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89 Cards in this Set

  • Front
  • Back
what three things occur with vascular changes in the inflammatory response?
1) vasodilation
2) increase permeability of vasculature by forming endothelial gaps
3) stasis (slowing blood flow in relevant area)
what three players are relevant with cellular changes in the inflammatory response?
1) circulating and resident local tissue cells
2) circulating leukocytes
3) resident immune cells (macrophage, etc.)
what 5 events occur that are considered the cardinal features of acute inflammation?
1) rubor (redness)
2) tumor (swelling)
3) calor (heat)
4) dolor (pain)
5) functio laesa (loss of function)
what are the two types of edema?
1) transudate
2) exudate
transudate
filtrate of plasma caused by abnormal increase in hydrostatic pressure (blood pressure) or decrease in plasma oncotic pressure (osmotic pressure exerted by proteins in the blood that pull water into circulation)
what is transudate not associated with?
not inflammation
not increased vascular permeability. very few WBCs in transudate
exudate
inflammatory edema resulting from increased in blood vessel permeability. high WBC, higher specific gravity
what causes exudate?
1) vascular flow changes
2) vascular permeability changes
what are the steps of vascular flow change associated with acute inflammation exudate?
1) immediately arterioles vasoconstrict for a few seconds
2) vasodilation occurs because of prostaglandin stimulation
3) combination of (1) and (2) increase blood flow
what are the basic steps of vascular permeability change associated with acute inflammation exudate?
1) increase in microvasculature
2) exudate moves into surrounding tissue
3) concentrated blood left after exudate moves out of circulation undergoes stasis
what are the mechanisms involved in increased vascular permeability?
1) formation of endothelial gaps in venules
2) direct endothelial injury that causes necrosis and detachment
3) leukocyte-mediated endothelial injury
4) increased transcytosis
5) leakage from new blood vessels
how is the formation of endothelial gaps in venules accomplished when trying to achieve an increase in vascular permeability?
endothelial cells contract leaving gaps between adjacent cells.
this is the first response and only lasts for 30 minutes
what is known as the immediate, transient response in regard to vascular permeability?
formation of endothelial gaps in venules
what chemical mediators contribute to the formation of endothelial gaps in venules?
1) histamine
2) bradykinin
3) leukotrienes
how is the direct endothelial injury accomplished when trying to achieve an increase in vascular permeability?
cells are damaged by burns, severe bacterial trauma, chemicals/toxins and necrotize leaving behind massive holes
what is known as the immediate, sustained response in regard to vascular permeability?
direct endothelial injury
how is the leukocyte-mediated endothelial injury accomplished when trying to achieve an increase in vascular permeability?
mainly occurring in venules, leukocytes adhere to endothelial cells and become activated releasing proteolytic enzymes and ROS that cause injury
how is increased transcytosis accomplished when trying to achieve an increase in vascular permeability?
increase in endothelial cytoplasmic channels allow transcytosis. VEGF (vascular endothelial growth factor) is the major contributor
how is leakage from new blood vessels accomplished when trying to achieve an increase in vascular permeability?
new blood vessels are inherently leaky. new blood vessels are formed (angiogenesis) when inflammation occurs in order to increase overall vascular permeability and increase exudate at tissue site of inflammation.
inflammatory mediators general definition
increase blood flow that allow increased exudate
what are steps involved in extravasation?
1) adhesion
2) transmigration
3) chemotaxis
4) leukocyte activation
5) phagocytosis
margination
when stasis occurs, WBCs stock on the periphery of blood vessels which promotes adhesion during extravasation
what 4 families of cell adhesion molecules assist in extravasation?
1) integrins
2) Ig superfamily (ICAM-1, ICAM-2)
3) selectins
4) mucin-like glycoproteins
what 3 mechanisms are involved in leukocyte adhesion?
1) redistribution of adhesion molecules from cytoplasm to cell surface
2) induction of adhesion molecule synthesis
3) increase binding affinity of adhesion molecules
what are the names and function of the most important leukocyte adhesion molecules?
P-selectin, E-selectin = rolling adhesion
ICAM-1, VCAM-1 = arrested adhesion
PECAM = diapodesis and leukocyte migration
how is redistribution of adhesion molecules from cytoplasm to cell surface accomplished in the leukocyte adhesion process?
chemical mediators like histamine or thrombin stimulate expression.

ex. Weibel-Palade bodies store P-selectin and when histamine or thrombin stimulate these cytoplasmic bodies, they release P-selectin to be expressed on the cell surface
Weibel-Palade bodies
P-selectin containing granules that will release P-selectin when stimulated by histamine or thrombin to be expressed on the lumenal surface of a vascular endothelial cell
how is the induction of adhesion molecule synthesis accomplished in the leukocyte adhesion process?
ex. inflammatory chemical mediators like IL-1 and TNF induce the synthesis of E-selectin which will be expressed to slow down neutrophil rolling
how is the increase of binding affinity of adhesion molecules (integrins) accomplished in the leukocyte adhesion process?
ex. inflammatory chemical mediators like chemokines bind the leukocyte which induce conformational changes of adhesion molecules, which create higher affinity for binding molecules such as LFA-1:ICAM-1
how do chemoattractants cause leukocyte movement?
1) chemoattractants bind receptors on leukocytes
2) which activates intracellular phospholipase C
3) intracellular calcium levels increase
4) pseudopod formation in direction of chemoattractant caused by cross-linking of actin
5) cell moves in direction of pseudopod
6) pseudopod degrades
7) next closest chemoattractant causes process to repeat
what 5 essential chemoattractant stimulation steps are required for leukocyte activation at ground zero?
1) arachidonic acid metabolites are produced by leukocyte
2) degranulation and release of lysosomal enzymes
3) oxidative burst activated within leukocyte
4) secretion of cytokines by leukocyte
5) increased binding affinity of adhesion molecules
what are the three steps in phagocytosis?
1) recognition and attachment (opsonins, macrophage receptors)
2) engulfment (formation of phagosomes)
3) killing and degradation (oxygen-dependent and oxygen-independent)
why are neutrophils considered sloppy?
mid-engulfment, sometimes lysosomal contents are released into the environment before phagosomal vessicle closes
what is sequence of particles released into the tissue following acute injury?
1) edema
2) neutrophils
3) monocytes -> macrophages if extended (+2 days) inflammation is occurring
where do chemical inflammatory mediators originate from?
liver synthesized plasma residing or secreted from cells
amplification
several generations of mediator generated release of mediators increasing effect
histamine
generated and stored in mast cells causing vasodilation, vascular permeability, redistribution of P-selectin in endothelial cells, hallmark chemical mediator for inflammation
serotonin
derived from platelets with identical action as histamine
what are the two vasoactive amine chemical inflammatory mediators?
1) histamine (mast cell derived)
2) serotonin (platelet derived)
3 plasma protein systems?
1) complement system
2) kinin system
3) clotting system
what 3 main things does complement do in inflammatory response?
1) produces opsonins
2) produces chemotaxins and anaphylotoxins
3) lysis by MAC
complement-generated vasodilators and permeability increasing agents
C3a, C5a
complement-generated potent chemoattractant
C5a
complement-generated opsonin
C3b
kinin system activating agent
release of Factor XII (Hageman Factor) occurs when tissue damage occurs which in turn initiates the kinin and clotting systems
kinin system products
1) bradykinin - increases permeability, pain causing mediator
2) kallikrein - increases bradykinin production
clotting system activating agent
release of Factor XII (Hageman Factor) occurs when tissue damage occurs which in turn initiates the kinin and clotting systems
clotting system product
1) thrombin (factor IIa) - binds to PARs to increase inflammation, increases redistribution of P-selectin, increases production of prostaglandins, platelet activating factor and nitric oxide
what is the general role of prostaglandins, platelet activating factor and nitric oxide and what do they all have in common?
production of all three are stimulated by thrombin release in the clotting system and are all inflammatory chemical mediators
arachidonic acid metabolites (eicosanoids)
produced by leukocytes, platelets, endothelial cells and expressed in cell membranes and attached to phospholipids. metabolism of AA fuels cyclooxygenase and lipoxygenase pathways.
how does the anti-inflammatory effect of steroids work?
steroids inhibit phospholipases that cleave arachidonic acid metabolites (eicosanoids) from leukocyte membranes preventing their metabolism in the cyclooxygenase and lipoxygenase pathways (which would normally produce inflammatory inducing chemical mediators)
Cyclooxygenase pathway products
prostaglandins (all are pain and fever inducing):
1) prostacyclin (vasodilator)
2) thromboxane A2 (vasoconstrictor)
3) PGD2, PGE2, PGF2 (vasodilator)
what are the two pain causing chemical mediators of inflammation?
bradykinin
prostaglandins
how do aspirin and NSAIDs reduce inflammation?
inhibits cyclooxygenase pathway
Lipoxygenase pathway products
leukotrienes, lipoxins:
1) Leukotriene B4 (chemoattractant)
2) Leukotriene C4, D4, E4 (permeability, vasoconstriction)
3) Lipoxins A4, B4 (anti-inflammatory)
Platelet activating factor (PAF) function
chemoattractant, permeability, promotes synthesis of other chemical mediators
Cytokines
1) IL-1, TNF (leukocyte adhesion, fever, sleep, prostaglandin synthesis)
2) IL-8 (chemokine)
endogenous pyrogens
IL-1, TNF
NO (nitric oxide) origin and function
produced by endothelial cells and macrophages:
1) vasodilator by relaxation of smooth muscle surrounding blood vessels
2) combines powers with ROS
major vasodilators
prostaglandins, histamine, NO
fever inducers
IL-1, TNF, prostaglandins
pain inducers
prostaglandins, bradykinin
tissue damaging agents
neutrophil and macrophage lysosomal enzymes, oxygen metabolites, NO
edema causing mediators
vasoactive amines, C3a, C5a, bradykinin, leukotrienes C4/D4/E4, PAF, substance P
chemotaxis (chemoattractants)
C5a, leukotriene B4, TNF, IL-1, bacterial products
4 outcomes of acute inflammation
1) resolution
2) abscess formation
3) healing (regeneration, scarring)
4) chronic inflammation
resolution with regeneration details
only happens with short-lived injury with little major tissue destruction where tissue returns to normal morphology and function
resolution with scarring details
happens when substantial tissue destruction has occurred past point of regeneration, connective tissue replaces what used to be residual tissue
serous inflammation
plasma filtrate accumulates at site of inflammation that leads to blistering
fibrinous inflammation
acute inflammation where injury is serious enough to where large molecules can pass into tissue, such as fibrinogen. ex. fibrinous pericarditis
ulcers
local defect of inflammed tissue where irritated tissue sloughs off and leaves and open wound
suppurative or purulent inflammation
acute inflammation that is pus producing and usually produces and abscess
abscess formation
neutrophils within pus secrete enzymes that digest and destroy tissue (liquefactive necrosis). band of neutrophils surround cavity filled with pus and dead microorganisms.
outcome of abscess
cavity can collapse and form a scar or if it doesn't collapse, then microorganisms may burst from abscess and go septic
chronic inflammation
prolonged duration lasting over 48 hours which causes prolonged, ongoing tissue damage
how can you have chronic inflammation without acute inflammation?
3 ways:
1) persistent infections by certain microorganisms
2) prolonged exposure to toxins
3) autoimmune disease
chronic inflammation by persistent infections by certain microorganisms examples and reason that it does not cause acute inflammation
Mycobacterium tuberculosis, Treponema pallidum (syphilis), fungi, viruses, parasites exhibit low toxicity that won't cause acute, but over time will cause chronic
chronic inflammation by prolonged exposure to toxins examples
1) coal miner's lung
2) atherosclerosis due to persistent hypercholesterolemia
chronic inflammation by autoimmune diseases examples
1) RA
2) SLE
characteristics of chronic inflammation
1) macrophages instead of neutrophils
2) tissue destruction by macrophages
3) scarring and fibrosis
positive feedback loop with macrophage stimulation
macrophage releases IL-12 which stimulates T cells which release IFN-gamma which stimulates macrophage
granulomatous inflammation
inflammation due to granulomas
granuloma general definition and types
focal aggregate of macrophages
1) immune granuloma
2) foreign body granuloma
immune granuloma forms how?
1) macrophage phagocytose a substance that cannot be degraded (Mycobacterium tuberculosis, Treponema pallidum (syphillus)
2) indigestible substance is immunogenic so it induces a T cell response and macrophage transforms into epitheloioid cells
components of immune granuloma
1) epithelioid cells
2) Langhans-type giant cell (peripherally organized multi-nucleated macrophage c-c-c-combo!)
3) necrosis
4) lymphocyte, plasma, fibroblast collar around (2)

(pic)
foreign body granuloma forms how?
foreign body cannot be phagocytosed because it is too large, so macrophage will recruit macrophages and giant cells to surround the foreign body. no T cell response.
examples of foreign body granuloma
talc
asbestos
silica
surgical sutures
foreign body granuloma morphology
1) giant cell nuclei are scattered in cytoplasm
2) no collar
3) sometimes foreign substance can be visualized

(pic - suture)
what kind of granuloma is associated with Immune Granulomatous Disease?
immune granuloma