Chapter 3 - Inflammation Flashcards
3 important components of acute inflammation:
Hemodynamic changes, neutrophils, and chemical mediators
Hemodynamic changes in acute inflammation:
Initial transient vasoconstriction due to Thromboxan A2
Massive vasodilatation mediated by histamine, bradykinin, and prostaglandins
Increased vascular permeability
Blood flow slows (stasis) due to increased viscosity, allowing neutrophils to marginate
The mechanism of increased vascular permeability involves…
Endothelial cell and pericyte contraction
Direct endothelial cell injury
Leukocyte injury of endothelium
Hypersegmented neutrophils
(>5 segments) are related to…
Megaloblastic anemias (vitamin B12 or folate deficiencies)
Neutrophils: Primary (azurophilic) granules contain…
Myeloperoxidase, phospholipase A2, lysozyme and hydrolases
Elastase, defensins
Bactericidal permeability increasing protein (BPI)
Lysozyme mechanism:
Damages bacterial cell walls by catalyzing hydrolysis of 1,4- beta-linkages
Neutrophils: Secondary (specific) granules contain:
Phospholipase A2, Collagenase
Leukocyte alkaline phosphatase (LAP), Lactoferrin, Lysozyme
Vitamin B12-binding proteins
Macrophages: life span in tissue compartment
60–120 days
Macrophages: content
Acid hydrolases, elastase, and collagenase
Neutrophil margination and adhesion: Step 1
Endothelial cells express E- and P-selectin
Neutrophil margination and adhesion: Step 2
Neutrophils bind to the selectins and roll
Neutrophil margination and adhesion: Step 3
Neutrophils express integrins
Neutrophil margination and adhesion: Step 4
Integrins bind to cellular adhesion molecules (ICAM-1 and VCAM-1)
P-selectin is normally present in…
Weibel-Palade bodies of endothelial cells
Inflammatory mediators stimulate P-selectin to…
Move to cell surface
IL-1 and TNF induce production of …, … and … by endothelial cells
E-selectin, ICAM-1, and VCAM-1
Bacterial product that is a chemotactic factor to neutrophils
N-formyl-methionine
Oxygen-independent mechanisms:
Lysozyme
Lactoferrin
Acid hydrolases
Bactericidal permeability increasing protein (BPI)
Defensins
Myeloperoxidase deficiency: genetics
Autosomal recessive
Myeloperoxidase deficiency: presentation
Candida infections
In Myeloperoxidase deficiency the nitroblue tetrazolium test will be…
Positive
Histamine is produced by…
Basophils, platelets, and mast cells
Triggers for release Histamine include:
IgE-mediated mast cell reactions
Physical injury
Anaphylatoxins (C3a and C5a)
IL-1
Inflammation: Serotonin is produced by…
Platelets
Serotonin is produced by platelets and causes…
Vasodilation and increased vascular permeability
Kinin System: Activated Hageman factor (factorXII) converts:
Prekallikrein → Kallikrein
Kinin System: Kallikrein cleaves:
High molecular weight kininogen (HMWK) → Bradykinin
Effects of bradykinin
Increased vascular permeability, pain, vasodilation, bronchoconstriction, and pain.
Nitric oxide is produced by…
Macrophages
Thromboxan A2 is produced by … and causes … and …
Platelets
Vasoconstriction ; Platelet aggregation
Prostacyclin (PGI2) is produced by … and causes … and …
Vascular endothelium
Vasodilation; inhibition of platelet aggregation
Mediators of Pain:
Bradykinin
Prostaglandins (E2)
Prostaglandins that cause vasodilatation
PGE2, PGD2, and PGF2
Leukotrienes C4, D4, E4 causes…
Vasoconstriction
Lipoxins: concept
Antiinflammatory products that inhibit neutrophil chemotaxis
4 possible outcomes of acute inflammation:
Complete resolution with regeneration
Complete resolution with scarring
Abscess formation
Transition to chronic inflammation
Chemotactic factors for macrophages:
C5a, MCP-1, MIP-1α, PDGF, TGF-β
Composition of a Granuloma: Epithelioid cells
Centrally
Macrophages modified by IFN-γ
Enlarged cells with abundant pink cytoplasm
Composition of a Granuloma: Multinucleated giant cells
Centrally
Fusion of Epithelioid cells
Multinucleated giant cells: Langhans-type giant cell has … arrangement of nuclei) and foreign body type giant cell has … arrangement of nuclei
Peripheral ; Haphazard
Granuloma: location of Lymphocytes and Plasma cells a
Periphery
Typical feature of TB’s granuloma
Central Necrosis
Examples of Granulomatous diseases:
Tuberculosis Cat-scratch fever Syphilis Leprosy Coccidioidomycosis Schistosomiasis Foreign bodies Beryllium Sarcoidosis
6 major inflammation histologic patterns in infection
Exudative Necrotizing Granulomatous Interstitial Cytopathic/cytoproliferative No inflammation
Exudative inflammation in infections: example
Bacterial meningitis, bronchopneumonia, and abscess.
Necrotizing inflammation in infections: example
Necrotiz- ing fasciitis and necrotizing pharyngitis
Interstitial inflammation in infections: example
Myocarditis (Coxsackie virus) and hepatitis
Cytopathic/cytoproliferative inflammation in infections: example
Intranuclear/cytoplasmic inclusions (cytomegalic inclusion disease, rabies [Negri body]); Syncytia formation (respiratory syncytial virus and herpes virus); and apoptosis (Councilman body in viral hepatitis).
