Flashcards in L16- Amyloidosis and Pigmentation Deck (35):
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).
1- acute phase protein (liver)
3- abnormal fibrils
4- improperly folded proteins (soluble if correctly folded)
6- starch / amylose
-(1) H&E stain appearance
-In (2) stain it appears 'salmon red' and gives (3) characteristic under polarized light
-(4) EM appearance
1- 'glassy pink'
2- Congo Red stain
3- 'apple-green' bi-refringence (bi-refraction)
4- non-branching fibrils + non-fibrillary component (P component)
describe the two MAIN types of Amyloid proteins
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
(1) is a normal serum protein that binds/transports thyroxine and retinol. Its mutant form is referred to as (2).
2- familial amyloid polyneuropathies
_____ is amyloidosis seen in hemodialysis patients
_____ is a cerebral plaque in Alzheimer's disease
compare the mechanism of amyloidosis when it involves normal and mutant proteins
Normal- when produced in large amounts, they have tendency to associate, forming fibrils
Mutant- prone to misfolding and aggregation; produced at normal quantities
compare localized and systemic amyloidosis
-Local = one organ affected
-Systemic > one organ affected
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.
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)
_____ amyloid type is the predominant heriditary amyloidosis form
ATTR- transthyretin (binds thyroxine and retinol for plasma transport)
list the macroscopic features of amyloidosis
-Enlargement: excess extracellular space OR Atophy: due to amyloid involvement of BVs
-Waxy-pale in color
(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).
5- chronic renal failure
describe amyloidosis of the spleen
-common affected organ
-diffuse involvement of spleen
-markedly enlarged spleen -- splenomegaly
-Sago spleen = tapioca-like granules
-NO known consequences
describe amyloidosis of the liver
-common affected organ
-diffuse involvement of liver
-markedly enlarged liver -- hepatomegaly
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).
2- localized (senile localized amyloidosis- ATTR/transthyretin)
3- all layers and vessels
4- enlarged, waxy, pale
5- cardiac failure, arrhythmias, restrictive cardiomyopathy
list the 3 categories of Intracellular accumulations
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
what are the 3 mechanisms substances can accumulate in cell
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
(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).
1- carbons (often found with other pollutants in industry like asbestos, silica)
3- lymph nodes (anthracosis; anthracitic pigments in macrophages)
4- alveolar macrophages
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)
1- localized exogenous pigmentation
2- insoluble metallic pigment
3- vegetable pigments
4- dermal macrophages
5- pigments remaining in dermis for life
(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).
3- protect against UV light
4- other cells (freckles), nevus cells, melanophages
5- some tumors
NOTE- varies with race, absent in albinism
(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).
1- lipofusin (brown-gold)
2- liver, heart, brain
3- chronic wear and tear
4- breakdown of cell membranes
6- no known physiological effect
(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).
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
(1) is a pigment derived from breakdown of Hg. It is stored in (2) and its excess in cells is called (3).
2- spleen, liver, bone marrow
3- hemosiderosis (excess Fe in cells)
-(1) appearance with H&E
-(2) appearance with Prussian Blue stain
1- golden-brownish pigment (granular)
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).
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
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).
2- urate crystals
3- CK-mediated destruction of articular cartilage
Gout is a disorder in (1), and the following are risk factors: (2).
1- purine metabolism (A, G)
2- age, genetics, heavy EtOH consumption, obesity, certain drugs (thiazides)
(1)% cases of gout are primary due to (2) or (3)
(4)% case of gout are secondary due to (5), (6), (7)
2- unknown enzyme defect
5- inc nucleic acid turnover
6- chronic renal disease
7- inborn errors of metabolism
Give the Gross and Microscopic features of Gout
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)
secondary amyloid associated protein is related to the following conditions
-reactive systemic amyloidosis (chronic conditions)
-familial Mediterranean fever
transthyretin is elevated in the following conditions
-familial amyloidotic neuropathies
-systemic senile amyloidosis
elevated Calcitonin is a key sign ________ carcinoma
medullary carcinoma of the thyroid
β2 microglobulin is elevated in....
β2 amyloid aggregates in.....
alzheimer's disease (in the brain)