Lecture 4 - Healing and Repair Flashcards
what is fibrous repair?
replacement of functional tissue by scar tissue
what are the key components of fibrous repair?
- cell migration
- blood vessels - angiogenesis
- ecm production/remodelling
how does cell migration contribute to fibrous repair?
inflammatory cells - phagocytosis of debris and chemical mediators
endothelial cells - angiogenesis
fibroblasts/myofibroblasts - ecm proteins and wound contraction
how does angiogenesis contribute to fibrous repair?
development of new blood supply is vital to wound healing to provide access for cells and deliver o2 and nutrients
endothelial proliferation induced by proangiogenic factors such as vegf
preexisting vessels sprout new ones
endothelial proteolysis of basement membrane
migration of endothelial cells by chemotaxis
endothelial proliferation
endothelial maturation and tubular remodelling
recruitment of periendothelial cells
how does ecm contribute to fibrous repair?
supports and anchors cells separates tissue compartments sequesters growth factors allows communication between cells facilitates cell migration
what are the three stages of fibrous repair?
- inflammatory cell infiltrate
- clot replaced by granulation tissue
- maturation
describe inflammatory cell infiltrate
blood clot forms
ai around edges
ci - macrophages and lymphocytes migrate into the clot
describe the clot being replaced by granulation tissue
angiogenesis
fibroblasts/myofibroblasts migrate and differentiate
ecm produced by myo/fibroblasts
describe maturation
comparatively long lasting cell population falls collagen increases, matures and remodels myofibroblasts contract - reduces volume of defect vessels differentiate and are reduced left with fibrous scar
what is regeneration?
replacement of dead or damaged cells by functional, differentiated cells
describe stem cells
potentially limitless proliferation
daughter cells remain as stem cells or diffferentiate to a specialised cell type
what is a unipotent cell?
can only produce one type of differentiated cell
eg epithelia
what is a multipotent cell?
can produce several types of differentiated cell
eg haemotopoietic
what is a totipotent cell?
can produce any type of cell
eg embryonic stem cell
what is a labile cell?
normal state is active cell division: g1-m-g1
usually rapid proliferation
eg epithelial or haematopoietic cells
what is a stable cell?
resting state: g0
speed of regeneration variable
eg hepatocytes, osteoblasts, fibroblasts
what is permanent cell?
unable to divide: g0
unable to regenerate
eg neurones, cardiac myocytes
how do growth factors control regeneration?
promote proliferation of stem cells
promote expression of genes controlling cell cycle
hormones and proteins
autocrine, paracrine and endocrine release from many cell types
how does contact between basement membrane and adjacent cells control regeneration?
signalling through adhesion molecules
inhibits proliferation in intact tissue - contact inhibition
loss of contact promotes proliferation
exploited in cancer
describe healing by primary intention
incised wound
apposed edges
minimal clot and granulation tissue
epidermis regenerates
dermis undergoes fibrous repair
sutures out at 5-10 days - approx 10% strength
maturation of scar continues up to 2 years
minimal contraction and scarring, good strength
risk of trapping infection leading to abscess
describe healing by secondary intention
infarct, ulcer, abscess or any large wound
unapposed edges
large clot dries to form scab
epidermis regenerates from base up
repair process produces much more granulation tissue
how does secondary intention compare with primary intention?
produces more contraction to reduce volume of defect
produces a larger scar but not necessarily weaker
takes longer
what local factors influence the efficacy of healing and repair?
- type, size, location of wound
- apposition, lack of movement
- blood supply - venous or arterial
- infection
- foreign material including necrotic tissue
- radiation damage
what general factors influence the efficacy of healing and repair?
- age
- drugs and hormones
- general dietary deficiencies eg protein
- specific dietary deficiencies eg vitamin c or essential amino acids
- general state of health eg chronic diseases
- general cardiovascular status
how does cardiac muscle undergo healing and repair?
fibrosis
how does bone undergo healing and repair?
callus formation
how does the liver undergo healing and repair?
acute damage - regeneration
chronic damage - cirrhosis
hepatocytes have some regenerative capacity but architecture does not regenerate - imbalance leads to cirrhosis and nodules
how do peripheral nerves undergo healing and repair?
wallerian degeneration
proximal degeneration, distal proliferation (1mm/day)
how do central nerves undergo healing and repair?
no regenerative capacity
glial cells can proliferate - gliosis
how does muscle undergo healing and repair?
cardiac and smooth are permanent - replaced by a scar
vascular smooth muscle has some limited regeneration
skeletal has limited regenerative capacity due to satellite cells
