Tissue repair

Question 1

What are the 4 stages of healing?

Answer 1

Haemastasis
Inflammation
Proliferation
Remodelling

Question 2

How does haemastasis occur?

Answer 2

• Prevent bleeding + blood loss
• Ca2+ causes contraction and constriction of the vascular circular smooth muscle -> vasoconstriction
• hypoxia -> acidosis -> release of vasodilatory compounds
• Vasodilation
• Mast cells release histamine to increase vessel permeability and allow for leukocyte migration through the vessel wall

Question 3

Describe the intrinsic and extrinsic pathway of clot formation?

Answer 3

Intrinsic: endothelial damage activates factor XII + clotting proteins
Extrinsic : Endothelial damage releases tissue factor into the blood

Question 4

Describe the clotting cascade

Answer 4

• Endothelial damage activates platelets
• Endothelial damage releases tissue factor into the blood
• Tissue factor combines with factor Xa + factor XIIa to form thrombin
• thrombin activates clotting cascade and full platelet activation
• thrombin causes fibrinogen -> fibrin
• Factor 13 cross links fibrin to create a fibrin mesh

Question 5

Describe inflammation

Answer 5

Neutrophils migrate through the blood vessels in extravasation to the site of injury ( margination, rolling adhesion, diapedesis, penetration) facilitated by chemotaxis

Damaged cells and platelets release messengers causing macrophage migration to the wound

Lymphocytes lay down ECM and collagen for wound healing by fibrosis. Proliferation only starts when all debris is cleared from the wound

Question 6

What are the main stages in proliferation?

Answer 6

Angiogenesis
Fibroblasts lay down ECM, collagen and fibronectin to form granulation tissue which fills the wound
Myofibroblasts - wound contraction
Epithelialisation - closure of wound covered by sheet of epithelial cells

Question 7

What activates angiogenesis?

Answer 7

Platelets release PDGF, TGF beta and FGF

Question 8

Describe the function of fibroblasts in proliferation?

Answer 8

Clot produces TGFbeta and PDGF which stimulates migration of fibroblasts
Fibroblasts lay down ECM proteins, fibronectin + collagen to form granulation tissue to cover the wound

Question 9

Describe the role of myofibroblasts

Answer 9

Wound contraction

• Myofibroblasts have pseudopodia + promote angiogenesis
• Pulls actin + myosin filaments and cell bodies together to close the wound

Question 10

Describe re epithelialisation

Answer 10

Epithelial cells migrate to the wound to form a sheet of cells covering the wound
EMT -> cells gain motility + travel across the wound
Changes in cytokine concentrations cause change in phenotype from motile -> proliferative to repopulate wound with epithelial cells