Amyloidoses

Question 1

what is the stain commonly used to diagnose amyloidosis?

Answer 1

Congo red stain

Question 2

what is the tertiary structure of amyloid protein?

Answer 2

beta pleated sheet

Question 3

what type of amyloid is usually associated with monoclonal B-cell dyscrasias?

Answer 3

AL amyloid
(these used to be called primary amyloidosis)

Question 4

what amyloid producing disease is characterized by PMN leukocyte disfunction and recurrent episodes of serositis?

Answer 4

Familial Mediterranean Fever

Question 5

what type of amyloid is featured in familial Mediterranean fever and renal cell carcinoma?

Answer 5

AA amyloid

Question 6

what type of amyloid is seen in Alzheimer’s?

Answer 6

A beta amyloid

Question 7

what protein is the precursor for amyloid deposit in Islets of Langerhans in type 2 diabetics?

Answer 7

amylin (AKA islet amyloid polypeptide) becomes AIAPP

Question 8

what is the precursor protein for amyloid deposited in joints of chronic dialysis patients?

Answer 8

beta 2 microglobulin (invariant chain of MCH class I)

Question 9

what is the precursor protein for amyloid assoc with Creutzfeldt-Jacob disease?

Answer 9

prion protein (PrPsc)

Question 10

what is the amyloid precursor protein for familial amyloidotic polyneuropathy?

Answer 10

transthyretin (TTR)

- most common hereditary amyloidosis

Question 11

what is a definitive form of treatment for familial amyloidotic polyneuropathy?

Answer 11

liver transplant

Question 12

what cell type mediates amyloid turnover?

Answer 12

macrophages

Question 13

what type of heart disease is generally associated with amyloidosos?

Answer 13

restrictive cardiomyopathy: diastolic dysfunction and preserved systolic function

Question 14

what type of amyloid is assoc with Waldenstrom macroglobulinemia?

Answer 14

AH amyloid

Question 15

what type of protein is found in the urine of pts with plasma cell dyscrasia and amyloidosis?

Answer 15

Bence-Jones proteins

Question 16

How is clinical amyloidosis classified?

Answer 16

by the identity of the fibril protein accumulating

Question 17

amyloid-forming proteins can exist in what stable structures?

Answer 17

1 - native form

2 - beta sheets

Question 18

what form of amyloid-forming proteins can aggregate to form fibrils?

Answer 18

beta sheets

Question 19

what biophysical properties do all amyloid fibrils share?

Answer 19

1 - insoluble in physiologic solutions
2 - fairly resistant to proteolysis
3 - binds congo red dye to create green birefringence

Question 20

What is the risk of an abnormally high abundance of certain proteins that are present in low concentrations normally?

Answer 20

AMYLOID Deposition:
ex. serum amyloid A protein (chronic inflammation)
beta2 microglobulin (renal failure)

Question 21

True or False: Normal concentrations of proteins with amyloidogenic potential will not produce amyloidosis

Answer 21

False, if proteins with amyloidogenic potential are present for a long period of time at normal concentrations they can aggregate as seen in senile amyloidosis (transthyretin) and Alzheimer’s (beta protein)

Question 22

Can amyloidoses be acquired or inherited?

Answer 22

Yes, ex. monoclonal immunoglobulin light chains in AL amyloidosis and genetic amyloidogenic variants of transthyretin, lysozyme, apolipoprotein AI, and fibrinogen A alpha chain

Question 23

True or False: amyloid deposits are made solely of amyloid

Answer 23

False: they contain minor constituents such as GAGs, serum amyloid protein, apoE, laminin, collagen IV

Question 24

True or False: Females over 40 are most likely to have wild type transthyretin accumulate

Answer 24

FALSE: MEN OVER 60 make of 90% of the patient population for this disorder

Question 25

True or False: the pathologic effects of amyloid are due to inflammatory responses?

Answer 25

FALSE! amyloid provokes little to no inflammatory reaction | they impair function by physically obstructing things (not just large deposits)

Question 26

Does the amount of amyloid deposited indicate severity of dysfunction?

Answer 26

NO, it varies depending on person, organ and rate of deposition.

Question 27

How can we treat amyloidoses?

Answer 27

reduce the supply of amyloid precursors!

Question 28

What methods are used to detect amyloid?

Answer 28

1 - congo red stain | 2 - immunohistochemistry (depends on fibril protein type)

Question 29

all forms of amyloid consist of _________ ________ of ____________ arrays of fibrils.

Answer 29

all forms of amyloid consist of INTERLACING BUNDLES of PARALLEL arrays of fibrils

Question 30

What is the most common acquired amyloidosis?

Answer 30

systemic AL amyloidosis

Question 31

What type of amyloidosis may result from chronic infections or inflammatory diseases?

Answer 31

AA amyloidosis | why? long-term overproduction of acute phase reactant SAA

Question 32

what part of SAA forms the amyloid fibrils?

Answer 32

N-terminal cleavage fragment = single non-glycosylated polypeptide chain

Question 33

What infections may cause AA amyloidosis?

Answer 33

TB, leprosy

Question 34

What types of cell convert SAA into AA?

Answer 34

macrophages cleave SAA into AA via several proteinases

Question 35

What is the key to treating AA amyloidosis?

Answer 35

suppress the underlying inflammatory disorder

Question 36

Why is a rectal biopsy used to diagnose AA amyloidosis?

Answer 36

the AA amyloid deposits are widely distributed

Question 37

What are the transcriptional regulators of SAA?

Answer 37

IL-1, IL-6, TNF-alpha

Question 38

Which of the following organs may be directly affected by AL amyloidosis? Brain, Heart, Liver, Kidneys, Peripheral nerves

Answer 38

Virtually all organs EXCEPT the brain can be directly affected but those listed are most important clinically (except the brain)

Question 39

Which amyloidosis involves immunoglobulins?

Answer 39

AL amyloidosis: consists of the variable region of Ig light chains derived from kappa or lambda polypeptides

Question 40

ATTR amyloidosis almost always presents with ________ _________.

Answer 40

``` Restrictive cardiomyopathy (ATTR = transthyretin amyloidosis) ```

Question 41

Medullary carcinoma of the thyroid is associated with amyloid precursor?

Answer 41

procalcitonin (becomes ACal)

Question 42

Where in the brain are amyloid deposits never seen?

Answer 42

cerebral parenchyma (not seen in any form of acquired systemic visceral amyloidosis)

Question 43

What protein is beta-protein derived from and where is the precursor found?

Answer 43

amyloid precursor protein (APP), transmembrane protein in neurons and glia

Question 44

What is the link between Alzheimer's and Down Syndrome?

Answer 44

APP (which makes beta amyloid, which causes Alzhiemer's) is encoded on chromosome 21; some Down syndrome patients develop AD by 35

Question 45

What hereditary amyloidosis presents as cerebral amyloid angiopathy with recurrent cerebral hemorrhage and silent systemic deposits?

Answer 45

cystatin C amyloidosis | - only reported in Icelandic families

Question 46

most common hereditary renal amyloidosis

Answer 46

Hereditary fibrinogen A alpha-chain amyloid

Question 47

A 50 year old man presents with proteinuria, and hypertension. Despite your best efforts to treat him, he develops end-stage renal failure within 5 years. What is the most likely amyloidosis in this patient? And what is the mechanism of disease?

Answer 47

Hereditary fibrinogen A alpha-chain amyloid. | Mech: amyloid deposits in kidneys, spleen, and perhaps liver

Question 48

Because amyloid deposits accumulate along _______ __________, the deposits take on the architectural framework of the ________ ________.

Answer 48

because amyloid deposits accumulate along STROMAL NETWORKS, the deposits take on the architectural framework of the ORGANS INVOLVED

Question 49

``` Amyloid deposition can cause: A- Increased size of organs affected B - Organ Atrophy C - All of the above D- none of the above ```

Answer 49

C: amyloid add material to th organs where they deposit but they may also occulde blood vessels and impair circulation leading to atrophy

Question 50

Where do amyloid deposits tend to localize? and how does this affect cellular processes?

Answer 50

they localize between parenchymal cells and their blood supply interfering with normal nutrition and gas exchange

Question 51

What are two methods through which amyloidosis damages/ kills cells?

Answer 51

1 - blocking blood supply | 2 - direct toxic effect through protofibrils interacting with cell membranes

Question 52

What classic symptoms of amyloidosis should instantly indicate the diagnosis?

Answer 52

TRICK QUESTION! There is no single set of sx that point to amyloidosis - sx depend on underlying disease, type of amyloid and organ affects

Question 53

Enlargement of the tongue is associated with what type of amyloidosis?

Answer 53

AL amyloidosis

Question 54

What type of amyloid is associated with spongiform encephalopathies?

Answer 54

PrPsc (prion protein)

Question 55

what type of amyloid protein is associated with multiple myeloma?

Answer 55

AL amyloid (immunoglobulin precursor)