Wound healing

Question 1

What are the 4 stages of wound healing

Answer 1

Haemostasis
Inflammation
Proliferation
Remodelling

Question 2

What is haemostasis in wound healing

Answer 2

Skin has no wound
Platelets circulating within blood cells
Non-adhesive due to anti-thrombotic factors e.g. NO and prostacyclin

Question 3

Primary haemostasis

Answer 3

Vasoconstriction
Damaged cells release vasoconstrictors e.g. thromboxane A2, serotonin
Cause smooth muscle contraction in arterioles
Reduces blood flow to capillaries

Question 4

Secondary haemostasis

Answer 4

Platelet plug
Capillary wounding exposes sunendothelial matrix to blood
Platelets in subendothelial matrix adhere to vWF, mediated by integrins
Platelets contain collagen and fibrinogen: a2b1 binds collagen, a2b3 binds fibrinogen

Question 5

Secondary haemostasis

Answer 5

Fibrin generation
Xa cleaves prothrombin > thrombin
Thrombin cleaves fibrinogen to insoluble fibrin
Fibrin and platelets form meshwork

Question 6

Inflammation - neutrophils

Answer 6

Wounded cells release chemokines
Chemokines attract neutrophils to site
Neutrophils invade tissue and phagocytose pathogens

Degranulation: neutrophils release proteases from intracellular granules to destroy bacteria and pathogens. Also releases NO and ROS

Neutrophils produce DNA NETs to trap pathogens

Neutrophils can be cleared by apoptosis or macrophages

Question 7

Inflammation - monocytes

Answer 7

Monocytes circulate and monitor for damage
Monocytes enter tissue and differentiate to macrophages
Release pro-inflammatory cytokines and escalate response
MCP-1 macrophages attracts more monocytes - positive feedback
Clear bacteria and neutrophils

Question 8

Proliferation - macrophages

Answer 8

Macrophages secrete VEGF
VEGF = vascular endothelial growth factor
VEGF promote angiogenesis - formation of new blood vessels
Angiogenesis only happens in development and wound healing
Macrophages secrete ECM proteins, keratinocytes migrate here and close wound, attaching to fibronectin

Question 9

Proliferation - fibrocytes

Answer 9

Fibrocytes deposit cells at wounded site, sometimes too many
Can cause excessive scarring
This can cause inflammatory diseases such as pulmonary fibrosis
PF is scarring and thickening of tissue between alveoli

Question 10

Remodelling - macrophages

Answer 10

Clear away debris
Clear up excessively secreted ECM

Question 11

Angiogenesis

Answer 11

Formation of new blood vessels
VEGF triggers receptors on endothelial cells
This initiates transcription to cause new blood vessel sprouting
New vessels bypass the damage and infiltrate wounded site to supply oxygen and nutrients

Question 12

Re-epithelialisation

Answer 12

Epidermal stem cells are key to normal homeostasis, maintaining balance of losing and renewing keratinocytes
Epidermal stem cells are found in hair follicles and epidermal basal layer
During wound healing, stem cells migrate to site. They secrete TGF-b which binds to fibroblasts in the dermis and causes them to change from non-contractile to myo-contractile myofibroblasts
Myofibroblasts pull in the edges of the wound
Proliferation and migration of keratinocytes on ECM results in re-epithelialisation