58-Resolution and Repair Flashcards
How do you downregulate inflammation
Stop proinflammatory stimuli
Increase lipoxin
Nitric oxide production
Anti inflammatory cytokine secretion (IL-10 and TGF-B)
What does lipoxin do?
antifinflammatory, inhibit neutrophil adhesion and chemotaxis
From arachidonic acid, leukocyte enter tissue and leukotrienes get converted to lipoxins
What does nitric oxide do
reduce leukocyte recruitment and decrease platelet activation
What does cytokine IL10 do
Released by macrophage to down regulate macrophage (negative feedback) for anti inflammation
What does TGF-B do
suppress acute inflammation
Outcomes of acute inflammation
Complete restitution, no permanent damage, regain function Tissue replacement (fibrosis) Progress to chronic inflammation
What causes an acute inflammation to progress to chronic
Persistence of injurious agent
interference with healing
autoimmunity
Outcomes of chronic inflammation
Healing with or without scar
Tissue damage
What does organized mean
In growth of fibroblasts into the blood vessel wall, leads to scarring
A subtype of healing response
What is critical to the survival of an organism
Ability to repair damage
Functions of inflammatory response
Eliminate insult and tissue damage
Start process of repair
2 ways to heal
regeneration and scar formation
What is regeneration
Replace damaged cells and return to normal state, mild injury, no damage to underlying tissue
What is scar formation
Incapable of regeneration or supporting structures are severely damaged
Deposition of fibrous tissue, severe injury
Regeneration depends on what
proliferative ability of cell
Growth factors
Interactions between cells and matrix
Type soft proliferative tissues
labile, stable, permanent
What are labile tissues
Readily regenerate, continuously dividing
Intact basement membrane
Bone marrow, epithelial, GI
What are stable tissues
Normally quiet but can proliferate
parenchyma, endothelial, fibroblasts, smooth muscle
What are permanent tissues
Non proliferative
Terminally differentiated
Neurons and cardiac muscle
Types of stem cells
Embryonic and adult
Labile tissues
Characteristics of adult stem cells
Limited capacity of self renewal
Can only become cell from where it is found
What is asymmetric replication
1 daughter cell differentiates and matures
1 cell remains undifferentiated for self renewal
what are growth factors
Proteins that stimulate survival and proliferation, migration, and differentiation
What produces growth factors
Macrophages and lymphocytes
Except HFG (fibroblasts, stromal cells in liver)
VEGF (mesenchymal cells)
What are the growth factors
EGF TGF a and b HGF VEGF PDGF FGF
Types of ECM
Interstitial matrix
Basement membrane
What makes up basement membrane
Type 4 collagen
laminin
proteoglycan
What makes up interstitial matrix
fibrillar collagen
Elation
proteoglycan
hyaluronan
What does the ECM do
Regulate proliferation, movement, differentiation, reservoir for growth factors, mechanical support
TISSUE REGENERATION!! If ECM is destroyed=scar formation
When does scar formation occur
Severe or chronic tissue damage to cells or ECM
Injury to non dividing cells
Replace cells with connective tissue (fibrosis)
What is gliosis
Scarring in brain from glial cells (astrocytes)
Steps in scar formation
Injury
Inflammation
Translation tissue
Scar formation
What is angiogenesis
New vessel growth
What is fibrogenesis
Migration and proliferation of fibroblasts and depositing collagen
What is granulation tissue
Angiogenesis and fibrogenesis
When does repair begin
24 hours
When does graduation tissue appear
3-5 days
What mediates angiogenesis
VEGF
When is angiogenesis needed
Critical for healing
Collateral circulation for ischemic
Tumor growth
What are the steps for fibrogenesis
Migration and proliferation of fibroblasts
Deposition of ECM
What mediates fibrogenesis
TGF-B
What does TGF-B do
produce collagen, fibronectin, proteoglycan
Inhibit collagen degradation
What happens if you don’t have normal collagen synthesis
Wont heal normally
What is fibrinous
Containing fibrin
Insoluble protein from fibrinogen
What is fibrou
Containing fibroblasts and collagen
What is granulation tissue
Early scar
Highly vascular, fibroblasts, loose ECM, inflammatory cells
What is a granuloma
Inflammation with epithelioid macrophages
What synthesizes remodeling of scar
fibroblasts
What synthesizes degradation of scar
metalloproteinases (MMP)
Factors that influence tissue repair
Infection Nutrition Steroids (anti inflammatory) mechanical variables Poor perfusion Foreign bodies location keloid
What is the most important factor for tissue repair
infection
What nutrient is important for collagen synthesis
Vitamin c
What is a keloid
Accumulation of collagen, prominent raised scar
3 phases of wound healing
Inflammation
Translation tissue formation
Contraction of wound, ECM deposition, remodeling
