Acute inflammation
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Transcript of Acute inflammation
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• Egyptian papyrus - 3000 B.C.
• Celsus (Roman in 1st century A.D.)
Rubor - Tumor - Calor - Dolor
redness - swelling - heat - pain
• Virchow added functio laesa later
History
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What is inflammation?What is inflammation?
Inflammation – Inflammation – Protective response intended to eliminate Protective response intended to eliminate
the initial cause of cell injury and the the initial cause of cell injury and the necrotic cells and tissues arising from necrotic cells and tissues arising from the injurythe injury
Inflammation is intimately Inflammation is intimately associated with the repair process associated with the repair process which includes parenchymal cell which includes parenchymal cell regeneration and scarringregeneration and scarring
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Acute - minutes to daysAcute - minutes to days Characterized by fluid and protein Characterized by fluid and protein PMN’sPMN’s Exudate SG > 1.020Exudate SG > 1.020
Chronic - weeks to yearsChronic - weeks to years Lymphocytes and macrophagesLymphocytes and macrophages
ACUTE Inf - PMN’s (ACUTE Inf - PMN’s (PolyPolymorphonuclear morphonuclear Cells)Cells)
CHRONIC Inf - CHRONIC Inf - MonoMononuclear Cellsnuclear Cells
InflammationInflammation
EXUDATE
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Acute inflammation“The immediate and early response to an injurious agent”
Chronic inflammation “Inflammation of prolonged duration (weeks or months) in which active inflammation, tissue destruction, and attempts at repair are proceeding simultaneously“
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Exudate
• vascular permeability • high protein & cell debris
• SG > 1.020
Transudate
• normal vascular permeability • hydrostatic pres. plasma ultrafiltrate • low protein (mostly albumin) • SG < 1.012
Edema
• exudate or transudate ; interstitium or cavity
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Acute inflammation Acute inflammation major componentsmajor components
Transient vasoconstrictionTransient vasoconstriction VasodilatationVasodilatation Endothelial permeabilityEndothelial permeability Extravasation of PMNsExtravasation of PMNs
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Five classic local signs of Five classic local signs of acute inflammationacute inflammation
HeatHeat RednessRedness SwellingSwelling PainPain Loss of Loss of
functionfunction
Calor – vasodilatationCalor – vasodilatation Rubor – vasodilatationRubor – vasodilatation Tumor – vascular permeabilityTumor – vascular permeability Dolor – mediator release/PMNsDolor – mediator release/PMNs Functio laesa – loss of functionFunctio laesa – loss of function
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Vascular changes Vascular changes you need to know thisyou need to know this
Transient vasoconstrictionTransient vasoconstriction Vasodilation Vasodilation Exudation of protein rich fluidExudation of protein rich fluid Blood stasisBlood stasis MarginationMargination Emigration/TransmigrationEmigration/Transmigration
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Vascular changesProtein exits vessels :
intravascular osmotic pressure
intravascular hydrostatic pressure
Endothelial gaps at intercellular junctions:
* immediate transient response
* histamine, bradykinin, leukotrienes, substance P
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Vascular permeabilityVascular permeability Vasodilation – increased blood flowVasodilation – increased blood flow Increased intravascular hydrostatic pressureIncreased intravascular hydrostatic pressure Transudate Transudate - ultrafiltrate blood plasma - ultrafiltrate blood plasma
(contains little protein)(contains little protein) Again, this is very transient and just gets the Again, this is very transient and just gets the
process started. Think acute inflammation, think process started. Think acute inflammation, think EXUDATEEXUDATE
ExudateExudate - (protein-rich with PMNs) - (protein-rich with PMNs) Exudate is the characteristic fluid of acute Exudate is the characteristic fluid of acute
inflammationinflammation Intravascular osmotic pressure decreasesIntravascular osmotic pressure decreases Osmotic pressure of interstitial fluid increasesOsmotic pressure of interstitial fluid increases Outflow of water and ions - Outflow of water and ions - edemaedema
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How do endothelial cellsHow do endothelial cellsbecome permeable?become permeable?
Endothelial cell contractionEndothelial cell contraction Junctional retractionJunctional retraction Direct endothelial injury Direct endothelial injury
(immediate sustained response) (immediate sustained response) Leukocyte-dependent endothelial Leukocyte-dependent endothelial
injury injury Increased transcytosis of fluidIncreased transcytosis of fluid
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Direct endothelial injury Direct endothelial injury (immediate sustained (immediate sustained
response)response) Endothelial cell necrosis and detachmentEndothelial cell necrosis and detachment Result of severe injury or burnResult of severe injury or burn Occurs immediately and lasts until vessel Occurs immediately and lasts until vessel
repairedrepaired
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Occurs at sites of leukocyte Occurs at sites of leukocyte accumulationaccumulation
Due to leukocyte activation which Due to leukocyte activation which releases proteolytic enzymes and releases proteolytic enzymes and toxic oxygentoxic oxygen
Leukocyte-dependent Leukocyte-dependent endothelial injuryendothelial injury
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Leukocyte Cellular Leukocyte Cellular EventsEvents
Margination and RollingMargination and Rolling Adhesion and TransmigrationAdhesion and Transmigration Migration into interstitial tissueMigration into interstitial tissue
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SLOWING CONCENTRATION
Margination Rolling AdhesionTransmigration
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Selectins CAMS
Integrins
Mucin-like glycoproteins
(Sialyl-Lewis X PSL-1 & ESL-1)
Weak and transient binding
Results in rolling
Integrins upregulated and activated for increased affinity to CAMS
Results in firm adhesion
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MarginationMargination
Normal flow - RBCs and WBCs flow Normal flow - RBCs and WBCs flow in the center of the vesselin the center of the vessel
A A cell poorcell poor plasma is flowing plasma is flowing adjacent to endotheliumadjacent to endothelium
As blood flow slows, WBCs collect As blood flow slows, WBCs collect along the endothelium along the endothelium MarginationMargination
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Endothelial ActivationEndothelial Activation
The underlying stimulus causes The underlying stimulus causes release of mediators which activate release of mediators which activate the endothelium causing selectins the endothelium causing selectins and other mediators to be moved and other mediators to be moved quickly to the surfacequickly to the surface
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Selectins Selectins
Selectins bind selected sugars Selectins bind selected sugars SeSelected + lected + LectinsLectins (sugars) = Selectins (sugars) = Selectins
Some selectins are present on endothelial cells (E-Some selectins are present on endothelial cells (E-Selectin)Selectin)
Some selectins are present on leukocytes (L-Selectin)Some selectins are present on leukocytes (L-Selectin) Some selectins are present on platelets (P-Selectin)Some selectins are present on platelets (P-Selectin) Weak & transient bindingWeak & transient binding Results in Results in rollingrolling
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Fig 3-Fig 3-99
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RollingRolling
Selectins transiently bind to Selectins transiently bind to receptorsreceptors
PMNs bounce or roll along PMNs bounce or roll along Rolling Rolling
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AdhesionAdhesion
Mediated by integrins ICAM-1 and Mediated by integrins ICAM-1 and VCAM-1 VCAM-1
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TransmigrationTransmigration
Mediated/assisted by PECAM-1 & ICAM-1 Mediated/assisted by PECAM-1 & ICAM-1 (Integrins)(Integrins)
Diapedesis (cells crawling)Diapedesis (cells crawling) Primary in venulesPrimary in venules Collagenases degrade BM Collagenases degrade BM PermeabilityPermeability
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ChemotaxisChemotaxis
Movement toward the site of injury Movement toward the site of injury along a chemical gradientalong a chemical gradient Chemotactic factors includeChemotactic factors include
Complement components (20 serum Complement components (20 serum proteins)proteins)
Arachadonic acid (AA) metabolitesArachadonic acid (AA) metabolites Soluble bacterial productsSoluble bacterial products Chemokines, cytokinesChemokines, cytokines
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Phagocytosis & Phagocytosis & DegranulationDegranulation
Phagocytosis (engulf and destroy)Phagocytosis (engulf and destroy) Degranulation and the oxidative Degranulation and the oxidative
burst destroy the engulfed particleburst destroy the engulfed particle Recognition & attachmentRecognition & attachment
Opsonins coat target and bind to Opsonins coat target and bind to leukocytesleukocytes
EngulfmentEngulfment Killing/degradationKilling/degradation
OO22 dep: Reactive O dep: Reactive O22 species in species in lysosomes & EClysosomes & EC
OO2 2 indep: Bactericidal permeability indep: Bactericidal permeability agents, lysozyme, MBP, lactoferrinagents, lysozyme, MBP, lactoferrin
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Leukocyte-induced Leukocyte-induced tissue injurytissue injury
Lysosomal enzymes are released into the Lysosomal enzymes are released into the extracellular space during phagocytosis extracellular space during phagocytosis causing cell injury and matrix causing cell injury and matrix degradationdegradation
Activated leukocytes release reactive Activated leukocytes release reactive oxygen species and products of oxygen species and products of arachidonic acid metabolism which can arachidonic acid metabolism which can injure tissue and endothelial cellsinjure tissue and endothelial cells
These events underlie many human These events underlie many human diseases (e.g. Rheumatoid arthritis)diseases (e.g. Rheumatoid arthritis)
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Table 3-3Table 3-3GeneticGenetic DefectDefectLAD 1LAD 1 B chain of CD11/CD18 B chain of CD11/CD18
integrinsintegrinsLAD 2LAD 2 Sialylated Sialylated
oligosaccharideoligosaccharideNeutrophil-specific Neutrophil-specific granule deficiencygranule deficiency
Absence of neutrophil-Absence of neutrophil-specific granules specific granules
CGDCGD
X-linkedX-linked
ARAR
Defective chemotaxisDefective chemotaxisNADPH oxidatise NADPH oxidatise (membrane)(membrane)NADPH oxidase NADPH oxidase (cytoplasm)(cytoplasm)
MPO deficiencyMPO deficiency Absent MPO-H2O2 Absent MPO-H2O2 systemsystem
Chediak-Higashi syndromeChediak-Higashi syndrome Lysosomal defectLysosomal defectAcquiredAcquiredThermal injury, DM, CA, Thermal injury, DM, CA, sepsissepsis
ChemotaxisChemotaxis
Dialysis, DMDialysis, DM AdhesionAdhesionLeukemia, anemia, sepsis, Leukemia, anemia, sepsis, DM, neonates, DM, neonates, malnutritionmalnutrition
Phagocytosis & Phagocytosis & microbicidal activitymicrobicidal activity
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Leukocyte adhesion Leukocyte adhesion deficiency 1 (LAD-1)deficiency 1 (LAD-1)
Recurrent bacterial infectionsRecurrent bacterial infections Inflammatory lesions lack neutrophil infiltrateInflammatory lesions lack neutrophil infiltrate High numbers of neutrophils in the circulationHigh numbers of neutrophils in the circulation Neutrophils from patients can roll but do not Neutrophils from patients can roll but do not
stickstick chain of CD11/CD18 integrinchain of CD11/CD18 integrin Transfuse patients with normal neutrophils Transfuse patients with normal neutrophils
and they can emigrateand they can emigrate
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Mechanism of leukocyte Mechanism of leukocyte adhesion deficiency 1 adhesion deficiency 1
(LAD -1)(LAD -1)
Absence of integrins on neutrophilsAbsence of integrins on neutrophils Mutation in n-terminal region of the Mutation in n-terminal region of the
integrin integrin chain inhibits proper integrin chain inhibits proper integrin assemblyassembly
Normal function is restored following Normal function is restored following transfection of patient cells with cDNA for transfection of patient cells with cDNA for chain chain
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Chediak-Higashi Chediak-Higashi SyndromeSyndrome
This syndrome has been on every This syndrome has been on every board test since Noahboard test since Noah
Defect in chemotaxis and lysosomal Defect in chemotaxis and lysosomal degranulation into phagosomes degranulation into phagosomes
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Chronic Granulomatous Chronic Granulomatous DiseaseDisease
Defect in NADPH oxidase systemDefect in NADPH oxidase system Marked decrease in ability to kill Marked decrease in ability to kill
microorganismsmicroorganisms
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Chemical mediators of Chemical mediators of inflammationinflammation
Plasma-derived Plasma-derived Circulating precursors Circulating precursors Have to be activatedHave to be activated
Cell-derivedCell-derived Sequestered intracellular Sequestered intracellular Synthesized de novoSynthesized de novo
Most mediators bind to receptors on Most mediators bind to receptors on cell surface but some have direct cell surface but some have direct enzymatic or toxic activityenzymatic or toxic activity
Mediators are tightly regulatedMediators are tightly regulated
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Chemotacticfactors (eg. c5a)
Chemotacticfactors (eg. c5a)
Tissue injury
Tissue injury
Vasoactivemediators(eg. histamine)
Vasoactivemediators(eg. histamine)
Increased vascularpermeability
Increased vascularpermeability
Recruitment of inflammatory cells
Recruitment of inflammatory cells
EdemaEdema PMNsPMNs MonosMonos
Production of inflammatory
mediators
Production of inflammatory
mediators
Acute inflammation
Acute inflammation
Chronic inflammation
Chronic inflammation
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Plasma Mediator Systems - Interaction
1. Kinin
2. Clotting
3. Complement
4. Fibrinolytic
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C5
C5a
Plasminogen Plasmin
C3
C3a
Fibrin FSPs
Prothrombin Thrombin
Fibrinogen
XII
Kinin
Complement
Clotting
Fibrinolytic
Fibrinopeptides
Prekallikrein XIIa Kallikrein
High Mol. Wt. Kininogen Bradykinin
Plasma Mediator Systems - Interaction
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Kinin cascadeKinin cascade
Leads to formation of bradykininLeads to formation of bradykinin Bradykinin causes Bradykinin causes
Increased vascular permeabilityIncreased vascular permeability Arteriolar dilatation Arteriolar dilatation Smooth muscle contraction Smooth muscle contraction
Bradykinin is short lived (kininases)Bradykinin is short lived (kininases) Vascular actions similar to histamineVascular actions similar to histamine
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Complement systemComplement system
Role in immunity (C5-9 complex)Role in immunity (C5-9 complex) Membrane Attack Complex (MAC C5-9)Membrane Attack Complex (MAC C5-9) Punches a hole in the membranePunches a hole in the membrane
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Complement systemComplement system
Role in inflammation (c3a and c5a)Role in inflammation (c3a and c5a) Vascular effectsVascular effects
Increase vascular permeability and Increase vascular permeability and vasodilationvasodilation
Similar to histamineSimilar to histamine Activates lipoxygenase pathway of Activates lipoxygenase pathway of
arachidonic acid metabolism (c5a)arachidonic acid metabolism (c5a)
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Complement systemComplement system
Leukocyte activation, adhesion and chemotaxis Leukocyte activation, adhesion and chemotaxis (c5a)(c5a)
PhagocytosisPhagocytosis c3b acts as opsonin and promotes phagocytosis c3b acts as opsonin and promotes phagocytosis
by cells bearing receptors for c3bby cells bearing receptors for c3b
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Inflammatory Mediators Inflammatory Mediators from Complementfrom Complement
AnaphylatoxinsAnaphylatoxins::
C3a, C5a, & C4aC3a, C5a, & C4a trigger mast cells to release trigger mast cells to release histamine and cause vasodilatationhistamine and cause vasodilatation
C5aC5a also activates the lipoxygenase system in also activates the lipoxygenase system in PMNs and monocytes PMNs and monocytes release of release of inflammatory mediatorsinflammatory mediators
Leukocyte activation, adhesion, & chemotaxisLeukocyte activation, adhesion, & chemotaxis::C5aC5a activates leukocytes, promotes leukocyte activates leukocytes, promotes leukocyte
binding to endothelium via integrins and is binding to endothelium via integrins and is chemotactic for PMNs, monos, eos, & basoschemotactic for PMNs, monos, eos, & basos
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Inflammatory Mediators Inflammatory Mediators from Complementfrom Complement
PhagocytosisPhagocytosis::
C3b and C3biC3b and C3bi are opsonins are opsonins
ControlControl: :
Convertases are destabilized by "decay Convertases are destabilized by "decay accelerating factor" (DAF) accelerating factor" (DAF)
Inability to express DAF causes Inability to express DAF causes paroxysmal nocturnal hemoglobinuriaparoxysmal nocturnal hemoglobinuria
C1 inhibitor (C1INH) deficiency causes C1 inhibitor (C1INH) deficiency causes hereditary angioneurotic edemahereditary angioneurotic edema
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Vasoactive aminesVasoactive amines HistamineHistamine
Found in mast cells, basophils and Found in mast cells, basophils and plateletsplatelets
Released in response to stimuli Released in response to stimuli Promotes arteriolar dilation and venular Promotes arteriolar dilation and venular
endothelial contraction endothelial contraction results in widening of interendothelial cell results in widening of interendothelial cell
junctions with increased vascular junctions with increased vascular permeabilitypermeability
SerotoninSerotonin Vasoactive effects similar to histamineVasoactive effects similar to histamine Found in platelets Found in platelets Released when platelets aggregateReleased when platelets aggregate
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Bradykinin: Potent biomolecule
1. Vasodilatation
2. Increased vascular permeability
3. Contraction of smooth muscle
4. Pain on injection
5. Short life, kininase degrades
Bradykinin: Potent biomolecule
1. Vasodilatation
2. Increased vascular permeability
3. Contraction of smooth muscle
4. Pain on injection
5. Short life, kininase degrades
Factor XII activated by:
1. Plasmin
2. Kallikrein
3. Collagen & basement membrane
4. Activated platelets
5. Co-factor = HMWK
Factor XII activated by:
1. Plasmin
2. Kallikrein
3. Collagen & basement membrane
4. Activated platelets
5. Co-factor = HMWK
Vascular Permeability:
- Bradykinin
- Fibrionopeptides
- Fibrin Split Prod.
- Factor Xa
- Leukotrienes
Vascular Permeability:
- Bradykinin
- Fibrionopeptides
- Fibrin Split Prod.
- Factor Xa
- Leukotrienes
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Arachidonic Acid (AA)Arachidonic Acid (AA)
Where is it located?Where is it located? AA is a component of cell membrane AA is a component of cell membrane
phospholipidsphospholipids The breakdown of AA into its metabolites The breakdown of AA into its metabolites
produces a variety of biologic effectsproduces a variety of biologic effects
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Arachidonic acid Arachidonic acid metabolitesmetabolites
Metabolites of AA - short-range Metabolites of AA - short-range hormoneshormones
AA metabolites act locally at site of AA metabolites act locally at site of generationgeneration
Rapidly decay or are destroyedRapidly decay or are destroyed
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Arachidonic AcidArachidonic Acid
AA is released from the cell AA is released from the cell membrane by membrane by phospholipasesphospholipases which which have themselves been activated by have themselves been activated by various stimuli and/or inflammatory various stimuli and/or inflammatory mediatorsmediators
AA metabolism occurs via two major AA metabolism occurs via two major pathways named for the enzymes pathways named for the enzymes that initiate the reactions; that initiate the reactions; lipoxygenaselipoxygenase and and cyclooxygenasecyclooxygenase
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AA metabolites (eicosanoids)Cyclooxygenases synthesize
Prostaglandins
Thromboxanes
Lipoxygenases synthesize
Leukotrienes
Lipoxins
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PGG2
PGH2
PGI2
ProstacyclinTXA2
Thromboxane
PGD2 ; PGE2 PGF2
Vasodilatation
Inhibits Platelet Aggregation
Vasoconstriction
Promotes Platelet Aggregation
Vasodilatation Edema
PGI2
TXA2
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Arachidonic Acid Arachidonic Acid PathwaysPathways
you need to know thisyou need to know this LipoxygenaseLipoxygenase
5-HETE5-HETE ChemotaxisChemotaxis
5-HPETE5-HPETE Leukotriene Leukotriene
generationgeneration LeukotrienesLeukotrienes
VasoconstricitonVasoconstriciton BronchospasmBronchospasm Increased vascular Increased vascular
permeabilitypermeability
LipoxygenaseLipoxygenase 5-HETE5-HETE
ChemotaxisChemotaxis 5-HPETE5-HPETE
Leukotriene Leukotriene generationgeneration
LeukotrienesLeukotrienes VasoconstricitonVasoconstriciton BronchospasmBronchospasm Increased vascular Increased vascular
permeabilitypermeability
CyclooxygenaseCyclooxygenase ProstaglandinsProstaglandins
VasodilatationVasodilatation Increased vascular Increased vascular
permeabilitypermeability ProstacyclinProstacyclin
VasodilatationVasodilatation Inhibits platlelet Inhibits platlelet
aggregationaggregation Thromboxane A2Thromboxane A2
VasoconstrictionVasoconstriction Promotes platlelet Promotes platlelet
aggregationaggregation
CyclooxygenaseCyclooxygenase ProstaglandinsProstaglandins
VasodilatationVasodilatation Increased vascular Increased vascular
permeabilitypermeability ProstacyclinProstacyclin
VasodilatationVasodilatation Inhibits platlelet Inhibits platlelet
aggregationaggregation Thromboxane A2Thromboxane A2
VasoconstrictionVasoconstriction Promotes platlelet Promotes platlelet
aggregationaggregation
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Arachidonic Acid Arachidonic Acid PathwaysPathways
you need to know thisyou need to know this LipoxygenaseLipoxygenase
5-HETE, 5-HPETE, 5-HETE, 5-HPETE, LeukotrienesLeukotrienes
Spasm (Vaso, Spasm (Vaso, Broncho)Broncho)
LipoxygenaseLipoxygenase 5-HETE, 5-HPETE, 5-HETE, 5-HPETE,
LeukotrienesLeukotrienes Spasm (Vaso, Spasm (Vaso,
Broncho)Broncho)
CyclooxygenaseCyclooxygenase Prostaglandins - Prostaglandins -
EDEMAEDEMA Prostacyclin vs TXA2Prostacyclin vs TXA2
Vasodilatation vs. Vasodilatation vs. VasoconstrictionVasoconstriction
Platelet aggregationPlatelet aggregationInhibits vs. promotesInhibits vs. promotes
CyclooxygenaseCyclooxygenase Prostaglandins - Prostaglandins -
EDEMAEDEMA Prostacyclin vs TXA2Prostacyclin vs TXA2
Vasodilatation vs. Vasodilatation vs. VasoconstrictionVasoconstriction
Platelet aggregationPlatelet aggregationInhibits vs. promotesInhibits vs. promotes
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Arachidonic Acid Arachidonic Acid MetabolitesMetabolites
Participate in every aspect of acute Participate in every aspect of acute inflammationinflammation
Effective Anti-inflammatory agents Effective Anti-inflammatory agents act on AA pathwaysact on AA pathways Aspirin and Non-Steroidal Anti-Aspirin and Non-Steroidal Anti-
inflammatory Drugs (NSAID’s) - inflammatory Drugs (NSAID’s) - Cyclooxygenase pathCyclooxygenase path
Steroids act, in part, by inhibiting Steroids act, in part, by inhibiting Phospholipase A2Phospholipase A2
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Platelet-Activating Platelet-Activating Factor (PAF)Factor (PAF)
Another phospholipid-derived mediator Another phospholipid-derived mediator released by phospholipasesreleased by phospholipases
Induces aggregation of plateletsInduces aggregation of platelets Causes vasoconstriction and Causes vasoconstriction and
bronchoconstrictionbronchoconstriction 100 to 1,000 times more potent than 100 to 1,000 times more potent than
histamine in inducing vasodilation and histamine in inducing vasodilation and vascular permeabilityvascular permeability
Enhances leukocyte adhesion, chemotaxis, Enhances leukocyte adhesion, chemotaxis, degranulation and the oxidative burstdegranulation and the oxidative burst
It does everything!It does everything!
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CytokinesCytokines
Polypeptides that are secreted by cellsPolypeptides that are secreted by cells Act to regulate cell behaviorsAct to regulate cell behaviors Autocrine, paracrine or endocrine Autocrine, paracrine or endocrine
effectseffects These “biological response modifiers” These “biological response modifiers”
are being actively investigated for are being actively investigated for therapeutic use in controlling the therapeutic use in controlling the inflammatory response.inflammatory response.
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1. Macrophages make IL-1 & TNF-
2. T-cells make TNF- (lymphotoxin)
3. Can be autocrine, paracrine, endocrine
4. IL-1, TNF, IL-6 acute phase responses, fever, (appetite, slow wave sleep, circ. pmn, ACTH, corticosteroids)
5. TNF notable for role in septic shock and maintenance of body mass (cachexia in cancer from TNF- )
Lymphocyte function
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Selected Inflammatory Selected Inflammatory Cells & Their Cells & Their ChemokinesChemokines
Target CellTarget Cell Important ChemokinesImportant Chemokines
NeutrophilsNeutrophils IL-8, GroIL-8, Gro, , , , , others, others
MonocytesMonocytes MIP-1MIP-1, MIP-1, MIP-1, MCP-1,2,3, MCP-1,2,3
EosinophilsEosinophils EotaxinEotaxin
LymphocytLymphocyteses
LymphotaxinLymphotaxin
BasophilsBasophils IL-8, MIP-1IL-8, MIP-1, MCP-1,3, , MCP-1,3, RANTESRANTES
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Nitric OxideNitric Oxide NO is a soluble free radical gasNO is a soluble free radical gas Made by nitric oxide synthetase Made by nitric oxide synthetase
(NOS) in endothelium (eNOS), (NOS) in endothelium (eNOS), macrophages (iNOS), and specific macrophages (iNOS), and specific neurons in the brain (nNOS)neurons in the brain (nNOS)
Broad range of functions and effects Broad range of functions and effects that are short rangethat are short range
Vasodilatation by relaxing smooth muscle.Vasodilatation by relaxing smooth muscle. platelet aggregationplatelet aggregation Inhibits mast cellsInhibits mast cells Regulates leukocyte recruitmentRegulates leukocyte recruitment
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Outcomes of Acute Outcomes of Acute InflammationInflammation
ResolutionResolution FibrosisFibrosis Abscess formationAbscess formation Progression to chronic inflammationProgression to chronic inflammation