Chapter 3 - Inflammation Flashcards by Eduardo Danielli

3 important components of acute inflammation:

Hemodynamic changes, neutrophils, and chemical mediators

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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

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The mechanism of increased vascular permeability involves…

Endothelial cell and pericyte contraction

Direct endothelial cell injury

Leukocyte injury of endothelium

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Hypersegmented neutrophils

(>5 segments) are related to…

Megaloblastic anemias (vitamin B12 or folate deficiencies)

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Neutrophils: Primary (azurophilic) granules contain…

Myeloperoxidase, phospholipase A2, lysozyme and hydrolases

Elastase, defensins

Bactericidal permeability increasing protein (BPI)

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Lysozyme mechanism:

Damages bacterial cell walls by catalyzing hydrolysis of 1,4- beta-linkages

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Neutrophils: Secondary (specific) granules contain:

Phospholipase A2, Collagenase

Leukocyte alkaline phosphatase (LAP), Lactoferrin, Lysozyme

Vitamin B12-binding proteins

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Macrophages: life span in tissue compartment

60–120 days

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Macrophages: content

Acid hydrolases, elastase, and collagenase

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Neutrophil margination and adhesion: Step 1

Endothelial cells express E- and P-selectin

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Neutrophil margination and adhesion: Step 2

Neutrophils bind to the selectins and roll

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Neutrophil margination and adhesion: Step 3

Neutrophils express integrins

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Neutrophil margination and adhesion: Step 4

Integrins bind to cellular adhesion molecules (ICAM-1 and VCAM-1)

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P-selectin is normally present in…

Weibel-Palade bodies of endothelial cells

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Inflammatory mediators stimulate P-selectin to…

Move to cell surface

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IL-1 and TNF induce production of …, … and … by endothelial cells

E-selectin, ICAM-1, and VCAM-1

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Bacterial product that is a chemotactic factor to neutrophils

N-formyl-methionine

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Oxygen-independent mechanisms:

Lysozyme

Lactoferrin

Acid hydrolases

Bactericidal permeability increasing protein (BPI)

Defensins

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Myeloperoxidase deficiency: genetics

Autosomal recessive

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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). ```