Rapid Review·General Pathology
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CELLULAR INJURY
T2High yieldAmyloidosis
P208
Focus on
Any protein that misfolds into a β-pleated sheet, deposits extracellularly, and strangles the organ it lands in.
Key takeaways
One fibril, many proteins
The common mechanism
extracellular deposition of protein in an abnormal fibrillar, β-pleated sheet configuration → cell injury and apoptosis. The precursor protein differs by disease, but the fibril architecture never does.How to see it
Stains
Congo red gives red-orange under normal light and apple-green birefringence under polarized light. Amorphous pink on H&E.
What it does to each organ
Manifestations by organ
- Renal → nephrotic syndrome, the most common presentation.
- Cardiac → restrictive cardiomyopathy.
- GI → hepatosplenomegaly.
- Neuro → dementia, peripheral neuropathy.
- MSK → macroglossia, carpal tunnel syndrome.
- Skin → waxy thickening, easy bruising with periorbital purpura.
Naming the amyloid
| Type | Fibril Protein | Precursor / Association |
|---|---|---|
| AL (Primary) | Ig Light chains | Plasma cell dyscrasias (multiple myeloma) |
| AA (Secondary) | Serum Amyloid A | Chronic inflammation: RA, IBD, familial Mediterranean fever, protracted infection ("A" for inflammation) |
| Transthyretin (ATTR) | Transthyretin | Sporadic (wild-type) in aging, mainly cardiac; hereditary (mutant) causes familial amyloid polyneuropathy/cardiomyopathy |
| Dialysis-related | β2-microglobulin | ESRD on long-term dialysis → carpal tunnel |
| Alzheimer disease | β-amyloid | Cleaved from APP on chromosome 21, hence early onset in Down syndrome |
| Isolated atrial | ANP | Aging → ↑ risk of atrial fibrillation |
| Type 2 diabetes | Islet amyloid polypeptide (amylin) | Deposits in pancreatic islets |
| Medullary thyroid CA | Calcitonin | Secreted by the tumor cells themselves |
A man on hemodialysis for 15 years develops bilateral carpal tunnel syndrome. Which protein makes up the amyloid?
β2-microglobulin, which is not cleared by long-term dialysis in end-stage renal disease and deposits as dialysis-related amyloid.
How it's tested
Systemic amyloidosis is diagnosed by tissue biopsy, classically an abdominal fat pad aspirate, showing Congo red staining with apple-green birefringence under polarized light. That is the answer to "most appropriate next step" whenever a patient has nephrotic-range proteinuria plus a restrictive cardiomyopathy plus macroglossia.
The mechanistic layer: in AA amyloidosis, chronic IL-6-driven hepatic production of serum amyloid A over years is what deposits, so prolonged elevation of an acute-phase reactant is the direct cause. That is why longstanding RA or familial Mediterranean fever is always sitting in the stem.
Go deeper
First Aid "Amyloidosis"; Pathoma Ch. 2 "Amyloidosis"; Boards & Beyond. Anchor the Congo red apple-green birefringence and the source-protein map (AL = light chains/myeloma; AA = SAA/chronic inflammation; β2-microglobulin = dialysis; Aβ = Alzheimer; ATTR = cardiac).
High-yield images2
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(...) fever
(...) disease
(...)
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