Amyloidosis Flashcards
Define amyloidosis
A diverse group of diseases characterised by extracellular deposition of amyloid fibrils (abnormally folded proteins that have clumped together) in tissue
Explain the aetiology/risk factors of amyloidosis
An amyloid is any protein that has misfolded in the translation process. Amyloidosis is when there is a large amount of these proteins and they clump together and are deposited in tissues.
What are the 3 types of Amyloidosis?
Nomenclature; The A stands for amyloidosis.
Type AL - The L is for ‘light chain’ because this type is from when the light chain of monoclonal immunoglobin misfolds.
Type AA - This is from when the serum amyloid A protein misfolds.
Type ATTR - Famililal tranthyretin-associated amyloidosis. This is from when transthyretin misfolds/mutates. (genetic)
The proteins undergo conformational changes to adopt an anti-parallel beta-pleated sheet configuration
Summarise the epidemiology of amyloidosis
AA - incidence of 1-5% amongst patients with chronic inflammatory diseases
AL - 300-600 cases in the UK per year
Hereditary Amyloidosis - accounts for 5% of patients with amyloidosis
Recognise the presenting symptoms of amyloidosis
Renal - proteinuria, nephrotic syndrome, renal failure
Cardiac - restrictive cardiomyopathy, heart failure, arrhythmia, angina
GI - macroglossia (characteristic of AL), hepatosplenomegaly, gut dysmotility, malabsorption, bleeding
Neurological - sensory and motor neuropathy, autonomic neuropathy, carpal tunnel syndrome
Skin - waxy skin and easy bruising, purpura around the eyes (characteristic of AL), plaques and nodules
Joints - painful asymmetrical large joints, enlargement of anterior shoulder
Haematological - bleeding tendency (haemorrhage)
Which organs are impacted by AL? What does it cause?
Purpura around the eyes
Macroglossia
Easy bruising
- very typical amyloid signs
What is nephrotic syndrome?
How does amyloidosis cause it?
What are the 4 cardinal signs of nephrotic syndrome
Damage to the glomerulus leading to proteinuria
Deposition of amyloid in the glomerulus
Proteinuria, Hypoalbuminuria, Hyperlipideamia, Oedema
Identify appropriate investigations for amyloidosis
- Immuno globin free light chain assay
- Most sensitive for AL (light chain)
2.Urine & Serum immunofixation - find a monoclonal protein;
- finding an immunoglobin light chain suggests
multiple myeloma and amyloidosis
- Tissue Biopsy + staining;
- Positive = green birefringent when stained with
Congo Red
others;
Urine - check for proteinuria (complications i.e. nephrotic syndrome)
SAP Scan - radiolabelled SAP will localise the deposits of amyloid
Rheumatoid factor *
* because in rheumatoid arthiritis, serum amyloid A can be elevated.
Why does immunoglobin light chain discovery in serum or urine indicative of multiple myeloma as well as amyloidosis?
because too many light chains are prodcued in the bone in MM patients.
