Flashcards in Amyloidosis Deck (29):
What is amyloidosis?
deposition of amyloid in the extracellular space of tissues and organs, resulting in tissue and organ dysfunction
What's the characteristic appearance of amyloid in tissue sections?
on H&E stain, it looks amorphous, eosinophilic, hyaline and extracellular substances
can also be seen in the walls of small vessels
What's the special stain tpically used to visualize amyloid?
congo red - on polarization the red-stained amyloid exhibits a green birefringence
Is amyloidosis a single disease entity or a group of diseases?
group of diseases with different pathogenic mechanisms
How does amyloid injure adjacent cells?
It causes pressure atrophy of adjacent cells
What's the configuration of amyloid?
it's linear, non-branching fibrils in a characteristic cross-beta-pleated sheet configuration
What are the five types of amyloid protein we discussed?
AL (amyloid light chain)
What's the precursor protein and pathogenic mechanism for AL amyloid?
it's made up of either complete immunoglobulin light chains or just the amino-terminal fragments of the light chains - usually lambda, but sometimes kappa
this arises when free light chain is secreted by a monoclonal population fo plasma cells like in myeloma
WHat's the precsors protein and pathogenic mechanism fo AA myloid?
It's derived by proteolysis of a larger precursor protein in the serum called SAA (serum amyloid-associated) protein
production of SAA is increased in chronic inflammatory conditions
What's the precursor protein and pathogenic mechanism for beta-amyloid amyloidosis?
beta amyloid is derived from proteolysis of amyloid precursor protein
seen in cerebral plaques of alzheimer disease
What's the precursor protein for pathogenic mechanism for transthyretin amyloidosis?
TTR is normally a serum protein that binds and transports thyroxine and retinol - a mutation leads to its deposition of amyloid in heritable neuropathic and/or cardiomyopathic amyloidosis (or just from age in senile systemic amyloidosis)
WHat's the pathogenic mechanism for B2 microglobulin amyloidosis?
B2 microglobulin cannot be filtered out throuh dialysis membranes, so it can accumulate in patients on long term dialyasis (like over 20 years), resulting in hemodialysis-associated amyloidosis
Just having the amloid precursor protein does not result in amyloidosis. What else is necessary?
the patient has to be unable to break the amyloid down
Define systemic amyloidosis
involves several organ system
define localized amyloidosis
involves only one organ
define primary amyloidosis
amyloidosis associated with an immunocyte like a plasma cell or B-cell lymphocyte disorder
define secondary amyloidosis
amyloidosis that occurs as a complication of an underlying chronic inflammatory process like RA
What's the most common amyloidosis in the US?
primary AL amyloidosis
Do most cases of AL amyloidosis arise from a myeloma or a plasma cell dyscrasia?
plasma cell dyscrasia
What organs are commonly affected by primary AL amyloidosis?
heart, kidney, peripheral nerves, GI tract, respiratory tract
but pretty much any organ really
What's the second most common amyloidosis in the US?
reactive systemic amyloidosis = AA amyloidosis
What's the most common cause of reactive systemic (AA) amyloidosis?
chronic rheymatoid arthritis
but also from other connective tissue diseases and IBS, renal cell carcinoma and hodkin lymphoma
What organs are most commonly affected by reactive secondary (AA) amyloidosis/
kidney, liver, spleen
The beta-2 microgoluin deposition in hemodialysis-associated amyloidosis usually affects what in the body?
osteoarticular structures - so they get a sort of arthritis
What organs are most commonly affected by age-related (senile) systemic amyloidosis?
usually the heart, resulting in restrictive cardiomyopathy and arrhythmia
What mutation can be used to differentiate between age-related amyloidosis with normal TTR deposition and mutant TTR amyloidosis? In what group of people especially?
the Ile122 allele- particularly in older african americans
WHat are some clinical features that suggest amyloidossi?
waxy skin and easy bruising
enlarged muscles (tongue and deltoids)
symptoms of heart failure or cardiac conduciton abnormalities
peripheral and/or autonomic neuropathy
If you suspect a patient ha systemic amyloidosis, where can you take a tissue biopsy?
fat pad aspiration