Term
| What are the three stages of wound healing? |
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Definition
1. hemostasis and inflammation
2. granulation and proliferation
3. remodeling and maturation |
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Term
| What host factors modulate the rate of healing and eventual functional and/or cosmetic outcomes? (5) |
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Definition
1. nutrition
2. medications
3. underlying illness
4. wound depth
5. location |
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Term
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Definition
proteins released from specific cells and act as intracellular mediators
- include lymphokines and interleukins; mediates inflammation |
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Term
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Definition
| proliferation of fibroblasts, epithelial and endothelial cells are due to growth factors; they act on cellular receptors via phosphorylation of kinases which leads to second messengers and then nuclear transcription and cell proliferation |
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Term
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Definition
| act on the cell that produces it |
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Term
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Definition
| acting on an adjacent cell |
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Term
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Definition
| acting on the local environment |
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Term
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Definition
| acting on a distant cell; rare for wound healing |
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Term
1.How long does the hemostasis and inflammatory phase last?
2. what is the visible indicator of an immune response?
3. how soon after injury does vasoconstriction occur? |
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Definition
1. 2-5 days
2. inflammation - redness, heat, swelling
3. 10-15 minutes |
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Term
| What are three things that cause vasoconstriction in the first phase of wound healing?> |
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Definition
1. collagen - activates the clotting cascades intrinsic and extrinsinc paths
2. damaged cell membranes - release thromboxane A2 and prostaglandin 2A
3. platelets |
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Term
1. What is the first response cell in wound healing?
2. what is the primary component of the provisional matrix in the early wound? and what does it form?
3. what increases vascular permeability and faciliatates extravascular migration of inflammatory cells? |
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Definition
1. platelets
2. fibrin - clots
3. thrombin |
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Term
1. what chemokines do platelets release to stabalize the wound in clot formation (7)?
2. what does platelet degranulation activate? what is now attracted to the wound>
3. what factors do platelets secrete that stimulate the intrinsic clotting cascade?
4. platelets aggregate due to what? |
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Definition
1. EGF, fibronectin, fibrinogen, histamine, PDGF, serotonin, von Willebrand factor
2. complement cascade (c5a) - neutrophils
3. thrombin makes fibrinogen which makes fibrin
4. ADP |
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Term
| What follows vasoconstriction to allow serum leukocytes into the field of injury? |
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Definition
| capillary leak and vasodilation |
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Term
| Which serum factors contribute to vessel permeability? |
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Definition
| histamine, PGE1 and PGE2, kinins, C3a, C5a, leukotrienes |
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Term
| how does inflammation present? how long after injury does it stick around? |
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Definition
erythema, swelling, mild warmth
- 4 days |
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Term
what are the first leukocytes to migrate to the wound for inflammation? peaks in how long?
- which factor facilitates these cells moving into blood vessels? |
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Definition
1. neutrophils (PMN's)
24-72 hours
- TGF - beta |
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Term
| What are PMN's responsible for ? (4) |
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Definition
1. phagocytosis of bacteria and debris,
2. complement-mediated opsonization of bacteria
3. destruction of bacteria through oxidative burst mechanisms
4. break down fibrin |
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Term
WHich chemotactic agents are released to bring monocytes to the wound?
What do monocytes become? |
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Definition
FGF, TGF-beta and alpha, PDGF, C3a and C5a
- macrophages |
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Term
| what is the role of macrophages at the wound site?q |
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Definition
1. multiplication of endothelial cells and new BV's
2. duplication of smooth muscle cells
3. creation of the miliew secreted by the fibroblast - FGF< EGF< PDGF
4. phagocytosis |
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Term
| What enzymes and cytokines are secreted by macrophages? what do they do? |
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Definition
1. collagenases - debride the wound
2. IL and TNF - stimulate fibroblasts to produce collagen and promote angiogenesis
3. TGF stimulates keratinocytes |
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Term
| which step marks the transition into the proliferative phase? |
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Definition
| proliferative phase begins when the TGF stimulate keratinocytes |
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Term
When does the proliferative/granulation phase occur?
what cells is the most important in wound healing? |
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Definition
- 2 days to 3 weeks
- fibroblasts (a mesenchymal cell) |
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Term
As cells move into the wound with the help of integrins they lay down the stikcy _____.
- integrins also interact with what (3)? as the fibroblasts move along the fibirls
- what facilitates cell migration?
which enzymes cleave paths in the fibrin mesh? how are the modulated? |
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Definition
1. laminin 5
2. fibrin, fibronectin, vitronection
3. hyaluronic acid
4. Matrix metalloproteinases (MMP's) - TIMPs |
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Term
| Fibroblasts secrete ___ in 5-7 days. at the beginning _____ predominates but over time is replaced with _____ |
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Definition
collagen
- type III collagen
- type I collagen |
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Term
Angiogenesis is stimulated by what? (3)
it also requires ______ and _____ followed by ________ of endothelial cells |
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Definition
- high lactate, acid pH, low tissue O2
- eCM and basement membrane degredation,
- micgration, mitosis, and maturation of endothelial cells |
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Term
_______ regenerate the outer layers of capillaries while _____ produce the lining?
the most potent angiogenic agent is _____ |
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Definition
1. pericytes, endothelial cells
2. VEGF |
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Term
| The signal for cells the migrate isnt known but low ___ or high ___ may play a role. |
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Definition
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Term
How long is the remodeling/maturation phase?
- when does the wound have its peak amount of collagen? |
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Definition
3 weeks - 2 years
- 3 weeks |
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Term
what is the most potent stimulant for collagen synthesis?
scar tissue is only ___% as strong as the original tissue.
collagen is eventually broken down by _____.
what type of collagen is the major component of scars? |
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Definition
1. TGF-beta
2. 80
3. collagenases
4. type I |
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Term
| What GAG's can be found in the wound along with fibronectin? |
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Definition
| heparan sulfate, chondroiton sulfate, keratin sulfate, hyaluronic acid |
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Term
| What is NOT made in scars that is found in normal skin? |
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Definition
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Term
| which enzymes are designed to reshape and remodel intial collagen? |
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Definition
| collagenase, gelatinase, stomelysin, membrane type metalloproteinases |
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Term
proliferation of _____ leads to wound contraction
- contraction requires ____ but not ____ |
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Definition
myofibroblasts
- cell division but not collagen synthesis |
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Term
- when is max tensile strength achieved?
- what enzymes play a role in the synthesis and breakdown of collagen?
- as collagen type I increases, ___ and ___ decreased
- what are clinical signs of maturation? |
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Definition
1. 12th week
2. MMPs, TIMP's, and hyaluronidase under influence of cytokines TGF-beta, IL-1, EGF< PDGF
- proteoglycans and water
- less redness, less thickness, less induration |
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Term
| first intention surgical repair |
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Definition
| primary healing wound closure by direct approximation - bring edges in together |
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Term
| secondary intention surgical repair |
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Definition
| spontaneous healing - wound heals on own from bottom up |
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Term
| third intention surgical repair |
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Definition
| tertiary healing - delayed wound closure |
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Term
| What are nutritional deficiencies that negatively influence wound healing? |
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Definition
- protein deficiency inhibits collagen synthesis
- vit a - decreased production and stable collagen, delayed reepithelialization, increased infection
- vit c - delayed healing, scurvy, capillary fragility, unstable collagen likely to split
- vit k - reduced clotting factors II, VII, IX< X, increased hematoma
- zinc - decreased Vit a transport, decreased immune response, reduced lysyl oxidase, decreased collagen and protein synthesis
- cobalt, copper, iron, Mn, Selenium - decreased enzyme efficiency |
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Term
| Besides nutritional deficiencies what else affects wound healing negatively? |
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Definition
1. ionizing radiation - in all phases
2. glucocorticoid therapy - anti-inflammatory
3. drugs like alcohol, tobacco, anticoagulants, immunosuppressants, chemo
4. illnesses - diabetes, renal disease, CHD, thyroid disease
5. genetic - pseudoxanthoma elasticum, ehlers-danlos
6. age |
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Term
| WHat local factos play a role in delaying wound healing? (3) |
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Definition
1. primary and secondary infections
2. foreign bodies
3. hemorrhagic factors like ischemia - need oxygen to make collagen, to kill organisms with superoxide |
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Term
| Oxygen is also necessary for ____ and fibroblast proliferation |
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Definition
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Term
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Definition
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Term
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Definition
| - due to accumulation of excessive collagen - beyond original area of insult |
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Term
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Definition
insufficient healing - epithliam traversed before collagen came in
ex. acne |
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Term
| how does exudate give a good healing environement? |
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Definition
1. white blood cells
2. growth factors
3. enzymes and hormones |
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Term
| what is the most important mesenchymal cells involved in the structural aspect of wound healing? |
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Definition
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Term
| what provides the structural framework for proliferation in wound healing? |
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Definition
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