Healing and Repair Flashcards
Define regeneration
Restitution with no, or minimal, evidence that there was previous injury
Healing by primary intention
Superficial abrasion
What type of tissue can regeneration take place
Labile or stable
What is abrasion and ulceration
Abrasion - lose top few layers of cells
Ulceration is severe form of abrasion - injury into submucosa
What are labile tissues
Contain short live cells that are replaced from cells derived from stem cells
Constantly regenerating
Eg. Surface epithelia, haematopoietic tissue
What are stable tissues
Normally low level of replication but if necessary can undergo rapid proliferation
Both stem cells and mature cells proliferate
Eg. Liver parenchyma, bone fibrous tissue, endothelium
What are permanent tissues
Mature cells can’t undergo mitosis and no or only a few stem cells present
Eg. Neural tissue, skeletal muscle, cardiac muscle
Where are cells involved in regeneration derived from
Stem cells
What does asymmetric replication of stem cells mean
One stays as stem cells while other becomes a mature cell in differentiation
How do stem cells differentiate
Stem cells become transit amplifier progenitor and then different cells
Most are TA progenitor - involved in proliferation and give rise to differentiated cells
Stem cells need to be protected from mutation, so occasionally are in cell cycle
Describe the three types of stem cells
Unipotent - only give rise to one type of differentiated cell
Most adult stem cells
Eg. Epithelia
Multipotent - produce several types of differentiated cell
Eg. haematopoietic stem cells in bone marrow produce blood cells
Totipotent - can produce any type of cell and therefore any tissue in the body
Embryonic stem cells
What is fibrous repair and when does it occur
Healing with formation of fibrous connective tissue - scarring
Healing by secondary intention
Specialised tissue is lost
Occurs when collagen framework is damaged, on-going chronic inflammation or necrosis of permanent tissue
What is granulation tissue and its functions
Consists of developing capillaries, fibroblasts and myofibroblasts, chronic inflammatory cells
Functions - fills the gap, capillaries supply oxygen nutrients and cells, contracts and closes the hole
Explain the process of fibrous repair
- Haemostasis - blood clots
- Acute inflammation - neutrophils infiltrate and digest clot
- Chronic inflammation - macrophages and lymphocytes are recruited
- Granulation tissue forms - vessels sprout, fibroblasts and myofibroblasts make glycoproteins
- Early scar - vascular network, collagen synthesised, macrophages reduced
- Scar maturation - cells much reduced, collagen matures, contracts and remodels
What is the difference between regeneration and fibrous repair
Regeneration replaces dead cells with the same type of cells
Fibrous repair replaces dead cells with scar tissues and causes loss of function
Distinguish between primary and secondary healing intention
Primary intention occurs when the tissue surfaces have been closed
eg. surgical excision
Secondary intention occurs when there is significant tissue loss and the edges cannot be brought together
Lasts longer, more scarring, more susceptible to infection
What cells are involved in fibrous repair
Inflammatory cells
Phagocytosis debris - neutrophils + macrophages
Production of chemical mediators - lymphocytes, macrophages
Endothelial cells
Proliferation results in angiogenesis (formation of new blood vessels)
Fibroblasts and myofibroblasts
Produce extracellular matrix proteins - collagen
Responsible for wound contraction - contraction of fibrils within myofibroblasts
What are scars white and stretch
Scars become white as no regeneration of melanocytes
Scars may stretch as fibroblasts cannot lay down elastin
Epidermis cannot regenerate complex structures such as hair follicles and sweat glands
Describe collagen
Provides extracellular framework for all multicellluar organisms
Responsible for holding body together, including skeleton
Composed of triple helices of polypeptide alpha chains
Type I most common, found in hard and soft tissue
Type IV makes up basement membranes - secreted by epithelial cells
How is collagen made
- Polypeptide alpha chains (preprocollagen) synthesised in ER of fibroblasts and myofibroblasts
- Enzymatic modification steps including vitamin C dependent hydroxylation
- Alpha chains align and cross link to form procollagen triple helix
- Soluble procollagen is secreted
- Procollagen ends cleaved to give tropocollagen
- Tropocollagen polymerises to form microfibrils and then fibrils
- Bundles of fibrils form fibres
- Cross-linking between molecules produces tensile strength
- Slow remodelling by specific collagenases
Explain the role of growth factors
Local mediators important in would healing
Coded by proto-oncogene
Bind to specific receptors, stimulate transcription of genes that regulate entry of cell into cell cycle and the cell’s passage through it
Cyclin dependent kinase activated by cyclin and phosphorylates pRb to enter cell cycle
Restriction point on cell cycle - when beyond restriction point, cell no longer depends on growth factors
Produced by cells such as platelets, macrophages, endothelial cells
Growth factors include epidermal growth factor, vascular endothelial growth factor, platelet derived growth factor and tumour necrosis factor
Growth factors also involved in inhibition of division, locomotion, contractility, differentiation, viability, activation, angiogenesis
Explain contact inhibition
Signalling through adhesion molecules - cadherins bind cells to each other, integrins bind cells to the ECM
Inhibits proliferation in intact tissue, promotes proliferation in damaged tissue
Cells will grow and differentiate until it is touching another cell
Malignant cells do not stop growing and overlap over each other
Describe primary intention healing
Incised, closed, non-infected and sutured (stitched) wounds
Disruption of basement membrane continuity but death of only small number of epithelial and connective tissue cells
Epidermis regenerates until they join, then grow up to push scab off
Dermis undergoes fibrous repair
Minimal contraction and scarring of wounds
Eg. Surgical excision
Explain secondary intention healing
Excisional wound, wounds with tissue loss, inflected wounds
Eg. Infarct, ulcer, abscess
Open wound filed by abundant granulation tissue - grows in from wound margins
Considerable wound contraction to close wound
Substantial scar formation, new epidermis often thinner than usual
Takes longer than healing by primary intention
Contracture - scar over joint that will contract and cause deformity - physiotherapy needed
Explain the process of bone healing
- Haematoma - fills gap and surrounds injury
- Granulation tissue forms - cytokines activate osteoprogenitor cells
- Soft callus - at 1 week, fibrous tissue and cartilage within which woven bond forms
- Hard callus - after several weeks, initially woven bone - weaker and less organised than lamellar bone but can form quickly
- Lamellar bone - replaces woven bone, remodelled to direction of mechanical stress
Bone not stressed is resorbed and outlines is re-established
