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