Amyloidosis
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Direct answer
Amyloidosis is a group of disorders in which misfolded proteins deposit extracellularly as beta-pleated sheet fibrils that stain characteristically with Congo red, showing apple-green birefringence under polarised light. The systemic forms that matter for NEET-PG are AL (primary, from monoclonal light chains), AA (secondary, from the acute-phase protein serum amyloid A in chronic inflammation) and ATTR (from transthyretin, in senile and hereditary forms), each with its own precursor, organ preference and signature.
What you must remember
- Diagnosis by staining: amyloid is homogenous and eosinophilic on H&E, but Congo red with polarised apple-green birefringence is diagnostic; all fibrils share the serum amyloid P component.
- AL (primary) amyloidosis: lambda light chains from a plasma cell dyscrasia; the commonest systemic form; targets kidney (nephrotic syndrome), heart (restrictive cardiomyopathy), nerves and liver; periorbital purpura and macroglossia are classic clues.
- AA (secondary) amyloidosis: serum amyloid A deposited in chronic inflammation — rheumatoid arthritis, inflammatory bowel disease, chronic osteomyelitis, tuberculosis, bronchiectasis (leading causes in India); kidneys, liver and spleen are favoured, renal involvement dominating.
- ATTR amyloidosis: wild-type transthyretin in elderly men causing senile cardiac amyloid, often with carpal tunnel syndrome; hereditary variants carry point mutations such as Val30Met.
- Dialysis-associated amyloidosis: beta-2 microglobulin depositing in joints and carpal tunnels in long-term dialysis patients.
- Localised amyloid: medullary thyroid carcinoma stroma (procalcitonin-derived), islet amylin in type 2 diabetes, and cerebral amyloid in Alzheimer plaques and angiopathy.
- Diagnostic route: biopsy of abdominal fat pad, rectum or gingiva with Congo red staining; serum free light chains and immunofixation for AL; cardiac imaging for cardiac involvement.
Common confusion
AL versus AA generates the recurring confusion: AL arises from a plasma cell disorder and must be sought with serum and urine electrophoresis and free light chains, while AA complicates chronic inflammatory disease and is treated by controlling that disease — the precursor, not the deposit, defines the work-up. Students also mix organ preferences: cardiac involvement points to AL or ATTR, whereas AA characteristically spares the heart. The terms primary and secondary are historical — modern classification names the precursor protein (A plus the protein name), the language current exams prefer.
Exam-focused takeaway
NEET-PG stems on amyloidosis are recognition questions: the stain and its apple-green birefringence identify the deposit; the clinical setting names the type — nephrotic syndrome with a monoclonal band (AL), chronic tuberculosis or rheumatoid arthritis with renal amyloid (AA), senile heart failure (ATTR), or long-term dialysis with carpal tunnel (beta-2 microglobulin). Expect one-liners on amyloid P component, beta-pleated sheet structure, macroglossia and periorbital purpura, and biopsy site choice. Learn each type as precursor, cause and target organ — a compact grid worth full marks.
Frequently asked questions
What is amyloid and how is it diagnosed histologically?
Extracellular deposits of misfolded protein fibrils in a beta-pleated sheet conformation, stained orange-red by Congo red and showing apple-green birefringence under polarised light.
What is the difference between AL and AA amyloidosis?
AL comes from monoclonal light chains in plasma cell disorders; AA from serum amyloid A raised in chronic inflammation such as tuberculosis, rheumatoid arthritis or inflammatory bowel disease.
Which organs are affected in systemic amyloidosis?
Kidneys (nephrotic syndrome), heart (restrictive cardiomyopathy and conduction disease), liver, spleen, nerves, and soft tissues producing macroglossia and periorbital purpura, chiefly in AL.
What is ATTR amyloidosis?
Amyloid derived from transthyretin — wild-type causing senile cardiac and carpal tunnel amyloid in elderly men, and mutant hereditary forms causing familial amyloid polyneuropathy.
Which biopsy site is used to diagnose systemic amyloidosis?
Abdominal fat pad aspiration is the usual first choice, being simple and sensitive; rectal or gingival biopsies are alternatives, all Congo red confirmed.
Where does amyloid appear in endocrine disease?
Calcitonin-derived amyloid in the stroma of medullary thyroid carcinoma and islet amyloid (amylin) in the pancreas of type 2 diabetes are the classic localised endocrine deposits.