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Pathological Processes > Regeneration And Repair > Flashcards

Regeneration And Repair Flashcards

1
Q

What processes are involved in wound healing ?

A

1) injury which damages blood vessels
2) haemostasis ( blood clot )
3) inflammation ( chronic or acute )
4) this then either leads to regeneration OR repair

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2
Q

Define regeneration

A

Regrow the of cells.

This happens to the extent where tissue looks like it was never damaged,

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3
Q

Does regeneration occur with minor or major injuries ?

A

ONLY minor injuries for example superficial skin incisions or abrasian

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4
Q

In regeneration, where do the new cells come from ?

A

Stem cells which can differentiate into other cell types and self renew to maintain a constant tool of stem cells.

This replaces dead / damaged cells.

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5
Q

What are the three types of stem cells ?

A

1) totipotent
2) multipotent
3) unipotent

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6
Q

What are totipotent cells ?

A
  • produce ALL cell types
  • eg embryonic stem cells.
  • cells in the morula
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7
Q

What are multipotent cells ?

A
  • produces several cell types

- eg haemotopoietic stem cells.

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8
Q

What are potent cells ?

A

Produces ONE cell type. Eg epithelial stem cells.

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9
Q

Where are the stem cells ?

A

1) epidermis: in the basal layer there are unipotent stem cells which differentiate into squamous epithelial cells which move to the top of the epidermis where they then shed.
2) intestinal mucosa at the bottom the crypt : unipotent stem cells which differentiates into columnar epithelial cells.
3) Liver : between the hepatocytes there are unipotent stem cells which differentiates into more hepatocytes.

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10
Q

What are tissues classified into ?

A

They are classified based on their regeneration ability

1) Labile tissue
2) stable tissue
3) permanent tissue

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11
Q

What is labile tissueand give examples of labile tissue ?

A
  • tissue that continually regerates regardless of whether there is an injury or not.
  • for example cells in the stratum basale , haematopoietic tissue
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12
Q

What is stable tissue ?

A
  • tissue that does not normally replicate , however. Is stimulated they can replicate.
  • normally there is a low level of replication.
  • for example , liver , kidneys , pancreas , bone , endothelium , smooth muscle.
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13
Q

What is permanent tissue and give examples ?

A

Cells do NOT replicate

For example neurone , skeletal muscle , cardiac muscle , brain

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14
Q

In terms of the cell cycle , what stage are the labile cells at ?

A
  • the labile cells are contiously recycling - they are contiously entering the M stage of the cell cycle.
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15
Q

In terms of the cell cycle , at what stage are the stable cells ?

A
  • they have left the cell cycle at the G0 phas.

- but they can re enter the cell cycle through stimulation.

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16
Q

In terms of the cell cycle , at what stage are the permanent cells at ?

A
  • they have left cell cycle

- and they CANNOT re enter the cell cycle.

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17
Q

If there is injury to labile or stable tissues and the collagen framework is intact , what occurs ? ( regeneration or repair)

A

Regeneration.

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18
Q

If there is injury to labile or stable tissues and the collagen framework is destroyed , what occurs ? ( fibrous repair or regeneration )

A

Fibrous repair

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19
Q

If there is injury to the labile or stable tissues , and there is on going chronic inflammation , what occurs ? ( regeneration or repair )

A

Fibrous repair !

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20
Q

If there is injury to the permanent tissues , what occurs ?

A

Fibrous repair

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21
Q

How does a scar form?

A

1) Damage to blood vessels would cause a blood clot. This is called haemostasis. This is in order to prevent blood loss. This occurs from seconds to minutes.
2) Inflammation occurs - acute then chronic. This happens in order to digest the blood clot and for phagocytosis to occur. This happens from minutes - days.
3) Proliferation of fibroblasts , myofibroblasts which lays down new elastic tissue and collagen tissue. And proliferation of capillaries. This forms granulation tissue.
4) Remodelling : maturation of scar , reduced cell population , increased collagen. And myofibroblasts contract to close the wound. Fibrous scar is formed from the collagen.

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22
Q

What is the function of granulation tissue ?

A

1) fills the gap
2) capillaries supplies oxygen and nutrients to wound
3) contraction and closes defect

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23
Q

Name a few cells involved in fibrous repair

A

Neutrophils - phagocytosis, release of mediators

Macrophages - phagocytosis , release of mediators

Lymphocytes - eliminate pathogens , co ordinate other cells

Endothelial cells proliferation which generates new blood vessels - this is called angiogenesis.

Fibroblasts s

Myofibroblasts

24
Q

Describe characteristics of fibroblasts

A
  • they have spindle shaped nucleus
  • they have cytoplasmic extensions ( star shaped )
  • they secrete collagen and elastin to form the ECM.
25
Q

What are myofibroblasts?

A

They have features. Of both smooth muscle and fibroblasts.

  • where there is a wound , fibroblasts differentiates into myofibroblasts.
  • they also have spindle shaped nucleus , and cytoplasmic extensions ( star shaped )
  • because of their smooth muscle features, they contain actin which alllows for contraction of the wound - helping it close up.
26
Q

What is the most abundant protein in body ?

A

Collagen

27
Q

Where is type 1 collagen found ?

A

Bones

Tendons

Ligaments

Skin

Sclera

Cornea

Vessels

28
Q

Where is type 4 collagen found ?

A

Basement membranes

Lens

Glomerular

29
Q

Outline th eprocess or collagen synthesis

A

1) In the ER of fibroblasts/myofibroblasts, a single polypeptide alpha chain is synthesised. This is called Pre pro collagen.
2) Hydroxylation of the proline and lysine residues in the polypeptide occurs. This is important for the formation of hydrogen bonds. This process is vitamin C dependant.
3) triple helix formation of 3 alpha helix .Alpha chains crosslinked. This occurs in the cytoplasms of myo/fibroblasts. This is now called Pro collagen.
4) secretion of pro collagen out of cell into extracellular space . N and C terminal domains are removed. This is now called tropocollagen in extracellular space.
5) cross linking of tropocollagen to form collagen fibrils. Collagen fibrils aggregate into collagen fibres.

30
Q

What are diseases of defective collagen classified into ?

A

1) acquired

2) inherited

31
Q

What is an example of an acquired defective collagen disease ?

A

Scurvy

32
Q

What is the cause of scurvy

A

Vitamin C deficiency

33
Q

What are the consequences of scurvy

A
  • due to deficiency of vitamin C there is inadequate hydroxylation of pre pro colllagen. This leads to defective triple helix. Which leads to defective collagen.

As a result , it becomes difficult to heal wounds properly. Have the tendency to bleed. Tooth loss.

34
Q

What are three examples of inherited collagen disorders ?

A

1) Ehlers-Danlos syndrome
2) osteogenesis imperfecta
3) Alport syndrome

35
Q

What is ehlers danlos syndrome ?

A
  • collagen fibres lack adequate tensile strength.
  • this results in skin being hyperextensible , fragile , susceptible to injury and joints are hyper mobile.
  • wound healing is poor and patients have a pre disposition to joint dislocation.
  • because the collagen in internal organs is affected , patients can suffer from rupture and retinal detachment.
36
Q

What is osteogenesis imperfecta?

A

Mutation in the collagen 1 gene.

This leads to incorrect production;of collagen fibres.

This leads to weak bones , increased fracture risk , shortened height / stature.

blue sclera

This mainly affects neonates / children.

37
Q

What is Alport syndrome !

A 
X linked disease 
Type V1 (4’ collagen is abnormal and this results in dysfunction of the gomerular ,basement membrane , cochlea of the ear and the lens of the eye.

Patients are usually male.

This progresses to renal failure.

38
Q

How is regeneration and repair controlled ?

A

1CELL COMMUNICATION

1) direct cell - cell contact
2) local mediators eg growth factors
3) hormones

39
Q

How do growth factors which are chemical mediators work to control regeneration/ repair?

A
  • they are polypeptides that’s act on cell surface.
  • this causes cells to enter the cell cycle and proliferate as they continue to divide.
  • examples include : epidermal growth factor. Vascular endothelial. Growth factor. Platelet derived growth factor. Tumour necrosis factor.
40
Q

How does cell-cell contact control regeneration and repair ?

A
  • isolatedcells usually replicate until they encounter other cells.

Cadherins on surface of cells bind between cells. This inhibits further proliferation.

  • this process is defective in cancer.
41
Q

What are the two ways healing of the skin occurs ?

A

1) primary intention

2) secondary intention

42
Q

When does primary intention occur ? And what are features of primary intention skin healing

A
  • there is a wound with apposed edges.
  • in this case , minimal clot and granulation tissue forms.
  • epidermis regenerates
  • Dermis undergoes fibrous repair.
  • very small scar.
43
Q

When does secondary intention occur ? And what are features of secondary intention healing of the skin

A

This occurs when significant tissue loss.
- occurs when there are unapposed edges ( infection , ulcer , abscess )

  • features of this process include : Abundant clot , inflammation , and granulation tissue.
  • considerable wound contraction is required by myofibroblasts.
  • dermis requires significant repair. Epidermis regenerates from edges.
44
Q

Outline the process of fracture healing :

A
  1. Fracture damages blood vessels. So in order to prevent bleeding g , a haematoma forms. Granulation tissue forms ( myofibroblasts , fibroblasts )
    2) soft callus forms : new cartilage forms , collagen forms , elastic tissue forms. Osteoblasts form woven bone ( new bone) which is not strong - it is disorganised.
    3) hard callus then forms : woven bone gets re organised by osetoclasts. Into lamallae bone ( cancellous bone)
    4) Bone remodelling occurs : hard callus gets reorganised into original outline of bone.
45
Q

What are factors influencing wound healing classified into ?

A

1) local

2) systemic

46
Q

What are local influences of wound healing ?

A
  • size : small scratch would heal quicker

Location

Mechanical stress - if it’s an area where this is a lot of weight applied may take longer

Blood supply - if an area has anatomically poorer blood supply , heal less quicker

Local infection - if there is another infection , the body will have to deal with this on top of wound healing so would take longer

Foreign bodies

47
Q

What are examples of systemic influences on wound healing ?

A
  • age

Anaemia , hypoxia , hypovolaemia cam reduce blood supply to Affected area

Obesity

Diabetes ( sugar in blood ideal for microorganisms )

Drugs

Vitamin C defieicnes affect collagen stability

Malnutrition

48
Q

What are 6 complications of. Fibrous repair?

A

1) insufficient fibrosis
2) excessive fibrosis
3) adhesions
4) loss of function
5) disruption of architecture
6) excessive scar contraction

49
Q

What can insuffienct fibrosis lead to ? And when would this usually occur

A
  • insufficient fibrosis can lead to wound dehiscence ( wound re opens )
  • this usually occurs in obese people because there is increase pressure in the wound so it is more likely to open
  • elderly
  • malnutrition

Steroid use which causes skin to become thinner so sutures become difficult to hold onto the skin

50
Q

What is the scar produced from excessive fibrosis repair a.

A

Keloid scar

51
Q

What is adhesions - as an example or complications of fibrosis repair

A
  • bands of collagen / elastin in abdominal cavity after surgery which can cause intestinal obstructure problems
52
Q

What are complications of excessive scar contraction ?

A

Construction of tubes

Loss of function

Fixed joint flexures

Occasionally can impede their circulation

53
Q

Which people are at risk for developing keloid scars ?

A

Afro Caribbean

54
Q

How does a keloid scar differ from a hypertrophic scar ?

A

A hypertrophic scar is raised scar but doesn’t grow beyond the boundaries of the original wound.

It can regress .

Whereas keloid scars go beyond the edges of the wound and does not regress.

55
Q

Describe the healing and repair in brain

A

Neural tissue damage is permanent

Glial cells can proliferate and form scar tissue

56
Q

Describe the healing and repair in skeletal muscle

A

Skeletal muscle cells do not divide as skeletal muscle tissue is permanent

There is little regenerative capacity through satellite cells - these are a reserve pool for stem cells which generate myocytes after injury but any significant injury heals with a fibrous scar

57
Q

Outline the healing and repair of the liver

A

The liver has a remarkable capacity to regenerate

If part of the liver is removed , compensatory growth of liver tissue occurs and there is restoration of liver mass by enlargement of the lobes that remain.

Almost all hepatcyotes replicate during regernation

Pathological Processes (13 decks)

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