Healing and Repair Flashcards
1
Q
What are the outcomes of injury
A
- Tissue Injury
- Apoptosis (no inflammation) or Necrosis (acute inflammation)
- Healing (removal of injured tissue / noxious agent, regeneration and repair)
- Chronic Inflammation (failure to remove injured tissue / noxious agent)
2
Q
What is wound healing
A
- Wound: Circumscribed injury caused by external force, possibility to occur in all tissue types (skin, eyes, bone and organs)
- Healing: Body’s response to injury, attempt to restore normal structure and function, replacement of damaged tissue by new healthy tissue, highly organised / predictable
3
Q
What is regeneration of tissues dependent on
A
- Proliferation capacity of tissues
- Driven by growth factors
- Integrity of extracellular matrix
- Presence of stem cells differentiating to mature cells
4
Q
List classifications of cells based on replication potential
A
- Labile tissues
- Stable / quiescent tissues
- Permanent tissues
5
Q
What are labile tissues
A
- Cells are continuously lost and replaced
- Replacement by stem cells and proliferation of mature cells
- Cells remain in cell cycle, can proliferate rapidly after injury if stem cells are preserved
- Example: Basal layer of epidermis, haematopoietic stem cells
6
Q
What are stable / quiescent tissues
A
- Minimal replicative activity in normal state
- 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
- Example: Parenchymal cells (renal tubule epithelium) and mesenchymal cells (fibroblasts)
7
Q
What are permanent tissues
A
- Terminally differentiated post-mitotic cells
- Cannot re-enter the cell cycle (non-proliferative)
- “No” capacity to divide, replaced by scar tissue
- Exit cell cycle before G1 and are unable to re-enter
- Example: Cardiac myocyte’s, skeletal muscle, neurons
8
Q
Why is regeneration in healing important
A
- Growth (proliferation) and differentiation of new cells
- Replacement of damage or dead cells by cells identical to ones lost
- Complete restoration of original tissue with restoration of normal function
- Proliferation of parenchymal tissues and replacement of cells by surrounding specialised cells
- Labile and stable / quiescent tissues
9
Q
Why is repair in healing important
A
- 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, begins within 24h of injury
- Proliferation of connective tissue and replacement of lost tissue by granulation tissue (scar tissue)
- Permanent tissue
10
Q
What mechanisms are involved in repair and regeneration in healing
A
- Monocyte chemotaxis (chemokine, TNF, PDGF, FGF)
- Fibroblast migration / replication (PDGF, EGF, TNF, IL-1, FGF)
- Angiogenesis (VEGF, angio-proteins, EGF)
- Collagen synthesis (TNF-beta, PDGF)
- Collagenase secretion (PDGF, FGF, TNF)
11
Q
What is the function of skin and the layers
A
- Functions: Protection, thermoregulation, sensation and metabolic functions
- Layers: Epidermis, dermis and hypodermis
12
Q
What is the epidermis
A
- Stratified squamous epithelium
- Basal layer contains keratinocytes / melanocytes
- Basal cells divide and move up through layers (change appearance / differentiate)
- Barrier and protection against foreign bodies and substances, retains moisture
13
Q
What is the dermis
A
- Connective tissue, many fibroblasts (production and maintenance of structural elements of skin)
- Thin (hair, sweat / sebaceous glands) and thick (none of above)
- Papillary Layer: Loose connective, BV, nerves, sensory receptors
- Reticular Layer: Dense, irregular collagenous connective
14
Q
What is the hypodermis
A
- Adipose connective tissue
- Large blood vessels
- Fibroblasts (synthesise collagen and elastin)
15
Q
What is keratin
A
- Keratinocytes: Rapidly deciding stem cells
- Keratinised Squamous Epithelium: Water in cell cytoplasm mainly replaced by keratin, outer layer contains dead cells, epidermis of the skin
16
Q
List the phases of wound healing
A
- Haemostasis / Coagulation
- Inflammation
- Proliferation or Granulation
- Maturation or Remodelling
17
Q
What is haemostasis and coagulation
A
- Vessel rupture and bleeding
- Vascular response (5-10min)
- Platelets aggregate
- Growth factors, hormone and cytokine release
- Vasoconstriction occurs to limit blood loss
- Platelet degranulation and release of cytokines and growth factors
- Fibrin formation and coagulation
- GFs increase size / number of cells, inhibit apoptosis, initiate proliferation, migration and differentiation
18
Q
What are the 3 types of inflammation
A
- Early: Commences 2-3h and peaks at 2-3 days, edema, neutrophil infiltration and degradation of necrotic cells, complement activation, cytokine repair
- Late: Monocyte infiltration, differentiation of monocytes into macrophages, lymphocyte infiltration and cytokine repair
- Chronic: Uncontrolled, pathological
19
Q
What is proliferation / granulation
A
- Proliferation: 3-5 days following injury, overlaps with inflammatory phase
- Granulation: Inflammatory cells, fibroblasts and keratinocytes, neo-vasculature, collagen, proteoglycans
- Scar Formation: Epithelialisation, fibroplasia, angiogenesis and wound contraction
20
Q
What are the steps involved in scar formation (proliferation / granulation)
A
- Epithelialisation: Migration, formation of epithelium, basal cell proliferation, seal between wound / environment
- Fibroplasia: Migration of fibroblasts, attach fibrin matrix, deposit collagen, elastin, fibronectin
- Angiogenesis: Formation of BV, increased perfusion of healing factors, scar formation and resorption
- Wound Contraction: Day 5-15, centripetal movement of wound edges, concurrent with collagen synthesis
21
Q
What is maturation / remodelling
A
- 5-7 days after injury
- Remodelling of ECM
- Fibroblasts initiate collagen lysis
- Increasingly organised collagen
- Restoration of tensile strength of injured skin
- Vascular maturation and progressive vascular regression
22
Q
What are factors that affect wound healing
A
- Type, location and extend of injury
- Infection
- Nutrition
- Steroids
- Mechanical Factors
- Poor blood supply (ischaemia)
- Movement
- Exposure to UV light facilitates healing
- Foreign bodies
- Ionising radiation / chemo
- Uncontrolled Diabetes
- Age
23
Q
What is cutaneous wound healing and types of repair
A
- Cutaneous: Relating to, or affecting the skin
- Types of Repair: Primary and secondary intention
24
Q
What is healing by first intention
A
- Clean and uninfected
- Surgically incised (wounds with opposed edges)
- Without much loss of cells and tissues
- Epithelial regeneration is principal mechanism of repair
- Edges of wound are approximated by surgical sutures
- Disruption of epithelial basal membrane
- Complications infrequent
- Results in a linear / hairline scar
25
Q
What is healing by second intention
A
- Separated irregular edges
- Open with large tissue defect
- At times infected
- Inflammatory reaction more intense
- Complications frequent
- Fibrosis, larger area of granulation tissue
- Wound contraction mediated by action of myo-fibroblasts
- Melanocytes do not migrate into healing wounds leading to hypo-pigmentation
26
Q
How does healing of a laceration occur
A
- Laceration: Deep cut / tear of skin, initial haemorrhage
- Signs: Damaged cells, plasma in wound, neutrophils, increase BV / capillary permeability
Healing: - Clot and scab form
- Macrophages clean up debris
- New capillaries formed
- Fibroblasts deposit new material to replace the old
- Neutrophils replace macrophages
- Epithelial cells grow and scab falls off
- Remodelling phase
27
Q
What are aberrations of healing
A
- Keloids: Healing with excessive fibrosis, excess granulation/excess collagen, grow beyond borders of original wound, don’t resolve spontaneously, genetic
- Hypertrophic Scarring: Accumulation of excess collagen, decreased lysis, scars stay within limit of original wound, tend to regress spontaneously, generally seen soon after tissue injury
28
Q
How do different tissues heal
A
- Mucosal: Good regeneration, lost and replaced continuously, some bacteria delay wound healing and some are beneficial
- Nervous: Nerve cells not replaced in CNS, scar tissue can slow nerve conduction
- Solid Organs: Tissue replaced by fibrous scar
