U01.04.010 Amyloidosis

Amyloidosis is a condition characterized by the abnormal aggregation of proteins or their fragments into β-pleated linear sheets. These insoluble fibrils lead to cellular damage and apoptosis. Amyloid deposits can be visualized using various staining techniques.

Visualization of Amyloid Deposits

Congo Red Stain:
- Nonpolarized Light: Amyloid deposits appear red or orange.
- Polarized Light: Amyloid deposits show apple-green birefringence.
H&E Stain: Reveals amyloid deposits in glomerular mesangial areas. Additionally, the tubular basement membranes are enlarged when viewed under light microscopy.

Common Types of Amyloidosis

Type	Fibril Protein	Description
Systemic
Primary Amyloidosis	AL (from Ig light chains)	Seen in plasma cell disorders (e.g., multiple myeloma).
Secondary Amyloidosis	Serum Amyloid A (AA)	Associated with chronic inflammatory conditions (e.g., rheumatoid arthritis, IBD).
Dialysis-related Amyloidosis	β2-microglobulin	Occurs in patients with ESRD and/or on long-term dialysis.
Localized
Alzheimer Disease	β-amyloid protein	Derived from amyloid precursor protein (APP).
Type 2 Diabetes Mellitus	Islet amyloid polypeptide (IAPP)	Caused by amylin deposition in pancreatic islets.
Medullary Thyroid Cancer	Calcitonin	Associated with calcitonin deposition.
Isolated Atrial Amyloidosis	ANP	Common with aging; increases risk of atrial fibrillation.
Systemic Senile Amyloidosis	Normal (wild-type) transthyretin (TTR)	Predominantly affects cardiac ventricles; cardiac dysfunction is more gradual than in AL amyloidosis.
Hereditary
Familial Amyloid Cardiomyopathy	Mutated transthyretin (ATTR)	Causes ventricular endomyocardium deposition, leading to restrictive cardiomyopathy and arrhythmias. 5% of African Americans carry a mutant allele.
Familial Amyloid Polyneuropathies	Mutated transthyretin (ATTR)	Results from a transthyretin gene mutation.

Common Types of Amyloidosis

Points to Remember

Amyloidosis is marked by the deposition of insoluble protein fibrils, leading to cellular damage and tissue dysfunction.
Primary amyloidosis (AL) is linked with plasma cell disorders, while secondary amyloidosis (AA) is associated with chronic inflammation.
Amyloid deposits can be identified through specific staining techniques, including Congo red and H&E stains.
Different types of amyloidosis affect various organs and systems, with systemic and localized forms presenting distinct clinical manifestations.
Early diagnosis and understanding of the type of amyloidosis are crucial for effective management and treatment.

USMLE Step 1 Review Series

Curriculum

U01.04.010 Amyloidosis

Visualization of Amyloid Deposits

Common Types of Amyloidosis

Points to Remember

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