Wound Healing

Front 1

What are the four layers of skin? Where do stem cells reside. How long does it take for cells to move from bottom to top?

Back 1

From bottom to top layers:

Stratum basale (stem cells here) --> Stratum spinosum --> Stratum granulosum --> Stratum corneum.

It takes 28 days for cells to move to top, where they apoptose.

Front 2

What are the three classes of tissues, and give examples of each.

Back 2

1.) Labile -- continuously dividing -- Hematopoeitic tissue and Surface epithelium (GI, skin, uterus, urinary tract, exocrine organs).

2.) Stable Tissues -- quiescent and don't replicate unless induced -- Liver, kidney, pancreas, endothelial cells, fibroblasts and smooth muscle cells.

3.) Permanent Tissues (post-mitotic) -- permanently differentiated -- brain and heart.

Front 3

What are the stages in the cell cycle and what are the check points? What regulates the check points?

Back 3

G0 (quiescence) --> G1 --> S (DNA synthesis --> G2 --> M (mitosis)

Progression is regulated by CYCLINS, which form complexes with CDK's (cyclin-dependent kinases).

Front 4

When are CDK's suppressed and what releases this suppression?

Back 4

CDK's are suppressed during G1 phase (pre-synthesis phase), then released from suppression via growth factors.

Front 5

What do these acronyms stand for?

VEGF, TGF-Beta, PDGF, EGF, FGF

Back 5

Vascular Endothelial Growth Factor, Transforming Growth Factor, Platelet Derived Growth Factor, Epidermal Growth Factor, Fibroblast Growth Factor.

Front 6

What keeps fetuses from forming scars?

Back 6

Fetuses do not have TGF-Beta, and thus do not form scars. They also have higher levels of hyluronan, which inhibits scarring.

Front 7

VEGF is produced by ______ cells. It is induced by _______. What does it do?

Back 7

*Produced by connective tissue (mesenchymal) cells (in ECM).
*Induced by HYPOXIA.
*Mitogenic for endothelial cells, also increases its motility.

Front 8

TGF beta is produced by ______ (cells). It is chemotactic for _____. It causes ______ migration and proliferation. It ____(increases or decreases)___ the synthesis of collagen and ECM. It also inhibits the production of ______, which effectively _____(increases or decreases)_____ the degradation of collagen.

Back 8

Macrophages and Platelets
Monocytes
Fibroblast
Increases
MMPs (metalloproteases)
Decreases

Front 9

This is probably the MOST IMPORTANT growth factor in wound healing.

Back 9

TGF-beta

Front 10

This growth factor is produced by platelets, macrophages, and endothelial cells. It's chemotatic for PMNs, Macrophages, Fibroblasts, and Smooth Muscle cells. It STIMULATES THE PRODUCTION of MMP's, fibronectin, and hyaluronic acid. And it stimulates angiogenesis.

Back 10

PDGF

Front 11

____ growth factor stimulates MMP's while ____ growth factor inhibits MMP's.

Back 11

Platelet-Derived (PDGF)
Transforming (TGF-beta)

Front 12

This growth factor is produced by activated macrophages. It's mitogenic for keratinocytes and fibroblasts. Also, it stimulates keratinocyte migration and GRANULATION TISSUE FORMATION.

Back 12

EGF

Front 13

This growth factor is produced by macrophages, is chemotatic for fibroblasts, is mitogenic for fibroblasts and keratinocytes, stimulates keratinocyte migration, angiogenesis, and WOUND CONTRACTION and matrix deposition.

Back 13

FGF

Front 14

Growth factors bind to what type of receptor?

Back 14

Tyrosine Kinase

Front 15

Intracellular proteins RAS, PI3 kinase, PLC-gamma, MAP-kinase are all involved in pathways involving what type of receptor?

Back 15

Tyrosine Kinase

Front 16

Epinephrine, Vasopressin, Serotonin, Histamine, Glucagons, Chemokins all bind to what kind of receptor? What are the intercellular proteins involved?

Back 16

G-protein coupled (seven transmembrane receptor)

cAMP or IP3 pathways.

Front 17

____ are dimeric transmembrane receptors. ___ are monomeric transmembrane receptors. _____ are seven transmembrane receptors.

Back 17

*Tyrosine Kinase Receptors
*Receptors w/out intrinsic enzyme (JAK/STAT's)
*G-protein coupled Receptors

Front 18

What is in ECM (at a basic level ... 3 things)

Back 18

Fibers, cells, ground substance

Front 19

What sorts of things can be found in the basement membrane?

Back 19

Type IV collagen (non-fibrillar), proteoglycans (negatively-charged GAGs), and laminin.

Front 20

What sorts of things can be found in the intersitital matrix?

Back 20

Fibrillar collagens, elastin, Proteoglycan and hyaluronan, integrins.

Front 21

Intercellular communicates with extracellular via ______, which adhere on the extracellular (ECM) side to _____ and _____. (These also tell the cell what's top from bottom, main reason why ECM is important.)

Back 21

Integrins
Fibronectin
Laminin

Front 22

In the injurious phase of inflammation, macrophages are activated by _____ (cell), via _____ (cytokine). From there, macrophages release ______ (list a bunch of stuff).

Back 22

T-cells
IFN-gamma
ROS, Growth Factors, Proteases, Cytokines, Angiogenic factors, Clotting Factors ... overall a bad thing, cause scars.

Front 23

What are four steps in tissue regeneration (prevention of scarring)?

Back 23

1.) angiogenesis
2.) migration and proliferation of fibroblasts
3.) deposition of collagen
4.) Remodeling (reorganization) of collagen (scars are DISORGANIZED).

Front 24

What's the difference between vasculogenesis and angiogenesis

Back 24

the term angiogenesis denotes the formation of new blood vessels from pre-existing ones (capillary sprouts), while vasculogenesis is the term used for the formation of new blood vessels when there are no pre-existing ones (from bone marrow).

Front 25

Tissue repair is a balance between collagen synthesis and degradation. _____ destroy matrix when activated by proteases and plasmin. _____, which are synthesized by mesenchymal cells, inhibit these matrix destroyers -- ultimately controlling the remodeling process and keeping degradation in check.

Back 25

MMP's
TIMP's -- (Tissue Inhibitor of Metalloproteases)

Front 26

TGF-beta and Steroids _____stimulate/inhibit___ MMP, while PDGF, EGF, and IL-1/TNF _____stimulate/inhibit____ MMP.

Back 26

Inhibit
Stimulate

Front 27

What are the classic stages of would repair, and what timeline do they follow?

Back 27

*Inflammation -- until 48 hours
*New Tissue Formation -- 2-10 days after injury
*Remodeling -- 1-12 months after repair.

Front 28

Cirrhosis is due to healing by fibrosis (scar) after inflammation. The inflammation destroys both the cells and ______. ____ is implicated in excessive collagen formation.

Back 28

Matrix (no matrix = no restoration of tissue)
TGF-beta

Front 29

List the stages of cutaneous wound healing.

Back 29

1.) defect in skin
2.) fibrin fills in defect (scab forms)
3.) epithelial regeneration beneath scab.
4.) granulation tissue (angiogenesis)
5.) collagen remodeling

Front 30

What is granulation tissue.

Back 30

The perfused, fibrous connective tissue that replaces a fibrin clot in healing wounds. Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size it heals. NOT A GRANULOMA!

Front 31

Cell Migrations in Wound Healing: Platelets form a blood clot and secrete ____, _____, and _____. Neutrophils arrive within minutes. Macrophages move in as part of granulation tissue and secrete ______. ______ (cells) detach from the basement membrane at the wound edge and migrate on the matrix across the wound to fill in the defect, attaching to _______.

Back 31

Fibronectin, PDGF, TGF-beta
Fibronectin
Keratinocytes
Fibronectin

Front 32

Describe healing by primary intention. What is wound strength like after healing is done? What is second intention?

Back 32

Ex: surgical incision. Edges are easily joined together. Only a small amount of granulation tissue, and very little fibrosis. Wound strength is 70-80% of normal by 3 months.

Second is the opposite: large wound, edges not brought together (perhaps because of infection), lots of granulation tissue, scar formation and contracture.

Front 33

What nutritional element is essential for collagen?

Back 33

Vitamin C

Front 34

Glucocorticoids ___inhibit/promote____ inflammation with ___increased/decreased____ would strength and ___more/less___ fibrosis.

Back 34

inhibit
decreased
less

Front 35

Besides poor nutrition and glucocorticoids, what else impairs wound repair?

Back 35

*poor perfusion (i.e. diabetes/artherosclerosis)
*foreign bodies (ex: stitches)
*excessive ECM production = keloids
*Chronic inflammation = disabling fibrosis.

Front 36

What is dehiscence? What is keloids?

Back 36

Inadequate scar formation = dehiscence.

Excessive scar formation = keloids (genetic condition)