Tissue Repair

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Tissue Repair

Morphology of Granulation tissue

2 patterns

Late form

Fibrous granulation tissue

Inconspicuous capillaries and numerous plump activated fibroblasts

Early form

Vascular granulation tissue

Loose connective tissue matrix

Proliferating fibroblasts

Leukocytes

Occupied by

Macrophages and lymphocytes

Resolving inflammation

Proliferating capillaries and fibroblast

Wound Healing

Former site of tissue damage and active inflammation

2nd intention

Differences compared to 1st Intention healing

Parenchymal regen cannot fully reconstitute original architecture

wound contraction present

Fibroblast with smooth muscle characteristics

mediated by myofibroblast

Much larger amounts of grnulation tissue formed

More intense inflammatory rxn

Occurs in wounds with separated edges

First intention

1st Month

Tensile strength increases gradually thereafter

Dermal appendages destroyed by injury are permanently lost

Scar comprises of connective tissue covered by intact epidermis

Week 2

Leukocyte infiltration, Edema and increased vascularity disappeared

Continued proliferation of fibroblast and accumulation of fibrogen

Day 5

Epidermis recovers normal thickeness

Collagen bridges incision

Incisional space filled with granulation tissue

Day 3

Epithelial proliferation continues

Collagen fibers present at margin but do not bridge incision

Granulation tissue invades incisional space

Replacement of neutrophils by macrophages

24-48Hrs

Continuous thin epithelial layer formed

Fusing in midline beneath surface scab

Spurs of epithelial cells migrate and grow along margins

Epidermis at cut edge thickens due to mitotic activity of basal cells

Immediate response to injury

Acute inflamation occurs with appearance of neutrophils at edge of wound

Dehydration of clot form scab

Wound fills with clotted blood

Healing of clean wounds with opposed edges

2 Distinct Processes

Fibrosis

Non-dividing cells hence must heal by fibrosis instead

Skeletal muscle

Cardiac muscle

Neurons

Scar formation

Replacement of injured cells by connective tissue

4) Remodelling of Fibrous Tissue

Vascular regression continues as scar matures

Conversion of granulation tissue into scar

Dense collagen

Spindle shaped fibroblasrt

3) Deposition of ECM

Fibroblast proliferation decreases over time while ECM deposition increases

major portion of connective tissue formed by fibrillar collagens

2) Migration + Proliferation of Fibroblasts

Formation of granulation tissue framework

Proliferation triggered by GFs and Cytokines

1) Angiogenesis

d) Recruitment of periendothelial cells

Smooth muscle cells

Pericytes

c) Maturation of Cells

Inhibition and remodeling into capillary tubes

b) Migration and proliferation of Endothelial Cells

To angiogenic stimulus

a) Proteolytic Degradation

BM of parent vessel

Regeneration

Restitution of normal structure

Needs intact basement Membrane

Cells proliferate haphazrdly if BM disrupted

Needed for organized regeneration

Underlying supporting stroma of parenchymal cells

Replacement of injured cells by cells of same type

Stable Cells

Quiescent cells

E.g.

Parenchymal cells of glandular organs

Vascular endothelial cells

Mesenchymal cells

Considered to be G0 but can be stimulated into G1

Capable of rebuilding tissue of origin

Rapid division in response to stimuli

Normally low level or replication

Labile Cells

Stratified sq. cells of skin, columnar epithelium of GI tract

Regen. derived mostly from stem cells with unlimited regen capacity

Continuously dividing cells

Proliferate to replace cells

Follow cell cycle from one mitosis to the next