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Pathomorph - CREDIT 2 > Chapter 2 - pages 58-72 > Flashcards

Chapter 2 - pages 58-72 Flashcards

1
Q

What is repair?

A

Repair, sometimes called healing, refers to the restoration of tissue architecture and function after an injury.

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2
Q

How does repair/healing occur?

A

It occurs by two types of reactions: regeneration of the injured tissue and scar formation by the deposition of connective tissue

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3
Q

Regeneration:

A
  • some cells are bale to replace the damaged cells and essentially return to a normal state; this process is called regeneration
  • it occurs by proliferation of residual (uninjured) cells that retain the capacity to divide, and by replacement from tissue stem cells
  • it is the typical response to injury in the rapidly dividing epithelia of the skin and intestines, and some parenchymal organs, NOTABLY THE LIVER
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4
Q

Scar formation:

A
  • if the injured tissues are incapable of regeneration, or if the supporting structures of the tissue are severely damaged, repair occurs by the laying down of the connective (fibrous) tissue, a process that result in scar formation
  • the fibrous scar cannot perform the function of lost parenchymal cells , it provides enough structural stability that the injured tissue is usually able to function
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5
Q

Fibrosis:

A
  • most often used to describe the extensive deposition of collagen that occurs int he lungs, liver, kidney, and other organs as a consequence of chronic inflammation, or in the myocardium after extensive ischemic necrosis (infarction)
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6
Q

Infarction =

A

ischemic necrosis

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7
Q

Organization =

A

the term is used if the fibrosis develops in a tissue space occupied by an inflammatory exudate (as in organizing pneumonia affecting the lung)

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8
Q

fibrosis =

A

scarring

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9
Q

Which cell types proliferate during tissue repair?

A
  • remnants of the injured tissue (which attempt to restore normal structure)
  • vascular endothelial cells (to create new vessels that provide the nutrients needed for the repair process)
  • fibroblast (the source of the fibrous tissue that forms the scar to fill defects that cannot be corrected by regeneration)
  • the proliferation of these cells is driven by proteins called GROWTH FACTOR
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10
Q

What determines the adequacy of the repair process?

A
  • the production of polypeptide growth factors

- the ability of cells to divide in response to these factors

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11
Q

What determines the normal size of cell populations?

A
  • a balance among cell proliferation
  • cell death by APOPTOSIS
  • emergence of new differentiated cells from stem cells
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12
Q

What are the key processes int he proliferation of cells

A
  • DNA replication
  • mitosis
  • the cell cycle controls the sequence of these two events
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13
Q

Where in the cell cycle are the non-dividing cells?

A

they are in cell cycle arrest in the G1 phase or have exited the cycle and are in the G0 phase

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14
Q

Growth factors and the cell cycle:

A
  • growth factors stimulate the cells to transition from G0 into the G1 phase and beyond into DNA synthesis (S), G2, and mitosis (M) phases.
  • once cells enter the S phase, their DNA is replicated and they progress through G2 and mitosis
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15
Q

What regulates the progression in the cell cycle?

A

cyclins, whose activity is controlled by cyclin dependent kinases

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16
Q

How are the tissues of the body divided base on their proliferative capacities?

A
  • Labile (continuously dividing) tissues
  • Stable tissues
  • Permanent tissues
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17
Q

Labile (continuously dividing) tissues:

A
  • the cells here are continuously being lost and replaced by maturation from stem cells and by proliferation of mature cells
  • these cells can readily regenerate after injury as long as the pool of stem cells is preserved
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18
Q

Give examples of labile tissues:

A
  • hematopoietic cels in the bone marrow
  • the majority of surface epithelia, such as the stratified squamous surfaces of the skin, oral cavity, vagina and cervix
  • cuboidal epithelia of the ducts draining exocrine organs (e.g., salivary glands, pancreas, biliary tract)
  • columnar epithelia of the GI tract, uterus, and fallopian tube
  • transitional epithelium of the urinary tract
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19
Q

Stable tissues:

A
  • the cells here are quiescent and have only minimal replicative activity in their normal state
  • are capable of proliferating in response to injury or loss of tissue mass
  • with the EXCEPTION of liver, stable tissues have limited capacity to regenerate after injury
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20
Q

Give examples of cells of stable tissues:

A
  • constitute the parenchyma of most solid tissues, such as liver, kideny, and pancreas
  • the proliferation of these cells are particularly important in wound healing:
    • endothelial cells
    • fibroblast
    • smooth muscle cells
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21
Q

Permanent tissues:

A
  • the cells here are considered to be terminally differentiated and non-proliferative in postnatal life
  • injury to brain or heart is irreversible and result in scar, because neurons and cardiac myocytes cannot regenerate
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22
Q

Examples of cells of permanent tissues?

A
  • most neurons
  • cardiac muscle cells
  • skeletal muscle is usually classified as permantent tissue, but satellite cells attached to the endomysial sheath provide some regenerative capacity for this tissue
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23
Q

What characterises stem cells?

A
  • self-renewal capacity

- asymmetric replication

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24
Q

What types of stem cells do we have?

A
  • embryonic stem cells (ES cells)

- adult stem cells/tissue stem cells

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25
Q

Embryonic stem cells (ES cells):

A
  • the most undifferentiated stem cells
  • pluripotent
  • have extensive cell renewal capacity
  • can be maintained in a culture for over a year without differentiating
  • can be induced to form specialized cells of all three germ layers, including neurons, cardiac muscle, liver cells, and pancreatic islets cells
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26
Q

Where can we find embryonic stem cells (ES cells)?

A
  • inner cell mass of the blastocyst
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27
Q

Adult stem cells:

A
  • =tissue stem cells
  • less undifferentiated than ES cells
  • found among differentiated cells within an organ or tissue
  • much more limited self-renewal capacity
  • their lineage (ability to give rise to specialized cells) potential is restricted to some or all of the differentiated cells of the tissue or organ in which they are found
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28
Q

Main difference between adult stem cells and ES cells?

A

ES cells give rise to all cells of the body, while adult stem cells are involved in tissue homeostasis

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29
Q

Stem cell niche

A

are specialized microenvironment for stem cells

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30
Q

Regenerative medicine:

A
  • identify and isolate stem cells
  • has as its main goal the repopulation of damaged organs by using differentiated progeny of ES cells or adult stem cells
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31
Q

Induced pluripotent stem cells (iPS cells)

A

are derived by introducing into mature cells genes that are characteristic of ES cells. iPS cells aquire many characteristics of stem cells

32
Q

iPS cells =

A

induced pluripotent stem cells

33
Q

Growth factors definition:

A

most growth factors are proteins that stimulate the survival and proliferation of particular cells, and may also promote migration, differentiation, and other cellular responses.

34
Q

Growth factor and proto-oncogenes:

A

a major activity of growth factors is to stimulate the function of growth control genes, many of which are called proto-oncogenes because mutations in them lead to unrestrained cell proliferation characteristic of cancer (oncogenesis)

35
Q

How can signaling occur?

A
  • may occur directly in the same cell that produces the factor (autocrine signaling),
  • between adjacent cells (paracrine signaling)
  • over greater distances (endocrine signaling)
36
Q

Give example of hydrophobic ligands that can enter the cell:

A
  • vitamin D

- steroid and thyroid hormones

37
Q

Which types of plasma membrane receptors do we have?

A
  • receptors with intrinsic kinase activity
  • G protein-coupled receptors
  • receptors without intrinsic kinase activity
38
Q

Receptors with intrinsic kinase activity:

A

Binding of ligand to the extracellular portion of the receptor causes dimerization and subsequent phosphorylation of the receptor subunits.
Once phosphorylated, the receptors can bind and activate other intracellular proteins (e.g., RAS, phosphatidylinositol 3[PI3]-kinase, phospholipase Cγ [PLC- γ]) and stimulate downstream signals that lead to cell proliferation, or induction of various transcriptional programs.

39
Q

**G protein-coupled receptors:

A
  • =seven-transmembrane receptor
  • contains seven-transmembrane α-helix segments
  • After ligand binding, the receptors associate with intracellular guanosine triphosphate (GTP)-binding proteins (G proteins) that contain guanosine diphosphate (GDP).
    Binding of the G proteins causes the exchange of GDP with GTP, resulting in activation of the proteins.
    Among the several signaling pathways activated through G protein-coupled receptors are those involving cyclic AMP (cAMP), and the generation of inositol 1,4,5-triphosphate (IP3), which releases calcium from the endoplasmic reticulum.
  • more than 1500 members have been identified
40
Q

Receptors without intrinsic enzymatic activity:

A
  • usually monomeric transmembrane molecules with an extracellular ligand-binding domain; ligand interaction induces an intracellular conformational change that allows association with intracellular protein kinases called Janus kinases (JAKs).
    Phosphorylation of JAKs activates cytoplasmic transcription factors called STATs (signal transducers and activators of transcription), which shuttle into the nucleus and induce transcription of target genes.
41
Q

ECM def:

A

the ECM is a complex of several proteins that assembles into a network that surrounds cells and constitutes a significant proportion of any tissue.

42
Q

ECM:

A
  • sequesters water, providing turgor to soft tissues, and minerals, giving rigidity to bone.
  • regulates the proliferation, movement, and differentiation of the cells living within it, by supplying a substrate for cell adhesion and migration and serving as a reservoir for growth factors.
  • it is constantly being remodeled
  • its synthesis and degradation accompany morphogenesis, wound healing, chronic fibrosis, and tumor invasion and metastasis.
43
Q

Which forms does the ECM occur in?

A
  • interstitial matrix

- basement membrane

44
Q

Interstitial matrix:

A
  • present in the spaces between cells in CT, and between epithelium and supportive vascular and smooth muscle structures
  • synthesized by mesenchymal cells (e.g., fibroblast)
  • tends to form 3D , amorphous gel
  • its major constituents are fibrillar and non-fibrillar collagens, as well as fibronectin, elastin, proteoglycans, hyaluronate, and other elements
45
Q

Basement membrane:

A
  • seemingly random array of interstitial matrix in CT becomes highly organized around epithelial cells, endothelial cells, and smooth muscle cells
  • lies beneath the epithelium and is synthesized by overlying epithelium and underlying mesenchymal cells
  • tends to form platelike “chicken wire” mesh
  • its major constituents are amorphous non-fibrillar type IV collagen and laminin.
46
Q

What are the components of the ECM?

A
  1. fibrous structural proteins such as collagens and elastins, which confers tensile strength and recoil
  2. water-hydrated gels such as proteoglycans and hyaluronan , which permit resilience and lubrication
  3. adhesive glycoproteins that connect the matrix elements to one another and to cells
47
Q

What is collagen composed of?

A

three separate polypeptide chains braided into a ropelike triplehelix

48
Q

How many types of collagen have been identified?

A

30 types, some of which are unique to specific cells and tissues

49
Q

Which types of collagen form fibrils by virtue of lateral cross-linking of the triple helices?

A

collagen type I, II, III, and V

50
Q

Where does the tensile strength of the fibrillar collagen derive from?

A

it is derived from the cross-linking, which is the result of the covalent bonds catalyzed by the enzyme lysyl-oxidase. This process is dependent on vitamin C.

51
Q

What does the deficiency of the collagen types I, II, III, and V lead to?

A
  • osteogenesis imperfecta

- Ehlers-Danlos syndrome

52
Q

What about the other non-fibrillar collagen?

A

they may form basement membrane (type IV) or be components of other structures such as intervertebral disks (type IX) or dermal-epidermal junctions (type VII).

53
Q

What does the basement membrane contain?

A
  • type IV collagen
  • laminin
  • proteoglycan
54
Q

What does the interstitial matrix contain?

A
  • fibrillar collagens
  • elastin
  • proteoglycan and hyaluronan
55
Q

Elastin:

A
  • The ability of tissues to recoil and return to a baseline structure after physical stress is conferred by elastic tissue.
56
Q

Elastic fibers morphologically:

A
  • Morphologically, elastic fibers consist of a central core of elastin surrounded by a meshlike network of fibrillin glycoprotein.
  • Defects in fibrillin synthesis lead to skeletal abnormalities and weakened aortic walls (as in Marfan syndrome)
57
Q

What does the proteoglycans form

A

Proteoglycans form highly hydrated compressible gels conferring resilience and lubrication (such as in the cartilage in joints).

58
Q

What does the proteoglycan consist of?

A

They consist of long polysaccharides, called glycosaminoglycans or mucopolysaccharides (examples are dermatan sulfate and heparan sulfate), linked to a protein backbone.

59
Q

What is hyaluronan?

A

=hyaluronic acid

  • is a huge mucopolysaccharide without a protein core
  • it is also an important constituent of the ECM that binds water, and forms a viscous, gelatin-like matrix.
  • provides compressibility to tissues,
  • they also serve as reservoirs for growth factors secreted into the ECM (e.g., fibroblast growth factor [FGF], HGF).
60
Q

Describe the proteoglycans that are integral cell membrane protein:

A

they have roles in cell proliferation, migration, and adhesion—for example, by binding growth factors and chemokines and providing high local concentrations of these mediators.

61
Q

What is adhesive glycoproteins and adhesion receptors?

A

they are structurally diverse molecules involved in cell-to-cell adhesion, the linkage of cells to the ECM, and binding between ECM components.

62
Q

What does the adhesive glycoproteins include?

A

fibronectin (a major component of the interstitial ECM) and laminin (a major constituent of basement membrane); they are described here as prototypical of the overall group.

63
Q

What are adhesion receptors?

A

The adhesion receptors, also known as cell adhesion molecules (CAMs), are grouped into four familie-immunoglobulins, cadherins, selectins, and integrins.

64
Q

Fibronectin

A
  • is a large(450-kDa) disulfide-linked heterodimer
  • synthesized by a variety of cells, including fibroblasts, monocytes, and endothelium that exists in tissue and plasma forms.
  • have specific domains that bind to a wide spectrum of ECM components (e.g., collagen, fibrin, heparin, proteoglycans) and can also attach to cell integrins via a tripeptide arginine-glycine-aspartic acid (abbreviated RGD) motif.
65
Q

Where does the different fibronectin “work”?

A
  • tissue fibronectin forms fibrillar aggregates at wound healing sites;
  • plasma fibronectin binds to fibrin within the blood clot that forms in a wound, providing the substratum for ECM deposition and re-epithelialization.
66
Q

Laminin:

A
  • is the most abundant glycoprotein in basement membrane.
  • is an 820-kDa cross-shaped heterotrimer that connects cells to underlying ECM components such as type IV collagen and heparan sulfate.
  • mediate attachment to basement membrane
  • it modulates cell proliferation, differentiation, and motility.
67
Q

Integrins:

A
  • are a family of transmembrane heterodimeric glycoprotein chains that were introduced in the context of leukocyte adhesion to endothelium.
  • they are the main cellular receptors for ECM components, such as fibronectins and laminins.
  • present in the plasma membrane of most cells, with the exception of red blood cells.
  • they bind to many ECM components through RGD motifs, initiating signaling cascades that can affect cell locomotion, proliferation, and differentiation.
  • their intracellular domains link to actin filaments, thereby affecting cell shape and mobility.
68
Q

ECM function:

A
  • Mechanical support
  • Control of cell proliferation
  • Scaffolding for tissue renewal.
  • Establishment of tissue microenvironments.
69
Q

• Mechanical support:

A

for cell anchorage and cell migration, and maintenance of cell polarity

70
Q

• Control of cell proliferation:

A

by binding and displaying growth factors and by signaling through cellular receptors of the integrin family.
The type of ECM proteins can affect the degree of differentiation of the cells in the tissue, again acting largely through cell surface integrins.

71
Q

• Scaffolding for tissue renewal:

A

Because maintenance of normal tissue structure requires a basement membrane or stromal scaffold, the integrity of the basement membrane or the stroma of parenchymal cells is critical for the organized regeneration of tissues. Thus, although labile and stable cells are capable of regeneration, disruption of the ECM results in a failure of the tissues to regenerate and repair by scar formation.

72
Q

• Establishment of tissue microenvironments:

A

Basement membrane acts as a boundary between epithelium and underlying connective tissue and also forms part of the filtration apparatus in the kidney

73
Q

Angiogenesis:

A

the process of new blood vessel development from existing vessels, primarily venules

74
Q

Granulation tissue:

A

migration and proliferation of fibroblast and deposition of CT, which, together with abundant vessels and interspersed leukocytes, has a pink, granular appearance and hence is called granular tissue

75
Q

Which steps does the angiogenesis include?

A
  • vasodilation occuring in response to NO and increased permeability induced by VEGF
  • separation of pericytes from abluminal surface
  • migration of endothelial cells toward the area of tissue injury
  • proliferation of endothelial cells just behind the leading front of migrating cells
  • remodeling into capillary tubes
  • recruitment of periendothelial cells to form mature vessels
  • suppression of endothelial proliferation and migration and deposition of basement membrane
76
Q

What does the VEGF family of growth factors include:

A
  • VEGF-A, -B, -C, -D, and -E and placental growth factor (P1GF)

Pathomorph - CREDIT 2 (9 decks)

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