‣
- Limb growth is controlled in 3 axes by 3 different pathways
- AER (Apical Ectodermal Ridge) [Fibroblast Growth Factors gene] - Proximodistal
- ZPA (Zone of Polarising Activity) [Sonic hedgehog gene] - Radioulna
- Hox Gene coding for Sonic Hedgehog protein
- e.g., Radial Club hand defect, fibula hemimelia, Thumb duplication
- WnT (Wingless Type) [LMX1 gene] - dorsoventral
‣
- Limb bud forms at 4 weeks → complete at 8 weeks
- Arises from the Mesoderm with ectoderm overlying it → Somites grow into a limb bud
- Eventually
- Mesoderm develops into muscle, bone, tendon, cartilage
- Ectoderm develops into overlying skin
- Draw and explain the 3 axes of growth
- AER, ZPA, and WnT
‣
- Swanson (now outdated)
- Group 1: Failure of formation - Radial club hand, hypoplastic thumb, ulnar club hand
- 2: Differentiation - Syndactyly, Symbrachydactyly, Radioulnar Synostosis; Clinodactyly / Kirner's Deformity/ Camptodactyly; Congenital Clasped Thumb, Trigger Thumb
- 3: Duplication - Thumb duplication
- 4: Overgrowth
- 5: Undergrowth
- 6: Constriction Ring syndromes
- 7: Generalized abnormalities
‣
- Intramembranous ossification = Mesenchymal tissue transforms directly into bone (clavicle, flat bones)
- Clinically also seen in distraction osteogenesis
- Endochondral ossification = Begins with chondroblasts producing cartilaginous anlage which is resorbed and replaced with bone
- Appositional growth = Increases width of bone with osteoblasts being laid down under the periosteum
‣
- Physis zones–RPH(MDC)+M(PS)
- Resting Zone = Germinal cells, low oxygen tension
- Proliferation = Chondrocytes proliferate, high oxygen tension
‣
- Maturation - 5-fold increase in size, accumulate calcium
- Death - during "cell mediated apoptosis", Calcium is released
- Provisional Calcification zone
‣
- Cartilage removed and bone is laid down by osteoblasts
- Remodelled into lamellar bone to produce secondary spongiosa
‣
- Safranin O stains cartilage (also used as a counterstain in Gram staining)
‣
- Due to constraint provided by the perichondrial ring of LaCroix (a fibrous osseous structure that forms a strong supporting girdle around the physis), growth occurs longitudinally rather than horizontally
‣
- 3 main blood supplies:
- Epiphyseal artery - supplies secondary ossification center
- Metaphyseal artery - branches from the nutrient artery of diaphysis
- Perichondral artery - supplies the ring of LaCroix and forms anastomoses with epiphyseal and metaphyseal arteries
‣
- Longitudinal bone growth occurs through endochondral ossification at the physis, constrained by the perichondrial ring of LaCroix
- Appositional ossification in the osteogenic layer of the periosteum (inner cambium) causes diaphyseal widening
‣
‣
- PTH - Direct mitogenic effect stimulates chondrocyte proliferation
- Calcitonin - accelerates calcification
- Thyroxine - increases DNA synthesis and proliferation
- Growth hormone - increases cellular proliferation
- Sex hormones - stimulate physis closure
- Steroids - reduce cell proliferation
‣
- Vitamin D - affects provisional calcification → Rickets
- Vitamin C - deficiency leads to primary spongiosa defects → Scurvy
- Growth factors - FGF, TGF-Beta
‣
- Insulin-like growth factor, fibroblast growth factors (FGFR-3 defect in achondroplasia)
‣
- Reserve zone - Gaucher's, Dystrophic Dysplasia (affects cartilage - cauliflower ears)
- Proliferative zone - Achondroplasia, gigantism, Multiple Hereditary Exostosis (MHE)
- Hypertrophic zone - Rickets, Salter Harris, SCFE (Zone of PC)
- Primary spongiosa - Scurvy (Vitamin C deficiency)
- Secondary Spongiosa - Renal osteodystrophy, OI
‣
- Proximal ends of the phalanges and distal ends of the metacarpals
📖
My son, do not forget my teaching, but let your heart keep my commandments. Proverbs 3:1