Regeneration & Repair Flashcards
How does the ability to regenerate vary between types of cell?
LABILE CELLS: actively divide (G1 -> M -> G1) and rapidly proliferate
e.g. epithelia, haemopoietic cells
STABLE/QUIESCENT CELLS: stay in resting stage (G0) until prompted to enter growth cycle (variable regeneration speed)
e.g. hepatocytes, osteoblasts, fibroblasts
PERMANENT CELLS: unable to divide (G0) and unable to regenerate
e.g. neurones, cardiac myocytes
note: mitotic figures are the hallmark of cell proliferation
Define regeneration.
Replacement of dead or damaged cells by functional, differentiated cells.
note: stem cells can either differentiate or remain undifferentiated in order to maintain the stem cell pool
What factors affect cell regeneration?
Growth factors = promote proliferation of stem cells by promoting expression of genes that control the cell cycle
e.g. oestrogen, testosterone, growth hormone
Contact inhibition = cells in contact inhibit proliferation (adhesion molecules, e.g. E-cadherin), and loss of contact promotes proliferation
note: deranged in cancer
Define and describe fibrous repair.
FIBROUS REPAIR = replacement of functional tissue by scar tissue
Necrosis of labile or stable cells which destroys the collagen framework will cause fibrous repair and scarring
Angiogenesis (provides access to wound for inflammatory cells & fibroblasts + provides O2 & nutrients), cell migration, extracellular matrix production and remodelling
Cells involved: neutrophils & macrophages, lymphocytes, endothelial cells, fibroblasts & myofibroblasts
Describe the sequence of events in angiogenesis.
- Endothelial proteolysis of basement membrane
- Migration of endothelial cells via chemotaxis
- Endothelial proliferation
- Endothelial maturation
- Recruitment of periendothelial cells
note: VEGF = vascular endothelial growth factor (proangiogenic)
Describe the sequence of events of fibrous repair.
- Inflammatory cell infiltrate: blood clot forms, acute inflammation around edges, lymphocytes and macrophages migrate into clot
- Clot replaced by granulation tissue: angiogenesis (capillaries and lymphatics sprout and infiltrate), myo/fibroblasts migrate and differentiate and produce extracellular matrix, and collagen synthesised
- Maturation: cell population falls, collagen increases, matures and remodels, myofibroblasts contract, vessels differentiate and are reduced, and fibrous scar produced
How is fibrous repair controlled?
Inflammation: inflammatory cells recruited by chemotaxis
Angiogenesis: platelets and extracellular matrix produce angiogenic cytokines in response to hypoxia e.g. VEGF
Fibrosis: macrophages produce pro-fibrotic cytokines e.g. IL-1, TNF-alpha, & fibroblasts proliferate and produce the extracellular matrix
What is the difference between skin regeneration by primary or secondary intention?
Primary intention: incised wound (surgical)
Apposed edges close easily, minimal clot and granulation tissue
Epidermis regenerates & dermis undergoes fibrous repair
Transition from granulation tissue to scar tissue, minimal contraction & scarring
note: risk of trapping infection -> abscess
Secondary intention: any large wound with unapposed edges e.g. infarct, ulcer, abscess
Epidermis regenerates from base up
Much more granulation tissue produced, and eschar (scab) formed
More contraction required to reduce volume of defect
What are some local and systemic factors affecting wound healing?
LOCAL:
- type, size, location of wound
- apposition, lack of movement
- blood supply (arterial/venous)
- infection: gangrene (suppuration = formation of pus)
- foreign material e.g. dirt, glass, sutures, necrotic tissue
- radiation damage
SYSTEMIC:
- age
- drugs: hormones & steroids
- dietary deficiencies: general (protein), vit. C, essential amino acids
- general health (chronic diseases) e.g. diabetes (increased risk of infection & impaired fibrosis), rheumatoid arthritis
- infection
Describe how hepatocytes can regenerate, and how this may go wrong.
Hepatocyte loss: recovery possible
Damaged architecture -> fibrous scarring with regenerative nodules
- cirrhosis
Partial resection may allow regeneration
Describe how kidney cells can be regenerated, and how this may go wrong.
Epithelium can be regenerated but architecture cannot.
Acute tubular necrosis: ischaemic episode/exposure to toxins
- > loss of tubular epithelium -> inflammation
- > destruction of glomerulus/scarring -> loss of filtration
- > intestinal fibrosis -> impaired reabsorption
Describe how muscle cells can regenerate, and how this may go wrong.
Skeletal muscle: limited capacity for regeneration by satellite cells
Cardiac muscle: if only the contractile proteins are lost it is possible to synthesise new cells within the old endomysium; otherwise regeneration is not possible
Smooth muscle: can regenerate
Describe how nerves regenerate, and how this may go wrong.
CNS: no effective regeneration of neurones, but glial cells proliferate in response to injury by gliosis
PNS: proximal few axons degenerate and subsequent distal axons degenerate + secondary myelin fragmentation if present (Wallerian degeneration)
- > proliferation of Schwann cells
- good apposition: axons regrow along original channels
- poor apposition: cut ends proliferate in a disordered manner (amputation neuroma)
note: axonotmesis = Wallerian degradation where the axons and myelin sheath are intact, but the Schwann cells and the epi/peri/endoneurium are not
Describe how bone can regenerate, and how this may go wrong.
Replaced/resorbed by action of osteoblasts/osteoclasts originating from progenitor cells of periosteum
Describe how cartilage can regenerate, and how this may go wrong.
CARTILAGE CANNOT REGENERATE!!!
