Healing and repair Flashcards
Healing required regrowth of 2 things which are?
Cells and extracellular matrix
what are 3 things healing depends on?
- The type of tissue that is injured
- The nature of the injury
- Sufficient blood supply (angiogenesis)
What sort of cells are contained in the epidermis, dermo-epidermal junction and dermis?
Which part has an abundant extracellular matrix
What sort of structures make up the extracellular structure in the dermis?
What is the main receptor which cell bind to ECM?
Integrin
Main receptor type by which cells bind to ECM
What is the difference between primary and secondary intention in wound healing?
Healing by primary intention occurs in wounds with dermal edges that are close together (e.g a scalpel incision).
It is usually faster than by secondary intention, and occurs in four stages.
Healing by secondary intention occurs when the sides of the wound are not opposed, therefore healing must occur from the bottom of the wound upwards.
What are the 4 stages of primary intention and secondary intention
Haemostasis – the action of platelets and cytokines forms a haematoma and causes vasoconstriction, limiting blood loss at the affected area
The close proximity of the wound edges allows for ease of clot formation and prevents infection by forming a scab
Inflammation – a cellular inflammatory response acts to remove any cell debris and pathogens present
Proliferation – cytokines released by inflammatory cells drive the proliferation of the fibroblasts and the formation of granulation tissue
Angiogenesis is promoted by the presence of growth mediators (e.g VEGF), allowing for further maturation of the granulation tissue; the production of collagen by fibroblasts allows for closure of the wound after around a week
Remodelling – devascularisation of the region occurs, and the fibroblasts undergo apoptosis
Ends in a complete return to function - very little scarring
Secondary intention
It occurs in the same four stages as primary intention:
Haemostasis – a large fibrin mesh forms, which fills the wound
Inflammation – an inflammatory response acts to remove any cell debris and pathogens present
There is a larger amount of cell debris present, and the inflammatory reaction tends to be more intense than in primary intention
Proliferation – granulation tissue forms at the bottom of the wound
This is an important step, as the epithelia can only proliferate and regenerate once granulation tissue fills the wound to the level of the original epithelium; once the granulation tissue reaches this level, the epithelia can completely cover the wound
Remodelling – the inflammatory response begins to resolve, and wound contraction can occur
Label this
What are the steps for angiogenesis
What is fibroplasia?
Fibroblast proliferation and migration
• Production of collagen, proteoglycans and elastin to re-form the ECM
Re-epithelialisation
- Keratinocyte migration from edge of wound and skin appendages begins within 24h of injury
- Keratinocyte proliferation is inhibited until migration is complete
- Depends upon reestablishment of the dermoepidermal junction
What can be seen in this histology during the wound contraction and scarring?
Macrophages, fibroblasts and endothelial cells produce _______ which stimulate healing in epidermis and dermis
growth factors
What major receptors on ECM initiate growth factor signalling pathways?
What is upregulated to allow ECM to be remoddled?
What inhibits this process?
1) Integrins
2) Matrix metalloproteinases (MMP)
3) TIMP(Tissue inhibitors of metalloproteinases)
What are the effects of these growth factors
What factors influence wound healing:
systemic:
Local:
Systemic:
Nutrition
– Metabolic status
– Circulatory status
– Hormones
• Local
– Local blood supply
– Infection
– Foreign body
– Mechanical factors
What are the wound strengths at 1 week
1 month
3 months
Wound strength ~10% at 1 week
50-60% at 1 month
70-80% plateau at 3 months
What did this person form and who usually gets them?
An uncommon complication from wound healing (particularly in people with darker skin), are keloid scars, whereby there is excessive collagen production, leading to extensive scarring. This can occur in both primary and secondary intention healing.
what is this pathological healing
Contractures
What are causes of chronic leg ulcers?
poor blood circulation.
diabetes.
hypertension (high blood pressure)
heart disease.
high cholesterol.
kidney disease.
increased pressure in the legs.
smoking.
Where is the ECM predominantly confined in in the liver?
What is it mainly composed of?
What stain is used here?
1) ECM confined to -> portal tracts (thin layer in contact with hepatocytes
2) Collagen
3) Reticulin - type 3 collagen stain
How do liver cells regenerate?
what changes happen when the liver is injured?
Stellate cell (store vit A) -> maintain normal basement membrane
What is the difference between liver resolution and repair?
Resolution you get back the actual liver
Repair -> cirhossis -> regnerating nodules surrounded by fibrous tissue
What cells in the liver produce growth factors and cytokines to stimulate healing?
Stellate and Kupffer cells
What is the function of hepatocyte growth factor
What is the function of TGF-B in the liver?
What is the deposited collaged remoddelled using what growth factors?
1) Hepatocyte growth factor (HGF) plays a key role in stimulating hepatocytes to enter cell cycle
2) TGF-β is one of the key regulators of fibrosis
3) As in skin, the deposited collagen is remodelled by MMPs and TIMPs
Factors affecting development of cirhossis
Time course of liver injury – Paracetamol overdose causes severe liver injury at one point in time – does not lead to cirrhosis – Alcohol generally causes much less severe injury but over a longer time period – can cause cirrhosis
• Anatomic site of injury
– Damage to parenchyma (e.g. alcohol) causes classical cirrhosis with fibrosis mediated largely by stellate cells in the sinusoids
– Damage to portal tracts (e.g. PBC) causes a biliary pattern of fibrosis mainly affecting portal structures
Clinical consequences of cirrhosis
Jaundice
- Spider naevi, plamar erythema, gynaecomastia, splenomegaly, flapping tremor • Loss of parenchymal function: impaired protein synthesis, processing drugs and hormones and production of clotting factors
- Portal hypertension
- Infection (spontaneous bacterial peritonitis)
- Hepatocellular carcinoma
What changes happened to this myocardium
Acute myocardial infarction first and then fibrous scar in the myocardium
Fibroblast and myofibroblast procude matrix proteins in response to inflammatory cytokines released by what cells?
What are the inflammatoy cytokines released?
What are the fibrogenic factors?
1) macrophages and inflammatory cells
2) TNF-a, IL-1, IL6
3) TGF-B, PDGF and angiotensin 2
Consequences of myocardial fibrosis are
Contractile dysfunction
• Arrhythmia
Myocardial rupture
- Pericarditis
- Ventricular aneurysm
- Papillary muscle dysfunction
name types of labile cells
stable cells
permanent cells
