L7 - regeneration and repair Flashcards
Define regeneration
Regeneration is the growth of cells and tissues to restore a tissue to it’s pre-injury state (more ideal)
What tissues can undergo regeneration
Superficial damage to skin and mucosal membranes/ liver
What cells have almost zero degenerative capacity and when they heal they replace with scar tissue causing loss of function?
cardiac muscle/cartilage/neural tissue
What cells are responsible for regeneration?
Stem cells - they differentiate to become the lost cells
Judging by what tissues can completely regenerate, where are three locations of stem cells?
Epidermis of skin/intestinal mucosa (bottom of crypts)/liver (between hepatocytes and bile ducts)
Define the following and give examples of each
a) labile tissue
b) stable tissue
c) permanent tissue
labile - contains short lived cells which are regularly replaced by stem cells - surface epithelial/haempoeitic tissues
stable - normally a low level of replication but can undergo rapid proliferation by both stem and mature cells if necessary - liver, bone, endothelium
permanent - mature cells cannot divide and only a few stem cells are present -
Neural tissue, skeletal muscle, cardiac muscle
Which categories of tissues can undergo regeneration?
Labile and stable as long as the tissue damage is not too extensive
What is the alternative to regeneration?
Fibrous repair (is this resolution?) -> scar formation
Describe the three major stages of scar formation (I have a diagram for this)
1) clot and inflammatory cell infiltrate - Haemostasis-> blood clot forms -? -> acute inflammation (exudate) -> chronic inflammation
2) Clot replaced by granulation tissue - (consists of developing capillaries, fibroblast, myofibroblasts and chronic inflammatory cells) so angiogenesis
3) Maturation - Myofibroblasts contract, vessels mature, cell population falls, collagen remodels -> scar formation
What is the function of granulation tissue?
Fills the gap in the wound, angiogenesis supplies oxygen and cells to the area
So then what cells are involved in fibrous repair judging from the stages of scar formation?
neutrophils, macrophages, lymphocytes, fibroblasts, myofibroblasts, endothelial cells (proliferation results in angiogenesis)
Briefly describe the structure of collagen
a triple helix of alpha chains
Fibrillar collagens (I-III) are responsible for tissue strength whilst amorphous collagens (IV-VI) are responsible for the ____ ____
Basement membrane
Give an example of a tissue that type I collagen is found in
bones/tendons/ligaments/skin/blood vessels
Give two disorders of collagen and explain their pathophysiology
Scurvy - Vitamin C deificiency -> vitamin C is required for effective crosslinking in collagen formation -> weak collagen
Ehlers-danlos syndrome - defective conversion of procollagen to tropocollagen
Osteogenesis imperfecta - collagen deficiency (Col1A mutation)
Alport syndrome - abnormal type IV collagen -> defective basement membranes
Give symptoms of scurvy, ehlers danlos syndrome, osteogenesis imperfecta and Alport syndrome
Scurvy - poor wound healing/tooth loss/scars open as fresh wounds
Ehlers-danlos syndrome - hyperextensible skin and poor wound healing
osteogenesis imperfecta - blue sclera, recurrent bone fractures
Alport syndrome - renal failure (X-linked thus patients usually male)
What is healing by primary intention?
Think - state of wound, number of cell died and amount of granulation tissue
incised, closed, non-infected wounds/ Small number of epithelial cells die/minimal granulation tissue and clot
What is healing by secondary intention?
excised, open, infected wounds/ lots of cell death/ abundant granulation tissue
Healing by secondary intention leaves a bigger scar and takes longer T/F?
T
Give the five stages of fracture healing
1) haematoma formation and clot
2) granulation tissue forms (inflammatory cells)
3) Soft callus formation (cartilage)
4) hard callus formation (woven bone)
5) Replacement by lamellar bone and remodelling
Give two local factors which can influence wound healing
Size of wound/location of wound/blood supply/infection/foreign bodies
What is formed if there is overproduction of fibrous scar tissue?
Keloid scar/obstructions due to big scars e.g. oesophageal stricture
Give some complications of fibrous repair
Formation of adhesions which compromise organ function /loss of tissue function/keloid scar formation/excessive scar contraction causing obstruction of tubes (e.g. oesophageal stricture)
Why does cartilage not have a good ability to regenerate?
Poor blood supply, lymphatic drainage and innvervation
Skeletal muscle can regenerate a bit by a limited number of satellite cells but it can compensate by what?
Hypertrophy (This is the principle of body building)
Explain how peripheral nerves heal
Distal to the site of damage the neuron degenerates (Wallerian degeneration). The proximal stumps of the degenerated axons sprout and elongate, they use the schwann cells of the distal degenerated axons to guide them back to where they need to go
Bone has a good regenerative capacity, T/F?
T
Give some systemic factors which affect wound healing
Age/anaemia/obesity/diabetes/malignancy/steroid/vitamin deficiency/malnutrition
What is a traumatic neuroma?
A disorganised proliferation of axons in nerve healing due to misalignment of the nerve endings. Can be see as a palpable painful nodule
How does a hypertrophic scar differ from a keloid scar?
Keloid scars grow beyond the boundaries of the wound
What population are at most risk of keloid scars?
Afro-carribean