MW L2 Acute Inflammation

Question 1

Aspects of RA that reflect acute inflammation

Aspects that reflect chronic

Answer 1

Acute: redness, chemical mediators, neutrophil recruitment
Chronic: cytokines, macrophage and lymphocyte recruitment

Question 2

What preformed mediators are released in acute inflammation

Answer 2

histamine

Question 3

What mediators are rapidly formed from membrane lipids

Answer 3

eicosanoids (PGE2, PGI2)
leukotrienes (LTB4)
PAF

Question 4

What do stimulated neurones release during local injury? (2)

Answer 4

Substance P

CGRP (calcitonin gene related protein)

Question 5

Proteinase activation results in production of mediators such as (2)

Answer 5

bradykinin
complement fragments (C3a and C5a)

Question 6

hours after local injury what is produced (3)

Answer 6

iNOS
COX-2
cytokines

Question 7

5 substances that cause vasodilation

Answer 7

Histamine
Eicosanoids
Neuropeptides
Bradykinin
Nitric oxide

Question 8

5 substances that increase vascular permeability

Answer 8

Histamine
Eicosanoids
PAF (platelet activating factor)
Bradykinin
C3a, C5a

Question 9

Which eicosanoids are vasodilators (2)
and
which increase vascular permeability (2)

Answer 9

Vasodilators: PGE2, PGI2

Increase permeability: LTB4, LTC4

Question 10

Vasodilators ………………….. with agents that increase vascular permeability

Answer 10

synergise

Question 11

Histamine and bradykinin increase plasma leakage by action on….

Answer 11

the endothelium

Question 12

What 4 neutrophil activators activate plasma leakage via neutrophil - dependent mechanism?

Answer 12

LTB4
fMLP
C5a
IL8

(so with no neutrophils nothing happens)

Question 13

Pathway of histamine synthesis

Answer 13

L-histidine (& histidine decarboxylase)
-> histamine

(& histaminase)
->Imidazolyl acetic acid

Question 14

Where is histamine stored?

Answer 14

Bound up in granules with heparin

Inside mast cells

Question 15

4 places mast cells are found

Answer 15

in skin, lungs, gut and nasal mucosa

Question 16

3 stimuli for histamine release

Answer 16

Type 1 immediate hypersensitivity via IgE
Chemicals (e.g. insect bite)
Mechanical injury to skin

Question 17

What response does histamine cause?

Answer 17

Triple response (flush, wheal and flare)

Question 18

What is flush?

Answer 18

arterial vasodilation

Question 19

What is wheal?

Answer 19

oedema formation

Question 20

what is flare?

Answer 20

axon reflex to release neuropeptides

Question 21

What is histamine’s effect on arterioles?

Answer 21

vasodilation via H1 receptors

Question 22

What is histamine’s effect on vascular post-capillary venules

Answer 22

permeability producing oedema

Question 23

What does H2 stimulation cause

Answer 23

gastric acid secretion

Question 24

What does H4 stimulation cause?

Answer 24

role in chemotaxis

Question 25

Hypersecretion of histamine results in what effect on the GI

Answer 25

excess acid production and formation of duodenal and peptic ulcers

Question 26

H1 is ….. coupled

Answer 26

Gq coupled

PLC —-> Ca2+

Question 27

H1 stimulation causes the release of …………. and ……….. which cause vasodilation

Answer 27

NO
and
neuropeptidases

Question 28

What is the effect of H1 on the airway and gut smooth muscle?

Answer 28

contraction

Question 29

H2 is coupled to..

Answer 29

Gs (adenylyl cyclase –> cAMP)

Question 30

H2 has what effect on smooth muscle

Answer 30

relaxation

Question 31

Chlorphenamie or newer drugs like loratadine are more lipophilic?

Answer 31

Loratadine

Question 32

H2 receptors are found on what cells?

Answer 32

Parietal cells

Question 33

H2 antagonists e.g. (2)

Answer 33

cimetidine and ranitidine

Question 34

Why do H2 antagonists interact with fuck loads of shit

Answer 34

inhibit p450

Question 35

Eicosanoids are derived from

Answer 35

arachidonic acid

Question 36

how many C in arachidonic acid

Answer 36

20

Question 37

Is arachidonic acid saturated?

Answer 37

no - unsaturated

Question 38

Where does arachidonic acid come from (2)

Answer 38

red meat or made indirectly via desaturation of linoleic acid

Question 39

What is the primary function of arachidonic acid?

Answer 39

component of membrane phospholipids

Question 40

What enzyme makes arachidonic acid and from what?

Answer 40

phospholipase A2

from phosphatidylcholine

Question 41

2 enzymes that metabolise arachidonic acid into two large groups of molecules

Answer 41

COX - into prostaglandins

5-lipoxygenase into leukotrienes

Question 42

Prostaglandins are further made into ……………….. and ……………

Answer 42

Thromboxanes (via thromboxane synthases)

and prostacyclins (via prostacyclin synthase)

Question 43

What does peroxidase do?

Answer 43

makes prostaglandin G2 into prostaglandin H2

Question 44

4 physiological functions of PGs

Answer 44

1. Initiation of labour (PGF2alpha and PGE2)
2. Inhibition of gastric acid secretion, increased gastric mucus production (PGE2)
3. Vascular (PGI2) - vasodilation and inhibition of platelet aggregation
4. Vascular (TXA2) - causes platelet aggregation and vasoconstriction

Question 45

What is COX1 for

Answer 45

housekeeping enzyme - constitutive -

normal of function of stomach, intestine, kidney and platelets

Question 46

What is COX-2 for

Answer 46

Induced particularly in inflammatory cells exposed to inflammatory stimuli

Question 47

What is COX-3 for?

Answer 47

found in animal brain tissue - relevance to human disease is controversial