Powerpoint-Chap3 Flashcards
What happens in wound healing
angiogenesis acute inflammation fibrobast and parenchymal regeneration ECM proteins scar formation remodeling of parenchymal elements remodeling CT
What layer is critical for regeneration and restoration of tissue
the ECM
What parts of our body can completely regenerate
epidermis, GI tract, epithelium and the RBCs
does the liver truly regenerate
no, compensatory hyperplasia
what is the term resolution when talking about wound healing
complete restoration to original function
What are labile cells
continuously dividing cells from M to G1 to S to G2 to M
what are types of labile cells
epidermis, mucosal epithelium, GI epithelium and stel cells
what are stable cells
low level replication
Go to G1 to S to G2 to M
what are types of stable cells
hepatocytes, renal tubular epithelium, pancreatic acini
stem cells
what is the proliferative potential of permanent cells
almost never divide, stuck in Go
what are examples of permanent cells
CNS neurons, cardiac and skeletal myocytes
What is a totipotent stem cell
very early embryonic
what is a pluripotent stem cell
in embryo- embryonic stem cell
what is a multipotent stem cell
in fetus and adult
what is a progenitor or lineage committed stem cell
closer to final destination
what is an induced pluripotent stem cell
embed nucleus of differentiated cell into cytoplasm of oocyte
What stem cell can make the placenta and fetal membranes
the totipotent
What is transdifferentiation
non stem cell transforms into different cell type
already differentiated stem cell creates cells outside already established differentiation path
what is transduction
genes from a host cell (bacterium) are incorporated into genome of bacterial virus (bacteriophage) and then carried to another host
what are the stem cells in skel m
satellite cells
what are the stem cells of GI tract
crypt cells
what are the stem cells in liver
oval cells
what layer are the stem cells of epidermis in
the basement membrane
where are the corneal stem cells
limbus
what factors influence regeneration
cell-cell interaction, conditioned medium, contact inhibition
Growth Factors
ECM
what are the 2 major components of the ECM
laminin and fibronectin
what are the parts of laminin
epithelia and fibroblasts
what are the parts of fibronectin
epithelia and fibroblasts
What are the 3 ways in which cells communicate
paracrine, autocrine, and endocrine
describe paracrine signaling
short term, local effects
what is autocrine signaling
cells tell themselves to do things
What is the role of platelet derived growth factor
activates fibroblasts, sm m, monocytes
what is the role of fibroplast growth factor
mitogenic fo rmost msesnchymal cells and induces endothelial cells to release proteolytic enzyme
important in scar formation
what is the role of epidermal growth factor
mitogenic for epithelial cells, fibroblasts, glial cells and SMC
what is the role of transforming growth factor
alpha is the same as epidermal growth factor
beta acts as a growth stimulator OR inhibitor
what is the role of VEGF
angiogenesis
what are the roles of IL 1 and TNF
induce fibroblast proliferation and collagen synthesis
TNF can also stimulate angiogenesis
What factor has a role in cachexia
TNF
What are the main growth factors for monocyte chemotaxis
FGF and TGF beta
what is keratinocyte growth factor
from fibroblasts and stimulates keratinocyte migration, proliferation and differentiation
What type of things stimulate G protein coupled receptors
odorants, light R
proteins, lipids, amines etc
What are the components of the ECM
collagen, elastin, proteoglycans, adhesive glycoproteins, integrins
what is the baseline structure for physical stress
elastin
what is the function of proteoglycans in ECM
help regulate ECM structure and permeability
modulate cell growth and differentiation
maintain cell morphology
what is the function of adhesive glycoproteins
induce fibronectin, laminin and vitreonectin
link ECM components to cells via cell surface integrins
what is the role of integrins in ECM
cell surface R that mediate adhesion of cells to ECM
What collagen makes up the basememnt membrane
collagen IV
what type of collagen makes up cartilage
type II
what collagen is involved in repair
collagen III
what connects hyularonidase to cell surface
CD44
what does granulation tissue look like on slide
soft, pink and granular
many fibroblasts
alot of new thin-walled capillaries
what is a granuloma
chronic inflammatory response (macrophages, multinucleate giant cells)
what do fibroblasts make
collagen
first type III then I
resulting in fibrosis with CT
what is a 1st intention or 2nd intention wound
1st can be closed because not too wide- can be approximated
2nd- leaves much larger scar, have to leave open, sometimes b/c size or infection already there and needs to drain
What are the steps of angiogenesis
proteolytic degradation of BM
migration of endothelial cells
proliferation of endothelial cells
maturation
What cells begin angiogenesis
endothelial precursor cells from the bone marrow and preexisting vessels
What agents can induce angiogenesis besides VEGF
hypoxia, TGFbeta, PDGF, TGF alpha
Which is the VEGF receptor for lymphatic endothelial cells
VEGFR-3
How do the tip cells talk to the cells behind them
there is negative feedback through notch signaling to say stop replicating so the blood vessels growth in one direction
What is the role of DLL4 in angiogenesis
dec sprouting, dec EC proliferation
inc vessel size and organization
what does VEGF drive
increase sprouting, EC proliferation and survival, decrease vascular organization
What is the role of granulation tissue in wound healing
anti-infection and protecting the wound surface
filling incision and wound
replacing necrotic tissue, effusion and other foreign body
vessels provide conduit for nutrients and cells
What are the characteristics of scar tissue
pale avascular tissue
collagen, fragments of elastic tissue, ECM and inactive fibroblasts
What are the advantages of scar tissue
resilient permanent patch
tensile strength, integrity and strength for tissue after healing
what are the actions of macrophages
debridement, removal injured tissue antimicrobial chemotaxis fibroblasts angiogenesis deposition of ECM
what factors from macrophages are released for matrix synthesis
TGF, EGF, PDGF, cytokines:TNF IL1 and IFNgamma
What is primary union of skin
healing by first intention
surgical incision with sutures, surgical glue
when do cells mirgrate into healing by first intention
24 hours
when does regeneration start in healing by first intention
3 days
when is the scar present in wounds by first intention
7-10 days
how long can it take for a scar to mature in a wound by first intention
1 month-2 years
what is involved in early scarring
capillaries bridge wound, lymph vessels near, macrophages scavenge, collagen type I, apoptosis
cross-linking of collagen (pink to white transition)
inflammation of wound peaks on what time scale
about a day
when is majority of matrix deposition taking place on wound healing time scale
about 3 days
3-10
what cells are proliferating through skin healing
epithelial and fibroblasts
what seals the wound by second intention
fibrin
What stimulates collagen synthesis in scarring
TNF IL1 IL4 IL13
from macrophages
what is the role of metalloproteinases
break down the collagen
what are conditions that interrupt healing process
vit deficiency glucocorticoids immune status infection DM
what is wound dehiscence
separation of layers of surgical wound
sutures break
what are healing abnormalities
contractures
cicatrization
pyogenic granuloma
What are keloids
excessive scar formation
what the most common cause of wound contracture
burns
what is the difference between hypertrophic scar and keloid
if scar is confined to area that is wounded- hypertrophic scar
what goes up in liver obstruction
all the liver enzymes. In addition- specifically bilirubin
widened chest and decreased tissue in lung is clinical key to what
emphysema
in heaptic necrosis what will a liver profile show
increased liver enzymes
Increased TLC and RV
decreased FEV1 is indicative of what
emphysema
why is a liver nodular if Px has hepatitis
normal architecture destroyed, hepatocytes regenerating forming nodules
What is a PAS stain used for? what color is it
to see fibrosis, glycogen
with diastase- to digest away glycogen
dark red
how do we stain for alpha 1 antitrypsin
using immunohistochemistry to make Ab for antigen. Then Ab to Ab that has brown chromogen
which type of genotype causes worst version of alpha1 antitrypsin deficiency
ZZ homozygous
If you have a null alleles for a1 antitrypsin would the immunohistochem work
no because wouldn’t have any of it
where do abnormally folded proteins build up in cells, and what is the net result
in the ER.
causing ER stress- signaling cytochrome C– apoptosis
what results from the ER trying to degrade misfolded proteins
oval cytoplasmic globular inclusions
hepatocellular degeneration, giant cell formation, cholestasis, cholangitis, cirrhosis
When ER releases contents what ion is important
Ca because that is activating all the phospholipases and everything starts degrading
what cell is mainly responsible for the scarring in hepatitis
macrophages
The development of regenerative nodules in liver can lead to what
DNA damage and neoplasia
What is scarring of liver called
cirrhosis
why does a1antitrypsin lead to emphysema
walls of alveoli destroyed because of increased secretion of elastase.
missing SA so causing hypoxia. also have fibrosis
how does a1antitrypsin deficiency cause fat necrosis
elastase break down skin and fat
What are Tx methods for a1antitrypsin deficiency
IV alpha1 antitrypsin and NSAIDs
with alpha1 antitrypsin deficiency and a FEV1 below 20% predicted what is the 2 year mortality
40%
With liver cirrhosis and alpha1 antitrypsin deficiency what is mean survival
2 years
