Handorf 3

Handorf 3

2
Repair objectives
3
Proliferative phase- under influence of substances discussed yesterday, fibroblasts are activated and collagen is laid down. Cells can either regrow or respond by fibrosis and scarring. Maturation is not necessarily static. Scars may be remodeled over again over time.
4
Morphostasis is balance between breakdown and regrowth.
5
Injure unicellular organism- gel or matrix forms at region of injury, then membrane repairs and matrix is resolved. There are several overlaid pictures on my computer version of this slide.
6
Human analog is complex system of enzymes called the clotting cascade.
7
Parenchymal cells do work in organ. They are the specialized tissues that carry out the function of the organ. Mesenchymal cells are structural framework cells. Cartoons: epithelial cells, hepatocytes, etc.
8
Phagocytic cells and proteolytic enzymes remove debris.
10
general structure of collagen
Fiber is bundle of overlying fibrils. Molecule is one triple helix of chains.
11
Basement membrane
Collagen gives structural strength
Laminin responsible for cell binding
Entactin responsible for Ca binding
Perlecan- electrostatic charge
12
Stain to show basement membrane in kidney- all dark staining is basement membrane. Diabetes could be thought of as a basement membrane disease- organ damage is largely done to basement membranes. Elevated glucose changes basement membrane structure.
13
functions
14
Cartoon of basic macromolecular structure of basement membrane.
15
ECM organized about bundles of collagen seen by H and E stain on left and in EM on right.
Under EM- see longitudinal and transverse collagen, like plywood. Improves tensile strength of tissue. Large cell is fibroblast. Left- blood vessels, nerves, etc,
16
ECM is a living domain. All components interact to perform functions.
17
Regeneration vs. Repair
18
Some organisms regenerate. Newt or salamander can grow a new limb. We are not that good, but some parts can regenerate (cut out half of your liver, it will grow back).
19
Liver regrowth is reallly compensatory hyperplasia. Generates more cells.
20
Granulation tissue is not granulomatous inflammation. Granuloma is specific subset of chronic inflammation due to inability to expel foreign substance. Failure of chronic inflammatory response. Granulation tissue –see slide. Red ring on heart yesterday was granulation tissue.
20 open skin injury- way it heals- capillary rich bed with fibroblasts fills in wound. Right- drawing. Richly anastamosing capillary beds with fibroblasts laying down ECM.
21
Right- tissue with anastamosing tissue at top. Base- capillaries begin to disappear, more mature collagen base. Left- higher power.
22 Granulation tissue- ECM and capillaries, often has resident inflammatory cells, which are probably there in a building rather than inflammatory role.
23
Diagram to put thing together. Scarring is related to proliferation of fibroblasts. Contraction of scar is due to contraction of collagen product. Definitive scar gives protective function to hold tissue together, but not as good as original.
24
Chart of Cytokines for cell proliferation
25
Primary intention- if you can reoppose epithelial structures, healing is by primary intention. Begins with fibrin plug, then epithelial regrowth, with regrowth in basement membrane and expulsion of scab. Scarring is usually minimal.
26
Secondary intention
Epithelial growth begins around base of wound, wind up with large blocklike scar which gets in way of reepithelialization of tissue.
27
Factors modifying repair
Motion- early processes are weak and easily torn apart.
Ionizing radiation diminishes blood supply.
Corticosteroids diminish healing ability
28
Complications
Dehiscence- rupture or failure of a wound to heal properly.
Non-healing ulcers- not infrequent in diabetics.
Kelods more common in African descent. Overexuberant collagen growth. Keloids of earlobes can happen with ear piercing.
Hypertrophic scars can extend into tissue (hand)
Calcification of tissue- complication of repair- example of scar under X ray- white. Ca does not make good structural repair. Easily damaged. This is not bone formation. Bone is built to be strong. Dystrophic Ca is like a precipitate. Can occur in any injured tissue.
29
Scarring results from massive injury.
If ECM is intact, there is high regenerative capacity.