Healing: Regeneration and repair Flashcards
Would healing involves which three processes?
Haemostasis
Inflammation
Regeneration(resolution) and repair
What is regeneration (or resolution)?
What does it require in order to take place?
The growth of cells and tissues to replace lost structures
Requires an intact connective tissue scaffold
It is essential for restoration of full functionality and “normal” appearance to the injured tissue
Tissues of the body are divided into what three groups what does this mean in each case?
Give examples of each
Labile- continuously dividing, proliferate throughout life to replace lost tissue e.g. surface epithelia
Stable- quiescent, normally low level of replication but can undergo rapid division in response to stimuli e.g.parenchymal cells of the liver, kidneys, WBCs
Permanent- non-dividing cells have left the cell cycle and can no longer undergo mitotic divisions
Define what is meant by the term “stem cell”
Cells that have a prolonged proliferative activity which show asymmetric replication(one daughter cell remains as a SC and the other differentiates into a mature, non-dividing cell
Embryonic stem cells are described as ____potent
Totipotent
Adult stem cells are described as ____potent or ____potent
Unipotent or Multipotent
For what three reasons might fibrous repair take place?
Destruction of collagen framework
On-going chronic inflammation
Necrosis of specialised parenchymal cells that cannot be replaced
!!Fibrovascular tissue grows there instead
Fibrous repair involves which 5 processes?
“FLAPS”
- Phagocytosis of necrotic tissue debris
- Proliferation of endothelial cells, angiogenesis
- Fibroblast and myofibroblast formation, synthesise collagen - Granulation tissue @ this stage!!!!!
- Granulation tissue becomes less vascular matures into fibrous scar
- Scar shrinks and matures (myofibrils contract)
Which is the most common type of collagen in the body?
Where is it present?
Type I collagen
Bones, tendons, ligaments, skin, blood vessels
Describe the structure of type I collagen
Triple helix of 3 polypeptide alpha chains
Repeating “gly-x-y”
How is collagen formed within the cell?
Preprocollagen produced in cell
Modified to Procollagen
Cleaved into Collagen fibrils
Cross-linked to produce tensile strength of collagen
Name 4 diseases that are caused by defects in collagen synthesis
Elhers- Danlos Syndrome (EDS) - collagen fibres lack tensile strength
Scurvy- vitamin C deficiency, no hydroxylation of procollagen
Osteogenesis Imperfecta - “brittle bone disease”- too little bone tissue, blue sclera
Alport syndrome - usually X-linked, defective type IV collagen, glomerular BM dysfunction
What factors control regeneration and repair?
Cell communicators an hormones- Autocrine, paracrine, endocrine Local mediators (GFs) Hormones Cell-cell contact Stroma-cell contact
Name 4 types of growth factor
EGF- epithelial cells, hepatocytes
VEGF- blood vessel development
PDGF- migration and proliferation of fibroblasts
TNF -fibroblast migration
Explain what is meant by contact inhibition?
Normal cells when they become isolated from other cels around them will replicate until they have cells touching them and then they will stop
What is “healing by primary intention” ?
Healing of incisional, closed, non-infected and sutured wounds (clean with opposed edges)
In wounds that heal by primary intention, there is __________ of the basement membrane continuity, but death of _________ of epithelial and ________________ cells
disruption
a limited number
connective tissue
Explain the process of healing by primary intention in 6 steps with the time frame for each
(Pen and paper probably needed)
Second to minutes: Haemostasis - severed arteries contract, narrow space fills with clotted blood, dehydration of surface clot, scab forms
Minutes to hours: Inflammation- neutrophils appear at the margins of the incision without bacteria stimulus. In sterile wounds number of leukocytes not enough to be “pus”
Up to 48 hours: Migration of cells- macrophages start to appear and begin to scavenge dead neutrophils. Secrete cytokines that attract fibroblasts and endothelial cells- capillaries start to appear. Deposition of BM by basal epidermal cells
3 days: Regeneration- macrophages replace neutrophils, granulation tissue invades space. Epithelial cells proliferate, fibroblasts produce collagen, angiogenesis progresses
7-10 days: Early scarring- wound filled with granulation tissue. Fibroblasts proliferate and deposit collagen fibres form a fibrous mass. Epidermis normalises and keratinises, but normal appendages e.g. hair and sweat glands don’t form. Regression of vascular channels
1 month-2 years: Scar maturation- scar is a mass of fibrous tissue with few cells and few vessels. Turns from pink to white as vessels disappear and has little elastic fibres- why they tend to stretch
What is “granulation tissue” ?
New tissue formed during wound healing containing fibroblasts- which lay down collagen, myofibroblasts and blood vessels
How would you describe healing by “secondary intention”?
When would you see this type of wound healing?
The wound is filled with granulation tissue which grows from the wound margins, a larger clot, more necrotic debris and more intense inflammatory reaction than in a wound healing by primary intention
In wounds with tissue loss, separated edges and infection
A considerable about of ______________ must take place in order to close the defect in healing by secondary intention
wound contraction
The epidermis of a scar formed in healing by secondary intention is often what, compared with that of wounds healed by primary intention?
Thinner
Explain the processes involved in healing of bone fractures
- Haematoma
- Fibrin mesh and granulation tissue, fibroblasts and inflammatory cells release cytokines- activation of osteoclasts and osteoblasts
- Soft callus forms (1 week)- made up of fibrous tissue and cartilage, forms bulge around fracture site
- Hard callus forms (several weeks)- Laid down by osteoblasts, initially woven bone
- Lamellar bone formation-more organised and stronger
- Remodelling of bone in response to mechanical stress
Name local factors that influence healing and repair
Size, location, type of wound Blood supply Denervation Local infection Foreign bodies Haematoma Necrotic tissue Mechanical stress Protection and surgical techniques
