2) to Be Able to Classify Amyloid Proteins

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 Associated Diseases AL (amyloid light chain) – derived from Multiple myeloma and other monoclonal B-cell plasma cells. Contains Ig light chains proliferations AA (amyloid-associated) – unique liver protein Chronic inflammatory conditions such as derived from serum-amyloid associated protein rheumatoid arthritis; also in heroin abusers, (SAA), also known as secondary amyoidosis chronic skin infections from skin-popping Minor Classes of Amyloid Associated Diseases Amyloid transthyretin (ATTR) is deposited in Several familial amyloidotic neuropathies and tissues. Transthyretin (TTR) is a normal serum Senile cardiac amyloidosis protein that transports thyroxine and retinol

Beta2-microglobulin – a component of MHC Chronic renal disease/hmoialysis-associated class I molecules and amyloid fibril (Aβ2m) amylidosis Beta-amyloid protein (Aβ) derived from the Alzheimer’s disease transmembrane amyloid precursor protein A-Cal, derived from the hormone procalcitonin Medullary carcinoma of the thyroid AIAPP – islet amyloid peptide Type II diabetes AANF – atrial naturitic factor 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.