Repair and regeneration Flashcards
how is healing divided?
repair and regeneration
what is the body’s main response to injury?
acute inflammation
what is the main role of acute inflammation?
to allow the immune system into the damaged area, clear away dead tissue and to protect against local infection
what is the ideal outcome?
resolution - when organised tissue replaces the damaged area with identical tissues in structure and function to the original - cell must be able to regrow and cell debris must be cleared
what happens if the damage is very severe?
the damaged cells cannot regrow and the architecture of the tissue is destroyed meaning that healing takes place by formation of a scar - fibrous repair
what is the basis of regeneration?
normal structure and function is preserved
what are the three things that result from acute inflammation?
repair, regeneration or chronic inflammation
what are the two most important factors in determining the outcome of the injury?
the ability of the cells to replicate and the ability of the cells to rebuild complex architectural structures
which cells will continuously go through the cell cycle?
cells of skin and GIT - those that need to be continually replaced due to exposure - labile cells
What are permanent cells and quiescent cells?
permanent have no chance of replication such as neurons and quiescent have a very slow rate of replication but can speed up when required such as liver
what happens in S phase and G2 to M phase?
in S phase there is chromosomal replication and between G2 and M there is the check for damaged or unduplicated DNA
what happens in G1 and between G1 and S?
in G1 there is centrosome duplication and between G1 and S there is check for DNA damage
what are the characteristics of a labile cell population?
active stem cell population, excellent regenerative capacity and high normal turnover rate
where is the active stem cell population found in epidermis?
in a particular part of the body of the epidermis at the basal layer
what are the characteristics of the stable/quiescent cell population?
good regenerative capacity, low physiological turnover rate but it can greatly increase if needed
what are the characteristics of permanent?
they have no regenerative capacity, are long life cells and have no physiological turnover
what are the characteristics of stem cells?
prolonged self renewal and asymmetric replication
what happens in the mitosis of stem cells?
one of the daughter cells will retain the characteristics of the stem cell but the others will progress along the differentiation pathway
what happens before stem cells reach the epidermis?
there is terminal differentiation
what is essential for regeneration to occur?
no severe local damage, complex architectural structures not damaged and connective tissue framework still present
what is cirrhosis?
it is the collapse of the reticulin - the normal architectural framework in the liver and therefore it cannot regenerate - usually occurs by persistent long term exposure to noxious agents - regenerative nodules are separated by a fibrous septum - imbalance between the hepatocyte regeneration and failure to reconstruct the architecture
what happens in regeneration when a labile cell population is lost?
it can be restored - cells at the edge of the defect can multiply to cover the defect - one they cover the defect proliferation stops - contact inhibition - epidermis grows from the base upwards
what is regeneration controlled by?
growth factors, cell to cell and cell to matrix interactions
what happens in repair?
healing by non-specialised fibrous tissue resulting in functional consequences
what is the difference between mechanical and electrical heart damage due to fibrous scar tissues?
mechanical: loss of pumping capacity
electrical: focus of the abnormal electrical activity resulting in arrhythmia or disruption to the cardiac conducting system giving heart block
what is organisation?
the repair of specialised tissue by formation of a fibrous scar - basic stereotyped pathological process
what occurs in organisation?
the production of granulation tissue on a scaffold of fibrin and then removal of dead tissue by phagocytosis
what is granulation tissue?
it is from endothelial cell proliferation and it is tissue with capillaries within it - important for inflammation and has white cells for phagocytosis of dead matter
what is responsible for contraction in wounds?
myofibroblasts - synthesis ECM and collagen and infiltrate the granulation tissue - acquire myofibrils - they have contractile capacity - found in granulation tissue
what is wound contraction important for?
reducing the volume of tissue for repair (up to 80%)
what happens to granulation tissue over time?
it becomes far less cellular and vascular and has more collagen
what is needed for primary intention?
clean, uninfected surgical wound, with good haemostasis and apposed edges
what can be a complication of bleeding?
haematomas - can push the sutures apart so edges are no longer apposed
what are sutures connected with?
a thin layer of fibrin which is then replaced by surface epidermis and collagen
what happens when epidermis overgrows?
if they do not stop growing and are not reabsorbed then the epidermis will grow into the wound and form an epidermal cyst / keratin filled cyst which results in implantation dermoid - inability to reconstruct the elastic network within the dermis
what is a scab formed from?
coagulated blood
what are the criteria for secondary intention?
wound edges are not apposed or apposition is not possible, large haematoma, infection, extensive loss of tissue, foreign
what are the differences in outcome for primary and secondary and why?
due to the more florid granulation tissue reaction there is more extensive scarring in secondary intention
what are the basics of secondary intention?
wound, covered by granulation tissue, contracting to form a scar
what other structures are similar to contractures from third degree burns?
oesophageal peptic strictures
how are contractures dealt with?
surgery and physiotherapy
how does healing occur after third degree burns?
repair - regeneration is not possible
why does scurvy lead to problems with wound healing?
scurvy is from a deficiency in vitamin C. Vitamin C is needed for collagen synthesis. Collagen is needed for wound healing
why do steroids impair wound healing?
they are immunosupressive and interfere with the formation of granulation tissue
why are keloid scars hard to treat?
once they are treated they can cause another
what is the basis of keloid scars?
can be genetically determines - after dermal injury there is excessive fibroblast proliferation and collagen production
what is callus formation?
during fracture healing there may be a new island of bone or cartilage made due to osteoblasts and fibroblasts resulting in a callus formation - this is an irregular woven structure
what replaces the callus formation?
lamellar bone which is stronger and is remodelled according to the stresses and strains on the body
how does cardiac healing occur?
the myocytes die and are replaced by fibrous tissue - repair
what do white areas on images of cardiac muscle represent?
granulation and scarring
what is a complication from a LT extensive MI?
transmural scar in the LV which results in a non-contractile cardiac aneurysm. Therefore instead of contracting the cardiac muscle keeps on distending and there is a saccular outpouch. This can fill with thrombus and cause further infarctions.
how is a haematoma formed in fracture healing?
haemorrhage within the bone from ruptured blood vessels within the bone marrow - provides a network or scaffold for repair
what is the process of fracture healing?
haematoma is organised, removal of necrotic fragments, osteoblasts then lay down disorganised woven bone (callus) , remodelling according to mechanical stress and replaced by lamellar ordered bone
what are the results of misalignment and what causes it?
caused by movement, interposed tissue or infection and the results are that it heals more slowly, poor functional result and increases the risk of degenerative disease in adjacent joints i.e. osteoarthritis
what is the risk of infection?
Slows healing and increases the risk of chronic osteomyelitis
what are pathological fractures?
fractures that have a primary disease of the bone or secondary involvement such as metastases and might need to be treated prior to sorting fracture
what are the supporting cells for neurons and how well differentiated are neurons?
the supportive cells for neurons are glial cells and neurons are terminally differentiated
what is gliosis?
proliferation of astrocytes, it occurs after an intracerebral haemorrhage as a cyst will be left due to removal of blood components and lysis
what controls healing?
complex network of cytokines
what happens initially after platelet aggregation at a wound site?
macrophage chemotaxis followed by cells at defect edges growing over
what stimulates granulation tissue formation?
epidermal growth factor
what are the functions of PDGF and TGF?
chemotaxis stimulation
what is the main function of TNF?
activates macrophages
what increases vascular permeability?
vascular endothelial cell growth factor
what is the function of transforming growth factor?
it replicates epithelial cells and hepatocytes
