Regeneration And Repair Flashcards
What is regeneration?
Regrowth of cells (with minimal evidence of injury)
When is regeneration possible?
Minor skin injuries (superficial skin incision/abrasion)
Physiological (blood cells in bone marrow)
Where do new cells come from?
Stem cells - replace dead and damaged cells
Types of stem cell
Totipotent - produce any cell (embryonic)
Multipotent - produce several types of cell (haemopoetic)
Unipotent - can produce one cell type (epithelial)
Example of stem cell locations
Epidermis - basal layer
Intestinal mucosa - bottom of crypts
Liver - between hepatocytes
Tissue regeration types
Labile
Stable
Permanent
Labile tissue
Continuous replication - always in cell cycle
Epithelium, haemopoetic tissue
Stable tissue
Low level of replication but can undergo rapid if injured - G0 of cell cycle (left but can re enter)
Liver, kidneys, pancreas, bone
Permanent tissue
No replication - left cell cycle and cannot re enter
Neurones, skeletal muscle, cardiac muscle
What does regeration require?
Intact conncective tissue architecture (to build upon)
What is fibrous repair?
Replacement of functioning tissue with a scar
When does a scar form eg fibrous repair?
Necrosis of permanent tissues
Collagen framework has been destroyed
On going chronic inflammation
4 stages of fibrous repair (scar formation)
Bleeding and haemostasis
Inflammation
Proliferation
Remodelling
BIPR
Bleeding and haemostasis stage
Prevents blood loss
Clot formed
Seconds - minutes
Inflammation stage
Acute then chronic
Digestion of blood clot and necrotic tissue (macrophage)
Minutes - days
Proliferation stage
Angiogenesis
Fibroblasts, myofibroblasts and extracellular matrix proliferates
Granulation tissue formed
Days - weeks
What is granulation tissue?
Fills gap - prevents pathogen entry
Capillaries can suplly oxygen and nutrients (angiogenesis)
Contracts (myofibroblasts) and closes wound
How can granulation tissue appear?
Pale yellow and shiny
Lots of ECM and branching immature blood vessels (eliptical) on H&E
Remodelling phase
Maturation of scar
Reduced cell population, increased collagen, myofibroblasts contract
Fibrous scar forms
Weeks - years
Cells involved in fibrous repair
Neutrophil & macrophage - phagocytosis, release inflammatory mediators
Lymphocyte - eliminate pathogens, co ordinate other cells
Endothelial cell - proliferation and angiogenesis
Fibroblast - secrete collagen and elastin (form ECM)
Myofibroblast - fibroblast+smooth muscle = wound contraction
How do fibroblasts and myofibroblasts appear on H&E?
Spindle shaped (elongated) nucleus
Star shape cytoplasmic projections (cant usually see)
Collagen stages names
Pre-pro collagen
Procollagen
Tropocollagen
Step 1 collagen synthesis
In ER of (myo)fibroblasts
Polypeptide alpha chain (pre pro collagen) Gets hydroxylated (Vit C dependent)
Forms procollagen
Step 2 collagen synthesis
Into cytosol
Alpha chains cross link to form triple helix
Stage 3 of collagen synthesis
Pro collagen leaves cell—> extracellular
C and N terminals cleaved off
Forms tropocollagen
Stage 4 collagen synthesis
Tropocollagen cross linked
Microfibrils —> fibrils —> fibres
Collagen synthesis overall
ER: Preprocollagen Hydroxylation Procollagen Triple helix
Extracellular: C and N terminals cleaved off Tropocollagen formed Tropocollagen cross linked Forms fibrils —> fibres
Diseases of defective collagen
Scurvy
Inherited:
Ehlers-Danlos
Osteogenesis Imperfecta
Alport syndrome
Scurvy - why?
Vitamin C deficiency
Unable to hydroxylate pre-procollagen
Defective triple helix and defective collagen
Scurvy symptoms/signs
Poor wound healing
Bruising
Bleeding of gums
Tooth loss
Ehlers Danlos syndrome
Collagen fibres lack tensile strength
Poor wound healing
Joint dislocation
Hypermobile joints
Rupture of colon/organs/arteries
Skin Ehlers Danlos
Hyperextensible
Fragile
Suceptible to injury
Osteogenesis imperfecta
Brittle bone disease
Skeletal fragility - little bone tissue
BLUE SCLERA - too little collagen so is not transparent
Hearing impairment
Dental abnormalities
Alport syndrome
X linked - MALE MORE AFFECTED
Type 4 collagen affected
Dysfunction of glomerulus basement membrane, cochlea of ear, lense of eye
Blood in urine, chronic renal failure (deafness, eye disorders)
How is regenration controlled?
Direct cell contact
Local mediators (growth factors)
Hormones
Cell to cell contact
Contact inhibition - isolated cells replicate until they encounter other cells
Cadherins bind and prevent proliferation
Cancer cell to cell contact
Cadherins are defective
Continued proliferation = multilayers
Growth factors
Polypeptides that act on cell surface receptors
Cause cell to enter cell cycle —> proliferate
Growth factor examples
Epidermal GF
Vascular Endothelial GF
Platelet derived GF
Tumour necrosis factor
Two types of skin healing
Primary intention
Secondary intention
Primary intention
Apposed edges (near eachother/sutured)
Minimal clot/granulation tissue = small scar
Epidermis regenerates, dermis fibrous repairs
Secondary intention healing
Unapposed edges (infection/ulcer/abcess) Significant tissue loss = lots of contraction needed
Abundant clot, inflammation, granulation tissue
Dermis - repair
Epidermis regenerates from edges
Fracture healing stages
Haematoma (granulation)
Soft callus (fibrous/cartilage) woven bone
Hard callus (woven bone to lamellar bone)
Remodelling (original outline)
How long for soft and hard callous formation?
1 week soft
Several weeks hard
How long for a fracture to be completely remodelled?
Months/years
Local factors influencing wound healing
Size Location Blood supply Infection Foreign bodies
Systemic factors influencing wound healing
Age Anaemia/hypoxia/hypovolaemia (less O2) Obesity Diabetes (neuropathy/vessel damage) Drugs Vitamin deficiency (Vit C) Malnutrition
Complications of fibrous repair
Insufficient fibrosis - dehiscence (opening)
Excessive fibrosis - keloid scar
Adhesions - fibrous bands (can obstruct tubes)
Loss of function/architecture
Excessive contraction - constriction of tubes Fixed flexion (contractures)
When does insufficient fibrosis often occur?
Obese
Elderly
Malnutrition
Steroid use
