Amyloidosis Flashcards Preview

IHO Week 6 > Amyloidosis > Flashcards

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)
AA (amyloid-associated)
Beta-amyloid protein
transthyretin (TTR)
B2 microglobulin


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
renal dysfunction
peripheral and/or autonomic neuropathy
imparied coagulation


If you suspect a patient ha systemic amyloidosis, where can you take a tissue biopsy?

fat pad aspiration


What tests can be done to detminer the type of amyloid present?

immunohistochemistry, liquid chromatopgraphy or mass spect

or protein electrophoresis for monoclonal light chain protein (AL)