Healing and Repair Flashcards
What are some solutions to Tissue Damage?
- Resolution - dead cellular material and debris are removed by phagocytosis (macrophages) and the tissue is left with its original architecture
- Regeneration - lost tissue is replaced by proliferation of cells of the same type, which reconstruct the normal architecture
- Replacement/Repair by fibrosis - A fibrous scar that is produced from granulation tissue replaces lost tissue
What is the mechanism of Regeneration and Replacement/Repair by Fibrous Tissue in Healing and Repair?
- Cell Migration
- Proliferation
- Differentiation
- Cell-matrix interactions
What is the key determinant of regeneration?
Inducing resting cells to enter cell cycle
What is cell proliferation controlled by
- Cell Cycle
- Chemical factors - Growth Stimulators/Factors (Eg. EGF), Growth Inhibitors
- Interactions of cells with ECM
What are the functions of growth factors?
- Cell Survival
- Cell Locomotion
- Cell Contractility
- Cell Differentiation
- Angiogenesis
Types of cells classified based on Proliferative Capacity
- Labile Cells (Constant State of Renewal/Division) - Epidermis, Epithelium of GIT, Bone Marrow
- Stabile Cells (Potential to replicate when necessary with an appropriate stimulus) - Liver, Renal Tubules
- Permanent Cells (Do not replicate) - Neuronal Cells, Heart Muscle Cells
What are the key components of Repair by Connective Tissue and Fibrosis
- Phagocytosis of necrotic debris and other foreign material
- Angiogenesis
- Migration and Proliferation of Fibroblasts
- Deposition of Extracellular Matrix (ECM) and collagen to confer mechanical strength
- Remodelling - maturation and organisation of fibrous tissue to consist of almost entirely dense collagen
What is the process of Angiogenesis?
- Degradation of the basement membrane of parent vessel to allow for formation of a capillary sprout
- Migration of endothelial cells towards angiogenic stimulus
- Proliferation of endothelial cells
- Maturation of endothelial cells - lumen formation
- Recruitment of periendothelial cells for support and maintenance
Where does Fibrosis occur
Within the granulation tissue framework of new blood vessels and loose ECM that initially forms at repair site.
What is the result of Fibrosis
Synthesis of Collagen and Fibronectin to develop strength in healing wounds
What is Tissue Remodelling?
It is the replacement of granulation tissue with a scar. It mainly involves changes in the composition of ECM.
What is the timeline of repair by connective tissue/fibrosis?
- Inflammation - clot formation and chemotaxis
- Proliferation - Re-epithelialisation, Granulation tissue, Early matrix
- Maturation - Collagen matrix, Wound contraction
- Remodelling - Collagen Accumulation
What are the types of wound healing
- Primary Healing by first intention - wounds with opposed edges (clean surgical wounds)
- Secondary Healing by second intention - wounds with separated edges (large tissue defect, more extensive loss of cells and tissues)
What is the process of first intention wound healing?
Day 1:
Neutrophils appear towards clot
Epidermis at edges proliferate and thickens
Day 3:
Granulation Tissue formation
Continuous but thin epithelium, gradually thickens
Day 5:
Angiogenesis maximal
Formation of collagen to bridge the incision
Epidermis recovers normal thickness
Week 2:
Accumulation of collagen and proliferation of fibroblasts
Beginning of scar formation
Month 1: Scar tissue (increases tensile strength)
What are the differences between secondary and primary wound healing?
Primary Intention Healing: Closed skin edges Minimal Granulation Tissue Early Suturing Minimal Scarring Minimal Tissue Loss Rapid Healing Minimal risk of infection No scar contraction Complete Re-epithelialisation
Secondary healing: Open skin edges Larger defect - more necrotic and fibrin debris - stronger inflammatory reaction Larger amounts of granulation tissue formed Wound contraction (larger surface wounds) No suturing Extensive scarring Extensive tissue loss Delayed healing Extensive risk of infection Scar Contraction Incomplete Re-epithelialisation
Types of wounds which undergo primary healing
Wounds closed by sutures (stitches), staples, or adhesive tape (eg. well-repaired lacerations, well reduced bone fractures, healing after flap surgery)
Types of wounds which undergo secondary healing
Wounds which are allowed to granulate, and hence may result in a broader scar. The surgeon may pack the wound with a gauze or use a drainage system. (Eg. Gingivectomy, gingivoplasty, tooth extraction sockets, poorly reduced fractures)
Why must secondary wounds be cared for daily?
To encourage wound debris removal to allow for granulation tissue formation.
When does Resolution occur?
When there is little tissue destruction
What determines whether Regeneration occurs?
- Whether cells are able to regenerate
- Tissue Architecture (simple structures are easler to reconstruct than complex ones)
- Amount of Tissue Loss (large loss of area of tissue will heal by scar formation instead)
What are Growth Factors?
They function as ligands that bind to specific receptors to deliver signals to target cells. This stimulates transcription of genes that may be silent in resting cells (Control cell cycle entry and progression)
List s Growth Factors
- Epidermal Growth Factor (EGF)
- Transforming Growth Factor-a (TGF-a)
- Hepatocyte Growth Factor (HGF)
- Vascular Endothelial Growth Factor (VEGF)
- Platelet Driven Growth Factor (PDGF)
- Fibroblast Growth Factor 2 and 2 (FGF-1,2)
- Transforming Growth Factor-b (TGF-b)
List 9 Factors that affect Wound Healing
- Bacterial Infection (Decrease O2 content, Collagen Lysis, Prolonged Inflammation)
- Devitalised Tissue and Foreign Body (Retards Granulation Tissue formation and healing)
- Cytotoxic Drugs - 5FU, MTX, Cyclosporine, FK-506
- Chemotherapy
- Radiation (Collagen synthesis abnormal, fibrosis of vessel)
- Diabetes (Impedes the early phase of response)
- Malnourishment - Low albumin (less than 3) and Vit C count
- Smoking (Vasoconstriction, Atherosclerosis, Decreased oxygen delivery)
- Steroids (inhibits macrophages, PMNs, fibroblast collagen synthesis, cytokines, and decreased wound tensile strength)
What diseases are associated with Abnormal Wound Healing? Name 6
- Osteogenesis Imperfecta (Type I collagen defect)
- Ehler-Danlos Syndrome (Collagen Disorder)
- Marfan Syndrome (Fibrillin Defect - collagen)
- Epidermolysis Bullosa (excessive fibroblasts, treatment with phenytoin)
- Scurvy - Vit C deficiency (required for proline hydroxylation)
- Cancer (Cachexia, Anorexia, Altered host metabolism, Protein catabolism, Abnormal inflammatory cell response, Impaired healing - decreased chemotaxis and phagocyte function, risk of infection)
