Cell Growth, Fibrosis, Wound Healing Flashcards
general timeline for tissue repair
Inflammation (contain injury and agent)
Repair (2 parts) - regeneration and fibrosis or fibroplasia
regneration
recovery of original tissue by cell growth, proliferation, migration, and differentiation
labile cells
capable of regeneration - continually dividing cells like surface epithelia
stable cells
infrequentnly dividing cells - liver and smooth muscle
permanent cells
rarely / non-dividing cells like neurons and skeletal muscle cells
gliosis
scaring mechanism in the central nervous system
fibrosis/fibroplasia
scaring - last means of repair for a tissue
depends on the regenerative capacity of the tissue or the extend of the injury or defect
location of adult stem cells
reside permanently in most organs
liver adult stem cells
ovalocytes- in the ducts of Hering
become activated following fulminant hepatic failure and chronic liver disease (process will be slowed)
stellate cells
skeletal muscle stem cells which have the ability to regnerate
3 mechanisms of regeneration in surface epithelium
- increase number of dividing stem cells
- expanding the number of cells in the replicating compartment
- decreasing replication time
healing involves combination of..
regeneration and fibroplasia
cardiac insufficiency, portal hypertension and liver failure, chronic respiratory failure, joint disability and deformity can be caused from…
diseases that are complicated by fibroplasia
steps in tissue repair
- inflammation
- cell proliferation and migration
- synthesis of extracellular matrix (ECM)
- Remodeling of ECM
mainly responsible for the formation and function of granulation tissue
growth factors
angiogenesis from pre-existing vessels
- degradation of basement membrane
- migration of endothelial cells
- proliferation of endothelial cells
- Maturation and tube formation
2 domains in ECM structure and properties
- Basal Membrane- cells can adhere to and move along - necessary for re-epitheliazation of ulcer
Consist of non -fibrill collagens, laminin, heparan sulfate, proteoglycan and other glycoproteins - Interstitial Matrix- prominent element in connective tissue- fibrill collagen and non-fibrill collagen, elastin, hyaluronate - PROMINANT IN LAYER 3 (ecm formation)
3 properties of ECM
- stuff between cells giving tissues the physical characteristics like tugor, elasticity, rigidity
- reservoir for molecules like growth factors
- adherence capbilities for the cells
ECM structure -3 elements (macromolecules)
fibrous structural proteins
cell adhesion proteins (CAMs)
Gel of protoeglycans and hyalluronan
metalloproteinases
remodelling is achieved by this in a process of degradation of collagen and other ECM proteins by this enzyme
inflammation (step 1) associated with what layer?
Layer 1
Necrosis and Acute Inflammatory Exudate
Tissue elements and molecular elements in Layer 1 - acute inflammation and necrosis
Tissue: Fibrin, neutrophils, macrophages, platalets
Molecular:
Interleukins, Interferons, Tumor Necrosis Factor
Growth Factors: PDGF FGF
myeloperoxidase
Neutrophil granulocytes = secrete the myeloperoxidase - carry out their immune function - enzyme
*this digests cells and and signals the second layer
Tissue elements and molecular elements in Layer 2- granulation tissue
Cellular : Capillaries, Fibroblasts, Macrophages Molecular Elements EGF/TGF-alpha PDGF FGF VEGF - angiogenisis TGF-beta Angiopoietins
Step 2 in tissue repair corresponds with what level in ulcer
step 2 = cell proliferation and migration
Layer 2- the granulation tissue layer
Step 3 in tissue repair corresponds with what level in ulcer
Step 3 = synthesis of ECM Layer 3 of the ulcer- granulation tissue AND ECM
Step 4 in tissue repair corresponds with what level in ulcer
step 4 = remodeling of ECM and layer 4 in ulcer = fibrosis scar
Describe Layer 3- synthesis of extracellular matrix
ECM - 2 domains (basal and interstitial) and 3 elements - fibrous structural proteins, CAMs, and Gel of proteoglycans and hyaluronan
granulation tissue
capillaries, fibroblasts, macrophages
CAMs
one of the elements of the ECM structure
Cadherins, Integrins, Fibronectin, Laminin
Fibrous structural proteins
one of the elements of the ECM structure
Collagens, Elastins
ECM functions
Tissue Texture- turgor, elasticity, rigidity
Resoivoir - growth factors
Substratum matrix- cell adherence and migration
events in layer IV
Remodeling of ECM and formation of collagen plates
Regression of blood vessels
Wound contraction
Collagenases, Gelatinases, Stromelysins are all?
Matrix metalloproteinases
local factors effecting wound healing
Blood supply, denervation, infection, , foreign body, necrotic tissue, mechanical stress, surgical technique, type of tissue
Systemic factors affecting wound healing?
diabetes, malnutrition, steroids, uremia, hypoxia, vitamin C defiency, malignant disease
ki67?
marker for surface epithelial proliferation
paracrine signaling with FGF
derived from macrophages causing fibroblasts to proliferate into granulation tissue