Amyloidosis
- Definition: Extracellular eosinophilic deposition of a protein
- It is a mucoprotein.
- Amyloid deposit is insoluble, consists of 95% fibrils.
- Called "Amyloid" due to its resemblance to starch in staining characteristics, as it contains sugar groups.
Organ Involvement and Appearance:
- Most common organ affected:
- Kidney.
- Most common organ in old people/specific
- Heart - Restrictive cardiomyopathy
Most Common Cause of Death
- For primary amyloidosis: Cardiac failure.
- For secondary amyloidosis: Renal failure.
Mnemonic:
- Old people/Primary amyloidosis → Heart
- Secondary/most common organ → Kidney
Specimen Collection:
- Localized amyloidosis:
- Requires local biopsy.
- Generalized amyloidosis:
- Collected via abdominal fat pad aspirate >> rectal biopsy.
- Or gingival/tongue biopsy.
Staining Techniques:
- Gross Staining (Lugol's iodine):
- Applied to the cut surface of the organ.
- Produces a mahogany brown colour.
- Adding H2SO4:
- If colour changes to blue, it indicates amyloidosis.
- If colour remains intact, it is not amyloidosis.
- Microscopic Stains:
Stain | Colour/Characteristic |
H&E | Pink |
PAS | Magenta |
Congo Red (Light microscopy) | Salmon pink |
Congo red (Polarizing microscopy) | Apple green birefringence (best stain) |
Methyl violet/crystal violet | Metachromatic stain |
Thioflavin S & T (UV light) → TUV | Immunofluorescence |
Microscopy & Structure:
- Electron Microscopy (EM):
- Reveals non-branching fibrils.
- Fibrils are of indefinite length.
- Fibril diameter is 7.5-10 nm.
- X-ray crystallography:
- Shows fibrils composed of paired filaments.
- Reveals a Cross beta pleated sheets structure.
- This structure causes apple green birefringence on Congo red staining.
Imaging:
- Scintigraphy:
- Used to determine the extent of amyloidosis.
CLASSIFICATION
Type | Subtype / Condition | Associated Protein / Characteristic |
Systemic | Primary (1°) | AL (Light chain) |
ㅤ | Secondary (2°) | AA Malignancy ◦ RCC ◦ Lymphoma (Hodgkins) Autoimmune ◦ SLE ◦ RA Chronic infections ◦ TB ◦ Osteomyelitis ◦ Bronchiectasis Except CHRONIC BRONCHITIS PATHOGENESIS ↑ IL6, INF γ → → Stimulate Hepatocyte → SAA protein → AA protein |
ㅤ | Dialysis-Related | ABeta2 (Beta 2 Microglobulin Amyloid) "Two kidneys to two beta" |
Hereditary | Familial Amyloid Neuropathy | mutated ATTR "Nerves is eminent mutant" |
ㅤ | Cardiomyopathy | mutated ATTR |
ㅤ | Familial Mediterranean Fever | AA |
Localised | Alzheimer's | ABeta (Beta Amyloid) "One brain so one beta" |
ㅤ | Type 2 Diabetes Mellitus (T2DM) | Islet amyloid polypeptide |
ㅤ | Medullary Carcinoma of Thyroid | ACal (Calcitonin Amyloid) |
ㅤ | Atrial Amyloidosis | ANP |
ㅤ | Systemic Senile Cardiomyopathy | Wild ATTR |
Amyloid Protein | Associated Disease(s) | Mnemonic |
AL (Light Chain Amyloid) | Multiple Myeloma (plasma cell tumor producing light chains). | ㅤ |
AA (Amyloid-Associated Protein) | All chronic inflammations (except chronic bronchitis), Any cancers (e.g., RCC, Hodgkin's), Familial Mediterranean Fever. | ㅤ |
ACal (Calcitonin Amyloid) | Medullary Carcinoma (produces calcitonin). | ㅤ |
ABeta (Beta Amyloid) | Alzheimer's disease (beta plaques in brain). | "One brain so one beta" |
ABeta2 (Beta2-Microglobulin Amyloid) | Hemodialysis patients. | "Two kidneys to two beta" |
ATTR (Transthyretin Amyloid) | ㅤ | ㅤ |
- Senile Amyloidosis | Increase in quantity of transthyretin (associated with old age). | "A lot of age, a lot of quantity" |
- Familial Amyloidotic Polyneuropathy | Mutant transthyretin (nerve-related). | "Nerves is eminent mutant" |
SPECIFIC DEPOSITION SITES
Organ | Specific Deposition Site / Effect |
Kidney | Mesangium |
Heart | Subendocardial |
Blood Vessels | Subendothelial |
Liver | Space of Disse |
Spleen | Red pulp: Lardaceous spleen Lal is red |
ㅤ | White pulp: Sago spleen Sabuana is white |
Skin | Causes pinch purpura |
Joints | Leads to carpal tunnel syndrome |
GIT | Causes organomegaly (Organs become big, fat) |
Other organs | Also organomegaly (Organs become big, fat) except Kidney → Shrinkage in later stages |
- General Appearance:
- Affected organs look waxy ("candle wax appearance").
- Exception:
- Kidney may shrink in later stages (early stages: big and fat).
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