Rheumatic Heart Disease

Question 1

central tolerance

Answer 1

developing lymphocytes

central lymphoid organs
-negative selection

Question 2

peripheral tolerance

Answer 2

mature lymphocytes

peripheral tissues

• t reg functions
• anergy
• cell death

Question 3

molecular mimicry

Answer 3

cross-reactive Th1 cells recognize both self and microbial epitope

• release cytokines and chemokines
• recruits macrophages and activate B cells

Question 4

epitope spreading

Answer 4

tissue damage and release of self antigens

• further activation of lymphocytes
• more self antigens released

Question 5

bystander activation

Answer 5

non-specific activation of self-reactive lymphocytes

inflammation
infiltration of tissue
complement fixation
perpetuates response

Question 6

cryptic antigens

Answer 6

differential processing of self antigens by DCs
-IFN-gamma activates DCs

uptake and processing of self-antigens
activates self-reactive lymphocytes

Question 7

hit and run

Answer 7

infection long before disease evident

Question 8

latency

Answer 8

infection may be occult

Question 9

timing

Answer 9

different phases of susceptibility

Question 10

strains

Answer 10

same beast, different outcomes

Question 11

patient differences

Answer 11

fertile-field hypothesis

Question 12

fertile field

Answer 12

temporary time following infection which can vary depending on type, location, and duration

Question 13

group A beta-hemolytic streptococcal tonsillopharyngitis

Answer 13

acute onset

• submandibular adenopathy
• fever
• resolves 3-4 days with no treatment

Question 14

titers of GAS?

Answer 14

M protein
streptolysin O
DNAses
pyrogenic exotoxins
hyaluronidase

Question 15

long term of GAS?

Answer 15

scarlet fever
bacteremia
post-strep golmerulonephritis
TSS
acute rheumatic fever
rheumatic heart disease

Question 16

structure of GAS?

Answer 16

hyaluronic capsule
F protein
GlcNAc
M protein

Question 17

exotoxins of GAS?

Answer 17

streptolysin O
pyrogenic exotoxin A B C
DNAse B
streptokinases
hyaluronidase
SIC

Question 18

M protein

Answer 18

mucoid strain (heavily encapsulated)

superantigen***
-interacts with V-beta region of TCR

strain specific - 3,5,18,24

Question 19

acute rheumatic fever

Answer 19

inflammatory disease of connective tissue
5-15 years old

previous sore throat

Question 20

treatment of ARF?

Answer 20

penicillin G or erythromycin

-to prevent spread

Question 21

polyarthritis

Answer 21

symptom of ARF
-cross-reactive hyaluronic acid

treatment: aspirin, corticosteroids

Question 22

carditis

Answer 22

symptom of ARF

• cross reactive M protein
• mimics cardiac myosin

pancarditis - entire heart
-cardiomegaly
-new murmur - apical systolic
valve - mitral

Question 23

carditis murmur?

Answer 23

apical systolic

Question 24

carditis valve?

Answer 24

mitral

Question 25

subQ nodules and erythema marginatum?

Answer 25

symptom of ARF

• cross reactive GlcNAc
• connective tissue carbohydrate

Question 26

sydenham’s chorea

Answer 26

symptom of ARF

• virulence factor GlcNAc
• chorea minor, St Vitus dance

involuntary movement and muscle weakness
-disappears during sleep***

treatment: sedatives, corticosteroids

Question 27

Jones criteria for diagnosis of ARF?

Answer 27

two major OR one major and two minor
-along with evidence of streptococcus pyogenes

MAJOR: carditis, polyarthritis, chorea, erythema marginatum, subQ nodules

MINOR: arthralgia, fever, elevated ESR or CRP, EKG prolonged PR interval

Question 28

stage 1 of rheumatic valve disease?

Answer 28

cross-reactive antobodies

MIMICRY

Question 29

stage 2 of RVD?

Answer 29

antibody attach to valves

MIMICRY

Question 30

stage 4 of RVD?

Answer 30

infiltration of CD4 and CD8 T cells

-BYSTANDER AND EPITOPE SPREADING

Question 31

stage 5 of RVD?

Answer 31

neurovascularization with further recruitment of T cells

BYSTANDER, CRYPTIC AGS, and EPITOPE SPREADING

Question 32

Rheumatic Heart DIsease

Answer 32

must have had previous ARF

residual cardiac involvement
-atrial fib, scarring/calcification, stenosis

valve replacement common

Question 33

Jaccouds arthritis?

Answer 33

periarticular fibrosis

Question 34

histology of RHD?

Answer 34

chordae tendonae shortened

-edges of valve thick and deformed

Question 35

aschoffs nodules

Answer 35

pathognomonic

-focal perivascular inflammatory lesions with lymphocytes, plasma cells, and aschoff cells

Question 36

aschoff cells?

Answer 36

large basophilic multinucleat cells

Question 37

anichkovs myoctes?

Answer 37

elongated nuclei with distinct chromatin pattern

• cross section owl eyes
• longitudinal catepillars

Question 38

most associated with ARF?

Answer 38

HLA-DR7

also TGF-B1, TNF-alpha, TLR-2

several genes predispose individual to ARF