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Medical Pathology - Robin's Basic Pathology > Lecture 05 - Inflammatory Mediators > Flashcards

Lecture 05 - Inflammatory Mediators Flashcards

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USMLE® Step 1 flashcards
1
Q

Inflammatory Mediators

A
  1. Cell derived

2. Plasma derived protein

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2
Q

Cell Derived Inflammatory Mediators: 1. Vasoactive Amines

A
  1. Histamine: transient effect –> 15’
    - vasodilation
    - increased vessels permeability
    - endothelium activation
    Stimulator:
  2. Stress
  3. IgE on mast cells
  4. Anaphylatoxins: C5a, C3a
  5. Cytokines: IL-1,8
  6. Neuropeptides
  7. Histamine Releasing Peptide
  8. Serotonin: by platelet, neuroendocrine cells of GI tract, mast cells of ????
    Roles:
    - neurotransmitter in GI tract
    - vasoconstriction
    Stimulator:
    Platelet aggregation
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3
Q

Cell Derived Inflammatory Mediators: 2. Eicosanoids

A

Metabolites of arachidonic acid (linoleic acid) –> phospholipase:

  1. LTs, LXs: arachidonic acid –> 5-lipoxygenase –> 5-HPETE –> 1. LTs 2. 12-lipoxygenase –> LXs
    - LTC4,D4,E4 –> bronchospasm, increased vascular permeability
    - LXA4,B4 –> neutrophil adhesion and chemotaxis inhibition
  2. PGs: arachidonic acid –> cyclooxygenase –> PGG2 –>PGH2 –> …
    - PGI2 (prostacyclin): vasodilation, inhibition of platelet aggregation
    - PGB4: PMN activator, chemotaxis, ROS generation, release of lysosomal enzymes
    - TXA2 –> vasoconstriction, promotion of platelet aggregation
    - PGD2,E2,F2: vasodilation, edema
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4
Q

Phospholipase Inhibitors

A
  • -> no arachidonic acid –> no LTs or PGs
  • Corticosteroids
  • Dexametazone
  • prednisone
  • prednisolone
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5
Q

COX Inhibitors

A

–> no PGs
- maximum pain endurance increased
- GI tract toxicity –> COX-2(inflammation specific) inhibitor
NSAIDs
- ibuprofen
- ketoprofen
- naproxen
- mefenamic acid(COX-2)
- aspirin(COX-2)
- piroxicam
- indomethacin
- phenylbutazone

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6
Q

Lipoxygenase Inhibitor

A
  • zileuton

- montelukast –> LT receptor antagonist

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7
Q

Cell Derived Inflammatory Mediators: 3. PAF

A 
Based on phospholipids
Roles:
1. Platelet aggregation and activation
2. Increased vascular permeability
3. Chemotaxis an adhesion
4. Leukocyte aggregation
5. Stimulation of other mediators
Sources: 
Mast cells/basophils
Neutrophil
Monocytes/macrophage
Endothelium
Platelets
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8
Q

Cell Derived Inflammatory Mediators: 4. Cytokines

A 
Produces more leukocytes
TNF, IL-1 by macrophages when activated --> bacteria, immune complex, toxin, trauma, other cytokines
Level of activity:
1. Acute Phase Reaction
2. Effect on Endothelial cells
3. Effect on Fibroblasts
4. Effect on Leukocytes
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9
Q
  1. Acute Phase Reaction
A

fever, sleepiness, loss of appetite, APP, shock, increased neutrophils

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10
Q
  1. Effect on Endothelial cells
A

increase leukocyte adhesion, increased PGI2, increased thrombi activity, decreased anti-thrombi activity, increased production of IL-1,6 and PDGF

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11
Q
  1. Effect on Fibroblasts
A

increased fibroblast, secretion of collagen and collagenase + protease, PGE synthesis induction

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12
Q
  1. Effect on Leukocytes
A

increased secretion and production of IL-1,6

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13
Q

Systemic Effects of a Local Inflammation

A
  1. IL-1,6, TNF –> brain stem –> fever
  2. IL-1,6 –> liver –> APP
  3. IL-1,6, TNF –> increased leukocyte production
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14
Q

Pathological Effect of Local Inflammation

A
  1. TNF –> heart –> low output –> septic shock
  2. TNF –> endothelium –> thrombosis
  3. TNF, IL-1 –> skeletal muscle –> insulin resistence
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15
Q

Cell Derived Inflammatory Mediators: 5. Chemokines

A
  1. CXC –> neutrophils
  2. CC –> monocytes
  3. C –> lymphocytes
    - chmetaxis and leukocyte activation
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16
Q

Cell Derived Inflammatory Mediators: 6. ROS

A

source: neutrophils. lymphocytes

- cytotoxic agent

17
Q

Cell Derived Inflammatory Mediators: 7. NO

A 
a free radical
source:
1. endothelial cells --> eNOS --> anti-inflammation
2. macrophages --> iNOS --> microcidal --> inflammation
roles:
1. vasodilation
2. decreased leukocyte migration
3. platelet activation inhibition
4. microcidal
18
Q

Cell Derived Inflammatory Mediators: 8. Lysosomal Enzymes

A
  1. primary:
    - myeloperoxidase (MPO): green puss
    - lyzozyme (muramidase): hydrolysis of bacterial cell wall
    - acid hydrolase
    - elastase
    - BPI
    - Defensin
    - phospholipase A2
  2. secondary
    - lactoferin: anti-bacterial/fungal
    - collagenase
    - alkaline phosphatase
19
Q

Cell Derived Inflammatory Mediators: 9. Neuropeptide (substance P)

A 
source:
secreted by nerves in lung and GI tract
role:
pain signaling 
vasodilation
increased vascular permeability
20
Q

Plasma Derived Inflammatory Mediator: 1. Kinin System

A

factor XII (hageman) –> XIIa

  1. clotting cascade: XI –> IX –> X –> II (thrombin) –>
  2. I(fibrin) –> clot formation
  3. fibrinopeptide –> chemotaxis, increased vascular permeability
  4. kinin cascade: calcarin–> HMWK –> bradikinin
    - trombin: leukocyte adhesion, activation and acute inflammation
    - calcarin: plasminogen to plasmin –> fibrin desolation, C3 to C3a
21
Q

Plasma Derived Inflammatory Mediator: 2. Complement System

A

Ag-Ab complex –> C1 –> C3 convertase –> C5 convertase –> MAC

22
Q

Acute Inflammation Types

A
  1. Serous: low protein liquid –> blisters
  2. Fibrinous
  3. Suppurative –> abscess
  4. Ulcers: when epithelium is involved

Medical Pathology - Robin's Basic Pathology (9 decks)

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