Lecture 14 Flashcards

1
Q

What are the possible outcomes of an injury?

A
  1. Injury is too severe and overwhelms the patient resulting in their death
  2. The acute (to subacute) inflammatory response removes the injury tissue and any noxious agent and the tissue heals and repairs
  3. The acute (to subacute) inflammatory response fails to remove the injured tissue and the noxious agent persists making the tissue chronic
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2
Q

Define the term healing and repair and differentiate between them:

A

Refers to the restoration of tissue architecture and function after injury (can be inflammatory/non inflammatory). Repair = used for parenchymal (organ) and connective tissues. Healing = used for surface epithelia

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3
Q

What are the two different types of healing and repair that will occur and explain the difference in the functional capacity between them?

A
  1. Regeneration = proliferation of residual cells and maturation of stem cells to replace damaged cells (full functional capacity returned)
  2. Connective tissue deposition - if the injured tissue is incapable of complete repair then replacement by fibrous connective tissue (scar formation) will occur (loss of function or reduced function
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4
Q

What are the intrinsic factors that determine whether a tissue will regenerate or form scar tissue?

A
  1. Cellular factors (organ constituent cells, stem cells, inflammatory cells)
  2. Chemical mediators (growth factors)
  3. Stromal factors (ECM)
  4. Adhesion molecules
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5
Q

What are the extrinsic factors that determine whether a tissue will regenerate or form scar tissue?

A
  1. Additional factors (temperature, nutrition, infectious agents, drugs etc)..
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6
Q

What are the 3 different types of proliferative cell potentials and what is an example of each?

A
  1. Labile cells - most epithelial cells (continually dividing cells) -readily regenerate
  2. Stable cells - mesenchymal cells, parenchymal cells. Cells in GO that can be stimulated to return to G1 - limited regeneration
  3. Permanent cells - cardiac myocytes, neutrons (skeletal muscle). Cells have left the cell cycle - no regeneration = scar tissue
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7
Q

Complete the following statement below:
More residual cells (__(1)___) driven in to the growth phase, ___(2)_____ the likelihood of regeneration without scarring. Proliferation of residual cells driven by signals from __(3) __ and __(4)___. __(5)___ produced by cells near site damage. ___(6)____ activated by tissue injury, also epithelial and stromal cells. Residual cells also use ___(7)___ to bind to ECM proteins and signals from interns further stimulate proliferation.

A
  1. labile cells
  2. greater
  3. growth factors
  4. ECM
  5. GF
  6. macrophages
  7. integrins
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8
Q

What is the function of stem cells in regeneration?

A

Proliferation of residual cells in supplemented by the development of mature cells from stem cells. In adults the most important stem cells are the tissue stem cells. In adults the most important stem cells are the tissue stem cells.

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9
Q

What are the two different types of adult stem cells?

A
  1. Bone marrow haematopoietic cells (HSC) - progenitor and stromal - broad differentiation potential
  2. Tissue stem cells: located in niches within most organ systems: Multi-potential adult progenitor cells (MAPCS)
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10
Q

Why is phagocytosis important in healing?

A

Phagocytosis is important for the removal of injurious agents and damaged/dead tissue so that healing can occur.

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11
Q

What are the pro-inflammatory cytokines produced in inflammation?

A

IL-1, TNF-a, IL-6

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12
Q

What are the growth factors that macrophages produce that are necessary for the wound healing process?

A

PGDF, FGF, TGF a & b, VEGF

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13
Q

What is the function of the fibroblasts in healing?

A

The extracellular matrix protein components are involved in the tensile strength and the integrity of the wound. The growth factors involved include keratinocyte growth factor and IGF-1. They are also heterogeneous as some will become contractile (myofibroblasts) critical in wound contraction.

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14
Q

What early growth factor to the endothelial cells respond to and what growth factor do they then produce themselves?

A

respond to early growth factors such as VEGF and then produce important growth factors themselves (PDGF).

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15
Q

How are tissue fibroblasts activated in the tissue repair process?

A

Fibrin degradation products and oedema activate tissue fibroblasts which then amplifies the repair process.

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16
Q

What are the factors involved in epithelial cell proliferation?

A

EGF, TGFa (tyrosine kinase receptor) & HGF

17
Q

What factors involved in vascular proliferation?

A

VEGF

18
Q

What factor is involved in migration & proliferation of mesenchymal cells?

A

PDGF

19
Q

What factor is involved as a pleiotropic growth inhibitor for epithelial cells & leukocytes and stimulated fibroplasia?

A

TGF-b

20
Q

What are the main cytokines?

A

IL, IFN, TNF

21
Q

What are the signalling mechanisms in cell growth

A
  1. Binding of growth factor (ligand) to receptor
  2. Signal transduction: Receptor dimerisation & phosphorylation (activation)
  3. Production of second messengers
  4. Cellular response
22
Q

How does the Hypoxia inducible factor (HIF) work?

A

O2 present = HIF protein degradation

decreased O2 = HIF protein not hydroxylated and forms active complex that results in gene transcription of various factors which stimulate wound healing and angiogenesis

23
Q

What are the two components of the extracellular matrix?

A
  1. The interstitial matrix

2. The basement membrane

24
Q

What are the two different types of adhesion molecules and provide an example of each?

A

Cell surface adhesion molecules - glycoproteins and Integrins

Matrix adhesion proteins: Fibronectin, Osteonectin, vWF and collagen