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Pathology MBBS > Other Inflammations And Mediators > Flashcards

Other Inflammations And Mediators Flashcards

1
Q

Examples of primary or preformed cell derived mediators of inflammation

A

Histamine
Serotonin
Lysosomal enzymes

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2
Q

Examples of newly synthesised cell derived mediators of inflammation

A 
PAF
NO
Prostaglandin
Leukotrienes
Cytokine
Chemokines
Free radicals
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3
Q

Plasma derived mediators of inflammation are

A

Complement
Coagulation
Kinin

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4
Q

Stain for mast cell

A

Toluidine blue

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5
Q

Histamine

A 
Richest source: mast cell
Earliest to be released
Causes:
1. Vasodilation
2. Vasoconstriction (larger vessels)
3. Increased vascular permeability
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6
Q

Triggers of histamine

A

C3a,C5a
IL-1, IL-8
Physical agents like heat, trauma,…

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7
Q

Serotonin

A

Sources: platelets (major), enterochromaffin cells of GIT
Functions: same as histamine

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8
Q

Lysosomal enzymes that take part in inflammation are located in

A 
Granules of neutrophils
Of two types:
1. Primary/azurophillic
Large, coarse
2. Secondary
Small , fine
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9
Q

Primary granules of neutrophils contain

A 
MPO (myeloperoxidase)
BPI (Bacterial Permeability Increasing protein)
Lysozyme 
Neutral proteases
Neutrophil elastase
Defensins
Phospholipase A2
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10
Q

Secondary granules of neutrophils contain

A 
Lysozyme
Lactoferrin
Type 4 collagenase
Phospholipase A2
Gelatinase 
Alkaline phosphatase
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11
Q

ANCA

A

Anti Neutrophilic Cytoplasmic Antibody

Two types:
1. C ANCA
Anti proteinase 3
2. P ANCA
Anti MPO ANCA
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12
Q

PAF

Sources, functions

A 
All leukocytes, mast cells and platelets
Most potent inflammatory mediator 
Function:
1. Increased platelet aggregation
2. Vasodilation
3. Increased permeability
4. Bronchospasm
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13
Q

The major arachidonic acid producing step

Clinical significance

A

Phospholipids of the cell membrane are acted by phospholipase to produce arachidonic acid
Steroids generally inhibit this step as a result steps are generally anti inflammatory (broad spectrum anti inflammatory)

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14
Q

Products produced by the cyclooxygenase pathway of arachidonic acid

A
  1. PGI2 prostacyclin
  2. TXA2 thromboxane A2
  3. PGD2, PGE2, PGP-2alpha : prostaglandins
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15
Q

Products of lipoxygenase pathway of arachidonic acid

A
  1. Leukotrienes

2. Lipoxins

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16
Q

Cycloxygenase pathway

A 
Arachidonic acid ➡️ PGG2➡️ PGH2➡️:
1. PGI2
2. PGD2, PGE2, PGF2 alpha
3. TXA2
There are two cycloxygenase enzymes: COX-1 and COX-2 (inducible)
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17
Q

PGI2 and TXA2

A

Prostacyclin
Vasodilation
Decrease platelet aggregation
Role in inflammation

Thromboxane A2
Vasoconstriction
Increases platelet aggregation
Role in hemostasis

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18
Q

General functions of PHD2, PHE2 and PGF2 alpha

A

Causes vasodilation
Bronchospasm
Increased vascular permeability

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19
Q

Specific functions of prostaglandins

A

PGE2 - causes fever and pain
PGD2 and PGF2 alpha - role in neutrophil chemotaxis and
PGF2 alpha - uterine and bronchial smooth muscle contraction

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20
Q

Lipoxygenase pathway of arachidonic acid

A

Arachidonic acid ➡️ 5-HPETE➡️ LTA4 ➡️:

  1. LTB4 (chemotactic)
  2. LTC4 ➡️ LTD4➡️ LTE4 (these cause increased vascular permeability and bronchospasm)
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21
Q

Lipoxin functions

A

Anti inflammatory:

  1. Inhibits neutrophil chemotaxis
  2. Inhibits NK cell activity
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22
Q

Leukotrienes antagonists

A

Montelukast, zafurlukast
Bronchodilators
Treatment of bronchial asthma

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23
Q

Aspirin and other NSAIDs

A

Inhibits COX-1 and COX-2

Inhibits cycloxygenase pathway

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24
Q

Different types of chemokines

A
  1. C-X-C chemokines: neutrophil
  2. C-C chemokines: all except neutrophils
  3. C chemokines: lymphocytes
  4. CX3C chemokines: monocytes
    a,b,g,d
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25
Q

C-X-C chemokines

A

Alpha chemokine
Chemokine specific for neutrophil
Example: IL-8

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26
Q

C-C chemokines

A

Beta chemokine
Specific for all leucocytes except neutrophils
Eg.,
1. eotaxin -eosinophils
2. MCP-1 : monocytes
3. MIP-1 alpha: both monocytes and macrophages

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27
Q

C chemokine

A

Gamma chemokine
Specific for lymphocytes
Example: lymphotaxin

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28
Q

CX3C chemokine

A

Delta chemokine
Specific for monocytes
One example: fractalkine

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29
Q

Important application of chemokine receptor

A

Chemokine receptors like CXCR4 and CCT5 act as co-receptors for HIV

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30
Q

Characteristics of chronic inflammation

A
  1. Infiltration of tissues by mononuclear cells
  2. Tissue destruction
  3. Attempts at healing by angiogenesis and fibrosis
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31
Q

Macrophages of the body

A
  1. Liver: kupffer cells
  2. Brain: microglial cells
  3. Spleen and lymph nodes: sinus histiocytes
  4. Kidney: mesangial cells
  5. Placenta: Haufbauer cells
  6. Lungs: pulmonary alveolar macrophages or dust cells
32
Q

Classical activation of macrophage steps

A
  1. Induced by interferon-gamma and endotoxin
  2. Produced IL-1, 6, 12
  3. M1 macrophage produced
33
Q

Mechanism of action of classically activated M1 macrophage

A
  1. ROS
  2. NO
  3. Lysosomal enzymes

Kills the bacteria
Causes tissue destruction

34
Q

Activation of macrophages via the alternate pathway

A
  1. Induced by IL-4 and IL-13
  2. Produces IL-10 and THF-beta
  3. M2 macrophage
35
Q

Action of alternatively activated M2 macrophages

A
  1. Anti inflammatory

2. Fibrosis (TGF-beta)

36
Q

Granuloma

A

Collection of modified or activated macrophages called epitheloid cells surrounded by collar of lymphocytes and sometimes giant cells

37
Q

Giant cell is formed by

A

Fusion of epitheloid cells

38
Q

Types of giant cells

A
  1. Foreign body giant cell
  2. Langhan’s giant cells
  3. Touton giant cell
  4. Tumour giant cell
  5. Reed-Sternberg cells
  6. Osteoclastic tumour giant cell
  7. Warthin Fikendy giant cell
39
Q

Foreign body giant cells

A

Haphazard nuclei like tumour giant cells

40
Q

Langhan’s giant cells

A

Nuclei arranged as horse shoe

Characteristic of TB

41
Q

Touton giant cell

A

Nuclei surrounded by fat droplets

Characteristic of xanthoma

42
Q

Warthin Fikendy giant cell is seen

43
Q

Mechanism of granuloma formation

A

It is a type 4 hypersensitivity reaction

  1. Antigen reacts with CD4 TH1 cells
  2. Interferon-gamma is produced
  3. Activates macrophage
  4. Granuloma formation
44
Q

List of granulomatous diseases

A
  1. TB
  2. Sarcoidosis
  3. Leprosy
  4. Syphillis
  5. Chronic granulomatous disease
  6. Cat scratch disease
  7. Crohn’s disease
  8. Wegner’s granulomatosis
  9. Berylliosis
  10. Churg Strauss syndrome
45
Q

Granuloma classification

A
  1. Immune granuloma
  2. Foreign body granuloma:
    Haphazard nuclei
46
Q

Caseating granuloma is seen in

A
  1. TB
  2. Histoplasmosis
  3. Coccidiomycosis
  4. Syphillis
47
Q

Non caseating granuloma

A
  1. TB
  2. Sarcoidosis
  3. Crohn’s disease
  4. Hodgkins lymphoma
48
Q

Naked granuloma

A

Absences of lymphocytic collar

Seen in sarcoidosis

49
Q

Stellate granuloma

A

Cat scratch disease

50
Q

Durks granuloma

A

Seen in P. falciparum malaria

51
Q

Doughnut granuloma/ fibrin granuloma

A

Seen in Q fever

52
Q

Eosinophilic granuloma

A

Seen in Churg Strauss syndrome

53
Q

Necrotising granuloma

A

Wegner’s granulomatosis

54
Q

NO formation

A

Also know as endothelium derived relaxation factor (EDRF)

Produced from arginine by NO synthetase via cGMP pathway

55
Q

NO synthetase

A

3 forms

  1. eNOS- endothelial
  2. nNOS-neuronal
  3. iNOS- inducible
56
Q

Function of NO

A
  1. Vasodilator
  2. Smooth muscle relaxation
  3. Decreases platelet aggregation
  4. Microbicidal via PAN
57
Q

Cytokines of acute inflammation

A
  1. IL-1: fever
  2. IL-6
  3. TNF-alpha:
    Most important in systemic inflammatory response syndrome, cancer cachexia
58
Q

Functions of cytokines of acute inflammation

A
  1. Produce systemic effects of inflammation:
    fever, increased sleep, increased ESR, decreased appetite
  2. Endothelial activation
  3. Chemotaxis: IL-8
59
Q

Cytokines of chronic inflammation

A
  1. IL-12
  2. IL-17
  3. IFN-gamma (interferon):
    Important for granuloma formation
60
Q

Most fibrogenic cytokine

A

TGF-beta

Transforming growth factor-beta

61
Q

Anti inflammatory cytokines

A

IL-4,6: both pro and anti inflammatory
IL-10,13
TGF-beta (fibrogenic)

62
Q

Complement system

A 
Series of 20 proteins activated by three pathways:
1. Classical: 
starts with activation of C1
2. Alternate: “” C3
3. Lectin/mannose binding pathway: “” C1
63
Q

The various pathways of complement activation are activated by

A 
1. Classical:
Ag-Ab complexes
2. Alternate:
LPS, cobra venom, endotoxins
3. Lectin/mannose binding pathway: by lectin or mannose
64
Q

Most critical step in complement cascade

A

Formation of C3

65
Q

Final step of complement cascade

A

C5b-9 membrane attack complex

66
Q

Different types of chemokines

A
  1. C-X-C chemokines: neutrophil
  2. C-C chemokines: all except neutrophils
  3. C chemokines: lymphocytes
  4. CX3C chemokines: monocytes
    a,b,g,d
67
Q

Functions of complement proteins

A 
1. Act as anaphylactic toxins:
C3a, C5a
2. Opsonins:
C3b
3. Killing of microbes:
C5b-9 (membrane attack complex)
4. Chemotactic agents:
C5a
68
Q

Diseases caused by complement protein deficiencies

A
  1. Hereditary angioneurotic edema
  2. Risk of SLE
  3. Risk of pyogenic infection
  4. Paraoxysmal nocturnal haemoglobinuria
69
Q

Hereditary angioneurotic edema

A

Deficiency of the complement protein C1 inhibitor (C1 INH)

70
Q

Deficiency of C2 or early components of complement leads to

A

Risk of SLE systemic lupus erythematosis

71
Q

Deficiency of C3 or late components of complement proteins

A

Risk of pyogenic infection

72
Q

Kinin cascade

A

Produces bradykinin

  1. Pre Kallikrein➡️ kallekrein by factor 12 Hageman factor
  2. High molecular weight kininogen is produced
  3. Bradykinin is produced
73
Q

Bradykinin function

A
  1. Increased vascular permeability
  2. Pain
  3. Vasodilation
  4. Bronchospasm
74
Q

Coagulation cascade factors

A
  1. Fibrinogen: can act as opsonin
  2. Thrombin:
    link between coagulation and inflammatory pathway
    Redistribution of E selectin
  3. Fibrinopeptides:
    Chemotaxis
75
Q

Deficiency regulators of complements like CD55, CD59

A

Paraoxysmal nocturnal haemoglobinuria

PNH

76
Q

Alpha 1 anti trypsin deficiency is seen in

A

Panacinar emphysema

Liver disease

77
Q

Microscopy of alpha 1 anti trypsin

A

PAS positive

Globules in hepatocytes

Pathology MBBS (17 decks)

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