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)
What are hemangiomas?
Benign tumors of endothelial cells that usually occur in the skin
What is a Keloid?
An exuberant scar that tends to progress beyond the site of initial injury and recurs after excision
Why is a critical part of keloid formation called “maturation arrest?”
For two reasons 1. Changes in the ration of type II to type I collagen (higher) 2. Overexpression of fibronectin in keloid lesions
A nodule with chronic inflammatory cells, multinucleated giant cells, and extensive fibrosis are indicative of what adaptive response?
Granulomatous inflammation (a subtype of chronic inflammation that develops when acute inflammatory cells are unable to digest the injurious agent
How do giant cells form in granulomatous inflammation?
Fusion of macrophages within the lesion
What disease process is associated with the development of broad collagenous scars within hepatic parenchyma? What is the term for this characteristic?
Chronic Liver Injury; Cirrhosis
What is hepatocyte behavior in chronic liver injury?
Hepatocytes form regenerative nodules that lack central veins and expand to obstruct blood vessels and bile flow
What two PE findings would correlate with an adequate number of regenerated but disconnected hepatocytes as in cirrhosis?>
Jaundice and Portal Hypertension
Does Fulminant (developing or progressing suddenly) hepatic necrosis regenerate if the patient survives?
Yes
Is hepatocellular carcinoma associated with tumor fibrosis? Regeneration?
Yes; No
Portal vein thrombosis is a complication of embolism. Does it cause hepatic fibrosis?
No
How do superficial abrasions heal?
Regeneration mediated by stem cells or stabile cells that are able to progress through the cell cycle and fully restore normal tissue organization and function
By what means is wound surface predominantly reepthelialized ?
Cellular Migration
What is Fibrosis?
aberrant healing with deposition of collagen-rich scar tissue
When does granulation tissue appear?
During the repair of deep wounds
Describe when and how healing by primary intention occurs
Primary intention healing minimizes myofibroblast activity for a wound with minimal tissue loss and whose edges closely apposed. This healing requires only minimal cell proliferation and neovascularization and results in a small scar
When do basal epithelial cells at the wound margin become activated ? Why?
When the contact of basal cells with eachother is disrupted. This response is to reestablish contact with other basal cells through extensive cell migration and mitosis.
What is the process of cell migration and mitosis then its cessation to maintain epithelial continuity known as ?
Contact Inhibition of growth and motility
Deep wound healing include what activities? (not in order)
Collagen deposition, myofibroblast differentiation, platelet activation, angiogenesis
What adhesive molecule dominates the “provisional matrix” during early wound healing?
Fibronectin
Describe fibronectin structure during the initial stage of healing
Fibronectin in the extravasated plasma is cross-linked to fibrin, collagen, and other extracellular matrix components by the action of transglutaminases. This cross-linking provides a provisional stabilization of the wound during the first several hours.
Fibronectin, cell debris, and bacterial products are __________, because they recruit cells to a wound site
Chemoattractants
What are selectins?
Sugar-binding glycoproteins that mediate the initial adhesion of leukocytes to endothelial cells at sites of inflammation
Where can Selectins, Cadherins, and Integrins be found?
At the cell surface. They are not part of the extracellular matrix.
What powers the locomotion of Leukocytes? Fibroblasts? Epithelial cells?
Membrane extensions called lamellipodia; Filopodia- fingerlike membrane protrusions; regulated by Integrins
What is the function of integrins?
These are glycoproteins transmembrane adhesion receptors that allow the leading edge of the cell membrane to adhere to the extracellular membrane. They transmit mechanical and chemical signals that regulate ell survival, proliferation, differentiation , and migration.
What kind of molecules are laminins?
basement membrane glycoproteins
What is the function of Selectins?
They mediate the recruitment of neutrophils in acute inflammation but do not mediate directed cell migration at the site of tissue injury.
Describe when and how healing by secondary intention occurs
In secondary intention, the area of hemorrhage and necrosis can’t be fully corrected surgically. The wound edges are far apart and there is lots of tissue loss. Healing requires myofibroblasts to induce wound contraction. Much cell proliferation and neovascularization (granulation tissue) is also necessary to heal. A large scar is formed as a result of replacing granulation tissue.
How long after a traumatic laceration would fibroblasts, myofibroblasts, and capillary sprouts be most abundant?
3-5 days
When activated fibroblasts begin to form collagen and synthesize a variety of extracellular proteins, how do they change shape?
Oval to Bipolar
How long after a traumatic laceration would neutrophils be most abundant?
12-24 hrs
How long after a traumatic laceration would macrophages be most abundant?
24-48 hrs
When macrophages release cytokines and chemoattractants, what are they doing?
Orchestrating the formation of granulation tissue
What is the role of TGF-beta in wound healing?
It enhances the synthesis of collagen and fibronectin and decreases metalloproteinase transcription and matrix degradation.
Why is collagen formation is dependent on Cu?
A Cu-dependent enzyme, lysyl oxidase mediates covalent cross-linking in collagen synthesis that is important for tensile strength of a wound
Damage to the brain induces what processes?
Capillary growth and Gliosis
What is Gliosis?
Proliferation of astrocytes and microglia, the equivalent of scar formation elsewhere. It remains permanently.
How long after spinal cord injury is axonal regeneration expected?
up to 2 weeks
Where in the CNS does axonal regeneration occur?
hypothalamohypophysial region, where glial and capillary barriers do not interfere with axonal regeneration
What fluid is necessary for axonal regeneration?
extracellular fluid containing plasma proteins
A contracture is ____
an exaggeration of myofibroblasts and cell sustained contraction
When does a traumatic neuroma occur?
If the cut ends of a peripheral nerve are not in perfect alignment or are prevented from establishing continuity by inflammation
What are the characteristics of a neuroma?
a lesion consisting of disorganized axons and proliferating Schwann cells and fibroblasts
Are gangliomas, ganglioneuromas, and hamartomas benign or malignant?
benign
In what blood vessels are the major components of the inflammatory response?
Capillary and postcapillary venule
What is diapedesis?
Emigration of RBCs and WBCs from the vascular space in the the extravascular tissue
What activates endothelial cells , loss of vascular integrity, fluid and plasma leakage from the intravascular compartment and diapedesis?
Changes in the vascular wall due to injury
What histological finding is expected in a peptic ulcer?
Destruction of mucosa and full-thickness replacement of the muscularis with collagen-rich connective tissue.
On which curvature of the stomach is an ulcer most likely to cause chronic gastritis?
Lesser
On which curvature of the stomach is an ulcer associated with NSAIDS?
Greater
Grossly, what do chronic peptic ulcers resemble?
Gastric carcinoma
Contraction and scarring of gastric ulcer may cause what abnormality?
Pyloric stenosis
Describe the lining of the gastric mucosa of diverticula of the stomach
It is Normal
