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PCM1 Exam 1 > GP 12 - Tissue Repair: Regeneration, Healing, and Fibrosis > Flashcards

GP 12 - Tissue Repair: Regeneration, Healing, and Fibrosis Flashcards

1
Q

Define and differentiate repair, healing, regeneration, and scar formation.

A
  • Repair - restoration of tissue structure and function following injury. It consists of:
    • Regeneration - production of new cells to replace old/damaged ones
    • Scar Formation - the laying down of fibrous tissue during repair
    • Healing - tissue response to a wound, inflammatory reaction in an internal organ, or to cell necrosis in organs incapable of regeneration. It is a broad term that includes varying degrees of both regeneration and scar formation
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2
Q

Define and differentiate fibrosis and organization.

A

Fibrosis - the laying down of fibrous tissue that occurs during chronic inflammation

Organization - the laying down of fibrous tissue that occurs in a tissue space filled with inflammatory exudates

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3
Q

List the steps of the cell cycle and briefly describe what happens in each of them.

A
  • G1 - cell is performing regular duties, grows in size, and duplicates its centrosomes
  • S - chromosome duplication
  • G2 - rapid cell growth and protein synthesis in preparation for mitosis
  • M - mitosis
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4
Q

What do growth factors do and what cell type is the most important source of growth factors across the body?

A

They act to enchance cellular progression through the cell cycle.

Macrophages

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5
Q

What are the two basic forms of ECM and their primary components?

A

Basement membrane and interstitial matrix

  • Fibriller proteins (collage, elastin, etc.)
  • Adhesive molecules
  • Hydrated gel
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6
Q

What are the primary jobs of the adhesive molecules in the ECM? Give the two big examples of these molecules.

A

Connect cells and ECM components to each other

Deliver signals regarding cellular proliferation and differentiation

  • Laminin
  • Fibronectin
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7
Q

What are the two classes of hydrated gels seen in the ECM? What are their primary purposes?

A

Glycosaminoglycans (GAGs) and Proteoglycans

They give individual organs their turgor, lubrication, and resilience. They also store growth factors

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8
Q

What are the primary functions of ECM?

A
  • Mechanical support
  • Cell growth and maintenance of cell differentiation
  • Scaffolding during tissue repair
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9
Q

Regarding ability to regenerate, how are tissues classified? Give examples of each type.

A
  • Labile Tissues - continuously being lost and replaced by tissue stem cells (intestinal epithelium, epidermis, haemopoietic tissues)
  • Stable Tissues - tissues without stem cells but, when injured, their cells can exit G0 to reenter the cell cycle (liver, kidney, pancreas, endothelium, fibroblasts, smooth muscle cells)
  • Permanent Tissues - consist of terminally differentiated cells that are incapable of further division (brain and cardiac myocytes)
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10
Q

Can healing occur in tissues consisting of only permanent cells?

A

Yes, but only by scar formation

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11
Q

When does scar formation occur? Give major examples.

A

When repair cannot be accomplished by regeneration alone

  • Extensive injury in any tissue
  • Injury to permanent tissue
  • Un-drained pus
  • Foreign body
  • Some infectious agents
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12
Q

List the basic steps of scar formation

A
  1. Maintenance of hemostasis - stop bleeding
  2. Inflammation - clearance of invaders
  3. Cellular Proliferation
    1. Epithelial cells cover wound area
    2. Endothelial cells create new blood vessels
    3. Fibroblasts lay down ECM
  4. Tissue remodeling
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13
Q

What is Granulation Tissue? Describe its gross and microscopic morphology.

A

Granulation tissue is new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process.

Morphology:

  • Gross - pink, soft and has a granular appearance
  • Microscopic - proliferation of fibroblasts and new, thin-walled, delicate capillaries in a loose ECM, often with admixed inflammatory cells, mainly macrophages
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14
Q

What are the primary proliferating cell types in granulation tissue? What are these cells doing?

A
  • Epithelial cells - covering the wound area
  • Enothelial cells - angiogenesis
  • Fibroblasts - laying down ECM
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15
Q

When is angiogenesis typically seen in adults? Which growth factor is the strongest stimulator of angiogenesis? What stimulates the release of this growth factor?

A
  • During Tissue Repair
  • In tumors
  • In ischemia

The strongest growth factor to stimulate angiogenesis is Vascular Endotherlial Growth Factor (FEGF). It’s release is stimulated by ischemia.

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16
Q

List the steps of angiogenesis

A
  1. Vasodilation
  2. Recruitment of endothelial precursor cells (EPCs) to injury site
  3. Formation of capillary sprout
  4. Proliferation of endothelial cells behind the leading point of the sprout
  5. Canalization and formation of lumina
  6. Recruitment of periendothelial cells
  7. Inhibition of endothelial cell proliferation

Refer to image

17
Q

What is fibroplasia, when does it occur, and what are the key steps involved in it?

A

Fibroplasia is the deposition of connective tissue into a wound and it occurs simultaneously with angiogenesis during wound healing.

  1. Transforming growth factor-β (TGFβ), platelet derived growth factor (PDGF), and fibroblast growth factor-2 (FGF2) are released by cells within the granulation tissue
  2. Fibroblasts are recruited, they proliferate, and deposit ECM
  3. Some of the fibroblasts differentiate into myofibroblasts which contract and close the wound
  4. Some formed blood vessels regress
  5. Scar contracts
18
Q

What is the purpose of tissue remodeling after an injury and how does this occur?

A

Tissue remodeling serves to structural reorganize an organ in order to withstand mechanical stress. Collagen and other ECM components are in continous dyanamic states of synthesis and degradation.

19
Q

List the types of signaling pathways that respond to growth factors. What is the end result of these pathways?

A
  • Receptors with intrinsic kinase activity - PI3 Kinase, MAP-kinase, and IP3 pathways
  • Receptors without intrinsic kinase activity - JAK/STAT pathway
  • GPCR pathways

When a growth factor stimulates any one of these pathways, the end result is always txn factor activation

20
Q

What are the four phases to cutaneous wound healing?

A
  1. Hemostasis
  2. Inflammation
  3. Proliferation
  4. Remodeling
21
Q

List the important steps to the proliferative phase of cutaneous wound healing.

A
  1. Migration of keratinocytes
  2. Proliferation of keratinocytes
  3. Differentiation of keratinocytes into stratified squamous epithelium
  4. Reconstitution of the basement membrane
22
Q

What are the key changes that occur during the remodeling phase of cutaneous wound healing?

A

Collagen fibers are initially layed at vertical angles to the surface. During the remodeling phase, the are rearranged to lie across the wound gap.

23
Q

T/F - the tensile strength of a scar is greater than that of the skin before injury.

A

False

The highest tensile strength a scar can reach is 80% of that of the original skin

24
Q

What is the difference between 1st intention (aka - primary union) and 2nd intention (aka - secondary union) cutaneous healing?

A

In 2nd intention healing:

  • The clot is larger, leading to more granulation tissue
  • The wound gap is wider, which means that wound contraction to approximate edges is required
  • There is more necrotic tissue, leading to more inflammation

First intention healing occurs when the wound is minor, clean cut, or stitched together well.

25
Q

List the primary factors that can retard wound healing.

A

Local Factors - infection, poor blood supply, excessive movement, presence of foreign material, irradiation

Systemic Factors - nutritional status, drugs (steroids), comorbidities (cancer)

26
Q

Wound healing is tightly regulated, what can occur if that regulation is disturbed?

A

Excessive Scar Formation - fibrosis, keloid formation, hypertrophic scar, adhesions and contractures

Deficient Healing - chronic ulcer (when healing gets locked in the inflammatory phase) and/or weak wound where the edges may separate (scar dehiscence).

27
Q

List the phases to bone fracture healing? In what key way does bone fracture healing differ from cutaneous healing?

A
  1. Hematoma formation
  2. Immobilization by callus formation
  3. Repair of the fracture gap
  4. Remodeling

Healing of bone restores the structure of and function of the bone completely with no scar formation.

28
Q

What common complications can occur with bone fracture healing?

A
  • Infection (bone fracrures are usually sterile though)
  • Delayed Union - delayed ossification after fibrous union, could lead to non-union
  • Mal-union - healing with angulation
29
Q

List the primary factors that influence bone fracture healing.

A

Local Factors - excessive mobility, infection, and interposition of muscles

Systemic Factors - vitamin C deficiency

30
Q

What are these tissues and what are the key differences between them?

A

Left - granulation tissue

Right - mature scar

The granulation tissue consits mostly of cells while the mature scar is mostly ECM (collagen)

31
Q

What is this?

A

A keloid

32
Q

What is this?

A

A keloid

PCM1 Exam 1 (40 decks)

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