*Pathology (2) Flashcards
Why are mediators of inflammation short lived?
They are only produced as long as the stimulus is present
How long do neutrophils survive outside of a blood vessel?
A couple of hours
What are the 4 possible sequels after acute inflammation`?
Resolution Suppuration Repair, organisation, and fibrosis Chronic inflammation *may not be mutually exclusive
what does what one of the 4 possible sequels of inflammation that occurs depend upon? (3)
Site of injury (different organs have different capacities for repair and different vascular supplies)
Type of injury (severity, pathogenicity of organism)
Duration of injury (can be removed, is it sustained)
What is resolution?
Complete restoration of the tissue to normal after removal of inflammatory components
How much cell death occurs with resolution?
Minimal amounts
What kind of tissues does resolution occur in?
Tissues that have capacity to repair e.g GI tract
Tissues that have a good vascular supply for delivery of WBCs and removal of injurious agents
What is suppuration?
Formation of pus
What is pus formed from?
Living, dying and dead cells (neutrophils, bacteria and inflammatory debris (fibrin))
What is an abcess?
Collection of pus
What is an empyema?
A collection of pus in a body cavity
When does repair occur
When a tissue is injured and cannot be wholly regenerated
What are the 3 phases of repair?
Phagocytosis to clear debris
Organisation
Epithelial regeneration to cover wound
When does repair occur in contrast to resolution? (4)
When injury produces lots of necrosis
if injury produces a lot of fibrin that isn’t easily cleared
if there is a poor blood supply = difficulty removing debris
Mucosa where damage goes beyond the basement membrane favours healing by organisation and repair and not resolution (substantial tissue damage meaning the tissue is unable to regenerate and is instead replaced by fibrous tissue - resolution occurs a scaffolding to occur)
What is organisation?
Fibroblasts secrete ECM and new vessels grow into region -> formation of granulation tissue
What happens in granulation tissue formation? (organisation)
Defect is slowly infiltrated by capillaries and then by myofibroblasts
Deposit collagen and smooth muscle cells
Has a very red look
What is fibrosis?
Formation of excess fibrous connective tissue in an organ/ tissue in a reparative/ reactive process
If this is in response to injury it is called scarring
“patch job”
Causes a loss of function
When does scarring and fibrosis of the liver occur?
Liver can regenerate but if overwhelmed it undergoes scarring and fibrosis = cirrhosis resulting in liver failure
When is chronic inflammation favoured?
Suppuration
Persistence of injury e.g. foreign material
Persistence of infection
type of injury e.g. autoimmune, transplant rejection
What is chronic inflammation characterised by?
Lymphocyte
Macrophage (monocyte within tissue)
What is a granuloma?
A collection of immune cells known as histiocytes
“aggregate of epithelia histiocytes”
What is a histiocyte?
A stationary phagocytic cell present in connective tissue
When does a granuloma form?
When the immune system attempts to wall off substances it perceives as foreign but is unable to eliminate
e.g. endogenous - keratin, bone, crystals
Exogenous - talc, asbestos, suture materials, oil
What are some examples of diseases that cause granulomas?
Specific infections Parasites Worms Eggs Syphilis Mycobacterium - including TB
What is “cheesy necrosis”?
Tuberculous granulomas - caseous necrosis
What is an infarction?
Death of tissue after loss of oxygen
Why does muscle need O2?
To produce ATP for energy required to contract
What happens if a cell has no ATP?
Na/K ATPase fails = increased K = swelling
Calcium pump fails = increased intracellular calcium
Increased calcium stimulates:
ATPase (makes things worse)
Phospholipase (membrane damage)
Proteases (membrane and cytoskeleton damage)
Endonuclease (DNA damage and breakdown)
Mitochondrial permeability (release pro death factors)
What is the time frame for the myocardium being without oxygen but only causing reversible damage?
20 minute window
Why is there no point in using clot busting drugs after 30 minutes for clot causing loss of blood supply to myocardium?
After 20 minutes there is non-reversible injury - the cells will die anyway
After 20 minutes of loss of blood supply to myocardium, would you see any changes at autopsy?
No however do see changes on ECG
What happens after the 20 minutes window for the myocardium?
Cell death due to hypoxic injury - pathological and results in necrosis
What are the first signs of a hypoxic injury to the myocardium? (4)
Cells shrink due to being pygnosis
Become red
Nucleus shrinks and becomes dark
Marginal contraction bands appear
What is pygnosis?
the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis
What is contraction band necrosis?
type of uncontrolled cell death (necrosis) unique to cardiac myocytes
What happens in the first 24 hours of hypoxic injury to the myocardium?
Cell contents leaked
Complement cascade initiated
acute inflammation -vascular changes
What is pavementing?
A condition occurring during inflammation in which leukocytes adhere to the linings of capillaries.
What is diapedesis?
the passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation
What is the cell associated with acute inflammation?
Neutrophils
What is the functions of neutrophils? (2)
Phagocytic properties (mop up dead cells) Cytokine production
What is necrosis?
Cell death usually due to inadequate blood supply
What are the 3 main types of necrosis?
Caseous
Liquefactive
Coagulative
What is coagulative necrosis?
Cell death with some structure of cells left as “ghost outline” before complete phagocytosis of materials
When necrosis is full thickness, what may all that holds the heart wall together?
Necrosis
Neutrophils
What is the risk associated with necrosis of the heart muscle?
What time frame is this most likely to occur in?
Risk of cardiac rupture
Greatest at 3-7 days
What are the next possible phases after acute inflammation of the myocardium?
Suppuration? - no, as there is no persistence of injury and if there is then death usually occurs
therefore chronic inflammation usually occurs with either:
Repair, organisation and fibrosis (restitution)
Resolution
What happens to the neutrophils in the cardiac muscle as time progresses?
What can be seen at autopsy at this point?
Neutrophils fade away and are gradually replaced by macrophages
The presence of macrophages causing a yellow appearance (microscopically macrophages are seen)
when does resolution of the myocardium occur?
Resolution occurs when the injury has a short duration and if the injury is mld and the blood supply is good
In an MI the blood supply is poor
Generally once cell death has occurred then resolution is unlikely in the heart
What happens during restitution of the heart?
Gradual process
Progressive scarring
Macrophages fade away and are replaced by fibroblasts
Fibroblasts lay down collagen
When does restitution occur after an MI?
Occurs progressively after 2 weeks and is complete at 6 weeks
Therefore if an MI occurred more than 6 weeks ago we can’t date it
What are 2 examples of complications that occur post-MI due to scarring of the heart?
Heart failure (loss of muscle = reduced pumping ability) Arrhythmia (damage of pacemaker system)
