Healing And Repair Flashcards
What are the 4 stages of healing
1) clotting phase
2) inflammation phase
3) proliferative phase
4) maturation phase
What is regeneration
Replacement with functional differentiated cells
What is repair
Production of a fibrous scar and changes in tissue structure/architecture
During what type of inflammation would regeneration occur
Acute inflammation
What are the 3 main cell types in regeneration and repair
Labile cells
Stable cells
Permanent cells
What are labile cells
- normal state is active cell division
- rapid regeneration
What are stable cells
- variable rates of regeneration
- rapid proliferation in response to injury
What are permanent cells
- unable to divide
- unable to regenerate
Give an example of a liable cell
Keratinocytes
Give an example of permanent cells
Nerve fibres
What happens during the coagulation phase
Haemostasis
- clot formation
- mitosis of labile/stable cells
What is the inflammation phase
- macrophages, neutrophils phagocytose and degrade infectious agent
- stimulation of certain cells (keratinocytes, fibreoblasts) to start regenerating and/or repairing tissue
What is involved in the proliferative phase
- formation of granulation tissue
- fibroblasts drive the process of fibrosis
- new connective tissue which is rich in collagen (granulation tissue)
- angiogenesis (new blood vessels)
- growth factors essential
What is essential for the proliferation phase
Growth factors
What is angiogenesis
Formation of new blood cells
What is granulation tissue
New connective tissue developed during healing
- rich in collagen
Describe the first phase of granulation tissue formation
Vascular granulation tissue
- mix of proliferating capillaries, fibroblasts, immune cells
- new capillaries are relatively leaky allowing cells and fluid into the tissue
What is the second phase of granulation tissue formation
- fibrous granulation tissue
- over time capillaries regress and immune cells return to the blood
- mature fibroblasts lay down collagen
What are the two mechanisms by which angiogenesis can arise
-sprouting
-intrussusceptive (splitting)
What drives angiogenesis
Vascular endothelial growth factor (VEGF) which is proved by innate immune cells
What is sprouting
New blood vessels sprout from other blood vessels
What is splitting
Capillaries split to form new blood vessels
What are growth factors that play a key role in healing and repair
- cytokines
- hormones
What is the role of cytokines and hormones in healing and repair
They promote or inhibit cell growth and differentiation
They bind to receptors on cell surfaces, homeostatic production
What can an alteration in the growth factors during healing and repair cause
Alteration in this balance, dysregulated cellular proliferation and survival of abnormal cells
Name some functions of growth factors
- promote cell survival
- locomotion
- contractibility
- differentiation
- angiogenesis
Growth factors have … receptors on ….
Growth factors have unique receptors on target cells
What is fibrosis
The term used to describe the extensive deposition of collagen and formation of excess fibrous connective tissue
What is fibrosis driven by
Fibrosis is driven by fibroblasts and macrophages
What is the key macrophage subset that drives fibrosis
Anti inflammatory subset M2
These are essential in the process of healing and repair, they produce essential growth factors and engulf and degrade
What happens to the granulation tissue in the maturation phase
The granulation tissue is remodelled to match the tissue before infection, collagen fibres are cross linked along tension lines and tensile strength is regained
A fibrous scar can remain in this stage
Describe the inflammatory stage in fracture healing
- hematoma formation (blood clot within the tissue) at the fracture
- occurs within 48 hours
- acute inflammatory response - inflammatory infiltrate scavenge of debris and dying tissue
- bone cells deprived of oxygen/blood supply dies off
Describe the repairing phase 1 of fracture healing
- capillaries form into hematoma
- occurs within weeks
- fibroblasts produce collagen fibres
- Osteoblasts form spongy bone
- granulation tissue form
- granulation tissue becomes the fibrocartilage callus (soft callus)
Describe the repairing stage 2 in fracture healing
- cells involved in bone remodelling (chondrocytes and osteoblasts)
- remaining granulation tissue is ossified (turned to bone)
- formation of hard bone callus at fracture site (known as fracture callus or woven bone)
- occurs within months
Describe the remodelling phase in fracture healing
- osteoclast and osteoblasts remodel teh bone callus
- cortical bone replaces woven bone
- takes months or years to repair
