Amyloidosis Flashcards
Amyloidosis
A condition associated with a number of inherited and inflammatory disorders in which extracellular deposits of fibrillar proteins are responsible for tissue damage and functional compromise. The fibrils are collections of mis-folded proteins.
Stain used to detect amyloidosis
Congo red, which shows apple-green birefringence under polarized light. Birefringence is caused by the cross B-pleated configuration of amyloid fibrils
Three common forms of amyloid
1) Amyloid Light Chain Protein, made of complete immunoglobulin light chains, amino-terminal fragments of light chains, or both things. Think Bence-Jones! (Remember cryoglobulinemia?)
2) Amyloid-Associated, which is derived from a unique non-Ig protein made by the liver; circulates bound to HDL
3) B-amyloid protein, which is the core of cerebral plaques found in Alzheimer disease
Amyloid Light Chain Protein => consequence
Possible plasma cell tumors
Amyloid-Associated => consequence
Production increased in acute phase inflammatory states and sticks around for chronic phase
Other components of amyloid
Serum amyloid P component, proteoglycans, and highly sulfated glycosaminoglycans
How does amyloidosis happen?
Mis-folded proteins accumulate outside of the cell instead of being degraded intracellularly in proteosomes.
Primary amyloidosis
Amyloid light chain
Associated with some plasma cell disorder (like clonal proliferation of an Ig that is prone to form amyloid due to its physiochemical properties)
Usually systemic in distribution
Usually AL type
Secondary amyloidosis
Amyloid-Associated
Occurs as a complication of an underlying chronic inflammatory or tissue-destructive process
Also called reactive systemic amyloidosis
Complicates RA, ankylosing spondylitis, and inflammatory bowel disease (Crohns and ulcerative colitis)
Seen most commonly in renal cell carcinoma and Hodgkin lymphoma
Hereditary/familial amyloidosis
A separate, heterogenous group with several distinctive patterns of organ involvement.
Most well-known is familial Mediterranean fever, in which IL-1 is excessively produced.
There can also be deposition in peripheral and autonomic nerves, causing amyloidotic polyneuropathies, which consist of mutant TRRs prone to misfiling and aggregation due to alterations of structure from mutation.
Transthyretin (TTR)
A normal serum protein that, when mutated, is deposited. Seen in a group of genetically determined disorders referred to as familial amyloid polyneuropathies.
Hemodialysis-Associated Amyloidosis
Affects dialysis patient population, but incidence has decreased with better technology
Caused by deposition of B2-microglobulin
Will likely present with carpal tunnel that compresses the median nerve.
Amyloid of Aging
Amyloid deposition that occurs with aging
Proteins are typically derived from normal TRR.
Histology of Amyloidosis
Amyloid deposition is always extracellular and begins between cells, often closely adjacent to basement membranes.
Amyloidosis in kidney
Typically occurs in glomeruli, and vasculature also affected
Deposition in blood vessels may result in ischemia of organ.
Gives rise to proteinuria that may cause nephrotic syndrome; progressive obliteration of glomeruli leads to renal failure, the common cause of death.
