Wound Healing II

Question 1

(3i) Compare and contrast the similarities between embryonic stem cells, induced pluripotent stem cells and adult stem cells.

Answer 1

EST: taken from blastocyst, capable of becoming any cell type and capable of self renewal

induced pluripotent stem cells are cells taken from differentiated tissue and which have certain genes transducer to produce a cell with induced pluripotency

adult stem cells are more progenitor cells as they have restricted differentiation potential but have self-renewing capacity in a given tissue (potential to transdifferntiate in vitro)

Question 2

(3ii) Using exposure to a massive dose of ionizing radiation as an example, describe the physiologic consequences of eradicating the hematopoietic stem cell pool.

Answer 2

ionizing radiation (gamma, X-ray and particulate radiation) causes DNA damage through highly reactive free radical species; cells have difficulty reproducing due to this DNA damage (G1->S check point)

Question 3

(4i) Describe the 5 functions of ECM.

Answer 3

1. provide turgor by sequestering water or rigidity by sequestering minerals
2. reservoir for secreted growth factors
3. framework for cells to adhere, migrate and proliferate in
4. mediate cell-cel interaction
5. site of remodeling during wound healing

Question 4

(4) What are the two types of ECM?

Answer 4

interstitial matrix and basement membrane

Question 5

(4) Name the 3 general materials that compose ECM.

Answer 5

fibrous structural proteins
cell adhesion proteins
proteoglycans and hyaluronic acid

Question 6

(4i) What is the function of the fibrous structural protein collagen?

Answer 6

Vitamin C dependent cross linking is important for the developing a framework of ECM

(type IV is non-fibrillar found in basement membranes while type III is the first collagen to be laid down in wounds, replaced by type I)

Question 7

(4) What is the function of fibrous structural proteins elastin, fibrillin and elastic fibers?

Answer 7

elastic fibers are composed of a core of elastin surround by fibrillin, functioning as an important and flexible ECM support for cells

Question 8

(4) Name the two secreted cell adhesion proteins and their function(s).

Answer 8

fibronectin (binds numerous molecules) and laminin- key for securing cell-cell interactions

fibronectin adds structural integrity to clot, chemotactic for many cells, substrate for cellular adhesion and substrate for other ECM protein attachment and assembly

laminin is primarily in basement membranes, similar functions as fibronectin

Question 9

(4) Name the two surface bound cell adhesion proteins and their functions.

Answer 9

integrins: transmembrane receptors that facilitate cell-cell interaction and cell ECM interaction
cadherins: facilities cell-cell interactions between similar cell types and cell junctions, linked to cytoskeleton by cantenins

Question 10

(4) What are the functions of proteoglycans and hyaluronic acid?

Answer 10

proteoglycans important for cell-cell communication

hyaluronic acid as an important molecule that binds water and provides turgor for the cell

Question 11

(5i) What are the 4 phases of wound healing?

Answer 11

hemostasis phase
inflammatory phase
proliferative phase
maturation phase

Question 12

(5) What are the main goals of each wound healing phase?

Answer 12

hemostasis- stop the bleeding

inflammatory: clear pathogens and prepare for repair
proliferative: repair
remodeling: form a strong scar

Question 13

(5i) What are the key steps in the hemostasis phase?

Answer 13

platelets activate and aggregate, forma fibrin/fibronectin plug, platelets release thromboxane (transient vasoconstriction) and histamine (vasodilation and increased vascular permeability)

Question 14

(5i) Name the primary stages of the inflammatory phase

Answer 14

first neutrophil then macrophage infiltration, later fibroblasts become the predominant cell and lay down early wound ECM (fibrin, fibronectin and hyaluronic acid)

Question 15

(5) Name the 5 phases of the proliferative phase.

Answer 15

angiogenesis (VEGF)
granulation tissue (PDGF and TGF-b)
fibroplasia (TGF-b**, PDGF, EGF and FGF)
epithelialization (EGF, KGF and FGF)
contraction (myofibroblasts)

Question 16

(5) What key processes occur during the maturation phase.

Answer 16

collagen production and degradation equalibrize and type III is replaced by type I; hyaluronic acid is repaved with proteoglcans

Question 17

(6) Discuss local factors of wound healing v. systemic factors

Answer 17

local: vascular supply, infection, necrosis, foreign material, movement and radiation
systemic: circulatory compromise, nutritional status, DM, obesity, hormones (*glucocorticoids) and chemotherapy

Question 18

(6) Explain why fibrosis is an important element of wound healing

Answer 18

considered stronger tissue replacement, particular important in the case of persistent stimulus that causes chronic activation of macrophages and lymphocytes; also an important tissue process for tissues that cannot regenerate

Question 19

(6) Name 6 names of penetrating injury.

Answer 19

abrasion (scratch), laceration (often after impact), incision, avulsion (flap), amputation and puncture

Question 20

(6) Contrast wound healing by primary intention and secondary intention.

Answer 20

in primary intention, the wound is closed with stitches or staples, used in a clean wound

in delayed primary intention, the wound is closed after granulation is judged clean and viable

in surgical wound healing by secondary intention, a wound is left open to heal from below used when the wound is considered contaminated or necrotic