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Growth Plate Anatomy

- See:
        - Enchondral Ossification
        - Limb Development
        - Growth Deformities of the Limbs
        - Pediatric Bone Circulation
        - Physeal Bone Bridge
        - Salter Harris Classification

- Undifferentiated or Resting Cartilage Cells:
    - immediately adjacent to epiphysis are irregularly scattered cartilage cells, called the resting cell zone;
    - this is germinal layer that supplies the developing cartilage cells;
    - ratio of extracellular matrix to cell volume is high and the cells are in a relatively quiescent state;
    - injury to this layer results in cessation of growth;
    - the groove of Ranvier contains cells which flow into the into the cartilage in this layer of the growth plate;
          - the function is to supply chondrocytes for increasing the width of the growth plate;

- Zone of Proliferating Cartilage:
    - location in which bone length is created by active growth of cartilage cells;
    - chondrocytes assume a flattened appearance, begin to divide, and become organized into columns
    - on metaphyseal side, cartilage cells become aligned into well-defined columns, known as zone of cellular proliferation;
           - it is at base of these columns that mitotic activity is found;
    - in this small area, two or three cells thick, occurs cell division upon which entire growth in length of bone depends;
    - failure of these cells to thrive results in cessation of growth at end of bone;

- Hypertrophic Cell Zone (Maturation Zone):
    - there is no active growth in this layer (no cellular division) and the chondrocytes begin to terminally differentiate;
    - layer in which chondrocytes become enlarged, swollen, and vacuolated in process of maturation leading to cell death;
          - they hypertrophy at expense of extracellular matrix (collagens and proteoglycans), & these enlarged cartilage cells;
          - synthesis of extracellular matrix permits newly divided cells to separate from each other;
    - columns of cartilage cells extend toward metaphysis, being constantly lengthened by cell division occurring at the base;
    - cells nearer the metaphysis begin to undergo changes that ultimately lead to their destruction;
    - marked increase in alkaline phosphatase enzyme activity;
          - this enzyme increases the concentration of phosphate ions, which are required in the calcification process;
          - in hypophosphatasia, there is an absence of alkaline phosphatase and there is deficient mineralization of the matrix and
                  widening of the growth plate;
    - this is weakest portion of the epiphyseal plate (salter harris fractures occur thru this zone);
    - in rickets, there is failure of calcification which causes accumulation of cells in the hypertrophic layer;
    - type X collagen production:
           - short-chain collagen found only in the hypertrophic zone;
           - mutations here may cause Schmid metaphyseal chondrodysplasia;

- Zone of Provisional Calcification:
    - is area where, w/ death of chondrocyte & production of AP, longitudinal bars of cartilage matrix become calcified;
           - these chondrocytes prepare the matrix for calcification, which then serves as a template for osteoblastic bone formation;
    - last two or three cells in column of cartilage cells are in fourth zone, the zone of provisional calcification.
           - it is in this area that extracellular chondroid matrix becomes impregnated with calcium salt;
           - this calcification of matrix is required for subsequent steps,  including:
                   - invasion of cartilage cells by blood vessels from metaphysis;
                   - destruction of cartilage cells;
                          - this provides space for the ingress of vascular channels and bone-marrow stromal cells;
                   - formation of bone along remaining walls of calcified cartilage matrix;
    - juncture between epiphyseal plate & metaphysis is secured by welding of metaphyseal bone to calcified cartilage matrix.
    - collagen type X, may play a role in the calcification of this cartilage;
           - references:
                   - Localization of type X collagen in canine growth plate and adult canine articular cartilage.  
                   - Does osteoarthrosis depend on growth of the mineralized layer of cartilage

- Physeal Growth Arrest:
    - differential diagnosis:
           - internal fixation (K wires)
           - chemotherapy
           - radiation
           - thermal injury
           - immobilization
           - infection
           - arterial insufficiency
           - extravasation of IV medicines

Characterization of aggregating proteoglycans from the proliferative, maturing, hypertrophic, and calcifying zones of the cartilaginous physis.

Growth plate physiology and pathology.

Quantitation of chondrocyte performance in growth-plate cartilage during longitudinal bone growth

Differential growth by growth plates as a function of multiple parameters of chondrocytic kinetics.