calcium metabolism, rickets and osteomalacia
TRANSCRIPT
May 3, 2023 1
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
May 3, 2023 5
CALCIUM REGULATION
1,25 Dihydro cholecalciferol Parathyroid hormone Calcitonin Parathyroid hormone related protein (PTHrP) Miscellaneous hormones : Glucocorticoids, Growth hormone, Estrogen
May 3, 2023 6
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
May 3, 2023 7
FUNCTIONS OF VITAMIN-D• Increases calcium absorption in intestine
May 3, 2023 8
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
May 3, 2023 10
ACTION OF PTH
In addition, Increases the phosphate excretion in kidneys
CALCITONIN
May 3, 2023 11
• Produced by the parafollicular cells / C cells of thyroid gland.
STRUCTURE: Molecular weight – 3500 Aminoacids-32
May 3, 2023 12
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
May 3, 2023 16
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
May 3, 2023 17
PATHOPHYSIOLOGY OF RICKETS
May 3, 2023 18
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
May 3, 2023 21
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
May 3, 2023 30
LABORATORY FINDINGS
serum calcium
serum phosphorus
serum alkaline phosphatase
May 3, 2023 31
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
May 3, 2023 32
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.
May 3, 2023 34
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 :
May 3, 2023 36
Radiological findings• Looser’s zone
• Triradiate pelvis
• Protrusio acetabuli
May 3, 2023 37
LABORATORY FINDINGS
serum calcium
serum phosphorus
serum alkaline phosphatase
Bone marrow biopsy is the gold standard for the diagnosis of osteomalacia
May 3, 2023 38
TREATMENT
• Treatment of the underlying cause.
• Vitamin D supplementation • PO4 supplements if low serum PO4 is present
• Ca supplements for calcium deficiency
May 3, 2023 39