S4) Healing and Repair Flashcards
What are the three processes involved in wound healing?
- Haemostasis – as vessels are open
- Inflammation – as there has been tissue injury
- Regeneration (aka resolution) and/or repair – as structures have been injured or destroyed
What is regeneration?
Regeneration is the growth of cells and tissues to replace lost structures e.g. epithelia of skin and GI tract can regenerate after injury
Which cells replicate in regeneration?
New differentiated cells are mainly derived from stem cells as many terminally differentiated cells can’t divide
What are stem cells?
Stem cells are cells with prolonged proliferative activity which show asymmetric replication
- one daughter cell remains a stem cell while the others differentaiate inot mature, non-dividing cells.
What is asymmetric replication?
In asymmetric replication one of the daughter cells remains as a stem cell while the other differentiates into a mature, non-dividing cell
Whereabouts in the tissues are the stem cells?
Varies between tissues:
- Epidermis – basal layer adjacent to the basement membrane
- Intestinal mucosa – bottom of crypts
- Liver – between hepatocytes and bile ducts
Identify and describe the three different kinds of stem cells in terms of their regenerative capacity
- Unipotent – most adult stem cells, as they only produce one type of differentiated cell e.g. epithelia
- Multipotent – produce several types of differentiated cells e.g. haematopoietic stem cells
- Totipotent – can produce any type of cell and therefore any tissue of the body e.g. embryonic stem cells
Tissues of the body are divided into three groups on the basis of their proliferative activity.
What are these groups?
- Labile
- Stable
- Permanent
What are labile tissues?
Labile tissues are continuously dividing tissues which proliferate throughout life replacing cells that are destroyed
E.g. surface epithelia lining mucosa, columnar epithelia of GI tract and uterus, urothelium, cells of bone marrow and haematopoietic tissues
What are stable tissues?
Stable tissues are quiescent tissues which normally have a low level of replication can undergo rapid division in response to stimuli (induced to enter the cell cycle)
E.g. parenchymal cells of the liver, kidneys and pancreas, fibroblasts, bone osteoclasts and smooth muscle cells, vascular endothelial cells
What are permanent tissues?
Permanent tissues are non-dividing tissues which contain cells that have left the cell cycle and can’t undergo mitotic division in postnatal life
E.g. neurones, skeletal and cardiac muscle cells
Explain the role of stem cells in the three different groups of cells based on their proliferative activity
- Labile tissues contain cells that are short-lived and are continually being replaced by cells derived from stem cells
- In stable tissues the mature cells as well as stem cells are involved in proliferation in response to stimuli
- Permanent tissues contain terminally differentiated cells which cannot replicate
In what circumstances can regeneration occur?
- If the damage occurs in a labile/stable tissue
- If the tissue damage is not extensive (intact connective tissue scaffold)
What is fibrous repair?
- Fibrous repair is healing with formation of fibrous connective tissue (scar)
- Specialised tissue is lost and healing by secondary intention occurs
When does fibrous repair occur?
- If there is significant tissue loss
- If permanent or complex tissue is injured
- If there is ongoing chronic inflammation
How can we determine whether fibrous tissue or regeneration will occur?
In 6 steps, explain how a scar forms
⇒ 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
Granulation tissue has a granular appearance and texture.
What does it consist of?
- Developing capillaries
- Fibroblasts and myofibroblasts
- Chronic inflammatory cells
What does granulation tissue do?
- Fills the gap
- Capillaries supply oxygen, nutrients and cells
- Contracts and closes the hole
Describe the six steps involved in fibrous repair
Which cells are involved in fibrous repair and what do they do?
- Inflammatory cells:
I. Phagocytosis of debris (neutrophils, macrophages)
II. Production of chemical mediators (lymphocytes, macrophages)
- Endothelial cells: proliferation results in angiogenesis
- Fibroblasts and myofibroblasts:
I. Produce extracellular matrix proteins
II. Wound contraction (myofibroblasts)
Identify some diseases that occur due to defects in collagen synthesis
- Scurvy
- Ehler-Danlos syndrome
- Osteogenesis imperfecta
- Alport syndrome
What is Ehlers-Danlos syndrome?
- Ehlers-Danlos syndrome is a heterogeneous group of 11 inherited disorders due to the defective conversion of procollagen to tropocollagen
- Collagen fibres lack adequate tensile strength, hence the skin is hyperextensible, fragile and susceptible to injury and joints are hypermobile
What is osteogenesis imperfecta?
- Osteogenesis imperfecta (aka brittle bone disease) is a disease where patients have too little bone tissue and hence extreme skeletal fragility
- They present with blue sclerae (translucent – little collagen), hearing impairment and dental abnormalities
Growth factors are particularly important in wound healing.
What do they do?
Growth factors bind to specific receptors, stimulate transcription of genes that regulate entry of cell into the cell cycle and the cell’s passage through it
What is contact inhibition?
Contact inhibition is signalling through adhesion molecules:
- Cadherins bind cells to each other
- Integrins bind cells to the extracellular matrix
- when cells come into contact with each other this tells the cell to stop replicating to prevent over production of cells
What does contact inhibition do?
- Inhibits proliferation in intact tissue
- Promotes proliferation in damaged tissues
Where is contact inhibition altered?
Contact inhibition is altered in malignant cells
When does healing by primary intention occur?
Occurs in incised, closed, non-infected and sutured wounds:
- Disruption of epithelial basement membrane continuity
- Death of a limited number of epithelial and connective tissue cells
- Minimal clot and granulation tissue
What occurs in healing by primary intention?
- Epidermis regenerates (basal epidermal cells deposit basement membrane, fuse in midline beneath scab, undermine scab which falls off)
- Dermis undergoes fibrous repair
- Sutures out at about 10 days (approx. 10% normal strength)
- Minimal contraction & scarring (good strength)
When does healing by secondary intention occur?
- Excisional wound, wounds with tissue loss and separated edges, infected wounds e.g. infarct, ulcer, abscess
- Open wound filled by abundant granulation tissue
Healing by secondary intention involves the same processes as healing by primary intention but more so.
What occurs in healing by secondary intention?
- Considerable wound contraction occurs to close wound (myofibroblasts appear after 1 week)
- Substantial scar formation, new epidermis often thinner than usual
- Takes longer than healing by primary intention
