Nelson- Amyloidosis

Question 1

Define amyloidosis

Answer 1

group of disorders where amyloid is deposited in extracellular space of tissues and organs> tissue organ and dysfunction

Question 2

What is the characteristic appearance of amyloid in tissue sections?

Answer 2

Pathological proteins w similar physical properties (4-6 fibrils wound around one another)

Linear non branching fibrils in cross beta pleated sheet configuration > characteristic staining

Question 3

What special stain is used to view amyloidosis?

Answer 3

H&E- amorphous, eosinophillic, hylaline, extracelluar substance–> pressure atrophy of adjacent cells

Congo red- appears red

On polarization= red stained amyloid exhibits green birefringence

Question 4

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

Answer 4

Group of disorders that have amyloid deposited in places

Question 5

How does amyloid injure adjacent cells?

Answer 5

Deposited amyloid–> tissue and organ dysfunciton

Question 6

What are the 5 types of amyloid protein?

Answer 6

AL- amyloid light chain
AA- amyloid associated
AB- beta amyloid protein
TTR- transthyretin
B2- microglobluin

Question 7

AL- pathological mechanism

Answer 7

monoclonal population of plasma cells>
produces free Ig light chain protein>
AL

Question 8

AL- precursor proteins

Answer 8

complete Ig light chains (lamda L)

amino terminal fragments of L chains or both

Question 9

AA- pathological mecahnism

Answer 9

Increased SAA production + enzyme defect>
incomplete SAA break down>
deposition

**SAA production increased in inflammatory conditions> chronic inflammation

Question 10

AA- precursor proteins

Answer 10

Proetolysis of serum amyloid protein (SAA)

often associated w/ high density lipoprotein

Question 11

AB- precursor proteins

Answer 11

Proetolysis of amyloid precursor protein

Question 12

AB- pathological mechanism

Answer 12

Found in cerebral plaques and walls of cerebral vessels in Alzheimers disease

Question 13

TTR- precursor protein

Answer 13

Mutated TTR

Normal serum protein that binds and transports thyroxine and retinol

Question 14

TTR- pathological mechanism

Answer 14

Mutated TTR (Heritable neuropathic/cardiomyopathic amyloidosis) >
amyloid deposition

Non-mutated TRR (senile systemic amyloidosis) > TRR deposition in heart of aged pts

Question 15

B2 microglobulin- precursor protein

Answer 15

normal serum protein

Question 16

B2 microglobluin- pathological mechanism

Answer 16

Cannot be filtered through dialysis membranes>
accumulates in long term dialysis

(hemodialysis associated amyloidosis)

Question 17

What can cause localized amyloidosis?

Answer 17

prion diseases>

accumulation in CNS

Question 18

What is the mechanism for amyloidosis?

Answer 18

abnormal protein folding into fibrils>
increased resistance to normal degradation>
accumulation of mysfolded protein

(classified by type of protein produced)

Question 19

Define systemic amyloidosis

Answer 19

involving several organ systems

Question 20

Define localized amyloidosis

Answer 20

involving a single organ (heart)

Question 21

Define primary amyloidosis

Answer 21

associated w/ an immunocyte (plasma cell, B cell disorder)

Question 22

Define secondary amyloidosis

Answer 22

complication of an underlying chronic inflammatory process

Question 23

Define hereditary/familal amyloidosis

Answer 23

group of heterogenous heritable forms of amyloidosis w/ several distinctive patterns of organ involvement

Question 24

Describe primary amyloidosis.

AL- most common type in the US

Answer 24

Monoclonal proliferation of plasma cells>
production of monoclonal IgL/Ig H chains (w/out H chain= bence jones protein)>
AL/AH>
systemic>
heart, kidney, periohperal nerve, GI tract

Question 25

What type of light chain deposition is seen in pts w/ multiple myeloma?

Answer 25

Monoclonal free L chain> | deposition

Question 26

Describe reactive systemic amyloidosis. 2nd most common type

Answer 26

Chronic inflammatory condition (RA), ct disorder, inflammatory bowel disorder> serum AA> AA amyloidosis (high density apolipoproteins)> systemic> kidney, liver, spleen

Question 27

What is the most common type of amyloidosis in the developing world and why?

Answer 27

AA is most common b/c of chronic infectious disease

Question 28

AA (reactive) is associated w/ what cancers?

Answer 28

REneal cell carcinoma Hodgkin lymphoma

Question 29

Describe hemodialysis associated amyloidosis.

Answer 29

``` Prolonged periods of dialysis to treat end stage renal disease> B2 microglobulin> Ab2m> deposition of B2 microglobulin> bone structures ```

Question 30

Describe Heredofamilial amyloidosis (two types)

Answer 30

``` Mutated TTR (heritable/cardiomyopathic amyloidosis)> amyloid deposition ``` Non-mutated TTR (senile systemic amyloidosis)> TTR deposition in heart of aged pts

Question 31

Describe age related systemic amyloidosis

Answer 31

Cardiac amyloidosis d/t normal TTR Normal TTR protein> deposition in heart> cardiomyopathy and arrhythmia *elderly 70-80s

Question 32

What is a hereditary type of amyloidosis commonly seen in african americans?

Answer 32

Mut in Ile22 indicates cardiac amyloidosis d/t mut TRR | mut allele commonly seen in African americans-> screen for this

Question 33

Describe localized (organ specific) amyloidosis

Answer 33

Nodular deposition in lung, larynx, skin, urininary bladder, tongue, orbi *limited to 1 organ/tissue most common: amyloid plaques and amyloid laden cerebral vessels in AD

Question 34

What precursor protein is associated w/ alzheimers and where is it distributed?

Answer 34

APP> AB cerebral plaques cerebral vessels

Question 35

What organ systems are most commonly affected by systemic amyloidosis?

Answer 35

kidneys, heart , liver

Question 36

What are some of the key clinical sxs associated w/ systemic amyloidosis?

Answer 36

``` waxy skin easy bruising enlarged muscles heart failure cardiac conduction abnormalities heptatomegaly renal dysfunciton peripheral/autnomic neuropathy impaired coagulation (factor X def) ```

Question 37

How do you dx amyloidosis/

Answer 37

Gold standard: tissue biopsy w/ amyloid stainging

Question 38

How do you dx suspected systemic disease?

Answer 38

fat pad aspiration (from abdomen) or rectal biopsy

Question 39

How do you determine the type of ayloid present?

Answer 39

immunohistochemistry liquid chromatography mass spec

Question 40

How do you treat amyloidosis? AA AL Dialysis realted herediatry forms w/ TTR

Answer 40

Varies w/ amt of amyloid produced AA- target underlying infection/inflamm disorder AL- underlying PC disorder Dialysis related- alter mode of dialysis or renal transplant herediatry forms w/ TTR- liver transplant