Session 4 - Regeneration and Repair Flashcards
Recap:
- What happens after acute inflammation?
- Define chronic inflammation
- What is fibrosis?
After acute inflammation?
- Complete resolution
- Repair with connective tissue (fibrosis) - if there has been substantial tissue destruction
Chronic inflammation: Prolonged inflammation with associated repair
Fibrosis - deposition of collagen
What processes are invovled in wound healing?
- *Regeneration
- **Define
- Type of injuries it is associated with
- Is regeneration also pathological?
Injury -> Haemostasis -> Inflammation -> Either Regeneration or Repair
- *Regeneration** = Regrowth of cells (minimal evidence of injury - goes back to the way it was before)
- Injuries associated: Minor injuries e.g. superficial skin incision/abrasion
- Regeneration can also be physiological e.g. production of blood cells in bone marrow
Regeneration: Stem cells (this is where the new cells come from)
- What are stem cells, what do they replace?
- Types of stem cells
- Where are stem cells?
- What are the different tissue types? Which can regenerate?
- Stem cells are cells that can differentiate into other cell types AND self-renew. They replace dead/damaged cells.
- Types of stem cells:
=Totipotent (produce all cell types e.g. embryonic stem cells)
= Multipotent (produce several cell types e.g. haematopoietic stem cells)
= Unipotent (produce one cell type e.g. epithelial stem cells) - Where are stem cells: Epidermis (basal layer), Intestinal mucosa (bottoms of crypts), liver (between hepatocytes)
- Which tissue types can regenerate:
= Labile tissue: Continuous replication of cells, if damaged can regenerate e.g. epithelium, haematopoietic tissue
= Stable tissue: Normally low level of regeneration, but can undergo rapid replication if required e.g. liver, kidney, pancreas, bone, endothelium, smooth muscle
= Permanent tissue: Cells do not replicate e.g. neurones, skeletal muscle, cardiac muscle, can only heal by REPAIR
= Permanent tissue
Which tissue types can regenerate?
Fibrous repair/repair define
How to know if it is regeneration or repair?
Which type of injury leads to which type of healing?
Regeneration of cells and tissues… requires an intact connective tissue architecture
- Structure of tissue needs to be maintained
- If significant damage to connective tissue architecture, healing has to take place through REPAIR
Fibrous repair = The replacement of functioning tissue with a SCAR
Which type of injury leads to which type of healing? See pic below
How does a scar form? 4 steps and explain them
4 steps in scar formation:
- Bleeding and haemostasis: Preventation of blood loss, seconds - minutes
- Inflammation: Acute then chronic inflammation, digestion of blood clot (neutrophils remove toxins and debris microbes, nicrotic tissue that has died due to injury) - minutes to days
- Proliferation of: capillaries (angiogenesis), fibroblasts, myofibroblasts, extracellular matrix -> results in granulation tissue - days to week
- Remodelling: Maturation of scar - Reduced cell population, increased collagen deposition, myofibroblasts contract -> Fibrous scar - weeks to years
Granulation tissue - what is granulation tissue? What is it’s function?
Granulation tissue:
- Granulation tissue is vascularized tissue that forms as chronic inflammation evolves. The new capillaries make the tissue appear pink and granular, thus the name. Histologically, one can observe macrophages and proliferating fibroblasts within granulation tissue.
- Functions: fills the gap, capillaries supply oxygen and nutrients, contacts and closes the defect
Cells Involved in Fibrous Repair
- Neutrophil
- Macrophage
- Lymphocyte
- Endothelial cell
- Fibroblast
- Myofibroblast
Collagen
- Collagen synthesis
Collagen synthesis: CHADPOGRL
Intracellular -
- Cleavage of signal peptides from Preprocollagen
- Hydroxylation of proline and lysine (DEPENDANT ON VITAMIN C)
- Addition of N linked oligosaccharides and galactose in endoplasmic reticulum
- Disulphide bridge formation
- Procollagen is transported to Golgi
- O-linked glycosylation in Golgi
- Golgi - exocytosis as procollagen
Extracellular -
- Removal of N/C terminal peptides using procollagen peptidase to form tropocollagen
- Lateral aggregation to form fibrils
Tropocollagen crosslinked - Mulitple tropocollagen’s crosslinked to form microfibril, microfibrils cross linked to form fibril, fibrils are bound together to form collagen fibre.
Diseases of Defective collagen
Defective collagen:
Acquired - Scurvy
– Vitamin C deficiency
Inadequate hydroxylation of pre-pro collagen, defective triple helix = defective collagen.
—- Unable to heal wounds, tendency to bleed, tooth loss
Inherited - Ehlers-Danlos Syndrome, Osteogenesis Imperfecta, Alport Syndrome
How are Regeneration and Repair Controlled?
1. Direct cell-cell/cell-stroma contact
Contact inhibition - isolated cells replicate until they encounter other cells, cadherins bind between cells, inhibit further proliferation
– When cadherins in different cells come in contact with one another, they send a signal into the cells, telling them to stop dividing.
– Cadherin’s are defective in cancer, if cadherins are defective, they won’t be able to tell cells to stop dividing
2. Growth factors
Sometimes cells can enter cell cycle in the absence of stimulation by growth factors -> can lead to cancer
Healing of Skin
- Primary intention
- Secondary intention
Primary intention:
Incised wound, apposed edges (sutured) ->
minimal clot and minimal granulation tissue ->
Epidermis regenerates and dermis undergoes fibrous repair
—- small scar
Secondary intention:
Significant tissue loss, unapposed edges (infection/ulcer/abscess) ->
Results in abundant clot, lots of inflammation and lots of granulation tissue
-> Considerable wound contraction required (myofibroblasts) ->
Dermis requires significant repair, Epidermis regenerates (but can’t always) from edges
—- Significant scar formation, takes a long time to heal, may get reinfected
Fracture healing (4 steps)
- Haematoma surrounds the injury - granulation tissue forms
- Soft callus (1 week) - Fibrous tissue and cartilage, woven bone
- Hard callus (several weeks) - Woven bone gradually organised into lamellar bone
- Remodelling (months-years) - Lamellar bone remodelled to original outline of bone
Factors influencing wound healing - local
Factors influencing wound healing - systemic
Local: Size of wound, location, blood supply, local infection, foreign bodies
Systemic: Age, anaemia, hypoxia, hypovolaemia, obesity, diabetes, drugs, vitamin deficiencies, malnutrition
Complications of fibrous repair
Insufficient fibrosis (wound dehiscence, leads to opening up of previous wounds) occurs in - obesity, elderly, malnutrition, steroid use
Excessive fibrosis - Keloid scar
Adhesions - Fibrous bands, can cause obstruction of tubes
Loss of function - Replicament of specialised tissue by fibrous tissue
Disruption of architecture
Excessive scar contraction (constricgtion of tubes) - fixed flexion deformities (contractures)
