L27- tissue repair and fibrosis Flashcards
(28 cards)
list the different outcomes of tissue injury
regeneration, healing, fibrosis
describe regeneration
caused by superficial tissue damage or some inflammatory responses.
the restoration of tissue to original state by replacing lost structures
requires intact scaffold, requires stem cells to be intact
describe healing
Caused by deep wounds
Formation of scar tissue
requires extracellular matrix, collagen deposition occurs and you get scars
describe fibrosis
caused by persistent tissue damage
formation of excessive fibrous tissue (this can affect organ function)
regeneration in mammals
typically cannot regenerate whole complex structures
- however deers regenerate antlers annually
what is compensatory growth
when an organ attempts to regenerate fully but does not completely
examples of compensatory growth in mammals
liver - a partial hepatectomy where more than 25% of the liver remains can regenerate the whole liver. It will be structurally different in size but functionally the same
kidney - unilateral nephrectomy where one kidney is removed the remaining kidneys can grow to the mass of two kidneys combined
these both occur via hyperplasia/hypertrophy
Identify differences between tissue regeneration, tissue repair
and fibrosis
what are the factors that influence tissue repair
- Extent of tissue damage
- Location of injury damage (function and intrinsic capacity to heal)
- Duration of injurious agent
- Infection (delays healing, prolongs inflammation)
- Poor perfusion (e.g. Peripheral vascular disease or diabetes, compromises wound healing)
- Nutritional status (protein deficiency, Vit C inhibit collagen synthesis)
- Steroids (anti-inflammatory effects may influence TGFβ production = less collagen = weak scar)
- Mechanical stress (tension on a wound)
- Foreign body (perpetuate chronic
inflammation)
what is healing and repair
- restoring tissue to normal function
- process of cell regeneration and repair of damaged or necrotic tissue
3 types of cells in stages of growth for tissue repair
Labile - continuously dividing cells (GI, hematopoietic cells)
Stable - quiescent cells (G0) that
proliferate following damage (fibroblasts, epithelial cells)
Permanent - terminally differentiated
cells eg. Cardiac myocytes in heart,
neuronal cells
Regulation of healing and repair
- Most important control: inducing resting cells to enter cell cycle
- Balance of stimulatory or inhibitory factors
- Shorten cell cycle
- Decrease rate of cell loss - anti apoptotic mechanisms
forms of chemical signalling in cell response
Autocrine - cells respond to their own secreted factors
Paracrine - cells respond to signalling of nearby cells
Endocrine - cells respond to signalling from distant cells via the bloodstream
TGF- beta
sourced from: Platelets, T cells, Mφ, endothelial, keratinocytes, SMC, Fibroblasts
major cell targets: Fibroblast, chemotactic for many cells,
stimulates angiogenesis and collagen
production
what are the components of an extracellular matrix *
Non-cellular component within all tissues and organs occurring between epithelial, endothelial and SM cells
Interstitial matrix: form connective tissue made of fibrillar and non fibrillar collagens, elastin, fibronectin, proteoglycans, hyaluronate
Basement membrane: produced by epithelial and mesenchymal cells. Associated with basal cell surface
composed of amorphous non-fibrillar collagen (type IV), laminin, heparan sulfate, proteoglycan, glycoproteins
formation of scars
Granulation occurs to fill tissue space
Fibroblasts are a major source of ECM components as repair continues the proliferation of cells decrease and the production of collagen increases (3-days post injury)
Granulation tissue then becomes the scar made up of dense collagen, spindle fibres and elastic tissue fragments
Vascular regression leads to scar becoming pale from consistent remodelling
define extracellular matrix
A conglomerate of weaves, struts, glues and gels that interconnect cells and their cytoplasmic matrices
what are the main groups of biochemicals that make up the ECM
i) complex polysaccharides
ii) glycoproteins such as fibronectin, laminin
iii) proteoglycans
iv) various types and amounts of structural and insoluble collagen fibres and flexible elastic fibres
what is the function of the ECM
- Provides a scaffold for cells
- Provides spatial and locational (?) information to cells
- Controls activities such as proliferation, migration, differentiation
apoptosis - integrins - Acts as a sink for various growth factors (TGF) and cytokines (Oncostatin M)
outline the three stages of cutaneous wound healing
Inflammation (3hr - 5d): macrophages and leukocytes rush the area to clear away dead tissue and accumulate inflammatory cells
Proliferation (3d-1M): fibroblasts endothelial cells proliferate and enters the wound to form granulation tissue
Remodelling (3wk-2Y): collagen is degraded and remade, vascular regression, remaking to reutn to original state
outline the 7 steps of wound healing
- Inflammation to remove damaged and dead tissue
- Entry and proliferation of
connective tissue and
parenchymal cells - Formation of new blood vessels
- Synthesis of new ECM proteins
- Tissue remodelling
- Wound contraction - myofibroblasts
- Acquisition of wound strength
granulation tissue formation
At day 3 primitive granulation tissue (proliferating angioblasts, fibroblasts, myofibroblasts) begins to invade the incision space
FGF2 & VEGF from macs, keratinocytes & endothelial cells promote angiogenesis
Endothelial cells express integrins to sprout new blood vessels
what is the role of fibro/myofibroblasts in granulation synthesis
- Migrate to & proliferate at the site of injury
- Deposit ECM proteins
- PDGF, FGF2 & TGFβ from inflammatory cells & stimulate
fibroblasts - Wound contraction
what is primary intention
a wound is sutured and healed closed leading to minimal scarring
