Amyloid= ‘starch-like’ (Amylum—Latin)

Virchow in mid 19th century

Amyloids: Aggregations of un-degraded, pathologic

protein fibrils because of misfolding mechanisms.

Amyloidosis: a group of diseases.

Background:

Definition: Amyloid

“ A pathologic protein deposited between

the cells in various tissues and organs of the

body in a wide variety of clinical settings”.

Non-branching fibres

Indefinite length

Diameter of 7.5 –10 nm.

Cross-Beta-pleated sheet conformation:

X-ray crystallography

Infra-red spectroscopy

Physical nature of Amyloid:

95%--consists of fibril proteins.

5%--other glycoproteins

Three most important forms:

1. AL (amyloid light chain): from plasma cells,

2. AA (amyloid associated): from liver,

3. A-Beta amyloid (seen in cerebral lesions of Alzheimer's

disease)

Chemical nature:

SYSTEMIC:

Multiple myeloma—AL

Reactive systemic am—AA

Hemodialysis associated am—Ab2 microglobulins

Hereditary am—AA

Familial Mediterranean fever—AA

Familial amyloidotrophic neuropathy—AATR

Systemic Senile am—ATTR

Classification:

LOCALIZED AMYLOIDOSIS:

Alzheimer's disease –A-beta

Medullary carcinoma –A cal

Islet of Langerhans: AIAPP

Isolated atrial amyloidosis—AANF

Prion disease –PrPsc

Amyloid protein Precursor Syndrome or involved tissues

AL Immunoglobulin light chain Myeloma associated

AH Immunoglobulin heavy chain Myeloma associated

ATTR Transthyretin Familial

AA (Apo) Serum amyloid A Familial

Aβ2M β2 Microglobulin Familial

AApoAI Apolipoprotein AI Joints

Agel Gelsolin Aortic

ALys Lysosomes Familial

AFib Fibrinogen α chain Familial

Acys Cystatin C Familial

Aβ Aβ protein Alzheimer's

APrPsc Prion protein Spongiform encephalitis

ACal Calcitonin C-cell thyroid tumors

AIAPP Islet amyloid polypeptide Islets of Langerhans

AANF Atrial natriuretic factor Cardiac atria

APro Prolactin Aging pituitary, prolactinomas

AIns Insulin Iatrogenic

AKer Keratoepithelin Cornea

Normal proteins—when produced in excess; have inherent

tendency to fold improperly and form fibrils.

Mutant proteins—that are structurally unstable, prone for

misfolding and aggregation.

Two categories of proteins

AL type

Abnormal B cell lesion

Commonly associated with Plasma cell Myeloma & Other

monoclonal B cell lesions

Increased Light chain production.

Associated with Bence Jones Protein in Urine

AA type

Secondary to Chronic Inflammatory lesion:

Tuberculosis, Bronchiectasis, Osteomyelitis, Rheumatoid

arthritis, Inflammatory bowel disease, Ankylosing

Spondylitis, IV drug abusers.

Affected organ gets enlarged, firm and waxy appearance.

Painting the cut surface with iodine imparts a yellow color,

and that is transformed to blue-violet after application of

sulphuric acid.

Diagnosis: Congo-red dye: ordinary light gives pink/red color;

polarized light gives apple-green birefringence.

Morphology: Gross

1. Congo Red—View under Polarizing Microscopy—Apple

Green birefringence: Gold standard test.

2. Thioflavin T

3. Van Giessen (Khaki color)

4. PAS (Periodic Acid Schiff )Stain.

Amorphous, eosinophilic, hyaline extra-cellular

protein.

With progressive accumulation, produces pressure

atrophy of adjacent cells.

Microscopically:

Kidney: Focal to diffuse mesangial deposits, Nodular

Basement membrane deposits, Capillary loops, Interstitial

space, Wall of blood vessels

Liver: Hepatomegaly, Waxy surface

Heart: Dew drop like subendocardial nodules, In between

Myocardial fibres

Tongue: Macroglossia, Gingival swellings

Carpel tunnel syndrome.

Morphology:

SPLEEN:

Splenomegaly +

Splenic follicles, white pulp involved—SAGO spleen:

tapioca like granules on gross examination.

Splenic sinuses, red pulp involved– LARDACEOUS spleen

(map like-large deposits).

Qn

Depend on the site involved

Can be unsuspected finding in Autopsy

Can lead to serious organ dysfunction

Renal disease: Nephrotic syndrome

Cardiac: Conduction defects, Restrictive

cardiomyopathy

Hepatosplenomegaly

1. Abdominal fat

2. Tongue

3. Rectal mucosa

4. Renal biopsy

5. Bone marrow biopsy

Biopsy site: