*UNFINISHED* MOD Session 4 Flashcards
Define regeneration?
Replacement of dead or damaged cells by functional, differentiated cells
What are the daughter cells of a stem cell?
1) Stem cell
2) Specialised cell
Define unipotent, pluripotent and totipotent?
1) Can only produce one type of differentiated cell e.g. epithelia
2) Can produce several types of differentiated cell e.g. haematopoietic
3) Can produce any type of cell i.e. embryonic stem cells
What are labile cells?
E.g. epithelia or haematopoietic cells
Normal state is active cell division : G1-M-G2
Usually rapid proliferation
What are stable cells?
E.g. hepatocytes, osteoblasts, fibroblasts
Resting state G0
Speed of regeneration variable
What are permanent cells?
E.g. neurones, cardiac myocytes
Unable to divide - G0
Unable to regenerate
How and which growth factors are involved in controlling regeneration?
1) Promote proliferation in the stem cell production
2) Extracellular signals transduced into the cell
3) Promote expression of genes controlling cell cycle
4) Proteins e.g. EGF, PDGF, FGF…
5) Hormones e.g. oestrogen, testosterone, GH
How do contact between basement membranes & adjacent cells?
1) Signalling through adhesion molecules
2) Inhibits proliferation in intact tissue
3) ‘Contact inhibition’
4) Loss of contact promotes proliferation
What is fibrous repair?
Replacement of functional tissue by scar tissue
What is the main type of cell that undergoes fibrous repair when it is necrotic?
Permanent cells (labile and stable undergo either resolution if collagen framework is intact or undergo FR + Sc if collagen is destroyed)
What are the three main components of fibrous repair?
1) Cell migration
2) Blood vessels - angiogenesis
3) ECM + remodelling
Initiate fibrous repair by combining to form granulation tissue
Describe the three main cell types in fibrous repair?
1) Inflammatory cells
- Phagocytosis of debris - neutrophils, mac
2) Endothelial cells
- Angiogenesis
3) Fibroblasts/Myofibroblasts
- ECM proteins e.g. colagen
- Wound contraction
Describe the process of angiogenesis in fibrous repair?
1) Endothelial proteolysis of b.m.
2) Migration of endothelial cell via chemotaxis
3) Endothelial proliferation via VEGF
4) Endothelial maturation and tubular remodelling
5) Recruitment of periendothelial cells
Describe the role of the ECM in fibrous repair?
1) Supports and anchors cells
2) Separates tissue compartments e.g. b.m
3) Sequesters GFs
4) Allows communication between cells
5) Facilitates cell migration
Describe the 1st process of fibrous repair?
1) Inflammatory cell infiltrate
- blood clot forms
- A.I. around edges
- C.I. : macrophages and lymphocytes migrate into the clot
Describe the 2nd process of fibrous repair?
2) Clot replaced by granulation tissue
- angiogenesis - capillaries and lymphatics sprout and infiltrate
- myo/fibroblasts migrate and differentiate
- ECM is produced by myo/fibroblasts
(over time vascularity decreases and [ECM] increases)
Describe the 3rd process of fibrous repair?
3) Maturation
- comparatively long-lasting
- cell population falls
- collagen increases, matures and remodels
- myofibroblasts contract and reduce volume of defect
- vessels differentiate and are reduced
- left with fibrous scar
What is healing by primary intention?
1) Incised wound
2) Apposed edges
3) Minimal clot and granulation tissue
4) Epidermis regenrates
5) Dermis undergoes fibrous repair
6) Sutures out at ~10 days: approx. 10% normal strength.
7) Transition from granulation tissue to scar tissue
8) Maturation of scar continues up to 2 years
9) Minimal contraction & scarring, good strength
10) Risk of trapping infection - abcess
What is healing by secondary intention?
1) Infarct, ulcer, abcess or any large wound
2) Quantitative differences:
- unapposed wound edges
- large clot dries to form a ‘scab’ or ESCHAR
- epidermis regenrates from the base up
- repair process produces much more GRANULATION TISSUE
Give differences between secondary intention and primary intention healing?
1) Produces more contraction to reduce volume of defect
2) Produces a larger scar; not necessearily weaker
3) Takes longer
What local factors influence wound healing?
1) Type, size, location of wound
2) Apposition, lack of movement»_space;> skin wounds, bone fractures, severed nerves
3) Blood supply : Arterial, Venous
4) Infection: Suppuration, gangrene, systemic
5) Foreign material: dirt, glass, sutures, necrotic tissue
6) Radiation damage
What general factors influence wound healing?
1) Age
2) Drugs and hormones
3) General dietary deficiencies e.g. protein
4) Specific dietary deficiencies
- Vit C for collagen OH
- essential AAs
5) General state of health
- chronic diseases e.g. diabetes, RA etc.
6) General CV health
What are 3 complications of repair?
1) Insufficient fibrosis
- wound dehiscence; hernia; ulceration
- obesity, elderly, malnutrition, steroids etc
2) Excessive fibrosis
- cosmetic scarring; keloid; cirrhosis; lung fibrosis
3) Excessive contraction
- obst. of tubes & channels (strictures)
- limitation of joint (contractures)
