Healing and Repair Flashcards
Describe wound healing
Wound: Circumscribed injury caused by external force
- May occur in every type of tissue: e.g. skin, eyes, bones, organs
- Largest organ in the body is the skin
- Skin wound = break in integrity of skin
Healing: Body’s response to injury
- Attempt to restore normal structure and function
- Replacement of damaged tissue by new healthy tissue
- Involves two distinct processes; Regeneration
and Repair
Can take place simultaneously, depends on:
1.Can remaining cells divide?
2.Is there connective tissue stroma remaining?
Wound Healing: Regeneration and Repair:
- Proliferation capacity of tissues
- Driven by growth factors
- Integrity of extracellular matrix
- Stem cells -> mature cells
- Three groups:
1. Labile tissues
2. Stable tissues
3. Permanent tissues
- Classification of cells by replication potential
What is regeneration in regards to wound healing?
- Growth (proliferation) and differentiation of new cells
- Replacement of damage or dead cells by cells identical to the ones lost
- Complete restoration of original tissue with restauration of normal function
- Labile tissues can readily regenerate e.g. skin injuries - Stable tissues have limited capacity to regenerate – exception: liver
What is repair in regards to wound healing?
- Healing outcome in which tissues do not return to their normal architecture and function
- Replacement of damaged cell with scar tissue (connective tissue)
- Helps to hold organ together – function not restored
- Involves granulation tissue formation and contraction of the wound
- Permanent tissue injury results in scar
- Begins within 24h of injury - E.g. scarring of lung tissue in TB, healing of skin cuts
What are the classes of cells based on their replication potential (proliferation capacity)?
- Labile Tissues
- Stable Tissues (Quiescent Tissues)
- Permanent Tissues
Describe labile tissues and give examples
- Cells are continuously lost and replaced
- Replacement by stem cells & proliferation of mature cells
- Cells remain in the cell cycle
- E.g. Basal layer of the epidermis, haemopoietic stem cells (Can proliferate rapidly after injury as long as pool of stem cells is preserved)
Describe stable tissues and give examples
- Quiescent = only minimal replicative activity in normal state
- Can mitotically divide when stimulated
- Fully differentiated cells leave cell cycle at Go
- Proliferating stable cells divide symmetrically
(Both daughter cells are differentiated)
- Long lived cells, slow turn-over - Parenchymal cells of solid organs: e.g. renal tubule epithelium
- Mesenchymal cells: e.g. fibroblasts
Describe permanent tissues and give examples
- Terminally differentiated post-mitotic cells
- Cannot re-enter the cell cycle = non-proliferative (“No” capacity to divide )
- e.g. cardiac myocytes, skeletal muscle, neurons
- Injured permanent cells are replaced by scar tissue
- When damaged – healing by repair
What are examples of mechanisms involved in regeneration and repair?
Growth factors and cell to cell interactions are involved:
- Monocyte chemotaxis: chemokine, TNF, PDGF, FGF
- Fibroblast migration/replication: PDGF, EGF, TNF, IL-1, FGF
- Angiogenesis: VEGF, angioproteins, EGF
- Collagen synthesis: TNF-beta, PDGF
- Collagenase secretion: PDGF, FGF, TNF
What are the three layer of human skin and their functions?
Epidermis
- Barrier
- Protection against foreign bodies and substances
- Retains moisture
Dermis:
- Thermoregulation
- Sensation
Hypodermis:
- Metabolic Functions
Describe the epidermis with a focus on histology
Tissue: Stratified squamous epithelium
Basal layer contains keratinocytes and and melanocytes
Cells divide in the basal layer (Keratinocytes = rapidly dividing stem cells), and move up through the layers above
- changing appearance & differentiating
Keratin
What are the two types of squamous epithelium?
Keratinized Squamous Epithelium:
- Water in cell cytoplasm mainly replaced by keratin
- Outer layer contains dead cells
- Epidermis of the skin
Non-Keratinized Squamous Epithelium:
- Surfaces have to be kept moist
- Has living squamous cells at the surface
- Mechanical barrier that has selective permeability
- e.g. mucosa of oral cavity, esophagus, cornea
Describe the dermis with a focus on histology
Primary tissue type: Connective tissue
Thin skin: Contains hair follicles, sweat glands, sebaceous glands, blood and lymphatic vessels, sensory receptors and nerves
Thick skin:
- Does not contain hairs, sebaceous glands
- Hasthinner dermis than thin skin
- Fingertips, palms of hands and soles of feet
Many fibroblasts -> production and maintenance of structural elements of skin
Papillary layer:
- loose connective tissue
- contains most blood vessels, nerves, and sensory receptors
Reticular layer:
- dense, irregular collagenous connective tissue
Describe the hypodermis with a focus on histology
- Primary tissue type: Connective tissue
- Main tissue: adipose tissue
- Contains large blood vessels
- Contains fibroblasts -> synthesise collagen and elastin
What are the phases of wound healing?
- Homeostasis/Coagulation
- Inflammation
- Granulation and Proliferation
- Maturation and Remodelling
Describe the Homeostasis/Coagulation phase in wound healing?
Vessel rupture -> bleeding
Vascular response: after 5-10 min:
- Platelets aggregate, growth factor, hormone and cytokine release
- Vasoconstriction occurs to limit blood loss
Platelet degranulation: Release of cytokines and growth factors
Fibrin formation
Coagulation
Describe growth factors in wound healing
- Growth factors are endogenous signaling molecules that regulate cellular responses for the wound healing process
- Upregulated in response to tissue damage -> secreted by platelets, leukocytes, fibroblasts, and epithelial cells
- Binding to membrane or cytoplasmic receptors results in a cascade of events that activate the cellular machinery to facilitate wound healing, Increase size of cells, increase number of cells, inhibit apoptosis
Describe the Maturation and Remodelling phase in wound healing?
Day 5-7 after injury up to months/years
Remodelling of extracellular matrix composition over time
- Fibroblasts synthesise collagen
- Lysis by collagenase enzyme and metalloproteinases
Result:
- Collagen becomes increasingly organised
- Restoration of the tensile strength of injured skin
Vascular maturation and progressive vascular regression
- transforms vascularised granulation tissue into pale, largely avascular scar
Describe the Epithelialisation (migration) phase of scar formation
- formation of epithelium over a denuded surface
- basal cell proliferation and epithelial migration
- Migration of cells at wound edges over a distance of < 1 mm - Epithelial layer provides seal between the underlying wound and the environment
Describe the Fibroplasia phase of scar formation
Migration of fibroblasts into site of injury
Fibroblasts attach to fibrin matrix of clot and multiply
Fibroblasts produce and deposit collagen, elastin, fibronectin, glycosaminoglycans, proteases etc.
- Synthesis of extracellular matrix protein
(Wound begins to contract
)
Collagen synthesis during fibroplasia
Describe the Angiogenesis (and neovascularisation) phase of scar formation
- Formation of new blood vessels from existing vessels
- Rich blood supply is vital to sustain newly formed tissue (increased perfusion of healing factors)
- Scar formation and resorption
What are the types of cutaneous wound repair?
Cutaneous = relating to, or affecting the skin
Two clinically significant types of repair:
1. By Primary Intention (healing by primary union)
2. By Secondary Intention (healing by secondary union)
Describe healing by second intention?
Defined as wound with following characteristics:
- Separated irregular edges
- Open with large tissue defect
- At times infected
- Inflammatory reaction more intense
- Healing takes longer, complications frequent
- Fibrosis, larger area of granulation tissue
- Wound contraction mediated by action of myofibroblasts
- Melanocytes do not migrate into healing wounds ->hypopigmentation
Compare healing by primary vs secondary intention
Describe the process of wound healing of a laceration
- Laceration = deep cut or tear in skin or flesh
- Is an example of healing by primary intention
- Initial hemorrhage
- Damaged cells and mast cells leak histamine
(Dilated blood vessels, Increased blood flow)
- Increased capillary permeability - Plasma seeps into wound
- Neutrophils seen within 24h of incision
- Clot forms
- Scab forms on surface
- Neutrophils in tissue mainly replaced by macrophages
- Macrophages start to clean up dead cells and debris
- New capillaries grow into wound
- Fibroblasts deposit new collage to replace old material
- Fibroblastic phase begins day 3-4 and lasts up to 2 weeks
- Surface epithelial cells multiply and spread beneath scab
- Scab falls off
- Epithelium grows thicker
- Connective tissue forms only scar tissue
- Remmodelling phase
Describe hypertrophic scarring
- Accumulation of excess collagen with decreased lysis
- Scars stay within the limit of the original wound
- Tend to regress spontaneously
- Generally seen soon after tissue injury
Describe keloid scarring
- Keloid = healing with excessive fibrosis
- Excess granulation/excess collagen - Grow beyond the borders of the original wound
- Do not tend to resolve spontaneously - Genetic component
