Flashcards in MoD 4 (Healing & Repair) Deck (93):
The growth of cells and tissues to replace lost structures. This requires an intact tissue scaffold (cannot occur if extensive damage).
Define 'labile' tissue:
Tissue with continuously dividing cells
Define 'stable' tissue:
Tissue with quiescent cells
What is a quiescent cell?
A cell that has reversibly left the cell cycle (G0), as it is not dividing or preparing to divide.
Where can labile cells be found?
- Lining mucosa of secretory ducts of glands
- Epithelia of GI, uterus and urinary tract
Haemopoetic tissue (red bone marrow)
Where can stable cells be found?
Mesenchymal cells (ie fibroblasts, smooth muscle cells)
Parenchymal (functional) cells of Liver, Kidney and Pancreas
Define 'permanent' tissue:
Tissue containing non-dividing, terminally differentiated cells
Where can permanent cells be found?
- Skeletal muscle cells
- Cardiac muscle cells
What type of cell undergoes asymmetric replication?
What is meant by asymmetric replication?
When a stem cell replicates producing 1 stem cell and 1 stable/permanent cell.
Define fibrous repair:
The replacement of functional tissue with scar tissue
Fibrous repair occurs in response to what 3 triggers?
1 - Chronic inflammation
2 - Damage to collagen framework of a tissue
3 - Necrosis of specialised cells which cannot be replaced
What cell types are required for fibrous repair?
What is the role of endothelial cells in fibrous repair?
What is the role of fibroblasts in fibrous repair?
Synthesis of extracellular matrix proteins
What is the roles of macrophages/neutrophils in fibrous repair?
Phagocytosis of debris
Which growth factor stimulates angiogenesis?
Describe the key steps in angiogenesis:
- VEGF binds to endothelial cell = ACTIVATES
- Activated endothelial cell causes vasodilation and proteolysis of basement membrane
- Endothelial cells proliferate and migrate, then mature and undergo remodelling
- Periendothelial cells are recruited
What is Scurvy caused by?
Vitamin C deficiency
What is Scurvy?
Weak collagen formation due to vitamin C deficiency, causing bleeding gums and prolonged healing.
What are the symptoms of Scurvy?
Shortness of breath
Why does a vitamin C deficiency cause weak collagen (Scurvy)?
Vitamin C is required for Prolyl hydroxylase and Lysyl hydroxylase, which hydroxylate amino acid residues during collagen synthesis, allowing many cross-linkages to occur, increasing the strength of Collagen
What is Ehlers-Danlos syndrome?
Inherited disease which causes the defective conversion of Procollagen to Tropocollagen (Collagen types I-III have reduced tensile strength), this causing hypermobility of joints and hyperextensible fragile skin
What are the symptoms of Ehlers-Danlos syndrome?
- Hypermobility of joints
- Hperextensible fragile skin
- Poor wound healing
What is Alport syndrome?
Inherited disease affecting type IV collagen primarily in kidneys, cochlea and lens of eye.
Causes kidney failure, cataracts, progressive hearing loss, oedema
What is the name of the inherited condition which causes progressive fibrous repair of type IV collagen in the body?
Define growth factor:
Polypeptide coded for by proto-oncogenes, which act on specific cell surface receptors, stimulating gene transcription
In what types of cells does Epidermal Growth Factor cause mitosis?
- Epithelial cells
What type of cells produce Epidermal Growth Factor?
- Inflammatory cells (ie macrophages)
What does VEGF stand for?
Vascular Endothelial Growth Factor
What does VEGF cause?
- Chronic inflammation
- Wound healing
Process of new blood vessel formation during embryonic development of the CVS
What does PDGF stand for?
Platelet Derived Growth Factor
Which cells can produce/release PDGF?
- Smooth muscle cells
- Endothelial cells
- Tumour cells
What is the role of PDGF?
Causes migration and proliferation of fibroblasts, smooth muscle cells and monocytes
What does G-CSF stand for?
Granulocyte-Colony Stimulating Factor
What is the role of G-CSF?
Stimulates bone marrow to produce granulocytes (ie neutrophils)
What does TNF stand for?
Tumour Necrosis Factor
What is the role of TNF?
Induces fibroblast migration and proliferation, and collagenase secretion
What is the role of Cadherins?
Bind cell to each other
What is the role of Integrins?
Bind cells to the extracellular matrix
Describe the wound appearance if it is healing by primary intention:
- Opposed edges
- Clean cut (via scalpel)
- May be sutured
What are the 6 stages of wound healing?
3) Cell migration
6) Scar maturation
What is the 1st stage of wound healing, and what does it involve?
Arteries contract, clotted blood fills space and dehydrates, forming a scab
What is the function of a scab in wound healing?
Seals wound from outside environment
What is the 2nd stage of wound healing and what does it involve?
Neutrophils gather at the margins of the wound
What is the 3rd stage of wound healing and what does it involve?
Macrophages appear (phagocytose dead neutrophils and secrete cytokines for endothelial cells and fibroblasts)
Endothelial cells begin angiogenesis
Basal epidermal cells deposit basement membrane
What are the functions of Macrophages in wound healing?
- Phagocytose dead neutrophils and necrotic tissue
- Secrete cytokines for fibroblasts and endothelial cells
What is the function of endothelial cells in wound healing?
What is the role of basal epidermal cells in wound healing?
Deposit basement membrane
What is the 4th stage of wound healing and what does it involve?
Formation of granulation tissue
Proliferation of epithelial cells
Scab falls off
Activated fibroblasts secrete collagen
In which stage of wound healing does granulation tissue form?
Regeneration stage ~ 3 days after trauma
What is the 5th stage of wound healing, and what does it involve?
Fibroblasts proliferate and form scar
Epidermis keratinises (no sweat glands/hair follicles)
WBCs and Oedema disappears
Vascular channels regress
What is the 6th stage of wound healing and what does it involve?
Type III collagen is gradually replaced by type I collagen
May contract via myofibroblasts
In which direction does wound healing take place if healing by primary intention?
From the surface downwards
In which direction does healing take place if healing by secondary intention?
From the bottom up, towards the surface
What is the risk involved with healing by primary intention?
Infection may be trapped below sutures, may cause abscess formation
Describe the wound appearance if it is healing by secondary intention:
- Unopposed edges
- Large amount of tissue lost (due to infarct/abscess/ulcer/infection)
Apart from the appearance of the wound, what is the difference between healing by primary and secondary intention?
Healing by secondary involves:
- More clot formation
- More necrotic debris produced
- Increased inflammatory reaction
- More granulation tissue formed
- May require contraction
Which cell type mediates contraction of a wound?
List some local factors which may influence the efficacy of wound healing:
- Location of wound
- Mechanical stress applied
- Blood supply
- Protection used
- Size of haematoma formed
- Amount of necrotic tissue
- Size of wound
- Surgical techniques
List some systemic factors which may influence the efficacy of wound healing:
- General health
- O2 delivery (anaemia/hypovolaemia/hypoxia)
- Genetic disorders
- Dietary deficiencies
How do steroids affect wound healing and repair?
Delay, as inhibit collagen synthesis
How do antibiotics affect wound healing and repair?
Speed up, as prevent infection occurring
What are the main complications of fibrous repair?
- Insufficient fibrosis
- Excessive fibrosis
- Excessive contraction
What factors can increase the risk of insufficient fibrosis during wound healing and repair?
- Increasing age
- Dietary insufficiencies
What is a keloid?
Overgrowth of fibrous tissue due to an overproduction of collagen, which exceeds the border of the scar (expands outside the border of the original damage)
Which ethnicity is most at risk of keloid formation?
Which complication of fibrous repair may lead to strictures or contractures?
Which complication of fibrous repair may lead to keloid formation?
Excessive fibrosis (collagen synthesis)
Can cardiac muscle regenerate?
What is the outcome of repair in cardiac muscle?
Can the liver regenerate?
What type of cell is activated by hepatocyte damage?
Hepatic stellate cell
What is the role of a hepatic stellate cell in liver repair?
- Activates macrophages
- Secretes pro-inflammatories/cytokines to recruit T cells and Neutrophils
- Transdifferentiates into myofibroblasts
What cell type can a hepatic stellate cell transdifferentiate into?
What is the role of myofibroblasts in liver repair?
- Deposit Collagen type I
What type of collagen is deposited in liver repair?
Collagen type I
If the cause of injury to the liver is removed, what happens in the liver? (If cirrhosis has not occurred)
- Myofibroblasts transdifferentiate back into hepatic stellate cells
- Collagen is broken down and removed
- Hepatocyte regeneration
Can a peripheral nerve regenerate?
What is the speed of axon growth during repair?
~ 1-3 mm/day
Can cartilage regenerate?
Why can't cartilage repair itself following damage?
Cartilage is avascular, and lacks lymph drainage and innervation
What may the body replace hyaline cartilage with if damaged?
Can the CNS regenerate?
Which of the following can regenerate?
Cardiac muscle cells
Which cell type inhibits axon repair and/or remyelination in the CNS?
What is the automatic response of the CNS to injury?
Gliosis formation (scar) to prevent spread of damage
What forms in the CNS due to injury, to prevent spread of damage?
What is the most common cause of oesophageal strictures?
Name some symptoms of an oesophageal stricture:
- Trouble/pain when swallowing
- Unintentional weight loss
- Regurgitation of food
What causes Marfan syndrome?
Inherited defective fibrillin-1 gene