Tissue Repair and Fibrosis (Drake) Flashcards
Functional steps of tissue repair
1) Form temporary barrier via fibrin clot (scab)
2) Remove dead tissue via inflammation
3) Restore parenchyma via fibroblast growth, blood vessel growth, connective tissue matrix generation
4) Restore epithelia via epithelial cell division
Three morphological steps/phases of tissue repair
1) Inflammation (to remove dead tissue/debris), hemostatic plug (clot underneath and scab on surface) formation (first 24 hours)
2) Granulation tissue formation: angiogenesis, fibroblast ingrowth (to replace fibrin), epithelial regeneration (3-7 days)
3) Remodeling and scar formation (weeks to months)
How does the hemostatic plug form?
1) Blood cells sense tissue that is not blood vessels and release thrombin
2) Thrombin cleaves fibrinogen, forming fibrin
3) Fibrin serves function of collagen and allows crosslinking to stabilize tissue
4) Thrombin acts directly to, and also acts on platelets to release PDGF, which recruits fibroblasts and makes them proliferate
What happens in the acute inflammatory response?
1) Increased vascular permeability so tPA and plasminogen enter tissue
2) Neutrophils then macrophages come in and eat up dead tissue and FIBRIN
3) tPA turns plasminogen into plasmin. Plasmin breaks down FIBRIN
What is granulation tissue?
Consists of macrophages, lots of fibroblasts, lots of new capillaries
Angiogenesis
Formation of new capillaries (aka neovascularization)
Cells sense hypoxia and HIF increases tx of VEGF, FGF, which cause blood vessel growth
One epithelial cell moves out, replicates, creates a lumen and ultimately a new blood vessel
Fibroblasts and collagen synthesis
Migrate, proliferate, and synthesize collagen matrix after fibrin has been degraded
Migrate there via PDGF, EGF, FGF, TGFb, TNF, IL-1
Proliferate via PDGF, EFG, FGF, TNF
Synthesize collagen via TGFb, PDGF
During remodeling (third phase of tissue repair), what type of collagen do you have?
Initially have Type III collagen, then is replaced with Type I collagen
Myofibroblasts
During remodeling they anchor to the matrix, contract themselves to pull collagen more tightly into place
Matrix metalloproteinases (MMPs)
Degrade extracellular matrix
In tissue repair, they degrade collagen
Rough timetable of wound healing
Day 1: Hemostasis and inflammation begins; epithelial cells at margins begin migrating in
Day 2: Macrophages initiate fibrin removal
Day 3: Granulation tissue begins to form (angiogenesis and fibroblasts migrate in)
Day 5: Surface epithelium reaches normal thickness
Day 10: Fibroblasts proliferate and deposit collagen
Day 15: Vascularity starts to decrease
3 months: Vascularity reduced, tensile strength maximal 80% of normal skin
What types of cells can regenerate and what types cannot?
Can: Labile cells, continuously cycline
Can: Stable cells, in G0
Cannot: Permanent cells, are nondividing
Local factors that impair healing
1) Extent of injury
2) Non-apposition (can’t bring edges of skin together)
3) Poor stabilization
4) Poor vascularity
5) Infection
6) Foreign bodies
7) Radiation
Systemic factors that impair healing
Malnutrition
Vitamin C deficiency
Diabetes mellitus
Corticosteroids (interfere with inflammation)
Infection
Undesirable consequences of wound healing
Contractures: large scale scars that bridge a joint and restrict motion
Adhesions: scarring on serosal surfaces that causes two surfaces to fuse
Strictures: scarring inside a tubular structure that narrows its lumen (contraction of scar tissue)
Keloid: scars that don’t shrink and contract enough so appear excessively protuberant/large
