Introduction to Repair

Introduction to Repair

• Repair is the replacement of damaged tissue with new healthy tissue.

Learning Objectives

• Recognize types of repair
• List factors controlling repair
• Mention mechanisms controlling repair
• Stem cells and their types
• Examples of repair
• Healing by connective tissue
• Wound healing by primary and secondary intention

Types of Repair

• Regeneration: Replacement of damaged cells by new cells of the same type.
  • Example: Regeneration of intestinal mucosa, regeneration of epidermis.
• Healing by connective tissue: Replacement of damaged cells by connective tissue (fibrosis or gliosis).
  • Example: Healing of skeletal muscle, healing of liver after massive damage.

Cell Types

• Permanent: Cells unable to regenerate. Examples: neurons, cardiac muscle, skeletal muscle.
• Stable: Cells that can regenerate but have low activity. Examples: parenchyma of solid tissue, endothelial cells, fibroblasts, smooth muscle
• Labile: Cells that continuously divide and are lost/replaced. Examples: hematopoietic cells of bone marrow, surface epithelium (e.g., skin, intestinal lining).

Stem Cells

• These cells have the ability for self-renewal and multilineage potential, meaning they can differentiate into different types of cells. They have long-term viability.
• Types: Embryonic and Adult (1- Marrow (hematopoietic stem cells), 2- Non-Marrow (reserve))

Factors Affecting Repair

• Local factors: Infection, ischemia (reduced blood flow), foreign bodies, movement, mechanical stress, necrotic tissue.
• Systemic factors: Diabetes mellitus, ionizing radiation, advanced age, malnutrition, vitamin deficiencies, certain drugs, jaundice, uremia, malignancy.

Mechanisms Controlling Repair

• Growth factors (EGF, FGF, PDGF, TGF alpha and beta)
• Removal of chemical factors inhibiting mitosis (Chalones)
• Removal of contact inhibition
• Cell matrix interaction

Healing by Scar (Connective Tissue)

• Replacement of damaged tissue by granulation tissue.
• Granulation tissue matures into fibrous (scar) tissue.
• Steps of repair by scar:
• Hemostasis
• Inflammation
• Proliferation- Angiogenesis( New capillaries)
• Maturation of granulation tissue (scarring)
• Remodeling

Wound Healing (Types)

• Primary intention: Healing of clean, surgical wounds with minimal tissue loss. Steps:
  • Small blood clot, debris
  • Epithelialization
  • Granulation tissue formation
  • 10-14 days - scab separation
  • Scar formation-Months/years.
• Secondary intention: Healing of wounds with significant tissue loss. Steps:
  • Large blood clot, necrotic debris, pus
  • Granulation tissue formation
  • Epithelialization
  • Scar formation- Months/years.

Complications of Wound Healing

• Excessive healing: Hypertrophic scar, keloid
• Defective healing: Chronic ulcer, sinus, fistula, contracture, implantation cyst

Repair of Bone

• Steps in bone fracture healing:
  • Haematoma
  • Inflammation
  • Granulation tissue (soft callus)
  • Provisional callus (woven bone)
  • Hard osseous callus (lamellar bone)
  • Remodeling
  • Bone marrow regeneration

Repair of Liver

• Normal liver has intact framework
• Mild damage leads to regeneration.
• Massive damage leads to liver cirrhosis (significant disruption of healthy liver framework)

Nervous System Repair

• The nervous system is capable of both gliosis (scar tissue formation) and regeneration in the peripheral system. -Central nervous system does not regenerate well.

Applications of Stem Cells

• Treatment of diabetes, Alzheimer's
• Replacing damaged tissues (brain, muscle, liver, bone, cartilage)
• Regrowing human teeth and hair.

Summary

• The body has sophisticated mechanisms for tissue repair which involve different pathways, classifications and factors influencing them.
• Repair processes can be normal or abnormal, depending on various factors. Key cellular and biomolecular pathways involved in tissue repair were highlighted..