Regeneration And Repair (Session 4) Flashcards
What 3 processes are involved in wound healing?
- Haemostasis (formation of a blood clot)
- Inflammation
- Regeneration and/or repair
What is regeneration?
Regrowth of cells (with minimal evidence of injury)
What injuries is regeneration only possible?
- Minor injuries (superficial skin incision/abrasion)
- If the injury is more extensive than that, tissue has to heal by REPAIR
Is regeneration only done in response to injury?
Explain
- No
- It can also be physiological, e.g. production of new blood cells in bone marrow and new skin cells
Where do new cells come from?
Stem cells
What are stem cells? (4)
- undifferentiated cells
- can differentiate into other fully mature cell types
- can self-renew
- replace dead/damaged cells
What are the 3 main types of stem cell?
What do they do?
Give examples of each
- Totipotent
- produce all cell types
- eg. embryonic stem cells
(T for total) - Multipotent
- produce several cell types, but not all
- eg. haematopoietic stem cells
- Unipotent
- produce 1 cell type
- eg. epithelial stem cells
Give 3 examples of where in the tissues stem cells are found
- Stem cells in the epidermis - found in basal layer (unipotent)
- Stem cells in intestinal mucosa - bottom of crypts
- Stem cells in the liver - between hepatocytes
Tissue regeration types
Labile
Stable
Permanent
Labile tissue:
What it does in terms of regeneration + examples
- continuous replication of cells
- eg. epithelium, haematopoietic tissue
Stable tissue
What it does in terms of regeneration + examples
- normally low level of replication but can undergo rapid replication if required, if that tissue becomes injured or damaged
- eg. liver, kidneys, pancreas, bone, endothelium, smooth muscle
Permanent tissue
What it does in terms of regeneration + examples
Cells do not replicate - left cell cycle and cannot re enter - if damage occurs, they can only heal by repair
Neurones, skeletal muscle, cardiac muscle
Which stage of the cell cycle is each tissue type involved in?
labile - continuous cycling (G1,S,G2,M, back to G1)always in cell cycle
stable - left cell cycle, can re-enter if stimulated (G0)
permanent - left cycle, cannot re-enter
What is required for tissues to regennerate?
An Intact connective tissue/collagen architecture (to build upon)
What happens if there is significant damage to the connective tissue architecture of cells that usually regenerate?
- Regeneration cannot occur
- Instead, healing has to take place in a process called repair
What is fibrous repair?
Replacement of functioning tissue with a scar
In what cases does fibrous repair occur? (scar formation)
Necrosis of permanent tissues : Fibrous repair is the only option
Necrosis of labile or stable tissues:
- Collagen framework has been destroyed
- On going chronic inflammation
Then fibrous repair will occur
What does necrosis of permanent tissue lead to after an injury?
Fibrous repair (i.e. a scar)
What does necrosis of labile or stable tissue lead to after an injury?
- collagen framework intact = regeneration
- collagen framework destroyed = fibrous repair (ie. a scar)
- on-going chronic inflammation = fibrous repair (ie. a scar)
4 stages of fibrous repair (scar formation)
1) Bleeding and haemostasis
2) Inflammation
3) Proliferation
4) Remodelling
BIPR
Bleeding and haemostasis stage of scar formation (3)
- Formation of blood clot
- Prevention of blood loss
- Takes Seconds to minutes
Inflammation stage stage of scar formation (3)
- Acute then chronic
- Digestion of blood clot and necrotic tissue by macrophages and neutrophils
- Takes minutes to days
Proliferation stage stage of scar formation (4)
- proliferation of capillaries (angiogenesis)
- proliferation of fibroblasts and myofibroblasts which lay down extracellular matrix (containing collagen and elastin for tissue architecture)
- The proliferation of all of these results in tho production of granulation tissue
- takes days to weeks
What are the functions of granulation tissue? (3)
- Fills gap - to try and prevent pathogen entry
- Capillaries can supply oxygen and nutrients to the injured area (angiogenesis)
- Contracts and closes wound
What is this an image of?
Label 3 structures that are present
Granullation tissue under microscope with H and E Staining
1) Blood vessels:
- The empty spaces with RBC’s in them
- Lined by endothelial cells
- Abnormal shape (no tubular structure), instead branch in unusual ways (elliptical shape) as they are newly developing, formed because of angiogenesis
2) Chronic inflammatory cells (macrophages, lymphocytes, neutrophils, eosinophils, left over from inflammatory phase of scar formation)
3) Extracellular matrix - pink material (collagen and elastin being laid down as part of scar formation
T/F The vascularity of granulation tissue increases over time
F - The vascularity of granulation tissue decreases over time
How can granulation tissue appear?
Pale yellow and shiny
Remodelling phase (6)
Maturation of scar:
- Reduced cell population (ie apoptosis of inflammatory cells)
- Increased collagen deposition
- Myofibroblasts contract, bringing edges of wound closer together
- Fibrous scar forms
- Takes weeks to years
Which cells involved in fibrous repair, and what do they do? (6)
Neutrophils & macrophages:
- Phagocytosis
- Release inflammatory mediators that control and coordinate the inflammatory response
Lymphocytes:
- eliminate pathogens
- Co ordinate other cells involved in inflammatory processes
Endothelial cell:
- proliferation
- Angiogenesis
Fibroblast - secrete collagen and elastin which forms ECM
Myofibroblast :
- Express intracellular actin
- Wound contraction to make scar smaller and smaller
Name the following cells
How do fibroblasts and myofibroblasts appear on H&E? (4)
Spindle shaped (elongated) nucleus
Star shape cytoplasmic extentions (cant usually see)
- They are similar in appearance
- A myofibroblast is between a fibroblast and a smooth muscle cell
Where is collagen type 1 found? (7)
- Bone
- Skin
- Tendon
- Ligaments
- Sclera
- Cornea
- Vessels etc.
Where is type 4 collagen found? (3)
- Basement membrane
- Lens
- Glomerular filtration etc.
What are thee different names of collagen at different stage
Pre-pro collagen
Procollagen
Tropocollagen