Amyloidosis

1. Definition

• Amyloidosis = extracellular deposition of misfolded fibrillar proteins → tissue damage and organ dysfunction.
• Fibrils aggregate in a β-pleated sheet configuration → insoluble → disrupt function.
• Congo red stain → apple-green birefringence under polarized light (red-green dichroism).

2. Related Intracellular Protein Accumulations

• Excess protein presented: renal tubular reabsorption in massive proteinuria.
• ↑Synthesis: neoplastic Ig → Russell bodies (rER), Dutcher bodies (nuclei).
• Cell injury: alcohol → Mallory bodies (intermediate filament aggregates in hepatocytes).
• Abnormal folding: chaperone failure → accumulation (e.g. amyloid).

3. Major Amyloid Types

Type	Precursor	Association
AL (primary)	Ig light chains (λ>κ)	Plasma cell dyscrasia / multiple myeloma
AA (secondary)	SAA (acute-phase, liver)	Chronic inflammation (TB, RA, IBD)
Aβ	APP	Alzheimer disease plaques
TTR	Transthyretin (binds T4)	Familial amyloid polyneuropathy; senile cardiac amyloidosis

• AA pathway: inflammation → macrophages → IL-1/IL-6 → liver SAA → proteolysis → AA.
• Familial: Mediterranean fever (pyrin mutation → unregulated inflammation → AA).

4. Morphology

• Large deposits → enlarged, grayish, waxy firm organs; iodine + sulphuric acid → brown.
• Microscopy: extracellular amyloid → pressure atrophy of cells.
• Organs: kidney (most serious — glomeruli), spleen (sago/lardaceous), liver (Disse space), heart (subendocardial, between fibres).

5. Clinical

• Non-specific (weakness, fatigue, weight loss) → organ-specific:
  • Kidney: proteinuria, nephrotic syndrome, renal failure
  • Heart: restrictive cardiomyopathy, conduction disturbance
  • Liver: hepatosplenomegaly
• Median survival 1–3 years (amyloid cannot be removed).

💡 High-yield: Congo red → apple-green birefringence is the diagnostic hallmark. AL = multiple myeloma; AA = chronic inflammation; Aβ = Alzheimer; TTR = familial/senile cardiac. Kidney involvement carries the worst prognosis.