Regeneration and Repair Flashcards

1
Q

What are the 3 basic principles of wound healing

A
  1. Close the gap
  2. Repair it with a scar
  3. The smaller the scar, the better
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2
Q

What 3 processes are involved in wound healing?

A
  1. Haemostasis- as blood vessels are open
  2. Inflammation- as there has been tissue injury
  3. Regeneration
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3
Q

What is regeneration?

A

Regneration is the growth of cells and tissues to replace lost structures

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4
Q

Why can’t regeneration take place if injury is too extensive?

A

As regeneration requires an intact connective tissue scaffold

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5
Q

What happens if regeneration cannot take place?

A

A scar forms

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6
Q

Which cells replicate in regeneration?

A

Mainly stem cells

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7
Q

What factors induce cells to regenerate?

A
  • Growth factors in the microenvironment
  • cell to cell communication
  • Electric currents and nervous stimuli (amphibians)
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8
Q

Where are the stem cells located in:

1) Epidermis 2) Intestinal Mucosa 3) Liver

A

1) Epidermis- basal layer
2) Intestinal Mucosa- bottom of crypts
3) Liver- between hepatocytes and bile ducts

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9
Q

What are labile tissues? Give an example

A

Cells that proliferate through life, replacing cells that are destroyed

e.g. lining of mucosa of secretory ducts, columnar epithelia of GI tract, bone marrow

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10
Q

What are stable tissues? Give an example

A

Quiescent tissues that have a low level of replication but can undergo rapid proliferation if necessary

e.g. liver parenchyma, fibrous tissue, endothelium

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11
Q

What are permanent tissues? Give an example

A

Tissues with no ability to replicate

e.g. neural tissue skeletal and cardiac muscle

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12
Q

What is fibrous repair?

A

Healing with formation of a scar- fibrous connective tissue

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13
Q

When does fibrous repair occur?

A

If there is significant tissue loss or if a permanent tissue type is injured

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14
Q

In 5 steps, describe how scars are formed (fibrous repair)

A
  1. Phagocytosis of necrotic tissue debris
  2. Endothelial cell proliferation and angiogenesis
  3. Proliferation of fibroblasts and myofibroblasts to produce collagen and cause wound contraction- granulation tissue
  4. Granulation tissue becomes less vascular and matures into a fibrous scar
  5. Scar matures and shrinks when myofibroblast fibrils contract
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15
Q

What cells are in granulation tissue?

A
  • developing capillaries
  • fibroblasts and myofibroblasts
  • chronic inflammatory cells
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16
Q

What are the functions of granulation tissue?

A
  • fills the wound gap
  • capillaries supply oxygen, nutrients and cells
  • contracts and closes the hole
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17
Q

Why do people get scurvy?

A

Lack of Vitamin C

required for hydroxylation of pro collagen leads to reduced cross-linking and defective helix formation

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18
Q

What is Ehlers-Danlos syndrome?

A

Heterogenous group of 11 inherited disorders where there is defective conversion of pro collagen to tropocollagen

Affects Collagen V

19
Q

What are some of the symptoms of Ehlers-Danlos syndrome?

A
  • Skin is hyperextensible, thin, fragile and susceptible to injury
  • Joints are predisposed to dislocation
  • Large arteries and colon susceptible to rupture
  • Corneal rupture and retinal detachment can be seen
20
Q

What is Osteogenesis Imperfecta?

A

Brittle bone disease

patients have low bone density and skeletal fragility -blue sclerae

21
Q

What is Alport syndrome?

A

Usually X-linked disease (mainly males)

defect in Type IV collagen

22
Q

What are the symptoms of Alport syndrome?

A
  • Results in dysfunction of glomerular basement membrane, cochlea of ear and lens of eye Patients present with haematuria in childhood/ adolescence, progresses to renal failure
  • May also get neural deafness and eye disorders
23
Q

What is contact inhibition?

A

As cells grow, cadherins bind to each other and integrins bind to extracellular matrix

This inhibits proliferation of intact tissues and promotes proliferation of damaged tissues

24
Q

What is healing by primary intention?

A

Healing of incised, closed, non infected wounds i.e clean wounds with opposed edges

The basement membrane is disrupted but only a small number of epithelial and connective tissue cells have died

25
Describe the steps of healing by primary intention in 6 steps
**1) Haemostasis** (seconds-minutes) severed arteries contract and a scab forms **2) Inflammation** (minutes- hours) **Neutrophils** appear at the margin on incision **3) Migration of cells** (up to 48 hours) Macrophages start to appear and scavenge dead neutrophils and secrete cytokines to attracts fibroblasts **4) Regeneration** (3 days) Macrophages **replace** neutrophils and **granulation tissue invades space** **5) Early scarring** (7-10 days) Fibroblasts deposit **collagen** **6) Scar maturation** (1 month-2 years) Scar stretches and becomes **white**
26
Why are mature scars white?
As **capillaries disappear** over time making the scar look white
27
Why do mature scars stretch?
They have **little elastic fibres** so little ability to recoil
28
What is healing by secondary intention?
Healing for much **larger wound** with separated edges or infected wounds Open wound filled with abundant **granulation tissue**
29
What is the difference in the process of healing by secondary intention compared to
* The process is the same but **considerable wound contraction** must take place to close the defect * a scab normally forms * Whole process takes **longer** * **Substantial scar** formation occurs * new epidermis is often **thinner** than usual
30
What are the steps of bone healing?
1. **Haemotoma** fills gap 2. **Granulation tissue forms**- cytokines activate osteoprogenitor cells 3. **Soft callus** forms 4. **Hard callus** forms 5. **Bone remodelling** to lamellar bone by direction of mechanical stress
31
Name some local factors that affect wound healing
* Type, size, location of wound * mechanical stress * blood supply * local infection * foreign bodies
32
Name some general factors that influence wound healing
* age * anaemia, hypoxia, hypovolaemia * obesity * diabetes * genetics * drugs * vitamin deficiency * malnutrition
33
What is insufficient fibrosis?
When the **wound falls apart** (dehiscence) or **ulceration** Can happen in the obese, elderly, malnourished or on steroids
34
What are adhesions?
fibrous repair connections that form that can block tubes or compromise organs
35
Why might you get loss of function as a complication of fibrous repair?
Due to replacement of specialised functional parenchymal cells by scar tissue e.g. healed MI
36
What is a keloid scar?
**Overproduction** of fibrous scar tissue that exceeds the borders of the scar More common in Afro-Carribbeans
37
Why does cartilage not heal well?
It lacks blood supply
38
How well does cardiac tissue repair?
**Poorly**- limited regenerative capacity. can impact function
39
How well does liver repair?
**Liver repairs well** However, if architecture is severely damaged hepatocytes might not regenerate and cirrhosis occurs
40
What is gliosis?
Neural tissue is permanent and non-proliferative When CNS damage occurs, neural tissue is replaced by **proliferation of glial cells**
41
Why might polyfilament sutures be detrimental to wound healing?
They have a **large surface area for bacteria** to grow on Monofilament sutures are preferred
42
What happens to the vascularity of granulation tissue over time?
It decreases
43
What class of drugs is known to inhibit wound healing? Why?
**Corticosteroids** Known to inhibit collagen synthesis