topic 4: inflamation Flashcards
fyi: when does inflammation happen and what is the purpose
purpose: it is a protective response intended to eliminate the initial cause of cell injury and then remove necrotic (dead) cells and tissue resulting from the original insult
how it protects: dilute/destroy or neutralise harmful agents by extending the defence of the blood out into the tissues (blood cells, plasma proteins will come out from teh blood and then go cell injury area)
fyi
definition of inflmation
denoted by -itis
definition: a complex progression of blood vascular and tissue change that deveops in responseto tissue injury
inflammatory reaction and subsequent repair process can cause harm if
- uncontrolled: severe/prolonged inflammatory rn (eg harmful agent resists irradication)
- inappropriate: inflammatory cells and molecules (antibodies, immune cells) target self- antigens
inflammatory and repair process can be excerbated by further tissue damage or introduction of infection (eg self trauma)
difference between acute and chronic inflammation
period of onset:
acutre: rapid, chronic: gradual (persistant inflmmatory response for longer than 10-14 days, up to a yr or more)
cells invloved/visible microscopically:
acute: predominantly neutrophils (in fluid and plasma protein exudate- fluid from blood vessel high conc in plasma protein) chronic inflammmation (predominantly mononucleur cells: plasma cells, lymphocytes and macrophages: they come later after initial (acute) respose)
characteristic appearance:
acute: usually exudative ( protein rich fluid coming from blood to surrounfing damaging tissues)
chronic: usually not exudative (usally no exudative phase) ( invloves tissue destruction and repair ( vascular proliferation and fibrosis)
difference between acute and chronic inflmaation: period of onset
acute: rapid onset
chronic: gradual onset
difference between acute and chronic inflmaation: duration of inflammation
acute: shorter duration (mins-few days)
chronic: longer durations (days-yrs)
difference between acute and chronic inflmaation: cells invloved/visible microscopically
acute: predominantly neutrophils (can be found in fluid and plasma proteins exudate)
chronic: mononuclear cells: plasma cells, lymphocytes, macrphages
difference between acute and chronic inflmaation: characteristic appearance
acute: usually exudative(escape of protein rich fluid from the blood to surrounding damage tissues)
chronic: usually not exudative. involves tissue destruction and repair (vasular proliferation and fibrosis)
aim of acute inflmmation
rapidly contain, dilute and remove harmful stimulus bu delivering immune cells and plasma proteins to site of injury + prepare tissur for repair
fyi
causes of acute inflmmation
bacterial infection
trauma (cuts)
foreign bodies
immune reaction (hypersensitivty, eg autoimmune disease-> can cause chronic inflammation)
tissue necrosis (death due to ischemia/physical/chemical injury)
what happens after acute inflamation
- harmful stimulus removed-> anti-inflmmatory mechanism kicks its (to stop inflammation, no need anymore cos remove alr), acute inflamation subsides and tissue returns to its normal state of function
- harmful stimulus persists-> acute inflmmation progresses to chronic inflammation
what are the five cardinal (most noticable signs) signs of acute inflammation
1.redness
2.heat
3.swelling
these three are due to vascular changes and cellular recruitment
4.pain
5.loss of function
these two is due to mediators of inflammation and leukocyte mediated damage
what are the three phases acute inflamation (local effect)
- vascular phase
- exudative phase
- cellular phase
describe the three phases of acute inflmmation
- vascular phase (changes in blood vessel diameter) : arteriole vasodilation-> locally increased blood flow-> engorgement of downstream capillary bed ( sweeling of capillaries after major arterioles) also known as hyperaemia.
-takes few minutes to days (causes cardinal signs: redness and heat) - exudative phase- escape og fluid from blood surrounding extravascular tissue
direct damage of endothelial cells lining the capillaries or contraction of the endothelial cells of the capillary lining-> causing increased vascular permeability
gaps form in capillary wall between the endothelial cells-> allow escape of protein rich fluid (containing RBC,platelets, plasma protein, water, electrolyte) into the surrounding tissue. - cellular phase- recruitment of leukocyes-primarily neutrophils, to site of injury
4
leukocytes are activated to 1.ingest and kill bacterial at the site of the injury,2. remove dead/dying cells and foreign substances 3. direct other cells of the imflmmatory preocess to the site
they may also injure normal host tissues surrounding the the site of teh injury (releaase enzymes to destroy, nomrla cells near injury also get digested- thats why chronic inflmation, persistant this process cause fibrosis aka scaring)
leukocyts recruited and activated at sites of injry perform these functions:
1. phagocytosis
2. produce sybstance that destroy phagocytosed microbes and dead tissues (lysosomal enzymes, proteases)
3. produce more mediators to amplify the inflmatory reactions (eg cytokines)
fluid exudate may become cellular exudate if more leukocytes migrate to the site of injury
describe the vascular phase of acute inflammation
vascular phase (changes in blood vessel diameter) : arteriole vasodilation-> locally increased blood flow-> engorgement of downstream capillary bed ( sweeling of capillaries after major arterioles) also known as hyperaemia.
-takes few minutes to days (causes cardinal signs: redness and heat)
describe the exudative phase of acute inflammation
exudative phase- escape og fluid from blood surrounding extravascular tissue
-direct damage of endothelial cells lining the capillaries
or
contraction of the endothelial cells of the capillary lining-> causing increased vascular permeability
gaps form in capillary wall between the endothelial cells-> allow escape of protein rich fluid (containing RBC,platelets, plasma protein, water, electrolyte) into the surrounding tissue.
current cardial signs: redness and heat (from vascuar phase), swelling (from exudative phase)
describe the cellular phase of acute inflammation
leukocytes are activated to
1.ingest and kill bacterial at the site of the injury,
2. remove dead/dying cells and foreign substances
3. direct other cells of the imflmmatory preocess to the site
they may also injure normal host tissues surrounding the the site of teh injury (releaase enzymes to destroy, nomrla cells near injury also get digested- thats why chronic inflmation, persistant this process cause fibrosis aka scaring)
leukocyts recruited and activated at sites of injry perform these functions:
1. phagocytosis
2. produce sybstance that destroy phagocytosed microbes and dead tissues (lysosomal enzymes, proteases)
3. produce more mediators to amplify the inflmatory reactions (eg cytokines)
fluid exudate may become cellular exudate if more leukocytes migrate to the site of injury
current cardinal signs: redness, heat (from vascular phase), swelling (from exudative phase) , loss of function and pain (sustances used to destroy phagocytosed microbes and dead tissue also destroying normal cell)
why do endothelial cells contract
inflammatory/immune cell eg mast cells, lukocytes are stimulatedf, they release chemical mediators (histamine) that are stored in intracytoplasmic granules.
these chemical mediators bind to receptors on the endothelial surface and cause them to contract, resulting in gaps between endothelial cells
gaps are so large that proteins (albumin, globulin, fibrinogen) can now escape into the tissues.
what are the differrent types of acute inflmmation
1.serous inflmmation
2. fibrinous inflmmation
3.suppurative inflammation
serous inflmmation
serous effusion in serious cavity
outpouring of watery, protein-poor fluid from serum or secretions of mesothelial cells (lining serous cavity-fluid filled space-eg pleural cavity)
eg, burns, blisters
fibrinous inflammation
more severe injury (more than serous) resulting in greater vascular permeability-> large molecules eg fibrinogen able to pass endothelial lining of capillaries.
extravascular fibrin accumulates, appearas as eosinophillic (opink) meshwork of threats or amirphous (lack definitive shape) coagulum (when fibrinogen becomes fibrin- solidifies)
suppurative inflmation
presence of pus/large amounts of purulent exudate (yellow/green fluid produced by body in response to infection/inflammation-think pimple) –>consists of neutrophils, necrotic cell,edema fluid (fruid due to increase vascular permeability)
eg ulcers( tissue necrosis and inflmation occuring at/near the surface
absess (eg bac inside tissue-pus inside)
review of neutrophil in inflmmation
-Characteristic of acute inflammation.
-Segmented nuclei, intracytoplasmic granules containing antimicrobial factors and enzymes (eg. proteases).
-Short lifespan and dies in the process of attacking bacteria.
-First defence against invading microbes and involved in initial removal of dead tissues.
-Motile (moving to site of injury) – attracted to site of injury by chemical mediators (eg cytokines)
what are the steps for recruitment of leukocytes- mainly neutrophils
- margination, adhesion, rolling
- firm adhesion to vessel wall
- transmigration between endothelial cells
- migration in extravascular tissue to site of damage
what is the local effect of acute inflmmation (at the site of injury)
recruitment of leukocytes
describe 1. marginating, adhesion and rolling dtage of neutrophil recruitment
-exudation of fluid into extravascular(outside vessles) tissues cause RBC to become more concentrated, blood viscosity increases (more thick-cos less fluid, more RBC), circulation slows down (stasis)
smaller RBC move faster than larger leukocytes. leukocytes are pushed towards the vessle wall due to laminar flow.
leukocytes tumble along the vessle wall, transeintly (temporarily) sticking along the way
describe 2. firm adhesion to vessel wall
chemoattractants cytokines (chemokines) secreted by cells at site of injury activates the leukocytes that are rolling along the vessle wall
activated leukocytes adhere more firmly to vessel wall near site of injury (cos theres where the chemokines are reelased)
describe 3. transmission between endothelial cells
leukocytes stop and squeeze through the intracellular junctions of endothelial cells
describe 4. migration in extravascular tissue to site of damange
leukocytes travel through extravascular tissues until they reach the site of damange
leukocytes are attracted to the site of injury by substances produced by bacteria (eg LPS) , complement proteins (cytokines) and other mediators producedin response to tissue damage and immunological reactions.
describe the process of leukocyte recruitment (neutrophil)
(1) Margination, adhesion, rolling
* Exudation of fluid into extravascular tissues causes RBCs to become more concentrated, blood viscosity increases, circulation slows down (stasis).
* Smaller RBCs move faster than larger leukocytes. Leukocytes are pushed towards the vessel wall due to laminar flow.
* Leukocytes tumble along the vessel wall, transiently sticking along the way.
(2) Firm adhesion to vessel wall
* Chemoattractant cytokines (chemokines) secreted by cells at site of injury activate the leukocytes that are rolling along the
vessel wall.
* Activated leukocytes adhere more firmly to vessel wall near site of injury
(3) Transmigration between endothelial cells
* Leukocytes stop and squeeze through intercellular junctions of endothelial cells.
(4) Migration in extravascular tissues to site of damage
* Leukocytes travel through extravascular tissues until they reach the site of damage.
* Leukocytes are attracted to site of injury by substances produced by bacteria, complement proteins and other
mediators produced in response to tissue damage and immunologic reactions.
what are the systemic effect of acute inflmmation (affecting entire body)
- increased body temp
(Chemical mediator of inflammation circulating in blood and acting on temperature regulatory centres in brain)
2.Changes in blood: increased production & release of neutrophils; anaemia
- Neutrophils are the predominant leukocytes activated in acute inflammation.
- Chemical mediators of inflammation can inhibit RBC production by bone
marrow. (both produced in bone marrow- BM priritising neutrophil production to RBC production)
3.Pain
- Chemical mediators of inflammation (cytokines) and contents of intracytoplasmic granules of neutrophils stimulate nerves.
- Fluid accumulation results in pressure on tissue components and nerves.
4.Depression, malaise (discomfort, weak) , anorexia, nausea
-Effects of pain or chemical mediators on brain.
5.Muscle pain
-Chemical mediators (cytokines, proteases) breakdown muscles.
6.Weight loss
- Effects of chemical mediators on appetite centres of brain.
- Muscle breakdown.
- Loss of appetite due to nausea, anorexia, pain.
i c pd wm ( i see pdiddy liking men and women)
what are the systemic effects of acute inflammation
i c pd mw
1.increase body temp
2.changes in blood- increased production and release of neutorphils, anemia
3.pain
4.depression, malaise, anorexia, nausea
5.muscle pain
6..weght loss
what are the harmful effects of acute inflammation
EESSSI
- excessive tissue damage
- severe systemic effects
- excessive loss of serum
- severe fibrin exudation
- supperative exudate
- inflammation of vessel wall
harmful effects of acute inflmation
- excessive tissue damage:Normal tissues surrounding site of injury may be digested by enzymes released by activated
neutrophils (eg. proteases) - severe systemic effects: severe loss of appetite, pain and wight loss
- excessive loss of serum: (serum exudate) causes marked swelling, pain (pressure on nerves) irritation(due to heat/pain) (self-trauma- causes more serum to come of blood). May result in shock if fluid loss is severe.
- severe fibrin exudation: Formation of fibrous scar tissue at site of injury can damage or hinder normal
function of organ. - Suppurative exudate
* Suppurative exudate becomes walled off by fibrous tissue, forming an abscess. Anabscess that bursts internally can lead to septic peritonitis/pericarditis/septic shock. - Inflammation of vessel walls
* Cause excessive leakiness of blood vessels, resulting in excessive blood loss, inappropriate clotting of blood and impair blood supply (ischaemia, infarction)
esssi
outcomes of acute inflmmation depends on
- nature and intensity of injury
- Site and tissue affected
- Ability of host to mount a response
what are the three main outcomes from acute inflammation (sequelae)
- resolution
- progression to chronic inflmmation
- scaring or fibrosis
(healing of pus/absess formation can also results in fibrosis)
(healing of chronic inflmamation also can cause fibrosis)
what is resolution refer to and impact
Type of injury: trauma, bacterial infections, toxin
* Injury is limited or short-lived, with minimal/no tissue damage, and tissue is capable of replacing
any irreversibly injured cells.
* Restoration to histologic and functional normalcy
proegression to cronic inflmmation
Harmful stimuli is not removed (eg. autoimmune disease), too large or persistent injury, affected
tissues are unable to regrow.
End result: usually result in scarring, but may also restore normal structure and function
scaring or fibrosis
Substantial (significant) tissue destruction, or when tissues do not regenerate.
* Increased vascular permeability → results in severe fibrin exudate or extensive neutrophilic
infiltrates
