MOD S5 - Healing & Repair Flashcards Preview

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Flashcards in MOD S5 - Healing & Repair Deck (32)
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What is fibrous repair?

-Fibrous repair is the replacement of functional tissue by scar tissue


What are the stages of fibrous repair?

Initial inflammation
Granulation tissue


What is granulation tissue?

A combination of capillary loops and myofibroblasts


Describe the initial inflammation stage of fibrous repair

Inflammatory cell infiltrate
Blood clot forms
Acute inflammation around edges
Chronic inflammation - macrophages and lymphocytes migrate into clot


Describe what occurs after the initial inflammation stage in fibrous repair

-Clot replaced by granulation tissue
-Key components - these initiate fibrous repair by combining to form granulation tissue formation:
>Cell migration
>Blood vessels - angiogenesis
>Extracellular matrix production/remodelling


Describe the maturation stage of fibrous repair

Comparatively long lasting
Cell population falls
Collagen increases, matures and remodels
Myofibroblasts contract, reducing volume of defect
Vessels differentiate and are reduced
Fibrous scar is end result


Describe control of fibrous repair

Poorly understood
Inflammatory cells recruited by chemotaxis
Angiogenesis occurs due to angiogenesis cytokines
Fibrosis occurs due to macrophages releasing pro-fibrotic cytokines causing fibroblast proliferation


Describe cell migration in fibrous repair

-Inflammatory cells
>Phagocytosis of debris - macrophages and neutrophils
>Chemical mediators - macrophages and lymphocytes
-Endothelial cells
>ECM proteins eg collagen
>Wound contraction


Describe angiogenesis in fibrous repair

-Proangiogenic growth factors eg VEGF induce endothelial proliferation
-Pre-existing blood vessels sprout new vessels
-Endothelial proteolysis of basement membrane
-Migration of endothelial cell by chemotaxis
-Endothelial maturation and tubular remodelling
-Recruitment of periendothelial cells


Describe the function of the extracellular matrix

Supports and anchors cells
Separates tissue compartments
Sequesters growth factors
Allows communication between cells
Facilitates cell migration


Describe regeneration

The replacement of dead or damaged cells by functional, differentiated cells which originate from stem cells


Briefly describe stem cells

Undifferentiated cells which can proliferate to produce either more stem cells in order to maintain the stem cell pool OR produce cells which can differentiate into a specialised cell type


What is the difference between uni potent, toti potent and pluripotent?

Uni potent cells can only differentiate into one type of cell eg epithelial cells
Pluripotent cells can differentiate into several types of cell eg haemopoietic cells
Toti potent cells can differentiate into any type of cell eg embryonic cells


Do all cells have the same propensity for regeneration

Labile cells regenerate fastest
Stable cells regeneration is variable
Permanent cells cannot regenerate


Describe and give an example of labile cells

Normal state is active cell division
Usually rapid proliferation
Eg epithelial or heamatopoietic cells


Describe and give an example of stable cells

Normal state is G0 so not active division
Variable speed of proliferation
Eg hepatocytes, osteoblasts, fibroblasts


Describe and give an example of permanent cells

Unable to divide
Unable to regenerate
Eg neurones, cardiac monocytes


What factors control regeneration?

Growth factors
Contact between basement membranes and adjacent cells


How do growth factors control regeneration?

Promote proliferation of stem cell population
Promote expression of genes controlling cell cycle
Hormones (oestrogen, testosterone, growth hormone)
Autocrine, paracrine and endocrine


How does contact between basement membranes and adjacent cells control regeneration?

Signalling through adhesion molecules
Inhibits proliferation in intact tissue by contact inhibition
Loss of contact promotes proliferation
Exploited in cancer


Describe healing by primary intention

Incised wound
Apposed edges
Minimal clot/granulation tissue
Epidermis regenerates
Dermis undergoes fibrous repair
Sutures out at 5-10 days. ~10% of normal strength
Maturation of scar continues up to two years
Minimal contracture and scarring, good strength
Risk of trapping infection/abcess


Describe healing by secondary intention

Infarct, ulcer, abscess or any large wound
Quantitative differences:
Unapposed wound edges
Large clot dries to form clot
Epidermis regenerates from the base upwards
Repair process produced a large amount of granulation tissue
Takes a long time to heal completely


Compare healing by primary and secondary intention

1ary is a small, clean wound whereas 2ndary is larger
2ndary produces much more granulation tissue
2ndary has more contraction to reduce the volume of the defect
2ndary leaves a larger (but not necessarily weaker) scar
2ndary takes longer to heal than 1ary


Discuss local factors affecting the efficacy of healing and repair

Type, size & location of wound
Apposition, lack of movement (skin/bone/nerve damage)
Blood supply (arterial & venous)
Infection (systemic, gangrenous)
Foreign material (dirt, glass, sutures, necrotic tissue)
Radiation damage


Discuss general factors affecting the efficacy of healing and repair

Drugs (eg steroids) and hormones
General dietary deficiencies eg protein
Specific dietary deficiencies eg vitamin c, amino acid
General state of health (chronic diseases eg diabetes)
General cardiovascular status


What may be a complication/failing of healing in cardiac muscle?

Fibrosis occurs
Aka functional muscle cells are replaces by non-contracting non-conducting scar tissue


What is a special aspect of healing in bone

Callus formed
(Read up on this - see TOB)


What is a special aspect of healing in the liver?

In chronic damage, cirrhosis occurs
In cirrhosis, hepatocytes retain some ability to regenerate but liver architecture is gone
This leads to nodules of regenerating hepatocytes surrounded by fibrotic scarring
Note: in acute damage regeneration occurs


What is a special aspect of healing in peripheral nerves?

Wallerian degeneration
Proximal degeneration, distal proliferation (~1mm/day)


What is a special aspect of healing in the CNS?

No regenerative capacity
Glial cells can regenerate (Gliosis)