Session 4 - Healing and Repair Flashcards
What is resolution in terms of healing and repair?
The temination of inflammation whereby the tissues return to being fully functional as they were previously
What is regeneration?
The replacement of dead or damaged cell by functional, differentiated cells
What are differentiated cells derived from, and what is this derivation controlled by?
Derived from stem cells, under the control of hormones and growth factors
What is the purpose of stem cell division?
Self-renewal or differentiation
What are three types of stem cell differentiation?
Unipotent - Can produce only one type of differentiated cell
Multipotent - Can produce several types of differntiated cell
Totipotent - can produce any type of differntiated cell
What is fibrous repair?
Replacement of a functional tissue by scar tissue
What are labile tissues?
Normal state is active cell division, which usually proliferate rapildy epithelia)
What is a stabile tissue?
Not normally dividing at a significant rate. Speed of regeneration variable.
(hepatocytes, osteoblasts, fibroblasts)
What is a permenant tissue?
Unable to divide
Unable to regenerate (neurones)
What are two types of wond repair?
Healing by primary intention and healing by secondary intention
When does healing by primary intention take place?
When edges are opposed
What occurs in healing by primary intention?
There is minimal clot and granulation tissue formation
Epidermis regenerates
Dermis undergoes fibrous repair
Maturation of scar continues up to 2 years
Risk of trapping infection > abcess
When does healing by secondary intention take place?
Unopposed wound edges, the healing of which causes large clot to form.
How does secondary intention healing progress?
- Epidermis regenerates beneath
- Repair process produces much more granulation tissue
- Longer process – produces a larger scar
- Late contraction by myofibroblasts to reduce the volume of defect
What are three key factors involved in wound repair?
Cell migratiom
Angiogenesis
Extracellular matrix production and remodelling
What occurs in cell migration in wound repair?
Inflammatory cells, endothelial cells and myofibroblasts all play a role
What do inflammatory cells do in the cell migration stage of wound repair?
Neutrophils & Macrophages phagocytose debris
Lymphocytes and macrophages chemically mediate wound repair
What do endothelial cells do in the cell migrate stage of wound repair?
Angiogenesis
What do myofibroblasts do in the cell migration phase of cell repair?
Produce extracellular matrix proteins, and are responsible for wound contraction
Why is adequate blood supply vital to wound healing?
Provide access to the wond for inflammatory cells and fibroblasts
Delivers oxygen and other nutrients
What is the proliferation of blood vesels in angiogenesis induced by?
Growth factors such as vascular endothelial growth factor (VEGF)
What is the process of angiogenesis in wound repair?
- Endothelial proteolysis of basement membrane
- Migration of endothelial cells via chemotaxis
- Endothelial proliferation, maturation and tubular remodeling
- Recruitment of periendothelial cells
What is the function of extracellular matrix production & remodelling
- Supports and anchors cells
- Separates tissue compartments e.g. basement membrane
- Sequesters growth factors
- Allows communication between cells
- Facilitates cell migration
What is the structure of type 1 collagen?
- Triple alpha helix: gly-x-y structure
- x and y usually hydroxy-proline or hydroxy-lysine – hydrogen bonding promotes strength
- Glycine is the only amino acid small enough to fit at the centre of the helix
What is the function of type 1 collagen?
- Non-elastic
- Strong
- Rigid
- Found in abundance in connective tissue
What types of factors can effect the efficacy of healing and repair?
Local factors and general factors
Give 6 local factors affecting the efficacy of local factors
- Type, size and location of wound
- Apposition, lack of movement e.g. keep ends of frature immobile and apposed
- Blood supply: arterial and venous – hastens healing and repair
- Infection: gangrene, suppuration (formation of abcesses)
- Foreign material
- Radiation damage e.g. during chemotherapy
Give 6 general factors which effect efficacy of healing and repair?
- Age
- Drugs, e.g. steroids – inhibit inflammatory response & hormones
- General dietary deficiences e.g. protein – reduced immune response
- Specific dietary deficiences e.g. vit C – scurvy
- General state of health
- General CVS status
What two factors can defective repair establish itself as?
Insufficient fibrosis
Excessive fibrosis
What can cause insufficient fibrosis?
o Wound dehiscence, hernia, ulceration
o Due to obesity, age, steroids, malnutrition etc
What can cause excessive fibrosis?
o Cosmetic scarring
o Keloids
o Cirrhosis
o Lung fibrosis
o Contractures: fibrous healing which produces distortion or limitation of movement of the tissues and is most often seen in patients with full thickness burns
- Skin graft and splinting helps prevention
Describe the healing process of cardiac muscle
- Cardiac myocytes are permanent cells
* Damaged repaired by fibrosis
Describe the healing process of bone
- Damage is not replaced by scar tissue but by bone
- Haematoma > macrophages and osteoclasts (procallus) > proliferation of fibroblasts > cartilage forms callus > cartilage reabsorbed and replaced by osteoblasts
Describe the healing process of the liver
- Only organ in the body capable of regeneration
- Hepatocytes can re-enter the cell cycle and undergo mitosis
- Evidence of stem cells, ovalocytes which can differentiate into hepatocytes
Describe the healing process of nerve cells
- Severed nerve can be repaired by Wallerian Regeneration
1. Schwann cells line up in the basement membrane tube
2. Synthesise growth factors
3. GFs attract axonal sprouts formed at the proximal terminal of the damaged axon
4. Basement membrane tube provides passage for the nerves which will innervate the muscle and skin
