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PA9.1-2 | Amyloidosis — Summary & Reflection
REFLECT
Take 3–4 minutes before reading the summary.
- Without looking back, classify the following into AL, AA, ATTR, or localised: (a) A dialysis patient with carpal tunnel syndrome; (b) a 60-year-old man with myeloma and macroglossia; (c) an elderly man with echocardiographic hypertrophy and low ECG voltage; (d) medullary thyroid carcinoma stroma.
- A colleague says, "All amyloid looks the same on H&E — why bother typing it?" Draft a 2-sentence rebuttal explaining why protein typing changes management.
- Why is the abdominal fat pad the preferred first biopsy site rather than the kidney, even when the kidney is clearly affected on clinical grounds?
KEY TAKEAWAYS
Amyloidosis — Core Framework
What: Extracellular deposits of misfolded proteins sharing a β-pleated sheet secondary structure. Insoluble, resistant to proteolysis.
How to recognise it:
• H&E: amorphous, homogeneous, eosinophilic extracellular hyaline material
• Congo red + polarised light: apple-green birefringence — pathognomonic
• Gross: waxy, lardaceous, enlarged firm organs
Classification by protein:
| Type | Protein | Disease link |
|---|---|---|
| AL | Immunoglobulin light chain | Plasma cell dyscrasia / myeloma |
| AA | Serum amyloid-associated (SAA) | Chronic inflammation (RA, TB, IBD) |
| Aβ2M | β2-microglobulin | Long-term haemodialysis |
| ATTR | Transthyretin | Familial (mutation) / Senile (cardiac) |
| Aβ | Amyloid-β peptide | Alzheimer disease, Down syndrome |
| Endocrine | Calcitonin / Amylin | Medullary thyroid Ca / Type 2 DM |
Pathogenesis: Protein overproduction or structural instability → misfolding → β-sheet aggregation → fibril nucleation (seeding) → extracellular accumulation → pressure atrophy + ischaemia
Organs and consequences:
• Kidney (most common, most lethal): nephrotic syndrome → renal failure
• Heart: restrictive cardiomyopathy, ECG-echo mismatch
• Spleen: sago (follicular) or lardaceous (diffuse) pattern
• Tongue: macroglossia (AL hallmark)
• Nerves: sensorimotor + autonomic neuropathy
Diagnosis: Abdominal fat pad aspiration (first choice) + Congo red histology; type with IHC or mass spectrometry
Treatment principle: Eliminate the source of the precursor protein