Amyloidosis
4 INTRODUCTION.. Amyloidosis is a general term refer to the extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins.
5 Amyloidosis types.. AL amyloidosis: due to deposition of protein derived from immunoglobulin light chain fragments. protein is detectable in urine and/or serum symptoms and signs: heavy proteinuria (usually in the nephrotic range) edema hepatosplenomegaly unexplained heart failure carpal tunnel syndrome AL amyloidosis: due to deposition of protein derived from immunoglobulin light chain fragments. protein is detectable in urine and/or serum symptoms and signs: heavy proteinuria (usually in the nephrotic range) edema hepatosplenomegaly unexplained heart failure carpal tunnel syndrome
6 AA amyloidosis: may complicate chronic diseases such as.. rheumatoid arthritis (RA) spondyloarthropathy inflammatory bowel disease chronic infections The most common organ system involved in AA amyloid is the kidney (about 80 percent). This is usually characterized by glomerular amyloid deposition, typically leading to the nephrotic syndrome, Cardiac and other organ involvement may also be seen. AA amyloidosis: may complicate chronic diseases such as.. rheumatoid arthritis (RA) spondyloarthropathy inflammatory bowel disease chronic infections The most common organ system involved in AA amyloid is the kidney (about 80 percent). This is usually characterized by glomerular amyloid deposition, typically leading to the nephrotic syndrome, Cardiac and other organ involvement may also be seen.
7 Dialysis-related amyloidosis: Due to deposition of fibrils derived from beta-2 microglobulin, which accumulate in patients with end-stage renal disease who are being maintained for prolonged periods of time by dialysis.
8 Age-related (senile) systemic amyloidosis: Deposition of otherwise normal (wild-type) transthyretin in myocardium and other sites may result in a form of amyloidosis that is referred to as systemic senile amyloidosis (SSA) Age-related (senile) systemic amyloidosis: Deposition of otherwise normal (wild-type) transthyretin in myocardium and other sites may result in a form of amyloidosis that is referred to as systemic senile amyloidosis (SSA)
9 Organ-specific amyloid: Amyloid deposition can be isolated to a single organ, such as skin eye heart pancreas genitourinary tract Examples: Alzheimer disease in which plaques and amyloid-laden cerebral vessels are composed of the beta protein (Ab). Organ-specific amyloid: Amyloid deposition can be isolated to a single organ, such as skin eye heart pancreas genitourinary tract Examples: Alzheimer disease in which plaques and amyloid-laden cerebral vessels are composed of the beta protein (Ab).
10 CLINICAL MANIFESTATIONS type of precursor protein tissue distribution amount of amyloid deposition amount of amyloid deposition
12 DIAGNOSIS.. confirmed only by tissue biopsy history and clinical manifestations findings on imaging. confirmed only by tissue biopsy history and clinical manifestations findings on imaging.
13 Biopsies.. can be obtained from either clinically uninvolved sites, such as subcutaneous fat, minor salivary glands, or rectal mucosa; or from dysfunctional organs (eg, kidney, nerve). Aspiration or biopsy of subcutaneous fat with Congo red staining and examination using polarizing microscopy has an overall sensitivity of 57 to 85 percent and a specificity of 92 to 100 percent for primary (AL) or secondary (AA) amyloidosis The diagnostic sensitivity is higher in those with multiorgan involvement who are suspected of having systemic amyloidosis Fat pad aspiration or biopsy has a low sensitivity for amyloidosis in patients with a single involved organ. Biopsies.. can be obtained from either clinically uninvolved sites, such as subcutaneous fat, minor salivary glands, or rectal mucosa; or from dysfunctional organs (eg, kidney, nerve). Aspiration or biopsy of subcutaneous fat with Congo red staining and examination using polarizing microscopy has an overall sensitivity of 57 to 85 percent and a specificity of 92 to 100 percent for primary (AL) or secondary (AA) amyloidosis The diagnostic sensitivity is higher in those with multiorgan involvement who are suspected of having systemic amyloidosis Fat pad aspiration or biopsy has a low sensitivity for amyloidosis in patients with a single involved organ.
14 Histopathology and protein analysis.. The amyloid deposits appear as amorphous hyaline material on light microscopy. The fibrils bind Congo red (leading to green birefringence under polarized light) and thioflavine T (producing an intense yellow- green fluorescence). The amyloid deposits appear as amorphous hyaline material on light microscopy. The fibrils bind Congo red (leading to green birefringence under polarized light) and thioflavine T (producing an intense yellow- green fluorescence).
15 Imaging scanning.. Examples: speckled appearance of the myocardium on ech