Year 1 embryology limbs_CM_2024 (1)

Page 4: Limb Development Defects

  • Fundamental events in limb development occur from weeks 4 to 8 of embryological period

Page 6: Gastrulation

  • Occurs in the third week of gestation

  • Establishes three primary germ layers:

    • Ectoderm

    • Mesoderm

    • Endoderm

Page 7: Gastrulation Process

  • Components: Yolk Sac, Hypoblast, Epiblast

  • Epiblast cells migrate to form primitive streak, creating mesoderm

  • Transformation of hypoblast into endoderm

  • First mesodermal tissue to differentiate is the notochord

Page 8: Mesoderm Types

Mesodermal Contribution:

  • Paraxial Mesoderm: Forms somites, which send signals to induce the growth of the lateral plate mesoderm.

  • Lateral Plate Mesoderm: Contributes to limb formation, condenses and grows outward, initiating limb bud development.

Page 14: Initial Limb Bud Appearance

  • Upper limb bud becomes visible at 24 days gestation

Limb Bud Development

  • Limb Bud Formation:

    • Begins with ectodermal thickening at the tip of the limb bud, forming the Apical Ectodermal Ridge (AER).

    • AER: Directs the differentiation of underlying mesoderm, which elongates into the limb.

  • Digit Formation (Weeks 5-8):

    • Distal limb ends expand into digital plates.

    • Programmed Cell Death (Apoptosis) in the AER and between future digits shapes the fingers and toes.

    • Proximal before distal, upper before lower

  • By week 8, limbs appear similar, roughly 1cm long

Page 19: Digit Separation

  • 48 days: Cell death in AER leads to separate ridges for digits

  • 51 days: Interdigital spaces result from cell death

  • 56 days: Complete digit separation

Page 21: Formation Mechanism

  • Cartilaginous precursors form first, ossification begins around weeks 8 to 12

Page 22: Ossification Types

  • Intramembranous Ossification: Bone forms directly from connective tissue membrane (e.g., skull)

  • Endochondral Ossification: Bone forms through replacing hyaline cartilage models (e.g., long bones)

Page 25: Endochondral Process

  • Initial template is hyaline cartilage (6 weeks) which develops into bone through multiple stages of cell differentiation

Stages of Endochondral Ossification:

  1. Chondrocyte Hypertrophy: Cells in cartilage enlarge, and the matrix begins to calcify.

  2. Periosteum Formation: Blood vessels convert the perichondrium into periosteum.

  3. Primary Ossification Center: Osteoblasts form bone in the center, spreading towards the ends.

  4. Growth in Length & Thickness: Osteoblast and osteoclast activity increases bone size.

  5. Secondary Ossification: develops in the centre of the epiphyses

  6. Completion: Growth ceases as primary and secondary ossification centers fuse.

Page 31: Muscle Development

  • Limb muscles originate from somites; somites further divide into:

    • Dermatome: Dermis

    • Myotome: Muscles

    • Sclerotome: Bone of the axial skeleton

Page 32: Muscle Positioning

  • Muscles invade limb buds in 5th week, forming:

    • Anterior Ventral Side: Flexors, pronators, adductors

    • Posterior Dorsal Side: Extensors, supinators, abductors

Limb Rotation:

  • Upper limbs rotate laterally.

  • Lower limbs rotate medially, creating distinctive patterns in dermatomes.

Nerve Growth:

  • Nerve roots grow between somites, forming a plexus that invades each limb including the muscles and the skin categorised by myotomes and dermatomes

Page 38: Dermatomes for Upper and Lower Limbs

Upper Limb

  • C5: Over deltoid

  • C6: Over thumb

  • C7: Middle finger

  • C8: Medial forearm

  • T1: Over axilla

Lower Limb

  • L4: Over tibia (medial)

  • L5: Over fibula (lateral)

  • S1: Under 5th toe

  • S2: Over popliteal fossa

  • S3: One sits on S3

Page 39: Congenital Limb Abnormalities Overview

  • Reduction Defects:

    • Meromelia: Partial limb absence.

    • Amelia: Complete limb absence.

    • Adactyly: Absence of digits.

  • Duplication Defects:

    • Polydactyly: Extra fingers or toes.

  • Fusion and Growth Disorders:

    • Syndactyly: Fusion of digits.

    • Gigantism: Excessive growth of limb parts.

    • Club Foot: Foot is turned inward, often seen with syndactyly.

Page 45: Teratogenic Factors

  • Thalidomide can cause limb defects such as phocomelia

    • Phocomelia: Arms or legs attached near the trunk, grossly underdeveloped