PP 4 Regeneration + Repair Flashcards
What happens after acute inflammation?
Complete resolution
Repair with connective tissue
Chronic inflammation meaning
Prolonged inflammation with associated repair
Process of wound healing
1- injury
2- haemostasis
3- inflammation
4- regeneration + repair
Haemostasis meaning
Stop blood flow out due to formation of blood clot
Regeneration meaning
Regrowth of cell
Minimal evidence of injury
What is regeneration only possible with?
- Minor injuries e.g. superficial skin incision/abrasion
- Connective tissue architecture must be intact
Types of stem cells
Totipotent
Multipotent
Unipotent
Totipotent meaning
Examples
Produce all cell types
e.g. Embryonic SC
Multi potent meaning
Example
Produce several cell types in one category
e.g. Haematopoietic SC
Unipotent meaning
Example
Produce one cell type
e.g. Epithelial SC
Stem cell locations
- Epidermis - basal layer
- Intestinal mucosa - bottom of crypts
- Liver - between hepatocytes
Which tissue types can regenerate?
Labile tissue
Stable tissue
What tissue cant regenerate?
Permanent tissue
Describe labile tissue
Examples
- Continuous replication of cells
- Continuously cycling cell cycle
e.g. epithelium, haematopoetic tissue
Describe stable tissue
Examples
- Normally low levels of replication
- Can undergo rapid replication if needed
- Have left cell cycle - in G0, but can re-enter
e.g. kidneys, liver, pancreas, bone, smooth muscle
Describe permanent tissue
Examples
- Cells do not replicate
- Heal by repair
- Left cell cycle, cannot reenter
e.g. neurones, skeletal + cardiac msucle
Repair meaning
Replacement of functioning tissue with a scar
Process of scar formation
1- bleeding + haemostasis - prevents blood loss
2- inflammation - digestion of blood clot
3- proliferation - ^ capillaries, fibroblasts, myofibroblasts
4- remodelling - maturation of scar
Describe proliferation in scar formation
- days to weeks
- Angiogenesis
- Increased fibroblast and myofibroblasts > granulation tissue
Function of granulation tissue
Fills the gap
Contracts and closes the hole
Capillaries supply oxygen, nutrients + cells
Angiogenesis meaning
Development of new blood vessels
Function of angiogenesis in scar formation
New capillaries provide O2 + nutrients
Contract and close the gap
Describe remodelling in scar formation
- Decreased cell population
- Increased collagen from fibroblast
- Myofibroblasts contract
- Fibrous scar is formed
Cells involved in fibrous repair
Neutrophils
Macrophages
Lymphocyte
Endothelial cell
Fibroblast
Myofibroblasts
What do fibroblasts and myofibroblasts look like?
Spindle shaped nucleus
Cytoplasmic extensions
Fibroblast function
Secret collagen and elastin
Forms the extracellular matrix
What do myofibroblasts have that fibroblasts don’t?
What function does this give them?
Myofibroblasts contain actin
Wound contraction
Examples of where type 1 collagen is found
Bones
Tendons
Ligaments
Skin
Vessels
Sclera
Examples of where type 4 collagen is found
Basement membrane
Lens
Glomerular filtration
Outline the synthesis of collagen
1- preprocollagen undergoes vit C dependent hydroxylation of proline + lysine
2- precollagen formed - 3 PPC cross linked to form triple helix
3- C and N terminals of PC cleaved
4- tropocollagen formed
5- TP cross link formation
6- microfibrils, fibrils + collagen fibres made
Examples of diseases of defective collagen
ACQURIED
- Scurvy
INHERITED
- Osteogenesis imperfecta
- Alport syndrome
- Ehlers-Danilo’s syndrome
Describe scurvy
- vit C deficiency
- inadequate hydroxylation of PPC > defective triple helix > defective collagen
- unable to heal wounds
- tooth loss
- tendency to bleed
Cause of scurvy
Vit C deficiency
Scurvy symptoms
Tooth loss
Insufficient wound healing
Tendency to bleed
Red gums
Inherited diseased of defective collagen examples and symptoms
Osteogenesis imperfecta
Alpert syndrome
Ehlers-Danlos syndrome
Hyper flexibility
Stretchy/fragile skin
Blue sclera (OI)
Weak bones
Poor wound healing
Ways of cell communication
Direct cell-cell contact
Local mediators - growth factors
Hormones
Explain cell to cell contact
- Isolated cells replicate until they encounter other cells
- Cadherins bind between cells
- further proliferation inhibited
What method of communication do growth factors use?
Autocrine
Paracine
Autocrine meaning
Messengers acts on the cell itself
Paracrine meaning
Communication in a short distance to adjacent cells
What do growth factors cause?
The cell to leave G0 + enter cell cycle + proliferate
Growth factor examples
Epidermal GF
Vascular endothelial GF
Platelet derived GF
Tumor necrosis factor
What do epidermal GF induce?
mitosis in epithelial cells, hepatocytes and fibroblasts
What do vascular endothelial GF induce?
Angiogenesis in tumours
Chronic inflammation
Wound healing
What do platelet derived GF cause?
Migration + proliferation of fibroblasts, smooth muscle + monocytes
What does tumour necrosis factor cause?
Migration + proliferation of fibroblasts
Collagenase secretion
Fracture healing process
1- haematoma formation
2- soft callus formation
3- hard callus formation
4- remodelling
Haematoma meaning
Solid swelling of blood
When do soft calluses form in fracture healing?
After 1 week
What forms woven bone?
Fibrous tissue and cartilage
Describe soft callus formation
After 1 week
Fibrosis tissue + cartilage laid down > woven bone
Woven bones lacks tensile strength
When do hard calluses form in fracture healing?
After several weeks
Describe hard callus formation
After several weeks
Woven bone gradually organised into lamellar bone (hard, strength, structure)
When does remodelling occur in fracture healing?
Month to years
Describe remodelling in fracture healing
Months to years
Lamellar bone remodelled to original outline of bone
Local factors influencing would healing
Size
Location
Blood supply
Denervatin
Protection
Mechanical stress
Necrotic tissue
Local infection
Foreign bodies
Systemic factors influencing wound healing
Age
Anaemia, hypoxia, hypovolaemia- poor O2
Diabetes
Drugs
Vitamin deficiencies
Malnutrition
How does diabetes influence wound healing?
Blood supply to damaged areas affected
Decreased infection resistance
Complications in fibrous repair
Loss of function
Excessive fibrosis
Adhesions
Disruption of architecture
Excessive scar contraction
Explain loss of function complications in fibrous repair
Specialised tissues replaced by fibrous tissue
What does excessive fibrosis form?
Who is at higher risk of this?
Keloid scar
Afro-Caribbean population
What can adhesions in fibrosis repair causes?
Obstruction of tubes due to fibrous bands from inappropriate fibrosis
What can excessive scar contraction cause?
Constriction of tubes
Fixed flexion deformities
Types of skin healing
Primary intention
Secondary intention
When does primary intention occcur?
Small, non infected apposed edged injury
What happens to the epidermis and dermis in primary intention?
Epidermis regenerate
Dermis undergoes fibrous repair > scar
Primary intention process
1- haemostasis
2- inflammation
3- migration of cells
4- regeneration
5- early scarring
6- scar maturation
Describe haemostasis in primary intention
Seconds to minutes
Arteries contract > space fills with blood
Scab forms > bacterial entry prevention
Describe inflammation in primary intention
Minutes to hours
Neutrophils appear at edges
Describe migration of cells in primary intention
Up to 48 hours
- Macrophages phagocytose dead neutrophils +
secrete cytokines e.g. fibroblast, endothelial
cells
Describe regeneration in primary intention
3 days
- Macrophages replace neutrophils
- Granulation tissue invades space
- Epithelial call proliferation > epidermis thickens > scab falls off
- angiogenesis continues
Describe early scarring in primary intention
7-10 days
Fibroblasts deposit collagen fibres > scar
Describe scar maturation in primary intention
1 month - 2 years
Capillaries disappear over time > white scar left
When does secondary intention occur?
Significant tissue loss
Infected, unopposed edged injury
What is needed in secondary intention but not in primary?
Large injury
Myofibroblast contraction needed
What happens to the epidermis and dermis in secondary intention?
Epidermis regenerates from edge
Dermis undergoes significant repair
Cardiac muscle healing
- Permanent cells
- Very limited regenerative capacity
- Myocardial infarction > scar formation >
compromises cardiac function
Liver healing
Stable cells
Can regenerate well if needed
Hepatocytes regenerate first then non-parenchyma cells
Peripheral nerve healing
- Axons degenerate in damage
- Axon regrowth occurs at 1-3mm/day
- Schwann cells guide axons back to nerve
innervation
How fast does axon regrowth occur?
1-3mm/day
Cartilage healing
Doesn’t heal well
Lacks blood supply, innervation + lymphatic drainage
Why does cartilage not heal well?
Lacs blood supply, innervation + lymphatic drainage
CNS healing
Neural tissue is permanent
When damaged, CNS supportive elements (glial cells) replace them
What replaced damaged neural tissue?
Glial cells
What is would dehiscence?
When an unstable wound splits open
What is proud fresh?
When granulation tissue grows out and protrudes from wound
Treatment of proud flesh
Surgical removal by scraping or cutting
Common complication from wound healing
Infection
Four types of ulcers
Venous
Arterial
Diabetic
Pressure
What causes diabetic ulcers?
Diabetic peripheral neuropathy
What causes arterial ulcers?
Peripheral vascular disease
What causes pressure ulcers?
Pressure on bony prominence
What causes venous ulcers?
Stasis dermatitis
Common locations for pressure ulcers
Elbows
Sacrum
Heels
Why are headed wounds hairless?
Hair follicles don’t regenerate in areas of damaged skin as they are a complex structure
Why don’t hair follicles regenerate after being damaged?
They are a complex structure
Why are headed wounds lighter/whiter?
- melanocytes don’t regenerate
- fibrous scar with less small blood vessels
Why are headed wounds stretched?
Elastic fibres don’t regenerate in areas of damaged skin
This meaning scars stretch as they mature
Why are scars stretch as they mature?
Elastic fibres don’t regenerate in areas of damaged skin
What are abdominal adhesions?
Bands of fibrous tissue that form between abdominal tissues + organs
What is Alpert syndrome?
Condition with abnormal type IV collagen
What is abnormal is Alport syndrome and what does this result in?
Type IV collagen
Dysfunction of the glomerular basement membrane, cochlea of ear + lens of eye
Presentation of Alport syndrome?
Haematuria as children
Neural deafness
Eye disorders:
- Keratoconus - thinning of cornea
- Lenticonus - protrusion of lens capsule
- Cataracts
How do skeletal muscle fibres undergo repair after damage?
Contain satellite cells that retain their mitotic ability + act as muscle stem cells
How do corticosteroids inhibit wound healing?
Immunosuppressive
Inhibit collagen synthesis
What is Ehlers-Danlos syndrome?
- Inherited disorder due to defective conversion of procollagen to troprocollagen due to no lysyl oxidase
- Collagen fibres lack adequate tensile strength»_space; skin is hyperextensible ‘stretchy skin’ + susceptible to injury + joints are hypermobile
What are the associated risks of Ehlers-Danlos syndrome?
Poor wound healing
Predisposition to joint dislocation
Rupture of colon, large arteries + cornea
Retrial detachment
What is osteogenesis imperfecta?
Presentations
Brittle bone disease
Patients have too little bone tissue > extreme skeletal fragility
Blue sclera - little collagen
Hearing impairment
Dental abnormalities
What type of drugs inhibit wound healing?
Corticosteroid - immunosuppressive + inhibit collagen synthesis
How long do each of the processes last in scar formation?
- bleeding + haemostasis: second to minutes
- inflammation: minutes to days
- proliferation: days to weeks
- remodelling: weeks to years
