Healing and Repair Flashcards
Define regeneration
Growth of cells and tissues to replace lost structures e.g. epithelia of skin and GI tract
Requires intact connective tissue scaffold
What is meant by labile, stable and permanent cell populations?
Refers to proliferative capability
Labile = continuously dividing e.g. surface epithelia. Actively dividing
Stable = quiscent in resting state G0. Have low level replication but can replicate in response to stimuli e.g. hepatocytes, osteoblasts
Permanent = Non-dividing tissue e.g. neurones and cardiac myocytes G0
What is meant by the term Stem cell
A cell that has potentially limitless proliferation as it is not terminally differentiated
What is the difference between cells that are unipotent, multipotent and totipotent and give an example of each
- Unipotent- only produces one type of differentiated cell
e. g. epithelia - Multipotent - Can produce several types of differentiated cell e.g. haemopoietic
- Totopotent and produce any type of cell i.e. embryonic stem cell
When does fibrous repair occur
- Loss of collagen framework
- Ongoing chronic inflammation
- Necrosis of specialised cells that can’t be replaced
Outline fibrous repair
- Phagocytosis of necrotic tissue debris
- Proliferation of endothelial cells –> angiogenesis
- Proliferation of fibroblasts and myofibroblasts –> collagen, wound contraction
- Granulation tissue becomes scar
- Scar matures and shrinks
Which cell types are key in fibrous repair
Neutrophils and macrophages –> phagocytosis
Lymphocytes and macrophages –> chemical mediators
Endothelial cells –> angiogenesis
Fibroblast/Myofibroblasts –> ECM proteins e.g. collagen, wound contraction
Explain the process of angiogenesis
- Endothelial proteolysis of basement membrane
- Migration of endothelial cell via chemotaxis
- Endothelial proliferation
- Endothelial maturation and tubular remodelling
- Recruitment of periendothelial cells
Why is angiogenesis important in wound healing
Provides accès to the wound for inflammatory cells and fibroblasts
Delivery of O2 and other nutrients
What does granulation tissue contain?
- Collagen
- ECM
- New vessels
Define Autocrine, Paracrine and Endocrine signalling
Autocrine - Cells respond to signalling molecules that they themselves have produced
Paracrine - Cells produce a signalling molecule that acts on adjacent cells
Endocrine - Hormones are made in the gland and migrate travel to target cells in the blood
What is the action of growth factors
- Proliferation/inhibition
- Cell locomotion
- Contractility
- Differentiation
- Viability
- Activation
- Angiogenesis
What is the action of EGF?
Mitogenic for epithelial cells, hepatocytes and fibroblasts
Produced by keratinocytes, macrophages and inflammatory cells
What is the action of VEGF?
Potent inducer of blood vessel development (vasculogenesis)
Role in angiogenesis
What is the action of PDGF?
-Migration and proliferation of fibroblasts, smooth muscle cells and monocytes
-Stored in alpha granules of platelets
Also produced by macrophages and endothelial cells
What is the action of tumour necrosis factor?
- Fibroblast migration
- Fibroblast proliferation
- Collagenase secretion
What is contact inhibition?
Cells replicate until they touch other cells then they stop therefore only form a monolayer
What is the name of the molecules that bind to each other and give an example
Cadherin
e.g. e-cadherin
What is the name of the molecule that binds ECM to cells
Intergrins
When does healing by primary intention occur?
Incised, closed, non-infected, sutured wounds
Clean wounds with opposed edges
Briefly outline healing by primary intention
- Haemostasis - Narrow space is filled with blood, dehydration of surface clot and scab formation
- Inflammation - Neutrophils appear at margin of incision
- Migration of cells - Macrophages appear and activate, cytokine release –> attract fibroblasts and endothelial cells
- Regeneration - Macrophages replace neutrophils. Granulation tissue invades. Epithelial cell proliferation thickens, scab falls off. Angiogenesis continues. Activated fibroblasts produce collagen
- Early scarring - wound filled with granulation tissue. Lots of collagen deposited. Regression of vascular channels
- Scar maturation - Scar is mass of fibrous tissue with many collagen fibres, few cells and few vessels
Why are scars hairless?
As the skin normalises and keratinises but appendages such as hair follicles don’t form
What colour are healed scars?
White as the capillaries disappear
When is healing by secondary intention seen?
Excisional wounds, wounds with tissue loss and separated edges, infected wounds
