Medical brain notes 15

  COMPOSITION OF AMYLOID Amyloidosis is a group of diseases characterized by the deposition of an extracellular protein that has specific properties. ·              Individual molecular subunits form  β -pleated sheets. Amorphous eosinophilic extracellular deposits of amyloid are seen on the H&E stain. These deposits stain red with the Congo red stain, and apple green birefringence of the amy-loid is seen on the Congo red stain under polarized light.   ·              The fibrillary protein of amyloid varies with each disease. Also present in amy-loid are serum amyloid P (SAP) and glycosaminoglycans (heparan sulfate).

  SYSTEMIC TYPES OF AMYLOID Primary amyloidosis  has amyloid light chain (AL) amyloid, whose fibrillary pro-tein is made of kappa or lambda light chains. Primary amyloidosis may be seen in plasma cell disorders (multiple myeloma, B-cell lymphomas, etc.) but most cases occur independent of other diseases. Reactive systemic amyloidosis  (secondary amyloidosis) has amyloid-associatedprotein, whose precursor is serum amyloid A (SAA), an acute phase reactant produced by the liver which is elevated with ongoing chronic inflammation and neoplasia. Reactive systemic amyloidosis can be seen with a wide variety of chronic diseases, including rheumatoid arthritis, systemic lupus erythematosus, tuberculo-sis, bronchiectasis, osteomyelitis, inflammatory bowel disease, and cancer. Familial Mediterranean fever  has AA type amyloid with fibrillary protein composedof serum amyloid A (SAA). This autosomal recessive disease is characterized by recur-rent inflammation, fever, and neutro...

  LOCALIZED TYPES OF AMYLOID Senile cerebral amyloidosis  (Alzheimer disease) has A β type amyloid with fibrillaryprotein composed of  β -amyloid precursor protein ( β APP). It is found in Alzheimer plaques and in cerebral vessels. The gene for  β APP is located on chromosome 21. Senile cardiac/systemic amyloidosis  has ATTR type amyloid with fibrillary proteincomposed of transthyretin. This type of amyloidosis is seen in men older than 70 years and may cause heart failure as a result of restrictive/infiltrative cardiomyopa-thy. Four percent of African Americans have a transthyretin (TTR) V1221 mutation with 1% being homozygous, serving as a risk for cardiac disease.   Endocrine type amyloidosis   is seen in medullary carcinoma of the thyroid (procal-citonin), adult-onset diabetes (amylin), and pancreatic islet cell tumors (amylin).

  CLINICAL FEATURES In  systemic forms  of amyloidosis, the kidney is the most commonly involved organ, and patients may experience nephrotic syndrome and/or progressive renal failure. Cardiac involvement may cause restrictive cardiomyopathy and conduction dis-turbances. Other clinical features include hepatosplenomegaly and involvement of the gastrointestinal tract, which may produce tongue enlargement (macroglossia, primarily in AL type) and malabsorption. Diagnosis  in systemic forms of amyloidosis can be established with biopsy of therectal mucosa, gingiva, or the abdominal fat pad; Congo red stain shows apple green birefringence under polarized light of amyloid deposits. The prognosis of systemic amyloidosis is poor. AL amyloidosis is diagnosed by serum and urinary protein electrophoresis and immunoelectrophoresis. Proteomic analysis is another diag-nostic tool.