Fiser Chapter 14. WOUND HEALING

Question 1

Order of wound healing

Answer 1

1. Inflammation
2. Proliferation
3. Remodeling

Question 2

Inflammation phase (days 1-10)

Answer 2

PMNs, macrophages, EPITHELIALIZATION (1-2 mm/day)

Question 3

Proliferation phase (5 days to 3 weeks)

Answer 3

Fibroblasts, COLLAGEN DEPOSITION, neovascularization, GRANULATION TISSUE, type 3 collagen replaced with type 1

Question 4

Remodeling phase (3 weeks to 1 year)

Answer 4

Decreased vascularity, net amount of collagen does not change, although significant production and degradation occur, collagen CROSS LINKING occurs

Question 5

How fast do peripheral nerves regenerate?

Answer 5

1mm/day

Question 6

Order of cell arrival to wound?

Answer 6

1. Platelets
2. Neutrophils
3. Macrophages
4. Lymphocytes
5. Fibroblasts (proliferation and remodeling)

Question 7

Predominant cell type in days 0-2?

Answer 7

PMNs

Question 8

Predominant cell type in days 3-4?

Answer 8

Macrophages

Question 9

Predominant cell type in days 5 onward?

Answer 9

Fibroblasts

Question 10

True or false, reopening a wound results in quicker healing the 2nd time?

Answer 10

True, as cells are already present there

Question 11

Most important factor in healing open wounds (secondary intention)

Answer 11

Epithelial integrity

-unepithelialized wounds leak serum and protein, and promote bacteria

Question 12

Most important factor in healing close wounds (primary intention)

Answer 12

Tensile strength

-Depends on collagen deposition and cross-linking of collagen

Question 13

Strength layer of bowel

Answer 13

Submucosa

Question 14

Weakest time point for small bowel anastomosis

Answer 14

3-5 days

Question 15

How do myofibroblasts communicate?

Answer 15

Gap junctions

-Involved in wound contraction and healing by secondary intention

Question 16

Does the perineum or leg has better wound contraction?

Answer 16

Perineum

Question 17

Collagen types

Answer 17

I: Most common; skin, bone, tendon; primary collaged in a HEALED WOUND
II: Cartilage
III: Increased in HEALING wound; vessels; skin
IV: BM
V: Cornea, widespread

Question 18

Hydroxylation (prolyl hydroxylase) and cross-linking of proline residues in collagen need what?

Answer 18

• Alpha-ketoglutarate
• Vitamin C
• Oxygen
• Iron

-d-Penicillamine inhibits collagen cross-linking

Question 19

Collagen has a lot of what amino acid?

Answer 19

Proline (every 3rd aa): proline cross-linking improves wound tensile strength

Question 20

Tensile strength of a wound gets how good?

Answer 20

80% pre-wound max

Question 21

Predominant collagen type in healing wound

Answer 21

1-2 days: type 3

3-4 days: type 1, and replaces type 1 by 3 weeks

Question 22

When does a wound reach maximum tensile strength?

Answer 22

8 weeks (80%)

Question 23

When is maximum collagen accumulation in a healing wound reached?

Answer 23

2-3 eweks, after that the amount stays the same, but you have continued cross-liking to improve strength

Question 24

What is essential for wound healing?

Answer 24

• Moist environment
• Oxygen delivery (fluids, no smoking, pain control, revasc, supplemental O2 if needed): want transcutaneous oxygen measurement TCOM > 25 mm Hg
• Avoid edema (leg elevation)
• Remove necrotic tissue

Question 25

Impediments to wound healing

Answer 25

- Bacteria > 10^5/cm^2 - Devitalized tissue and foreign bodies - Cytotoxic drugs (5FU, methotrexate, cyclosporine, FK-506, etc can impair wound healing in 1st 14 days after injury) - DM: impedes early-phase inflammation response, hyperglycemia causes poor leukocyte chemotaxis - Albumin <3.0 - Steroids: inhibit macrophages, PMNs, and collagen synthesis by fibroblast; also decreases wound tensile strength - Wound ischemia: fibrosis, pressure, atherosclerosis, venous stasis, smoking, radiation, edema, vasculitis

Question 26

How does DM impede wound healing?

Answer 26

Hyperglycemia causes poor leukocyte chemotaxis

Question 27

How do steroids prevent wound healing?

Answer 27

Inhibiting macrophages, PMNs, and collagen synthesis by fibroblasts; decrease wound tensile strength

Question 28

How can you counteract effect of steroids on wound healing?

Answer 28

Vitamin A 25,000 IU per day

Question 29

Diseases associated with abnormal wound healing

Answer 29

Osteogenesis imperfect: type 1 collagen defect Ehlers-Danlos syndrome Marfan's syndrome: fibrillin defect Epidermolysis bullosa: excessive fibroblasts, tx phenytoin Scurvy (vit D def) Pyoderma gangrenosum

Question 30

Leg ulcers usually due to what?

Answer 30

90% due to venous insufficiency Tx: unna boot (elastic wrap)

Question 31

Scar revisions

Answer 31

Scars have a lot of proteoglycans, hyaluronic acid, and water Wait for 1 year to allow maturation; may improve with age Infants heal with little or no scarring

Question 32

How does cartilage get nutrients without blood vessels?

Answer 32

Diffusion of oxygen and nutrients

Question 33

What effect does denervation have on wound healing?

Answer 33

None

Question 34

What effect does chemo have on wound healing?

Answer 34

None after 14 days

Question 35

Keloid versus hypertrophic scars

Answer 35

Keloids: dark skinned, autosomal dominant; collagen goes beyond original scar; tx intra-lesional steroid injection, silicone, pressure garments, XRT Hypertrophic scar tissue: dark skinned; flexor surfaces of upper torso; collagen stays within confines of original scar; often occurs in burns or wounds that take a long time to heal; tx steroid injection, silicone, pressure garments

Question 36

Plateletgranules: alpha and dense

Answer 36

Alpha granules: PF4 (aggregation), beta-thrombomodulin (binds thrombin), PDGF (chemoattractant); transforming growth factor beta TGF-beta (modulates above responses) Dense: contain adenosine, serotonin, calcium

Question 37

What are the platelet aggregation factors?

Answer 37

PF4, TXA2, thrombin