L4 Healing and Repair Flashcards
In addition to adaptation and death, what is another possible outcome of cell injury?
Repair (healing)
When is the repair of injured cells initiated?
When inflammation begins
What are the two forms of healing/repair?
- Regeneration
2. Scar formation
What is regeneration?
The replacement of damaged cells by replicating cells of the same type
What is scar formation?
Replacement of damaged cells by connective tissue
True or false - regeneration and scar formation are mutually exclusive.
False - they may occur simultaneously
In regeneration, the ___ of the tissue remains intact.
Extracellular matrix
What are the three cell types with respect to division capacity?
- Labile (always regenerating)
- Stable (regenerate when stimulated)
- Permanent (cannot regenerate)
What is the extracellular matrix?
A network of interstitial proteins that comprises a significant portion of most tissues
What are the 4 major functions of the ECM?
- Mechanical support
- Control of cell proliferation via growth factors
- Scaffold for regeneration
- Boundary between epithelium and underlying connective tissue
What are the two forms of ECM?
- Interstitial matrix
2. Basement membrane
What are the 3 major components of the ECM?
- Fibrous structural proteins (collagen and elastin)
- Water hydrated gels (proteoglycans and hyaluronan)
- Adhesive glycoproteins
___ attach the epithelium to the basement membrane.
Integrins
What are some examples of labile tissues?
- HSC of bone marrow
- Squamous epithelium of skin, oral cavity, cervix, vagina
- Columnar epithelium of GI tract
What is the classic example of stable tissue (and a few others)?
- Liver
- Kidney, pancreas
- Smooth muscle cells, fibroblasts, endothelial cells
___ cells line the blood vessel walls.
Endothelial
What are three examples of permanent tissue?
- Neurons (brain)
- Myocytes (heart)
- Skeletal muscle (mostly)
Regeneration depends on what two major factors?
- Growth factors
2. Integrity of ECM
What is another major source of growth factors in addition to the ECM?
Macrophages
What are the two main reasons scars form?
- Injured tissues are incapable of regeneration
2. ECM severely damaged/stem cells lost
What are the two major components of connective tissue?
- Dense bands of collagen
2. Fibroblasts
What are the pros and cons of scar formation?
Pro: scar usually provides enough structural stability for injured tissue to continue to function
Con: connective tissue cannot perform function of lost parenchymal cells
What are the 4 steps in scar formation?
- Tissue injury
- Inflammation (macrophages)
- Formation of granulation tissue
- Scar formation (remodeling)
What is angiogenesis?
New blood vessel development from existing vessels
What are pericytes?
Cells with contractile properties
Angiogenesis is often seen in what three situations?
- Healing
- Development of collaterals at sites of ischemia
- Tumor growth
What is an important mediator of angiogenesis?
VEGF (vascular endothelial growth factor)
What is an important inducer of VEGF?
Hypoxia
___ synthesize connective tissue proteins. Recruitment and activation of this cell is driven by what three growth factors?
Fibroblasts
PDGF, FGF, TGF-beta
What is specialized tissue that fills in defects in organs when non-regenerative cells and/or connective tissue framework is destroyed?
Granulation tissue
What are the components of granulation tissue?
Proliferating fibroblasts laying down type III collagen (immature connective tissue) and proliferating new blood vessels
What is the process of transforming granulation tissue into a scar? What type of connective tissue is seen here?
Remodeling; type I collagen
What type of stain makes mature collagen blue?
Trichrome stain
What do myofibroblasts do?
Contract the wound
What is involved in healing by first intention?
- Clean, uninfected surgical incision approximated by sutures
- Epithelial regeneration principle mechanism of repair
- Small scar
- Minimal contraction of wound
What is involved in healing by second intention?
- Large skin wound, extensive destruction, edges not approximated
- Large clot, more intense inflammation
- Wound granulates in without closing gap with sutures
- Healing process is the same but takes longer
- Wound contraction by myofibroblasts
What are some factors which impair repair?
- Infection
- Nutrition deficiencies
- Glucocorticoids
- Poor perfusion
- Diabetes mellitus
- Foreign bodies
- Type of tissue
- Extent of injury
- Location of injury
What three nutritional components are important in wound healing?
- Vitamin C
- Zinc
- Copper
What is the function of Vitamin C in wound healing?
Cofactor for hydroxylation reactions (cross-linking of lysine and proline in collagen synthesis)
What is the function of zinc in wound healing?
Cofactor for metalloenzymes (collagenase)
What is the function of copper in wound healing?
Cofactor for lysyl oxidase (cross links lysine and hydroxylysine)
What is an accumulation of an exuberant amount of collagen that presents with raised scars and grow beyond the wound boundaries?
Keloid
What is a hypertrophic scar?
Excess production of scar tissue localized to the wound
What is excessive deposition of collagen and other ECM components in a tissue/organ?
Fibrosis
What is contracture?
Excessive myofibroblast activity in a wound causing constriction of the skin
What is dehiscence?
Opening of a healing or partially healed wound with separation of its edge
