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Healing from Inflammation (Angiogenesis (mechanisms (mobilisation of…
Healing from Inflammation
Regeneration
involves the replacement of damaged cells with identical type of cells
only a few organs/tissues are capable of regeneration
liver, epidermis, gastric epithelium, hematopoietic cells
tissues require the presence of stem cells and an intact extracellular matrix
the ECM used for cell migration and to maintain cell polarity; it contains essential cells and chemicals for repair
the ECM provides structure to the tissue without it regeneration isn't possible
Repair
involves the formation of scar tissue
fibroblasts synthesize and secrete collagen fibres to form dense fibrous connective tissue
scar tissue doesn't have the same function as the original tissue
mature scars have few blood vessels and are comprised of dense collagen
as repair continues, the # of endothelial cells and fibroblasts decreases
fibroblasts deposit increasing amounts of ECM
collagen synthesis begins 3-5 days after injury and continues for several weeks
Growth Factor
induces cell division
released by platelets, endothelial cells, macrophages, fibroblasts
bind to cell membrane receptors and trigger cell division
activation of receptor takes place inside the cell
signalling cascade is then triggered
the transcription of genes involved in cell division is activated
ECM
Components
Basement Membrane- basal lamina
epithelial cells sit on a thin BM
interstitial (extracellular) matrix
what's found between connective tissue cells, between epithelial cells and between smooth muscle cells
mesh between the cells that have fibroblasts
granulation matrix (provisional)
a temporary patch, characteristic of wound repair
later serves as a platform for migration of repair cell such as macrophages, epidermal/endothelial cells and fibroblasts
Functions
provides support for anchorage and migration of cells
inflammatory cells use ECM as support to move to site of injury
gives cells a polarity (top and bottom)
cells of the interstitial epithelium
contributes to control of proliferation and differentiation
firmly anchored cells tend to proliferate more than poorly-anchored cells
involves integrins
basement membrane sets boundaries for different microenvironments
epithelium v. underlying connective tissue
forms part of the kidney's filtration system
important guide during repair
loss of BM leads to disorganized repair and nonfunctional tissue
regulatory molecules are stored in the ECM
fibroblast GF is stored bound to proteoglycans in the ECM
these molecules are released when tissue is damaged
medicate rapid activation of fibroblasts and recruitment of other inflammatory cells for repair
Angiogenesis
early step in healing process
formation of new blood vessels
needed in order to bring repair mediators to site (cells, nutrients, fluid)
creates granulation tissue
mechanisms
mobilisation of endothelial precursor cells (EPC) from bone marrow
EPCs migrate from bone marrow to site of damage and can differentiate into endothelial cells
mobilisation of pre-existing endothelial cells
new blood vessels branch off pre-existing vessels
endothelial cells divide repeatedly, extending outward from existing blood vessels
cytokines and GF activate existing endothelial cells
Granulation Tissue
migration of fibroblasts to the site of injury and their subsequent proliferation is triggered by multiple GF
released from platelets, macrophages, endothelium
repair phase begins when macrophages begin showing up
ingest debris from initial damage or damage caused by neutrophils, secrete collagenase in order to further break down damaged tissue
secrete GF for fibroblast and they begin multiplying and secreting new collagen
also stimulate angiogenesis
granulation tissue is converted into a scar (fibroblasts, dense collagen, elastic tissue, other ECM components)
vascular regression takes place and eventually transforms the richly vascularized granulation tissue into pale, avascular scar
Tissue Remodelling
architecture of the scar becomes reoriented to increase the tensile strength of the wound
simultaneous synthesis and degradation of collagen fibres and other ECM components
Matrix metalloproteases (MMPs) are responsible for
ECM degradation
produced by fibroblasts, macrophages, neutrophils, synovial cells, and some epithelial cells
allow cells to move through the ECM
digest clotting factors, various adhesion molecules, ECM proteins
Healing by Primary Intention
minimal damage, without infection
involves coagulation and inflammation
clot seal the wound (thrombus) and prevents microorganisms from entering the wound and prevents loss of fluid
thrombus is made of fibrin which forms mesh that traps platelets and RBC
neutrophils and macrophages ingest and digest cellular debris and release chemical mediators/GF for the migration and proliferation of fibrous and endothelial cells
following coagulation & inflammation, granulation tissue develops (5 days-3 weeks)
characterized by extensive angiogenesis and the proliferation and migration of fibroblasts
newly formed blood vessels are leaky, leading to exudation and deposition of plasma proteins in the ECM (fibrogen and fibronectin)
deposited proteins provide support for the migration of fibroblasts and endothelial cells
secondary intension involves damage that is more considerable than primary intention