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General Pathology > 2.1b - Tissue Renewal and Injury > Flashcards

2.1b - Tissue Renewal and Injury Flashcards

1
Q

REGENERATION

A

Growth of the cells and tissues to replace the lost
of structure; requires an intact connective tissue
scaffold

also,
tissues are able to replace the damaged components and essentially return to a normal state

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2
Q

REPAIR

A

Combination of regeneration and scar formation by deposition of collagen

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3
Q

What is fibrosis?

A

Fibrosis is an extensive deposition of collagen

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4
Q

SCAR FORMATION

A

Predominant healing process that occurs when ECM framework is damaged

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5
Q

Proliferation of endometrial cells under estrogen stimulation

AND

Thyroid stimulating hormone that enlarges the gland during pregnancy

These cases are examples of what type of cell proliferation?

A

Physiologic Cell Proliferation

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6
Q

Two types of cell proliferation

A

Physiologic

Pathologic

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7
Q

Nodular prostatic hyperplasia

AND

Nodular goiters (increased serum levels of TSH)

These cases are examples of what type of cell proliferation?

A

Pathologic cell proliferation

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8
Q

Repair of damaged tissues occurs by two types of reac- tions: regeneration by proliferation of residual (unin- jured) cells and maturation of tissue stem cells, and the deposition of connective tissue to form a scar

A

regeneration by proliferation of residual (uninjured) cells and maturation of tissue stem cells

AND

the deposition of connective tissue to form a scar

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9
Q

Three groups of tissue grouped by their regenerative capacity

A

1 - Labile (continuously dividing) tissue

2 - Stable (quiescent) tissues

3 - Nondividing (permanent) tissiue

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10
Q

The following are examples of what type of cell proliferative activity?

  • surface epithelia
  • lining mucosa of all the excretory ducts of the glands of the body
  • columnar epithelium of the GIT & uterus
  • transitional epithelium of the urinary tract and cells of the BM
  • hematopoietic tissues
A

Labile (continuously) dividing tissues

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11
Q

True or False

Quiescent (or stable) tissues never undergo rapid division

A

False.

cells from these tissues can undergo rapid division in response to stimuli

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12
Q

Quiescent (or stable) tissue are considered to be in which stage of the cell cycle?

A

onsidered to be in the G0 stage of the cell cycle but can be stimulated to enter G1

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13
Q

The following are examples of what type of proliferative cell activity?

  • parenchymal cells of liver,
  • kidneys
  • pancreas
  • mesenchymal cells (fibroblasts and smooth muscle)
  • vascular endothelial cells
A

Quiescent (or stable) tissue

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14
Q

Which of these is/are examples of quiescent cells?

a. columnar epithelium of the GIT & uterus
b. kidneys
c. neurons
d. mesenchymal cells

A

b. kidneys

d. mesenchymal cells

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15
Q

Major types of non-dividing (permanent) tissue - 3

A

neurons

skeletal muscle cells

cardiac muscle cells

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16
Q

How are neuron replaced?

A

glial cells

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17
Q

How are skeletal cells replaced?

A

satellite cells

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18
Q

Cardiac muscles respond to injury by? (regeneration)

A

scar formation

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19
Q

Mechanisms by which stem cells are maintained

A
  1. Obligatory asymmetric replication

2. Stochastic Differentiation

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20
Q

What type of stem cell differentiation results in two daughter cells?

A

stochastic differentiation

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21
Q

Where do adult stem cells (somatic) reside?

A

microenvironments called Niches

composed of mesenchymal, endothelial and other cell types

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22
Q

What type of stem cells made knockout mice possible?

A

embryonic stem cells

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23
Q

Where in the body are adult stem cells present?

A

In tissue that continuously divide (bone marrow, skin, GI tract lining)

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24
Q

Normal differentiation of adult stem cells

A
  • Hematopoietic stem cells
  • Bone marrow stromal cells (mesenchymal stem cells)
  • Neural stem cells in the brain
  • Epithelial stem cells in the lining of the digestive tract
  • Skin stem cells
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25
Q

Plasticity and trans-differentiation of adult stem cells

A
  • Hematopoietic stem cells: brain cells (neurons, oligodendrocytes, and astrocytes); skeletal muscle cells; cardiac muscle cells; and liver cells.
  • Bone marrow stromal cells: cardiac muscle cells and skeletal muscle cells.
  • Brain stem cells: blood cells and skeletal muscle cells.
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26
Q

Stem cells of:

Bone Marrow

A

HEMATOPOIETIC STEM CELLS

MARROW STEM CELLS

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27
Q

Stem cells of:

Liver

A
  • contains stem cells/progenitor cells in the Canals of Hering, called Oval cells
  • differentiating into hepatocytes and biliary cells
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28
Q

Stem cells of:

Brain

A
  • neural stem cells (NSCs)
  • subventricular zone (SVZ) and dentate gyrus of the hippocampus
  • generating neurons, astrocytes & oligodendrocytes
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29
Q

Stem cells of:

skin (location)

A
  • Hair follicle bulge
  • Interfollicular areas of surface epidermis
  • Sebaceous glands
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30
Q

Stem cells of:

intestinal epithelium

A
  • small intestine, crypts are monoclonal structures derived from single stem cells
  • Villus is a differentiated compartment
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31
Q

Stem cells of:

Skeletal and Cardiac Muscle

A
  • satellite cells
  • located beneath the myocyte basal lamina
  • can generate myocytes after injury
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32
Q

Stem cells of:

cornea

A
  • limbal stem cells

- transparency of the cornea depends on the integrity of the outermost corneal epithelium, maintained by the LSC

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33
Q

What is the Canals of Hering?

A

(junction between the biliary ductular system & parenchymal hepatocytes)

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34
Q

What type of brain cells can be regenerated?

A

neurons

astrocytes

oligodentrocytes

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35
Q

Replication of cells is stimulated by - 2

A

growth factors

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36
Q

Cell cycles

A
  • G1 (presynthetic)
  • S Phase (DNA synthesis)
  • G2 (premitotic)
  • M (mitotic)
  • Quiescent cells that have not entered the cell cycle are in the G0 State
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37
Q

G1 aka

A

(presynthetic)

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38
Q

S Phase

A

(DNA synthesis)

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39
Q

G2

A

(premitotic)

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40
Q

M

A

(mitotic)

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41
Q

Growth factors involved in regeneration and wound healing - 7

A
  • EPIDERMAL GROWTH FACTOR (EGF)
  • TRANSFORMING GROWTH FACTOR A (TGF-a)
  • HEPATOCYTE GROWTH FACTOR (HGF)
  • PLATELET DERIVED GROWTH FACTOR (PDGF)
  • VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF)
  • FIBROBLAST GROWTH FACTOR
  • TRANSFORMING GROWTH FACTOR B (TGF-B)
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42
Q

Epidermal growth factor is:

mitogenic for
produced by

A

Mitogenic for variety of epithelial cells, hepatocytes, fibroblasts

produced by keratinocytes, macrophages & other inflammatory
cells

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43
Q

TGF-a is:

extracted from
cell proliferation in

A
  • extracted from sarcoma virus-transformed cells
  • in embryos and adults and
  • in malignant transformation of normal cells to cancer
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44
Q

growth factors involved in angiogenesis - 4

A
  • vascular endothelial growth factor (VEGF)
  • Fibroblast growth factor
  • platelet derived growth factor (PDGF)
  • transforming growth factor - b (TGF-B)
45
Q

Functions of Fibroblast growth factor

A
  • wound factor
  • New Blood Vessel Formation (Angiogenesis)
  • Hematopoiesis
  • Development
46
Q

pleiotropic functions of TGF-B

A

a) Growth inhibitor for most epithelial cells

b) Potent fibrogenic agent that stimulates
produced by macrophages,
variety of endothelial
cells cells,
including smooth
fibroblasts chemotaxis & enhance production of collagen, fibronectin and proteoglycans;

c) inhibits collagen degradation
d) involved in the development of fibrosis in chronic inflammatory conditions (lungs, kidneys & liver).
e) Has strong anti-inflammatory effect but may enhance some immune functions.

47
Q

Ligands of receptors with intrinsic tyrosine kinase activity

A

most growth factors and insulin

48
Q

Ligands of receptors lacking intrinsic tyrosine kinase activity that recruit kinases

A

cytokine

IL-2, IL-3, other interleukins

interferons

erythropoietins,

granulocyte colony- stimulating factor

growth hormone

prolactin

49
Q

Ligands of G-Protein Coupled Receptors

A

chemokines

vasopressin

serotonin

histamine

epinephrine

NE

calcitonin

glucagon

PTH

corticotropin

rhodopsin

50
Q

Ligands of steroid hormone receptors

A

thyroid hormone

vitamin D

retinoids

51
Q

Transcription Factors that regulate cell proliferation - 2

A

c-MYC

c-JUN

p53

52
Q

How is restoration of liver mass achieved? without the regrowth of the resected lobe, instead growth occurs by enlargement of the remaining lobe (COMPENSATORY GROWTH or
COMPENSATORY HYPERPLASIA).

A
  • without the regrowth of the resected lobe
  • instead growth occurs by enlargement of the remaining lobe

(COMPENSATORY GROWTH or COMPENSATORY HYPERPLASIA).

53
Q

What is the endpoint of liver regeneration?

A

restitution of the functional mass rather than the reconstitution of
the original form

54
Q

Macromolecules that constitute the ECM

A
  1. Fibrous structural proteins:
    a) Collagen
    b) Elastin
  2. Adhesive glycoproteins (CAMs)
    a) Immunoglobulins
    b) Cadherins
    c) Integrins
    d) Selectins
55
Q

Collagen:

common/uncommon

chemical composition

A
  • Most common protein providing extracellular framework for all multicellular organisms
56
Q

What is required for the hydroxylation of procollagen?

A

vitamin c

57
Q

Collagen One is the main component of?

A

bONE

58
Q

Collagen Two is the main component of?

A

carTWOlage

59
Q

Collagen Three is the main component of?

A

reTHREEculate

60
Q

Collagen Four is the main component of?

A

FLOOR - forms the basement membrane

61
Q

Four main families of Cell Adhesion Molecules (CAM)

A
  1. Immunoglobulins
  2. Cadherins
  3. Integrins
  4. Selectins
62
Q

Integrins binds what to what? - 2

A

cells and ECM

cell-to-cell

63
Q

Most abundant glycoprotein in the BM

A

Laminin

64
Q

What provides mechanism for the transmission of mechanical force & activation of intracellular signal transduction pathways?

A

Cadherins & Integrins

through binding to actin & intermediate filaments

65
Q

Proteoglycans

A

Integral membrane proteins & through their binding to other proteins and the activation of growth factors & chemokines, act as modulators of inflammation, immune responses, and cell growth & differentiation

66
Q

Structural families of Proteoglycans and CAGs include:

A

 HEPARAN SULFATE

 CHONDROITIN/DERMATAN SULFATE

KERATAN SULFATE

HYALURONAN

67
Q

Where are Proteoglycans abundantly found?

A

abundantly found in heart valves, skin & skeletal tissues, synovial fluid, vitreous of the eye & umbilical cord

68
Q

When does Proteoglycan concentration increase?

A

its concentration increases in inflammatory; diseases (rheumatoid arthritis, scleroderma, psoriasis, & osteoarthritis)

69
Q

What is a scar?

A

Scar is most often used in connection to wound healing in the skin used to describe replacement of parenchymal cells in any tissue by collagen

70
Q

Main healing process is repair by deposition

A

of collagen and other ECM components, causing formation of scar

71
Q

Basic Features of Repair by Connective Tissue

A
  1. Deposition
  2. Inflammation
  3.  Angiogenesis
  4.  Migration & proliferation of fibroblasts
  5.  Scar Formation
  6.  Connective tissue remodeling
72
Q

Repair and Regeneration are influenced by:

A
  1. Proliferative capacity of the cells of the tissue
  2. The integrity of the ECM
  3. Resolution or chronicity of the injury & inflammation
73
Q

Vasculogenesis is defined as

A

the differentiation of endothelial precursor cells (angioblasts) into endothelial cells and the de novo formation of a primitive vascular network

vessels are assembled during embryonic development in which a primitive vascular network is established from endothelial cell precursor (ANGIOBLASTS) or from dual hemopoietic/ endothelial cell precursors (HEMANGIOBLASTS)

74
Q

angiogenesis is defined as

A

the growth of new capillaries from pre-existing blood vessels

also occur by recruitment of endothelial progenitor cells (EPC) from the bone marrow

75
Q

most important growth factor in adult tissues undergoing physiologic angiogenesis (proliferating endometrium) & angiogenesis occurring in chronic inflammation, wound healing, tumors & diabetic retinopathy

A

VEGF (Vascular endothelial Growth Factor)

76
Q

VEGF (Vascular endothelial Growth Factor) is secreted by

A

many mesenchymal & stromal cells

77
Q

Which receptor is the most important for angiogenesis?

A

Tyrosine kinase receptor

78
Q

First step in angiogenesis

A

recruitment of endothelial progenitor cells (EPC) from the bone marrow

79
Q

Important proteins in angiogenesis

A

Angiopoietins 1 & 2 (Ang) , PDGF, & TGF-B

participates in stabilization process

80
Q

Ang1 – interacts with

A

receptor on endothelial cells (Tie2) to recruit periendothelial cells

81
Q

PDGF – participates in the recruitment of

A

smooth muscle cells

82
Q

TGF-B – stabilized newly formed vessels

A

by enhancing production of ECM proteins

83
Q

ECM proteins as regulators of Angiogenesis

A
  1. Integrins – critical for formation and maintenance of newly formed vessels
  2. Matricellular Proteins – destabilized cell- matrix interactions promoting angiogenesis
  3. Proteinases – important in tissue remodelling during endothelial invasion
84
Q

Integrins – critical for

A

formation and maintenance of newly formed vessels

85
Q

Matricellular Proteins – destabilize

A

cell- matrix interactions promoting angiogenesis

86
Q

Proteinases – important in tissue

A

remodelling during endothelial invasion

87
Q

CUTANEOUS WOUND HEALING sequence

A
  1. Inflammation - Initial Injury causes platelet adhesion
    & aggregation, & formation of a clot in the wound surface
    leading to inflammation.
  2. Proliferation – formation of granulation tissue, proliferation & migration of connective tissue cells,
    re-epithelialization of wound surface
  3. Maturation – involves ECM deposition, tissue remodelling & wound contraction.
88
Q

Inflammation - Initial Injury causes platelet

A

adhesion& aggregation, & formation of a clot in the wound surface leading to inflammation

89
Q

Proliferation – formation of

A

granulation tissue, proliferation & migration of connective tissue cells, re-epithelialization of wound surface

90
Q

Maturation – involves ECM ….

A

deposition, tissue remodelling & wound contraction.

91
Q

In which step of cutaneous wound healing does angiogenesis occur?

A

Proliferation

92
Q

When the injury involves only the epithelial layer, the principal mechanism of repair is

A

epithelial regeneration

also called primary union

or healing by first intention

93
Q

How does First Union and Second Union differ?

A

Second union’s inflammatory reaction is more intense, there is development of abundant granulation tissue, accumulation of ECM and formation of a large scar, and wound contraction by the action of myofibroblasts.

94
Q

In Cell Proliferation & Collagen Deposition:

Migration of fibroblasts to the site of injury is driven by

A

chemokines (TNF, PDGF, TGF-B, and FGF)

95
Q

Cell Proliferation & Collagen Deposition:

Proliferation is triggered by

A

multiple growth factors: (PDGF, EGF, TGF-B, FGF, IL-1 & TNF)

96
Q

Scar Formation

A

Leukocytic infiltrate, edema, & increased vascularity disappear during the second week

Increased accumulation of collagen within the wound area & regression of vascular channels

 Original granulation tissue scaffolding is converted into a pale avascular scar, composed of spindle shaped fibroblasts, dense collagen, fragments of elastic tissue & ECM components.

 By the end of first month, scar is made of acellular connective tissue devoid of inflammatory infiltrate

97
Q

Duration from which an incisional surgical wound achieved its maximal strength:

A
  1. Aftersutureremovalusuallyattheendofthe first week, wound strength is approximately 10% that of unwounded strength.
  2. Wound strength increases rapidly over the next 4 weeks, slows down at the third month, & reaches plateau at about 70-80% of the tensile strength
  3. Recoveryoftensilestrengthresultsfromthe excess of collagen synthesis over collagen degradation during the first 2 months of healing
98
Q

Local factors that influence wound healing

A
  1. Infection
  2. Mechanical factors
  3. Foreign bodies
  4. Size, location & type of wound
99
Q

Systemic factors that influence wound healing

A
  1. Nutrition
  2. Metabolic status
  3. Circulatory status
  4. Hormones
100
Q

Which is/are systemic factors that influence wound healing?

  1. Foreign bodies
  2. Hormones
  3. Infection
  4. Nutrition
A
  1. Hormones

4. Nutrition

101
Q

Contractures - Commonly seen after

A

serious burns that can compromise joint movements

102
Q

inadequate formation of granulation tissue or assembly of scar that leads to two types of complication :

A

Wound dehiscence and Ulceration

103
Q

Wound dehiscence is a

A

surgical complication in which a wound ruptures along a surgical incision.

104
Q

Wound can ulcerate due to

A

inadequate vascularization during healing

105
Q

Hypertrophic scars generally develop after t

A

hermal or traumatic injury that involves the deep layers of the dermis.

106
Q

Hypertrophic scar

A

Accumulation of excessive amounts of collagen may

give rise to a raised scar –

107
Q

Interchangeably used with the term Scar

A

Fibrosis

108
Q

What protein is always involved as an important

fibrogenic agent in scar formation?

A

TGF-B is always involved as an important

fibrogenic agent

109
Q

Fibrotic Disorders:

A

 Liver cirrhosis

 Systemic sclerosis

 Fibrosing diseases of the lungs ( pulmonary
fibrosis, pneumoconioses, drug, radiation-
induced pulmonary fibrosis) 

 Chronic Pancreatitis

 Glomerulonephritis

 Constrictive pericarditis

General Pathology (5 decks)

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