Tissue Repair and Fibrosis (Drake) Flashcards Preview

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Flashcards in Tissue Repair and Fibrosis (Drake) Deck (18):
1

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

2


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)

3


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

4


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

 

5


What is granulation tissue?


Consists of macrophages, lots of fibroblasts, lots of new capillaries

6


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

7


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

8


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

9


Myofibroblasts


During remodeling they anchor to the matrix, contract themselves to pull collagen more tightly into place

10


Matrix metalloproteinases (MMPs)

Degrade extracellular matrix

In tissue repair, they degrade collagen

11

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

12


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

13


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

14


Systemic factors that impair healing


Malnutrition

Vitamin C deficiency

Diabetes mellitus

Corticosteroids (interfere with inflammation)

Infection

15


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

16


Fibrosis


Formation of excess fibrous connective tissue in organ or connective tissue

(excessive collagen deposition)

17


Fibrotic disorders

Cirrhosis

Pulmonary fibrosis

Scleroderma (autoimmune, excessive collagen deposition)

18


What skin layer is the wound healing/scar formation occurring it?


Dermis

(you look straight through the epidermis!)