Wound healing & tissue repair Flashcards
Fibrosis is defined as
The extensive deposition of collagen in a scar
Scar formation is defined as
Activated fibroblasts expressing type I collagen in an area of damaged extracellular matrix
Labile tissue
Cells that are continuously lost a regenerated (skin, hemopoietic cells, GI/uterus/ epi,)
Stable tissues
Cells are quiescent (meaning they can go in/out of G0) They only proliferate in response to injury or loss of tissue mass
(Liver, pancreas, endothelial, fibroblasts)
Permanent tissue
Never divides/regenerates
Heart, skeletal muscle, neurons
Which cytokine is made by the kupffer cells and acts on hepatocytes to make liver parenchyma receptive to growth factor signals in order to regenerate?
IL-6
Which growth factors act on primed hepatocytes to stimulate cell metabolism and proliferation?
EGF -> EGFR
HGF -> C-MET
What cytokine helps hepatocytes return to the quiescence stage of the cell cycle?
TGF-B
Cutaneous wound healing:
First intention
Wound is clean & uninfected, wound edges are approximated by sutures and it will heal by primary union/first intention.
Thin scar
Cutaneous wound healing:
Second intention
Larger wounds that cause extensive loss of cells/tissue & contaminated wounds where the edges can’t be approximated.
Healing involves:
- granulation tissue
- extensive collagen deposition
Causing a big scar or contracture
Cutaneous wound healing:
Third intention/Delayed primary intention
Leave wound to clear infection then close, usually slow filling of a wound cavity or ulcer by granulation tissue
Repair by connective tissue deposition:
- Inflammation
- Angiogenesis
- Migration & proliferation of fibroblasts
- Scar formation
- Connective tissue remodeling
What factor mediated the formation of blood clots?
VEGF causes increased vessel permeability + edema, air hits the external surface of the clot hardening it into a scab (RBCs, fibrin, fibronectin, & compliment proteins)
Angiogenesis is described as
The formation of new blood vessels which support the repair process, its mediated by VEGF
Angiogenesis from preexisting vessels:
What does FGF-2 promote
Endothelial cell proliferation &
Macrophages, fibroblasts, & epithelial cells to cover the damaged epidermis
Angiogenesis from preexisting vessels:
What do PDGF & TCF-B factors help mediate
They both help in wound stabilization:
PDGF (recruits smooth muscle cells)
TGF-B (suppresses endothelial proliferation/migration & enhances ECM proteins)
Formation of granulation tissue:
Granulation tissue is formed by
Proliferation of fibroblasts, angiogenesis, a loose ECM, inflammatory cells, and macrophages
Fibroblasts & endothelial cells start proliferating 24-72 hrs to form granulation tissue and usually resolve in 5-7 days
Deposition of connective tissue steps: 1
Migration and proliferation of fibroblasts in the injury
Deposition of connective tissue steps: 2
Deposition of ECM proteins made by fibroblasts with growth factors PDGF, FGF-2, & TGF-B
Deposition of connective tissue:
TGF-B stimulates what?
- Fibroblast migration & proliferation
- More synthesis of collagen and fibronectin
- Inhibits metalloproteinases causing less degradation of ECM
Deposition of connective tissue:
What are the main rolls of fibroblasts?
- They induce the migration & proliferation of keratinocytes (FGF-7)
- & They induce deposition of type 3 collagen
Deposition of connective tissue:
Myofibroblasts
In larger wounds myofibroblasts express smooth muscle cells, alpha actin, and vimentin. They help contraction of the scar tissue
Remodeling connective tissue:
Roles of
Vitamin C
Copper
Zinc
Vitamin C (cross-linking collagen bundles by hydroxylation)
Copper ( a co-factor for lysyl oxidase to cross link hydroxyl groups)
Zinc (a co-factor along with MMP to modulate conversion of type 3 collagen to type 1) note defect here can lead to keloids
Deposition of connective tissue:
Excessive collagen deposition is inhibited by
TIMP’s Tissue Inhibitor Metalloproteases
Dehiscence/rupture of a wound is most likely in which procedure?
Abdominal surgery because the increase in abdominal pressure
Ulceration of wounds can occur because of what?
Inadequate vascularization during healing
ex. Patients with atherosclerotic peripheral vascular disease with lesions in the lower extremities tend to ulcerate.
Hypertrophic scarring is described as
Excessive deposition of parallel collagen that doesn’t cross over the original boundaries of the wound, this typically happens with more traumatic injuries impacting the deep layers of the dermis
Keloids are described as
Excessive deposition of disorganized collagen that extends past the boundaries of the original wound and it doesn’t regress.
Note its because of genetic predisposition that’s usually seen in African American patients
Exuberant granulation is described as
The formation of excessive granulation tissue which protrudes above the surrounding skin and blocks re-epithelialization
Contractures are described as
An exaggeration of the normal healing process that causes deformities in the wound and surrounding tissue
Tend to happen in the palms, soles, and ant aspect of the thorax after serious burns
Note they can’t reduce joint movement
