Revision: Healing and Repair

Question 1

Define fibrous repair

Answer 1

Replacement of functioning tiss. by scar tiss.

Question 2

Cells in fibrous repair

Answer 2

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

Question 3

Angiogenesis

Answer 3

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)

Question 4

ECM in fibrous repair

Answer 4

Formed from myo/fibroblast secretions

functions: -supports and anchors cells
- separates tiss. compartments eg BM
- sequesters GF
- communication between cells
- facilitates cell migration

Question 5

Main components of fibrous repair

Answer 5

1 Cellular migration of inflamm. cells, endoth. and myo/fibroblasts

2 Angiogenesis

3 Production and remodelling of ECM

Question 6

Steps in fibrous repair

Answer 6

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

Question 7

1st step in fibrous repair

Answer 7

Inflamm. cells infiltrate: blood clot forms, AIR around edge, CIR (macrophages and lymphocytes) migrate to centre

Question 8

2nd step in fibrous repair

Answer 8

clot is replaced by granulation tiss.: Angiogenesis, myo/fibroblasts multiply, differentiate and secrete the ECM,

Question 9

3rd step in fibrous repair

Answer 9

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

Question 10

what is granulation tiss?

Answer 10

a combination of capillary loops and myofibroblasts

Question 11

Definition of regeneration

Answer 11

replacement of dead/damaged cells by functioning, differentiated cells derived from stem cells

Question 12

Stem cells

Answer 12

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

Question 13

Regeneration: Categories of cells

Answer 13

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

Question 14

primary intention healing of a skin wound

Answer 14

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

Question 15

secondary intention healing of a skin wound

Answer 15

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

Question 16

compare primary -> secondary intention of wound healing

Answer 16

shorter time

apposed wound edges -> less wound contraction required

less granulation tiss.

smaller scar

Question 17

Factors affecting the efficacy of wound healing and repair

Answer 17

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

Question 18

structure and function of collagen

Answer 18

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

Question 19

Healing of a bone frx

Answer 19

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

Question 20

Healing and repair of cardiac muscle

Answer 20

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

Question 21

Healing and repair of a peripheral nerve

Answer 21

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