Chapter 1.5 Amyloid Flashcards
Define amyloid. Where does it tend to be found?
misfolded protein that deposits in extracellular space (outside cell! tends to deposit around blood vessels!)
damages tissue
(multiple proteins can deposit as amyloid)
Describe the configuration and staining of amyloid.
B-pleated sheet configuration
Congo red staining and apple-green birefringence under polarized light
Describe systemic vs localized amyloidosis.
deposits in multiple organ systems (diffuse)
localized -particular organ
What is primary amyloidosis? Systemic or localized? What type of amyloid and what derived from? What is it associated with?
primary amyloidosis-
systemic deposition of AL amyloid dervied from Ig light chain
associated with plasma cell dyscrasias (abnormalities of plasma cell- overprod. of light chain which can leak out into blood and then can become misfolded and deposit in tissue creating primary amyloidosis)
What is secondary amyloidosis? Systemic or localized? What type of amyloid and how is it derived?
systemic deposition of AA amyloid derived from SAA
SAA is acute phase reactant (anytime inflammation there is increase SAA) that is increased in chronic inflammatory states (autoimmune diseases, Lupus, Chrones), malignancy, and Familial Mediterranean fever
(SAA can become AA and deposit as amyloid)
Describe Familial Mediterranean fever. What causes it?
How does it present clinically?
What is it an example of?
ex: secondary amyloidosis
Dysfunction of neutrophils (AR); persons of Med. origin (neutrophils activated and create attack of acute inflammation that is not drive by infection but driven by misfunction of neutrophils)
presents w fever and acute serosal inflammation (serosal surface of heart = pericardium ..would present as mimicking MI, serosal surface of abdomen= mimick acute appendicitis)
during attack acute phase reactants prod; high SAA during attacks deposits as AA amyloid
What are classical clinical findings of systemic amyloidosis?
Nephrotic syndrome (large loss of protein, greater than 3.5g of protein over 24 hrs in urine); kidney is most common organ involved
Restrictive cardiomyopathy (disease of heart in which we can’t fill heart properly bc wall of heart becomes less compliant/bendable bc of filling of heart with amyloid so can’t pump well and get eventual heart failure) or arrhythmia
Tongue enlargement, malabsorption (wall of bowel can become thickened), and hepatosplenomegaly
What does diagnosis of systemic amyloidosis require?
Requires tissue biopsy (red staining and green polarized light)
abdominal fat pad and rectum are easily accessible targets
Can amyloid be removed?
Damaged organs must be transplanted
amyloid cannot be removed
Describe senile cardiac amyloidosis.
What type of amyloid?
What group of people are affected?
LOCALIZED
Non-mutated serum transthyretin (2nd most common protein in blood, this protein can deposit in heart over long time) deposits in heart
usually asymptomatic
25% of individuals greater than 80 years of age
Describe Familial amyloid cardiomyopathy.
Mutated serum transrethyrin deposits in heart
leads to restrictive cardiomyopathy (wall of heart full of amyloid, then cannot expand, less compliant, cannot fill, restricted from filling and thus cannot pump properly and then patient eventually goes into cardiac failure
5% of African Am. carry mutated gene
How do senile cardiac amyloidosis and familial amyloid cardiomyopathy differ?
senile cardiac amyloidosis- NON mutated serum transthyretin *asymptomatic
familial amyloid cardiomyopathy - MUTATED serum transthyretin, *leads to disease (restrictive cardiomyopathy
Describe NIDDM (Type II)
localized amyloidosis
T2DM problem is resistance to insulin
- amylin deposits in islets of pancreas
- derived from insulin
What type of amyloid protein is present in Alzheimer’s disease?
Where is this protein derived from?
A-beta amyloid deposits in brain, forming amyloid plaques
Derived from B-amyloid precursor protein (gene that prod. that protein is on chromosome 21)
-most individuals w Down Syndrome (3 copies of Chromosome 21 often develop Alzheimer’s by age of 40, early on-set)
Dialysis-associated amyloidosis.
What type of amyloid?
Where does it deposit?
Explain mechanism.
B2-microglobulin (MHC I on all nucleated cells and platelets, B2 microglobulin provides support for MHC I to be expressed on surface of cells) deposits in joints
occurs in patients on dialysis (on dialysis B2M is not filtered well from the blood so it builds up in the blood and can deposit in joints as LOCALIZED amyloidosis)
