1
Q
What animals display true wound healing (regeneration to original state) rather than just wound repair?
A
Reptiles and amphibians
(liver and fetal tissue are the exceptions in mammals)
2
Q
Wound repair results in formation of what? Generated from what cells
A
- Scar tissue
- Fibroblasts
3
Q
4 phases of wound repair
A
1) Hemostasis
2) Inflammation
3) Repair/proliferation
4) Remodeling and scar formation
sometimes hemostasis and inflammation are grouped together
4
Q
What is present at the end of hemostasis?
A
Fibrin clot
5
Q
First inflammatory cells on the scene in wound healing? Recruited by what?
A
- Neutrophils
- Platelets
6
Q
What cells in the late phase of inflammation recruit fibroblasts?
A
Macrophages
7
Q
Wound repair steps by major cell types involved
A
- Tissue injury -> blood spills to site of injury
- Platelets contact exposed collagen -> release clotting factors, GFs, and cytokines
- Neutrophils are recruited and participate in phagocytosis
- Macrophages arrive -> more phagocytosis and growth factors
- Fibroblast migrate to injury site -> produce new extracellular matrix
- Crosslinked fibroblasts form scar tissue
8
Q
Goals of hemostasis
A
- Stop hemorrhage
- Recruit inflammatory cells
- Form a clot/scaffold
9
Q
Factors released by damaged cells
A
- histamine
- serotonin
- catecholamine
10
Q
First non-inflammatory cells to arrive at injury site
(think about hemostasis)
A
Platelets
11
Q
What interaction causes platelet activation?
A
Platelet exposure to collagen
12
Q
What factor mediates adherence of platelets to collagen?
A
Von Willebrands Factor
13
Q
Components of dense granules of platelets
A
Serotonin, ADP, ATP
14
Q
Function of thromboxane
A
Stimulate platelet cross-linking
15
Q
Function of dense granule contents
A
- vasoconstriction
- adherence to site of injury
16
Q
Contents of platelet alpha granules
A
- fibrinogen
- Fibronectin
- PDGF (platelet derived growth factors)
- P-selectin
17
Q
Platelet-derived growth factor function during the hemostasis/inflammation phase of wound healing
A
- Attract neutrophils and macrophages
- Initiates chemotaxis of smooth muscle cells and fibroblasts
- Induces myofibroblast phenotype
18
Q
TGF-Beta1 function during the hemostasis/inflammation phase of wound healing
A
- Elicits rapid chemotaxis of neuts and monocytes
- Perpetuates inflammatory cell response
- Intra-cellular signaling pathways
19
Q
Diagram of the Coagulation Cascade
A
Oof
20
Q
Factors of the Intrinsic (activated partial thromboplastin time) pathway of the coagulation cascade
A
- Factor XII -> Factor XIIa
- Factor XI -> Factor XIa
- Factor IX -> Factor IXa
- Factor VIIIa
*memory tool: Not $12 but $11.98
21
Q
Factors of the Common Pathway (PT and APTT) of the coagulation cascade
A
- Factor X -> Factor Xa
- Factor Va
*memory tool: Small change 10 and 5?
22
Q
Final product of the common pathway of the coagulation cascade
A
Fibrin
23
Q
Factors of the extrinsic pathway of the coagulation cascade
A
- Tissue Factor
- Factor VII -> Factor VIIa
24
Q
Function of the fibrin clot
A
- Hemostasis
- Microorganism barrier
- Matrix scaffold for cell attachment
- Growth factor reservoir (PDGF and TGF play a role throughout wound healing)
25
Purpose of clot lysis
Limit platelet aggregation and clot formation
26
Molecules involved in clot lysis
- Plasminogen activator
- Anti-thrombin III (AT III)
- Protein C
27
Role of plasminogen activator
Initiates clot lysis
28
Role of prostacyclin C
Limit platelet aggregation
29
Main actions of neutrophils in the inflammatory process (starts within minutes of injury and is ongoing for ~72h)
- Debridement
- Production of critical cytokines
30
Basic stages of neutrophil extravasation
- rolling
- activation and firm adhesion
31
TNF-alpha also promotes what activity of leukocytes in relation to endothelial cells?
Promotes capture, rolling, and adhesion of leukocytes on their surface
32
4 Stages of leukocyte (neutrophil) migration through blood vessels
- Margination
- Rolling
- Adhesion
- Transmigration
33
What molecules are involved in the binding of glycoproteins on lymphocytes to cause rolling/slowing of the leukocytes that will be extravasated?
Selectins
- E-selectin (endothelium)
- P-selectin (endothelium and platelets)
- L-selectin (leukocytes)
34
Interaction between endothelial molecules ICAM-1 (intercellular adhesion molecule) and VCAM-1 (vascular cell adhesion molecule) with what type leukocyte receptor causes adhesion and arrest of leukocytes during the process of leukocyte migration through blood vessels?
**Integrins for tight connection**
- CD11 (LFA-1component)
- CD18 (Mac-1 component)
35
What endothelial molecule is essential for leukocyte migration (diapedesis) through the endothelium (transmigration)?
CD31/PECAM-1
36
Neutrophils are removed from the wound site by what cells?
Macrophages
37
At what time period in normal wound healing do monocytes/macrophages predominate?
Within 24-48h
38
M1 macrophages responsible for phagocytosis, cytotoxicity, and tissue injury) are classically activated by what molecules?
- IFNgamma
- LPS
- TNFalpha
39
Factors released by M1 macrophages
- ROS
- RNS
- TNFalpha
- IL-1
- IL-6
- IL-12
- IL-23
- chemokines
40
Alternatively activated M2 cytokines involved in tissue repair and immune suppression are activated by what molecules?
- IL-4
- IL-13
- IL-10
- TGF-Beta
41
Factors released by M2 macrophages
- IL-10
- TGF-Beta
- PDGF
- VEGF
- EGF
- arginase
42
Main cells involved in the Repair phase of wound healing
- Macrophages (M2)
- Fibrocytes
- Endothelial cells
- Keratinocytes
43
Main goals of the repair phase and stages of this
Lesion closure:
- Granulation tissue formation
- Fibroplasia/wound contracture
- Angiogenesis
- Re-epithelialization
44
At what time point after an injury occurs does the repair phase occur
2-10 days after injury
45
Rudimentary tissue that grows and covers the wound bed after injury
Granulation tissue
46
Components of granulation tissue
New blood vessels, fibroblasts, inflammatory cells, endothelial cells, myofibroblasts, new ECM components, fibronectin, hyaluronan
47
Main role of fibroblasts
Protein synthesis (collagen, elastin, and proteoglycan production)
48
Cross-linking of lysl and hydroxylysyl to form collagen fibers is possible to due to hydrolysis of the alpha chains by what enzyme?
Lysyl hydroxylase/LH1
49
Role of MMPs and other proteases in fibroplasia
Organization of the hot mess of collagenous tissue that was created?
50
What condition triggers fibroplasia
Hypoxia
51
Main growth factor of wound healing released by fibroblasts and platelets as well as other cells
TGF-Beta1
52
What cells store the most TGF-Beta1
Platelets
53
Most important (fibrillar) collagens involved in wound healing
Type I and III
54
Main collagen found in granulation tissue
Type III
55
During the remodeling phase of wound healing, type III collage is replaced by what other type of collagen?
Type I
56
Most prominent collagen in vessels and hypertrophic scars
Type IV
57
What inhibits wound contraction?
excessive tension and necrotic tissue
58
Factors involved in wound contraction
- PDGF
- TGF-Beta
59
Role of PDGF in wound contraction
- stimulates contraction (platelets and macrophages, not fibroblasts)
- induces fibroblast differentiation into myofribroblasts
60
Role of TGF-Beta1 in wound contraction
- stimulates fibroblast contraction
- stimulates myofibroblast differentiation
- stimulates fibroblasts to product hyaluronan (a GAG) and RHAMM (cell surface receptor for HA)
61
The main/first GAG present in wound healing
Hyaluonan/hyaluronic acid
62
The GAG HA, synthesized at the plasma membrane, promotes what in wound healing?
Promotes cell movement
63
Factors and conditions that stimulate angiogenesis/neovascularization
- macrophag-released cytokines
- hypoxia
- lactic acid
- growth factors (VEGF and bGFG)
64
Role of Vascular Endothelial Growth Factor (VEGF) in wound healing
- stimulates angiogenesis
- induces neovascularization
- induces synthesis of MMPs
65
Role of Basic Fibroblast Growth Factor (bFGF) in wound healing
Stimulates angiogenesis
66
Where do cells in re-epithelialization come from
- Migration of adjacent keratinocytes
- bulge-located stem cells
67
Name for broad, flattened protrusions extending from the leading edge of motile cells that are essential for cell migration and cell crawling
Lamellipodia
68
Keratinocyte "leap frog over one another tissue components during re-epithelialization until they establish contact with another keratinocyte. What can keratinocytes migrate over?
- Dermal collagens I, III, and V
- fibronectin
- fibrin
- tenascin
- vitronectin
69
Keratinocytes will not cross over what?
Intact BMZ
70
Main cells involved in remodeling and scar tissue formation
Fibrocytes and myofibroblasts
71
Mediators of remodeling and scar formation
- MMPs
- serine proteases
- Growth factors
72
At the end of wound repair, the tensile strength of the skin is about what % of the original
70-80%
73
Predominant collagen type in scar tissue?
Type I
74
Characteristics of wound repair in DOGS
- Inflammatory response starts early
- Granulation tissue formation begins in the center of the wound and covers the entire wound in about 7.5 days
- Form more direct cutaneous vessels
75
Characteristics of wound repair in CATS
- Granulation tissue formation begins at wound periphery
- Delayed collagen productions
- Granulation bed forms over 19 days
76
Characteristics of wound repair in HORSES
- Inflammatory response is generally weak and prolonged
- Formation of granulation tissue is exuberant
77
Scar tissue that invades healthy skin and has no myofibroblasts
Keloid
78
Characteristics of hypertrophic scar tissue
- widely paced collagen
- abundance of myofibroblasts
- doesn't invade other tissue
79
Horse equivalent of keloids
"Proud flesh" or equine exuberant granulation tissue
(characterized by increased TGF-Beta1 and mast cell hyperplasia)
80
Main goals of bandaging
- control swelling
- immobilization
81
3 main layers of bandages
- dressing
- absorption
- holding of previous layers in place
82
Main goals of wound dressing
- cover wound and provide protection
- absorb excess exudate
- stimulate repair
83
Manuka honey is best used during what phases of wound healing?
inflammatory and repair phase
84
Use/benefits of honey as a wound dressing
- debridement
- hyperosmotic effects (dehydrates microorganisms, reduces tissue edema)
- stimulates granulation tissue formation
85
Granulated sugar has what effect as a wound dressing?
Hyperosmotic effects (not the best and has to be 1cm thick, also it hurts)
86
Benefits of using fish skin as a wound dressing
- Excellent skin adherence
- Induces growth factors (EGF and FGF)
- Antimicrobial activity
87
Benefits of negative pressure wound therapy
- debridement
- aids contraction
- increased perfusion
- reduced edema
- removes detrimental cytokines
88
Contraindications for negative pressure wound therapy
- active bleeding
- neoplasia
- necrotic tissue/eschars
89
Uses for HBOT
- sepsis, peritonitis, chronic/non-healing wounds, etc
90
HBOT benefits
- Hyperoxygenation
- Leukocyte oxidative killing capacity
- Synergistic with antibiotics and antifungals
(fluoroquinolones, aminoglycosides, beta-lactams, amphotericin B)
91
HBOT contraindications
- pneumothorax or pneumomediastinum
- uncontrolled seizure activity (can't do anything about it once they're in the chamber)
- comatose or unconscious patients
92
THE growth factor for wound healing
TGF-Beta
ACVD Exam
flashcards
Decks in class (24)
# Cards
-
Allergy and Hypersensitivity368
-
Otology167
-
Infectious Disease557
-
Staph and Resistance AWM REF 202543
-
Parasitology250
-
Structure and Function - Skin Barrier and Cornification143
-
Structure and Function - Basement Membrane Zone126
-
Structure and Function - Glands, Vessels, Sensory systems, and lymphatics63
-
Structure and Function - Cornification disorders68
-
Structure and Function - Collagen and Extracellular Matrix102
-
Structure and Function - Melanogenesis72
-
Structure and Function - Wound Healing92
-
Structure and Function - Hair Follicles120
-
Immune-Mediated Diseases248
-
Equine Derm175
-
Pharmacology315
-
Endocrine/Internal Med212
-
Histopathology (and a little Cytology)116
-
Oncology313
-
Nutritional/Environmental/Traumatic133
-
Large Animal (non-equine)92
-
Genodermatoses64
-
Psychoneurodermatology97
-
Exotics137
