Amyloidosis

Question 1

What is amyloidosis?

Answer 1

deposition of amyloid in the extracellular space of tissues and organs, resulting in tissue and organ dysfunction

Question 2

What’s the characteristic appearance of amyloid in tissue sections?

Answer 2

on H&E stain, it looks amorphous, eosinophilic, hyaline and extracellular substances

can also be seen in the walls of small vessels

Question 3

What’s the special stain tpically used to visualize amyloid?

Answer 3

congo red - on polarization the red-stained amyloid exhibits a green birefringence

Question 4

Is amyloidosis a single disease entity or a group of diseases?

Answer 4

group of diseases with different pathogenic mechanisms

Question 5

How does amyloid injure adjacent cells?

Answer 5

It causes pressure atrophy of adjacent cells

Question 6

What’s the configuration of amyloid?

Answer 6

it’s linear, non-branching fibrils in a characteristic cross-beta-pleated sheet configuration

Question 7

What are the five types of amyloid protein we discussed?

Answer 7

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

Question 8

What’s the precursor protein and pathogenic mechanism for AL amyloid?

Answer 8

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

Question 9

WHat’s the precsors protein and pathogenic mechanism fo AA myloid?

Answer 9

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

Question 10

What’s the precursor protein and pathogenic mechanism for beta-amyloid amyloidosis?

Answer 10

beta amyloid is derived from proteolysis of amyloid precursor protein
seen in cerebral plaques of alzheimer disease

Question 11

What’s the precursor protein for pathogenic mechanism for transthyretin amyloidosis?

Answer 11

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)

Question 12

WHat’s the pathogenic mechanism for B2 microglobulin amyloidosis?

Answer 12

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

Question 13

Just having the amloid precursor protein does not result in amyloidosis. What else is necessary?

Answer 13

the patient has to be unable to break the amyloid down

Question 14

Define systemic amyloidosis

Answer 14

involves several organ system

Question 15

define localized amyloidosis

Answer 15

involves only one organ

Question 16

define primary amyloidosis

Answer 16

amyloidosis associated with an immunocyte like a plasma cell or B-cell lymphocyte disorder

Question 17

define secondary amyloidosis

Answer 17

amyloidosis that occurs as a complication of an underlying chronic inflammatory process like RA

Question 18

What’s the most common amyloidosis in the US?

Answer 18

primary AL amyloidosis

Question 19

Do most cases of AL amyloidosis arise from a myeloma or a plasma cell dyscrasia?

Answer 19

plasma cell dyscrasia

Question 20

What organs are commonly affected by primary AL amyloidosis?

Answer 20

heart, kidney, peripheral nerves, GI tract, respiratory tract
but pretty much any organ really

Question 21

What’s the second most common amyloidosis in the US?

Answer 21

reactive systemic amyloidosis = AA amyloidosis

Question 22

What’s the most common cause of reactive systemic (AA) amyloidosis?

Answer 22

chronic rheymatoid arthritis

but also from other connective tissue diseases and IBS, renal cell carcinoma and hodkin lymphoma

Question 23

What organs are most commonly affected by reactive secondary (AA) amyloidosis/

Answer 23

kidney, liver, spleen

Question 24

The beta-2 microgoluin deposition in hemodialysis-associated amyloidosis usually affects what in the body?

Answer 24

osteoarticular structures - so they get a sort of arthritis

Question 25

What organs are most commonly affected by age-related (senile) systemic amyloidosis?

Answer 25

usually the heart, resulting in restrictive cardiomyopathy and arrhythmia

Question 26

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?

Answer 26

the Ile122 allele- particularly in older african americans

Question 27

WHat are some clinical features that suggest amyloidossi?

Answer 27

waxy skin and easy bruising
enlarged muscles (tongue and deltoids)
symptoms of heart failure or cardiac conduciton abnormalities
hepatomegaly
renal dysfunction
peripheral and/or autonomic neuropathy
imparied coagulation

Question 28

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

Answer 28

fat pad aspiration

Question 29

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

Answer 29

immunohistochemistry, liquid chromatopgraphy or mass spect

or protein electrophoresis for monoclonal light chain protein (AL)