2.1b - Tissue Renewal and Injury Flashcards
(109 cards)
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
2
Q
REPAIR
A
Combination of regeneration and scar formation by deposition of collagen
3
Q
What is fibrosis?
A
Fibrosis is an extensive deposition of collagen
4
Q
SCAR FORMATION
A
Predominant healing process that occurs when ECM framework is damaged
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
6
Q
Two types of cell proliferation
A
Physiologic
Pathologic
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
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
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
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
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
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
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
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
15
Q
Major types of non-dividing (permanent) tissue - 3
A
neurons
skeletal muscle cells
cardiac muscle cells
16
Q
How are neuron replaced?
A
glial cells
17
Q
How are skeletal cells replaced?
A
satellite cells
18
Q
Cardiac muscles respond to injury by? (regeneration)
A
scar formation
19
Q
Mechanisms by which stem cells are maintained
A
- Obligatory asymmetric replication
2. Stochastic Differentiation
20
Q
What type of stem cell differentiation results in two daughter cells?
A
stochastic differentiation
21
Q
Where do adult stem cells (somatic) reside?
A
microenvironments called Niches
composed of mesenchymal, endothelial and other cell types
22
Q
What type of stem cells made knockout mice possible?
A
embryonic stem cells
23
Q
Where in the body are adult stem cells present?
A
In tissue that continuously divide (bone marrow, skin, GI tract lining)
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
25
Plasticity and trans-differentiation of adult stem cells
- 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.
26
Stem cells of:
Bone Marrow
HEMATOPOIETIC STEM CELLS
MARROW STEM CELLS
27
Stem cells of:
Liver
- contains stem cells/progenitor cells in the Canals of Hering, called Oval cells
- differentiating into hepatocytes and biliary cells
28
Stem cells of:
Brain
- neural stem cells (NSCs)
- subventricular zone (SVZ) and dentate gyrus of the hippocampus
- generating neurons, astrocytes & oligodendrocytes
29
Stem cells of:
skin (location)
- Hair follicle bulge
- Interfollicular areas of surface epidermis
- Sebaceous glands
30
Stem cells of:
intestinal epithelium
- small intestine, crypts are monoclonal structures derived from single stem cells
- Villus is a differentiated compartment
31
Stem cells of:
Skeletal and Cardiac Muscle
- satellite cells
- located beneath the myocyte basal lamina
- can generate myocytes after injury
32
Stem cells of:
cornea
- limbal stem cells
| - transparency of the cornea depends on the integrity of the outermost corneal epithelium, maintained by the LSC
33
What is the Canals of Hering?
(junction between the biliary ductular system & parenchymal hepatocytes)
34
What type of brain cells can be regenerated?
neurons
astrocytes
oligodentrocytes
35
Replication of cells is stimulated by - 2
growth factors
36
Cell cycles
- G1 (presynthetic)
- S Phase (DNA synthesis)
- G2 (premitotic)
- M (mitotic)
- Quiescent cells that have not entered the cell cycle are in the G0 State
37
G1 aka
(presynthetic)
38
S Phase
(DNA synthesis)
39
G2
(premitotic)
40
M
(mitotic)
41
Growth factors involved in regeneration and wound healing - 7
- 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)
42
Epidermal growth factor is:
mitogenic for
produced by
Mitogenic for variety of epithelial cells, hepatocytes, fibroblasts
produced by keratinocytes, macrophages & other inflammatory
cells
43
TGF-a is:
extracted from
cell proliferation in
- extracted from sarcoma virus-transformed cells
- in embryos and adults and
- in malignant transformation of normal cells to cancer
44
growth factors involved in angiogenesis - 4
- vascular endothelial growth factor (VEGF)
- Fibroblast growth factor
- platelet derived growth factor (PDGF)
- transforming growth factor - b (TGF-B)
45
Functions of Fibroblast growth factor
- wound factor
- New Blood Vessel Formation (Angiogenesis)
- Hematopoiesis
- Development
46
pleiotropic functions of TGF-B
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
Ligands of receptors with intrinsic tyrosine kinase activity
most growth factors and insulin
48
Ligands of receptors lacking intrinsic tyrosine kinase activity that recruit kinases
cytokine
IL-2, IL-3, other interleukins
interferons
erythropoietins,
granulocyte colony- stimulating factor
growth hormone
prolactin
49
Ligands of G-Protein Coupled Receptors
chemokines
vasopressin
serotonin
histamine
epinephrine
NE
calcitonin
glucagon
PTH
corticotropin
rhodopsin
50
Ligands of steroid hormone receptors
thyroid hormone
vitamin D
retinoids
51
Transcription Factors that regulate cell proliferation - 2
c-MYC
c-JUN
p53
52
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).
- without the regrowth of the resected lobe
- instead growth occurs by enlargement of the remaining lobe
(COMPENSATORY GROWTH or COMPENSATORY HYPERPLASIA).
53
What is the endpoint of liver regeneration?
restitution of the functional mass rather than the reconstitution of
the original form
54
Macromolecules that constitute the ECM
1. Fibrous structural proteins:
a) Collagen
b) Elastin
2. Adhesive glycoproteins (CAMs)
a) Immunoglobulins
b) Cadherins
c) Integrins
d) Selectins
55
Collagen:
common/uncommon
chemical composition
- Most common protein providing extracellular framework for all multicellular organisms
56
What is required for the hydroxylation of procollagen?
vitamin c
57
Collagen One is the main component of?
bONE
58
Collagen Two is the main component of?
carTWOlage
59
Collagen Three is the main component of?
reTHREEculate
60
Collagen Four is the main component of?
FLOOR - forms the basement membrane
61
Four main families of Cell Adhesion Molecules (CAM)
1. Immunoglobulins
2. Cadherins
3. Integrins
4. Selectins
62
Integrins binds what to what? - 2
cells and ECM
cell-to-cell
63
Most abundant glycoprotein in the BM
Laminin
64
What provides mechanism for the transmission of mechanical force & activation of intracellular signal transduction pathways?
Cadherins & Integrins
through binding to actin & intermediate filaments
65
Proteoglycans
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
Structural families of Proteoglycans and CAGs include:
HEPARAN SULFATE
CHONDROITIN/DERMATAN SULFATE
KERATAN SULFATE
HYALURONAN
67
Where are Proteoglycans abundantly found?
abundantly found in heart valves, skin & skeletal tissues, synovial fluid, vitreous of the eye & umbilical cord
68
When does Proteoglycan concentration increase?
its concentration increases in inflammatory; diseases (rheumatoid arthritis, scleroderma, psoriasis, & osteoarthritis)
69
What is a scar?
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
Main healing process is repair by deposition
of collagen and other ECM components, causing formation of scar
71
Basic Features of Repair by Connective Tissue
1. Deposition
2. Inflammation
3. Angiogenesis
4. Migration & proliferation of fibroblasts
5. Scar Formation
6. Connective tissue remodeling
72
Repair and Regeneration are influenced by:
1. Proliferative capacity of the cells of the tissue
2. The integrity of the ECM
3. Resolution or chronicity of the injury & inflammation
73
Vasculogenesis is defined as
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
angiogenesis is defined as
the growth of new capillaries from pre-existing blood vessels
also occur by recruitment of endothelial progenitor cells (EPC) from the bone marrow
75
most important growth factor in adult tissues undergoing physiologic angiogenesis (proliferating endometrium) & angiogenesis occurring in chronic inflammation, wound healing, tumors & diabetic retinopathy
VEGF (Vascular endothelial Growth Factor)
76
VEGF (Vascular endothelial Growth Factor) is secreted by
many mesenchymal & stromal cells
77
Which receptor is the most important for angiogenesis?
Tyrosine kinase receptor
78
First step in angiogenesis
recruitment of endothelial progenitor cells (EPC) from the bone marrow
79
Important proteins in angiogenesis
Angiopoietins 1 & 2 (Ang) , PDGF, & TGF-B
participates in stabilization process
80
Ang1 – interacts with
receptor on endothelial cells (Tie2) to recruit periendothelial cells
81
PDGF – participates in the recruitment of
smooth muscle cells
82
TGF-B – stabilized newly formed vessels
by enhancing production of ECM proteins
83
ECM proteins as regulators of Angiogenesis
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
Integrins – critical for
formation and maintenance of newly formed vessels
85
Matricellular Proteins – destabilize
cell- matrix interactions promoting angiogenesis
86
Proteinases – important in tissue
remodelling during endothelial invasion
87
CUTANEOUS WOUND HEALING sequence
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
Inflammation - Initial Injury causes platelet
adhesion& aggregation, & formation of a clot in the wound surface leading to inflammation
89
Proliferation – formation of
granulation tissue, proliferation & migration of connective tissue cells, re-epithelialization of wound surface
90
Maturation – involves ECM ....
deposition, tissue remodelling & wound contraction.
91
In which step of cutaneous wound healing does angiogenesis occur?
Proliferation
92
When the injury involves only the epithelial layer, the principal mechanism of repair is
epithelial regeneration
also called primary union
or healing by first intention
93
How does First Union and Second Union differ?
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
In Cell Proliferation & Collagen Deposition:
Migration of fibroblasts to the site of injury is driven by
chemokines (TNF, PDGF, TGF-B, and FGF)
95
Cell Proliferation & Collagen Deposition:
Proliferation is triggered by
multiple growth factors: (PDGF, EGF, TGF-B, FGF, IL-1 & TNF)
96
Scar Formation
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
Duration from which an incisional surgical wound achieved its maximal strength:
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
Local factors that influence wound healing
1. Infection
2. Mechanical factors
3. Foreign bodies
4. Size, location & type of wound
99
Systemic factors that influence wound healing
1. Nutrition
2. Metabolic status
3. Circulatory status
4. Hormones
100
Which is/are systemic factors that influence wound healing?
1. Foreign bodies
2. Hormones
3. Infection
4. Nutrition
2. Hormones
| 4. Nutrition
101
Contractures - Commonly seen after
serious burns that can compromise joint movements
102
inadequate formation of granulation tissue or assembly of scar that leads to two types of complication :
Wound dehiscence and Ulceration
103
Wound dehiscence is a
surgical complication in which a wound ruptures along a surgical incision.
104
Wound can ulcerate due to
inadequate vascularization during healing
105
Hypertrophic scars generally develop after t
hermal or traumatic injury that involves the deep layers of the dermis.
106
Hypertrophic scar
Accumulation of excessive amounts of collagen may
| give rise to a raised scar –
107
Interchangeably used with the term Scar
Fibrosis
108
What protein is always involved as an important
| fibrogenic agent in scar formation?
TGF-B is always involved as an important
| fibrogenic agent
109
Fibrotic Disorders:
Liver cirrhosis
Systemic sclerosis
Fibrosing diseases of the lungs ( pulmonary
fibrosis, pneumoconioses, drug, radiation-
induced pulmonary fibrosis)
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Chronic Pancreatitis
Glomerulonephritis
Constrictive pericarditis
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