4. Healing And Repair Flashcards by Amy Brown

What 3 processes are involved in wound healing?

Haemostasis
Inflammation
Regeneration/resolution and repair of destroyed structures

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What is regeneration?

The growth of cells and tissues to replace lost structures with minimal evidence of previous injury.

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What type of injury can easily heal by regeneration?

Abrasions - superficial and only damage cells from epidermis and dermis

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What must be intact for regeneration to take place?

Stem cells remain undamaged

Connective tissue scaffold

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Which cells replicate to regenerate lost structures, why only these?

Stem cells

Terminally differentiated cells can no longer divide

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What type of replication do stem cells demonstrate?

Assymetric - when they divide, one cell stays as a stem cell and the other differentiates

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Where can stem cells be found in skin?

Epidermis - basal layer adjacent to the basement membrane

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Where can stem cells be found in the GI tract?

Bottom of the gastric crypts

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What are the 3 different types of stem cells?

Unipotent
Multipotent
Totipotent

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What are unipotent stem cells?

Can only differentiated into one type of cell. E.g epithelia
Most stem cells are unipotent

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What is an example of a multipotent stem call?

Haematopoietic stem cells - can produce several types of differentiated cell

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What is an example of a totipotent stem cell?

Embryonic stem cells - can produce any type of cell

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Most adult stem cells are ___potent.

Unipotent

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What are labile tissues?

Continuously dividing tissues - in the cell cycle

Short-lived cells

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What are examples of labile tissues?

Surface epithelia
Haematopoietic tissues
Cells of bone marrow
Columnar epithelia of GI tract

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What are stable tissues?

Tissues that normally have low level of replication but can undergo rapid proliferation in response to stimuli.

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Give examples of stable tissue.

Liver parenchymal cells, bone, endothelium of blood vessels.

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What are permanent tissues?

Cells that are non-dividing. Cannot undergo mitosis as have no/few stem cells.

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Give examples of permanent tissues.

Skeletal muscle
Cardiac muscle
Neural tissue

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What stage of the cell cycle are labile, stable and permanent tissues in?

Labile - continuously cycling
Stable - G0, resting but can re-enter
Permanent - left the cell cycle, cannot re-enter

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In what circumstances can regeneration take place?

If a labile or stable tissue

If not extensive - connective tissue scaffold remains

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How will damage to permanent tissues heal?

Fibrous repair and scarring

What is fibrous repair?

Healing with formation of fibrous connective tissue - scar

Healing by secondary intention

When does fibrous repair occur?

Significant tissue loss - secondary intention
Permanent tissue injured
Ongoing chronic inflammation

What processes are involved in fibrous repair?

1. Phagocytosis of necrotic tissue debris 2. Proliferation of endothelial cells which results in angiogenesis 3. Proliferation of fibroblasts and myofibrolasts - collagen synthesis and wound contraction 4. Scar matures and shrinks due to contraction

What cells are involved in fibrous repair?

Inflammatory cells - phagocytes - engulf debris Endothelial cells - angiogenesis Fibroblasts and myofibroblasts - collagen, wound contraction

Why are new scars red?

Lots of blood vessels still present

How do old scars differ to new scars?

White - melanocytes do not regenerate Hairless - hair cells and sweat glands not regenerated Stretch - fibroblasts lay down collagen but not elastin

What are symptoms of scurvy?

Unable to heal wounds - tendency to bleed Tooth loss Old scars break down and open as fresh wounds

What are symptoms of Ehlers-Danlos syndrome?

Hyperextensible, fragile skin Joints hypermobile and prone to dislocation Would healing poor

What are signs of osteogenesis imperfecta?

Skeletal fragility Blue sclera - too little collagen Hearing impairment and dental abnormalities

What defect is present in Alport syndrome?

Abnormal Type IV collagen. | Dysfunction of glomerular basement membrane, cochlea of ear and lens of eye

What are the signs of alport syndrome?

Usually male - X linked Present with haematuria and progress to chronic renal failure Neural deafness and eye disorders

Which mediators are most important in controlling growth and repair?

Growth factors

Which genes code for growth factors?

Proto-oncogenes

What is contact inhibition, how does it differ in regeneration and neoplasia?

Isolated cells will replicate until they have cells touching them, when they will stop. Occurs in wound healing but is altered in malignant cells.

What adhesion molecules bind cells to each other?

Cadherins

Which adhesion molecules bind cells to the EC matrix?

Integrins

Which wounds will heal by primary intention?

incisional, closed, non-infected and sutured wounds. | Epidermis regenerates

Outline the process of healing by primary intention.

1. Haemostasis 2. Inflammation 3. Migration of cells 4. Regeneration 5. Early scarring 6. Scar maturation

What type of wounds will heal by secondary intention?

Excisional wounds Wounds with tissue loss and separated edges Infected wounds E.g ulcer, abscess

How does healing by secondary intention differ to process of primary intention?

More granulation tissue Larger clot and more debris creates a larger inflammatory reaction. More wound contraction needed to close space. Increased scar formation New epidermis is thinner Takes longer!

Outline how bone heals after a fracture.

``` Haematoma Granulation tissue Soft callus Hard Callus Lamellar bone ```

What local factors influence wound healing?

1. Type, size and location of wound 2. Blood supply 3. Local infection 4. Foreign bodies 5. Protection

What systemic factors can influence wound healing?

1. Age 2. Anaemia, hypoxia and hypovolamia 3. Obesity - increased tension 4. Diabetes 5. Malignancy 6. Genetic disorders 7. Malnutrition 8. Drugs

Which type of drug will delay wound healing?

Steroids - inhibit collagen synthesis

What are the complications associated with fibrous repair?

Insufficient fibrosis - hernia, ulceration Excessive fibrosis - keloid scar Excessive contraction - obstruction of tubes, joint contractures Loss of function - MI in myocardium

Why doesn't cartilage heal well?

Lacks blood supply, lymphatic drainage or innervation.

How do peripheral nerves heal?

Axon of severed nerve undergoes wallerian degeneration. Use vacated schwann cells to guide them back to the tissue that the nerve innervated. Axon grows approx 1-3mm/day

How does central nervous tissue regenerate?

Permanent tissue, so when tissue damage occurs in CNS the neural tissue is replaced by proliferation of glial cells.

What is a traumatic neuroma?

Benign proliferation of a nerve following damage. Forms a nodule during regeneration, very painful.

Which people are at higher risk of keloid scar formation?

Afro-caribbean

What type of tissue can grow to form 'proud flesh'?

Granulation tissue