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CALCIUM METABOLISM, RICKETS AND OSTEOMALACIA

R.SETHUPATHYFINAL YEAR MBBS

STANLEY MEDICAL COLLEGE

CALCIUM

Blood coagulation Muscle contraction Transmission of nerve impulses Formation of skeleton ,etc.

Total body calcium – 1100 g 99 % in bones

CALCIUM LEVELS IN THE BODY Plasma calcium : 9 – 11 mg / dL {5 mEq / L or 2.5 mmol / L}

GLOMERULAR FILTRATE250 mmol

DIET

25mmol (1000 mg)

GIT

FECES

22.5mmol

ABSORPTION

15 mmol

SECRETION

12.5 mmol

REABSORPTION

247.5 mmol

ECF

35 mmol

URINE

2.5 mmol

BONE

EXCHANGEABLE

100 mmol

STABLE

27,200 mmol

RAPID

EXCHANGE

500 mmol

REABSORPTION

7.5 mmol

FORMATION

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CALCIUM REGULATION

1,25 Dihydro cholecalciferol Parathyroid hormone Calcitonin Parathyroid hormone related protein (PTHrP) Miscellaneous hormones : Glucocorticoids, Growth hormone, Estrogen

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7 DEHYDROCHOLESTEROL

SUNLIGHT

VITAMIN D3 CHOLECALCIFEROL

25 HYDROXYLASE

25-HYDROXY CHOLECALCIFEROL

24α HYDROXYLASE

24, 25 DI-HYDROXY CHOLECALCIFEROL

1, 25 DI-HYDROXY CHOLECALCIFEROL

1α HYDROXYLASE

VITAMIN-D

SKIN

LIVER

KIDNEY

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FUNCTIONS OF VITAMIN-D• Increases calcium absorption in intestine

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FUNCTIONS

• Promotes phosphate absorption by the intestines.• Decreases renal excretion of calcium & phosphate.• Increases both bone resorption and bone

mineralization

PARATHYROID HORMONE• FOUR parathyroid glands located behind the

thyroid gland

CHIEF CELLS

PTH

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ACTION OF PTH

In addition, Increases the phosphate excretion in kidneys

CALCITONIN

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• Produced by the parafollicular cells / C cells of thyroid gland.

STRUCTURE: Molecular weight – 3500 Aminoacids-32

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ACTION OF CALCITONIN

• Decreases absorptive action of osteoclasts.• Deposits exchangeable Ca in bone salts.• Decreases the formation of osteoclasts.

DECREASES SERUM CALCIUM LEVEL

PARATHYROID HORMONE RELATED PROTEIN ( PTHrP)

• Produced by different tissues of our body• Binds to PTH receptors• Marked effect on growth and development of

cartilage in utero.• Defect in PTHrP – severe skeletal deformities.

LONG TERM

GLUCOCORTICOIDSglucocorticoids

Inhibits osteoclasts

Decrease calcium level

Inhibits calcium and phosphate absorption from intestine

Increases Ca and P excretion

osteoporosis

Decreases osteoblast activity

SHORT TERM

GROWTH HORMONE Increases intestinal absorption of CalciumIGF – I Stimulates protein synthesis in boneESTROGENS Prevents osteoporosis by inhibiting certain

cytokinesINSULIN Increases bone formation

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RICKETS• Disease of growing bone• Occurs in children before fusion of epiphysis

OSTEOID FORMATION OF BONES IS NORMAL

MINERALISATION OF OSTEOID IS INADEQUATE

SOFTENING OF BONES AND DEFORMITIES

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PATHOPHYSIOLOGY OF RICKETS

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Rickets classification

Type 1 rickets Type 2 rickets

TYPE 1 RICKETSNUTRITIONAL RICKETS•Commonest rickets in developing countries•<4 years

CONGENITAL VITAMIN-D DEFICIENCY•Maternal vitamin -D deficiency during pregnancy

INTESTINAL RICKETS•Decreased calcium absorption in conditions like sprue, steatorrhoea, celiac disease.

RENAL RICKETS•Renal osteo-dystrophy, Vitamin-D resistant rickets, fanconi syndrome, renal tubular acidosis

RICKETS DUE TO HEPATIC FAILURE•Failure of liver hydroxylation of Vitamin-D

DEFECTS IN VITAMIN D METABOLISM

TYPE 2 RICKETSDecreased phosphate intake

Decreased phosphate absorption

Increased phosphate excretion

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CLINICAL SYMPTOMS

CLINICAL SIGNS HEAD• Delayed closure of anterior fontanelle. • Frontal bossing.

CRANIOTABES• Softening of cranial bones leads ping-pong ball consistency of

the cranial bones.• Detected by applying pressure at the occiput or parietal bones.

THORAX

• Rachitic Rosery

• Harrison’s sulcus

• Pigeon chest deformity

EXTREMITIES -Enlargement of wrists and ankle -Valgus or varus deformities -Windswept deformity -Bowing of long bones -Coxa vara.

BACK

• Scoliosis• Kyphosis• lordosis

Widening ofGrowth plate

After treatment

RADIOLOGICAL FINDINGSTHICKENING OF THE GROWTH PLATE

Fraying Cupping

CUPPING AND FRAYING OF METAPHYSIS

INCREASED TRANSLUCENCY OF BONES

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LABORATORY FINDINGS

serum calcium

serum phosphorus

serum alkaline phosphatase

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TREATMENTVITAMIN D

6,00,000 IU SINGLE DOSE

GOOD RESPONSE

400 IU/DAYVITAMIN D

POOR RESPONSE

REPEAT THE INITIAL DOSE

GOOD RESPONSE

400 IU/DAY VITAMIN D

POOR RESPONSE

REFRACTORY RICKETS FURTHER INVESTIGATIONS

Symptomatic hypocalcemia –100 mg/kg

IV calcium gluconate followed by oral calcium or calcitrol -0.05mcg/kg/day

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DEFORMITIES CORRECTIONMILD DEFORMITY MERMAID SPLINTS ORTHOPAEDIC SHOES

SEVERE DEFORMITY CORRECTIVE OSTEOTOMIES

PREVENTION1.Exposure to sunlight 2.Food fortified with Vitamin A and Vitamin D. 3.Daily intake of 400 IU vitamin D by

supplementation.4.Lactating mothers should receive

supplementation with milk or vitamin D to ensure prevention of rickets in their babies.

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OSTEOMALACIA

• osteopenia with disordered calcification leading to higher proportion of osteoid (unmineralized) tissue after epiphyseal closure (in adulthood)

• Insidious in onset• Same pathogenesis as rickets

CLINICAL PRESENTATION :

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Radiological findings• Looser’s zone

• Triradiate pelvis

• Protrusio acetabuli

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LABORATORY FINDINGS

serum calcium

serum phosphorus

serum alkaline phosphatase

Bone marrow biopsy is the gold standard for the diagnosis of osteomalacia

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TREATMENT

• Treatment of the underlying cause.

• Vitamin D supplementation • PO4 supplements if low serum PO4 is present

• Ca supplements for calcium deficiency

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