Tissue repair

Question 1

Cutaneous wound healing stages

Answer 1

Injury (to epidermis and dermis)

Coagulation (platelet activation and fibrin deposition)

Early Inflammation ~ first 24hrs PMN recruitment

Late Inflammation ~48hrs macrophage recruitment, angiogenesis

Granulation Tissue Formation ~72hrs recruitment and proliferation of endothelial cells and fibroblasts infiltrate

Extracellular Matrix Deposition via fibroblast collagen synthesis

Remodelling weeks to months - scar formation

Question 2

First intention healing

Answer 2

Incisional wound is replaced by a scar

Question 3

Second intention healing

Answer 3

Open wound is filled by granulation tissue and scar formation, in the case of infection, pus is produced by the wound.

Question 4

Granulation tissue

Answer 4

Opposite of necrosis.

It is new connective tissue full of newly forming blood vessels needed for wound healing.

Granulation tissue is pink in colour (new blood vessels)and ‘granular’ due to punctate haemorrhage.

Question 5

Cells in granulation tissue

Answer 5

Stem cells

Endothelial cells

Fibroblasts

Macrophages

Question 6

Stem cell role in granular tissue

Answer 6

Give rise to temporary wound associated cells and then differentiated specific cells.

The stem cells arise from niches within the tissue.

Generate fibroblasts

Question 7

Endothelial cell role in granular tissue

Answer 7

Give rise to capillary buds and promote angiogenesis

Question 8

Fibroblast cell role in granular tissue

Answer 8

Lay down Extracellular Matrix (ECM), produces structural framework.

Fibroblasts are stimulated to divide, migrate into wounds and produce collagen

Fibroblasts secrete glycosaminoglycans (GAGs)

Question 9

Collagen in healing

Answer 9

Initially type III collagen laid down by fibroblasts

Then replaced with type I

Question 10

What cytokines regulate fibroblasts

Answer 10

Fibroblasts are regulated by cytokines including: PDGF - platelet derived growth factor FGF - fibroblast growth factor TGF-b - transforming growth factor

Question 11

Macrophage cell role in granular tissue

Answer 11

Essential regulators

Secreting growth factors and cytokines that entice and stimulate fibroblasts, endothelial precursor cells and (in skin wounds) keratinocytes.

They also oversee the deposition and remodelling of extracellular matrix material.

Question 12

Clotting stages (brief)

Answer 12

Fibrin deposition Initiated by platelet activation

Fibrinogen -> Fibrin via Thrombin

Fibrin crosslinked by activated Factor XIII

Question 13

Fibrinolysis (brief)

Answer 13

Plasminogen -> Plasmin

Question 14

Plasminogen activators and inhibitors

Answer 14

Activators - Two types tPA (endothelial cells) and uPA (macrophages & PMN)

Inhibitors of plasmin (e.g. PAI-1, a2 antiplasmin & a2 macroglobulin)

Question 15

Angiogenesis (brief)

Answer 15

Endothelial Cell Migration (via fibronectin)

Endothelial Cell Proliferation (mediated by VEGFs and TGFa)

Proteolysis of ECM (via collagenases, tPA, uPA)

Tube formation

The result of angiogenesis is new capillary growth or ‘sprouting’

Question 16

Failure of wound healing in organisation and scarring

Answer 16

Failure of hepatic regeneration and fibrotic response to toxic insult e.g. Cirrhosis of the liver, where hepatocytes die and are replaced by fibroblasts.

Excessive fibrotic response to foreign bodies e.g silicosis form silica dust inhalation

Replacement of normal tissue with a fibrous scar following ischaemia e.g. Myocardial infarct

Question 17

Failure of wound healing continued ulceration

Answer 17

Failure to restore normal function e.g. arterial & venous leg ulcers

Failure of wound repair in diabetes due to reduced arterial flow

Question 18

What cytokines are important in orchestrating cellular activities in wound repair

Answer 18

TGF-beta/IL-1/FGF 7 or 10/PDGF/VEGF/IGF-1

Question 19

Which function is associated with fibroblast activity?

Answer 19

Secrete collagen III & collagen I, glycosaminoglycans GAGs, regulated by cytokines including PDGF, FGF, TGF-beta, IL-1,

Question 20

Which function is associated with endothelial cells?

Answer 20

Angiogenesis

Question 21

Which clinical complication is the consequence of excessive repair?

Answer 21

Keloid, hypertophic scars

Question 22

Which factors will delay wound healing?

Answer 22

Malnutrition (e.g. vitamin C, protein, Zn++)

Bacterial infection (e.g. MRSA)

Presence of foreign bodies (e.g prothesis)

Immunosuppression (e.g. steroids, chemotherapy, age)

Poor blood supply (venous stasis and poor perfusion)

Insulin-dependent Diabetes

Question 23

Excessive deposition of collagen at the site of the skin wound is a complication seen in…

Answer 23

Keloid (is also seen in hypertrophic scars but to a lesser extent)

Question 24

Scar tissue has a higher tensile strength than unwounded skin (T/F)

Answer 24

False (maximum 80% of unwounded skin)