Flashcards in Pathology - Regeneration And Repair Deck (43):
What are the key processes involved in wound healing?
- haemostasis, as vessels are open
- inflammation, as there has been tissue injury
- regeneration/repair, as structures have been damaged
What is tissue regeneration?
Restitution with no/minimal evidence that there was a previous injury (healing by primary intention, superficial abrasions)
What is the difference between an abrasion and an ulcer?
An ulcer is an injury which affects the submucosa, while abrasions just affect the mucosa.
What are stem cells?
Cells that have the ability to proliferate - they show prolonged proliferation activity. They exhibit 'asymmetric replication'.
Where are stem cells found in tissues?
- epidermis: basal layer adjacent to the basement membrane
- intestinal mucosa: bottom of crypts
- liver: between hepatocytes and bile ducts
What are unipotent stem cells?
- these are most of the adult stem cells
- only produce one type of differentiated cell
What are multipotent stem cells?
Produce several types of differentiated cell, eg. blood cells are derived from multipotent stem cells in bone marrow
What are totipotent stem cells?
Embryonic stem cells which can produce any type of cell and therefore any tissue of the body
What are labile tissues?
These contain short lived tissues that are replaced quickly from cells derived in stem cells, eg. surface epithelia, haematopoietic tissues. Continually cycling through cell cycle.
What are stable tissues?
Tissues which normally have a low level of replication but if necessary can undergo rapid proliferation, both stem cells and mature cells present, eg. liver parenchyma, bone, fibrous tissues endothelium. In stage G0 of the cell cycle.
What are permanent tissues?
Tissues containing mature cells which can't undergo mitosis, no/few stem cells present, eg. neural tissue, skeletal muscle, cardiac muscle. Not in the cell cycle any more.
In which tissues can tissue regeneration take place?
In labile/stable tissue, if tissue damage is not extensive
What is fibrous repair?
Healing with formation of fibrous connective tissue (scar).
When does fibrous repair occur?
Occurs in cases of significant tissue loss and if permanent/complex tissue is injured
When would regeneration be able to occur rather than fibrous repair?
If necrosis of labile/stable tissues has occurred but the collagen framework is intact.
Outline scar formation from haemostasis to scar maturation
- seconds to minutes: haemostasis
- minutes to hours: acute inflammation
- 1-2 days: chronic inflammation
- 3 days: granulation tissue forms
- 7-10 days: early scar
- weeks-2 years: scar maturation
What does granulation tissue consist of?
- developing capillaries
- fibroblasts and myofibroblasts
- chronic inflammatory cells
What are the functions of granulation tissue?
- fills gap of wound
- capillaries supply oxygen, nutrients and cells
- contracts and closes hole
Outline the stages of fibrous repair
1) blood clots
2) neutrophils infiltrate and digest clot
3) macrophages and lymphocytes are recruited
4) vessels sprout, myo/fibroblasts make glycoproteins
5) vascular network forms, collagen synthesised, macrophages reduced
6) cells much reduced, collagen matures, contracts and remodels
Which cells are involved in fibrous repair?
- inflammatory cells (phagocytosis of debris and production of chemical mediators)
- endothelial cells (proliferation results in angiogenesis)
- fibroblasts and myofibroblasts (produce extracellular matrix proteins and wound contraction)
Why are old scars often white?
Melanocytes often do not regenerate after damage
Where is type I collagen found?
Bones, tendons, ligaments, skin, sclera, cornea, blood vessels, hollow organs
Where is type IV collagen found?
Makes up basement membranes (secreted by epithelial cells)
Give some diseases that are the result of defective collagen synthesis?
- scurvy (acquired)
- Ehlers-Danlos syndrome (inherited)
- osteogenesis imperfecta (inherited)
- Alport syndrome (inherited)
How does scurvy cause issues with collagen?
Inadequate vitamin C dependent hydroxylation of procollagen alpha chains leads to reduced cross-linking and defective helix formation
Give some symptoms of scurvy
- unable to heal wounds and tendency to bleed
- tooth loss (collagen in periodontal ligament has short half life, so normal collagen is replaced by defective collagen)
- old scars break down and open up as fresh wounds (collagen turnover remains high after healing process appears clinically complete)
Give some symptoms of Ehlers-Danlos syndrome
- wound healing poor
- skin is hyperextensible, thin, fragile and susceptible to injury
- joints are hypermobile and predisposed to dislocation
- in some forms, prone to rupture of colon, large arteries or cornea and retinal detachment
Why does people with osteogenesis imperfecta have blue sclera?
Too little collagen within them meaning they are translucent. They also have hearing impairment and dental abnormalities
Why are patients with Alport syndrome usually male?
It is an X-linked disease
What is Alport syndrome?
Abnormal type IV collagen leading to dysfunction of glomerular basement membrane, cochlea of ear and lens of eye. Causes neural deafness and eye disorders, and presents with haematuria progressing to renal failure
Give some methods by which cells signal each other
- local mediators
- direct cell-cell or cell-stroma contact
What are growth factors?
Polypeptides which act on cell surface receptors. They are coded by proto-oncogenes and bind to specific receptors, stimulating transcription of genes which regulate entry of cell into cell cycle and its passage through it
Give some functions of growth factors
Cell proliferation, locomotion, contractility, differentiation, viability, activation, angiogenesis
What is contact inhibition?
This is when cells touch each other and then stop dividing due to signalling through adhesion molecules. It inhibits proliferation in intact tissue, and promotes it in damaged tissues. This is altered in malignant cells
What is healing by "primary intention"?
Incised, closed, non-infected and sutured wounds (so basically a sharp, clean cut) heal with minimal clot and granulation tissue. There is disruption of basement membrane continuity but death of only a small number of epithelial and connective tissue cells.
How does the epidermis regenerate when healing by primary intention?
Basal epidermal cells at edge of cut creep over denuded cells (approx. 0.5 mm/day), deposit basement membrane, fuse in midline beneath scab and undermine scab which falls off
What is healing by "secondary intention"?
This occurs when an excisional wound/wound with tissue loss and separated edges/infected wound heals by filling with abundant granulation tissue which grows in from the wound margins.
How is the wound contracted in healing by secondary intention?
Myofibroblasts appear and contract
How is the donor site able to heal quickly in split skin grafts?
All the major structures are left behind, which are lined with epithelial cells which can grow out and out quickly allowing the skin to grow back
How does bone heal?
- haematoma fills gap and surrounds injury
- granulation tissue forms and cytokines activate osteoprogenitor cells
- at one week, a soft callus has formed which consists of fibrous tissue and cartilage within which woven bone forms
- after several weeks, woven bone forms a hard callus
- harder and more organised lamellar bone replaces the woven bone, and is remodelled to the direction of mechanical stress.
- unstressed bone is resorted and bone outline is re-established
What LOCAL factors can influence wound healing?
- type, size, location of wound
- mechanical stress
- blood supply
- local infection
- foreign bodies
Give some examples of GENERAL factors which can influence wound healing
- anaemia, hypoxia and hypervolaemia
- genetic disorders
- drugs (eg. steroids interfere with collagen synthesis)
- vitamin deficiency