L16- Amyloidosis and Pigmentation

Question 1

Amyloid is mainly a product of (1) and when it abnormally deposits in ECM it is called (2). Amyloid deposition is composed of (3), produced by the abnormal aggregation of (4). Amyloid deposits also bind (5), giving it a distinct staining characteristic that resembles (6).

Answer 1

1- acute phase protein (liver)
2- amyloidosis
3- abnormal fibrils
4- improperly folded proteins (soluble if correctly folded)
5- proteoglycans
6- starch / amylose

Question 2

Amyloidosis:

• (1) H&E stain appearance
• In (2) stain it appears ‘salmon red’ and gives (3) characteristic under polarized light
• (4) EM appearance

Answer 2

1- ‘glassy pink’
2- Congo Red stain
3- ‘apple-green’ bi-refringence (bi-refraction)
4- non-branching fibrils + non-fibrillary component (P component)

Question 3

describe the two MAIN types of Amyloid proteins

Answer 3

1) AL amyloid = amyloid light chain: derived from plasma cells containing Ig light chains; seen in multiple myeloma
2) AA amyloid = amyloid-associated: derived from non-Ig protein, synthesized in Liver; seen in chronic inflammatory conditions

Question 4

(1) is a normal serum protein that binds/transports thyroxine and retinol. Its mutant form is referred to as (2).

Answer 4

1- transthyretin

2- familial amyloid polyneuropathies

Question 5

_____ is amyloidosis seen in hemodialysis patients

Answer 5

β-2 microglobulin

Question 6

_____ is a cerebral plaque in Alzheimer’s disease

Answer 6

β-amyloid

Question 7

compare the mechanism of amyloidosis when it involves normal and mutant proteins

Answer 7

Normal- when produced in large amounts, they have tendency to associate, forming fibrils

Mutant- prone to misfolding and aggregation; produced at normal quantities

Question 8

compare localized and systemic amyloidosis

Answer 8

• Local = one organ affected

- Systemic > one organ affected

Question 9

Primary and Secondary amyloidosis are types of (1) amyloidosis. Primary is associated with (2) and involves (3) amyloid type. Secondary, aka (4), is associated with (5) and involves (6) amyloid type.

Answer 9

1- systemic amyloidosis
2- plasma cell proliferation
3- AL (derived from Ig light chain)
4- reactive systemic amyloidosis
5- inflammation (TB, bronchiectasis, chronic osteomyelitis)
6- AA (via liver)

Question 10

_____ amyloid type is the predominant heriditary amyloidosis form

Answer 10

ATTR- transthyretin (binds thyroxine and retinol for plasma transport)

Question 11

list the macroscopic features of amyloidosis

Answer 11

• Enlargement: excess extracellular space OR Atophy: due to amyloid involvement of BVs
• Firm consistency
• Waxy-pale in color

Question 12

(1) is the most commonly affected organ by amyloidosis, specifically affecting the (2) part. (1) is markedly (3) in size and (4) is a common presentation. Eventually (5) develops and the patient must go on (6).

Answer 12

1- kidney
2- glomeruli
3- enlarged
4- proteinuria
5- chronic renal failure
6- dialysis

Question 13

describe amyloidosis of the spleen

Answer 13

• common affected organ
• diffuse involvement of spleen
• markedly enlarged spleen – splenomegaly
• Sago spleen = tapioca-like granules
• NO known consequences

Question 14

describe amyloidosis of the liver

Answer 14

• common affected organ
• diffuse involvement of liver
• markedly enlarged liver – hepatomegaly

Question 15

Amyloidosis of the heart can result from (1) or (2) amyloidosis. Deposits are seen in the (3) part of the heart. The heart appears as (4) and can the following complications, (5).

Answer 15

1- systemic
2- localized (senile localized amyloidosis- ATTR/transthyretin)
3- all layers and vessels
4- enlarged, waxy, pale
5- cardiac failure, arrhythmias, restrictive cardiomyopathy

Question 16

list the 3 categories of Intracellular accumulations

Answer 16

1) normal cellular components (water, lipid, protein, carbs)
2) abnormal substance: exogenous (mineral, infectious agent / its products) or endogenous (abnormal synthesis/metabolism)
3) pigment: exogenous or endogenous

Question 17

what are the 3 mechanisms substances can accumulate in cell

Answer 17

1) Normal Endogenous- normal OR inc production, AND inadequate metabolism/removal
2) Normal/Abnormal Endogenous- genetic/acquired defect in metabolism
3) Abnormal Exogenous- deposits/accumulated b/c no mechanism of degradation or transport

Question 18

(1) is the most common pollutant and is a common exogenous pigment. It accumulates in (2) and its (3) tissues as it is phagocytosed by (4).

Answer 18

1- carbons (often found with other pollutants in industry like asbestos, silica)
2- lungs
3- lymph nodes (anthracosis; anthracitic pigments in macrophages)
4- alveolar macrophages
(usually asymptomatic)

Question 19

tattooing is a form of (1) pigmentation as it results from the introduction of (2) and (3) into skin, which are phagocytosed by (4) and resulting in (5)

Answer 19

1- localized exogenous pigmentation
2- insoluble metallic pigment
3- vegetable pigments
4- dermal macrophages
5- pigments remaining in dermis for life

Question 20

(1) is an insoluble, brown-black pigment produced by (2) in the skin. It functions to (3). It can be stored in (4) and produced alternatively by (5).

Answer 20

1- melanin
2- melanocytes
3- protect against UV light
4- other cells (freckles), nevus cells, melanophages
5- some tumors
NOTE- varies with race, absent in albinism

Question 21

(1) is considered the aging pigment, where it can be seen in the following organs: (2). It indicates (3) of the cell. It results from (4) in the cell, and is found in (5) of the cell. It is normal in small amounts and functions to (6).

Answer 21

1- lipofusin (brown-gold)
2- liver, heart, brain
3- chronic wear and tear
4- breakdown of cell membranes
5- lysosomes
6- no known physiological effect

Question 22

(1) is a pigment derived from breakdown of senile RBCs. It is normally found in (2) and is visible if (3) and (4) happens. Presence is indicated by (5).

Answer 22

1- bilirubin
2- bile (along with bile salts, lipids)
3- excess bilirubin production (hemolysis)
4- inability to excrete bile (obstruction)
5- Jaundice: yellow-golden skin and conjunctiva

Question 23

(1) is a pigment derived from breakdown of Hg. It is stored in (2) and its excess in cells is called (3).

Answer 23

1- hemosiderin
2- spleen, liver, bone marrow
3- hemosiderosis (excess Fe in cells)

Question 24

Hemosiderin:

• (1) appearance with H&E
• (2) appearance with Prussian Blue stain

Answer 24

1- golden-brownish pigment (granular)

2- blue

Question 25

Extreme Fe deposition is called (1). Excess Fe occurs due to one of the following: (2), (3), (4). Complications of Fe deposition are the following: (5).

Answer 25

1- hemochromatosis (brown pigmentation)
2- excess intestinal Fe absorption
3- excess RBC breakdown (hemolysis)
4- multiple transfusions
5- DM, cirrohosis, high risk of hepatocellular carcinoma

Question 26

Gouty arthritis is caused by (1) and results from the deposition of (2) in soft tissues and joints. The result of this deposition is (3).

Answer 26

1- hyperuricemia
2- urate crystals
3- CK-mediated destruction of articular cartilage

Question 27

Gout is a disorder in (1), and the following are risk factors: (2).

Answer 27

1- purine metabolism (A, G)

2- age, genetics, heavy EtOH consumption, obesity, certain drugs (thiazides)

Question 28

(1) % cases of gout are primary due to (2) or (3)

4) % case of gout are secondary due to (5), (6), (7

Answer 28

1- 90%
2- unknown enzyme defect
3- HGPRT

4- 10%
5- inc nucleic acid turnover
6- chronic renal disease
7- inborn errors of metabolism

Question 29

Give the Gross and Microscopic features of Gout

Answer 29

Gross- tophi (large inflammatory deposits seen in small joints of feet/hands), arthritis with cartilage destruction

Microscopic: tophi (crystals + inflammation), foreign body giant cells, Urate Crystals (needle shaped, orange under polarized light)

Question 30

secondary amyloid associated protein is related to the following conditions

Answer 30

• reactive systemic amyloidosis (chronic conditions)

- familial Mediterranean fever

Question 31

transthyretin is elevated in the following conditions

Answer 31

• familial amyloidotic neuropathies

- systemic senile amyloidosis

Question 32

elevated Calcitonin is a key sign ________ carcinoma

Answer 32

medullary carcinoma of the thyroid

Question 33

β2 microglobulin is elevated in….

Answer 33

hemodialysis

Question 34

β2 amyloid aggregates in…..

Answer 34

alzheimer’s disease (in the brain)

Question 35

amyloid light chain is elevated in the following conditions

Answer 35

multiple myeloma