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Pathological Processes > 6. Regeneration And Repair > Flashcards

6. Regeneration And Repair Flashcards

1
Q

Name 3 processes involved in wound healing

A

Haemostasis
Inflammation
Regeneration and/or repair

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2
Q

What is regeneration?

A

Restitution with no, or minimal, evidence that there was a previous injury

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3
Q

What is needed for regeneration to take place?

A

Damage to tissue is not extensive, requires an intact tissue scaffold (needs to be an abrasion)

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4
Q

What type of cells replicate in regeneration?

A

Stem cells

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5
Q

What stems cells are uni potent and what do they produce?

A

Most adult stem cells, one produce one type of differentiated cell

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6
Q

What stem cells are multipotent and what do they produce?

A

Haematopoietic stem cells in bone marrow, produce several types of differentiated cell

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7
Q

What stem cells are totipotent and what do they produce?

A

Embryonic stem cells, produce any type of cell and so any tissues of the body

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8
Q

What are labile tissues and give an example of one

A

Continually dividing tissues, contain short-lived cells that are replaced from cells derived from stem cells eg surface epithelia

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9
Q

What are stable tissues and give an example of one

A

Normally low level of replication, but can undergo rapid proliferation if needed. Both stem cells and mature cells proliferate. Eg parenchymal cells of liver, kidney, pancreas

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10
Q

What are permanent tissues and give an example of one

A

Mature cells that can’t undergo mitosis and no or only a few stem cells present eg neural tissue

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11
Q

In what tissue types can regeneration take place?

A

Labile or stable tissue, not permanent tissues

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12
Q

What is fibrous repair? Why does it occur?

A

Healing with formation of a fibrous connective tissue (scar) due to loss of specialised tissue

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13
Q

When does fibrous repair occur?

A

With significant tissue damage in stable or labile tissue, or if permanent or complex tissue is damaged

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14
Q

What are the 6 stages of scar formation in order?

A

Haemostasis - blood clots.
Acute inflammation - neutrophils infiltrate and digest clot.
Chronic inflammation - macrophages and lymphocytes recruited.
Granulation tissue formation - vessels sprout, (myo)fibroblasts make glycoproteins.
Early scar - vascular network, collagen synthesised, macrophages reduced.
Scar maturation - cells reduced, collagen matures, contracts and remodels.

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15
Q

What does granulation tissue consist of? What cells are involved in each and what do they do?

A

Developing capillaries - endothelial cells for angiogenesis.
Fibroblasts and myofibroblasts - for collagen production (extracellular matrix) and would contraction (fibrils within myofibroblasts).
Chronic inflammatory cells - macrophages for phagocytosis of debris, lymphocytes for production of chemical mediators.

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16
Q

What are the functions of granulation tissue in fibrous repair (scar formation)?

A

Fills the gap
Capillaries supply oxygen, nutrients and cells
Contracts and closes hole

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17
Q

What collagen types are responsible for tissue strength?

A

Fibrillation collagens I-III

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18
Q

What collagen types are amorphous and make up structures such as basement membranes?

A

Collagens IV-VI

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19
Q

What is collagens structure and function?

A

Triple helices of various polypeptide alpha chains.

Provides extracellular framework.

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20
Q

How is procollagen made within the cell?

A

Polypeptide alpha chains synthesised in ER of (myo)fibroblasts.
Enzymatic modification including vitamin C dependant hydroxylation.
Alpha chains align and cross-link forming soluble procollagen triple helix which is secreted.

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21
Q

How is collagen assembled from procollagen?

A

Procollagen cleaved to tropocollagen.
Polymerises to form microfibrils then fibrils, which form collagen fibres.
Cross-linking produced tensile strength and there is slow remodelling by specific collagenases.

22
Q

How does scurvy lead to tooth loss, old scar break down and bleeding?

A

Vitamin C deficiency.
Vitamin C needed from hydroxylation of procollagen alpha chains, so reduced cross-linking and defective helix formation.
Lacks strength, vulnerable to enzymatic degradation, and particularly affects collagen supporting blood vessels.

23
Q

What causes hyperextensible fragile skin, hypermobile joints, colon rupture, large arteries and retinal detachment in patients with ehlers-danlos syndrome?

A

Genetic disorder.
Defective conversion of procollagen to tropocollagen.
So fibres lack adequate tensile strength, and there is poor wound healing.

24
Q

What causes skeletal fragility and blue sclera in osteogenesis imperfecta?

A

Too little collagen leads to extreme skeletal fragility and makes sclera translucent.

25
Q

What gender are patients with Alpert syndrome normally and why?

A

Male, X-linked recessive

26
Q

What causes patients with Alpert syndrome to have dysfunction of glomerular basement membrane, cochlea or ear, lens of eye, and haematuria in children/adolescents progressing to renal failure?

A

Type IV collagen abnormal

27
Q

What 3 ways can cell to cell signalling be via?

A

Hormones
Local mediators (eg growth factors)
Direct cell-cell or cell-storms contact

28
Q

How are regeneration and repair triggered and controlled?

A

Cells communicate with each other to produce a proliferative response

29
Q

With cell signalling by local mediators and hormones, what is autocrine communication?

A

Cells respond to signalling molecules that they themselves produce

30
Q

With cell signalling by local mediators and hormones, what is paracrine communication?

A

Cell produces signalling molecules which then act on adjacent cells, which are often of a different cell type

31
Q

With cell signalling by local mediators and hormones, what is endocrine communication?

A

Hormones synthesised by cells in an endocrine organ, then conveyed in blood stream to target cells to effect physiological activity

32
Q

What are growth factors?

A

A type of local mediator.
Polypeptides that act on cell surface receptors.
Coded by proto-oncogenes.
Important in wound healing.
Bind to specific receptors, stimulate transcription of genes that regulate entry of cell into cell cycle and the cells passage through it.

33
Q

Name 3 other effects that growth factors can have other than cell proliferation

A

Locomotion
Contractility
Viability

34
Q

What are the actions of the growth factor tumour necrosis factor?

A

Induced fibroblast migration, fibroblast proliferation, collagenase secretion.

35
Q

Give 3 examples of cells what produce growth factors

A

Platelets, macrophages, endothelial cells

36
Q

What is contact inhibition and how does it work? What are cadherins and integrins?

A

Inhibits proliferation of intact tissue, promotes proliferation in damaged tissues, by signalling through adhesion molecules.
Cadherins - bind cells to each other.
Integrins - bind cells to the extracellular matrix.

37
Q

What happens with contact inhibition in malignant cells?

A

Is altered

38
Q

When does healing by secondary intention occur?

A

Fibrous repair - excisional wound, wounds with tissue loss and separated edges, infected wounds. Open wound filled by abundant granulation tissue, grows in from wound margins.

39
Q

When does healing by primary intention occur?

A

Regeneration - incised, closes, non-infected, sutured wounds. There is disruption of basement membrane continuity, but death of only a small number of epithelial and connective tissue cells. Minimal clot and granulation tissue.

40
Q

What occurs in healing by primary intention?

A

Epidermis regenerates (basal epidermal cells at edge move over denuded cells, deposited basement membrane, fuse in midline beneath scab, scab falls off), dermis undergoes fibrous repair, remove sutures at 10 days, minimal contraction and scarring, good strength.

41
Q

What happens in healing by secondary intention?

A

Same process as in primary intention, but to a greater extent and takes longer. Considerable wound contraction required (initially occurs as scab contracts, myofibroblasts appear and contract). New epidermis often thinner than usual.

42
Q

What does the shape of a scar depend on and why?

A

Depends on original shape of wound. Contracts as if margins are drawn into the centre.

43
Q

Why does the donor site heal in split skin grafts?

A

Leave hair follicles and other glands behind, as isn’t that deep, so can heal well as the epithelial cells lining these structures can regenerate.

44
Q

How does bone heal?

A

Haematoma.
Granulation tissue forms, cytokines released by platelets and inflammatory cells that activate osteoprogenitor cells.
Soft callous (fibrous tissue and cartridge) forms.
Hard callous (initially woven bone laid down by osteoblasts).
Lamellar bone replaces woven bone, remodelling takes place.

45
Q

Name 4 local factors that can influence wound healing

A 
Type, size, location of wound
Mechanical stress
Bloody supply
Local infection
Foreign bodies
46
Q

Name 6 general factors that can influence wound healing

A 
Age
Anaemia, hypoxia, hypovolaemia
Obesity
Diabetes
Genetic disorders
Drugs
Vitamin deficiency
Malnutrition
47
Q

Give 3 examples of complications of fibrous repair and an example of a consequence of each

A

Insufficient fibrosis - eg wound dehiscence in obesity.
Overproduction of fibrous scar tissue - eg keloid scar.
Excessive scar contraction - obstruction of tubes eg oesophageal stricture.

48
Q

What healing, if any, takes place in cardiac muscle?

A

Limited regenerative capacity, MI followed by scar formation, which can compromise cardiac function.

49
Q

What healing, if any, takes place in the liver?

A

Completely regenerates and restores liver mass. Almost all hepatocytes replicate during regeneration, which is then followed by replication of non-parenchymal cells.

50
Q

What healing, if any, takes place in peripheral nerves?

A

Axons degenerate, proximal stumps sprout and elongate, Schwann cells vacated by the distal degenerated axons guide them back to the tissue that the nerve innervates. Axon growth occurs at approx 1-3mm/day.

51
Q

What healing, if any, takes place in cartilage?

A

Does not heal well as lacks blood supply, lymphatic drainage or innervation

52
Q

What healing, if any, takes place in the CNS?

A

Is neural tissue, so is permanent, when damaged the CNS neural tissue is replaced by proliferation of CNS supportive elements (glial cells).

Pathological Processes (14 decks)

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