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Flashcards in Amyloidosis Deck (21)
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1

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.

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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

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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

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Amyloid Light Chain Protein => consequence

Possible plasma cell tumors

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Amyloid-Associated => consequence

Production increased in acute phase inflammatory states and sticks around for chronic phase

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Other components of amyloid

Serum amyloid P component, proteoglycans, and highly sulfated glycosaminoglycans

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How does amyloidosis happen?

Mis-folded proteins accumulate outside of the cell instead of being degraded intracellularly in proteosomes.

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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

9

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

10

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.

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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.

12

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.

13

Amyloid of Aging

Amyloid deposition that occurs with aging

Proteins are typically derived from normal TRR.

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Histology of Amyloidosis

Amyloid deposition is always extracellular and begins between cells, often closely adjacent to basement membranes.

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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.

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Amyloidosis in spleen

Possible splenomegaly

Two patterns of deposition: 1) limited to splenic follicles; or 2) within red pulp

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Amyloidosis in liver

Possible hepatomegaly

First appears in space of Disse, then encroaches on adjacent hepatic parenchymal cells and sinusoids

Affected hepatocytes disappear and regenerate, usually maintaining normal liver function

18

Amyloidosis in Heart

Can appear in any form of systemic amyloidosis

Deposits begin as subendocardial accumulations and within the myocardium between muscle fibers.

Can eventually cause damage to conduction system

May appear as insidious congestive heart failure with arrhythmias and conduction disturbances.

19

Symptoms

Depend on the magnitude of the deposits and on the site or organs affected. Clinical manifestations are at first non-specific, then gradually increase in seriousness and specificity.

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Diagnosis

Depends on the histological demonstration of amyloid deposits on tissues

Kidney, abdominal fat, rectal or gingival tissues, serum and urine protein, and bone marrow can all be sampled.

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Prognosis

Sucks for those with generalized amyloidosis

Better for those with reactive system amyloidosis