Development of Appendicular Skeleton PDF

Development of Appendicular Skeleton Dr Toqeer Ahmed  Begins with the activation of a group of Development of Limb mesenchymal cells in the lateral mesoderm. Mesenchyme is derived from dorsolateral...

Development of Appendicular Skeleton Dr Toqeer Ahmed  Begins with the activation of a group of Development of Limb mesenchymal cells in the lateral mesoderm. Mesenchyme is derived from dorsolateral cells of somites that migrate into the limb bud to form the muscles – Somatic layer of Lateral plate mesoderm) The limb buds (at the end of 4 th wk) First appear as elevations of the ventrolateral body wall UL buds--by day 26 or 27 LL buds---by day 27 or 28 Consists of mesenchymal core derived from somatic layer of LPM, covered by cuboidal layer of ectoderm. Growth and Elongation By proliferation of the mesenchyme Splits into flexor and extensor components Progress zone Apical ectodermal ridge (AER). A multilayered epithelial structure at the apex of the limb, induced by the underlying mesenchyme Exerts an inductive influence on the adjacent mesenchyme that initiates growth and development of the limbs in a proximodistal axis. Group of mesenchymal cells establishing the A/P axis of limb Growth and Elongation Skeletal elements of each limb proceeds proximo-distally Digital rays Mesenchymal condensations outlining the pattern of the digits or fingers Apoptosis. End of 8th wk. Upper limb 27 32 41 46 50 52 DAYS Lower limb 28 36 46 49 52 56 DAYS Osteogenesis Chondrification of mesenchymal model…6th week Primary ossification centres..8-12 wks Secondary ossification centers (except lower end of femur)…after birth Fusion of primary and secondary canters… late adolescence Clavicle is only long bone developing intramembranous Development of joints Starts in 6th week, completing quickly by 8th week. Develop from condensation of mesenchyme between two developing bone. Interzone mesenchyme differentiates to fibrous Fibrous joints tissue Interzone mesenchyme Cartilagenous differentiates to fibrocartilage joints Cavitation of mesenchyme. Peripheral mesenchyme differentiates into Synovial joints surrounding structures. Development of Bone Ossification/ Osteogenesis  8th week of IUL Intramembranous Arise directly within the membranes in which they are located. ossification Bone is formed by differentiation of mesenchymal cells into osteoblasts. Endochondral or intracartilagenous Axial skeleton that bear weight ossification Steps of intramembranous ossification 1. Codensation & then vascularization of mesenchymal cells at specific areas 2. Formation of primary ossification centre Differentiation of mesenchymal cells to osteoprogenitor cells 3. Deposition of bone matrix by osteoblasts 4. Some of the osteoblasts are trapped in their own matrix & become osteocytes 5. Formation of periosteum & compact bone Surface bone filled in by bone deposition, converting spongy bone to compact bone tables. Endochondral/ Intra-cartilagenous Ossification  2. Formation of Bone collar, Periosteum & Primary ossification centre. Perichondrium produces 1. Hyaline cartilage formation osteoblasts in place of Mesenchyme develops into chondrocytes hyaline cartilage with Perichondrium _ periosteum perichondrium in location of 3. Vascular invasion of primary 4. Formation of secondary ossification ossification centre, allowing inflow of center & secondary marrow cavity in osteoblasts and osteoclasts creating Epiphysis hollow centered filled with blood (primary Center may appear in only one epiphysis marrow cavity) (wrist bones) or both (bones of arm, forearm, legs, thighs) 5. Epiphyses become filled with spongy bone Cartilage remains bw diaphysis & 6. Epiphysial plate ossifies (after epiphysis (epiphyseal plate) and as adolescence) and is replaced by Epiphysial articular cartilage. line at the end of longitudinal growth. Growth of Endochondral Bone begins in the second trimester (12th wk) of fetal life and continues into early adulthood. Growth of long bones depends on the presence of epiphyseal cartilage throughout the growth period. Epiphyseal Plate: layer of hyaline cartilage bw epiphysis and diaphysis (Site of interstitial growth (growth in length) of bone) Zone of Resting cartilage Farthest away from medullary cavity of diaphysis and nearest the epiphysis Zone of cell Proliferation: Chondrocytes are slightly larger, multiplying and lining up in small rows of flattened lacunae. (like a stack of coins) Zone of cell hypertrophy: Chondrocytes cease dividing and become enlarged, thinning of lacunae wall Zone of calcification: Temporary calcification of cartilage matrix bw columns of lacunae. Zone of Ossification: Mergence of lacunae Invasion with capillaries & bone forming cells Bone Growth in Width (Only by appositional growth at the bone’s surface) Periosteal cells differentiate into osteoblasts and form bony ridges and then a tunnel around periosteal blood vessel. Concentric lamellae fill in the tunnel to form an Osteon. Intramembranous Endochondral Ossification Ossification Develops within mesenchymal Involves cartilaginous model tissue without prior involvement which later ossifies of cartilage Chondrocytes and osteoclasts Chondrocytes and osteoclasts not involved involved Takes less time to form a bone Takes a longer time to form a bone Stops at year 2. Stops at year 18 & 20 in females & males respectively Important in the formation of flat Important in the formation of bones long bones Myogenesis. Migration of myogenic precursor cells from dermomyotome regions of the somites Differentiation into myoblasts Aggregation of myoblasts to form a large muscle mass in each limb bud. Dorsal (extensor) and ventral (flexor) components  Upper limb Rotation Laterally through 900 on its longitudinal axis future elbows point dorsally Extensor muscles lie on the lateral and posterior aspects of the limb Lower limbs Medially through almost 900 – future knees face ventrally – Extensor muscles lie on the anterior aspect of the lower limb. Cutaneous Innervation – Upper limb buds lie opposite C4– T2 segments. – Lower limb buds lie opposite the lower four lumbar and upper two sacral segments. Cutaneous Innervation Motor axons enter the limb buds during the 5th week and grow into the dorsal and ventral muscle masses. Sensory axons follow Peripheral nerves grow from the developing limb plexuses. Blood supply Limb buds Branches of the intersegmental arteries arising from the aorta forming a network throughout the mesenchyme. The primordial vascular pattern Angiogenesis Primary axial artery and its branches Drain into a peripheral marginal sinus. A peripheral vein  Molecular regulation Expression of HOX A, D signaling factor FGF 10+ TBX5 FGF 10+TBX5 4 craniocaudal FGF 10 by gene UL gene LL axis prelimb LPM. BMP 5 in mesenchyme of ZPA is activated by developing bud FGF 4,8 from AER leads to formation of AER SHH for patterning along anteroposterior axis.  Limb defects Fourth and the fifth weeks of gestation are the most sensitive period for induction of the limb defects. 3.4 per 10,000 affecting the upper limb Incidence is 6 per 10,000 live births 1.1 per 10,000 affecting the lower. Often associated with other birth defects involving the craniofacial, cardiac, and genitourinary systems. Initially abandoned but now being Thalidomide used in AIDS and malignancies Amelia Meromelia (partial absence of limb) Micromelia Phocomelia (hands and feet attached close to trunk) Polydactyly Digits defects Extra digit Syndactyly  Digits defects Brachydactyly short digits Ectrodactyly Absence of digit  Gene mutations Hand-foot genital Syndrome (HOX13 Holt-Dram syndrome (TBX5 gene) mutations) Almost all types of limb defects Fusion of carpal bones, affecting the upper limb brachydactyly Heart valvular defects Malformation of uterus in females and hypospadias in males  Gene mutations Osteogenesis imperfecta/ Brittle bone disease (mutations in the COL1A1 or COL1A2 genes that are involved in production of type I collagen) Shortening, bowing and hypomineralization of the long bones of the limbs prone to fractures.  Marfan syndrome (mutations in the FIBRILLIN [FBN1] gene) Dislocated lens Aortic aneurysm Sternal abnormalities Short torso Unusually long arms and fingers Long thin bones Flat feet Cleft Hand and Cleft Foot Abnormal cleft b/w 2nd & 4th metacarpal/ metatarsal bones & soft tissues. The 3rd M/C, M/T & phalangeal bones are almost always absent. Rest of digits may be fused. Congenital Clubfoot Familial, genetic (PITX1) Arthrogryposis [congenital joint contractures] Usually involves multiple joints. Caused by neurological, muscular or joint defects  Amniotic bands Craniosynostosis-radial aplasia syndrome [Baller—Gerold syndrome]. synostosis in one or more cranial sutures with absent radius. Congenital hip dislocation Underdevelopment of the acetabulum and head of the femur. Breeach delivery Transverse limb deficiencies structures distal to a transverse plane are partially or completely absent. Disruption of AER or vascular abnormalities. Bone Age an indicator of the skeletal and biological maturity of an individual. Ossification studies Assessment of in the hands and maturation age wrists of children by radiologist Prenatal analysis of fetal bones by ultrasonography Medicolegal provides information importance about fetal growth and gestational age.