What is amyloid?

  1. What is amyloid?
    Misfolded proteins that accumulates in extracellular space and damages tissue. Amyloid can’t be
    removed and damaged organs must be transplanted
  2. What are characters of amyloid?
    • Misfolded proteins have B-sheet arrangement
    • Amyloid are congo red positive (appear apple-green under polarized light)
    Fig - apple-green appearing amyloid under polarized light
    • Amyloid can be deposited systemically or locally
  3. What are 2 types of systemic amyloidosis?
    Primary amyloidosis - When Ig light chain deposits systemically (in form of AL amyloid), it’s called
    primary amyloidosis. It’s associated with plasma cell dyscrasias (disease) - when plasma cells make
    ton of light chain, they will deposit.

    Secondary amyloidosis - when SAA protein deposits systemically (in from of AA amyloid), it’s called
    2ndary amyloidosis. SAA is acute phase reactant that is increased in chronic inflammatory states,
    malignancy, and Familial Mediterranean fever.
  4. What is familial mediterranean fever (HY)?
    It’s genetic disease with dysfunction of neutrophils that causes systemic amyloidosis. It’s usually
    seen in people of mediterranean origin.

    • Pt will have high SAA that deposits at AA amyloid
    Pt may present with acute fever and serosal inflammation (serosal inflammation of heart might
    mimic MI, of gut may mimic appendicitis)
    What are classic findings of systemic amyloidosis?
    • Kidney is most commonly involved - nephrotic syndrome is seen
    • Restrictive cardiomyopathy or arrhythmia
    • Hepatosplenomegaly, malabsorption, large tongue
  5. How do you diagnose amyloidosis?
    Requires tissue biopsy (needs to be congo-red positive) - usually take from rectum or abdominal
    fat pads
  6. Describe senile cardiac amyloidosis (a type of local amyloidosis).
    Caused due to deposition of non-mutated serum transthyretin in heart. Transthyretin is 2nd most
    common protein in blood.

    1.5 Amyloidosis
    Cellular injury Page 5.1
    common protein in blood.
    • Usually asymptomatic and seen in 25% of people >80 year
  7. Describe familial amyloid cardiomyopathy (a type of local amyloidosis).
    • Caused due to deposition of mutated serum transthyretin in heart.
    • Leads to restrictive cardiomyopathy
    • Usually seen in african americans (5% carry mutation)
  8. Describe how type 2 diabetes has local amyloidosis in it.
    Due to insulin resistance, pancreas produces lots of insulin. A byproduct amylin is also produced
    that deposits in islets of pancreas and cause amyloidosis.
  9. Describe how alzhimer’s has local amyloidosis in it.
    B-amyloid precursor protein (BAPP) on chromosome 21 makes AB amyloid plaques. (Most
    individuals with Down’s syndrome have Alzheimer’s by 40 year age)
  10. Describe how dialysis can cause local amyloidosis in joints.
    Beta2 microglobulin is a protein that structurally supports MHC-I on cell surface. In dialysis, B2-
    microglobulin isn’t filtered well from blood. It then builds up in joints and cause amyloidosis.
  11. Describe how medullary thyroid cancer can cause local amyloidosis in thyroid.
    In MTC, overproduction of calcitonin leads to formation of calcitonin amyloid plaques in thyroid.
    (In FNA of thyroid, seeing tumor cells in amyloid background makes MTC more probable)