Healing and Repair Flashcards
What is regeneration/resolution vs Fibrous repair/organisation?
Regeneration is growth of cells to replace lost ones - requires connective tissue scaffold to not be lost
Fibrous repair is fibrovascular connective tissue growing into area of tissue loss (significant or complex tissue lost)
What three processes does wound healing involve?
Haemostats
Inflammation
Regeneration
What is primary vs secondary intention healing?
Primary is regeneration
Secondary is fibrous repair
Which type of repair to labile, stable and permanent cells undergo?
Labile/Stable - Regeneration
Permanent - Fibrous repair
How do stem cells replicate?
Asymmetrically - produce one ‘self’ cell and one differentiated cell
What is a labile tissue? Give example
Proliferate through life - mitosis
E.g. skin epithelia, columnar epithelium of GI and uterus, transitional epithelia of GI, cells of bone marrow and haemopoeitic tissues
What is a stable tissue? Give examples
Quiescent but can undergo proliferation if needed
e.g. parenchymal cells of liver, kidneys, pancreas, SMCs, vascular endothelial cells, resting lymphocytes and other WBCs mesenchymal cells e.g.: osteoclasts, fibroblasts
What is a permanent tissue? Give examples?
Contain cells that have left the cell cycle and cannot undergo mitosis
e.g. neurones, cardiac myocytes, skeletal muscle cells.
What is required for cells that are terminally differentiated to be able to regenerate? What if they can’t regenerate?
Stem cells
Otherwise will undergo secondary intention healing
What are the 4 stages of fibrous repair post inflammation?
1) Phagocytosis of debris
2) Proliferation of endothelial cells - angiogenesis - granulation tissue
3) Fibroblasts and myofibroblasts secrete collagen & wound contraction
4) Matures into scar - less vascularisation and contracts
Which cells are unipotent multipotent totipotent?
Uni - produce 1 cell line e.g. epithelia
Multi - produce many e.g. haematopoeitic
Toti - embyonic
Why is a scar white and hairless? Why do they stretch?
Often no regeneration of melanin or hair follicles etc
Stretch as they produce collagen but not elastin so don’t recoil with growth e.g.
Which three ways can cells communicate in regeneration and repair? Which is the most important?
Endocrine - hormones
Paracrine - local mediators e.g. growth factors
Autocrine - cell to cell contact or cell-connective tissue contact
What are growth factors? Which 4 major growth factors are important in wound healing?
They are ‘local hormones’ polypeptide protooncogenes that bind to cell surface receptors and stimulate transcription of genes that promote mitosis
1) EGF
2) PDGF
3) VEGF
4) TNF
Name three cells involved in wound healing that produce growth factors
Macrophages
Platelets
Endothelial cell
What is EGF? What does it do? Name 3 cells it is mitogenic for
Epidermal growth factor - mitogenic for epithelial cells, hepatocytes and fibroblasts.
What is VEGF? What does it do?
Vascular endothelial growth factor - angiogenesis and vasculogenesis in tumours, chronic inflammation and wound healing
What is PDGF? What does it do?
Platelet derived growth factor - causes migration and proliferation of fibroblasts SMCs and monocytes
What is TNF? What does it do?
Tumour necrosis factor - induced fibroblast migration, proliferation and collagenase secretion
What is contact inhibition? When is it altered?
Where isolated cells will proliferate until touching cells around them and inhibit proliferation.
Malignant cells may not have contact inhibition
How would an infected, excisional (loss of tissue), or jagged wound heal?
Secondary intention
What are the 6 stages of wound healing from injury (with time scales)
Seconds to minutes- Haemostasis (contraction of B vessel and clot)
Minutes - hours - Inflammation (neutrophils)
Up to 48 hours - Migration of cells (macrophages, platelets, fibroblasts)
Up to 3 days - Regeneration - granulation tissue (angiogenesis)
7-10 days - Early scaring (vessels still present)
Up to 2 years - Mature scar
Name some differences between primary and secondary intention healing
Primary - clean non infected wound
Secondary - complex/deep wound, considerable contraction, considerable granulation, scarring, takes longer, infection will delay healing, larger clot at beginning.
What kind of factors affect wound healing?
Infection Size/shape of wound Method of injury Blood supply there Any foreign objects Mechanical stress
Age Diabetes Smoking Genetic problems e..g Ehlers Danlos Anaemia Vitamin deficiency - e.g. Scurvy Malnutrition Drugs - e.g. steroids (inhibit collagen synthesis)
Explain how secondary intention leads to loss of function in the heart?
Post MI Fibrous repair Replaces myocytes Can't do myocyte contracting function Can lead to HF
What are fibrous adhesions and why do they occur?Where?
2nd intention repair that adheres parts of tissue/organs to other parts e.g. bowel to bladder - pain and rupture/blocks tubes e.g. fallopian tube
Give an example where 2nd intention healing leads to disruption of complex tissue relationships within an organ
Liver - cirrhosis (fibrosis loss of parenchymal cells etc)
What is a keloid scar?
Overproduction of scar tissue - overproduction of collagen that exceeds the border of the scar.
What can cause a joint contracture? What happens if severe?
2nd intention healing e.g. afterburns that prevents a limb fully extending for example as scars don’t contain elastin.
If severe can even impair blood circulation
What is in granulation tissue? What is it’s function?
All inflammatory stuff - fluid, epithelial cells, macrophages, early angiogenesis, fibrin, collagen, etc. Aims to heal ared
What is proud flesh?
Over granulation - can be seen over height of wound. Can remove by burning or surgically
Why are old scars sometimes turned into new wounds in scurvy?
Due to increased collagen breakdown in scars, and diminished collagen synthesis in scurvy patients = breakdown of scar and new wound
What predisposes to keloid scaring?
Afro-caribbean Infection Immunosuppressed Diabetes Foreign bodies
etc
Myofibroblasts are really important in primary union?
No more in secondary intention
primary union just means primary intention
