B4-096 Amyloidosis Flashcards
1
Q
amyloid plaques stain what color?
A
apple-green birefringence
2
Q
what stain is used to visualize amyloid plaques?
A
congo red
3
Q
amyloid plaques form [….] sheets
A
beta pleated
4
Q
what molecule causes the native proteins to stick together?
A
heparin sulfate
5
Q
AL is caused by
A
more cells making protein
6
Q
ATTR is caused by
A
unstable protein in the native state
7
Q
aggregation is […] and […]
A
slow; self catalyzing
8
Q
caused by monoclonal light chains
A
AL
9
Q
seen in plasma cell disorders
A
AL
10
Q
seen in chronic inflammatory conditions
A
AA
11
Q
familial mediterranean fever
A
AA
12
Q
seen in patients with end stage renal disease/long term dialysis
A
beta 2 microglobulin
13
Q
TTR is produced by
A
the liver and chorid plexus
14
Q
carries T4 and retinol
A
TTR
15
Q
TTR normally exists as a
A
tetramer
16
Q
in ATTR, amyloid forms as a result of
A
dissociated TTR monomers
17
Q
TTR
A
transthyretin
18
Q
primarily affects peripheral nerves and heart
A
ATTRv
19
Q
decreased protein stability, proteins more readily dissociate
A
ATTRv
20
Q
caused by germline mutations
A
ATTRv
21
Q
which affected tissue has the worse long term prognosis?
A
heart
22
Q
caused by both increased concentration and loss of protein stability as a result of aging
A
ATTRwt
senile
23
Q
primarily affects heart
A
ATTRwt
24
Q
AL is primarily caused by aggregation of what type of light chains
A
lambda
25
increased concentration due to neoplastic plasma cell clone
AL
26
in systemic AL, the clone is usually in
bone marrow
27
in localized AL, the clone is typically in
tissue
28
primarily affects heart and kidney
AL
29
AL light chains are
highly toxic
30
Abeta2m is decreasing in prevalence due to
improved dialysis filters
31
mainly affects osteoarticular tissues
Abeta2m
32
serum amyloid A protein is an
acute phase reactant
33
primarily affects kidney
AA
34
what has reduced the prevalence of AA in developed countries?
eradication of chronic infection and improved treatment of autoimmune diseases
35
clinical severity depends on
tissue tropism
36
examples of local, benign amyloidosis
* insulin injection site
* seminal vesicle
* islet amyloid pancreatic
37
primary sources of mortality of amyloidosis
**cardiomyopathy**
renal failure
coagulopathy
38
coagulopathy: amyloidosis causes both [...] and [...] disorders
bleeding; clotting
39
amyloid and precursor proteins bind [...] causing bleeding
X
40
amyloidosis coagulopathy can result in acquired
vWF deficiency
41
clotting in amyloidosis is caused by
left atrial stasis and damage
| risk of thrombi
42
anticoagulation is only
partially protective
43
how does amyloidosis affect the kidney?
infiltrates glomerulus --> proteinuria -->nephrotic syndrome --> renal failure
44
bone and soft tissue red flags for amyloidosis
* carpal tunnel
* spinal stenosis
* biceps tendon rupture
* fracture
* macroglossia (AL)
45
red flags for amyloidosis in the nervous system
* peripheral neuropathy (ATTRv esp.)
* syncope
* gastroparesis
46
muscalaris mucosae infiltration leads to gastrophoresis in
AL
47
mucosal infiltration leads to malabsorption in
AA
48
as contractility in the heart fails, there is no ability for LV dilation to preserve EF causing
reliance on heart rate
49
drugs poorly tolerated in amyloidosis
* beta blockers
* ACE/ARB
* digoxin
* Ca+ channel blockers
50
drugs well tolerated in amyloidosis
* loop diuretics
* aldosterone antagonists
51
cardiomyopathy is characterized by
* HFpEF
* restrictive physiology
* arrhythmias
52
massively underdiagnosed
ATTRv
| 25% penetrance
53
average time from symptoms to diagnosis for amyloidosis is
2 years
54
what condition has a 100% correlation with amyloid deposits
lumbar spinal canal stenosis
| ligementum flavum
55
classic ECG for cardiac amyloidosis
* low voltage
* poor p wave progression
56
common echo findings for cardiac amyloidosis
* biatrial enlargement
* thickened spetum
* concentric LVH
* hyperechoic
basically, infiltrative disease
57
low voltage ECG + increased LV septum...think...
infiltrative disease
58
what finding on cardiac MRI is both sensitive and specific for cardiac amyloidosis?
late gadolinium enhancement
59
on strain imaging, cardiac amyloidosis shows
* basal predominance
* apical sparing
* unique acoustic speckles
60
what major findings are highly specific for cardiac amyloidosis
* apical sparing on strain echo
* infiltrative pattern on MRI
61
serum free light chain assay is very sensitive for
AL
62
qualitative for disease monitoring of AL
serum free light chain assay
63
grade 2-3 PYP scan is diagnostic of
ATTR
64
# next best step following
* amyloid suspected on clinical findings
* monoclonal protein present
* PYP grade 1-3
cardiac biopsy
| definitely AL, ATTR has not been excluded based on PYP grading
65
# next best step following
* amyloid suspected on clinical findings
* monoclonal protein present
* PYP grade 0
* AL
* consider non-cardiac biopsy
| ATTR is excluded based on PYP grading
66
# next best step following:
* amyloid suspected on clinical findings
* monoclonal protein excluded
* PYP grade 2-3
* ATTR diagnosed
* TTR genotyping
67
# next best step following
* amyloid suspected on clinical findings
* monoclonal protein excluded
* PYP grade 1
cardiac biopsy
68
# next best step following
* amyloid suspected on clinical findings
* monoclonal protein excluded
* PYP grade 0
excludes AL and ATTR, consider alternate diagnosis
69
mainstay treatment for ATTR
tafamidis
| causes less dissociation
70
treatment option for ATTRv
liver transplant
71
management of ATTR is based on 3 options
* TTR reduction
* stabilization
* fibril degradation
72
TTR reduction is only available for
ATTRv
73
ideal therapy for AL
stem cell transplant
| many patients are ineligible due to cormorbidities
74
associated with chronic inflammation from chronic infection or autoimmunity and frequently involves kidneys
AA
75
stabilizes TTR tetramers
tafamidis
76
prevents fibril formation and is protective against damage by TTR monomers
doxycycline
77
* cause mRNA degradation
* interfere with translation of TTR
patisiran
inotersan
78
silences the TTR gene and reduces serum TTR concentrations
patisiran/inotersan
79
will eliminate TTRv but not affect overall levels of TTR
liver transplant
80
stabilizes TTR but does not reduce levels
tafamadis
