1.5 Amyloid

Question 1

What is amyloid?

Answer 1

Misfolded protein that deposits in the extracellular space damaging tissues

Question 2

Though amyloid can be many different proteins, what are their shared characteristics?

Answer 2

Beta-pleated sheets

Congo red staining and apple-green birefringence under polarized light

Question 3

Systemic amyloidosis can be primary or secondary. Describe primary amyloidosis

Answer 3

Systemic deposition of AL amyloid which is derived from immunoglobulin light chain
Associated with plasma cell dyscrasias where the plasma cells overproduce light chain

Question 4

Systemic amyloidosis can be primary or secondary.

Describe secondary amyloidosis

Answer 4

Systemic deposition of AA amyloid which is derived from serum amyloid-associated protein (SAA)

SAA is an acute phase reactant increased by inflammatory states, malignancy, and Familial Mediterranean Fever (FMF)

FMF is dysfunction of neutrophils and presents with fever and serosal inflammation that can mimic appendicitis, arthritis, or MI; high SAA during attacks leads to deposition of AA amyloid

Question 5

What are the classic clinical findings of systemic amyloidosis?

Answer 5

Nephrotic syndrome of the kidneys is the most common organ involved
Restrictive cardiomyopathy or arrhythmia
Tongue enlargement, malabsorption, HSM

Question 6

Describe senile cardiac amyloidosis

Answer 6

Localized amyloidosis
Non-mutated serum transthyretin deposits in the heart
Usually asymptomatic, present in 25% of individuals over 80

Transthyretin is the second most common protein in blood

Question 7

Familal amyloid

Answer 7

Localized amyloidosis
Mutated serum transthyretin deposits in heart causing restrictive cardiomyopathy
5% of African american carry mutated gene

Question 8

Amyloid associated with DM II

Answer 8

Localized amyloidosis

Amylin (derivative of insulin) deposits in islets of pancreas

Question 9

Alzheimers amyloidosis

Answer 9

A beta-amyloid (from beta-amyloid precursor protein) deposits in brain forming amyloid plaques
Gene for beta-APP found on chromosome 21 causing Down Syndrome patients to develop Alzheimers by age 40

Question 10

Dialysis associated amyloidosis

Answer 10

Localized amyloidosis
Beta2-microglobulin deposits in joints

Beta2-microglobulin acts as a structural protein for MHC I proteins on all nucleated cells, not filtered out well during dialysis leading to build up in the body and deposit in joints

Question 11

Amyloidosis associated with Medullary carcinoma of the thyroid

Answer 11

Tumor of C-cells that produce calcitonin which deposits within the tumor leading to ‘tumor cells in an amyloid background’