3. Repair, Regeneration, and Fibrosis Flashcards
What are some pathologic findings in CHF, 24 hrs after the onset of vascular occlusion?
Microscopic signs of coagulative necrosis
What are some pathologic findings in CHF, 2-5 days after the onset of vascular occlusion?
Polymorphonuclear leukocytes and macrophages predominate
What are some pathologic findings in CHF, 1 week after the onset of vascular occlusion?
Infarct is invaded by capillary rich granulation tissue
What are some pathologic findings in CHF,weeks-months after the onset of vascular occlusion?
The necrotic myocardium is replaced by collagen-rich scar tissue
What defense mechanism is vascular congestion and edema indicative of?
Acute Inflammation
What is the initial phase of the repair reaction?
Hemorrhage which involves the formation of a fibrin clot that fills the gap created by the wound
What ‘s the difference between a clot and a scab?
A clot is also known as a thrombus. It becomes a scab after drying out. A thrombus is formed primarily from plasma fibrin and is rich in fibronectin.
What is the purpose of a clot on wounded skin?
- Barrier to invading microorganisms. 2. Prevent loss of plasma and tissue fluid
What is an initial source of growth factors in the clot formation process?
The contracting platelets within a thrombus.
When does a scab detach?
After a thrombus undergoes proteolysis and in penetrated by regenerating epithelium
When does a accumulation of acute inflammatory cell occur after within the repair reaction?
After the formation of the initial fibrin clot.
In wound repair, when do myofibroblasts begin to accumulate?
after 3 days
What is a mature scar tissue composed of ? What common cardiomyopathy can this be found?
Type I collagen, MI
What is early granulation tissue matrix composed of ?
Proteoglycans, glycoproteins and Type III collagen. (this is temporary and is removed by digestion and is replaced by a definitive matrix)
What increases wound strength?
extracellular cross-linking of the newly synthesized Type I collagen
Cartilage is composed of what type collagen?
Type II
Basement Membranes are composed of what type collagen?
Type IV
Where can types V and VI Collagen be found?
In various organs.
What cells are responsible for wound contraction? Wound Contracture?
Myofibroblasts are responsible for both wound contraction and contracture
How do myofibroblasts facilitate wound contraction?
They express alpha-smooth muscle actin, desmin, and vimentin, and they respond to pharmacologic agents that cause smooth muscle to contract. They also form syncytia, in which the myofibroblasts are bound together by tight junctions.
How do myofibroblasts differ from fibroblasts?
Fibroblasts tend to be solitary cells surrounded by collagen fibers while myofibroblasts form syncytia
How do endothelial cells respond to growth factors during wound healing?
they form capillaries which are necessary for the delivery of nutrients and inflammatory cells. Once repair has been achieved, most of the newly formed capillaries are obliterated and then reabsorbed, leaving a pale
What nutritional factors is required for proper collagen assembly? How is it involved?
Vitamin C is a powerful , biologic reducing agent that is necessary for the hydroxylation of proline residues in collagen.
In vitamin C deficiency, what is lost in collagen? What are Scurvy patients at risk for?
Tensile strength ; Dehiscence because previously healed wounds can bust open.
What are the two main components of granulation tissue?
Cells (mostly fibroblasts, myofibroblasts, and macrophages) and proliferating capillaries. Granulation tissue is fluid laden and its cellular constituents supply antibacterial antibodies and growth factors.
Where do fibroblasts and myofibroblasts derive from ?
mesenchymal stem cells
What is Angiogenesis?
Divisions of endothelial cells that form capillaries from adjacent blood vessels
Do Macrophages supply growth factors?
yes
How do Matrix Metalloproteins participate in wound healing?
they help cells migrate by degrading matrix proteins. They also disrupt cell- cell adhesions and release bioactive molecules stored in the matrix
Collagenase, Gelatinase, and Stromelysin are members of what protein family?
Matrix Metalloprotein s(MMPs)
alpha1 antitrypsin and alpha 2-macroglobulin share what characteristic in common?
They are Proteinase Inhibitors that bind to MMPs and reduce their activity.
Lysozyme is a ____________ product of ______________ that degrades ____________.
Lysozyme is a secretory product of neutrophils that degrades bacterial cell walls.
What would be the most likely adaptive outcome of a surgery induced renal cortical infarct? Why?
Scar formation. Healing by fibrosis occurs because the extracellular matrix is destroyed in most renal diseases causing an incomplete repair and regeneration.
What proliferates in renal tubule repair?
Proliferation of endogenous renal progenitor (stem) cells
Order the following parts of the renal tissue in order of increasing regenerative capacity. (medullary tubules, cortical tubules, glomeruli)
Glomeruli (none), medullary tubules (less), cortical tubules (maximal)