wound healing Flashcards
key growth factor in wound healing
PDGF (chemotaxis; activate fibroblasts, macs (to secrete GFs for prolif and angio), PMNs, smooth mm cells; angiogenesis; epithelialization; accelerates wound healing)
tissue injury exposes 3 things.
collagen, platelet activating factor, tissue factor
platelet activating factor?
generated by phospholipase in endotheliu to increase inflammatory cells and activate plts
chemotactic factors for inflammatory cells?
PDGF, IL8, LTB4, C5a, C3a, PAF, TNFa, IL1f
chemotactic factors for fibroblasts?
PDGF, EGF, FGF
angiogenesis factors?
hypoxia, PDGF, EGF, FGF, Il8
epithelialization factors?
PDGF, EGF, FGF
bradykinin
released in Type I hypersensitivity
peripheral vasodil, pulm vasocon, bronchoCONstriction, increased permeability
inactivated by ACE in lungs
histamine release?
mast cells (tissue), basophils (blood)
nitric oxide NO = endothelium derived RELAXING FACTOR
arginine precursor
NO activated guanylate cyclase, inc cGMP to dilate SMOOTH MUSCLE.
what has the opposite effect of nitric oxide?
endothelin (constrict smooth muscle)
what causes fever?
IL-1 cytokine (PGE2 mediated in hypothalamus)
NSAIDs effect on fever?
decrease PGE2 synthesis. decrease fever.
IL-10
decreases the inflammatory response.
interferons…?
inhibit viral replication (activate macs, NK cells, T cells)
acute phase reactants?
released by IL-6 mostly
CRP (activate complement)
amyloid A
fibrinogen
haptoglobin
ceruloplasmin
a1 antitrypsin, C3
*(stop: albumin, prealb, transferrin)
adhesion molecules? ROLLING ADHESION
L-selectin (leukocytes) bind E-selectins (endothelial) and P-selectins (plt)
B2 integrins (CD 11/18 molecules)? ANCHORING ADHESION
B2 integrins on leukocytes bind ICAMs on endothelial cells
anchor and help diapedesis (migration into cell)
classic complement pathway
unique: C1, C2, C4
activated buy IgG or IgM and antigen.
alternative complement pathway
unique: B, D, P
activated by endotoxin, bacteria, others
common complement?
C3
what electrolyte required for both complement pathways?
Mg
C3a C4a C5a are also referred to as
anaphylotoxins (increase vasc perm, bronchoconstr, activate mast/baso)
MAC membrane attack complex complement
C5b, C6b, C7b, C8b, C9b
cause cell LYSIS via hole in cell membrane
opsonization?
targeting of Ag for immune response
mediated by C3b and C4b
PGI2 and PGE2 fxn
vasoDILATION, bronchoDILATION, increase permeability, inhibit plt
NSAIDs vs ASA on COX
NSAIDs inhibit reversibly
ASA inhibits irreverisbly and inhibit plt adhesions by decreasing TXA2
steroids on COX
inhibit phospholipase so phospholipids cannot become arachidonic acid (so decrease inflammation)
lipoxygenase pathway (leukocyte derived)… leukotrienes.
also arachidonic precursors.
LTC4 LTD4 LTE4 fxn
slow reacting substance of anaphylaxis…
bronchoCONSTRICTION, vasoCONSTRICTION then increased permeability (wheal and flare)
LTB4
chemotactic for inflammatory cells
NE vs E release
NE released from sympathetic postganglionic neurons AND medulla
Epi just released from medulla
hormones released with inflammation?
CRF, ACTH, ADH (keep water), GH, Epi, NEpi
superoxide anion radical O2-
made by NADPH oxidase
cell defense: superoxide dismutase
CGD: NADPH issue can’t make O2-
hydrogen peroxide H2O2
made by: xanthine oxidase
cell defense: glutathione peroxidase, catalase
wound healing phases?
- inflammation (1-10 days)
- proliferation (5 days - 3 wks)
- remodeling (3 wks - 1 yr)
what type of collagen in proliferation phase?
3 to 1 … by the end of 3 wks
how fast is epithelialization & p. nerve regen?
1-2 mm/day
remodeling is what action in wound healing?
crosslinking of type I collagen
main cell type at 2 days, 4 days, 5+ days in wound healing?
0-2: PMN
3-4: mac
5+: fibroblasts**
fibronectin?
released by fibroblasts, chemotactic for macs, anchors fibroblasts.. makes up provisional matrix with HYALURONIC ACID
fibroblasts replace fibronectin-fiber with…?
collagen
most important factor in healing open wounds vs closed wounds?
open: epithelial integrity (secondary intention)
closed: tensile strength (primary intention)
strength layer of bowel?
submucosa
when to take out sutures
face: 1 wk
other: 2 wks
weakest time for bowel anastomosis?
3-5 days
myofibroblast function in scar; how to communicate
smooth muscle-fibroblast; communicate via gap junction
healing by secondary intention - wound contraction!
type I collagen
MC. skin, bone, tendon, healed wound
type II collagen
cartiage
type III collagen
wound healing…. blood vessels, skin
happens day 8 thru 1 year
type IV collagen
basement membrane
type V collagen
everywhere.. cornea
collagen synthesis reagents?
a-ketoglutarate, vit C, oxygen, iron, prolyl hydroxylase (hydroxylation)
what cross links in collagen?
proline (q3 amino acid)
scar strength compared to original tissue?
80% @ 8 wks
maximum collagen amount (uncrosslinked) at what time?
3 wks
d-penicillamine on cross linking?
inhibits collagen cross linking
transcutaneous oxygen measurement necessary for wound healing?
25+ mm Hg
how does DM affect wound healing?
hyperglycemia causes poor leukocyte chemotaxis
what vitamin couteracts effects of steroids on wound healing?
vitamin A 25000 IU qd
osteogenesis imperfecta?
type I collagen defect
ehlers danlos syndrome?
collagen disorders
marfans
fibrillin defect (CT protein)
epidermolysis bullosa?
excessive fibroblasts
tx: phenytoin
pyoderma gangrenosum
wound healing issue; treat with STEROIDS
DFI?
diabetic foot infection. mostly Charcot’s joint (2nd MTP joint)
when to stop chemotherapy if anticipating wound healing?
14 days
how does cartilage get blood flow?
it doesn’t… diffusion only for nutrients and oxygen
alpha granules in plt - contents?
plt factor 4,
factor V and VIII (coagulation factors)
vWF
fibrinogen
B-thrombomodulin (binds thrombin)
PDGF
TGF-B (modulates above responses)
dense granules in plt - contents?
adenosine, serotonin, calcium
plt aggregation factors?
TXA2, thrombin, plt factor 4
rate of wound infection
clean: 1-2% infection
clean contaminated: 5-10%
contaminated 15-30%
dirty >30%
treat venous leg ulcers?
Unna boot (elastic wrap) > pentoxifylline or aspirin
