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Pathology Ch.3
LECOM OMS1
113
Pathology
Professional
12/08/2011

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Term
the G2/M checkpoint checks DNA after replication and monitors whether the cell can safely enter mitosis
Definition
etiology, pathogenesis, molecular and morphologic changes, and clinical manifestations.
Term
Regeneration is
Definition
a series of events that contain cell damage and initiate the healing process
Term
Fibrosis describes
Definition
collagen deposition due to EMC injury or chronic inflammation.
Term
Proliferation of endometrial cells under estrogen stimulation during the menstrual cycle and the thyroid-stimulating hormone-mediated replication of cells of the thyroid that enlarges the gland during pregnancy are examples of _______ proliferation
Definition
physiologic
Term
labile tissues are _____
Definition
continuously dividing
Term
quiescent tissues are ______
Definition
stable and have low levels of replication
Term
permanent tissues are ____
Definition
nondividing
Term
Examples of quiescent tissues are _____.
Definition
parenchymal cells of liver, kidneys, and pancreas; mesenchymal cells such as fibroblasts and smooth muscle; vascular endothelial cells; and lymphocytes and other leukocytes
Term
_______ cells are quiescent in adult mammals but proliferate in response to injury.
Definition
Fibroblasts, endothelial cells, smooth muscle cells, chondrocytes, and osteocytes
Term
Nondividing tissues include ______.
Definition
neurons and skeletal and cardiac muscle cells
Term
skeletal muscle has regenerative capacity, through the differentiation of the ______.
Definition
satellite cells that are attached to the endomysial sheaths.
Term
Stem cells are maintained via _____ and _____.
Definition
obligatory asymmetric replication and stochastic (symmetric) differentiation
Term
The inner cell mass of blastocysts in early embryonic development contains pluripotent stem cells known as _____.
Definition
Embryonic Stem cells.
Term
Differentiated cells of adult tissues can be reprogrammed to become pluripotent by _______.
Definition
transferring their nucleus to an enucleated oocyte
Term
What are iPS cells
Definition
pluripotent reprogrammed stem cells without the use of an embryo.
Term
What are transit amplifying cells?
Definition
cells that lose the capacity of self-perpetuation, and give rise to cells with restricted developmental potential known as progenitor cells.
Term
HSCs and MSCs are found in _____.
Definition
bone marrow
Term
MSCs migrate to _______.
Definition
injured tissues and generate stromal cells or other cell lineages
Term
The liver contains stem cells/progenitor cells in the _______.
Definition
canals of Hering (the junction between the biliary ductular system and parenchymal hepatocytes)
Term
oval cells are found in the ____ and can differentiate into ______
Definition
Canals of Hering / hepatocytes and biliary cells
Term
NSCs (also known as neural precursor cells) can generate ______
Definition
neurons, astrocytes, and oligodendrocytes
Term
In the small intestine, crypts are ______.
Definition
monoclonal structures derived from single stem cells
Term
growth and regeneration of injured skeletal muscle occur by _____
Definition
replication of satellite cells
Term
limbal stem cells (LSCs) maintain _______.
Definition
the outermost corneal epithelium
Term
Quiescent cells that have not entered the cell cycle are in the ____ state
Definition
G0
Term
The rls of replication is _____
Definition
the G1/S transition, known as a restriction point
Term
Rb is a ____
Definition
cyclin-dependent kinases (CDKs)
Term
Rb phosphorylation brings about ___.
Definition
release of the Rb/E2F complex, which activates E2F and allows it to stimulate transcription of genes whose products drive cells through the cycle.
Term
The G1/S checkpoint monitors _____.
Definition
the integrity of DNA before replication
Term
The G2/M checkpoint checks ____
Definition
DNA after replication and monitors whether the cell can safely enter mitosis
Term
Epidermal growth (α EGF) is found in ______ and functions to ______.
Definition
Platelets, macrophages, saliva, urine, milk, plasma / Mitogenic for keratinocytes and fibroblasts; stimulates keratinocyte migration and granulation tissue formation
Term
Transforming growth factor α (TGF-α) is found in ______ and functions to ______.
Definition
Macrophages, T lymphocytes, keratinocytes, and many tissues Similar to EGF;/ stimulates replication of hepatocytes and most epithelial cells
Term
Heparin-binding EGF (HB-EGF) is found in ______ and functions to ______.
Definition
Macrophages, mesenchymal cells / Keratinocyte replication
Term
Hepatocyte growth factor/ scatter factor HGF is found in ______ and functions to ______.
Definition
Mesenchymal cells Enhances proliferation of hepatocytes, epithelial cells, and endothelial cells / increases cell motility, keratinocyte replication
Term
Vascular endothelial cell growth factor (isoforms A, B, C, D) VEGF is found in ______ and functions to ______.
Definition
Many types of cells Increases vascular permeability; mitogenic for endothelial cells / angiogenesis
Term
Platelet-derived growth factor (isoforms A, B, C, D) (PDGF) is found in ______ and functions to ______.
Definition
Platelets, macrophages, endothelial cells, keratinocytes, smooth muscle cellsChemotactic for PMNs, macrophages, fibroblasts, and smooth muscle cells; activates PMNs, macrophages, and fibroblasts/ causes migration and proliferation of fibroblasts, smooth muscle cells, and monocytes to areas of inflammation and healing skin wounds
Term
Fibroblast growth factor FGF is found in ______ and functions to ______.
Definition
Macrophages, mast cells, T lymphocytes, endothelial cells, fibroblasts / wound repair, angiogenesis, hematopoesis, and development
Term
Transforming growth factor β is found in ______ and functions to ______.
Definition
Platelets, T lymphocytes, macrophages, endothelial cells, keratinocytes, smooth muscle cells, fibroblasts / blocks the cell cycle, is a fibrogenic agent, and is anti-inflammatory.
Term
Keratinocyte growth factor (also called FGF-7) KGF is found in ______ and functions to ______.
Definition
Fibroblasts / Stimulates keratinocyte migration, proliferation, and differentiation
Term
Tumor necrosis factor TNF is found in ______ and functions to ______.
Definition
Macrophages, mast cells, T lymphocytes / Activates macrophages; regulates other cytokines; multiple functions
Term
Receptors with intrinsic tyrosine kinase activity include _____.
Definition
EGF, TGF-α, HGF, PDGF, VEGF, FGF, c-KIT ligand, and insulin.
Term
Using ____ , GRB-2 triggers the ____ cascade.
Definition
GTP-GDP, SOS and RAS / MAP kinase cascade
Term
inositol 1,4,5-triphosphate (IP3) is an intrinsic tyrosine kinase activity and functions to increase _______.
Definition
concentrations of calcium
Term
Diacylglycerol activates the _____ that in turn activates ______.
Definition
serine-threonine kinase protein kinase C / various transcription factors
Term
Janus Kinase (JAK) receptors include ____.
Definition
Ccytokines, such as IL-2, IL-3; interferons α, β, and γ; erythropoietin; granulocyte colony-stimulating factor; growth hormone; and prolactin.
Term
______ signal through the hepatohelical G-protein coupled receptors.
Definition
chemokines, vasopressin, serotonin, histamine, epinephrine and norepinephrine, calcitonin, glucagon, parathyroid hormone, corticotropin, and rhodopsin
Term
G protein-coupled receptors use ___ as second messengers.
Definition
calcium and 3',5'-cyclic adenosine monophosphate (cAMP)
Term
When tyrosine kinase goes through the PI3 kinase (phosphatidylinositol 3-kinase) pathway, it activates
Definition
protein kinase B, also known as Akt
Term
Steroid hormone receptors are generally located in the _____ and function as ____-dependent transcription factors.
Definition
nucleus / ligand
Term
Ras, Raf, MEK, and ERK are all part of the _____ cascade.
Definition
MAP kinase
Term
c-MYC, c-JUN, and p53 are all ______.
Definition
transcription factors
Term
Restoration of liver occurs by ___
Definition
enlargement of the lobes that remain after the operation, a process known as compensatory growth or compensatory hyperplasia.
Term
What are the functions of the ECM?
Definition
mechanical support, maintenance of differentiation, scaffolding for tissue renewel, establishment of microenvironments, and storage and presentation of regulatory molecules.
Term
The basement membrane is composed of _____.
Definition
Type IV vollagen, laminin, proteoglycan
Term
Interstitial matrix is composed of _____.
Definition
Fibrillar collagens, elastin, proteoglycan and hyaluronan
Term
Type I Collagen is distributed in ____ and its genetic disorders cause _____.
Definition
Ubiquitous in hard and soft tissues Osteogenesis imperfecta / Ehlers-Danlos syndrome-arthrochalasias type I
Term
Type II Collagen is distributed in ____ and its genetic disorders cause _____.
Definition
Cartilage, intervertebral disk, vitreous / Achondrogenesis type II, spondyloepiphysea dysplasia syndrome
Term
Type III Collagen is distributed in ____ and its genetic disorders cause _____.
Definition
Hollow organs, soft tissues / Vascular Ehlers-Danlos syndrome
Term
Type V Collagen is distributed in ____ and its genetic disorders cause _____.
Definition
Soft tissues, blood vessels / Classical Ehlers-Danlos syndrome
Term
Type IX Collagen is distributed in ____ and its genetic disorders cause _____.
Definition
Cartilage, vitreous, intervertebral disks / Stickler syndrome
Term
Type IV Collagen is distributed in ____ and its genetic disorders cause _____.
Definition
Basement membranes / Alport syndrome
Term
Type VI Collagen is distributed in ____ and its genetic disorders cause _____.
Definition
Ubiquitous in microfibrils / Bethlem myopathy
Term
Type VII Collagen is distributed in ____ and its genetic disorders cause _____.
Definition
Anchoring fibrils at dermal-epidermal junctions / Dystrophic epidermolysis bullosa
Term
Type XV and XVIII Collagens are distributed in ____ and their genetic disorders cause _____.
Definition
Transmembrane collagen in epidermal cells / Benign atrophic generalized epidermolysis bullosa
Term
Type Collagen is distributed in ____ and its genetic disorders cause _____.
Definition
Endostatin-forming collagens, endothelial cells/ Knobloch syndrome (type XVIII collagen)
Term
Gly-X-Y is characteristic of _____.
Definition
the collagen triple helix
Term
Tyoe IV collagens form structural _____.
Definition
sheets instead of fibrils
Term
Collagen fibril formation is formed by ______ using ______ as a cofactor.
Definition
oxidation of lysine and hydroxylysine residues by the extracellular enzyme lysyl oxidase / vitamin C
Term
Elastic fibers have a core of ____ surrounded by ____.
Definition
elastin / fibrillin
Term
Genetic defects in fibrillin result in ______.
Definition
Marfan's Syndrome
Term
Cell Adhesion Molecule (CAMs) can be classified into _____.
Definition
immunoglobulin family CAMs, cadherins, integrins, and selectins
Term
Integrins bind to ECM proteins such as _____ in order to _____.
Definition
fibronectin, laminin, and osteopontin establish cell-to-cell contact
Term
Fibronectin binds to _____.
Definition
collagen, fibrin, proteoglycans, and cell surface receptors
Term
Fibronectin consists of ____.
Definition
two glycoprotein chains, held together by disulfide bonds
Term
Laminin is the most abundant glycoprotein in the basement membrane and has binding domains for both ______.
Definition
ECM and cell surface receptors
Term
Cadherins and integrins link the cell surface with the cytoskeleton through binding to ______.
Definition
actin and intermediate filaments
Term
Integrin-cytoskeleton complexes function as activated receptors and trigger a number of signal transduction pathways, including_______.
Definition
the MAP kinase, PKC, and PI3K pathways
Term
What 2 types of junctions do cadherins form?
Definition
zonula adherens, small, spotlike junctions located near the apical surface of epithelial cells, and desmosomes, stronger and more extensive junctions, present in epithelial and muscle cells
Term
Cadherins and catenins play a major role in regulating _____.
Definition
cell motility, proliferation, and differentiation and contact inhibition
Term
SPARC, thrombospondins, and osteoponin are all ___.
Definition
adhesive proteins
Term
heparan sulfate, chondroitin/dermatan sulfate, keratan sulfate are synthesized at ____ and are composed of ___.
Definition
at the Golgi and RER / long repeating polymers of specific disaccharides attached to a core protein
Term
The 4 GAG families are: ____.
Definition
heparan sulfate, chondroitin/dermatan sulfate, keratan sulfate, and hyaluronan (HA)
Term
Repair by connective tissue deposition includes what 5 features?
Definition
* inflammation
* angiogenesis,
* migration and proliferation of fibroblasts,
* scar formation
* connective tissue remodeling.
Term
What are the 5 steps of Angiogenesis from Preexisting Vessels ?
Definition
Vasodilation (NO, VEGF), Degradation fo the basement membrane (MMPs), Migration, Proliferation and Maturation of endothelial cells, Recruitment of periendothelial cells
Term
____ is the most important growth factor in adult tissues undergoing physiologic angiogenesis (e.g., proliferating endometrium) as well as angiogenesis occurring in chronic inflammation, wound healing, tumors, and diabetic retinopathy.
Definition
VEGF
Term
VEGF is secreted by many _____.
Definition
mesenchymal and stromal cells
Term
VEGF is induced by ____.
Definition
Hypoxia, TGF-β, PDGF, TGF-α
Term
How does VEGF stimulate the notch pathway?
Definition
it promotes the proper branching of new vessels and prevents excessive angiogenesis by decreasing the responsiveness to VEGF
Term
Dll4 blockade causes ______.
Definition
an increase in capillary sprouting and endothelial cell (EC) proliferation, creating vessels that are disorganized and have a small lumen size
Term
VEGF blockade _____.
Definition
decreases capillary sprouting, and the proliferation and survival of ECs.
Term
What are the 3 phases of cutaneous wound healing?
Definition
inflammation, proliferation, and maturation
Term
Healing of a clean, uninfected surgical incision approximated by surgical sutures is referred to as ______.
Definition
healing by primary union or by first intention
Term
The formation of abundant granulation tissue, and extensive collagen deposition, leading to the formation of a substantial scar, which generally contracts is referred to as ______.
Definition
healing by secondary union or by second intention
Term
At what time does granulation tissue fills the wound area with maximal neovascularization?
Definition
5 to 7 days
Term
Fibroblasts and vascular endothelial cells proliferate and form granualtion tissue during what time?
Definition
the first 24 to 72 hours of the repair process
Term
Neutrophils appear at the margins of the incision within what time?
Definition
within 24 hours
Term
Neutrophils are largely replaced by macrophages within what time?
Definition
48 to 96 hours
Term
Spurs of epithelial cells move from the wound edge along the cut margins of the dermis, depositing basement membrane components as they move withn what time?
Definition
24 to 48 hours
Term
___ is the most important fibrogenic agent
Definition
TGF-β
Term
The scar is made up of acellular connective tissue devoid of inflammatory infiltrate, covered by intact epidermis during what time?
Definition
By the end of the first month
Term
During remodeling, degradation of collagen and other ECM proteins is achieved by
Definition
matrix metalloproteinases (MMPs)
Term
ADAM is an important ___.
Definition
MMP
Term
Chemotaxis and proliferation of fibroblasts and keratinocytes is promoted by ___.
Definition
PDGF, TGF-Beta, TNF, IL-1, KGF-7
Term
When sutures are removed from an incisional surgical wound, usually at the end of the first week, wound strength is approximately ___ that of unwounded skin.
Definition
10%
Term
Wound strength reaches a plateau at about ____ of the tensile strength of unwounded skin
Definition
70% to 80%
Term
Systemic factors of wound healing include _____.
Definition
Nutrition metabolic status, circulatory status, and hormones (glucocortocoids ar eanti-inflammatory)
Term
Local factors of wound healing include_____.
Definition
Infection, mechanical factos, foreign bodies, and size of the wound
Term
Inadequate formation of granulation tissue or assembly of a scar can lead to _____.
Definition
wound dehiscence and ulceration
Term
Desmoids, or aggressive fibromatoses are the result of
Definition
Exuberant granulation
Term
A hypertrophic scar that grows beyond the boundaries of the original wound and does not regress it is called a _______.
Definition
keloid
Term
Fibrosis most often indicates the _____.
Definition
deposition of collagen in chronic diseases
Term
Cytokines such as TNF, IL-1, IL-4, and IL-13 result in increased ____ synthesis.
Definition
collagen
Term
____ is practically always involved as an important fibrogenic agent.
Definition
TGF-β
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