Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PA20309 > Inflammation > Flashcards

Inflammation Flashcards

1
Q

What is the ‘Triple Therapy’ for RA?

A

A treatment with 3 csDMARDS

Methotrexate, Sulfasalazine and Hydroxychloroquine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are Matrix Metalloproteinases (MMPs)?

A

Enzymes that break down collagen

Active at neutral pHs, and require Zn2+

Activated by the removal of propeptides by other proteases

Can be inhibited by Tissue Inhibitors of Metallo-Proteinases (TIMPs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the main ‘risk’ genes for RA?

A

Genes in the MHC region

Eg, HLA-DRB1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Explain the Reactive Oxygen Species pathway

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is LAD-1?

A

An adhesion deficincy

Leukocytes do not adhere to extracellular material or endothelium

Leukocytes deficient in the B2 integrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is Rheumatoid Arthritis?

A

The persistant joint inflammation (of synovium) of at least 3 joint areas

Early morning stiffness of at least 30 min duration

1% of people in the UK have RA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are Anti-Citrullinated Protein Antibodies (ACPA)?

A

These are highly specific for RA

Can be found in the body up to 14yrs before the onset of RA symptoms

Can predict erosive and progressive disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the main active ingrediant in Sulfasalazine?

A

Sulfinpyradone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is Leflunomide?

A

A new DMARD

Inhibits dihydro-oroate dehydrogenase –> used in the ynthesis of pyrimidines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Explain Prostanoid receptors

A

PGE2 (prostaglandins)–> EP1 - 4 Act on very specific GPCRs on target cells

PGI2 (prostacyclin) –> IP

Thromboxane receptor = TP

PGD2 –> DP1 + 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the effect of RONS?

A

Activation of inflammatory gene transcription

Amino acid modifications

DNA damage –> cell apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the EP3 receptor?

A

A prostaglandin receptor

Activates leukocytes and mast cells

Promotes oedema formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are Chemokines?

A

Chemotactic Cytokines

Produced in responce to bacteria, TNF and IL-1

Act on GPCRs

2 Types

CXC –> Neutrophil attractants

CC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are eicosanoids?

A

Oxidation products of 20carbon long fatty acids

Primerily from Arachidonic Acid

Main type is prostaglandins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are chemotaxins?

A

Molecules that attract and activate leukocytes (increasing integrin avidity and affinity)

2 types…

Non Selective

Selective = Chemokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Explain how low dose aspirin is beneficial……and how therefore taking a COX-2 selective NSAID can have adverse effects

A

Aspirin is selective to COX-1, and so prevents (pro-thrombotic) thromboxane from platelets, which will decrease the chances of clotting)

This is effective as platelets cannot remake proteins as they have no nucleus, so this effect occurs for a period of time. Also the endothelial produced PGI2 is unaffected

However, when a COX-2 inhibitor is used, PGI2 production stops, and so clotting becomes much more common, as the pro-thrombotic thromboxane is still present (as COX-1 isn’t inhibited)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the key indications of poor outcome in RA?

A

Genetics –> eg, the HLA-DRB1 genotype present

Lab Results –> RF or ACPA presence…..high CRP level

Clinical Assessment –> Many active joints and poor scores

Low educational / social-economical circumstances

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is Rheumatoid Factor?

A

Antibodies that bind to the Fc domain of IgG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the 2 neuropeptides that can positively feedback on histamine release and oedema formation?

A

NKA (Neurokinin A)

CGRP

20
Q

Explain which each of the 3 selectins are

A

L - Expressed on inactivated leukocytes

This causes leukocyte activation, which increases avidity (stickability)

There is rapid shredding of the selectin by proteolytic cleavage (shedase)

P - Expressed on platelets and endothelium

Start in granules, and are rapidly translocated to the cell surface upon activation

E - Endothelial expression is induced by cytokines or LPS

Required ‘de novo’ synthesis –> made on demand –> so takes time (hours)

Their expression is inhibited by glucocorticoids

21
Q

What is Rituximab?

A

A B cell depleting monoclonal anti-CD20 antibody

22
Q

What are the 5 cardinal signs of inflammation?

A

Heat

Redness

Swelling

Pain

Loss of Function

23
Q

What is the enzyme that primarily controls steroid biosynthesis?

A

HMG-CoA Reductase

Produces mevalonic acid

24
Q

What are the 3 things that plasma proteases are used to create, in reference to inflammation

A

Kinins (Bradykinin) –> Increases permeability/vasodialtion and pain

Complement –> Activates leukocytes, mast cell degranulation, and bacterial lysis and opsonisation

Clotting Cascade –> Amplifies the kinin and complement pathways

Also causes thrombosis and platelet activation

25
Q

What are Leukotrienes (LTs)? And what are their actions?

A

A classic eiconisoid

Bronchoconstriction

Oedema

Chemotaxis

Present in inflammation

26
Q

What is a selectin?

A

A lectin-like adhesion molecule

So bind to carbohydrate molecules weakly

Important in the tethering of leukocytes to the endothelium

27
Q

What is leukocyte adhesion deficiency II (LAD-II)?

A

Patients have defective fucose (a CHO) metabolism

So leukocytes do not express the correct ligands for selectins….. which causes a reduced ‘rolling’ response (for E/P selectins only)

So less white blood cells where the inflammation has taken place

Reccurent infections without pus

28
Q

What are integrins?

A

Heterodimeric proteins that re expressed on the surface of leukocytes

Important for ‘Firm Adhesion’

When leukocytes are activates, a conformational change of the integrin occurs, increasing avidity (stickiness) and affinity

29
Q

What is Angioedema?

A

Deep cutaneous and mucosal swelling

Can be induced from ACE inhibitors

Driven mainly from mast cell degranulation (release of histamine) –> due to the activation of plasma proteases

30
Q

How does Oedema (swelling) occur?

A

H1 receptor binding of histamine causes endothelial-derived Nitric Oxide to be released, causing arteriolar dialation

The endothelium then contracts, which makes venules leaky –> increasing permeability

31
Q

What are fevers regulated by?

A

PGE2 in the anterior hypothalamus

32
Q

What do Aspirin and Ibuprofen do?

A

Aspirin - Acetylates COX irreversibly (covalent bond)

Ibuprofen - Competitive inhibitor of COX, preventing arachidonate from binding

33
Q

Explain anti-LT therapies

A

Glucocorticoids - Indirect inhibition of the formation of anachidonic acid (and so all other pathways)

Zileutin - Blocks the conversion of anachidonic acid to leukotrienes via the enzyme 5-lipoxygenase

Montelukast/Zafirlukast - A leukotriene receptor antagonist

34
Q

What is Abatacept?

A

Blocks the interaction of CD80 and CD86 on CD28 of T cells

35
Q

What are the 2 ways that plasma leakage can occur?

A

Neutrophil Dependent

H1 receptors and histamine

This means that just using an H1 antagonist will not remove all inflammatory mediaters!!

36
Q

What do Serine and Cysteine proteinases do?

A

Break down matrix proteins, like Elastin, proteoglycans and chondroitin sulfate

Inhibited by serpins

Eg, Neutrophil Elastase

37
Q

What type of MMP inhibitor targets the active site Zn2+?

A

Hydroxamate

38
Q

What are the 4 main physiological functions of prostanoids?

A

Initiation of labour

Inhibition of of gastric acid secretion, increased gastric mucus production

Inhibition of platelet aggregation and vasodialation (PGI2 - Prostacyclins)

Platelet aggregation and vasoconstriction (TXA2 - Thromboxane)

39
Q

What is the effect of proteases in angioedema?

A

ACE inhibitors block the breakdown of bradykinin –> increasing the inflammation

Hereditary factors can include increased complement and bradykinin activation –> by increasing kininogenase and decreasing protease inhinitors

40
Q

What is ICAM and VCAM?

A

Ligands for integrins

ICAM - Intracellular Adhesion Molecule

ICAM-2 = Expressed basally on endothelium

ICAM-1 = Induced by cytokines

Binds B2 integrins

VCAM - Vascular Cell Adhesion Molecule

Induced by cytokines

Binds A4 integrins

41
Q

What is a lectin?

A

A molecule that binds to carbohydrates

42
Q

What is the DAS28 score?

And what is the HADQI score?

A

DAS28 - Provides a number on a scale of 1-10 which indicates the current activity of the disease

HADQI - A score 0-3 which tells us how much difficulty they are having in performing various activities

43
Q

Explain the stages of inflammation over time after a local injury (eg, seconds –> mins –> hours)

A

Seconds - Pre-formed substances like histamine are released

NKA, CGRP (peptides) and eiconisoids (lipid membranes) are released/produced

Minutes - Production of bradykinin and complement fragments following proteinase activation

Infiltration cell products are released

Hours - Transcription/translation of proteins like COX-2 and cytokines

44
Q

What are the 5 main types of drug treatments for RA?

A

Analgesics –> Paracetamol

NSAIDs –> Ibuprofen (COX) and Celecoxib (COX-2)

Glucocorticoids –> Prednisolone

csDMARDS –> Methotrexate

bDMARDS –> Biologics

45
Q

What are the 4 stages of Leukocyte Diapedesis?

A

Circulating

Tethering/Rolling

Firm Adhesion

Transmigration

46
Q

What is the monoclonal antibody that targets the A4 integrin?

A

Natalizumab (Tysabri)

Inhibits T lymphocyte interactions with brain endothelium

PA20309 (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions