Wound Healing Flashcards
What is the basic plan for the healing of every wound?
1) Close the gap
2) Repair it with a scar
(The smaller the scar the better)
What are the processes involved in wound healing?
1) Haemostasis - as vessels are open
2) Inflammation - as there has been tissue injury
3) Regeneration and repair - as structures have been injured or destroyed
What is regeneration?
Restitution with no, or minimal, evidence that there was a previous injury
What is the difference between an abrasion and an ulcer?
Abrasion - superficial damage to the skin, no deeper than the epidermis
Ulcer - goes far deeper, into the submucosa
What are stem cells?
Cells with prolonged proliferative activity
What is meant by asymmetric replication of stem cells?
When they divide, one of the cells remains a stem cell while others mature into a cell of some type
Where are stem cells in the epidermis?
Basal layer adjacent to basement membrane
Where are stem cells in the intestinal mucosa?
Bottom of crypts
Where are stem cells in the liver?
Between hepatocytes and bile ducts
What are unipotent cells?
Most adult stem cells - only produce one type of differentiated cell
What are multipotent cells?
Cells that can produce several types of differentiated cell eg haematopoietic stem cells
What are totipotent cells?
Cells that can produce any type of cell and therefore any tissues of the body
(Embryonic stem cells)
What are labile tissues?
Contain short-lived cells that are replaced from cells derived from stem cells
What are stable tissues?
Contain cells with a low level of replication but if necessary can undergo rapid proliferation, both stem cells and mature cells proliferate
What are permanent tissues?
Contain mature cells that can’t undergo mitoses and no or only a few stem cells
What are some examples of labile tissues?
Surface epithelia, haematopoietic tissues
What are some examples of stable tissues?
Liver parenchyma, bone, fibrous tissue, endothelium
What are some examples of permanent tissues?
Neural tissue, skeletal muscle, cardiac muscle
What is a scar?
Healing with formation of fibrous connective tissue
What determines whether an injury will lead to regeneration or fibrous repair?
Whether or not the collagen framework is still intact and whether there is on-going chronic inflammation
How does a scar form?
Seconds-minutes: haemostasis
Minutes-hours: acute inflammation
1-2 days: chronic inflammation
3 days: granulation tissue forms
7-10 days: early scar
Weeks-2 years: scar maturation
When are stitches removed after an injury?
7-10 days - when there is an early scar
What does granulation tissue consist of?
- Developing capillaries
- Fibroblasts and myofibroblasts
- Chronc inflammatory cells
What are the functions of granulation tissue?
- Fills the gap
- Supply of oxygen, nutrients and cells by capillaries
- Contraction
What are the stages of fibrous repair?
1) Blood clots
2) Neutrophils infiltrate and digest clot
3) Macrophages and lymphocytes are recruited
4) Vessels sprout, fibroblasts make glycoproteins
5) Vascular network, collagen synthesised, macrophages reduce
6) Maturity, less cells, collagen matures, contracts and remodels
Which cells are involved in fibrous repair?
- Inflammatory cells eg neutrophils, macrophages, lymphocytes
- Endothelial cells - proliferation results in angiogenesis
- FIbroblasts and myofibroblasts - produce ECM proteins, responsible for wound contracation
Why do older scars appear white?
This is because you don’t get regeneration of melanocytes
Why do older scars stretch?
This is because fibroblasts can’t lay down elastin
Can hair follicles regenerate?
No
Which are the fibrillar collagens?
Types I-III - responsible for tissue strength
Which are the amorphous collagens?
Types IV-VI - basement membrane
Which type of collagen makes up basement membranes?
Type IV (secreted by epithelial cells)
Name some diseases that are the result of defective collagen synthesis
Scurvy, Ehlers-Danlos syndrome, osteogenesis imperfecta, Alport syndrome
How is alport syndrome inherited?
X-linked
Which type of collagen is abnormal in alport syndrome?
Type IV - dysfunction of glomerular BM, cochlea of ear and lens of eye
What are the types of cell signalling?
Autocrine, intracrine
Paracrine
Endocrine
What are growth factors?
Polypeptides coded by proto-oncogenes that bind to specific receptors, stimulate transcription of genes that regulate entry of cell into cell cycle and the cell’s passage through it
Apart from cell proliferation, what other effects can growth factors have?
- Inhibition of division
- Locomotion
- Contractility
- Differentiation
- Viability
- Activation
- Angiogenesis
What are some examples of growth factors?
Epidermal growth factor, vascular endothelial growth factor, platelet derived growth factor, tumour necrosis factor
What are growth factors produced by?
Cells such as platelets, macrophages, endothelial cells
Outline contact inhibition
As the cells grow and cadherins bind cells to each other, they continue to proliferate but as the integrins bind cells to the ECM they stop proliferated so that they just fill the space
What is an example of wound healing by primary intention?
Healing of incised, closed, non-infected and sutured wounds
Disruption of BM continuity but death of only small number of epithelial and connective tissue cells
What happens to the epidermis in healing by primary intention?
It regenerates - basal epidermal cells at edge of cut creep over denuded cells (approximately 0.5mm a day), deposit BM, fuse in midline beneath scab and undermine scab which falls off
What are some examples of wound healing by secondary intention?
Excisional wound, wounds with tissue loss and separated edges, infected wounds (eg infarct, ulcer, abscess)
Open wound filled by abundant granulation tissue - grows in from wound margins
In healing by secondary intention, what must take place to close the wound?
Considerable wound contraction - initially occurs as scab contracts when it dries, after 1 week myofibroblasts appear and contract
What are the stages of bone healing?
1) Haematoma - fills gap
2) Granulation tissue forms - cytokines activate osteoprogenitor cells
3) Soft callus forms - fibrous tissue and cartilage within which woven bone forms
4) Hard callus forms - Initially woven bone, weaker and less organised
5) Lamellar bone - replaces woven bone, remodelled to direction of mechanical stress
What are some local factors that can influence wound healing?
1) Type, size, location
2) Mechanical stress
3) Blood supply
4) Local infection
5) Foreign bodies
What are some general factors that can influence wound healing?
1) Age
2) Anaemia, hypoxia
3) Obesity
4) Diabetes
5) Genetic disorders
6) Drugs
7) Vitamin deficiency
8) Malnutrition
What are some complications of fibrous repair?
1) Wound dehiscence, hernia, ulceration
2) Formation of adhesions
3) Loss of function due to replacement of specialised functional cells by scar tissue
4) Disortion of architecture interfering with function eg liver cirrhosis
5) Overproduction of fibrous scar tissue (Keloid scar)
6) Excessive scar contraction
What is the effect of steroids on wound healing?
Wound won’t heal as well
