regeneration and healing reviewer

REGENERATION AND HEALING

Definitions

  • Regeneration: Growth of cells to replace lost tissues without injury.

  • Healing: A reparative tissue response to a wound, inflammation, or necrosis; often leads to fibrosis (injury).

Granulation Tissue

  • Characteristics: Organizing inflammation; involves neovascularization (formation of new blood vessels).

  • Regeneration: Replacement of lost structures is dependent on the type of normal turnover of the original tissue; differs from compensatory growth.

HEALING (Repair)

Requirements for Healing

  • Needs a wound, inflammatory process, or necrosis.

  • Many disease appearances (e.g., atherosclerosis) are a result of healing.

  • Typically ends with scar formation, leading to fibrosis, which can follow inflammation.

  • Requires a connective tissue scaffold for repair, with fibrosis occurring in proportion to damage to the extracellular matrix (ECM).

Outcomes of Inflammation

  • Fibrosis: One of three possible outcomes, following healing.

  • Various cellular responses include:

    • Proliferation: Hormonal influences from steroids, EPO, CSF, growth factors (GFs).

    • Differentiation: Compared to multiplication; uni-directional gain and loss of cell populations.

    • Apoptosis: Key concept in neoplasia.

CELL CYCLE

Phases of the Cell Cycle

  • G0: Quiescent phase (not a dominant phase).

  • G1: Pre-synthetic phase with cell growth taking place.

  • S Phase: DNA synthesis, longer in continuously turning over cells; S-phase in tumor cells can be prognostic.

  • G2: Pre-mitotic phase, concluding final preparations for division.

  • M Phase: Mitotic phase (includes prophase, metaphase, anaphase, telophase, cytokinesis).

STEM CELLS AND TISSUE REGENERATION

Types of Stem Cells

  • Totipotential Stem Cells: Found in embryonic development.

  • Adult Stem Cells:

    • Marrow (Hemocytoblast): Hematopoietic stem cells.

    • Non-Marrow Reserve: Contribution to tissue regeneration.

Growth Factors and Cytokines

  • Polypeptides involved in:

    • Locomotion

    • Contractility

    • Differentiation

    • Angiogenesis (new blood vessel formation).

GROWTH FACTORS

Key Growth Factors

  • Epidermal Growth Factor (EGF): Produced by platelets and macrophages; promotes keratinocyte migration and fibroblast function.

  • Transforming Growth Factor (TGF):

    • TGF-alpha: Similar functions to EGF, acts on hepatocytes.

    • TGF-beta: Chemotactic for many cells, inhibits epithelial cells, has fibrogenic effects, and possesses anti-inflammatory properties.

  • Hepatocyte Growth Factor (HGF): Stimulates motility and proliferation in epithelial cells.

Role of Other Cytokines

  • Interleukins: Functions include chemotaxis and regulation of other cytokines.

  • Interferons: Activate macrophages and inhibit fibroblasts.

EXTRA CELLULAR MATRIX (ECM)

Functions

  • Maintains cell differentiation and scaffolding.

  • Establishes the microenvironment and serves as storage for growth factors.

Types of Collagen

  • Collagen Types:

    • Type I: Major component of bone.

    • Type II: Main component of cartilage.

    • Type III: Main component of reticular fibers.

    • Type IV: Forms basement membranes.

WOUND HEALING

Stages of Wound Healing

  1. Injury Response: Clot formation, inflammation initiation.

  2. Granulation Tissue Formation: Collagen deposition, angiogenesis, and re-epithelialization.

  3. Wound Contraction and Remodeling: Gradual strengthening and maturation of scar tissue.

Healing Intentions

  • First Intention: Smooth edges of wounds lined up.

  • Second Intention: Edges not aligned, leading to increased granulation and fibrosis.

Factors Retarding Healing

  • Local Factors:

    • Decreased blood supply, infection, mechanical stress, necrotic tissue, hematoma.

  • Systemic Factors:

    • Age, anemia, malignancy, malnutrition, obesity, organ failure.