MOD S5 - Healing & Repair Flashcards
(32 cards)
What are the stages of fibrous repair?
Initial inflammation
Granulation tissue
Maturation
What is fibrous repair?
-Fibrous repair is the replacement of functional tissue by scar tissue
What is granulation tissue?
A combination of capillary loops and myofibroblasts
Describe the initial inflammation stage of fibrous repair
Inflammatory cell infiltrate
Blood clot forms
Acute inflammation around edges
Chronic inflammation - macrophages and lymphocytes migrate into clot
Describe what occurs after the initial inflammation stage in fibrous repair
-Clot replaced by granulation tissue
-Key components - these initiate fibrous repair by combining to form granulation tissue formation:
>Cell migration
>Blood vessels - angiogenesis
>Extracellular matrix production/remodelling
Describe the maturation stage of fibrous repair
Comparatively long lasting Cell population falls Collagen increases, matures and remodels Myofibroblasts contract, reducing volume of defect Vessels differentiate and are reduced Fibrous scar is end result
Describe control of fibrous repair
Poorly understood
Inflammatory cells recruited by chemotaxis
Angiogenesis occurs due to angiogenesis cytokines
Fibrosis occurs due to macrophages releasing pro-fibrotic cytokines causing fibroblast proliferation
Describe cell migration in fibrous repair
-Inflammatory cells >Phagocytosis of debris - macrophages and neutrophils >Chemical mediators - macrophages and lymphocytes -Endothelial cells >Angiogenesis -Fibroblasts/myofibroblasts >ECM proteins eg collagen >Wound contraction
Describe angiogenesis in fibrous repair
- Proangiogenic growth factors eg VEGF induce endothelial proliferation
- Pre-existing blood vessels sprout new vessels
- Endothelial proteolysis of basement membrane
- Migration of endothelial cell by chemotaxis
- Endothelial maturation and tubular remodelling
- Recruitment of periendothelial cells
Describe the function of the extracellular matrix
Supports and anchors cells Separates tissue compartments Sequesters growth factors Allows communication between cells Facilitates cell migration
Describe regeneration
The replacement of dead or damaged cells by functional, differentiated cells which originate from stem cells
Briefly describe stem cells
Undifferentiated cells which can proliferate to produce either more stem cells in order to maintain the stem cell pool OR produce cells which can differentiate into a specialised cell type
What is the difference between uni potent, toti potent and pluripotent?
Uni potent cells can only differentiate into one type of cell eg epithelial cells
Pluripotent cells can differentiate into several types of cell eg haemopoietic cells
Toti potent cells can differentiate into any type of cell eg embryonic cells
Do all cells have the same propensity for regeneration
No
Labile cells regenerate fastest
Stable cells regeneration is variable
Permanent cells cannot regenerate
Describe and give an example of labile cells
Normal state is active cell division
Usually rapid proliferation
Eg epithelial or heamatopoietic cells
Describe and give an example of stable cells
Normal state is G0 so not active division
Variable speed of proliferation
Eg hepatocytes, osteoblasts, fibroblasts
Describe and give an example of permanent cells
Unable to divide
Unable to regenerate
Eg neurones, cardiac monocytes
What factors control regeneration?
Growth factors
Contact between basement membranes and adjacent cells
How do growth factors control regeneration?
Promote proliferation of stem cell population
Promote expression of genes controlling cell cycle
Hormones (oestrogen, testosterone, growth hormone)
Autocrine, paracrine and endocrine
How does contact between basement membranes and adjacent cells control regeneration?
Signalling through adhesion molecules
Inhibits proliferation in intact tissue by contact inhibition
Loss of contact promotes proliferation
Exploited in cancer
Describe healing by primary intention
Incised wound
Apposed edges
Minimal clot/granulation tissue
Epidermis regenerates
Dermis undergoes fibrous repair
Sutures out at 5-10 days. ~10% of normal strength
Maturation of scar continues up to two years
Minimal contracture and scarring, good strength
Risk of trapping infection/abcess
Describe healing by secondary intention
Infarct, ulcer, abscess or any large wound
Quantitative differences:
Unapposed wound edges
Large clot dries to form clot
Epidermis regenerates from the base upwards
Repair process produced a large amount of granulation tissue
Takes a long time to heal completely
Compare healing by primary and secondary intention
1ary is a small, clean wound whereas 2ndary is larger
2ndary produces much more granulation tissue
2ndary has more contraction to reduce the volume of the defect
2ndary leaves a larger (but not necessarily weaker) scar
2ndary takes longer to heal than 1ary
Discuss local factors affecting the efficacy of healing and repair
Type, size & location of wound
Apposition, lack of movement (skin/bone/nerve damage)
Blood supply (arterial & venous)
Infection (systemic, gangrenous)
Foreign material (dirt, glass, sutures, necrotic tissue)
Radiation damage
