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| Amyloidosis | ||
| Etiology •Unknown. Developments in the pathogenesis of various forms and genetic factors are progressing. | ||
| Pathogenesis •Each type of amyloid is composed of a specific protein made of polypeptide chain units derived from proteolysis of specific precursor proteins. •Proteolysis and synthesis of specific amyloid protein occurs in macrophages. Specific inciting molecular mechanisms are unknown. •Despite variety of different precursor proteins and types of resulting amyloid, various types share common features: •Identical light microscopic appearance and ultrastructure of filaments 75-100 angstroms thick; •Filaments made of beta-pleated polypeptide chains (in contrast to more common alpha-helices in protein synthesis); •Selective staining with congo red dye, with resulting diagnostic bright green fluorescence under polarized light., | ||
| Epidemiology •Different for each of at least 12 types of amyloid. •Amyloid AL (primary amyloid): Associated with multiple myeloma or macroglobulinemia. •Amyloid AA (secondary amyloid): Associated with chronic debilitating disease, infectious (TB), neoplastic (Hodgkins Disease), diseases of unknown cause, possibly autoimmune (rheumatoid arthritis). •Others & Associated diseases: AB & Alzheimer's disease; AScr & Creutzfeld Jakob disease; ATTR & systemic senile amyloidosis, & familial types; AB2M & chronic renal dialysis; AIAPP (islets of Langerhans) & and type II diabetes; ACal (procalcitonin) & medullary carcinoma of the thyroid gland. •Other rare familial types. | ||
| General Gross Description •May not be visible grossly if primarily distributed in the walls of small blood vessels, or in early minimal deposition in any organ. •Advanced cases involving the heart, liver, spleen, or kidneys have a light tan yellow discoloration, with a characteristic stiff wax-like consistency. •This is due to the extensive replacement of the tissues by amyloid with enlargement of the organs. •Examples: | ||
| General Microscopic Description •Characteristic but not pathognomonic deposition of hyalin-like material in interstices of affected organs and walls of capillaries and small arteries and veins. •Advanced cases result in replacement of parenchyma by pressure atrophy with associated organomegaly. •Uptake of congo red stain with green fluorescence under polarized light considered pathognomonic. •Examples: | ||
| Clinical Correlation •Varies with different types. •Cases with AA and AL types may develop heart failure, liver failure, or nephrotic syndromes with later renal failure. Macroglossia characteristic of AL. •AB and AScr types are components of lesions of Alzheimer's disease, and Creutzfeld Jakob disease, respectively. •Important to avoid liver biopsy in cases of suspect liver involvement because of hemorrhage resulting from "cracking" of diseased wax-like parenchyma. •All organs may be involved. Diagnosis may be apparent in biopsies of gastrointestinal tissues, muscles, and bone marrow. | ||
| References 1. Majno G and Joris I. Cells, Tissues, and Disease. Cambridge: Blackwell, 1996, pp. 268-281. (uniquely lucid) • Cotran RS, Kumar V, Robbins SL: Robbins Pathologic Basis of Disease. 5th ed. Philadelphia, W.B. Saunders, 1994, pp. 231-238. Please be patient during transfer. Medline will open in a new window. To return, close the Medline Window Amyloidosis
| Synopsis by: J. Hasson, MD (T41000M55100)[566]
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