S4) Healing and Repair Flashcards

1
Q

What are the three processes involved in wound healing?

A
  • Haemostasis – as vessels are open
  • Inflammation – as there has been tissue injury
  • Regeneration (aka resolution) and/or repair – as structures have been injured or destroyed
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2
Q

What is regeneration?

A

Regeneration is the growth of cells and tissues to replace lost structures e.g. epithelia of skin and GI tract can regenerate after injury

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3
Q

Which cells replicate in regeneration?

A

New differentiated cells are mainly derived from stem cells as many terminally differentiated cells can’t divide

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4
Q

What are stem cells?

A

Stem cells are cells with prolonged proliferative activity which show asymmetric replication

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5
Q

What is asymmetric replication?

A

In asymmetric replication one of the daughter cells remains as a stem cell while the other differentiates into a mature, non-dividing cell

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6
Q

Whereabouts in the tissues are the stem cells?

A

Varies between tissues:

  • Epidermis – basal layer adjacent to the basement membrane
  • Intestinal mucosa – bottom of crypts
  • Liver – between hepatocytes and bile ducts
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7
Q

Identify and describe the three different kinds of stem cells in terms of their regenerative capacity

A
  • Unipotent – most adult stem cells, as they only produce one type of differentiated cell e.g. epithelia
  • Multipotent – produce several types of differentiated cells e.g. haematopoietic stem cells
  • Totipotent – can produce any type of cell and therefore any tissue of the body e.g. embryonic stem cells
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8
Q

Tissues of the body are divided into three groups on the basis of their proliferative activity.

What are these groups?

A
  • Labile
  • Stable
  • Permanent
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9
Q

What are labile tissues?

A

Labile tissues are continuously dividing tissues which proliferate throughout life replacing cells that are destroyed

E.g. surface epithelia lining mucosa, columnar epithelia of GI tract and uterus, urothelium, cells of bone marrow and haematopoietic tissues

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10
Q

What are stable tissues?

A

Stable tissues are quiescent tissues which normally have a low level of replication can undergo rapid division in response to stimuli (induced to enter the cell cycle)

E.g. parenchymal cells of the liver, kidneys and pancreas, fibroblasts, bone osteoclasts and smooth muscle cells, vascular endothelial cells

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11
Q

What are permanent tissues?

A

Permanent tissues are non-dividing tissues which contain cells that have left the cell cycle and can’t undergo mitotic division in postnatal life

E.g. neurones, skeletal and cardiac muscle cells

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12
Q

Explain the role of stem cells in the three different groups of cells based on their proliferative activity

A
  • Labile tissues contain cells that are short-lived and are continually being replaced by cells derived from stem cells
  • In stable tissues the mature cells as well as stem cells are involved in proliferation in response to stimuli
  • Permanent tissues contain terminally differentiated cells which cannot replicate
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13
Q

In what circumstances can regeneration occur?

A
  • If the damage occurs in a labile/stable tissue
  • If the tissue damage is not extensive (intact connective tissue scaffold)
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14
Q

What is fibrous repair?

A
  • Fibrous repair is healing with formation of fibrous connective tissue (scar)
  • Specialised tissue is lost and healing by secondary intention occurs
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15
Q

When does fibrous repair occur?

A
  • If there is significant tissue loss
  • If permanent or complex tissue is injured
  • If there is ongoing chronic inflammation
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16
Q

How can we determine whether fibrous tissue or regeneration will occur?

A
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17
Q

In 6 steps, explain how a scar forms

A

Seconds - minutes: haemostasis

Minutes - hours: acute inflammation

1 - 2 days: chronic inflammation

3 days: granulation tissue forms

7 - 10 days: early scar

Weeks - 2 years: scar maturation

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18
Q

Granulation tissue has a granular appearance and texture.

What does it consist of?

A
  • Developing capillaries
  • Fibroblasts and myofibroblasts
  • Chronic inflammatory cells
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19
Q

What does granulation tissue do?

A
  • Fills the gap
  • Capillaries supply oxygen, nutrients and cells
  • Contracts and closes the hole
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20
Q

Describe the six steps involved in fibrous repair

A
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21
Q

Which cells are involved in fibrous repair and what do they do?

A
  • Inflammatory cells:

I. Phagocytosis of debris (neutrophils, macrophages)

II. Production of chemical mediators (lymphocytes, macrophages)

  • Endothelial cells: proliferation results in angiogenesis
  • Fibroblasts and myofibroblasts:

I. Produce extracellular matrix proteins

II. Wound contraction (myofibroblasts)

22
Q

Identify some diseases that occur due to defects in collagen synthesis

A
  • Scurvy
  • Ehler-Danlos syndrome
  • Osteogenesis imperfecta
  • Alport syndrome
23
Q

What is Ehlers-Danlos syndrome?

A
  • Ehlers-Danlos syndrome is a heterogeneous group of 11 inherited disorders due to the defective conversion of procollagen to tropocollagen
  • Collagen fibres lack adequate tensile strength, hence the skin is hyperextensible, fragile and susceptible to injury and joints are hypermobile
24
Q

What are the associated risks of Ehlers-Danlos syndrome?

A
  • Poor wound healing
  • Predisposition to joint dislocation
  • Rupture of colon, large arteries or cornea
  • Retinal detachment
25
Q

What is osteogenesis imperfecta?

A
  • Osteogenesis imperfecta (aka brittle bone disease) is a disease where patients have too little bone tissue and hence extreme skeletal fragility
  • They present with blue sclerae (translucent – little collagen), hearing impairment and dental abnormalities
26
Q

What is Alport syndrome?

A
  • Alport syndrome is an X-linked disease wherein Type IV collagen is abnormal resulting in dysfunction of the glomerular basement membrane, the cochlea of the ear and the lens of the eye
  • Patients, usually male, present with neural deafness, eye disorders and haematuria which progresses to chronic renal failure
27
Q

The control of regeneration and repair is a poorly understood and complex process wherein cells communicate with each other to produce a proliferative response.

How does cell communication occur?

A

Cell to cell signalling can be via:

  • Hormones
  • Local mediators (e.g. growth factors)
  • Direct cell-cell or cell-stroma contact
28
Q

What are growth factors?

A
  • Growth factors are polypeptides that act on specific cell surface receptors, coded for by proto-oncogenes
  • They can be considered as ‘local hormones’ as they act only over a short distance or even on the secreting cell itself
29
Q

Growth factors are particularly important in wound healing.

What do they do?

A

Growth factors bind to specific receptors, stimulate transcription of genes that regulate entry of cell into the cell cycle and the cell’s passage through it

30
Q

Apart from cell proliferation, what other effects can growth factors have?

A
  • Locomotion
  • Contractility
  • Differentiation
  • Activation
  • Angiogenesis
31
Q

Provide four examples of growth factors

A

Produced by cells such as platelets, macrophages, endothelial cells:

  • Epidermal growth factor
  • Vascular endothelial growth factor
  • Platelet-derived growth factor
  • Tumour necrosis factor
32
Q

What is contact inhibition?

A

Contact inhibition is signalling through adhesion molecules:

  • Cadherins bind cells to each other
  • Integrins bind cells to the extracellular matrix
33
Q

What does contact inhibition do?

A
  • Inhibits proliferation in intact tissue
  • Promotes proliferation in damaged tissues
34
Q

Where is contact inhibition altered?

A

Contact inhibition is altered in malignant cells

35
Q

What is meant by healing by primary intention and healing by secondary intention?

A

These are descriptions of wound healing related to the size of the wound and the amount of lost tissue

36
Q

When does healing by primary intention occur?

A

Occurs in incised, closed, non-infected and sutured wounds:

  • Disruption of epithelial basement membrane continuity
  • Death of a limited number of epithelial and connective tissue cells
  • Minimal clot and granulation tissue
37
Q

What occurs in healing by primary intention?

A
  • Epidermis regenerates (basal epidermal cells deposit basement membrane, fuse in midline beneath scab, undermine scab which falls off)
  • Dermis undergoes fibrous repair
  • Sutures out at about 10 days (approx. 10% normal strength)
  • Minimal contraction & scarring (good strength)
38
Q

When does healing by secondary intention occur?

A
  • Excisional wound, wounds with tissue loss and separated edges, infected wounds e.g. infarct, ulcer, abscess
  • Open wound filled by abundant granulation tissue
39
Q

Healing by secondary intention involves the same processes as healing by primary intention but more so.

What occurs in healing by secondary intention?

A
  • Considerable wound contraction occurs to close wound (myofibroblasts appear after 1 week)
  • Substantial scar formation, new epidermis often thinner than usual
  • Takes longer than healing by primary intention
40
Q

Which factors affect wound healing?

A
  • Local factors
  • Systemic factors
41
Q

Which five local factors affect wound healing?

A
  • Foreign bodies
  • Local infection
  • Mechanical stress
  • Blood supply
  • Type, size, location of wound

Mnemonic: FISST

42
Q

Which eight systemic factors influence wound healing?

A
  • Malnutrition
  • Age
  • Diabetes
  • Drugs
  • Obestity
  • Genetic disorders
  • Anaemia, hypoxia and hypovolaemia
  • Vitamin deficiency

Mnemonic: MAD DOG AV

43
Q

Describe the six complications of fibrous repair

A
  • Formation of fibrous adhesions compromising organ function / blocking tubes e.g. pleural adhesions

- Loss of function due to replacement of specialised functional parenchymal cells by non-functioning collagenous scar tissue e.g. myocardial scar

- Overproduction of fibrous scar tissue e.g. keloid scar (common in Afro-Carribeans)

- Excessive scar contraction causing obstruction of tubes can impair blood circulation if severe e.g. intestinal obstruction after surgery

- Insufficient fibrosis e.g. wound dehiscence, hernia, ulceration (obesity)

  • Disruption of complex tissue relationships within an organ e.g. liver cirrhosis
44
Q

Describe the special aspects of healing and repair in the following tissue structures:

  • Cardiac muscle
  • Liver
  • Peripheral nerve
  • Cartilage
  • Central nervous system
A
  • Cardiac muscle – myocardial infarction is followed by scar formation
  • Liver – removal or liver results in regeneration by compensatory growth of liver tissue through hypertrophy of remaining hepatocytes
  • Peripheral nerve – proximal stumps of degenerated axons sprout and elongate using Schwann cells (approx 1-3mm/day)
  • Cartilage – limited as lacks blood supply, lymphatic drainage or innervation
  • Central nervous system – damaged neural tissue is replaced by proliferation of CNS supportive elements (glial cells)
45
Q

What is scurvy?

A
  • Scurvy is a disease which results from a deficiency of vitamin C which is required for hydroxylation of procollagen
  • Defective collagen production presents with impaired wound healing and bone formation, fragile capillaries, resulting in abnormal bleeding
46
Q

Why do old scars break down and open up as fresh wounds in scurvy?

A
  • Collagen turnover in scars remains high long after the healing process appears clinically complete
  • Normal collagen is replaced by defective collagen and consequently old scars open up
47
Q

What are pressure sores?

A
  • Pressure sores are ulcerated areas of skin caused by continuous pressure from the weight of the body on that area resulting in skin ischaemia
  • Skin compression leads to damage of the underlying tissues and blood vessels, commonly occurring over bony prominences e.g. heels, sacrum, elbows, hips
48
Q

Which patients are most at risk of pressure sores?

A
  • Elderly
  • Immobile
  • Paralysis or altered sensation
  • Rheumatoid arthritis
  • Diabetes mellitus (affects sensation)
49
Q

How can pressure sores be prevented?

A
  • Changing the patient’s position as much as possible
  • Pillows, fleece under the heels, special mattresses and beds
  • Treat the patient’s general condition
50
Q

How can presure sores be treated?

A
  • Pain relief
  • Dressings
  • Antibiotics (if any signs of infection)
  • Surgery

I. Debridement – remove dead/damaged skin

II. Plastic surgery – close a pressure ulcer that doesn’t heal