7.2.1 Inflammation: Mediators and Targets Flashcards

1
Q

What is acute inflammation and what are the 5 cardinal signs?

A

Immediate response to injury with short duration

  • Rubor (redness)
  • Calor (heat)
  • Tumor (swelling)
  • Dolor (pain)
  • Functio laesa (loss of function)
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2
Q

What is chronic inflammation and why does it occur?

A

On-going, repeat cycles, flare-up of inflammation.
- Stimulus not effectively removed
- Stimulus overwhelms system
- Stimulus by-passes immune response
- Lack of effective resolution and repair
- Immuno-suppressed

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3
Q

What do mediators of inflammation do?

A

Required for resolution and repair following inflammatory insult. Cause vascular and cellular changes, inflammatory pain and pruritus in inflamed tissue.

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4
Q

What are cytokines?

A

Peptides that work in medium-long term by inducing cellular changes. Druggable.
Released into circulation to cause acute phase proteins by liver and increase temp., blood flow, vascular permeability

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5
Q

What are chemokines?

A

Chemoattractant cytokines that cause inflammatory cell recruitment.

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6
Q

What mediators are stored in cells?

A
  • Histamine
  • Neuropeptides
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7
Q

Where is histamine stored and how does it produce its effects?

A

Store in mast cells, platelets, basophils
Activates cell surface receptors
Mass histamine release = hypersensitivity and anaphylactic reaction

H1 receptor involved in inflammation

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8
Q

Inflammatory mediators can be

A

Stored in cells
Synthesised by activated cells
Derived from precursors in plasma

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9
Q

Give examples of mediators synthesised on cell activation

A

Lipid mediators:
- prostaglandins
- leukotrienes
- platelet activating factor (PAF)

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10
Q

Describe the synthesis of prostaglandins

A

Cell activation -> phospholipase A2

Cell membrane phospholipid -P A2-> arachidonic acid

arachidonic acid -COX-> pGs and Tx

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11
Q

Describe the actions of NSAIDs

A

Non-Steroidal Anti-Inflammatory Drugs
NSAIDs block the action of COX so prevents conversion of arachidonic acid to PGs and Tx

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12
Q

Describe the synthesis of leukotrienes (LTs)

A

Arachidonic acid -(5-LO)-> LTs

Can be blocked experimentally

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13
Q

Describe the actions of leukotriene D4 receptor antagonists

A

Zafirlukast (Accolate)
Monolukast (Sigulair)

Reduce bronchoconstriction
Asthma prophylaxis

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14
Q

Describe the synthesis of platelet activation factor and what is its action?

A

Cell membrane phospholipid -lyso-PAF-> PAF

Platelet aggregation
Chemoattractant for leukocytes
Oxidative burst

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15
Q

Give 5 examples of mediators derived from precursors in plasma

A
  • Bradykinin (BK)
  • Factors of the complement system (C5a)
  • Opsinogens
  • Chemoattractants
  • Pore-forming complex
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16
Q

What is bradykinin role and how is it inactivated?

A

Increases bloodflow = redness and heat
Sensitisation of sensory nerve endings = pain

Inactivated by ACE in lungs and kidney