pathoma amyloidosis Flashcards
What is amyloid?
Amyloid is a misfolded protein that deposits in the extracellular space, damaging tissues.
What are the shared features of proteins that deposit as amyloid?
- β-pleated sheet configuration.
- Congo red staining with apple-green birefringence under polarized light
How can amyloid deposition occur?
Deposition can be systemic (involving multiple organs) or localized (affecting a single organ).
What is systemic amyloidosis, and how is it classified?
Systemic amyloidosis is amyloid deposition in multiple organs and is divided into:
- Primary amyloidosis: AL amyloid derived from immunoglobulin light chain.
- Secondary amyloidosis: AA amyloid derived from serum amyloid-associated protein (SAA).
What conditions are associated with primary amyloidosis?
Plasma cell dyscrasias, such as multiple myelom
What is the origin of secondary amyloidosis, and what conditions increase SAA levels?
- Secondary amyloidosis involves systemic deposition of AA amyloid, derived from SAA.
- Conditions increasing SAA: chronic inflammatory states, malignancy, and Familial Mediterranean Fever (FMF).
What is Familial Mediterranean Fever (FMF), and how does it relate to amyloidosis?
FMF is an autosomal recessive dysfunction of neutrophils, common in individuals of Mediterranean origin.
Characterized by episodes of fever and acute serosal inflammation, leading to high SAA levels and AA amyloid deposition.
What are the classic clinical findings of systemic amyloidosis?
- Nephrotic syndrome (kidney is most commonly involved).
- Restrictive cardiomyopathy or arrhythmia.
- Tongue enlargement, malabsorption, and hepatosplenomegaly.
How is systemic amyloidosis diagnosed and treated?
Diagnosis: Tissue biopsy (commonly abdominal fat pad or rectum).
Treatment: Damaged organs must be transplanted; amyloid cannot be removed.
What is localized amyloidosis?
Amyloid deposition confined to a single organ.
What is senile cardiac amyloidosis?
Deposition of non-mutated serum transthyretin in the heart.
Usually asymptomatic and seen in 25% of individuals over 80 years of age.
What is familial amyloid cardiomyopathy, and what population is commonly affected?
Mutated serum transthyretin deposits in the heart, leading to restrictive cardiomyopathy.
5% of African Americans carry the mutated gene.
What protein deposits in the islets of the pancreas in type II diabetes mellitus?
Amylin (derived from insulin)
What is the amyloid associated with Alzheimer disease, and what chromosome is its precursor gene found on?
Aβ amyloid (derived from β-amyloid precursor protein).
The gene for β-APP is located on chromosome 21.
Why do individuals with Down syndrome have a higher risk of developing early-onset Alzheimer disease?
The gene for β-amyloid precursor protein is located on chromosome 21, which is trisomic in Down syndrome. Most individuals with Down syndrome develop Alzheimer disease by age 40.
