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Path - Acute inflamm (ii) (Chemical Mediators (vasoactive amines…
Path - Acute inflamm (ii)
Chemical Mediators
tightly regulated
plasma-derived
circulating prescursors that must be activated
cell-derived
sequestered (hidden) intracellularly, synthesised de novo
most bind to cell surface Rs, some have direct enzymatic/toxic activity
vasoactive amines
cause vasodilation + leakage
histamine
in mast cells, platelets + basophils
released in response to stimuli
causes art dilation, ven contraction
widens cell junctions + increases permeability
serotonin
in platelets
released when platelets aggregate
similar effects to histamine
plasma proteases
Complement
classical activation via antigen-Ig complex, then C1 binds
alternative activation via microbial surface
MAC C5-9 forms pore in pathogen membrane (lysis)
C3a + C5a together air vasc permeability + vasodilation
C3b = opsonin
C5a aids leucocyte activation, adhesion + chemotaxis
Kinin
cascade, leads to bradykinin formation
increased vasc permeability
art dilation
non-vasc smooth muscle contraction
pain
short-lived (inactivated by kininase)
Clotting
factor 12 (Hageman factor) = key to activation
fibrin formation
Phospholipid-derived products
arachidonic acid metabolites
AA = component of cell membrane phospholipids
released from membrane via phospholipase A2 (inhibited by steroids)
metabolised via COX (inhibited by aspirin + NSAIDs) to PGs + prostacyclin (PGI2)
metabolised by LOX to LTs
participate in every form of inflamm
PGE2 causes fever, pain, vasodilation + increased permeability
PGD2 causes vasodilation + increased permeability
PGI2 causes vasodilation, permeability + inhibits platelet aggregation
LTB4 attracts + activates neutrophils
LT C4+D4+E4 cause vasospasm, bronchospasm + increased permeability
thromboxane A2 causes vasoconstriction + platelet aggregation
PAF induces platelet aggregation, vasoconstriction, bronchoconstriction, leukocyte adhesion, chemotaxis, degranulation (antimicrobial substances released from host cell vesicles
CKs
short-acting soluble mediators
produced by many cells
multifunctional systemic effects
NO
toxic to bacteria
causes vasodilation + tissue damage
lysozymes
eradicate bacteria
cause tissue damage
Inflamm disadvantages
impaired function
tissue destruction
mechanical effect (e.g. epiglottitis narrows airway)
impaired flow (e.g. acute meningitis inflamm activates haem system, leading to tiny thrombi)
Outcomes of acute inflamm
resolution - healing + repair
abscess formation (walled off pus collection)
progression to chronic
Inflamm benefits
toxin dilution
pathogen destruction
debris removal
aids transport of nutrients, O2, Igs + drugs to site in injury
fibrin delays bacterial spread
stims immune system
bacterial products aid chemotaxis
Pyrogens
cause macrophages to release IL1 + TNF
increase COX activity on pervasc cells of hypothal to produce more PGE2
resets thermostat - fever