L5: The Process of Healing in Health and Disease

Learning Obejectives

• Describe the process of healing

• Compare healing by primary intention with that by secondary intention

• List the factors which promote or adversely affect healing

• Explain the complications that may arise as a consequence

• Identify the processes of repair and regeneration in the healing of various tissues

Introduction

Definitions

• Repair: replacement of lost tissue by granulation tissue → form scar (fibrous) tisssue

• Regeneration: replacement of lost tissue by tissue similar in type → proliferation of surrounding undamaged specialised tissue

Types of cells in terms of regenerative capacities

• Labile cells

  • continue to multifply throughout life

  • example: epidermis, alimentary, respoiratory, haemopoietic bone marrow

• Stable cells

  • normally cease multiplication when growth ceases

  • retain mitotic ability → allow regeneration of damaged tissues

  • example: liver, pancreas, endocrine organs

• Permanent cells

  • lose capacity to proliferate in infancy

  • example: nerve cells, cardiac muscles

Process of healing

Mechanism

• Growth factors

  • chronic inflammation

  • effects on angiogenesis, chemotaxis, mitogenesis, collagen synthesis

  • examples: fibroblast growth factors, vascular endothelial growth factors, interleukin-1 epidermal growth factor

• cell-cell and cell-matrix interaction

  • formation of monolayer of cells after proliferation

  • importance: cease proliferation after the injury is healed

• Extracellular matrix synthesis and collagenisation

  • wound strength: related to proliferation of fibroblasts, collagen and other extracellular elements in healing wounds

Healing of skin wound

Primary intention (clean wound or incision with minimum of space between margins)

• escape of blood and exudate

• clotted blood and fibrin with dehydration → scab

• acute inflammation in 1st 24 hours

• proliferation and migration of basal epithelial cells of epidermis →undermine superficial blood clot

• granulation tissue formation: migration and proliferation of fibroblasts and endothelial cells

• thin branching bundles of collagen fibrils

• increase in mature collagen fibres → form scar

• loss of vascularity and shrinkage of scar

Secondary intention (open or excised woun with separated edges)

• greater tissue loss

• more inflammatory eudate and nercotic materials to remove

• more granulation tissue → greater scare and mroe deformity

• wound contraction by myofibroblasts

• slower processes and increased liability to infection

Factors affecting wound healing

Local factors

• types fo wounding agents

• infection

• foreign bodies in wound → chronic inflammation

• poor blood supply → comprimise healing

• excessive movement

• poor apposition of margin → larger haematoma formation

• poor wound contraction due to tissue tethering (skin over tibia)

• infiltration by tumour

• previous irradiation

General factors

• poor nutrition → impair collagen formation

• excessive glucocorticosteroid production or administration → immunposupression

• systemic disease → poor blood supply

Complications

• infection: delay healing

• wound dehiscence

• implantation: epidermoid cyst formation if epithelial cells flow to healing wound

• excessive tissue formation

  • granulation tissue

  • keloid (collagenous tissue) → raised area of scar tissue

• pigmentary changes: rusty colour due to deposition of haemosiderin

• parinful scar: peripheral nerve growing haphazaardyly into scar→ traumatic neuroma

• weak scar: due to contiuous strain, stretching → incisional hernia

• cicatrisation: late reduction in size of scar and frequent production of great deformity

• neoplasia: squamous cell carcinoma in scars

Repair and regeneration of different tissues

Epithelial ulceration

• regeneration fo epithelial cells

• extensive ulceration: difficult to resore the normal architecture → may form scar

Bone fractures

• haematoma formation

• traumatic inflammation

• demolition: fragments of bones detach from blood supply → necrosis and removed by macrophages and osteoclasts

• granulation tissue formation

  • New capillaries and mesenchymal cells grow into the area (from periosteum/cancellous bone).

  • Periosteum’s deeper layer cells can form new bone

• callus formation

  • Osteoblasts or chondroblasts create woven bone or cartilage to bridge fracture ends.

  • Cartilage forms if movement occurs; later calcifies and dies.

• lamellar bone formation

  • Calcified cartilage is replaced by lamellar bone

  • Osteoclasts remove temporary callus; osteoblasts lay osteoid → form lammelar bone

• remodelling: coni=tinused osteoclastic removal and osteoblastic laying down of bone

Cartilage, tendon and muscles

• cartilage regeneration

  • poor

  • repair occurs by growth of fibrous tissue

• tendon regeneration: slow but good

• cardiac muscle has no regeneraive capacity

• skeletal muscle: satellite cells

• smooth muscle: good regeneration capacity

Nervous tissue and nerves

• Central Nervous System (CNS) Injury

1. No Regeneration:

   • Damaged CNS neurons do not regenerate.

   • Repair involves glial scarring (astrocytes form glial tissue, not fibrous tissue).

2. Key Cells Involved:

   • Macrophages: Derived from microglia (CNS-specific immune cells) and blood monocytes.

   • Astrocytes: Form scar tissue, blocking regeneration.

• Peripheral Nervous System (PNS) Injury

1. Regeneration Possible (if cell body survives and injury is distal):

   • Wallerian Degeneration: Axon and myelin sheath distal to injury disintegrate.

   • Schwann Cells:

     • Proliferate to form pathways for axon regrowth.

     • Guide axonal sprouts from the proximal stump to reconnect.

2. Outcomes:

   • Successful Regeneration: If sprouts reach the distal stump (slow process: ~1-3 mm/day).

   • Failed Regeneration:

     • Traumatic Neuroma: Painful mass if sprouts grow randomly (e.g., nerve transection).

     • Cell Death: If injury is proximal or affects the nerve cell body.

• Axonal Neuropathy (Non-Traumatic Damage)

  1. Causes:

     • Diseases (e.g., diabetes) or toxins (n-Hexane, acrylamide, carbon disulphide).

  2. Features:

     • Giant Axonal Swelling: Toxins cause neurofilament accumulation in axoplasm → swollen axons.

     • Retrograde Degeneration ("Dying Back"):

       • Damage starts at distal axon (e.g., feet/hands) and progresses toward the cell body.

       • Myelin degeneration follows.