Tissue Repair and Anatomy Quiz

Regeneration and Repair

• Regeneration and repair are processes that restore tissue architecture and function after injury.
• Regeneration involves the proliferation of surviving cells to replace the damaged or lost tissue.
• Connective tissue deposition involves laying down fibrous connective tissue to replace damaged tissue when regeneration is not possible.

Learning Objectives

• Describe the effects of regeneration and repair on an organ or tissue.

Outline

• Introduction
• Regeneration
• Connective tissue deposition
• Cutaneous wound healing
• Pathological aspects of repair

Terminology

• Connective tissue: Tissues providing structure, mechanical strength and support for specialized tissues.
• Connective tissue structure components:
  • Extracellular matrix (ECM): fibrous structural proteins (e.g., collagen), ground substance and basement membrane.
  • Support cells (stromal cells): Responsible for making ECM (e.g., fibroblasts).
  • Blood vessels, lymphatic vessels and nerves: Providing nutrients and factors required for tissue growth.

Organ Examples

• Skin (cutaneous organ):
  • Specialized tissue: epidermis (outer epithelial cell layer).
  • Connective tissue: dermis (mesh of elastin and collagen fibers).
• Liver (parenchymal/solid organ):
  • Specialized tissue: hepatocytes (type of parenchymal cell).
  • Connective tissue: delicate network of extracellular matrix (e.g., reticulin).

Terminology Continued

• Collagen: Main fiber type in connective tissue, excess deposition is called fibrosis or scar formation.

Tissue Repair

• Regeneration alone is not practical for humans in most cases.
• Instead, a combination of regeneration and connective tissue repair is relied upon.
• Several cell types proliferate during repair:
  • Surviving functional cells.
  • Vascular endothelial cells (provide nutrients and growth factors).
  • Fibroblasts (source of fibrous/scar tissue).
• Ability of a tissue to repair itself is the intrinsic proliferative capacity.

Proliferative Capacity

• Different cells have various regenerative capacities.
• A cell's intrinsic proliferation capacity depends on how much time is spent in different phases of the cell cycle.
  • G₀: Resting phase.
  • Active phases: Remaining phases of the active cell cycle (G₁, S, G₂ & M).

Three Main Tissue Types

• Body tissues are categorized based on their proliferative capacity.
  • Labile tissue: Consistently divides; high regenerative capacity. (e.g., gastrointestinal epithelium, skin, oral mucosa, bone marrow.)
  • Stable tissue: Minimal proliferation, but capable of entering G₁ in response to injury. (e.g., cells of connective tissue like fibroblasts and smooth muscle cells; solid organs such as kidney, pancreas, adrenal glands.)
  • Permanent tissue: Cannot proliferate (e.g., neurons and cardiac muscle cells)

Labile Tissues

• Have high regeneration capacity; continuous cell renewal.
• Increased amount of stem cells. Rapid cell replacement in injury.
• Stem cells differentiate into the lost cell type.

Stable Tissues

• Regeneration can occur but is often limited.
• Connective tissue-like cells (fibroblasts, smooth muscle cells).
• Many solid organs are stable tissues (kidney, pancreas) but one exception is the liver.

Permanent Tissues

• Cannot undergo proliferation.
• Tissue death results in repair via connective tissue deposition.
• Results in non-functioning scar tissue.
• Examples include neurons and cardiac muscle cells.

Regeneration Process

• Complex process involving the interaction of growth signals and control mechanisms.
• Influenced by growth factors, hormones and cytokines.
• Interaction of cells with the ECM.
• Mechanical support; scaffolding for tissue repair, and microenvironment maintenance.

Example: Liver Regeneration

• Occurs through priming and proliferation phases.
• Priming: Kupffer cell cytokines (IL-6) make hepatocytes respond to growth factors.
• Proliferation: Growth factors (HGF, TGF-α) stimulate hepatocyte entry into the cell cycle.

Limitations of Regeneration

• Regeneration cannot repair all types of injuries.
• Regeneration often isn't sufficient for severe or chronic injuries.
• Tissues with non-dividing cells cannot be regenerated.
• Connective tissue deposition results in fibrosis/scar tissue formation.
• Specific examples for liver (intact structure needed for regeneration; regeneration insufficient with inflammation/infection, with extensive damage to reticulin).

Repair by Connective Tissue Deposition

• Inflammatory phase: process begins within 24 hours, damaged tissue removed, cytokines and growth factors secreted.
• Proliferative phase: new blood vessels (angiogenesis), fibroblasts proliferate and deposit ECM, granulation tissue is formed.
• Remodeling phase: granulation tissue becomes a scar, matrix metalloproteinases degrade ECM, including collagen.

Cutaneous Wound Healing

• Involves epithelial regeneration and connective tissue formation.
• Healing processes grouped into primary, secondary or tertiary intent based on wound size, health and repair procedure used.
• Extensive vs minimal tissue types repaired ( primary vs secondary intention healing.)

Healing: Primary Intention

• Clean, uninfected opposed wound.
• Example: sutured incision.
• Epithelial regeneration predominates over fibrosis.
• Minimal wound contraction and scar formation.
• Dermal appendages are often lost.

Healing: Secondary Intention

• Large, infected, or chronic wounds.
• Example: ulcers, deep abrasions, severe burns.
• Fibrosis predominates over epithelial regeneration.
• More severe inflammatory response.
• Extensive granulation tissue and scar formation.

Wound Strength

• Healed skin is not as strong as original tissue.
• Strength increases over time after repair, but not to the original strength. Recovery time depends on depth and extent of tissue damage

Pathological Aspects of Repair

• Complications of wound healing classified into inadequate and excessive tissue repair.

Factors Influencing Tissue Repair

• Factors influencing wound healing (infection, foreign body presence, nutritional status - vitamins (C), hormonal status (steroids), perfusion/blood supply/oxygen, diabetes, mechanical factors such as pressure, type and extent of injury (labile vs. stable permanent tissue.))

Inadequate Tissue Repair

• Results from inadequate formation process components.
• Examples include:
  • Wound dehiscence: separation of surgical wound edges. (infection, mechanical factors)
  • Ulcers (venous leg ulcers - chronic venous hypertension, poor oxygen delivery; arterial ulcers - atherosclerosis, and diabetic ulcers – multifactorial)
  • Pressure ulcers (mechanical pressure, local ischemia)

Excessive Tissue Repair

• Results from excess formation process components.
• Examples include:
  • Hypertrophic scars: raised scars that do not go beyond original wound.
  • Keloid scars: raised scars that extend beyond original wound.
  • Proud flesh: exuberant granulation tissue
  • Wound contractures
  • Desmoid tumors: excess proliferation of fibroblasts and ECM.

In Summary

• Tissue repair can occur via regeneration or connective tissue deposition.
• Body tissues have different regeneration capacities.
• Tissues are repaired by replacement with connective tissue and scar tissue.
• Inadequate or excessive repair can cause health problems depending on the type/extent of tissue damage and presence of infections or foreign bodies.