Regeneration and Repair Flashcards
Give somewhere that unipotent stem cells can be found
Crypts of Lieberkuhns
Give somewhere that multipotent stem cells can be found
Haemopoietic tissue
Give somewhere that totipotent stem cells can be found
Embryo
Describe the difference between labile, stable and permanent stem cells with examples.
Labile - constant division, rapid proliferation e.g. epithelia, haematopoietic cells
Stable - normally in Go, at rest. Is able to enter the cell cycle, varied rate of regeneration depending on location. e.g. hepatocytes, osteoblasts, fibroblasts
Permanent - unable to divide, permanently in Go. Tissue cannot regenerate. e.g. neurons, cardiac myocytes.
Describe the role of growth factors in control of regeneration.
Promote proliferation, extracellular signals are transduced into the cell. Changes to transcription control the cell cycle.
Can be proteins - EGF, PGDF, FGF
Hormones - oestrogen, testosterone, growth hormone
Can be produced by many cell types e.g. inflammatory/mesenchymal
Describe contact inhibition
Signalling occurs through adhesion molecules, anti-proliferation signals. When lost, proliferation increases until they become re-attached.
Describe two situations in which fibrous repair and scarring is required.
Necrosis of permanent cells
Destruction of collagen framework by necrosis of labile/stable cells.
Describe the different cell types involved in fibrous repair.
Inflammatory cells - neutrophils/macrophages for phagocytosis. Lymphocytes/macrophages produced chemical mediators.
Endothelial cells - angiogenesis
Fibroblasts/myofibroblasts - ECM protein secretion/wound contraction
Describe angiogenesis.
Stimulated by VEGF.
Pre-existing vessels sprout new vessels, endothelial proteolysis of the basement membrane. Migration of endothelial cells by chemotaxis. Proliferate and form primitive blood vessels. They mature and remodel, linking back to the venous system. Supported by periendothelial cells.
Why is angiogenesis essential in regeneration and repair?
Delivers oxygen, nutrients, inflammatory cells and fibroblasts.
Describe the function of the ECM
Supports and anchors cells Separates tissue compartments Sequesters growth facts Communication between cells Facilitates cell migration
Describe the synthesis of fibrillar collagen.
Synthesised in the endoplasmic reticulum, chain modified by enzymes. Vitamin C-dependent hydroxylation is important.
Alpha chains align and form a triple helix: soluble pro-collagen. This is secreted then cleaved to tropocollagen which aggregates to form collagen.
What is the function of matrix glycoproteins?
Organise and orientate cells
Support cell migration.
e.g. fibronectin, laminin
What is the function of proteoglycans?
Matrix organisation
Cell support
Regulate availability of growth factors
e.g. hepatin sulphate proteoglycan
What is the function of elastin?
Provides tissue elasticity
Describe the mechanism of fibrous repair
Damage causes a blood clot, leading to acute inflammation with neutrophils.
Then chronic inflammation occurs, macrophages and lymphocytes migrate into the clot and digest it.
The clot becomes granulation tissue and angiogenesis begins, myofibroblasts and fibroblasts recruited.
The proportion of contents changes over time: vascularity and cells decrease, ECM proteins increase. Myofibroblasts contract to draw the edges of the wound together and blood vessels mature.
Describe the control of fibrous repair
Inflammatory cells are recruited by chemotaxis
Angiogenic cytokines (e.g. VEGF and bFGF) produced by platelets, ECM and others in response to hypoxia.
Macrophages produced by pro-fibrotic cytokines (e.g. TNF-alpha, IL-1, TGF-beta) causing fibroblast proliferation and ECM production.
Describe a wound that heals via primary intention
Incised wound with minimal tissue damage, wound edges can be drawn together. Minimal haemorrhage.
Describe a wound that heals via secondary intention
Large defect so the edges can’t be opposed. Large blood clot.
Describe the process of repair in primary intention.
Loss of contact inhibition in the epidermis, fibrous repair in the dermis. Granulation tissue eventually creates scar tissue.
Minimal contraction and scarring, good tensile strength.
Describe the process of repair in secondary intention.
Loss of contact inhibition, regenerate from the base upwards in the epidermis. Large amount of granulation tissue produces a large scar in the dermis, not necessarily weaker. Greater risk of complication.
Describe healing in bone fractures
Haematoma forms in the marrow cavity and periosteum. Granulation tissue forms with the ingress of osteoblasts and necrotic tissue is removed by phagocytes.
Soft callus of chondrocytes forms
Hard callus of women bone with a few disorganised islands of cartilage.
Lamellar bone then replaces this, and remodelling by mechanical stresses occur.
Give some local factors that influence healing.
Type, size and location
Apposition, lack of movement
Infection - suppuration, gangrene, systemic
Foreign material
Radiation damage - stops angiogenesis and affects myoblast/fibroblast recruitment
Give some general factors that influence healing.
Age
Drugs (steroids)
Hormones
General dietary deficiency (protein)
Specific dietary deficiency (vitamin C/essential amino acids)
General health (chronic disease e.g. diabetes/rheumatoid arthritis)
General cardiovascular status
Describe complications due to insufficient fibrosis
Wound dehiscence, herniation, ulceration
Seen in obese, elderly, steroids and malnutrition.
Inadequate strength with scarring.
Describe complication due to excessive fibrosis
Coal worker’s pneumoconiosis - accumulation of coal dust in the lungs, fibrosis occurs to isolate the coal.
Cosmetic scarring
Keloids - high risk in afro-caribbeans
Liver cirrhosis - turns the liver into nodules of differentiated hepatocytes with dense fibrous tissue separating them. Decreased function.
Stricture - obstruction of tubes and channels caused by chronic inflammation and fibrous repair. Can also cause contractures which limits joint movement.
Describe healing in cardiac muscle
Limited regenerative capacity and myocardial infarction followed by scar formation. This can compromise cardiac function.
Describe healing in the liver
Has the capacity to regenerate.
If part of the liver is removed, compensatory growth of liver tissue and restoration of mass by enlargement of the lobes that remain.
Almost all hepatocytes replicate during regeneration. This is followed by replication of non-parenchymal cells.
Describe healing in peripheral nerves
When a nerve is severed the axons degenerate by Wallerian degeneration.
Proximal stumps sprout and elongate. Use Schwann cells vacated by distal degenerated axons to guide them back to the tissue that the nerve innervates.
Grow at 1-3mm/day
Describe healing in cartilage
Can’t heal well due to a lack of blood supply, lymphatic drainage and innervation.
Describe healing in the central nervous system
Neural tissue is permanent and when tissue damage occurs this is replaced by glial cells.
