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Flashcards in RA Deck (46)
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1
Q

RA is a chronic inflammatory disease affecting primarily

A

synovium

2
Q

Epidemiology RA

A

female 30-50s

3
Q

Etiology of RA

A

genetic + envrio

HLA-D4 and smoking are the big ones
= predispose person to auto Abs against type 2 collagen and fibrinogen

4
Q

How does smoking contribute to the pathogenesis of RA? (potentially)

A

ok this might not be 100% right but I was piecing together info from the lecture and the textbook bc neither were very clear..

  • Activates enzyme that converts arg to citrulline. Citrulline is deposited in synovium and is attached to collagen and fibrinogen. It is recognized as a foreign substance and immune response is mediated against it →inflammation in synovium → destruction of joint
  • Also/Or smoking thought to cause citruallation: a process that modifies Ag (type II collagen and fibrinogen) to match the “shared epitope” of the HLA alleles
5
Q

Ab to Fc portion of IgG

A

rheumatoid factor

6
Q

What is the orignation of RF

A

bone marrow

7
Q

Auto Ab most specific to RA

A

ACPA

8
Q

predictor/assc with aggressive dz

A

high titers of RF and ACPA

9
Q

cause mast cell and basophil degranulation

A

ACPA

10
Q

systemic Ag that RA auto-Abs recognize

A

glucose phosphate isomerase

11
Q

joint Ag tht RA auto-Abs recognize

A

type II collage

also fibrinogen, proteoglycans

12
Q

How is the synovial lining altered in RA?

A

undergoes hyperplasia

FLS: invade and damage cartilafe by producing MMPs, serine proteases, cathepsins, aggrecanases

13
Q

What is the shared epitope

A

5 aa sequence on Beta chain of HLA-D4 MHC class II haplotypes that correspond to an Ag that is anthrogenic (molecular mimic of type II collagen)

14
Q

What infections are proposed to cause RA

A

mycobacterium, Parvo B19, MTB, EBV, retroviruses, enteric bacteria

15
Q

What other dz are assc with having increased titers of RF

A

SLE, Sjogren’s, Hep B and C, HIV, and chronic inflammation, SBE

16
Q

in synovium: create a toxic environment → cell damage → inflammation

A

ROS and nitrogen

17
Q

cause cells to accumulate in synovium

A

Deficiencies in apoptosis

p53

18
Q

provides nutrients to expanding synovium.

A

angiogenesis

19
Q

what stimulates angiogenesis

A

IL-8, FGF, and VEGF

20
Q

expressesa adhesion molecules that guide circulating cells into the joint under the influence of chemoattractants

A

Microvascular endothelium in the synovium

21
Q

What cells are found in the synovial effusions of RA pts

A

neutrophils and mononuclear cells

22
Q

Why do COX -2 inhib work as therapy for RA

A

prostaglandins and LTs are found in synovial effusions

23
Q

What are the cellular origins of the cytokines found in synovial effusions?

A

macrophages, fibroblasts > T cells

24
Q

the key inflammatory mediator in RA

A

TNF-a

25
Q

Cytokines in Synovium

A
TNF-a 
IL-1, 6, 8, 15, 17, 18, 33, 10
GM-CSF
INF-gamma
TGF-B 
FGF
26
Q

cytokines that activate chondrocytes and osteoclasts → joint destruction

A

TNF-a, IL-1, 6, and 8

IL-17

27
Q

cytokines that Activate MMPs and release prostaglandins

A

TGF-B and FGF

28
Q

activates osteoclasts, chondrocytes, macrophages, fibroblasts

A

IL-17

29
Q

cytokines secreted by T cells

A

INF-gamma and IL-17

30
Q

IL-17 activates

A

osteoclasts, chondrocytes, macrophages, fibroblasts

31
Q

What are targets for RA therapy that would control cytokine signaling

A
NFkB
MAP kinase
AP-1
JAK
Syk
32
Q

What do synovial lining cells produce that contibute to bone destruction

A

MMPs, serine proteases, cathepsins, aggrecanases

33
Q

What mediates cartialge and bone destuction in RA

A

synovial lining cells by secreting MMPs, serine proteases, cathepsins, aggrecanases

osteoclasts (activ by RANKL (<–IL-17)

Pannus (composed of macrophages and mesenchymal cells)

34
Q

invasive tissue of the synovium

What cells make it up

A

pannus

macrophages and mesenchymal cells

35
Q

systemic symptoms assc with RA

A

Fatigue, anorexia, weight loss, weakness, generalized aching and stiffness, low grade fever

36
Q

Articular presentation of RA

A

morning stiffness > 30 mins
swelling, warmth, and erythema around joint
atrophy of muscles
+/- flexion contractures

37
Q

What joints are most characteristically involved in RA

A

wrist and proximal hand (MCP and PIP)

38
Q

What finding is seen at MCP

A

ulnar deviation

39
Q

What finding is seen at the PIP? DIP?

A

Swan-neck (PIP) and Boutonniere deformities (DIP)

40
Q

What finding is seen at the wrist?

A

Volar subluxation with radial-ward rotation

41
Q

describe the pattern of joint involvement in RA

A

Mono or oligio → poly and SYMMETRICAL

42
Q

Why are flexion contractures seen in RA?

A

Fibrosis and tightening of tissues due to chronic inflammation

*Knee, hip, elbow

43
Q

Describe the synovial findings in RA

A
  • Exudative
  • Yellow
  • Elevated WBC
  • Decreased viscosity (due to proteases that eat up HA)
44
Q

joints invovled in RA

A

knee, hip, elbows, shoulder, wrist, hand

45
Q

Extra articular manifestations of RA

A

RA has a RIPPLE effect throughout the body

Rheum nodules (skin, lung, heart valves)
Interstitial fibrosis
Palpable purpura (vasculitis)
Pericarditis, PLeuritis 
Erosion of the Eyes, Entrapment (Nerve) syndromes 

+ dry eyes and mouth

46
Q

activate complement and IgE

A

ACPAs