Tissue Repair & Chronic Inflammation Flashcards
What type of injury does a scar become produced from
Prolonged and severe injury
Briefly explain scarring
Damage to connective tissue & intra cellular matrix which holds the tissue together and comes from a more prolonged and severe injury
What is normal homeostasis
A balance of proliferation and apoptosis
When an injury occurs, which two routes can a cell take
- regeneration
Or - repair
Which further two routes can a cell take other than regeneration
- renewing tissues
Or - stable tissues
What happens to renewing tissues
Complete regeneration:
Epidermis, GI tract epithelium, hematopoletic system
What happens to stable tissues
Compensatory growth of eg liver and kidney
Which further two routes can a cell take other than repair
- wound
Or - chronic inflammation
What happens to a tissue which forms a wound
Wound healing and scar formation (cannot compensate for injury)
What happens to a tissue during chronic inflammation
Fibrosis
Why would a tissue be unable to repair
If the injury persists and has to do with the type of injury, how severe it is and the time course of the injury
What happens to the tissue if the injury is mild
Tissue can heal without scarring as the scaffolding and connective tissue of cells remains intact
What happens to a cells which are unable to regenerate fully
Scarring
if injury persists eg from liver damage due to drinking
What type of cells are labile cells
Cells which divide and proliferate throughout life
What are labile cells derived from
Adult stem cells
What type of cells have a set life span
Labile cells
Give examples of labile cells
- Gut epithelium
- Corneal epithelium
- Blood cells
What example of cell is able to regrow and replenish at a mitotic rate
Epithelial cells
What is the name of corneal stem cells
Palisades of Vogt
What do palisades of Vogt do
Power our corneal stem cells and produce continual supply of corneal epithelial cells
Where are labile cells found within the cornea
Around the limbus
What do stable cells do
Usually divide slowly but if damaged can increase rate of cell division so can get tissue repair
Name examples of stable cells (can heal and grow but don’t usually turn over)
Hepatocytes eg liver Fibroblasts Vascular endothelial cells Smooth muscle cells Osteoblasts eg when bones break Renal tubular epithelial cells eg kidney
Where can pockets of stem cells which have the same effect of epithelial stem cells (to replenish) be found within the body
Gut & skin
What are permanent cells
Cells that cannot divide but may be capable of some cellular repair if the nucleus and Golgi are not impaired
Name examples of permanent cells
Neurons in retina (cannot get new cells to grow so if they’re gone they’re gone)
&
Cardiac myocytes
What needs to be initiated in order for cell growth and replenishment
The growth cycle
What is the growth cycle
To switch the cell on to divide and multiply
What can the growth cycle be done by
Particular signalling molecules eg growth factors
Or
Integrin signalling pathways
Can switch on mitotic pathway to replenish cells which have been killed
What do growth factors/chemical switches regulate
Cell proliferation
What are the three types of growth factors
Autocrine
Paracrine
Hormones
Explain the autocrine growth factor
Self signalling
Comes from the cell and binds to the receptor which initiates cell division
Explain the paracrine growth factor
Comes from damaged cell
Sends signals to adjacent cell telling them to divide and replace them
Explain the hormone growth factor
Signals to distant tissue to repair parts of the body such as muscle or bone peripheral tissue
Eg growth hormone
Where are receptors for signal transduction found
On the cell
Name three types of receptors for signalling transduction
- Intrinsic kinase activity
- G-protein coupled receptors
- Receptors lacking intrinsic kinase activity
What is intrinsic kinase activity
Growth factors which bind to the receptor and activate kinases
Give examples of intrinsic kinase activity growth factors
PI3-kinase
Mitogenic activated protein kinase (MAP)
PLC-y
What do kinases do
Activate transcription factors that regulate the cell cycle
ie phosphorelation & dephosphorelation coupling switches receptors on & off
Give examples of G protein coupled receptors
Serotonin Vasopressin Histamine (activated by G protein & increases vasodilation) Glucagon Corticotrophin
As part of the G protein coupled receptors, what is cAMP and calcium important for
Tight junction formation
Ion channels
Transcription factors
Give examples of receptors lacking intrinsic kinase activity
Interleukins
Interferons
Growth hormones
Prolactin
What do receptors lacking intrinsic kinase activity activate
JAK (Janus kinase family) activate transcription factors that shuttle to the nucleus
Receptors lacking intrinsic kinase activity don’t rely on…
Phosphorylation and dephosphorylation coupling eg MAP kinase
What does mitogenic protein activated kinase use to activate mitosis
Phosphorylation
What happens in the IP3 pathway
IP3 binds to the IP3 receptor in the endoplasmic reticulum
Which increases intracellular calcium
Intracellular calcium effects transcription and translation as well as fluid transport
And activates calcium getting chloride channels
Cells under stress are swollen so it gets rid of fluid
What does the MAP kinase pathway activate
Transcription and translation
What does the JAK/STAT pathway regulate
Growth initiation
What are cyclic amp and what do they affect
Families of G proteins
Which also affect transcription and translation
What are G protein coupled receptors found in
Rod outer segments eg rhodopsin and cyclic Gmp
List the properties of extra cellular matrix & cell matrix interactions
- mechanical support & anchorage for cell migration (needs collagen or fibrin to hold on to to move along)
- control cell growth through intergrin cellular receptors
- maintain cell differentiation via intergrin receptors
- scaffold for tissue renewal which requires as basement membrane if BM damaged results in a scar
- establishes tissue micro environment (barrier)
- storage & regulation of growth factors for rapid deployment is EGF, FGF
What is the extra cellular matrix important for
Cell stability and vitality
What do we get if the extra cellular matrix breaks
Scarring
What does the integrin cellular receptors integrate between
Cell membrane and its basement membrane of its partner
What does the maintenance of cell differentiation via intergrin receptors go into
Another cell type
If you take a cell away from its environment it will differentiate into some other cell type eg fibroblasts or immature cells
What happens to the cell without scaffolding
No tissue repair or renewal
If JAKs doesn’t rely on phosphorylation, what do they respond to
Cytokines
Which regulates growth differentiation and cell movement where all the receptors help to increase cell tight junctions, divide and become motile which increases fluid permeability etc
What happens to cells which are moved away from their micro environment eg removed from their basement membrane
Dedifferentiate and can’t maintain their identity
What happens to an RPE cell which has been moved from its micro environment
Lacks micro villi
Lacks differentiation
No regularity
No hexagonal shape
What are proteoglycans important for
Signalling proteins for cell differentiation
Name some examples of basement membranes
Type 4 collagen
Laminin
Proteoglycan
What do integrin receptors do
Anchor the cell down to eg collagen fibres to maintain cell communication and differentiation
What do integrins interconnect with in generic tissues
The basement membrane
Also
With the cellular matrix and fibroblasts
What do proteoglycans form
Extracellular matrix
What are proteoglycans attached by to connect with fibroblasts
Integrins
What is the interstitial matrix composed of
Fibrillar collagens
Elastin
Proteoglycan and
Hyaluronan
Describe the connection between integrin receptors to a cell nucleus
Direct lines like spiders webs with cytoskeletal attachments to the cell nucleus
What is the significance of intergrin receptors connecting to the cell nucleus via cytoskeletal attachments
If there’s disruption to intergrin receptors, the signal will go to the cytoskeletal attachments
Why do integrin receptors attach to the cytoskeletal attachments
So there’s a physical communication between the extra cellular environment and integrin receptors to the cell nucleus, which maintains differentiation and protein attachment, migration and form of the cell
What does damage to the extracellular matrix release
bFGF