2024 - Healing and Repair - year 1

HEALING

  • Replacement of destroyed or lost tissue by viable tissue

TISSUE RESPONSE TO INJURY

  • Initial response: acute inflammation

  • Phases of response:

    • Resolution

    • Regeneration

    • Repair by fibrosis

RESOLUTION

  • No tissue destruction occurs

  • Removal of damaging agents and cell debris

  • Tissue returns to pre-injury state

    • Example: mild heat injury

REGENERATION AND REPAIR

  • Regeneration: Replacement of lost tissue by the same type

  • Repair: Replacement of destroyed tissue by fibrous scar

FACTORS AFFECTING THE HEALING PROCESS

  • Ability to remove causative agent

  • Ability to clear inflammatory debris

  • Degree of architectural damage

  • Ability of cells to proliferate

  • Extent of extracellular matrix damage

TISSUE PROLIFERATIVE ACTIVITY

  • Types of cells:

    • Labile Cells:

      • Continuously dividing (e.g., epidermis, mucosal epithelium, GI tract epithelium)

      • Derived from stem cells

      • Injury can heal easily by regeneration

    • Stable Cells:

      • Normally low replication (e.g., hepatocytes, renal tubular epithelium)

      • Can be stimulated to divide

      • Heal by regeneration if supporting stroma and stem cells are intact

    • Permanent Cells:

      • Non-dividing (e.g., neurons, cardiac myocytes, skeletal muscle)

      • No regeneration ability

      • Replaced by connective tissue

CELL CYCLE

  • Phases:

    • G1

    • S (DNA Synthesis)

    • G2

    • M (Mitosis)

    • G0 (Resting)

POLYPEPTIDE GROWTH FACTORS

  • Important mediators affecting cell growth

  • Present in serum or produced locally

  • Exert pleiotropic effects:

    • Proliferation

    • Cell migration

    • Differentiation

    • Tissue remodeling

  • Regulate growth by controlling gene expression

STROMA

  • Components:

    • Extracellular matrix

    • Interstitial matrix

    • Basement membranes

    • Mesenchymal cells

    • Vessels

EXTRACELLULAR MATRIX

  • Regulates cell activities and composed of fibrous proteins, collagens, elastin, glycoproteins, and proteoglycans

CELL-CELL INTERACTIONS

  • Growth factors: EGF, PDGF, FGF, VEGF, TGF

  • Cytokines

  • Growth inhibitors

REGENERATION

  • Replacement of lost cells with the same type through division

  • Requires intact supporting framework

  • Controlled by stimulatory/inhibitory factors and cell-ECM interactions

REPAIR BY CONNECTIVE TISSUE

  • Healing by fibrosis occurs when:

    • Parenchymal and stromal cells are destroyed

    • Permanent cells die

    • Organization of inflammation occurs

  • Involves:

    • Production of granulation tissue and fibrosis

    • Angiogenesis: New blood vessels from old

    • Remodeling: Type III collagen replaced by type I collagen (enzyme collagenase requires zinc)

WOUND HEALING PHASES

  1. Inflammatory Phase: Hematoma, neutrophils, macrophages.

  2. Proliferative Phase: Epithelial proliferation, granulation tissue, new vessel formation.

  3. Remodeling Phase: Replacement of granulation tissue by a fibrous tissue and extracellular matrix (ECM) degradation

TYPES OF WOUND HEALING

  • Primary intention

  • Secondary intention

  • Source: RCSI

STAGES OF WOUND HEALING BY PRIMARY INTENTION

  • Day 1:

    • Wound filled with blood clot

    • Acute inflammation in surrounding tissue

    • Proliferation of epithelial cells

  • Day 2:

    • Macrophage activity

    • Epithelial coverage begins

  • Day 3:

    • Formation of granulation tissue

  • Day 5:

    • Collagen deposition

  • Day 7:

    • Sutures removed

WOUND STRENGTH

  • After suture removal (1 week), wound strength is 10% of unwounded skin (Walker’s Law)

  • By 3-4 months, strength increases to 80% of unwounded skin (Walker’s Law)

WOUND HEALING BY SECONDARY INTENTION

  • Secondary intention: Gap filled with granulation tissue, slower, more intense.

PATHOLOGIC ASPECTS OF WOUND HEALING

  • Risks of deficient or excessive scar formation

  • Contracture deformities

  • Rare malignant transformations.

HEALING EXAMPLES

  • Mucosal surfaces: Erosion (regeneration), ulceration (regeneration & fibrosis).

  • Liver: Regeneration in short-term injuries; cirrhosis in chronic cases.

  • Nervous system: CNS (gliosis), Peripheral nerves (regeneration).

  • Muscle: Cardiac (fibrosis), Skeletal (fibrosis).

FACTORS INFLUENCING HEALING

  • Local factors:

    • Poor vascular supply

    • Infection

    • Presence of foreign materials

    • Excessive movement

    • Poor approximation

    • Size, site, and type of injury

  • Systemic factors:

    • Age

    • Nutrition:

      • Proteins

      • Vitamin C (collagen formation)

      • Copper (collagen cross-linking)

      • Zinc (conversion of type III to type I collagen)

    • Metabolic status (e.g., DM)

    • Hormones (e.g., steroids)

    • Impact of malignancy

    • Effects of chemotherapy and radiotherapy