Flashcards in Cell repair and adaptations Deck (51)
Define tissue regeneration?
healing by primary intention meaning the tissue going back to normal with minimal or no evidence that there was a previous injury - only possible with minor injuries
What is the difference between an ulcer and an abrasion?
An abrasion is superficial, affecting only the epidermis and dermis. Ulcers are deeper, penetrating down into the submucosa
What is meant by asymmetrical replication of stem cells?
When a stem cell divides one daughter cell will become another stem cell the other will become the differentiated daughter cell
Where are stem cells found in the epidermis, liver and GI tract?
In epidermis- in basal layer (bottom)
In liver - between hepatocytes
intestinal mucosa- Near bottom of crypts
Name and describe the 3 types of stem cells
Unipotent: Can only divide to produce one type of differentiated cell (most adult stem cells)
Multipotent: Can divide into several types of cells (haematopoetic cells)
Totipotent: can become any cell type (embryonic stem cells)
What is a labile tissue? Give an example?
Labile tissues contain short lived cells and so are always being replaced by replicating stem cells
eg. epidermis, haematopoetic cells
What is a stable tissue? Give an example
Have normally low levels of replication, but if necessary mature and stem cells can undergo rapid proliferation
eg. liver, bone, fibrous tissue, endothelium
What is a permanent tissue? Give an example
the cells cannot undergo replication and there are few/ no stem cells present
eg. cardiac and skeletal muscle, neural tissue
When can tissue regeneration occur?
In labile and stable tissue when connective tissue framework is still in tact and no chronic inflammation
describe the process of healing by primary intention/scar formation
1. Haemostasis - (seconds to minutes) arterioles contract, clot and scab forms
2. Inflammation - (minutes to days) acute then chronic digestion of clot, including neutrophils.
3. Migration of cells (chronic inflammation) - macrophages scavenge dead neutrophils + release cytokines which attract fibroblasts. Angiogenesis starts and basement membrane cells proliferate and start to move towards each-other
4. Proliferation - (days to weeks) - GRANULATION TISSUE (fibroblasts and new capillaries) invade the space and epithelial cell proliferation undermines scab which then falls off
5. Early scar - fibroblasts proliferate and produce mass of collagen.
6. Remodelling - (weeks to years) - reduced cell population, increased collagen, myofibroblasts contract to form fibrous scar.
When does healing by primary intention occur?
What are the features
- When the wound is incised, with apposed edges (sutured).
- Minimal clot + granulation tissue. Epidermis regenerates, dermis undergoes fibrous repair. Small scar.
What is granulation tissue?
What are its functions?
A tissue with lots of fibroblasts, myofibroblasts, inflammatory cells and new capillaries which is granular in appearance and texture.
Its functions are to fill the gap, contract + close the gap, supply O2 and nutrients to cells and prevent infections.
How is cell regeneration and repair controlled? (3)
1) Growth factors - auto/paracrine signals coded for by proto-onco genes that stimulate cell proliferation, migration - e.g.: VEGF or EGF
2) Contact inhibition- when cadherins on adjacent cell membranes bind to each other they will stop proliferating. They will also only proliferate when the integrins are bound to the ECM. This inhibits proliferation of intact tissues an promotes proliferation in damaged tissues
Name 4 growth hormones, where they come from and where they act.
TUMOUR NECROSIS FACTOR- from macrophages amongst others, induces fibroblast migration, proliferation and collagenase secretion
EPIDERMAL GF- from keratinocytes, macrophages and inflammatory cells, act on epithilal, fibroblasts and hepatocytes
VASCULAR ENDOTHELILAL GF- induce angio and vasculogenesis
PLATELET DERIVED GF- Released from platelets, macrophages, endothilial cells, smooth muscle and fibroblasts. Acts on fibroblasts, smooth muscle and monocytes
In what cases does healing by primary intention and healing by secondary intention occur?
What are the features of healing by secondary intention?
- Primary when wound is incised with opposed edges. - -- Secondary when there's significant tissue loss with unopposed edges.
- Abundant clot, inflammation + granulation tissue
- Considerable wound contraction
- Dermis requires significant repair, epidermis regenerates from edges
Describe the process of bone fracture healing
1. haematoma forms from broken blood vessels
2. Macrophages infiltrate and remove debris, granulation tissue forms, these attract fibroblasts which starts to secrete collagen. Inflammatory cells secrete cytokines which activate oestoprogenitor, osteoclasts and oestoblasts
3. Soft callus forms, cartilage and fibrous tissue spans gap. The fibrocartilage callus expands larger than the width of the bone creating a bulge
4. Hard callus- osteoblasts lay down osteoid and woven bone is organised into lamellar bone
5. Remodelling - lamellar bone remodelled to original outline of bone
What local factors influence wound healing?
- Type, size and location of wound
- Blood supply to wounded areas (in face this is good = fast healing time)
- local infection
- foreign bodies
what systemic factors influence wound healing?
- Anaemia, hypoxia, hypovolaemia (co-morbidities related to blood supply)
- genetic factors
- Drugs (steroids= slow collagen synthesis)
- vitamin deficiency (scurvy= bad)
When is insufficient fibrosis (often leading to wound dehiscence) a common complication of fibrosis?
- following hernia, ulceration, surgery
- in ppl with obesity, elderly, malnourished and steroid users
What other complications are there to fibrous repair?
- Formation of adhesions - fibrous bands that cause obstruction of tubes
- Loss of function
- Disruption of complex tissue relationships and architecture
- Excessive scar contraction + fibrosis (can block tubes, contract across joints and lead to dysfunction)
- Overproduction of scar tissue (keloid scar)
What is a keloid scar? In what population are they most common?
overgrowth of fibrous tissue, due to an overproduction of collagen that exceeds the scar boundaries. They do not regress and cutting them off just creates another one.
Most common in afro- Caribbean.
Why do teeth fall out in scurvy?
- Vit C needed for hydroxylation of proline + lysine (in pre-pro collagen)
- Defective triple helix = defective collagen
- Unable to heal wounds, leading to tooth loss
What is ehlers- danlos syndrome?
- defective conversion of procollagen to tropocollagen
To what extent does cardiac muscle repair?
- very limited regenerative capacity, usually just scarring
- loss of function
To what extent and how does skeletal muscle repair?
- satellite cells (under basal lamina) stimulated to divide into skeletal muscle and fuse with existing cells to regenerate and repair damaged fibres
How do hepatocytes regenerate?
They can simply divide
Why cant cartilage regenerate?
- No blood supply, innervation or lymphatic drainage
How does the PNS regenerate?
- When nerve severed axon degenerates
- proximal stumps of degenerated axons sprout and elongate
- schwann cells guide axon back to tissue at 1-3 mm per day
What happens when the CNS is damaged?
The glial cells proliferate to fill the space but these do not function as the neurones did before