Flashcards in Wound Healing/Mini CPC Deck (43)
**Name three classes of transmembrane signaling receptors and the intracellular signaling pathways that they usually activate.
1. Kinase-coupled receptors
--Most GROWTH FACTORS
--Activates PI3, IP3, or MAP kinase pathways
2. Receptors without kinase activity
--Act through JAK/STAT pathway
--Release Ca and/or generate cAMP
Diagram the cell cycle.
G0 - quiescent, stable cells
G1 - growth
S - DNA replication (cyclin E)
G2 - more growth
M - mitosis (division of nucleus) (cyclin B)
Explain how cyclins and cyclin-dependent kinases regulate the cell cycle.
Have checkpoints between every phase
CDKs produced constitutively, activated by cyclins
Cyclins made according to stage of cell cycle, as cell responds to outside stimuli
List the key cellular types involved in wound healing. (4)
Leukocytes: neutrophils and **macrophages
State the role of collagen type I as an ECM element.
Provide structure and strength, especially in scarring
State the role of collagen type IV as an ECM element.
STRUCTURAL NETWORK on which to attach things
--Looks like chain-link fence
State the role of fibronectin as an ECM element.
Functions in CELL ATTACHMENT and MIGRATION
--Binds fibrin, heparan, collagen, integrin
State the role of laminin as an ECM element.
Functions in CELL ATTACHMENT
--Binds laminin, heparan, and cell
State the role of proteoglycans as an ECM element.
Include heparan, condrotin, dermatan sulfates
Functions in ECM WEAVING
Serves as reservoir for GROWTH FACTORS/CHEMOKINES
---Helps establish gradients of these
Explain the stages of scar formation from initial wound to collagen maturation.
1. Induction of an inflammatory process in response to initial injury -> removal of dead/damaged tissue by neutrophils/macrophages
2. Proliferation and migration of parenchymal and CT cells
3. Angiogenesis and granulation tissue
4. Synthesis of ECM proteins and collagen deposition
5. Tissue remodeling
6. Wound contraction
7. Acquisition of wound strength
List the functions served by macrophages in wound healing. (4)
Play an essential role!!
-Recruitment and maturation
-Phagocytosis/killing of microorganisms (wound decontamination)
-Phagocytosis of tissue debris (wound debridement)
Distinguish wound healing by primary vs. secondary intention.
Primary: something narrow (cut)
-Pull edges of wound together
-Very minimal scar
Secondary: for a larger area (scrape, burn, wide cut)
-Wound heals by deposition of a lot of collagen -> large scar -> contraction
Describe granulation tissue at the gross and histological levels.
Gross = watery looking tissue with tiny red dots
-Lots of thin-walled capillaries
**-Activated endothelial cells
**-Highly activated fibroblasts (big angry purple cells, often with tails)
**-Faintly basophilic ECM deposited
-Scattered neutrophils, macrophages, lymphocytes
List six systemic and four local factors that influence the success of wound healing.
1. Nutrition (scurvy, protein deprivation)
2. Metabolic status (diabetes is bad)
3. Circulation (ischemia is bad)
5. Genetic makeup
6. Medical treatment (steroids are bad)
2. Foreign bodies
3. Mechanical factors
4. Size, location, type of wound
List and describe six pathological outcomes/complications of wound healing.
1. Scar formation -> loss of function
2. Keloid formation
3. Desmoid (aggressive fibromatosis) - too much collagen deposition
4. Ulceration, esp. in poor circulation (diabetes)
5. Wound dehiscence (separation)
6. Scar contraction - can be like a dense collagenous tether
Define scar. What does a mature scar look like histologically?
Collagenous type of tissue repair, whether diffuse or linear
Mature collagen! Very dense, parallel
Define granulation tissue.
New connective tissue and tiny blood vessels that form on the surfaces of a wound during the healing process
The really immature connective tissue that is going to result in scar formation
Define keloid. What does it look like histologically?
The piling up of subcutaneous collagen in a way that does not stop
-Greater in people of African descent
-Predominately cosmetic problem
TONS of dense collagen with ACTIVE fibroblasts
State the role/importance of integrins.
Integrins: extend across cell membrane
-Have long sugars on external surface that associate with collagen, ECM proteins -> give cell something to anchor to and tell cell where it is
----Ex. If attached to laminin, know that side is bottom (basement membrane)
-Attach to actin cytoskeletal elements on inside -> signaling
Understand how cells "know" what is occurring in their surroundings.
Get signals from how they are anchored to the ECM
Receptor signaling as well
Know collagen synthesis (5 steps) and four major collagen types.
1. Produced in RER (short capped units)
2. Trimerized in Golgi
3. Exported into extracellular space
4. Caps on ends cleaved -> self-assembly into very long cables
5. Cross-linking between chains -> strong cables in parallel
Type 1: most abundant, in skin and bone; the basis of scarring
Type 2: major cartilage collagen
Type 3: in stroma of pliable tissues
Type 4: all basement membranes
Differential wound healing from regeneration. (3 major points)
Regeneration: tissue restored to totally NORMAL state
-Requires INTACT tissue scaffolding (esp basement membranes)
-New cells derived from division of stable cells/stem cell
Healing: normal state NEVER totally reestablished
-Occurs when tissue scaffolding has been altered/destroyed
-Involves creation of new tissue cells and COLLAGEN deposition (fibrosis/scarring)
What tissues have the ability to renew? Regenerate?
Renew = skin
Regenerate = liver, kidney
What are three simple mechanisms by which cell proliferation is increased to repair damage?
Shortening cell cycle
Pushing stable cells into cell cycle
Simulating stem cells -> parenchymal cells
True/false: Wound healing probably evolved from inflammation.
True/false: Chronic inflammation always results in fibrosis.
True/false: Stable cells on their own can enter the cell cycle.
FALSE, except in cancer
What cell is the main driver of wound contraction?
Collagen remodeled, wound constricts
True/false: The structure of a basement membrane is the same in all organs.
FALSE. It is unique for nearly every organ (except lung and kidney are the same)