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Pathology
Lecture 18 Amyloidosis
1) To understand the biochemistry and structure of amyloid proteins. Amyloid
proteins are composed of nonbranching fibrils of indeterminate length and 7.5-10nm
in diameter. The proteins can aggregate into an insoluble beta-pleated sheet
conformation. Chemically, they are made up of 95% fibrillary protein and 5%
glycoprotein (P component). There are 15 biologically distinct forms known to exist.
Extracellular in distribution, they mostly accumulate near basement membranes and
stain as amorphous eosinophilic structures.
2) To be able to classify amyloid proteins.
Major Classes of Amyloid
AL (amyloid light chain) – derived from
plasma cells. Contains Ig light chains
AA (amyloid-associated) – unique liver protein
derived from serum-amyloid associated protein
(SAA), also known as secondary amyoidosis
Minor Classes of Amyloid
Amyloid transthyretin (ATTR) is deposited in
tissues. Transthyretin (TTR) is a normal serum
protein that transports thyroxine and retinol
Beta2-microglobulin – a component of MHC
class I molecules and amyloid fibril (Aβ2m)
Beta-amyloid protein (Aβ) derived from the
transmembrane amyloid precursor protein
A-Cal, derived from the hormone procalcitonin
AIAPP – islet amyloid peptide
AANF – atrial naturitic factor
Associated Diseases
Multiple myeloma and other monoclonal B-cell
proliferations
Chronic inflammatory conditions such as
rheumatoid arthritis; also in heroin abusers,
chronic skin infections from skin-popping
Associated Diseases
Several familial amyloidotic neuropathies and
Senile cardiac amyloidosis
Chronic renal disease/hmoialysis-associated
amylidosis
Alzheimer’s disease
Medullary carcinoma of the thyroid
Type II diabetes
Isolated atrial amyloidosis
3) To know which diseases are associated with amyloid accumulation. (See above)
a. Systemic Amyloidosis: Immunocyte dyscrasias (primary amyloidosis), Reactive
systemic amyloidosis (secondary amyloidosis), Hemodialysis-associated
amyloidosis, and Hereditary amyloidosis.
b. Localized Amyloidosis: Senile cardiac, Senile cerebral (Alzheimer’s disease),
Endocrine (medullary carcinoma of thyroid and type II diabetes), and Isolated
atrial amyloidosis.
4) To appreciate the clinical manifestations of amyloid accumulation in organs.
Amyloidosis primarily affects the kidneys, liver, spleen, lymph nodes, adrenals, and
thyroid. The affected organs become enlarged, firm, and have a waxy appearance.
Kidneys – amyloid primarily in glomeruli. Spleen – two patterns are seen: “sago
spleen” amyloid is limited to splenic follicules and “lardaceous spleen” amyloid
involves splenic sinus walls. Liver – deposits in the space of Disse (liver basement
membranes). Heart – subendothelial accumulations expanding into the myocardium.
Symptoms vary depending on site of deposition. Diagnosis is made by biopsy.