Pain And Inflammation

Front 1

What is inflammation?

Back 1

The host response to injury (infection, trauma, hypersensitivity)

Front 2

What is the role of inflammation?

Back 2

Get molecules and cells that can help in the site of damage.

Front 3

describe vasodilation

Back 3

increased blood supply to site of damage. Delivelry of cells/molecules to area of damage. Causes redness and heat.

Front 4

What does vascular permeability allow?

Back 4

molecules to escape from capillaries.

Front 5

What kinds of plasma proteins escape capillaries?

Back 5

complement components, clotting components, fibrinolytic system, kinin system, Abs

Front 6

What is leukocyte extravasation?

Back 6

movement of white blood cells into tissues.

Front 7

what types of white blood cells predominate in the early stages of inflammation and what types predominate in the later stages?

Back 7

early= neutrophils

later= monocytes and lymphocytes.

Front 8

what is the function of mast cells and basophils?

Back 8

stimulate inflammation, they have granules which contain inflammatory mediators

Front 9

what do granulocytes (neutrophils and eosinophils) do?

Back 9

phagocytose and destroy invading organisms

Front 10

what do mononuclear phagocytes do?

Back 10

phagocytose and destroy, produces cytokines

Front 11

name 3 vasoactive inflammatory mediators

Back 11

1. Histamine 2. 5-hydroxytryptamine 3. Kinins

Front 12

Name 2 lipid inflammatory mediators

Back 12

1. Eicosinoids 2. Platlet activating factor (PAF)

Front 13

name 3 protein classes which can be used as inflammatory mediators.

Back 13

1. complement components 2. cytokines 3. chemokines

Front 14

Name the 5 general stages of inflammation

Back 14

1. Vasoconstriction

2. Dilation of small blood vessels

3. increased vascular permeability

4. Endothelial cell activation - alters endothelial cell activity

5. repair and resolution

Front 15

What are the 3 processes involved in the restoration of normal tissue architecture?

Back 15

1. Stromal cell remodelling

2. expression of proteases ( Break down collagen)

3. Changes in extracellular matrix composition

Front 16

how are inflammatory cells cleared?

Back 16

apoptosis

Front 17

what is the general action of histamine?

Back 17

act on blood vessels and causes increased vascular permeability

Front 18

Where is histamine stored before it is released?

Back 18

In granules of mast cells and basophils

Front 19

What other mechanism can be used in order for degranulation to occur ? (histamine)

Back 19

- Complement activation ( C3a and C5a)

- Action of molecules produced in response to tissue damage (e.g cytokines)

- mechanical damage

Front 20

Which receptors does histamine act on?

Back 20

H1, H2, H3, H4(in bone marrow)

Front 21

which histamine receptor stimulates inflammation?

Back 21

H1

Front 22

What is the action of the H1 histamine receptor when histamine binds?

Back 22

-vasodilation due to action on vascular smooth muscle

- causes endothelial cells to contract- formation of interepithelial gaps

- Constriction of smooth muscle- if it occurs in airways patient will experience shortness of breath. can be fatal.

Front 23

What does the kinin system generate?

Back 23

generates powerful vasoactive mediators which cause vasodilation

Front 24

What are the 2 vasoactive mediators produced by the kinin system?

Back 24

1. bradykinin 2. lysyl-bradykinin

Front 25

What does bradykinin do? (4 things)

Back 25

1. venular dilation

2. Increased vascular permeability

3. Stimulation of pain nerve endings

4. Smooth muscle contraction

Front 26

When is bradykinin made? (in response to what?)

Back 26

1. activation of cascades (clotting and plasmin system)

2. damaged tissue

Front 27

Describe the pathway to produce an active form of bradykinin

Back 27

prekallikrein--> Xlla (12a)--> kallikrein + high molecular weight kininogen --> Bradykinin

Front 28

describe the production of lysyl-bradykinin

Back 28

Prokallikrein + plasmin + Tissue enzyme --> tissue kallikrein + low molecular weight kinonogen --> lysyl-bradykinin

Front 29

What group of enzymes will inactivate bradykinin and lysyl-bradykinin? Why are they produced?

Back 29

1. Kinases

2. Produced in order to prevent too much damage

Front 30

Name 3 eicosanoids

Back 30

1. Prostaglandins (PG)

2. thromboxanes (TX)

3. leukotrienes (LT)

Front 31

What are eicosanoids produced from?

Back 31

phospholipids are converted to arachidonic aid by phospholipase A2.

Front 32

How is phospholipase A2 activated?

Back 32

Phosphorylation in response to stimuli. Such as C5a, bradykinin , general cell damage.

Front 33

How is leukotriene produced from arachidonic acid?

Back 33

By 5-lipoxygenase

Front 34

How are prostoglandins produced from arachidonic acid?

Back 34

By cyclo-oxygenase

Front 35

where is cyclo-oxygenase 1 found?

Back 35

the majority of cells

Front 36

where is cyclo-oxygenase 2 found?

Back 36

- Nowhere, it's release is stimulated by inflammatory signals

Front 37

What are the predominant prostonoids in acute inflammation?

Back 37

PGE2, PGI2 (from local tissue/blood vessels) and PGD2 (from mast cells)

Front 38

what two prostanoids are key in chronic inflammation and where are the released from?

Back 38

PGE2 and TXA2, released from mononuclear phagocytes

Front 39

Name the three prostanoids which are strong vasodilators

Back 39

1. PGE2 2. I2 3. D2

Front 40

Name the prostanoid which is pyrogenic (causes fever)

Back 40

PGE2

Front 41

how many classes of prostanoid receptor are there?

Back 41

5

Front 42

where is 5-lipoxygenase found in the body? (there are 4)

Back 42

lungs, platelets, mast cells and leukocytes

Front 43

What position in the arachidonic acid is the OH group added? What effect does this have?

Back 43

on C5, causes the resulting molecule (LTA4) to be v unstable

Front 44

Which leukotrine is a potent chemotactic factor fro neutrophils and macrophages?

Back 44

LTB4

Front 45

What do neutrophils do?

Back 45

increase adhesion moloecule

Front 46

what do macrophages do?

Back 46

stimulate proliferation and cytokine release

Front 47

What is the function of cytokines?

Back 47

promote infalmmation

Front 48

Name some pro-inflammatory cytokines

Back 48

1. TNF= tumour necrosis factor

2. IL1, IL-6, IL-8, IL-12

3. interferon-gamma

Front 49

Where is TNF produced?

What does it do?

Back 49

Made in mononuclear phagocytes

induces expression of adhesion molecules and chemokine production in endothelial cells. Also activate phagocytes

Front 50

What does IL-1 do? What symptoms does it induce?

Back 50

induce adhesion molecules and chemokines on endothelial cells. Causes fever, increased apetite and induces sleep.

Front 51

Where is IL-6 produced?

What effect does it have?

Back 51

In the liver.

responsible for the acute phase response

Front 52

When IL-6 is produced it causes an increased production in molecules which are associated with the innate immune response. Name these 4 molecules and give their function.

Back 52

1. Alpha-1-antitrypsin: protease inhibitors

2. Fibrogen: coagulation protein

3. C-reactive protein: complement activation

4. MBL: Complement activation

Front 53

what is the function of chemokines?

Back 53

Attract cells to inflammation site and control leukocyte migration

Front 54

What is the function of lysosomal compounds and what do they include?

Back 54

Cause tissue damage, include catitonic proteins and proteases.

Front 55

Name two vasoactive mediators that elicit pain.

Back 55

1. 5-HT

2. bradykinin

Front 56

As well as the two vasocative mediators what potentiates their effect?

Back 56

PGE2

Front 57

Outline the process of fever induction and the body response.

Back 57

Invading pathogen stimulates macrophages to release IL-1, IL-10 and TNF.

This stimulates PGE2 synthesis in the endothelial cells of the hypothalamus.

PGE2 alters the thermoregulatory set-point.

results in vasoconstriction and shivering

Front 58

What does fever help?

Back 58

1. host defence works better

2. faster lymphocyte division

3. bacterial/viral replication is inhibited

Front 59

What are the 4 detrimntal effects of inflammation?

Back 59

digestion of normal tissue (By proteases)

Swelling (e.g acute meningitis) also impedes blood flow

inappropriate/prolonged inflammatory response (cause wasting)

inflammatory disease(arthritis, IBD)

Front 60

Describe the general mode of action of glucocorticoids

Back 60

Enter cell and bind to cytoplasmic receptor GR-alpha and GR-beta. Transported into nucleus, alter gene expression

Front 61

Describe the general mode of action on NSAIDs

Back 61

Inhibit COX-1 and COX-2. This decreases the production of prostaglandin and thromboxan.

Front 62

What are effects of COX-1 inhibition ?

Back 62

Antipyretic effect (returns set point to normal)

Analgesic

anti-inflammatory- reduce vasodilation and oedema. Aspirin inhibits NFkB expression

Front 63

what are the irreversible side effects of Aspirin ?

Back 63

Irreversble inhibition of COX-1 and COX-2. Inhibits platelet aggregation so is used in patients who suffer from myocardial infarction. Increased gastric bleeding. Linked to Reye's syndrome in children