Amyloidosis Flashcards
What is an amyloid?
It is a misfolded protein that deposits in the extracellular space, thereby damaging tissues.
What are the shared features of amyloid proteins?
beta-pleated sheet configuration, Congo red staining and apple-green birefringence when viewed microscopically under polarized light Deposition can be systemic or localized,
What is primary amyloidosis?
It is systemic deposition of AL amyloid, which is derived from immunoglobulin light chain
What is primary amyloidosis associated with?
plasma cell dyscrasias (e.g multiple myeloma)
Secondary amyloidosis is?
systemic deposition of AA amyloid, which is derived from serum amyloid-associated protein (SAA).
What is SAA?
It is an acute phase reactant that is increased in chronic inflammatory states, malignancy, and Familial Mediterranean Fever (FMF).
What is FMF due to?
a dysfunction of neutrophils (autosomal recessive) and occurs in persons of Mediterranean origin.
What does FMF present with?
episodes of fever and acute serosal inflammation
FMF can mimic what?
appendicitis, arthritis, or myocardial infarction
How does FMF result in AA amyloid deposition in tissues?
High SAA during attacks deposits as AA amyloid in tissues
What is the most common organ involved in systemic amyloidosis?
kidney
What are the clinical findings of systemic amyloidosis?
Nephrotic syndrome, Restrictive cardiomyopathy or arrhythmia, Tongue enlargement, malabsorption, and hepatosplenomegaly
Diagnosis of systemic amyloidosis requires what?
tissue biopsy, Abdominal fat pad and rectum are easily accessible biopsy targets.
Damaged organs of systemic amyloidosis must be…
transplanted. Amyloid cannot be removed.
What is localized amyloidosis?
Amyloid deposition that is usually localized to a single organ
What is senile cardiac amyloidosis?
Non-mutated serum transthyretin deposits in the heart. Usually asymptomatic; present in 25% of individuals > 80 years of age
Familial amyloid cardiomyopathy
Mutated serum transthyretin deposits in the heart leading to restrictive cardiomyopathy, 5% of African Americans carry the mutated gene.
Non-insulin-dependent diabetes mellitus (type II)
Anylin (derived from insulin) deposits in the islets of the pancreas,
Alzheimer disease
amyloid beta (derived from J-amyloid precursor protein) deposits in the brain forming amyloid plaques
Gene for J-APP is present on…
chromosome 21.
Downs syndrome and Alzheimers?
Most individuals with Down syndrome (trisomy 21) develop Alzheimer disease by the age of 40 (early-onset).
Dialysis-associated amyloidosis
B-microglobulin deposits in joints,
Medullary carcinoma of the thyroid
Calcitonin (produced by tumor cells) deposits within the tumor (‘tumor cells in an amyloid background’).
