Basics: 1.5: Amyloid

Question 1

What do thyroid tumor cells in an amyloid background indicate?

Answer 1

medullary carcinoma of the thyroid

Question 2

This is systemic deposition of AL amyloid derived from the Ig light chain; assoc with plasma cell dyscrasias.

Answer 2

1a amyloidosis

Question 3

What is amylin?

Answer 3

an amyloid that is a byproduct of insulin that can deposit in the islets of the pancreas

Question 4

What is senile cardiac amyloidosis?

Answer 4

• non-mutated serum transthyretin deposits in the heart
• present in 25% of individuals >80yo
• usually asymptomatic

Question 5

What is 1a amyloidosis?

Answer 5

• systemic deposition of AL amyloid
  
  • derived from the Ig light chain
  • assoc with plasma cell dyscrasias

Question 6

What is systemic deposition of AA amyloid (derived from SAA) called?

Answer 6

2a amyloidosis

Question 7

What are non-mutated serum transthyretin deposits in the heart called?

Answer 7

senile cardiac amyloidosis

Question 8

dx?

• mutated serum transthyretin
• deposits in the heart
• leads to restrictive cardiomyopathy
• 5% of African Americans are carriers

Answer 8

familial amyloid cardiomyopathy

Question 9

Name the localized amyloidoses.

Answer 9

1. familial amyloid cardiomyopathy
2. senile cardiac amyloidosis
3. DM associated
4. Alzheimers
5. dialysis-associated amyloidosis
6. medullary carcinoma of the thyroid

Question 10

What is dialysis-associated amyloidosis?

Answer 10

• beta-2-microglobulin deposits in joints
  
  • in dialysis pts

Question 11

What is medullary carcinoma of the thyroid?

Answer 11

a thyroid tumor derived from C cells, leading to overproduction of calcitonin and then amyloid deposition in the thyroid

Question 12

Dx?

• beta-2-microglobulin deposits in joints

Answer 12

dialysis-associated amyloidosis

Question 13

How does amyloid look under the microscope?

Answer 13

congo red staining with apple green birefringence

Question 14

What is the usual configuration of amyloid-damaged tissue?

Answer 14

Beta-pleated sheets

Question 15

How can amyloidosis occur in Alzheimers disease?

Answer 15

• beta-amyloid precursor protein on chromosome 21 deposits into the brain as ABeta
  
  • forms amyloid plaques

Question 16

Systemic amyloidosis is divided into ____ and ____ types.

Answer 16

• 1a
• 2a

Question 17

How can amyloidosis occur in DM?

Answer 17

type 2 DM: too much insulin = insulin byproduct produced (amylin)amylin deposits into islets of the pancreas

Question 18

What are the features of Familial Mediterranean Fever?

Answer 18

dysfunction of the neutrophils causing activation w/o infectionauto recessive inheritance in persons of Mediterranean origin fever; serosal surfaces inflamed; tongue enlargement, hepatosplenomegaly, malabsorption

Question 19

How is amyloidosis definitively diagnosed?

Answer 19

a tissue biopsy (usu a fat pad- abdominal or rectal)

Question 20

What is the usual configuration of amyloid-damaged tissue?

Answer 20

Beta-pleated sheets

Question 21

What is restrictive cardiomyopathy?

Answer 21

• stiffened heart
• can’t dilate as well or pump properly
• leads to HF

Question 22

What is 2a amyloidosis?

Answer 22

systemic deposition of AA amyloid (derived from SAA)

Question 23

Where does amyloid most commonly deposit? What does this cause?

Answer 23

• the kidney
• nephrotic syndrome

Question 24

What is an amyloid?

Answer 24

a misfolded protein that deposits into the extracellular space –> tissue damage

Question 25

What is SAA?

Answer 25

* an acute phase reactant increased in: * inflammation * malignancy * Familial Mediterranean fever

Question 26

What kind of amyloidosis category does senile cardiac amyloidosis fall into?

Answer 26

localized amyloidosis

Question 27

What is familial amyloid cardiomyopathy?

Answer 27

* **mutated serum transthyretin** deposits in the heart * leads to restrictive cardiomyopathy * 5% of African Americans are carriers

Question 28

What is nephrotic syndrome?

Answer 28

a large loss of protein (\>3g in 24 hours) in the urine

Question 29

How are the affected organs treated in amyloidosis?

Answer 29

no tx- they have to be transplanted

Question 30

Where does amyloid tend to deposit?

Answer 30

around BVs

Question 31

What is the 2nd most common protein in the blood?

Answer 31

serum transthyretin

Question 32

What is the difference btw familial amyloid cardiomyopathy and senile cardiac amyloidosis ?

Answer 32

* familial = mutated serum transthyretin * senile = non-mutated serum transthyretin

Question 33

Why does dialysis-assoc amyloidosis occur?

Answer 33

* Dialysis pts have increased amounts if Beta-2-microglobulin in the blood bc it isn't filtered out properly * it then accumulates in joints

Question 34

What are the features of Familial Mediterranean Fever?

Answer 34

* dysfunction of the neutrophils causing activation w/o infection * auto recessive inheritance in persons of Mediterranean origin * fever; serosal surfaces affected

Question 35

Dx? * dysfunction of the neutrophils causing activation w/o infection * auto recessive inheritance in persons of Mediterranean origin * fever; serosal surfaces affected

Answer 35

Familial Mediterranean Fever

Question 36

What is the amyloid that is a byproduct of insulin that can deposit in the islets of the pancreas?

Answer 36

amylin

Question 37

What is a misfolded protein that deposits into the extracellular space called?

Answer 37

an amyloid

Question 38

How is medullary carcinoma of the thyroid definitively diagnosed?

Answer 38

fine needle aspiration of the thyroid

Question 39

What is AL amyloid derived from?

Answer 39

Ig light chain

Question 40

Where does amyloid most commonly deposit? What does this cause?

Answer 40

* the kidney * nephrotic syndrome

Question 41

2a amyloidosis can result from a \_\_\_\_\_, like autoimmune disease (SLE, RA, Crohn's, etc), \_\_\_\_\_\_, or \_\_\_\_\_.

Answer 41

* chronic inflammatory state * malignancy * Familial Mediterranean fever

Question 42

Why are amyloids bad?

Answer 42

they damage tissues

Question 43

What can happen to the heart in amyloidosis?

Answer 43

* restrictive cardiomyopathy * arrhythmia

Question 44

Amyloid deposition can be _____ or \_\_\_\_\_.

Answer 44

* systemic * localized

Question 45

What kind of amyloidosis is dialysis-associated?

Answer 45

localized

Question 46

2a amyloidosis can result from a \_\_\_\_\_, like autoimmune disease (SLE, RA, Crohn's, etc), or \_\_\_\_\_.

Answer 46

* chronic inflammatory state * malignancy

Question 47

What is AL amyloid derived from?

Answer 47

Ig light chain

Question 48

What is the link btw Alzheimers and Down Syndrome?

Answer 48

* the beta-amyloid precursor protein is on chromosome 21 and DS = trisomy 21 * early onset Alzheimers seen in DS individuals

Question 49

What is Beta-2-microglobulin?

Answer 49

a supportive protein for MHC-1 expression

Question 50

What is serum transthyretin?

Answer 50

the 2nd most common protein in the blood

Question 51

What is dialysis-associated amyloidosis?

Answer 51

beta-2-microglobulin deposits in joints

Question 52

What is AA amyloid?

Answer 52

an amyloid derived from SAA

Question 53

How is amyloidosis definitively diagnosed?

Answer 53

a tissue biopsy (usu a fat pad- abdominal or rectal)

Question 54

What is a large loss of protein (\>3g in 24 hours) in the urine called?

Answer 54

nephrotic syndrome

Question 55

Why does dialysis-assoc amyloidosis occur?

Answer 55

* Dialysis pts have increased amounts if Beta-2-microglobulin in the blood bc it isn't filtered out properly * it then accumulates in joints

Question 56

Where is the beta-amyloid precursor protein gene located?

Answer 56

on chromosome 21

Question 57

What is localized amyloidosis?

Answer 57

amyloid deposition localized to a single organ or tissue