Amyloidosis Flashcards
What is amyloidosis?
Amyloidosis is the name given to a group of acquired and hereditary disorders characterised by the extracellular deposition of insoluble proteins.
What causes amyloidosis?
Amyloidosis is caused by deposits consisting of fibrils of the specific protein involved, linked to glycosaminoglycans, proteoglycans and serum amyloid P. Protein accumulation may be localised or systemic, and the clinical manifestations depend on the organ(s) affected. Amyloid diseases are classified by the aetiology and type of protein deposited.
What are the systemic or acquired amyloidoses?
1) Reactive AA amyloidosis
2) Light chain amyloidosis
3) Dialysis associated amyloidosis
4) Senile systemic amyloidosis
What is reactive AA amyloidosis?
Here there is increased production of serum amyloid A as part of prolonged or recurrent acute inflammatory responses.
Predisposing conditions include - chronic infection (TB, bronchiectasis, chronic abscesses, osteomyelitis), chronic inflammatory disease (untreated RA, FMF)
> 90% of patients present with non selective proteinuria or nephrotic syndrome
What is light chain amyloidosis?
Increased production of monocloncal light chain.
Associated with monoclonal gammopathies including myeloma, benign gammopathies and plasmacytoma.
What are the associated features of light chain amyloidosis?
Restrictive cardiomyopathy, peripheral and autonomic neuropathy, carpal tunnel syndrome, proteinuria, spontaneous purpura, amyloid nodules and plaques
Macroglossia occurs rarely but is pathognomonic.
Prognosis is poor.
What is dialysis associated amyloidosis?
Accumulation of circulating β2-microglobulin due to failure of renal catabolism in kidney failure.
Carpal tunnel syndrome, chronic arthropathy and pathological fractures secondary to amyloid bone cyst formation. Manifestations occur 5–10 years after the start of dialysis
What is senile systemic amyloidosis?
Normal transthyretin protein deposited in tissues.
Age > 70 years.
Feature of normal ageing (affects >90% of 90-year-olds)
Usually asymptomatic.
What are the hereditary systemic amyloidoses?
> 20 forms of hereditary systemic amyloidosis.
Production of protein with an abnormal structure that predisposes to amyloid fibril formation. Most commonly due to mutations in transthyretin gene.
Autosomal dominant.
Peripheral and autonomic neuropathy, cardiomyopathy.
Renal involvement unusual.
10% of gene carriers are asymptomatic throughout life
How is amyloidosis diagnosed?
The diagnosis is established by biopsy, which may be of an affected organ, rectum or subcutaneous fat. The pathognomonic histological feature is apple-green birefringence of amyloid deposits when stained with Congo red dye and viewed under polarised light. Immunohistochemical staining can identify the type of amyloid fibril present. Quantitative scintigraphy with radiolabelled serum amyloid P is a valuable tool in determining the overall load and distribution of amyloid deposits.
