration
1) Changes in plasma protein concentration
- Increased [protein] Increased total [Ca2+]
2) Changes in anion concentration
- Increased [anion] increased fraction of Ca2+ that is
complexed – decrease ionized [Ca2+]
3)Acid base abnormality

10. Acid Base Abnormality

11. Calcium Homeostasis
 Blood calcium is tightly regulated by:
1) Principle organ systems:
Intestine
Bone
Kidney
2) Hormones:
Parathyroid hormone (PTH)
Vitamin D
Calcitonin

12. Parathyroid Gland
 Human beings have four parathyroid glands, which are
situated on the posterior surface of upper and lower
poles of thyroid gland.
 Parathyroid glands are very small in size, measuring
about 6 mm long, 3 mm wide and 2 mm thick, with
dark brown color.

14. Histology
 Made up of chief cells and oxyphil cells.
1. Chief cells:
 Secrete parathormone.
2.Oxyphil cells
 Degenerated chief cells and their function is unknown.
 May secrete parathormone during pathological
condition called parathyroid adenoma.

16. Parathormone
 Secreted by parathyroid gland
 Essential for the maintenance of blood calcium level
within a very narrow critical level.
 Maintenance of blood calcium level is necessary
because calcium is an important inorganic ion for
many physiological functions.

17. CHEMISTRY
 Parathormone is protein in nature, having 84 amino
acids.
 Its molecular weight is 9500.

18.  Half-life and Plasma Level
 Parathormone has a half-life of 10 minutes.
 Normal plasma level of PTH is about 1.5 to 5.5 ng/dL.

19.  Synthesis
 Synthesized from the precursor called pre-pro-PTH
containing 115 amino acids.
 First, the pre-pro-PTH enters the endoplasmic reticulum of
chief cells of parathyroid glands.
 There it is converted into a prohormone called pro-PTH,
which contains 96 amino acids.
 Pro-PTH enters the Golgi apparatus, where it is converted
into PTH.

20.  Metabolism
 60 – 70 % of PTH is degraded by Kupffer cells of liver, by
means of proteolysis.
 Degradation of about 20% to 30% PTH occurs in
kidneys and to a lesser extent in other organs.

21.  Actions Of Parathormone On Blood Calcium
Level
 Primary action of PTH is to maintain the blood calcium
level within the critical range of 9 to 11 mg/dL.
 PTH maintains blood calcium level by:
1. Resorption of Ca from Bones
2. Reabsorption Ca from the renal tubules (Kidney)
3. Absorption of Ca from Gastrointestinal tract.

22.  On Bones
 Parathormone enhances the resorption of calcium from
the bones by acting on osteoblasts and osteoclasts of
the bone.
 Resorption of calcium from bones occurs in two phases:
1. Rapid phase
2. Slow phase.

23. PTH ↑calcium and phosphate
absorption from the bone
Second phaseFirst phase
slowrapid
Days-weeksMinutes-hours
Proliferation of osteoclastsActivation of already existing
osteocytes /osteoblasts
Activated osteocytes/osteoblasts send
secondary signals to osteoclasts
Receptor protiens on
octeocytes/osteoblasts that bind PTH
and activate calcium pump
Osteoclastic absorption of bone itselfPromote calcium and phosphate
absorption

24.  On Kidney
 PTH increases the reabsorption of calcium from the renal
tubules along with magnesium ions an hydrogen ions.
 It increases calcium reabsorption mainly from distal
convoluted tubule and proximal part of collecting duct.
 PTH also increases the formation of 1,25- di-
hydroxycholecalciferol (activated form of vitamin D)
from 25-hydroxycholecalciferol in kidneys.

26.  On Gastrointestinal Tract
 PTH increases the absorption of calcium ions from the
GI tract indirectly.
 It increases the formation of 1,25-
dihydroxycholecalciferol in the kidneys.
 This vitamin, in turn increases the absorption of
calcium from GI tract.
 Thus, the activated vitamin D is very essential for the
absorption of calcium from the GI tract & PTH is
essential for the formation of activated vitamin D.

27. Parathyroid Hormone (PTH)

29. CALCITONIN
 Calcitonin secreted by parafollicular cells of thyroid
gland.
 It is a calcium-lowering hormone.
 It reduces the blood calcium level mainly by decreasing
bone resorption.

30. Effects of Other Hormones
 Growth hormone
 Growth hormone increases the blood calcium level by
increasing the intestinal calcium absorption.

 It is also suggested that it increases the urinary excretion
of calcium.
 However, this action is only transient.

31.  Glucocorticoids
 Decrease blood calcium by inhibiting intestinal
absorption and increasing the renal excretion of calcium

35. INTRODUCTION
 Elmer McCollum in 1922 noticed that vitamin A
deficient cod liver oil cured rickets in dogs. He named
it Vitamin D because it was the fourth vitamin to be
named.
 It is a fat soluble vitamin requires in the body for the
maintenance of calcium and phosphorus to support
different metabolic functions.

37. ANTI-MYCOBACTERIAL EFFECT
 Vitamin D stimulates the synthesis of cathelicidin,
an anti-microbial peptide that is particularly active
against Mycobacterium Tuberculosis.

41. METABOLISM

43. OVERVIEW OF CALCIUM
METABOLISM

45. VITAMIN D DEFICIENCY

46. Rickets is an entity in which mineralization is decreased at the level of
the growth plates, resulting in growth retardation and delayed skeletal
development.
Osteomalacia is found within the same spectrum, affects trabecular
bone, and results in undermineralization of osteoid bone

47. RICKETS

48. INTRODUCTION
 The term rickets is said to have derived from the
ancient English word wricken, which means "to
bend”.
 In several European countries, rickets is also called
English disease, a term that appears to stem from the
fact that at the turn of the 19th century, rickets was
endemic in larger British cities.

49.  Disease of growing bone due to unmineralized matrix
at the growth plates and occurs in children only
before fusion of epiphyses

50.  CAUSES OF RICKETS:
 1. VITAMIN D DISORDERS
 2. CALCIUM DEFICIENCY
 3. PHOSPHORUS DEFICIENCY
 4. RENAL LOSSES
 5. DISTAL RTA

51. Etiology
VITAMIN D DISORDERS
- Nutritional vitamin D deficiency
- Congenital vitamin D deficiency
- Secondary vitamin D deficiency Malabsorption
- Increased degradation
- Decreased liver 25-hydroxylase
- Vitamin D–dependent rickets type 1
- Vitamin D–dependent rickets type 2
- Chronic renal failure

52. CALCIUM DEFICIENCY
 Low intake
 Diet
Premature infants (rickets of prematurity)
 Malabsorption
 Primary disease
- Dietary inhibitors of calcium absorption

53. RENAL LOSSES
 X-linked hypophosphatemic rickets
 Autosomal dominant hypophosphatemic rickets
 Autosomal recessive hypophosphatemic rickets
 Hereditary hypophosphatemic rickets with hypercalciuria
 Overproduction of phosphatonin
 Tumor-induced rickets
 McCune-Albright syndrome
 Epidermal nevus syndrome
 Neurofibromatosis
 Fanconi syndrome
 Dent disease
 Distal renal tubular acidosis

54. PHOSPHORUS DEFICIENCY
Inadequate intake
Premature infants (rickets of prematurity)
 Aluminum-containing antacids

55. PATHOPHYSIOLOGY
 Overgrowth of epiphyseal cartilage due to inadequate
calcification and maturation
 Persistence of distorted irregular masses of cartilage
which project into marrow cavity.
 Deposition of osteoid matrix on inadequately
mineralised cartilagenous remnants.

56. PATHOPHYSIOLOGY
 Disruption of the orderly replacement of cartilage by
osteoid matrix with enlargement and lateral expansion
of osteochondral junction
 Abnormal growth of capillaries and fibrobkast in the
disorganised zone.
 Deformation of the skeleton due to loss of structural
rigidity of the developing bones.

57. CLINICAL FEATURES
 Peak incidence 6 months – 2 years
 Irritability
 profuse sweating while asleep
 hypotonia
 frequent respiratory infections.
 Failure to thrive
 Protruding abdomen.
 Delay in walking,delayed dentition
 Tetany.

58.  HEAD
 Craniotabes
 Frontal bossing
 Delayed fontanelle closure
 Delayed dentition; caries
 Craniosynostosis

59.  CHEST
 Rachitic rosary
 Harrison groove
 Respiratory infections and atelectasis
 BACK
 Scoliosis
 Kyphosis
 Lordosis

60.  EXTREMITIES
 Enlargement of wrists and ankles
 Valgus or varus deformities
 Anterior bowing of the tibia and femur
 Coxa vara
 Leg pain

61.  EXTREMITIES
 Enlargement of wrists and ankles
 Valgus or varus deformities
 Anterior bowing of the tibia and femur
 Coxa vara
 Leg pain

62.  EXTREMITIES
 Enlargement of wrists and ankles
 Valgus or varus deformities
 Anterior bowing of the tibia and femur
 Coxa vara
 Leg pain

63.  EXTREMITIES
 Enlargement of wrists and ankles
 Valgus or varus deformities
 Anterior bowing of the tibia and femur
 Coxa vara
 Leg pain

64.  HYPOCALCEMIC SYMPTOMS:
 Tetany
 Seizures
 Stridor due to laryngeal spasm

65.  Rachitic Rosary:

67.  Craniotabes:
 Softening of cranial bones.

68. KYPHOSIS

69.  Harrison groove:
 Horizontal depression along lower anterior chest.
 Due to pulling of softened ribs by diaphragm during inspiration.
 Softening of ribs  impairs air movement & predisposes to
atelectasis.
 Risk of pneumonia high in children with rickets

74.  RADIOLOGY:
 Decreased calcification  Thickening of growth plate.
 FRAYING: Edge of metaphysis loses its sharp border.
 CUPPING: Edge of metaphysis changes from convex or flat to
concave surface. Most easily seen at distal ends of radius, ulna,
fibula.
 Widening of distal end of metaphysis  Clinically causes
thickened wrists and ankles, and rachitic rosary.

75.  RADIOLOGY:
 Especially on PA view of wrist. Also in other growth plates.
 Other radiologic features:
- Coarse trabeculation of diaphysis - Generalized rarefaction.

79.  Clinical Evaluation.
 HISTORY REGARDING:
 1.Diet intake of Vit D, Calcium
 2.Sun exposure
 3.Maternal risk factors for vit D deficiency.
 4.Child's medication history.
 5.History of liver or intestinal disease – malabsorption of vit D
 6.History of Renal disease
 7.Family history of bone disease, short stature, unexplained
sibling death.
 8.History of dental caries, poor growth, delayed walking, waddling
gait, pneumonia, and hypocalcemic symptoms.

80. Treatment
Stoss therapy – 300000 – 600000 IU Vitamin D oral
or IM, 2-4 doses over one day
Alternatively high dose vit D, 2000-5000 IU/day over
4-6 wk
Followed by oral Vit D :
< 1 year of age - 400IU
> 1 years of age- 600IU
Symptomatic hypocalcemia – IV calcium gluconate
100 mg/kg followed by oral calcium or calcitrol -
0.05mcg/kg/day

81.  NUTRITIONAL VIT D DEFICIENCY:
 Prognosis.
 Most: Excellent response to treatment.
 Radiologic healing within 4 weeks.
 Laboratory tests normalize rapidly.
 Many of the bone malformations improve dramatically, but
children with severe disease may have permanent deformities.
 Short stature does not resolve in some children.
 Prevention.
 Universal administration of daily multivitamin containing 200–
400 IU of vitamin D to children who are breast-fed.
 For other children, diet should have sources of vitamin D.

82. PREVENTION
 To prevent rickets, health experts recommend
 a child should be breast-fed
 weaned and put on to cow's milk and other foods rich
in vitamin D and calcium, like eggs and dairy products
such as butter and leafy vegetables.
 Fish

83. T h a n k y o u . . .