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89 Cards in this Set
- Front
- Back
what three things occur with vascular changes in the inflammatory response?
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1) vasodilation
2) increase permeability of vasculature by forming endothelial gaps 3) stasis (slowing blood flow in relevant area) |
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what three players are relevant with cellular changes in the inflammatory response?
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1) circulating and resident local tissue cells
2) circulating leukocytes 3) resident immune cells (macrophage, etc.) |
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what 5 events occur that are considered the cardinal features of acute inflammation?
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1) rubor (redness)
2) tumor (swelling) 3) calor (heat) 4) dolor (pain) 5) functio laesa (loss of function) |
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what are the two types of edema?
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1) transudate
2) exudate |
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transudate
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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)
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what is transudate not associated with?
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not inflammation
not increased vascular permeability. very few WBCs in transudate |
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exudate
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inflammatory edema resulting from increased in blood vessel permeability. high WBC, higher specific gravity
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what causes exudate?
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1) vascular flow changes
2) vascular permeability changes |
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what are the steps of vascular flow change associated with acute inflammation exudate?
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1) immediately arterioles vasoconstrict for a few seconds
2) vasodilation occurs because of prostaglandin stimulation 3) combination of (1) and (2) increase blood flow |
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what are the basic steps of vascular permeability change associated with acute inflammation exudate?
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1) increase in microvasculature
2) exudate moves into surrounding tissue 3) concentrated blood left after exudate moves out of circulation undergoes stasis |
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what are the mechanisms involved in increased vascular permeability?
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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 |
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how is the formation of endothelial gaps in venules accomplished when trying to achieve an increase in vascular permeability?
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endothelial cells contract leaving gaps between adjacent cells.
this is the first response and only lasts for 30 minutes |
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what is known as the immediate, transient response in regard to vascular permeability?
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formation of endothelial gaps in venules
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what chemical mediators contribute to the formation of endothelial gaps in venules?
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1) histamine
2) bradykinin 3) leukotrienes |
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how is the direct endothelial injury accomplished when trying to achieve an increase in vascular permeability?
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cells are damaged by burns, severe bacterial trauma, chemicals/toxins and necrotize leaving behind massive holes
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what is known as the immediate, sustained response in regard to vascular permeability?
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direct endothelial injury
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how is the leukocyte-mediated endothelial injury accomplished when trying to achieve an increase in vascular permeability?
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mainly occurring in venules, leukocytes adhere to endothelial cells and become activated releasing proteolytic enzymes and ROS that cause injury
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how is increased transcytosis accomplished when trying to achieve an increase in vascular permeability?
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increase in endothelial cytoplasmic channels allow transcytosis. VEGF (vascular endothelial growth factor) is the major contributor
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how is leakage from new blood vessels accomplished when trying to achieve an increase in vascular permeability?
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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.
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inflammatory mediators general definition
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increase blood flow that allow increased exudate
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what are steps involved in extravasation?
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1) adhesion
2) transmigration 3) chemotaxis 4) leukocyte activation 5) phagocytosis |
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margination
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when stasis occurs, WBCs stock on the periphery of blood vessels which promotes adhesion during extravasation
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what 4 families of cell adhesion molecules assist in extravasation?
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1) integrins
2) Ig superfamily (ICAM-1, ICAM-2) 3) selectins 4) mucin-like glycoproteins |
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what 3 mechanisms are involved in leukocyte adhesion?
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1) redistribution of adhesion molecules from cytoplasm to cell surface
2) induction of adhesion molecule synthesis 3) increase binding affinity of adhesion molecules |
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what are the names and function of the most important leukocyte adhesion molecules?
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P-selectin, E-selectin = rolling adhesion
ICAM-1, VCAM-1 = arrested adhesion PECAM = diapodesis and leukocyte migration |
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how is redistribution of adhesion molecules from cytoplasm to cell surface accomplished in the leukocyte adhesion process?
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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 |
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Weibel-Palade bodies
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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
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how is the induction of adhesion molecule synthesis accomplished in the leukocyte adhesion process?
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ex. inflammatory chemical mediators like IL-1 and TNF induce the synthesis of E-selectin which will be expressed to slow down neutrophil rolling
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how is the increase of binding affinity of adhesion molecules (integrins) accomplished in the leukocyte adhesion process?
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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
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how do chemoattractants cause leukocyte movement?
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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 |
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what 5 essential chemoattractant stimulation steps are required for leukocyte activation at ground zero?
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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 |
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what are the three steps in phagocytosis?
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1) recognition and attachment (opsonins, macrophage receptors)
2) engulfment (formation of phagosomes) 3) killing and degradation (oxygen-dependent and oxygen-independent) |
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why are neutrophils considered sloppy?
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mid-engulfment, sometimes lysosomal contents are released into the environment before phagosomal vessicle closes
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what is sequence of particles released into the tissue following acute injury?
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1) edema
2) neutrophils 3) monocytes -> macrophages if extended (+2 days) inflammation is occurring |
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where do chemical inflammatory mediators originate from?
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liver synthesized plasma residing or secreted from cells
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amplification
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several generations of mediator generated release of mediators increasing effect
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histamine
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generated and stored in mast cells causing vasodilation, vascular permeability, redistribution of P-selectin in endothelial cells, hallmark chemical mediator for inflammation
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serotonin
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derived from platelets with identical action as histamine
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what are the two vasoactive amine chemical inflammatory mediators?
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1) histamine (mast cell derived)
2) serotonin (platelet derived) |
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3 plasma protein systems?
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1) complement system
2) kinin system 3) clotting system |
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what 3 main things does complement do in inflammatory response?
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1) produces opsonins
2) produces chemotaxins and anaphylotoxins 3) lysis by MAC |
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complement-generated vasodilators and permeability increasing agents
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C3a, C5a
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complement-generated potent chemoattractant
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C5a
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complement-generated opsonin
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C3b
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kinin system activating agent
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release of Factor XII (Hageman Factor) occurs when tissue damage occurs which in turn initiates the kinin and clotting systems
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kinin system products
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1) bradykinin - increases permeability, pain causing mediator
2) kallikrein - increases bradykinin production |
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clotting system activating agent
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release of Factor XII (Hageman Factor) occurs when tissue damage occurs which in turn initiates the kinin and clotting systems
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clotting system product
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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
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what is the general role of prostaglandins, platelet activating factor and nitric oxide and what do they all have in common?
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production of all three are stimulated by thrombin release in the clotting system and are all inflammatory chemical mediators
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arachidonic acid metabolites (eicosanoids)
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produced by leukocytes, platelets, endothelial cells and expressed in cell membranes and attached to phospholipids. metabolism of AA fuels cyclooxygenase and lipoxygenase pathways.
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how does the anti-inflammatory effect of steroids work?
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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)
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Cyclooxygenase pathway products
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prostaglandins (all are pain and fever inducing):
1) prostacyclin (vasodilator) 2) thromboxane A2 (vasoconstrictor) 3) PGD2, PGE2, PGF2 (vasodilator) |
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what are the two pain causing chemical mediators of inflammation?
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bradykinin
prostaglandins |
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how do aspirin and NSAIDs reduce inflammation?
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inhibits cyclooxygenase pathway
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Lipoxygenase pathway products
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leukotrienes, lipoxins:
1) Leukotriene B4 (chemoattractant) 2) Leukotriene C4, D4, E4 (permeability, vasoconstriction) 3) Lipoxins A4, B4 (anti-inflammatory) |
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Platelet activating factor (PAF) function
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chemoattractant, permeability, promotes synthesis of other chemical mediators
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Cytokines
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1) IL-1, TNF (leukocyte adhesion, fever, sleep, prostaglandin synthesis)
2) IL-8 (chemokine) |
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endogenous pyrogens
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IL-1, TNF
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NO (nitric oxide) origin and function
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produced by endothelial cells and macrophages:
1) vasodilator by relaxation of smooth muscle surrounding blood vessels 2) combines powers with ROS |
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major vasodilators
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prostaglandins, histamine, NO
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fever inducers
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IL-1, TNF, prostaglandins
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pain inducers
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prostaglandins, bradykinin
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tissue damaging agents
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neutrophil and macrophage lysosomal enzymes, oxygen metabolites, NO
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edema causing mediators
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vasoactive amines, C3a, C5a, bradykinin, leukotrienes C4/D4/E4, PAF, substance P
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chemotaxis (chemoattractants)
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C5a, leukotriene B4, TNF, IL-1, bacterial products
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4 outcomes of acute inflammation
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1) resolution
2) abscess formation 3) healing (regeneration, scarring) 4) chronic inflammation |
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resolution with regeneration details
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only happens with short-lived injury with little major tissue destruction where tissue returns to normal morphology and function
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resolution with scarring details
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happens when substantial tissue destruction has occurred past point of regeneration, connective tissue replaces what used to be residual tissue
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serous inflammation
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plasma filtrate accumulates at site of inflammation that leads to blistering
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fibrinous inflammation
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acute inflammation where injury is serious enough to where large molecules can pass into tissue, such as fibrinogen. ex. fibrinous pericarditis
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ulcers
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local defect of inflammed tissue where irritated tissue sloughs off and leaves and open wound
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suppurative or purulent inflammation
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acute inflammation that is pus producing and usually produces and abscess
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abscess formation
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neutrophils within pus secrete enzymes that digest and destroy tissue (liquefactive necrosis). band of neutrophils surround cavity filled with pus and dead microorganisms.
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outcome of abscess
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cavity can collapse and form a scar or if it doesn't collapse, then microorganisms may burst from abscess and go septic
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chronic inflammation
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prolonged duration lasting over 48 hours which causes prolonged, ongoing tissue damage
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how can you have chronic inflammation without acute inflammation?
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3 ways:
1) persistent infections by certain microorganisms 2) prolonged exposure to toxins 3) autoimmune disease |
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chronic inflammation by persistent infections by certain microorganisms examples and reason that it does not cause acute inflammation
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Mycobacterium tuberculosis, Treponema pallidum (syphilis), fungi, viruses, parasites exhibit low toxicity that won't cause acute, but over time will cause chronic
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chronic inflammation by prolonged exposure to toxins examples
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1) coal miner's lung
2) atherosclerosis due to persistent hypercholesterolemia |
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chronic inflammation by autoimmune diseases examples
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1) RA
2) SLE |
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characteristics of chronic inflammation
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1) macrophages instead of neutrophils
2) tissue destruction by macrophages 3) scarring and fibrosis |
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positive feedback loop with macrophage stimulation
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macrophage releases IL-12 which stimulates T cells which release IFN-gamma which stimulates macrophage
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granulomatous inflammation
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inflammation due to granulomas
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granuloma general definition and types
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focal aggregate of macrophages
1) immune granuloma 2) foreign body granuloma |
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immune granuloma forms how?
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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 |
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components of immune granuloma
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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) |
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foreign body granuloma forms how?
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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.
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examples of foreign body granuloma
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talc
asbestos silica surgical sutures |
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foreign body granuloma morphology
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1) giant cell nuclei are scattered in cytoplasm
2) no collar 3) sometimes foreign substance can be visualized (pic - suture) |
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what kind of granuloma is associated with Immune Granulomatous Disease?
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immune granuloma
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