Session 4 - Healing And Repair Flashcards
What does regeneration require for complete resolution?
An intact connective tissue scaffold
What are labile tissues?
Tissues which proliferate throughout life, replacing cells that are destroyed
Give some examples of labile tissues
Surface epethelia, lining mucosa of secretory ducts of glands, columnar epethelia of GI tract and uterus, cells of bone marrow and haemopoietic tissues
What are stabile tissues?
Tissues that normally have a low level of replication but cells in these tissues can undergo rapid division in response to stimuli
Give some examples of stable tissues
Parenchymal cells of liver, kidneys and pancreas, mesenchymal cells such as fibroblasts and smooth muscle cells, vascular endothelial cell, resting lymphocytes and other wbc’s
What are permanent tissues?
Tissues that contain cells that have left thee cell cycle and can’t undergo mitotic division in postnatal life
Give some examples of permanent tissues
Neurones, skeletal and cardiac muscle cells
What are stem cells?
Cells with prolonged proliferative activity
What are totipotent stem cells?
Stem cells that can give rise to any of the tissues in the human body (embryonic)
What are pluripotent stem cells?
Stem cells that can give rise to many types of cell
Eg haemetopoietic stem cells
What are unipotent stem cells?
Stem cells that can only give rise to one type of adult cell
What is fibrous repair?
When fibrovascular connective tissue grows into an area of damage
When may fibrous repair occur?
- If collagen framework is damaged
- If on-going chronic inflammation occurs
- If there is necrosis of specialised parenchymal cells that cannot be replaced
What are the processes that occur in fibrous repair?
- Phagocytosis of necrotic tissue debris
- Angiogenesis
- Proliferation of fibroblasts and Myofibroblasts
- Granulation tissue becomes vascularised -> fibrous scar
- Scar matures and shrinks due to contraction of Myofibroblasts
What happens in scurvy?
- Vit C deficiency
- Vit C required for hydroxyl action of ProCollagen
- makes sufferers unable to heal wounds properly
What happens in Ehlers-Danlos syndrome?
- collagen lacks tensile strength
- skin is hyper extensible, fragile and susceptible to injury
- joints are hyper mobile
- poor wound healing and predisposition to joint dislocation
What happens in Osteogenesis Imperfecta?
- brittle bone disease
- too little bone tissue
- blue sclera as not enough collagen to make them clear
What happens in Alport Syndrome?
- Type IV collagen abnormal
- dysfunction of glomerular basement membrane, cochlear of ear and lens of eye
- presents in boys with haematuria
- progresses to chronic renal failure
What is Autocrine signalling?
Cells respond to the signalling molecule that they produce
What is paracrine signalling?
Cells produce signalling molecule that acts on adjacent cells. The responding cells are close to secreting cells and are often a different cell type
What is endocrine signalling?
Hormones are synthesised in an endocrine organ, and are then conveyed in the bloodstream to target cells
What are growth factors?
- Polypeptides that act on specific cell surface receptors
- coded for by proco-oncogenes
- stimulate or inhibit cell proliferation
- Effect transcription of genes that regulate whether or not cells enter the cell cycle
What does epidermal growth factor do?
- Binds to epidermal growth factor receptor
- is mitogenic for epithelial cells, hepatocytes and fibroblasts
What does Vascular endothelial growth factor do?
- Causes both vasculogenesis and angiogenesis
- in tumours, chronic inflammation and wound healing
What does platelet derived growth factor do?
- stored in platelet alpha granules
- released on platelet activation
- also produced by macrophages, endothelial cells, smooth muscle cells and tumour cells
- causes migration and proliferation of fibroblasts, smooth muscle cells and monocytes
What do tumour necrosis factors do?
Induces fibroblast migration, proliferation and collagenase secretion
What is contact inhibiton?
When normal cells become isolated they will replicate until they touch other cells
What are adhesion molecules and give two examples of them and what they adhere to what?
Cells adhere to each other and the ECM by means of adhesion molecules.
Caherins - Binds cells to cells
Integrins - Binds cells to the ECM
When may healing my primary intention occur?
When there is an incisional, closed, non-infected and sutured wound.
There is damage to the basement membrane but number of CT and epithelial cells is limited
What are the stages of healing by primary intention?
- Haemostasis (severed arteries contract)
- Inflammation (Neutrophils appear)
- Migration of cells (macrophages appear, scavenge neutrophils)
- Regeneration (granulation tissue forms)
- Early scarring (wound is filled with granulation tissue)
- Scar maturation (mass of fibrous tissue lots of collagen)
When will healing by secondary intention occur?
When there is an excisional wound with tissue loss and unopposed edges
Define regeneration
Growth of cells and tissues to replace lost structures
What is the process of healing by secondary intention?
- wound is filled by abundant granulation tissue
- Large clot and necrotic debris
- considerable wound contraction must occur (after a week this occurs)
- Substantial scar formation
- healing will be delayed if infection occurs
Describe the process of healing bone fractures
- Haemotoma forms and fills and surrounds fracture site
- Fibrin mesh and granulation tissue forms
- Soft callus -fibrous tissue+cartilage, woven bone begins to form
- Hard callus -laid down by osteoblasts - initially woven bone
- Formation of lamellar bone
- Remodelling to match original contours of bone
Give some examples of local factors that influence healing and repair
(Long List)
- Size, Location and Type of wound
- Blood supply
- Denervation
- Local Infection
- Foreign Bodies
- Haematoma
- Necrotic tissue
- Mechanical Stress
- Protection (dressings)
- Surgical techniques (better techniques = better healing)
Name some systemic factors influencing healing and repair
Long List
- Age
- Anaemia, hypoxia + hypovolmia (lower total blood volume)
- Obesity
- Diabetes
- Malignancy
- Genetic disorders (Eg Ehlers-danlos syndrome)
- Drugs (Eg steroids inhibit collagen synthesis)
- Vit deficiency (less Vit C = weaker collagen)
- Malnutrition
Give some examples of harmful complications of fibrous repair
- formation of fibrous adhesions (may block tubes or stop function of organ)
- Loss of function due to replacement of parenchymal cells with collage nous scar tissue
- overproduction of fibrous scar tissue (keloid scar)
- excessive scar contraction causing obstruction of tubes, disfiguring (scars following burns) or joint contractures
What aspects of healing are present in Cardiac muscle?
- very limited, if any regenerative capacity
- MI is followed by scar formation
What aspects of healing are present in the Liver?
- remarkable capacity to regenerate
- remaining lobes enlarge to restore size
- almost all hepatocytes replicate in regeneration
What aspects of healing are present in Peripheral nerves?
- if a nerve is severed the axon degenerates
- proximal stumps of axons sprout and elongate
- use Schwann cell to guide them back to tissue
- grow around 1-3mm a day
What aspects of healing are present in cartilage?
- doesn’t heal well
- this is due to lack of blood supply, innervation or lymphatic drainage
What aspects of healing are present in the CNS?
- neural tissue is a permanent tissue
- if damage occurs to neural tissue it is replaced by the proliferation of glial cells
