Inflammation (1 and 2) Flashcards
Actue Inflammation (4):
- Onset: Fast, minutes or hours.
- Infiltrate: Mainly neutrophils.
- Tissue injury, fibrosis: Mild and self limited.
- Local and systemic signs: Prominent.
Chronic inflammation (4):
- Onset: slow, days.
- Infiltrate: monocytes/macrophages and lymphocytes.
- Tissue injury, fibrosis: severe and progressive.
- Local and systemic signs: less prominent, subtle.
Clinical features of inflammation (5):
- Rubor/redness.
- Calor/warmth.
- Tumor/swelling.
- Dolor/pain.
- Functio laesa/loss of function.
Leukocyte emigration to extravascular tissues (3):
- Margination and rolling.
- Activation and adhesion.
- Transmigration.
Transudate:
Fluid with low protein content.
Exudate:
Extravascular fluid that has a high protein concentration and contains cellular debris.
Pus:
Purulent exudate, exudate rich in leukocytes, the debris of dead cells and in some cases microbes.
Most common mechanism of vascular leakage:
Retraction of endothelial cells.
Leukocyte rolling:
Mediated by selectins.
- L, E, P
- Low affinity interactions, easily disrupted by blood flow.
Leukocyte adhesion:
Mediated by integrins.
- Slow down the leukocytes, bind more firmly.
- Causes leukocytes to stop rolling.
Leukocyte transmigration:
Mediated by CD31/PECAM-1
- Chemokines stimulate cells to migrate through interendothelial spaces toward the chemical concentration gradient.
Chemotaxins (5):
- N-formylmethionine.
- IL-8.
- C5a.
- TNF-alpha.
- LTB4.
Major opsonins (3):
- Mannose binding lectin.
- IgG.
- C3b.
Phagocytosis steps (3):
- Recognition and opsonization.
- Engulfment with subsequent formation of a phagosome.
- Killing or degradation of the ingested material.
ROS are produced by:
- NADPH oxidase.
- Oxidizes NADPH and in the process reduces oxygen to superoxide anion.
Hypochlorite created by:
Conversion of H2O2 with Cl- by MPO.
iNOS (3):
- Inducible NO synthase.
- Involved in microbial killing.
- Induced when macrophages or neutrophils are activated.
Chediak-Higashi disease (6):
- Autosomal recessive.
- Infants and children.
- Neutropenia with recurrent infections.
- Oculocutaneous albinism.
- Aberrant granules in neutrophils and other WBCs - giant lysosomes.
- Melanocytes - “giant” melanosomes.
Chronic granulomatous disease of infancy (4):
- X-linked recessive.
- Infants and children.
- Recurrent infections, especially by catalase-producing microorganisms.
- Basic defect is of NADPH oxidase.
Serous inflammation (3):
- Contains low MW proteins, especially albumin.
- Clear yellow fluid.
- No cells.
Fibrinous inflammation (3):
- Contains larger proteins, especially fibrin.
- Often coats a surface.
- No cells.
Ulcer:
- Local defect of the surface of an organ or tissue that is produced by necrosis of cells and sloughing of necrotic and inflammatory tissue.
Purulent inflammation
- Exudate contains neutrophils in addition to proteins.
Eosinophilic inflammation:
Eosinophil is prominent or predominant in exudate.
Hemorrhagic inflammation:
RBCs leak into the surrounding tissue due to damage to endothelial cells and vessel walls.
Cellulitis:
Diffuse area of acute inflammation composed of edema fluid, bacteria and neutrophils spread through tissue.
Abscess:
A focus of acute inflammation composed of pyogenic exudate and necrotic tissue.
Histamine sources (3):
- Mast cells.
- Basophils.
- Platelets.
Histamine actions (3):
- Vasodilation.
- Increased vascular permeability.
- Endothelial activation.
Serotonin (2):
- Platelets.
- Vasoconstriction.
Prostaglandin sources (2):
- Mast cells.
- Leukocytes.
Prostaglandin actions (3):
- Vasodilation.
- Pain.
- Fever.
Leukotriene sources (2):
- Mast cells.
- Leukocytes.
Leukotriene actions (3):
- Increased vascular permeability.
- Chemotaxis.
- Leukocyte adhesion and activation.
Platelet-activating factor sources (2):
- Mast cells.
- Leukocytes.
Platelet-activating factor actions (6):
- Vasodilation.
- Increased vascular permeability.
- Leukocyte adhesion.
- Chemotaxis.
- Degranulation.
- Oxidative burst.
ROS (2):
- Source: leukocytes.
- Action: killing of microbes, tissue damage.
Nitrous oxide sources (2):
- Endothelium.
- Macrophages.
NO actions (2):
- Vascular smooth muscle relaxation.
- Killing of microbes.
Chemokine sources (2):
- Leukocytes.
- Activated macrophages.
Chemokine actions (2):
- Chemotaxis.
- Leukocyte activation.
Kinin actions (4):
- Increased vascular permeability.
- Smooth muscle contraction.
- Vasodilation.
- Pain.
Preformed mediators (3):
- Histamine.
- Serotonin.
- Lysosomal enzymes.
Histamine (4):
- Causes dilation of arterioles.
- Increases permeability of venules.
- Principal mediator of the immediate transient phase of increased vascular permeability.
- Contraction of some smooth muscles.
Converts phospholipids to arachidonic acid:
Phospholipase.
Converts arachidonic acid to prostaglandins:
Cycloxygenase (COX-1 and COX-2).
Inhibits creation of prostaglandins:
COX-1 and COX-2 inhibitors.
- Aspirin, NSAIDs, indomethacin.
Converts arachidonic acid to leukotrienes:
5-Lipoxygenase.
Prostaglandins (4):
- Involved in the pathogenesis of pain and fever in inflammation.
- Generated by COX-1 and COX-2.
- COX-1 constitutively expressed.
- COX-2 induced by inflammatory stimuli.
Plasma derived chemical mediators (2):
- Factor XII (Hageman factor) activation.
- Complement activation.
C3a/C5a (3):
- Increase vascular permeability.
- Induce mast cell histamine release.
- C5a: chemotaxin.
Hageman factor activated by (4):
- Negatively charged surfaces.
- Bacterial LPS.
- Sodium urate crystals.
- Enzymes.
Bradykinin actions (4):
- Vasodilation.
- Increase vascular permeability.
- Bronchial smooth muscle contraction.
- Pain.
Activates the alternative pathway of macrophages:
IL-13 and IL-4.
Activates the classical pathway of macrophages:
IFN-gamma and microbes.
Acute phase proteins:
Plasma proteins synthesized in the liver, plasma concentration may increase as part of the inflammatory response.
ESR (3):
Erythrocyte sedimentation rate:
- Rate at which RBCs “settle” to the bottom of the tube.
- Determined by the amount of fibrinogen.
- Increased non-specifically in pts undergoing an inflammatory response.
C-reactive protein:
Non-specifically elevated in pts who are undergoing an inflammatory response.
Cytokines involved in acute inflammation (5):
- TNF
- IL-1
- IL-6
- Chemokines
- IL-17
Cytokines involved in chronic inflammation (3):
- IL-12
- IFN-gamma
- IL-17
TNF actions (2):
- Stimulates expression of endothelial adhesion molecules.
- Stimulates secretion of other cytokines.
IL-1 actions (2):
- Similar to TNF.
- Fever.
IL-17 action:
- Recruitment of neutrophils and monocytes.
IL-12 action:
Increased production of IFN-gamma.
IFN-gamma action:
Activation of macrophages.
Principal mediators or vasodilation (2):
- Histamine.
- Prostaglandins.
Principal mediators of increased vascular permeability (4):
- Histamine.
- Serotonin.
- C3a/C5a
- Leukotrienes.
Principal mediators of chemotaxis, recruitment and activation (5):
- TNF
- IL-1
- Chemokines
- C3a/C5a
- Leukotriene B4
Principal mediators of fever (3):
- TNF
- IL-1
- Prostaglandins
Principal mediators of pain (2):
- Prostaglandins
- Bradykinin
Principal mediators of tissue damage (2):
- Lysosomal enzymes.
- ROS.
