healing and regeneration

Question 1

collagen

Answer 1

• most common protein in animal world
• triple helix of three polypeptide a chains
• 27 different types, 41 genes dispersed on at least 14 chromosomes
• complex post translational modification and metabolism
• synthesized as procollagen via cleavage via cleavage of propeptides
• cross-linking requires calcium and vitamin C

Question 2

forms of genetic abnormalities of collagen

Answer 2

Ehlers-Danlos syndrome (heterogenous), 
Osteogenesis imperfecta (brittle bone disease-> multiple fractures, so can clinically seen as child abuse)

Question 3

organization of tissue components

Answer 3

high organized with specific architecture

• parenchymal elements
• stromal cells
• ECM
• vascular elements
• nerves

Question 4

what does regeneration seek to re-establish?

Answer 4

normal architecture of tissues, not just cells replacement

Question 5

healing and regeneration key cell type

Answer 5

macrophages activation of fibroblasts

-drives it through production of cytokines, growth factors

Question 6

healing and regeneration

Answer 6

induction of an inflammatory process with removal of damage and dead tissue

• proliferation and migration of parenchymal and connective tissue cells
• formation of new blood vessels (angiogenesis) and granulation tissue
• synthesis of ECM proteins and collagen deposition
• tissue remodeling, wound contraction, acquisition wound strength

Question 7

most common of genetic mutations?

Answer 7

collagen

Question 8

Fibroblasts

Answer 8

deposition of collagen is principle component of scar tissue
-increased collagen synthesis of fibroblasts
- TGF-beta causes fibroblast migration, fibroblast proliferation, synthesis of collagen and fibronectin, and decreased degradation by metalloproteinases
(mediated chronic fibrosisin many disease states (systemic scleroderma))

Question 9

Angiogenesis

Answer 9

can also occur by recruitment of endothelial progenitor cells from the bone marrow
-mediated by local production of FGF, VEGF (fibroblasts, macrophages, lymphocytes, endothelial cells, tumor cells)

Question 10

fibronectin

Answer 10

• binding sites for intergrin, collagen, everything

- binds cells to extracellular matrix

Question 11

if can not replace cells, what is in it’s place?

Answer 11

a scar

Question 12

what does angiogenesis require?

Answer 12

1. ) proliferation and migration of vascular endothelial cells towards angiogenic stimuli
2. ) cleavage of extracellular matrix for advancing capillary tubes
3. ) recruitment of peroicytes (capillaries) and smooth muscle cells for stabalization
4. ) migration cords of endothelial cells for new capillaries

Question 13

difference between stromal and parenchymal cells

Answer 13

stromal: intracellular component (collagen, fibronectine), need fibroblast cells
parenchymal: cells of the tissues. (liver-> hepatocytes)

Question 14

Proliferation of parenchymal cells

Answer 14

requires intact STROMAL cells

• mediated by polypeptide growth factors secreted by a number of cells involved in inflammation including fibroblasts, macrophages, endothelial cells, platelets, and T cells
• proliferation DENSITY dependent, contact inhibition regulates the degree of proliferations
• stop growing when come in contact with each other

Question 15

what do tumor cells need to do the successful to grow?

Answer 15

angiogenesis

Question 16

factors associated with proliferation of parenchymal cells?

Answer 16

FGF, PDGF, EGF, TGF-beta, IL-1, TNF

Question 17

how does maturation of tissues occur?

Answer 17

1. ) re-organization of vasculature-> solid cords of endothelial cells become patent, mainly new capillaries formed intiially, decreased in number with time
2. ) re-organization of extracellular matrix-> type III collagen depostied early, replaced by type I
   - cross-linking of collagen fibrils contributes to tensile strength (with age), dependent on vitamin C
   - complex control of synthesis, activation, inhibition, degradation
   - wound strength 10% first week, 70-80% by 3rd week

Question 18

healing by first intention (primary union)

Answer 18

Example: clean surgical incision

• limited cell death
• miniml damage to architecture-> INTACT basement membrane
• narrow tissue defect

Question 19

healing by second intention

Answer 19

-large tissue defects such as ulcers, abscesses, etc
-regeneration of local parenchymal cannot fill tissue defect and restore local architecture (because of necrosis)
-increase amounts of necrotic debris and exudate
-more intense inflammatory response to clear
-larger amounts of granulation tissue are required to fill tissue defect
-wound contraction-> occurs on maturation of granulation tissue and contracture of the scar
(scar smaller)

Question 20

Time frame of healing and regeneration

Answer 20

1-3 days (acute inflammation and activation of M)

3-7 days-> active proliferation of fibroblasts, angiogenesis, progressive accumulation of granulation tissue

weeks-> maturation of granulation tissue, replacement of tissue with fibrosis (if not regenerated)

Question 21

Factors that influences wound healing?

Answer 21

age
location of wound
degree of tissue destruction/presence of necrosis
presence of infection
adequacy of blood flow
metabolic status
nutritional status (Vit. C, Protein, Zinc, hormones)

Question 22

what are complications of wound healing?

Answer 22

• inadequate granulation tissue-> wound dehiscence
• wound ulceration-> inadequate vascularization, neuropathic ulcer (areas devoid of sensation)
• hypertrophic scars and keloids- (African americans)
• excessive granulation-> proud flesh
• contractures/pain
• adhesions
• pigmentary changes (very early on scars are pink, then as time goes on it turns white)