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Pathological Processes > Session 4 > Flashcards

Session 4 Flashcards

1
Q

What are the 3 wound healing processes involved?

A
  1. Haemostasis - stopping bleeding
  2. Inflammation (tissue injury)
  3. Regeneration and repair
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2
Q

What is the definition of regeneration?

A

The regrowth of cells and tissues to replace lost structures with minimal evidence of injury. Only possible with minor/superficial injury as it requires an intact connective tissue scaffold.

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3
Q

How are cells induced to regenerate?

A
  • Growth factors

- Cell-to-cell communication

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4
Q

What are labile tissues?*

A
  • Continuously dividing tissues
  • Proliferate throughout life to replace cells that are destroyed
  • Short-lived cells

e.g. bone marrow, haematpoietic cells, surface epithelia

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5
Q

What are stable tissues?*

A
  • Tissues that normally have a low level of replication but can undergo rapid division in response to stimuli
  • Can reconstruct tissue of origin
  • Mature cells in G0 but can enter G1

e.g. liver cells, mesenchymal cells (fibroblasts), smooth muscle cells

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6
Q

What are permanent tissues?*

A
  • Tissues with cells that have permanently left the cell cycle and cannot undergo mitotic division
  • No/few stem cells, cells are terminally differentiated
  • Effective proliferative response is not mounted

e.g. neurones, cardiac muscle cells

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7
Q

What are stem cells?

A
  • Cells with prolonged proliferative activity

- Asymmetric replication: one becomes a mature cell, one remains a stem cell

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8
Q

What are totipotent stem cells?

A

Stem cells that can differentiate into all cell types

e.g. embryonic stem cells

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9
Q

What are multipotent stem cells?

A

Stem cells that can differentiate into several different types of cell
(e.g. haematopoietic stem cells)

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10
Q

What are unipotent stem cells?

A

Stem cells that are only able to differentiate into one cell type
(most cells in the human body; lineage-specific)

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11
Q

How do permanent cells heal?

A
  • Replaced with a scar

- CNS: neurones replaced with glial cells

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12
Q

What is the regenerative capacity of tendons?

A

Poor as they have few cells and few blood vessels - secondary ruptures common

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13
Q

What is the regenerative capacity of adipocytes?

A

None - new fat cells formed by committed, undifferentiated cells that lie amongst

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14
Q

What is the regenerative capacity of epithelia?

A

Very good, especially surface epithelia

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15
Q

What is the regenerative capacity of the liver?

A

Very good - transplanted livers adjust to the size of their recipient in approx. 6 months

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16
Q

What is the regenerative ability of melanocytes?

A

Either too much/too little - why scars are paler

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17
Q

What is the regenerative ability of muscle?

A
  • Smooth: very good

- Striated: limited, from satellite cells

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18
Q

What is the regenerative ability of the central nervous system?

A

None in humans - neurones cease to multiply after birth, and severed axons do not grow back effectively

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19
Q

When does fibrous repair occur?

A
  • Collagen framework of tissue is destroyed
  • Chronic inflammation
  • Necrosis of specialised parenchymal cells
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20
Q

What are the processes involved in fibrous repair?

A
  • Phagocytosis of necrotic debris
  • Proliferation of endothelial cells - angiogenesis
  • Proliferation of fibroblasts/myofibroblasts to synthesise collagen and contract would (GRANULATION TISSUE)
  • Maturation into scar
  • Contraction
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21
Q

Why is collagen important?

A

Provides the extracellular framework for all multicellular organisms (eg. type 1: bones, tendons and ligaments)

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22
Q

What is the structure of collagen?*

A
  • Triple helix of three polypeptide alpha chains, gly-x-y repeating sequence
  • Preprocollagen produced in cell
  • Modified to procollagen - triple helix, secreted from cell
  • N and C terminals cleave to produce tropocollagen
  • Crosslinking
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23
Q

What is scurvy?

A
  • Vitamin C deficiency (required for hydroxylation of proline and lysine in procollagen)
  • Bleeding
  • Poor wound healing
24
Q

What is Ehlers-Danlos syndrome?

A
  • Collagen fibres don’t have tensile strength
  • Hyperextensible and fragile skin
  • Hypermobile joints - dislocation
  • Poor wound healing
  • Corneal rupture and retinal detachment
  • Colon rupture
25
Q

What is osteogenesis imperfecta?

A
  • Not enough bone tissue
  • Very fragile
  • Blue sclera (too little collagen)
  • Hearing impairment
26
Q

What is Alport syndrome?

A
  • X linked disorder
  • Abnormal type 4 collagen - dysfunction of glomerular basement membrane, cochlea and eye lens
  • Presentation with haematuria
  • Progresses to renal failure
27
Q

What controls regeneration and repair?

A

Cell to cell communication via local mediators, hormones or direct cell-cell contact

28
Q

What is autocrine cell communication?

A

Cells respond to their own signalling molecules.

29
Q

What is paracrine cell communication?

A

Cells producing signalling molecules that act on adjacent cells

30
Q

What is endocrine cell communication?

A

Hormones synthesised and are delivered in the blood stream to target cells to alter activity

31
Q

What are growth factors?

A

Polypeptides that act on cell-surface receptors - act over a short distance

  • Stimulate cell proliferation, inhibition, differentiation, activation and angiogenesis
  • Regulate entry of cell into cell cycle by binding to genes
32
Q

What is epidermal growth factor?

A

GF mitogenic for epithelial cells and fibroblasts

  • Produced by keratinocytes and macrophages
  • Binds to EGFR
33
Q

What is vascular endothelial growth factor (VEGF)?

A
  • Vasculogenesis

- Angiogenesis in tumours, chronic inflammation, wound healing

34
Q

What is platelet-derived growth factor?

A

Released on platelet activation

- Migration and proliferation of fibroblasts, monocytes and smooth muscle cells

35
Q

What is tumour necrosis factor (TNF)?

A
  • Induces fibroblast migration and proliferation

- Collagenase secretion

36
Q

What is contact inhibition and why is it important?*

A
  • Isolated cells that are activated replicate until they encounter another cell
  • Cadherins bind between cells and inhibit further proliferation
  • Defective in cancer cells!
37
Q

What are myelofibroblasts?*

A

Cells with fibroblastic and smooth muscle properties, can therefore contract the wound (have intracellular actin)

38
Q

What are fibroblasts?*

A

Cells with a spindle-shaped nucleus and cytoplasmic extensions

  • Secrete collagen and elastin
  • C + E form extracellular matrix
39
Q

What is healing by primary intention?

A
  • Occurs in incisional, closed, non-infected and sutured wounds
  • Where there is disruption of epithelial basement membrane continuity but not all cells are dead
  • More favourable healing and less scars
40
Q

What is the process of healing by primary intention?* !!!!!

A
  • Haemostasis: severed arteries contract and clotting occurs to form scab and prevent bacteria entering
  • Inflammation: neutrophils appear at margins to get rid of pathogens
  • Migration of cells: macrophages appear and scavenge dead neutrophils; secrete cytokines to attracts other cells
  • Regeneration: macrophages replace neutrophils and granulation tissue invades. Epithelial cells proliferate and scab falls off
  • Collagen production and angiogenesis
  • Early scarring: fibroblasts deposit collagen fibres. Oedema and vascularity disappear, skin appendages don’t form
  • Scar maturation: few elastic fibres and lots of collagen (little recoil), capillaries disappear so scars look white
41
Q

What is healing by secondary intention?

A
  • In wounds with significant tissue loss and unapposed edges, as well as abscesses (pull ends further apart)
  • Wound filled by granulation tissue
  • More intense inflammation
42
Q

What is the process of secondary intention?*

A
  • Would must contract more, and epidermis regenerates from the edges
  • Myofibroblasts appear and contract affter a weak
  • Final scar shape depends on original wound shape
  • Substantial scar formation
  • New epidermis thinner than usual
  • Healing delayed if infected
43
Q

What is the process of healing a bone fracture?*

A
  1. Haematoma forms - fills the gap around injury and provides foundation for growth
  2. Fibrin mesh and granulation tissue formed, and inflammatory cells release cytokines to activate osteoclastic and osteoblastic activity
  3. Soft callus forms - fibrous tissue and cartilage, begins the formation of woven bone by osteoblasts. forms a bulge around fracture site
  4. Hard callus - after several weeks, laid down by osteoblasts and is organised into lamellar bone by osteoclasts to add tensile strength
  5. Remodelling: occurs in response to mechanical stresses, and appears same as previous bone
44
Q

What are the local factors influencing regeneration and repair?

A
  • Size: small wounds heal quicker
  • Location
  • Mechanical stress (slower healing when bearing weight)
  • Blood supply
  • Local infection
  • Foreign body
  • Denervation
  • Necrotic - need more healing
  • Protection - helps wound healing and protection
  • Surgical techniques can minimise scarring
45
Q

What are the systemic factors affecting wound healing?

A
  • Age - children heal quicker
  • Anaemia, hypoxia and hypovolaemia slow healing
  • Obesity - increased weight bearing
  • Diabetes - impaired blood supply
  • Genetic disorder
  • Immunosuppressive drugs
  • Vit. C deficiency inhibits collagen synthesis
  • Malnutrition/protein loss - lack of essential substances
46
Q

What are fibrous adhesions?*

A
  • Fibrous bands common after abdominal operations

- Can block tubes if extend around organs

47
Q

Why is loss of function a complication?

A
  • Replacement of specialised cells by fibrous tissue

eg. heart - fibroblasts can’t conduct electrical current, can lead to arrhythmias

48
Q

What are keloid scars?*

A
  • Scars that occur during overproduction of fibrous tissue due to excess collagen
  • Don’t regress
  • Excision will produce another one
49
Q

What is disruption of architecture as a complication of repair?

A

Interferes with normal function (eg. liver cirrhosis)

50
Q

What is excessive scar contraction?*

A

The scar is too ‘tight’ and can obstruct tubes if in wrong location

  • Common when wound is over a FLEXION POINT (causes deformities - contractures)
  • Will need long term physiotherapy
51
Q

What is the healing capacity of cardiac muscle?

A
  • Very limited
  • MI is followed by scar formation
  • Compromised function
52
Q

What is the healing capacity of liver?

A
  • Restoration of liver mass by lobe enlargement

- If architecture & hepatocytes severely damaged, regeneration may not be possible and can result in cirrhosis

53
Q

What happens when a nerve is severed?

A
  • Axons degenerate
  • Proximal stumps of axons sprout and elongate
  • Axon growth at 1-3mm/day
54
Q

Why does cartilage not heal well?

A
  • Lack of blood supply

- No lymphatic drainage

55
Q

How does neural tissue heal?

A

Replaced by proliferation of CNS supportive elements, which are glial cells = gliosis.

  • Permanent tissue so doesn’t regenerate

Pathological Processes (10 decks)

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