Amyloid Flashcards
What is amyloidosis?
EXTRACELLULAR deposition of abnormal proteins either in a single organ (localised amyloidosis) or throughout the body (systemic amyloidosis)
What is the composition of amyloid and simple pathogenesis involved?
Composition
- Fibrillar component (90-95% of amyloid): B sheet fibrils
- Nonfibrillar component (5-10% amyloid)
Pathogenesis: accumulation of amyloid = cellular injury and apoptosis
Types of amyloidosis
Light chain amyloidosis (AL)
- Associated with plasma cell dyscrasias, eg: MM, waldenstrom macroglobulinaemia
Reactive amyloidosis (AA)
Etiology: secondary disease
- Chronic inflammatory conditions, eg: IBD, RA, SLE, vasculitis, FMF
- Chronic infectious diseases, eg: TB, bronchiectasis, leprosy, OM
- Tumours: RCC, lymphomas
Features of light chain amyloidosis (AL)
Light chain amyloidosis (AL)
- Associated with MM, waldenstrom macroglobulinaemia
- Increased production of light chains of immunoglobulins leading to deposition of amyloid light chains
- Rapidly progressive clinical course
- Heart: restrictive cardiomyopathy, AV block
- Kidney: nephrotic syndrome, type II RTA, diabetes insipidus
- Tongue: macroglossia
- Autonomic neuropathy
- GIT: malabsorption
- Bleeding disorders/splenomegaly
- MSK: carpal tunnel
Features of reactive amyloidosis (AA amyloidosis)
Etiology: secondary disease
- Chronic inflammatory conditions, eg: IBD, RA, SLE, vasculitis, FMF
- Chronic infectious diseases, eg: TB, bronchiectasis, leprosy, OM
- Tumours: RCC, lymphomas
Pathophysiology: chronic inflammatory process –> increased production of acute phase reactant SAA –> deposition of AA protein in various organs
Clinical Features:
- Kidney: nephrotic syndrome, type II RTA, nephrogenic DI
- Adrenal: primary adrenal insufficiency
- Liver + Spleen: hepatomegaly, splenomegaly
- GIT: malabsorption
- MSK: carpel tunnel syndrome
What should be considered in patients with long-standing inflammatory and/or infectious disease who present with kidney, liver or GI involvement?
Amyloidosis
Which one is rapidly progressive clinical course = light chain (AL) or reactive (AA) amyloidosis?
Light chain amyloidosis
Features of haemodialysis associated amyloidosis
- B2 microglobulin becomes AB2M amyloid protein
- Associated with long term HD, end stage renal disease
- ~10 years after starting HD
- Joints and tneonds
- Almost all individuals on long term HD will develop amyloid at some point
Diagnosis of amyloidosis
If systemic disease - abdominal fat or rectal mucosa biopsy with congo red stain
- Apple green birefringence under polarised light
Treatment for amyloidosis
- Treat the underlying disease
- If amyloidosis progresses rapidly, eg: light chain amyloidosis - corticosteroids, melphalan
