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91 Cards in this Set

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  • Back
What is tissue regeneration?
The growth of cells and tissues to replace lost structures.
What is healing?
The response of tissues to wounds, inflammation, or necrosis that consists of regeneration and scar formation.
What cells are capable of regeneration?
Only labile and stabile
When do labile stells undergo regeneration?
All the time
What are the labile cells that continuously regenerate?
-Epithelial (epidermal)
-GI
-Hematopoietic (bone marrow)
What stabile tissues are capable of regeneration?
-Liver
-Kidney
What do we call the regeneration of injured hepatic or kidney tissue?
Compensatory growth
What is the typical response to an acute wound?
Wound healing and scar formation
What is the typical response to a chronic wound?
Chronic inflammation and fibrosis
What is the difference between an acute and chronic injury?
-Acute injury will damage functional cells only
-Chronic injury damages the supporting framework as well
What 4 processes govern the size of a cell population?
-Stem cell input
-Proliferation
-Differentiation
-Death by apoptosis
3 labile cells:
-Bone marrow
-Epidermal
-GI
3 stabile cells:
-Hepatic
-Kidney
-Pancreatic
3 Permanent cells:
-Cardiac muscle
-Skeletal muscle
-Neurons
What cells are nonresponsive to radiation therapy for cancer?
Permanent cells
What disease would you not treat with radiation?
Teratoma
What type of repication do we see in stem cells?
Assymetric - one cell remains a stem cell, another differentiates.
What is required for compensatory growth?
An intact cellular framework
So in what type of liver injury can compensatory growth occur?
Acute, not chronic.
Where are adult stem cells located in the body?
In niches
What does embryonic endoderm differentiate into?
Epithelial cells of the
-liver
-lungs
-GI tract
What does mesoderm differentiate into?
1. Mesodermal progenitor cells
2. Hematopoietic progenitor cells
What do mesodermal progenitor cells give rise to?
-Myocytes
-Osteoblasts
-Chrondocytes
-Adipocytes
-Endothelium
What do hematopoietic progenitor cells give rise to?
-Bone marrow cells
-Red blood cells
What does ectodermal tissue give rise to?
-Keratinocyte precursors
-Neurons
-Oligodendrocytes
-Ependymal cells
What is the important factor that induces mesodermal progenitor cells to differentiate into endothelial cells?
VEGF
Why is VEGF important?
It is implicated in the vascularization of tumor tissue
Where are the stem cells in GI epithelial tissue found?
Above paneth cells, and below enteroendocrine cells - in the Crypts.
Where are stem cells for skin found?
In the hair follicle bulge
What are quiescent cells?
Stable cells like hepatocytes, renal cells, and pancreatic cells.
In what cell cycle phase are quiescent cells?
G-0
How do cells know what to do for tissue regeneration or healing?
By responding to autocrine, paracrine, and endocrine signaling
What type of signaling is important for hepatic compensatory regrowth?
Autocrine
What is another cellular process in which autocrine signaling is important?
Proliferation of antigen stimulated lymphocytes
What type of signaling is important for macrophage-fibroblast interaction in wound healing?
Paracrine
What are the molecules that act as signals to direct regeneration and healing?
-Growth factors
-Cytokines
What is TGF-beta?
A growth INHIBITOR
What specific cell growth is inhibited by TGF-b?
-Epithelial cells
-Leukocytes
What does TGF-b stimulate?
-Fibrosis
-Smooth muscle cell proliferation
How does TGF-b relate to inflammation?
It is a potent anti-inflammatory
What are the 4 major signal transduction mechanisms for cell signaling?
1. 7-transmembrane GPC receptors
2. Receptors with intrinsic tyrosine kinase activity
3. Receptors without it
4. Steroid hormone receptors
What are 4 ligands that use the 7-transmembrane GPC receptors?
1. Epinephrine
2. Norepinephrine
3. Glucagon
4. PTH
What type of collagen is found in the basement membrane?
Type IV
What disease exhibits thin basement membranes due to abnormal Type IV collagen?
Alport's syndrome
What is found in BM with type IV collagen?
-Laminin
-Proteoglycan
What holds epithelial cells to the basement membrane?
Integrins
What cells are found floating within the interstitial matrix?
Fibroblasts
What do fibroblasts secrete?
ECM components
What is the interstitial matrix made up of?
-Fibrillar collagens
-Elastin
-Proteoglycans
-Hyaluronate
What holds the interstitial matrix together?
Cell adhesion proteins
What is the most common protein in the animal world?
Collagen
What disease results from vit C deficiency? Why?
Scurvy - because there is poor hydroxylation of procollagen
What are the fibrillar collagens?
Types I, II, III, V, and XI
What types of collagen are defect in Osteogenesis imperfecta and Ehlers Danlos syndromes?
1-3 and 5
What is the nonfibrillar collagen?
IV
What 3 molecules interact to give tissues elasticity?
-Elastin
-Fibrillin
-Elastic fibers
What disease results in abnormal elastic fiber formation?
Marfan's syndrome
What is Marfan's syndrome?
An inherited defect in fibrillin
What is the classic symptom of Marfan's syndrome?
Acute aortic dissection
List the 4 types of CAM's:
-IgG family CAMs
-Cadherins
-Integrins
-Selectins
What is the structure of proteoglycans?
-Core protein
-Numerous GAGs
What is the general goal of tissue repair?
To restore tissue
What type of repair is better at fully reconstituting damaged tissue?
-Regeneration
What type of repair generally results in some scar formation?
-Wound healing
What is fibrosis?
Any abnormal deposition of connective tissue
What is the hallmark of healing?
Granulation tissue
What will mature granulation tissue on a trichrome show?
Much blue color due to the staining of collagen
What is a very important process that occurs in healing and allows for granulation tissue to develop?
Angiogenesis
What is the important angiogenic growth factor?
VEGf
What are 2 pathways by which angiogenesis can occur?
1. Mobilization of endothelial precursor cells EPCs from BM
2. Branching from pre-existing vessels
What is VEGf secreted by? (2 cells)
-Mesenchymal cells
-Stromal cells
What molecules stabilize newly formed vessels?
-Angiopoietins 1 and 2
What other cells need to be recruited during angiogenesis?
-Pericytes
-Smooth muscle cells
In what 3 pathologic conditions is VEGF implicated?
-Chronic inflammation
-Tumors
-Diabetic retinopathy
What important factor triggers scar formation?
TGF-beta - to cause fibrosis
What are the 3 basic phases in cutaneous wound healing?
1. Inflammation
2. Granulation tissue formation
3. Wound contraction
What wounds heal by first intention?
Those with opposed edges - like surgical incisions
What happens within the first 24 hours of healing by first intention?
PMNs move towards a central fibrin clot.
What happens by day 3 of healing by first intention?
Macrophages replace the PMNs to form granulation tissue
What happens by day 5 of healing by first intention?
The incisional space is filled with granulation tissue and the epidermis recovers.
What happens during the 2nd week of healing by first intention?
Collagen continues to accumulate and fibroblasts continue to proliferate
What happens by the end of the 1st month of healing by first intention?
The scar is devoid of inflammatory infiltrate
How is healing by 2nd intention different from by 1st intention?
The incision or wound is not opposed, but larger with separated edges.
How is the inflammatory response different in 2nd intention healing?
It is much more dramatic and intense
How is the epidermal repair in 2nd intention compared to 1st?
The epidermis is thinner
What is the effect of infiltration of myofibroblasts in 2nd intention healing?
The wound contracts in the weeks following repair
What gives the wounded area strength after repair?
Collagen deposition
What are 3 causes of deficient scar formation?
-Wound dehiscence
-Inadequate vascularization (PVD)
-Nonhealing wounds due to peripheral neuropathy
What are 3 examples of excessive repair formations?
-Keloid scars
-Proud flesh exuberant granulatn
-Desmoids
When does fibrosis occur?
When tissue damage is persistant and chronic
What are 3 examples of fibrotic diseases?
-Cirrhosis of the liver
-Chronic pancreatitis
-Pulmonary fibrosis