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Pathological Processes > Session 4: Regeneration and Repair > Flashcards

Session 4: Regeneration and Repair Flashcards

1
Q

Wound healing involves three processes. Which?

A

Haemostasis
Inflammation
Regeneration

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2
Q

There are three main factors of which cells are induced to regenerate. Which?

A

Growth factors
Cell-cell communication
Electric current and nervous stimuli

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3
Q

What three groups can tissues of the body be divided into based on their proliferative activity/regeneration?

A

Labile tissues
Stable tissues
Permanent tissues

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4
Q

Explain labile tissues and give examples.

A

Proliferation of cells throughout life in these tissues which replace cells that are destroyed.

Surface epithelia
Lining mucosa
Columnar epi of GI tract and uterus
Transitional epithelium of urinary tract
Cells of bone marrow
Haemopoietic tissue
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5
Q

Explain stable tissues and give examples.

A

Also called quiescent tissues. Normally a low level of replication but can undergo rapid proliferation in response to stimuli. This means that the cells are usually in G0 but can go to G1 in case of stimuli.

Parenchymal cells of the liver, kidneys and pancreas.
Mesenchymal cells such as fibroblasts, bone osteoclasts and smooth muscle cells.
Vascular endothelial
Resting lymphocytes
White blood cells

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6
Q

Explain permanent tissues and give examples.

A

Tissues containing cells that have left the cell cycle and will not divide anymore. This means that any damage to permanent tissue will lead to healing with scar tissue or in case of the CNS microglial cells will fill the cavity.

Neurones
Skeletal muscles
Cardiac muscle

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7
Q

What are stem cells and what are their roles?

A

Cells with prolonged proliferative activity which show asymmetric replication. They differentiate into mature non-dividing cells and are involved in tissue regeneration in tissue where regeneration is possible.

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8
Q

What is asymmetric replication?

A

When one stem cells stays a stem cell and the other one goes on to differentiate into the desired cell type.

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9
Q

Give some example of different ‘grades’ of stem cells. What are they and where are they found?

A

Totipotent which can differentiate into any cell only found in embryo.
Multipotent which can differentiate into a lot of different cells, can be found in adult stem cells, an example is haemopoietic stem cells (HSC).
Unipotent which differentiate into one specific lineage. This is the most common stem cell in adult stem cells.

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10
Q

Give the regenerative capacity of the following tissues:

  1. Bone
  2. Tendons
  3. Articular cartilage
  4. Adipocytes
  5. Epithelia
  6. Liver
  7. Mesothelia
  8. Smooth muscle
  9. Striated muscle
  10. Peripheral nerves
  11. CNS
A
  1. Very good
  2. Poor
  3. Poor
  4. None
  5. Very good
  6. Very good
  7. Good
  8. Very good
  9. Poor to none
  10. Poor
  11. None
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11
Q

Why would fibrous repair occur?

A

If the collagen framework of a tissue is destroyed, in case of chronic inflammation, in case of necrosis of specialised parenchymal cells that cannot be replaced -> fibrous repair will be initiated leaving a scar behind.

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12
Q

Outline the steps of fibrous repair.

A
  1. Phagocytosis of debris
  2. Proliferation of endothelial cells result in angiogenesis (formation of small capillaries).
  3. Proliferation of fibroblasts and myofibroblasts -> collagen synthesis and deposition and wound contraction. This forms granulation tissue.
  4. Granulation tissue becomes less vascular and mature into a fibrous scar.
  5. Scar matures and shrinks by contraction of fibrils in myofibroblasts.
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13
Q

Briefly outline collagen features.

A

Triple helix of alpha chains.
Gly-x-y repeating sequence.
Cross-linking between alpha chains strengthen the collagen.

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14
Q

Give examples of diseases due to collagen defects.

A

Scurvy - vitamin C def. for hydroxylation of procollagen -> unable to heal wounds adequately

Ehlers-Danlos Syndrome - Collagen fibres lack adequate tensile strength.

Osteogenesis imperfecta - Too little bone tissue and extreme skeletal fragility

Alport syndrome - X-linked disease. Abnormality in Type 4 collagen resulting in dysfunction of the glomerular basement membrane, cochlea of the ear and lens of the eye. Haematuria follows and chronic renal failure eventually. Neural deafness and eye disorders.

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15
Q

Symptoms of EDS.

A 
Hyperextensible skin
Fragile skin
Skin susceptible to injury
Poor wound healing
Hypermobility of joints
Rupture of colon and large arteries
Corneal rupture and retinal detachment
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16
Q

What kinds of cell communications are responsible for regeneration and repair?

A

Autocrine - the cell responds to signalling molecules that they produce themselves

Paracrine - adjacent cells produce local mediators which act on adjacent cells.

Endocrine - release of hormones by endocrine organ released into blood stream and act on distant tissue.

17
Q

What else besides local mediators are important in tissue repair and regeneration?

A

Growth factors.

18
Q

Give structure and features of growth factors. What are their roles?

A 
Polypeptides that act on specific cell surface receptors. Also called local hormones.
Stimulate cell proliferation or inhibition and regulate the entry of the cell into the cell cycle and the cell's passage through the cell cycle.
Also affect:
Cell locomotion
Contractility
Differentiation
Viability
Activation
Angiogenesis
19
Q

Give examples of growth factors.

A

Epidermal growth factor
Vascular endothelial growth factors
Platelet-derived growth factors
Tumour necrosis factors

20
Q

What are epidermal growth factors? What do they do and how are they produced?

A

Stimulate mitosis for epithelial cells, hepatocytes and fibroblasts.

They are produced by keratinocytes, macrophages and inflammatory cells.

21
Q

What are Vascular endothelial growth factor? What do they do and how are they produced?

A

Stimulates vasculogenesis and angiogenesis in tumours, chronic inflammation and wound healing.

22
Q

What are Tumour necrosis factor? What do they do and how are they produced?

A

Stimulates fibroblasts migration, proliferation and collagenase secretion.

23
Q

Another concept in wound healing that is important is contact inhibition. What is contact inhibition?

A

When normal cells become isolated from other cells they will start to replicate until they touch another cell. This forms a monolayer sheet of cells with no cell overlap. Adhesion molecules play an important role

24
Q

What are adhesion molecules that bind to each other called?

A

Cadherins

25
Q

What are adhesion molecules that bind between cell and ECM called?

A

Integrins

26
Q

When does healing by primary intention occur?

A

Occur in incisional, closed, non-infected and sutured wounds like clean wounds.
Where there is only death of a limited number of epithelial and connective tissue cells.

27
Q

Outline the process of healing by primary intentions as steps.

A
  1. Seconds to minutes - Where haemostasis occur.
    Arteries contract and narrow space fills with clotted blood. Dehydration of the surface clot and a scab is formed. This prevents bacteria from entering.
  2. Minutes to hours - Inflammation where neutrophils Wards off bacteria. The inflammation is triggered automatically without the presence of bacteria. This means that there is not enough of white cells to be classified as pus.
  3. Up to 48 hours - Migration of cells
    Where macrophages start to appear and begin to scavenge the dead neutrophils. The macrophages also secrete cytokines which will attract other cells such as fibroblasts and endothelial cells. Epidermal cells will deposit basement membrane component as they go and fuse in the midline beneath the scab.
  4. Three days - Regeneration
    Where macrophages entirely replace neutrophils. Granulation tissue invades space. Scab falls off. Fibroblasts produce collagen and angiogenesis progresses.
  5. Seven to ten days - Wound filled with granulation tissue.
    Fibroblasts proliferate and deposit collagen forming a scar. However hair and sweat glands don’t form which is why scars are hairless. White cells infiltrate, oedema and increased vascularity disappear.
  6. One month to two years - scar maturation.
28
Q

Explain secondary healing intention. When is it seen?

A

Seen in excision wounds or wound with tissue loss and separated edges and also seen in infected wounds.
Here in healing of secondary intent the wound is filled by abundant granulation tissue which grows in from the wound margins. There are larger clots and more necrotic debris, also the inflammatory response is more intense.
The scar formation is larger and more substantial.

29
Q

Give local factors influencing regeneration and repair.

A
  • Size, location and type of wound
  • Blood supply (avascular or not)
  • Denervation which impair healing
  • Local infection producing persistent tissue injury
  • Foreign bodies producing persistent inflammation
  • Haematoma which can slow healing if it is large and persistent
  • Nectrotic tissue
  • Mechanical stress
  • Protection (dressings) which help to keep the wound clean and protect against infection
  • Surgical techniques
30
Q

Give systemic factors influencing regeneration and repair.

A
  • Age
  • Anaemia, hypoxia and hypovolaemia
  • Obesity
  • Diabetes
  • Malignancy
  • Genetic disorders
  • Drugs (steroids/immunosurpressors)
  • Vitamin deficiency
  • Malnutrition or protein loss
31
Q

What are complications that can arise from fibrous repair in addition to delayed healing?

A
  • Formation of fibrous adhesions blocking tubes and compromising organ function
  • Loss of function due to replacement of specialised functional parenchymal cells by scar-tissue.
  • Distortion of architecture interfering with normal function like in liver cirrhosis
  • Overproduction of fibrous scar tissue like a keloid scar.
  • Excessive scar contraction causing obstruction of tubes and can even impair blood circulation.
32
Q

Healing of cardiac muscle.

A

Limited if any usually resulting in scar tissue formation in the heart.

33
Q

Healing of liver.

A

Remarkable capacity to regenerate.
Hepatocytes replicate first - followed by replication of non-parenchymal cells.
If the architecture is too damaged scar tissue and cirrhosis can follow.

34
Q

Healing of peripheral nerves.

A

Axon degenerates and the proximal stump will sprout and elongate. This is by they use of Schwann cells.

35
Q

Healing of cartilage.

A

Does not heal well as it lacks blood supply, lympathics and innervation.

36
Q

Healing of CNS.

A

Non-proliferative tissue so damage means that the neural tissue is replaced by proliferation of CNS supportive elements (glial cells) called gliosis.

Pathological Processes (14 decks)

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