Flashcards in Chp. 1 Amyloidosis Deck (13):
What is amyloid and where does it deposit?
What is the 2ndary protein configuration?
What staining is necessary to view it microscopically?
It is a misfolded protein that deposits in EXTRACELLULAR SPACES thereby damaging tissues. These proteins can deposit anywhere in the body; systemic or in one spot, but usually deposits AROUND BLOOD VESSELS.
Multiple proteins can deposit as amyloid are in a B pleated sheet configuration.
Seen with Congo Red staining or Apple-green birefringence
Can amyloid be removed?
How many classifications are there in systemic amyloidosis? How many in localized?
In systemic there are two classifications - Primary and Secondary Amyloidosis
In Local Amyloidosis there are 6 classifications.
1. Senile Cardiac
2. Familial Amyloid Cardiomyopathy
3. Non Insulin Dependent Diabetes (Type II)
5. Dialysis associated Amyloidosis
6. Medullary Carcinoma of the Thyroid
What is Primary Systemic Amyloidosis?
Primary is systemic deposition of AL AMYLOID which is derived from Ig Light Chain associated with plasma cell dyscrasias (i.e. Multiple Myeloma)
When plasma cells create Ig they create light and heavy chain in equal proportions. In dyscrasias, abnormal plasma cells make too much light chain. This excess light chain spills out into blood and becomes misfiled then deposits into tissues.
What is Secondary Systemic Amyloidosis?
It is systemic deposition of AA AMYLOID which is derived from Serum Amyloid-Associated Protein (SAA)
SAA is an acute phase reactant that is elevated during chronic inflammation (i.e. lupus, arthritis, Crohns, UC), malignancy, and FMF (familial mediterranean fever)
What is Familial Mediterranean Fever? How does it present?
FMF is a dysfunction of neutrophils (AR). They are activated for no good reason which causes a chronic inflammatory state. Presents with episodes of fever and acute serosal inflammation which can mimic:
Appendicitis, Arthritis, MI
Mutation of Pyrin on MEVF gene. Pyrin blocks the activation ofcaspase-IB. Caspase IB activates inflammation. w/o pyrin, get inflammation.
High SAA during an attack can deposit as amyloid in tissues
What are the clinical findings of systemic amyloidosis? How can it be diagnosed?
What happens to damaged organs in this case? Why?
Clinical findings: Diverse bc any organ can be affected; but most common findings are:
Nephrotic Syndrome (KIDNEY most involved organ!!!)
Restrictive Cardiomyopathy or Arrythmia
Tongue Enlargement, malabsorption, hepatosplenomegaly
Dx requires Bx (abdominal fat pad or rectum) with congo red or apple green birefringence.
Damaged organs must be transplanted bc the amyloid cannot be removed.
What is Senile Cardiac Amyloidosis?
This is when amyloid deposits in old people's hearts, lol
NON-MUTATED SERUM TRANSTHYRETIN deposits in the heart.
Usu asymptomatic, present in about 25% of people over 80 y/o
Normal part of aging so the protein isn't mutated.
What is Familial Amyloid Cardiomyopathy?
It is a localized amyloidosis where MUTATED SERUM TRANSTHYRETIN deposits in the heart leading to restrictive cardiomyopathy. This deposition in the heart makes it less compliant so it can't expand easily...its restricted
How does Type II DM lead to localized amyloidosis?
Amylin (derived from insulin) deposits in the Islets of the pancreas.
In Type II there is insulin resistance at the level of adipocytes and skeletal muscle. Excess insulin made until B cells "burn out". The production of excess insulin creates a byproduct called AMYLIN which deposits in the Islets. Classical finding.
How does Alzheimers lead to Amyloidosis?
AB amyloid deposits in the brain forming amyloid plaques.
AB amyloid is derived from B amyloid precursor protein (B-APP). The gene for B-APP is found on chromosome 21. Those with trisomy 21 (Downs) usu have early onset (40 y/o) Alzheimers bc they have three copies of this gene
How does dialysis lead to amyloidosis?
This is deposition of B2 micro globulin in joints of these dialysis patients.
B2 micro globulin provides structural support for MHC-1 which is a molecule on the surface of all nucleated cells and platelets. It has an intra and extra cellular domain.
W/O B2 microglobulin, MHC-I not expressed well on the cell surface
In dialysis, the B2 micro globulin is not filtered well from the blood so it builds up and deposits in joints as localized amyloidosis.