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RMS > Inflammatory mediators > Flashcards

Inflammatory mediators Flashcards

1
Q

What is the inflammatory response?

A
  • short term acute response
  • defensive
  • quickly resolved
  • innate, non-adaptive

(BUT the immune response is adaptive)

microvascular effects are triggered from a variety of cells and plasma around these vessels

involves local hormones, inflammatory mediators

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2
Q

Acute microvascular changes in the inflammatory response

A
  • release of inflammatory mediators
  • accumulation of inflammatory cells
  • repair and healing
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3
Q

types of inflammatory mediators produced

A
  • histamine- amine
  • bradykinin- peptide
  • nitric oxide
  • eicosanoid- lipid
    protaglandins
    leukotrienes
  • neuropeptides- peptides
    substance P
  • cytokines- peptides
    interleukin 1
  • complement
    PAF
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4
Q

what changes occur to the microcirculation?

A
  • increased blood flow in arterioles

- oedema formation and cell accumulation due to increased vascular permeability in the venules

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5
Q

in what cells, tissues and fluid does increased blood flow occur?

A
  • endothelial cells
  • inflammatory cells
  • sensory nerves
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6
Q

what vasodilators act on endothelial cells and inflammatory cells?

A
  • prostaglandins and nitric oxide
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7
Q

vasodilators that act on sensory nerves?

A

neuropeptides e.g. CGRP

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8
Q

Direct acting oedema producing mediators?

A
  • histamine
  • substance P
  • bradykinin
  • PAF
  • leukotrienes

cause plasma extravasation leading to oedema formation

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9
Q

5 steps in neutrophil- endothelial cell interactions

A

1) rolling
2) cell adhesion molecule expression CAM
3) adherence
4) extravasation
5) phagocytosis

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10
Q

mediators that lead to neutrophil accumulation in tissues

A

1) neutrophil activating agents
LTB4, C5a, IL-8

2) endothelial adhesion molecule stimulants
TNF, IL-1

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11
Q

what is histamine formed from?

source of histamine?

A

from L-histidine

mast cells and basophils

preformed/ release in allergic/ hypersensitivity (IgE) responses

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12
Q

What do H1 receptors mediate?

A
  • vasodilation/ increased blood flow
  • increased microvascular permeability
  • itch
  • gastric acid secretion
  • smooth muscle contraction e.g. bronchoconstriction
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13
Q

Name some H1 antagonists

A

chlorpheniramine

mepyramine

involved in allergy, hayfever and skin irritations

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14
Q

Sedating H1 receptor antagonist

A

chlorpheniramine

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15
Q

non sedating H1 receptor antagonist

A

terfenadine
cetirizine
astemizole

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16
Q

role of sensory C and A delta fibres

A
  • transmit sensory info to CNS
  • initiate reflexes
  • nociception (pain and itch)
  • release neuropeptides- substance P, CGRP and VIP
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17
Q

stimulants of sensory nerves, C and A delta fibres

A
  • mechanical (pressure)
  • temperature (cold and heat)
  • chemical (mediators & capsaicin)
18
Q

effect of histamine when injected into the skin

A

1) local reddening due to increased blood flow
forms a wheal (up to 1cm)

2) oedema- wheal at site of intradermal injection
3) axon reflex flare

mediated by sensory nerves C & A(delta) fibres

response is inhibited by H1 receptor antagonist

19
Q

what nerve fibres mediate itch?

A

5% of afferent C fibres in the skin

  • respond to histamine
  • insensitive to mechanical stimuli
  • conduct velocities of 0.5m/s
    (1/2 of that of normal C fibres)

anti-histamines are effective anti-itch agents

20
Q

what is NO synthesised from

A

L- arginine

  • constitutive nitric oxide synthase in endothelial cells and neurones (eNOS & nNOS)
  • synthesis of NO in other cells- macrophages involved inducible nitric oxide iNOS
21
Q

roles of NO

A
  • regulation of blood flow/pressure
  • host response to infection
  • neurotransmitter
  • pain

can react to yield further cytotoxic radicals e.g. peroxynitrite

22
Q

actions of nNOS

A
  • long term potentiation
  • coordination between neuronal activity and blood flow
  • pain modulation
23
Q

action of eNOS

A
  • regulation of vascular tone
  • inhibition of SMC proliferation
  • inhibition of platelet aggregation
24
Q

action of iNOS

A
  • cytotoxicity against bacteria, viruses and other microorganisms
25
Q

what is bradykinin

A

one of a family of peptides formed in the plasma by the activity of enzymes on tissue fluid substrates called kininogens

26
Q

what is bradykinin metabolised by

A

ACE

carboxypeptidase

27
Q

where is bradykinin found

A
  • in nasal cavity

during allergic rhinitis

28
Q

actions of B2 receptors

A
  • increased blood flow
  • increased microvascular permeability
  • nociception
  • bronchoconstriction
  • nasal blockage

are constitutive

29
Q

what are B2 antagonists used for ?

A

to inhibit the effect of some angioedemas

30
Q

action of B1 receptors

A
  • induced in inflammation

mediate similar responses

esp pain

31
Q

what two enzymes act on arachidonic acid and what do they form?

A

COX- PG’s and TXA

5- lipoxygenase- leukotrienes

32
Q

what are LT-antagonists or inhibitors used for?

A

in asthma

33
Q

what do PGE2 & PGI2 mediate?

A

released from endothelial cells and white blood cells

  • mediate increased blood flow and hyperalgesia
34
Q

action of PGD2

A

are released from mast cells and are less potent

35
Q

actions of LTC4 and LTD4

A

increase microvascular permeability and are bronchoconstrictors

36
Q

action of LTB4

A

a chemotaxin

recruits neutrophils to inflammatory sites

37
Q

name some non-selective inhibitors of PG’s

A
  • aspirin
  • ibuprofen
  • indomethacin

side effects on the gut and kidney

38
Q

name some COX-2 selective inhibitors

A
  • celecoxib
  • roecoxib
  • meloxicam

fewer gut side effects but adverse cardiac effects

39
Q

how does ice help in inflammation

A

suppress vasoactive components e.g. swelling

40
Q

local anaesthetics and noradrenaline

A
  • suppress sensory nerve activity

- reduce blood flow

RMS (8 decks)

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