Wound Healing Flashcards
Embryonic Stem Cells
Pluripotent; isolated from blastocysts
PDGF, FGF, VEGF-A bind GF-R’s on endothelial cells to induce vascular formation by
Endothelial proliferation
Recruitment of pericytes
Deposition of ECM proteins
What occurs during the hemostasis phase of wound healing
Vasospasm → relaxation
Platelets aggregate to expose collagen and a network of fibrin forms
Repair
Replacement of injured tissue
Describe the arrangement of blood vessels in granulation tissue
Arranged perpendicular to fibrosis
Growth factors and cytokines involved in angiogenesis
VEGF, angiopoietin, FGF
Permanent Cell - Non-Dividing Cell
Have left the cell cycle and cannot undergo mitotic division in postnatal life
_________________________
Neurons, Cardiac and Skeletal Muscle
Mechanism of wound healing by primary intention
- Simple Incision
- Sutured incision with acute inflammatory response (2-7 days)
- Redness and swelling
- Zone of acute inflammation; formulation of granulation tissue
- Healing Incison
- Epithelial proliferation and repair
- Maturing fibrous granulation tissue
- Linear fibrous scar (6-12 months)
Mechanism of wound healing by second intention
- Ragged, dirty or infected wound (2-3 days)
- Necrotic slough
- Acute inflammation
- Phase of rapid proliferation of vascular granulation tissue (1-2 weeks)
- Slough and scab
- Epithelial proliferation
- Vascular granulation tissue
- Zone of hyperemia
- Phase of granulation tissue maturation and wound contraction (3-6 weeks)
- Fibrous granulation tissue beginning to contract, pull wound edges closer
- Hyperemia
- Healed wound
- Pale depressed scar with puckering
The proliferation phase of wound healing occurs when? And can last for how long?
3-7 days
3-4 weeks
Quiescent - Stable Cells
Low level of replication; undergo rapid division in response to stimuli. Capable of reconstructing the tissue of orgin
_________________________
Smooth muscle, fibrocytes, vascular endothelial cells, chondrocytes, osteocytes
Collagen
Triple helices with lots of cross linkage providing tensile strength
Characteristics of epithelialization
Proliferate at denuded surfaces
Must disassemble connections to basement membrane and neighboring cells
Must express surface receptors that bind ECM
Regulated by contact inhibition
Tissues ability to return to normal depends on
Retention of ECM structural framework
Regenerative capacity of cells
Myofibroblasts
Form within wounds in response to TGF-beta
Increase with time and severity
Proud Flesh
Hypertrophic scar - excessive granulation tissue
T/F- Capillaries in granulation tissue are sturdy.
False
________________
Capillaries are fragile and bleed easily
When does healing begin?
Immediately after a wound develops
Process of degradation during inflammation phase of wound healing
Leukocytes clean up cell debris from the injury
Wound
Injured tissue
Tensile strength is diminished in what type of wound healing?
Secondary intention
Growth factors and cytokines involved in collagenase secretion
PDGF
FGF
TNF
TGF-beta inhibits
Growth factors are required for cellular
Proliferation
Differentiation
Angiogenesis
Formation of new blood vessels from existing ones
T/F: Proliferation phase of wound healing increases with age and disease.
False
_____________________
decreases
Growth factors and Cytokines involved in fibroblast migration/ replication
PDGF
EGF
FGF
TGF-beta
TNF
IL-1
Fibroplasia
Migration and proliferation of fibroblasts
Extracellular Matrix consists of
Collagen
Elastin
Fibronectin
Laminin
What phase of wound healing is required for return of tensile strength
Maturation
TGF-Beta
Produced by platelets and leukocytes
Important for fibroblast migration and proliferation, and collagen/ECM protein synthesis
Epithelialization
Regeneration of epithelium
Fibrosis
Scar formation by connective tissue remodeling
Microscopically, what is found at the center of the wound during degradation
Dead cells
Leukocytes
Cytokines
Serum/clotting proteins
ECM substances
Conditions that may cause impaired wound healing
Tension on a tissue
Prolonged inflammation
Disorders in collagen synthesis
Poor blood supply
Impaired ability of cellular regeneration
Factors that favor fibrosis
Severe and prolonged tissue injury
Loss of tissue framework
Large amounts of exudate/inflammation
Lack of renewable cell populations
Wound contraction is mediated by
Myofibroblasts
Fibrous Connective Tissue
Dense accumulation of fibroblasts and collagen
With time, collagen becomes more densely packed
Persists for years
What occurs during the proliferation phase of wound healing?
Regeneration of tissue
Granulation tissue formation
Stem cells influced by cytokines/growth factors
Fibroblasts proliferate to fortify the wound → collagen deposition
Wounds that can be healed by second intention
Gaping wounds
Septic wounds
Foreign bodies
Wound with delayed healing processes
Granulation Tissue
Distinctive arrangement of connective tissue fibers, fibroblasts and blood vessels
What occurs during the inflammation phase of wound healing?
Cardinal signs seen
ECM components are chemotactic
Degradation
Leukocytes secrete chemotactic and growth factors → proliferation phase
Growth factors and cytokines involved in monocyte chemotaxis
Chemokines
TNF
PDGF
FGF
TGF-beta
Mechanism of angiogenesis
- Proteolysis of ECM
- Migration and chemotaxis
- Proliferation
- Lumen formation, maturation and inhibition of growth
- Increased permeability through gaps and transcytosis
Phases of cutaneous wound healing
Hemostasis
Inflammation
Proliferation
Maturation
Proliferation phase of wound healing is limited by
Proliferative potential of cell types involved
Consequences of fibrosis
Loss of functional parenchymal tissue
Alteration of physical properties of tissue
What occurs during the maturation phase of wound healing?
Remodeling of granulation tissue, maturation of fibrosis and wound contraction
Re-establishment of cell interactions
Vascular regression
Labile - Continuously Dividing Cells
Proliferate throughout life, replacing those cells that are destroyed
_____________________________
Epithelial cells of liver, kidney, lung, pancreas, skin, mucous membranes
T/F: If inflammation is excessive, it can reduce healing.
True
Wounds that can be healed by primary intention
Wounds with opposed edges
Role of extracellular matrix in regeneration and repair
Liver regeneration with restoration of normal tissue after injury requires intact cellular matrix
If matrix is damaged the injury is repaired by fibrous tissue deposition and scar formation
Wound Contraction
Normal part of maturation phase
Can be bad when connective tissue contracts and place tension on surrounding tissues
May immobilize or deform tissue
Growth factors and cytokines involved in collagen synthesis
TGF-beta
PDGF
What induces fibroblasts to synthesize collagen?
Growth factors
Important source for epithelial regeneration
Stem Cells
The inflammation phase of wound healing occurs in what time frame
24-96 hours
Growth factor mechanism
EGF binds receptors on epithelial cells → activates MAPK → induces G0 phase cell cycle
Growth factors and cytokines involved in keratinocyte replication
HB-EGF
FGF-7
HGF
Maturation phase of wound healing occurs when and can last for how long?
Begins 3-4 weeks after injury
Can last for years
Results of the hemostasis phase of wound healing
Reduced blood loss
Binds edges of wound together
Initiate angiogenesis - PDGF, TGF-Beta
Describe the arrangement of fibroblasts and connective tissue in granulation tissue
Grow parallel to the wound surface
Tissue Stem Cells
Not pluripotent - restricted lineage specific differentiation capacity
Bone marrow - hematopoietic and mesenchymal cells
Skeletal muscle “satellite cells”
Matrix Metalloproteinases
Important for degrading the ECM