Revision: Healing and Repair Flashcards
Define fibrous repair
Replacement of functioning tiss. by scar tiss.
Cells in fibrous repair
1 Inflammatory cells: phagocytosis of debris - macrophages and neutrophils
-production of chemical mediators: macrophages and lymphocytes
2 Endothelial cells: angiogenesis
3 Fibroblasts: produce ECM prot.s eg collagen
-Myofibroblasts do the same but are also involved in wound contraction
Angiogenesis
A good blood supply is necessary for repair, to bring nutrients and also inflammatory cells and fibroblasts (it is exploited by malignant cells as well)
It is induced by proangiogenic growth factors eg VEGF
Pre-existing blood vessels sprout new ones
Steps: 1 endothelial proteolysis of BM
2 Migration of endothelia via chemotaxis
3 Endoth. proliferation
4 Endoth. maturation and tubular remodelling
5 recruitment of periendothelial cells (cells that reside next to and support endothelia)
ECM in fibrous repair
Formed from myo/fibroblast secretions
functions: -supports and anchors cells
- separates tiss. compartments eg BM
- sequesters GF
- communication between cells
- facilitates cell migration
Main components of fibrous repair
1 Cellular migration of inflamm. cells, endoth. and myo/fibroblasts
2 Angiogenesis
3 Production and remodelling of ECM
Steps in fibrous repair
1 Inflamm. cells infiltrate: Blood clot forms, AIR around edge of wound, CIR (macro.s and lympho.s) migrate into clot
2 Clot is replaced by granulation tiss.: Angiogenesis, myo/fibroblasts migrate, differentiate and produce the ECM
3 Maturation: takes a long time, cell population falls, collagen increases, matures (III->1), remodels, myofibroblasts contract to reduce vol. of deficit, vessels differentiate and reduce, left w/ a fibrous scar
1st step in fibrous repair
Inflamm. cells infiltrate: blood clot forms, AIR around edge, CIR (macrophages and lymphocytes) migrate to centre
2nd step in fibrous repair
clot is replaced by granulation tiss.: Angiogenesis, myo/fibroblasts multiply, differentiate and secrete the ECM,
3rd step in fibrous repair
Maturation: takes a long time, cell numbers fall, collagen increases in size, matures (III->I) and remodels, leaving a fibrous scar, myofibroblasts contract to draw the edge of the wound together, vessels differentiate and are reduced
what is granulation tiss?
a combination of capillary loops and myofibroblasts
Definition of regeneration
replacement of dead/damaged cells by functioning, differentiated cells derived from stem cells
Stem cells
potentially limitless proliferation, as its daughter cells can either remain as stem cells or can differentiate to specialised cell types
Unipotent: can only diff. to one cell type - eg epithelia
Multipotent: can diff. to many cell types eg haematopoietic
Totipotent: can diff. to ANY cell type ie embryonic
Regeneration: Categories of cells
Labile: continually dividing eg epithelia, haematopoietic
Stable: resting state is G0, but can be stimulated to divide eg hepatocytes, fibr/osteoblasts
Permanent: always in G0, unable to divide and regenerate eg neurones, skel and card. myocytes
primary intention healing of a skin wound
occurs in clean incised wounds w/ apposed edges
min. clot/granulation tiss., epidermis regenerates, dermis undergoes fibrous repair, sutures are taken out after 5-10 days, w/ 10% of normal strength
Transition from gran. tiss. -> scar tiss.: min. contraction and scarring w/ good strength, maturation of scar continues <2 yrs, risk of trapping infection -> abscess
secondary intention healing of a skin wound
occurs in a large skin defect
Cause: abscess, ulcer, infarct, any large skin wound
Result: unapposed edges, large clot dries -> scab, a lot of granulation tiss., epidermis regnerates from the base upwards
compare primary -> secondary intention of wound healing
shorter time
apposed wound edges -> less wound contraction required
less granulation tiss.
smaller scar
Factors affecting the efficacy of wound healing and repair
Local: apposition, infection, size, location, type of wound, blood supply, foreign material eg glass, dirt
General: age, drugs, general (eg prot.)/Specific (eg Vit. C) diet deficiencies, general state of health (chronic diseases eg diabetes) and general CVS state
structure and function of collagen
Structure: 3 alpha chains of left handed triple helices composed of tropocollagen
-> made of glycine-X-Y-Glycine-X etc, where most X and a lot of Y positions are formed either by proline or hydroxyproline
Function: Major component of ECM and gives cells their structure, great tensile strength and so is used in ligaments, tendons, bone, teeth, cartilage, fascia, gives skin strength and elasticity
Healing of a bone frx
1 Haematoma: formed from broken vessels in marrow and periosteum, provides framework for ingress of macro.s, endothelia, oste and fibroblasts, necrotic tiss is removed and cap.s develop
2 Soft Callus: callus= specialised mixture of cells, fibroblasts produce granulation tiss., osteoprogenitor cells develop from mesenchyme, aka procallus
3 Hard callus: osteoprogenitor cells -> osteoblasts, lay down collagenous osteoid, making a callus of woven bone in an iregular pattern
4 Remodelling: osteoblasts and clasts gradually replace woven with lamellar bone, initially spongy -> dense lamellar bone
Healing and repair of cardiac muscle
1 Infarct is initially invisible but then becomes eosinophilis w/ ICellular oedema
2 AIR, neutrophils infiltrate between dead cardiac fibres
3 This then is followed by replacement of tiss w/ granulation tiss.
4 Collagen scar forms and a white infarct is left
Healing and repair of a peripheral nerve
1 Axon is severed/damaged -> axon and myelin proximal degenerate and are removed by macrophages
2 BM is maintained however, and schwann cell proliferate and enlarge to form a tube
3 the axon can then grow through this tube, 1-2mm a day
