Healing/repair Flashcards
Irreversible injury to the myocardial fibers will have occurred when which of the following cellular changes occurs? A. Blebs on cell membranes B. Cytoplasmic sodium increases C. Glycogen stores are depleted D. Intracellular pH diminishes E. Nuclei undergo karyorrhexis
E. Nuclei undergo karyorrhexis - all the other processes are part of the injury process, but they are all reversible. When the nucleus disintegrates (karyorrhexis), it is beyond repair.
Possible outcomes of injured cells
Adaptation
Repair
Death
When does repair of injured cells begin?
Initiated when inflammation begins
What are the two parts of the healing process?
- Regeneration (replacement of damaged cells by replicating cells of the same type)
- Scar formation (replacement by connective tissue)
Both occur simultaneously
When can regeneration occur?
Connective tissue framework of tissue remains intact and cells must have capacity to divide
Two forms of interstitial protein network in the extracellular matrix
Interstitial matrix and basement membrane
Protein composition in the extracellular matrix
- Fibrous structural proteins (Collagens, elastins)
- Water hydrated gels (proteoglycans, hyaluronan)
- Adhesive glycoproteins
Define labile tissues
Continuously dividing cells that can be replaced by maturation from stem cells or proliferation of mature cells
Examples of labile tissues
- Hematopoietic cells of bone marrow
- Squamous epithelium of skin, oral cavity, cervix, vagina
- Columnar epithelium of GI tract
Define stable tissues
Low/no level of replication; locked in G0 of the cell cycle. However, they can rapidly divide upon stimulation.
Examples of stable tissues
Liver, kidney, pancreas, smooth muscle cells, fibroblasts
Define permanent tissues
Terminally differentiated; non-proliferative in postnatal life
Examples of permanent tissues
Neurons and myocytes
Where does scar formation not occur?
In the brain
Pro to scar formation
Scar usually provides enough structural stability for the injured tissue to continue function
Con of scar formation
Fibrous tissue cannot perform the original function of the lost parenchymal cells
Components of scar formation
- Angiogenesis
- Migration/proliferation of fibroblasts
- Formation/deposition of ECM by fibroblasts
- Maturation/organization of fibrous tissue elements
Important mediators of angiogenesis
VEGF, FGF, PDGF, and TGF-beta
What does VEGF do?
Promotes angiogenesis, increases vascular permeability, and stimulates endothelial cell migration/proliferation
What are the normal levels of VEGF in an adult tissue?
Low levels usually, but higher in podocytes of glomerulus and pigment epithelium of the retina
Inducer of VEGF
Hypoxia
In what pathology is VEGF indicated?
Kidney cancer
What do fibroblasts do?
Synthesize connective tissue proteins
Define granulation tissue
Specialized tissue that fills in defects in organs when non-regenerative cells and/or connective tissue framework is destroyed
Components of granulation tissue
Proliferating fibroblasts that lay down immature connective tissue (type III collagen) and new blood vessels
When is granulation tissue present?
Only during healing or attempt to heal destroyed tissue
Definition of organization
Process of transforming granulation tissue into a dense scar
What happens during organization?
With time, blood vessels become less prominent, collagen matures to type I collagen
What type of staining is used to determine the difference between mature scar and granulation tissue?
Trichrome stain that stains mature collagen blue
Myofibroblasts
Modified fibroblasts with functional features of contractile smooth muscle cells that will contract the wound
Healing by first intention
Clean, uninfected surgical incision that is approximated by surgical sutures; leaves a small scar, minimal contraction of wound
Healing by second intention
Large skin wound with extensive destruction, contamination, infection with unapproximated edges
Wound strength after 1 week
10% of normal; collagen is still being synthesized and modified
Wound strength after 3 months
70-80%
Fibrosis definition
Excessive deposition of collagen and other ECM components in a tissue
Eight factors influencing repair
Infection Nutrition Glucocorticoids Poor perfusion Diabetes mellitus Foreign bodies Stable/labile vs permanent cells Location of injury
Supplementation of which dietary deficiencies would be most appropriate for wound healing? A. Copper and vit D B. Folate and zinc C. Iodine and vit E D. Vit C and E E. Vit C and zinc
E. Vitamin C and zinc: vitamin C helps in collagen synthesis and zinc is a cofactor in collagenase
Keloid
Accumulation of exuberant amount of collagen, forming raised scars that grow beyond wound boundaries
In which population are keloids more common?
African-Americans
Aberrations
Hypertrophic scar; excess production of scar tissue localized to the wound that may regress
