Amyloidosis

Pathophysiology

1) deposition of fibrous, insoluble amyloid protein in extracellular matrices of body 2) clinically ranges from benign to severe sequelae 3) classification is based on fibril-forming protein 4) most common systemic types – primary (idiopathic), secondary, and familial amyloid polyneuropathy (FAP)

Signs and Symptoms

Primary type – 1) nephrotic syndrome 2) hepatomegaly 3) carpal tunnel 4) GI disturbance 5) cardiomyopathy with heart block 6) peripheral neuropathy 7) waxy plaques in skin Secondary type – 8) hepatomegaly 9) GI disturbances 10) proteinuria FAP-11) neuropathy 12) vitreous opacities 13) “scalloped pupils 14) GI disturbances 15) cardiomyopathy with heart block

Histology/Gross Pathology

1) abnormal B-pleated sheet conformation 2) presence of the nonfibrillar component SAP (serum amyloid P; pentraxin) 3) presence of glycosaminoglycans in deposits

Associated Conditions

1) multiple myeloma 2) osteomyelitis 3) leprosy 4) TB 5) rheumatoid arthritis 6) familial Mediterranean fever

Biochemistry

Primary-1) fibrils are M-antibody light chains Secondary – 2) in inflammation – Il-1/IL-6 stimulate excess production of serum amyloid A (component of HDL) that then deposits in tissues FAP – 3) fibrils are transthyretin (most common), apolipoprotein A-I, gelsolin, and cystatin C