0514 - Wound healing - AHF Flashcards
What is the extracellular matrix and why is it important?
It is the non-cellular component present within all tissues and organs, comprised of
- water
- fibrous proteins, e.g. collagens, elastins
- adhesive glycoproteins, e.g. fibronectins, laminins
- gel of proteoglycans and hyaluronan
It is important because it:
- provides form and structure
- retains water, giving tissue turgor (in “soft” tissues)
- retains minerals (in “hard” tissues)
- is a repository for growth factors
How do cells interact with and “attach” to extracellular matrix?
Cell adhesion occurs by focal adhesions (connecting the extracellular matrix to actin filaments of the cell) and hemidesmosomes (connecting the extracellular matrix to intermediate filaments like keratin); this adhesion is regulated by integrins (cell-surface proteins that bind cells to extracellular matrix structures and integrin proteins on the surface of other cells.
Outline the steps involved in tissue repair by fibrosis.
- angiogenesis (formation of new blood vessels; buds develop from existing vasculature; controlled via growth factors VEGF, TGF-β and local proteins (e.g. plasminogen activators, matrix metalloproteinases))
- fibroblasts migrate to the site, and then proliferate
- new extracellular matrix deposited (collagen, fibronectin)
- remodelling (maturation and organisation of fibrous tissues)
Normal wound healing has 4 main components, what are they?
- induction of an inflammatory response
- regeneration of parenchymal and connective tissue
- synthesis of extracellular matrix
- remodelling
Describe primary intention wound healing.
Days 1 - 3:
- fresh wound fills with thrombus
- surface clot dehydration forms a scab
- neutrophils migrate to the clot within 24 hours
- basal cells of adjacent epidermis start to divide and grow, depositing basement membrane components
- fibroblasts activated and start producing collagen and extracellular matrix (new tissue called granulation tissue)
- angiogenesis (aka neovascularisation)
Days 3 - 5:
- neutrophils largely replaced by macrophages
- epidermal regeneration and production of granulation tissue continue; an immature scar is formed by day 5
Week 2 onwards:
- fibroblast proliferation and collagen production continues
- inflammation, oedema and vascular proliferation subsides
- scar looks paler
Weeks to months:
- remodelling of the scar
How does healing by secondary intent differ from healing by primary intent.
- repair more complicated and takes longer
- subsequent function may be impaired
- more prominent scarring
- more fibrin and necrotic debris
- inflammatory response more intense
- more granulation tissue formed
What are some of the factors that influence wound healing?
- nutrition (e.g. protein deficiency, vitamin C deficiency)
- glucocorticoids (modifies inflammatory response, dulls induction of fibroplasia)
- infection
- mechanical factors (e.g. increased abdominal pressure due to bowel obstruction may result in wound dehiscence (wound rupture))
- individual variables (e.g. comorbidities)
- drugs
- radiotherapy
Describe some examples of abnormal wound healing.
Exuberant granulation (aka proud flesh): excessive granulation tissue protruding above the level of the skin; hinders epithelialisation Keloids: growth of extra fibrous tissue that forms smooth, hard growths that extend beyond the borders of the original wound Hypertrophic scars: growth of extra fibrous tissue that forms smooth, hard growths that do not extend beyond the borders of the original wound
What is fibrosis? List some examples.
Fibrosis is the formation of excess fibrous tissue in an organ or tissue; it can be a reactive, benign or pathological state. Examples include fasciitis (inflammation of the fascia; e.g. nodular fasciitis), fibromatosis (benign fibrous proliferations with a tendency for local recurrence; may be superficial or deep; e.g. Palmar fibromatosis (aka Dupuytren’s contracture).
Does an ulcer heal by primary or secondary intention?
Secondary, because it is a large tissue defect.
If a segment of a liver is donated to a child as a transplant, would the architecture of the liver ultimately be normal?
To a certain extent. Whilst the liver has incredible regenerative potential, that is, it can rapidly replace cells lost to disease, toxins (including alcohol) and senescence, these cells need a connective tissue “scaffold” (extracellular matrix) to cling to in order to preserve the normal architecture of the liver.
But if a region of the liver is removed then this scaffold goes too, meaning that there is nothing to guide regenerating cells to the correct locations and hence the regenerative capacity can be limited. Otherwise a liver damaged by cirrhosis ought to be able to grow a whole new liver alongside the shrunken damaged one, but this doesn’t happen.
For this reason removing a lobe of the liver - to cure a cancer or as a donor organ for instance - does not result in the regrowth of the excised lobe. Destroying some liver cells during a drinking binge, however, is repaired because the inert extracellular matrix persists and so new liver cells generated from local stem cells can take up the correct positions to restore the normal structure and function.
Is cirrhosis of the liver a picture of normal regeneration?
Cirrhosis of the liver is characterised by the replacement of hepatocytes by fibrotic tissue (fibrosis) and regenerative nodules, which can block the flow of blood through the liver. Because the hepatocytes are replaced by fibrotic tissue, not regenerated hepatocytes, the process of cirrhosis is not considered normal regeneration, it is instead liver deterioration.
In tuberculosis of the lung, following treatment, is the lung parenchyma normal or abnormal?
If not treated early enough, fibrotic tissue may remain.
In tuberculosis of the lung, as seen on x-ray, what tissue does a Ghon focus represent?
A Ghon focus is calcified/fibrotic lung lesion.
Following major surgery, would stitches be left in situ longer in a diabetic patient than another patient of the same age?
Yes, diabetes delays wound healing; hyperglycaemia leads to osmotic diuresis and subsequent decreased oxygenation and perfusion
