Pathology Ch 3 - Tissue Repair

Front 1

healing

Back 1

repair involving combo of regeneration and CT deposition

Front 2

scarring

Back 2

this occurs when tissues are intrinsically unable to regenerate, if underlying CT scaffolding is disrupted or following extensive exudates

Front 3

regeneration

Back 3

cell or tissue growth that replaces lost structures; requires intact CT scaffolding

Front 4

G0

Back 4

quiescent cells are in this phase of the cell cycle

Front 5

labile

Back 5

type of tissue in which cells proliferate throughout life, replacing those that are destroyed

Front 6

quiescent (stable)

Back 6

type of tissue in which cells are normally involved in low-level replication but are capable of rapid division in response to stimuli

Front 7

permanent

Back 7

type of tissue in which cells cannot undergo division in postnatal life

Front 8

stem cells

Back 8

these cells are characterized by prolonged self-renewal and asymmetric replication

Front 9

embryonic stem (ES) cells

Back 9

these pleuripotent stem cells are capable of differentiating into any tissue type

Front 10

adult stem cells

Back 10

these are cells located in reservoirs in normal adult tissue and have a restricted differentiation capability; lineage-specific

Front 11

hematopoietic stem cells (mesodermal lineage cells)

Back 11

these cells are capable of transdifferentiation into neurons, hepatocytes and other adult cell lineages

Front 12

plasticity

Back 12

breadth of differentiation potential

Front 13

multipotent adult progenitor cells (MAPCs)

Back 13

these cells proliferate in culture without senescence and have broad developmental capacity; they are found in bone marrow and multiple other tissue sites

Front 14

tissue stem cells

Back 14

these are typically responsible for generating the mature cells of the organ in which they reside

Front 15

canals of Hering (junction of hepatocytes and bile duct system); oval cells

Back 15

liver stem cells reside here and give rise to these

Front 16

satellite stem cells

Back 16

regeneraton of injured skeletal muscle is accomplished by profieration of ___

Front 17

proliferation, cell movement, contractility, differentiation and angiogenesis

Back 17

growth factors affect these processes of wound healing:

Front 18

epidermal and transforming growth factors (EGF ad TGF)

Back 18

these GFs exert their activity by binding to transmembrane molecules with intrinsic tyrosine kinase activity

Front 19

hepatocyte GF (HGF)

Back 19

this growth factor is produced by fibroblasts, endo cells and hepatocytes; also promotes embryonic development

Front 20

vascular endo GF (VEGF)

Back 20

growth factors that promote BV formation in early development and new BV growth

Front 21

vasculogenesis

Back 21

BV formation in early development

Front 22

angiogenesis

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new BV growth in adults

Front 23

platelet-derived GF (PDGF)

Back 23

this GF is found in platelet alpha granules and made by other cells; cause migration of fibroblasts, monocytes and smooth muscle cells

Front 24

fibroblast GF (FGF)

Back 24

these GFs bind to extracellular matrix heparan sulfate to form reservoirs of inactive fafctors

Front 25

TGF-beta

Back 25

GF that inhibits most epithelial cells and is an anti-inflam; promotes fibrosis

Front 26

bind target cell receptors, transmit intracellular signal (dimerization) to induce gene transcription and promote entry into cell cycle

Back 26

How do GFs signal for their activity?

Front 27

intrinsic tyrosine kinase which phosphorylate effector molecules

Back 27

receptors with intrinsic kinase activity associate with and activate:

Front 28

cytosolic protein kinases (JAKs that link activated receptors with STATs)

Back 28

receptor without intrinsic kinase activity associate with and activate

Front 29

a signal transducing G protein complex generating intracellular second messengers

Back 29

ligand binding of G protein-linked receptors activates:

Front 30

Ca and cAMP

Back 30

What are the second messengers associated with G protein-linked receptors?

Front 31

PI3 kinase, MAP-kinase and IP3

Back 31

What are the 3 pathways a ligand can follow when binding to a receptor with intrinsic tyrosine kinase activity?

Front 32

MAP-kinase pathway

Back 32

Which intrinsic tyrosine kinase pathway is associated with Ras/Raf?

Front 33

steroid hormones are lipophilic so they diffuse through the membrane

Back 33

How are steroid hormone receptors different than GF receptors?

Front 34

DNA binding and transcriptional regulation

Back 34

transcription factors have separate domains for

Front 35

post-translational modifications

Back 35

When transcription factors act do they rely on new synthesis or post-translational modifications?

Front 36

phosphorylation, release of constitutively bound inhibitors, dimerization

Back 36

What are some types of post-translational modifications?

Front 37

p53; DNA damage

Back 37

this tumor suppressor gene is activated in response to _____ and inhibits further progression through cell cycle

Front 38

collagen

Back 38

these CT proteins provide tensile strength

Front 39

triple helix and 3 polypeptide chains with glycine-X-Y repeating sequence

Back 39

basic structure of collagen

Front 40

1,2,3,5,11

Back 40

these are the fibrillar collagens

Front 41

1

Back 41

collagen of skin and bone is mostly

Front 42

2

Back 42

collagen of cartilage is mostly

Front 43

4

Back 43

this collagen type forms fibrils and is found in BMs

Front 44

extracellular space

Back 44

the terminal fragments of collagen are cleaved in this area:

Front 45

vit C

Back 45

this vitamin is required to cross-link and stabilize fibrils

Front 46

elastin

Back 46

inherited defects in fibrillin result in formation of abnormal ____

Front 47

immunoglobulin, cadherins, integrins and selectrins

Back 47

4 main families of cell adhesion proteins

Front 48

cadherins

Back 48

these mediate Ca-dep interactions with the same kind of receptor on cells; play a major role in cell motility and differentiation

Front 49

integrins

Back 49

these participate in cell-cell adhesion and adhesion to ECM

Front 50

fibronectin and laminin

Back 50

What do integrins bind to in the ECM?

Front 51

ligand binding to integrins causing clustering

Back 51

focal adhesion complexes are formed by:

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osteonectin

Back 52

this adhesion molecule is also known as SPARC and contributes to tissue remodeling after injury; is an angiogenesis inhibitor

Front 53

osteopontin

Back 53

this adhesion molecule regulates calcification and also mediates leukocyte migration

Front 54

proteoglycan and hyaluronic acid

Back 54

these ECM components have a core protein linked to 1 or more GAGs

Front 55

hyaluronic acid

Back 55

this ECM component binds large amounts of water

Front 56

fibrosis

Back 56

ECM deposition during chronic inflammation

Front 57

inflammatory response; proliferation and migration of CT cells; angiogenesis and formation of granulation tissue; synthesis of ECM proteins; tissue remodeling, wound contraction

Back 57

healing sequence:

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granulation tissue

Back 58

hallmark of healing; involves proliferation of fibroblasts and vascular EC

Front 59

new vessels that are leaky

Back 59

edema occurs in healing due to:

Front 60

branching of preexisting vessels and recruitment of endo precursor cells from bone marrow

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angiogenesis occurs due to:

Front 61

hemangioblast

Back 61

this precursor generates both hematopoietic stem cells and angioblasts in embryonic development

Front 62

plasminogen activator

Back 62

this disrupts EC cell-cell contact during angiogenesis

Front 63

VEGF and angiopoietins

Back 63

these are the most important growth
factors in angiogenesis

Front 64

fibroblast migration and proliferation; ECM deposition; tissue remodeling

Back 64

3 steps in scar formation:

Front 65

fibroblasts and collagen

Back 65

scar replaces granulation tissue and is composed mainly of what?

Front 66

matrix metalloproteinases (MMPs)

Back 66

these enzymes degrade ECM

Front 67

matrix metalloproteinases (MMPs)

Back 67

these enzymes require zinc for action

Front 68

tissue inhibitors of metalloproteinases (TIMP)

Back 68

these inhibit the enzymes that degrade ECM

Front 69

those with opposed edges (surgical)

Back 69

these types of wounds heal by first intention:

Front 70

wound contraction through the activity of myofibroblasts

Back 70

this is characteristic of second intention would healing:

Front 71

10%

Back 71

when sutures are removed, wound strength is:

Front 72

70-80%

Back 72

the plateau of wound strength is:

Front 73

inadequate granulation tissue or collagen deposition

Back 73

this causes wound dehiscence or ulceration

Front 74

Lamellipodia are cell membrane extensions that power the locomotion of leukocytes

Back 74

What are lamellipodia and what do they do?

Front 75

Via integrins

Back 75

How do the leading edges of in migrating cells adhere to the extracellular matrix?

Front 76

They anchor actin stress fibers

Back 76

How do the cytoplasmic domains of integrins function

Front 77

Perlecan

Back 77

Which extracellular matrix constituents modulates the network of associations among the other extracellular matrix constituents?

Front 78

Alpha helix

Back 78

What is the tertiary structure of collagen fibrils?

Front 79

Mature collagens are trimers of three alpha chains that form a triple helix

Back 79

How do collagen fibrils differ from mature collagens?

Front 80

Non-fibrillar collagens have globular domains that interrupt the triple helical segments

Back 80

How do fibrillar collagens differ from non-fibrillar collagens?

Front 81

It’s hyrophobicity, extensive covalent cross linking, and resistance to most proteolytic enzymes

Back 81

What factors are important in the stability of elastin?

Front 82

Laminins are hetero trimers that are the principal basement membrane glycoproteins

Back 82

What are the structure and function of laminins?

Front 83

As alternate splicing products of the same gene

Back 83

How are the different fibronectins synthesized?

Front 84

The glycosaminoglycan chains

Back 84

Which moieties(functional groups) are most responsible for the different functional characteristics of proteoglycans?

Front 85

Protein tyrosine kinase receptors for peptide growth factors, g protein coupled receptors for chemokines and intgrin receptors for extracellular matrix

Back 85

Which three receptor systems are key to initiating cell proliferation, migration, and gene expression in wound healing?

Front 86

Scar formation

Back 86

What is the predominant form of repair following an inflammatory response?

Front 87

The temporary extracellular organization of plasma derived matrix proteins and tissue derived components that accumulate at sites of injury

Back 87

What is provisional matrix?

Front 88

The transient specialized repair mechanism that replaces provisional matrix

Back 88

What is granulation tissue?

Front 89

Type three collagen

Back 89

What is the first type of collagen produced by fibroblasts during repair?

Front 90

Vascular endothelial growth factor or VEG-F

Back 90

What is the most important soluble mediator of angiogenesis?

Front 91

This association determines blood vessel patterning in wound healing

Back 91

What is the main effect of the association of VEG-F and glycosaminoglycans?

Front 92

Adherin’s junctions

Back 92

Which structures are made up of cadherin receptors?

Front 93

Re-epithelialization occurs by immigration of epidermal cells that begin at the wound margins

Back 93

How are wounds re-epithelialized and where does the process begin?

Front 94

By assembly of actin fibers when integrin fibers bind to fibronectin and other matrix molecules

Back 94

How is the epithelial cell mobility activated?

Front 95

A population of stem cells with a potential to differentiate and replicate

Back 95

What type of cell is necessary if regeneration is to occur?

Front 96

From preimplantation blastocysts

Back 96

From where do embryonic stem cells derive?

Front 97

Although pluripotent stem cells may differentiate into many different types of tissues, totipotent stem cells may differentiate into all tissues

Back 97

How are totipotent stem cells different from pluripotent stem cells?

Front 98

A scar restores anatomic integrity to the injured area while fibrosis interferes with the functionality of the injured structure

Back 98

How does scarring differ from fibrosis?

Front 99

Oval cells

Back 99

Hepatic injury as in fulminate (severe and sudden onset) hepatitis may lead to liver regeneration because of which cell population?

Front 100

Corticorenal tubles

Back 100

Restoration of renal tissue is most likely to occur when which portion of the nephron is injured?

Front 101

Alveolar type II cells

Back 101

What cell type is capable of re-epithelializing alveoli denuded of their lining cells?

Front 102

Wounds in the first two trimesters tend to heal without scarring

Back 102

Referring to interuterine injury, how do wounds to a fetus during the first two trimesters of pregnancy differ from those that occur afterwards?

Front 103

Increased mechanical stress on a wound

Back 103

What is the most common factor leading to wound dehiscence?

Front 104

Because of inadequate intrinsic blood supply, or poor revascularization during healing

Back 104

Why does ulceration of a wound generally occur?

Front 105

collagen formation

Back 105

neutralization of TGF will affect which inflam-response step?

Front 106

collagen deposition

Back 106

corticosteroids affect what part of the healing process?

Front 107

integrin

Back 107

intracytoplasmic cytoskeletal elements (like actin) interact with the ECM through this molecule to provide attachment and migration

Front 108

ras proteins

Back 108

What protein is involved in transducing the mitogenic signal from epidermal cell membrane to the nuclus?

Front 109

basic fibroblast GF (bFGF)

Back 109

What factor is most important in angiogenesis?