MoD Healing and Repair Flashcards
Define regeneration
The replacement of dead or damaged cells by functional differentiated cells.
Whats the difference between regeneration and repair?
In regeneration the normal structure is restored whereas in repair the normal structure is permanently altered - e.g. fibrosis.
Give examples of labile, stable and permanent cell populations, and what are the differences between each?
They vary on their ability to regenerate.
Labile - continuously dividing, normal state is active cell division e.g. epithelial and haematopoietic cells
Stable - they are usually in the resting state (G0) and only regenerate when stimulated (slow) e.g. hepatocytes, osteoblasts, fibroblasts
Permanent - permanently in the G0 state with no ability to divide or regenerate e.g. neurones, cardiac myocytes
What is the role of stem cells?
They are the the internal repair system to replace lost or damaged cells.
What are the 3 types of stem cell?
Unipotent: can only produce one type of differentiated cell e.g. epithelia
Multipotent: can produce several types of differentiated cells e.g. haematopoietic
Totipotent: can produce any type of cell e.g. embryonic stem cells
What controls regeneration and repair?
Growth factors (can be hormones such as oestrogen, GH or proteins e.g. VEGF, PDGF) They promote proliferation of the stem cells and promote expression of genes controlling the cell cycle.
Adhesion molecules that signal between basement membranes and adjacent cells. “Contact inhibition” occurs when tissue is intact however loss of contact promotes proliferation (can lead to cancer).
What is the difference between fibrous repair and regeneration/resolution?
Fibrous repair occurs in necrosis of permanent cell populations and necrosis of labile and stable cell populations where the collagen framework has been destroyed. Fibrous repair results in scarring.
Outline the 3 key steps in fibrous repair
- Cell migration
- Angiogenesis (new blood vessel formation)
- EC matrix production and remodelling
In cell migration (step 1 of fibrous repair), what cell types are involved and what is their function?
Inflammatory cells
Neutrophils and macrophages phagocytose debris
Lymphocytes and macrophages act as chemical mediators by attracting other cells
Endothelial cells
Needed for angiogenesis
Fibroblasts and myofibroblasts
Make EC matrix proteins, wound contraction
Outline the function and process of angiogenesis in fibrous repair
A blood supply is vital to wound healing - it provides access to the wounds for cells eg inflammatory cells and fibroblasts, and delivers O2 and nutrients.
Angiogenesis is initiated by VEGF and other growth factors
Preexisting BV sprout new vessels
Outline the function and process of extracellular matrix production in fibrous repair
Function - supports and anchors cells, secretes and stores growth factors, allows communication between cells
Made up of glycoproteins, proteoglycans, and elastin
What are the different types of collagen? (broad)
Fibrillar collagens (I-III) eg dermis, bone Uninterrupted helices form fibrils
Amorphous collagens (IV-VI) eg Interrupted so form sheets
Outline the synthesis of fibrillar collagens
Alpha chains synthesised in ER
Vit C dependent hydroxylation
Alpha chains cross link to produce procollagen triple helix
Soluble procollagen secreted
Procollagen cleaves to give tropocollagen
Tropocollagen forms fibrils then fibres
There can be slow remodelling by specific collagenases
Describe what can happen if there is a defect in collagen synthesis
Vit C deficiency: inadequate hydroxylation produces defective helices (weak). Particularly affects collagens supporting blood vessels so can result in haemorrhage. Skeletal changes in infants
Ehlers-Danlos syndrome: defective conversion from procollagen to tropocollagen. Results in hypermobile joints and skin stretch
Osteogenesis imperfecta: brittle bones
What is healing by primary intention?
Occurs when there is a clean, smooth incision with apposed edges. There is minimal clotting and granulation tissue. The scar is minimal and has good strength
Possible complication: sutures can trap infection inside causing an abscess
What is healing by secondary intention?
Occurs when there is a skin wound such as infarct, ulcer, or abscess (all have extensive loss of cells). The wound edges are unapposed, a large clot forms a stab and the repair process forms a lot more granulation tissues.
Takes longer to heal and there is a larger scar.
Outline the healing of bone fractures
Haematoma forms Necrotic tissue removed Capillaries develop Soft callus forms Hard callus forms Bone remodelling in the direction of mechanical stress
What factors affect healing and repair?
Local factors: Type, size and location of wound Apposition and lack of movement Blood supply INFECTION (most important) Foreign material
General factors:
Age
Drugs e.g. steroids inhibit collagen formation
Dietary deficiencies
General state of health e.g. diabetes, RA
General cardiovascular status
What are some complications of fibrous repair?
Insufficient fribrosis - the wound can herniate and ulcerate (esp abdomen)
Excessive fibrosis - cosmetic issues, keloids, cirrhosis
Excessive wound contraction - can obstruct tubes and channels (strictures), can limit joint movement (contractures)
What happens during healing of the myocardium?
Regeneration capacity is almost none, resulting in scar formation which may compromise cardiac function.
What is special about liver regeneration?
The liver has a remarkable capacity to regenerate. Part of the liver can be removed and there is compensatory growth of liver tissues. Almost all hepatocytes replicate during regeneration.
What occurs in peripheral nerve regeneration?
There is wallerian degeneration of the axons of a severed nerve. The axons then regenerate at a rate of 1-3mm per day. Schwann cells guide the growing axons to the tissue they innervate.
What is the regenerative capacity of cartilage?
Very little - lacks blood supply, lymphatic drainage and innervation.
What happens when there is damage to the central nervous system?
Neural tissue is permanent therefore the neural tissue is replaced by glial cells.
