Amyloidosis Flashcards
What are amyloids?
Amyloids are abnormal, starch-like extracellular protein deposits that form in organs and tissues of the body.
What are amyloids composed of?
Fibrillar proteins, glycosaminoglycans (heparan sulphate and dermatan sulphate) and a Serum Amyloid P component.
What are the universal features of amyloid?
Rigid, non-branching and insoluble structures.
Around 50-100Å in diameter.
Have a pathognomonic cross-β core structure.
Why is their clearance in vivo slow?
Amyloid deposits are usually ignored by phagocytic cells like macrophages.
How do diseases caused by amyloid deposits vary?
Local or systemic
Acquired (later age of onset) or inherited (mostly autosomal dominant in fashion).
How many different proteins can become mutated in amyloidosis?
37 different proteins or peptides have been recognised as causative agents of amyloid diseases.
What is the most common type of amyloidosis?
AL amyloidosis
What is the pathogenesis?
Some native proteins are found in a partially unfolded/ misfolded state.
Many conditions can favour the production of mis-folded proteins, including temperature, oxidation and pH.
When the misfolded proteins reach a critical concentration, they aggregate to form the amyloid template, causing the protein to assume the pathologic confirmation.
How does amyloidosis lead to cardiomyopathy?
Amyloid deposits cause the heart walls to stiffen, affecting the electrical conductivity of the cardiac cells.
E.g. Familial amyloid cardiomyopathy.
What is the prognosis of amyloidosis?
Survival is dictated by the precursor protein forming amyloid deposition and the type of organ involved.
What are the three phases in the formation of amyloid deposits.
Lag phase - where the native protein is present
Nucleation - where high concentrations of misfolded proteins activate process of aggregation and cross beta-sheet oligomers start to form.
Elongation - which can proceed at low concentration of the precursor protein. All the stabilisation proteins and surrounding proteins in the blood bind to the template formed by nucleation and lead to the formation of amyloid fibres.
Why are amyloid deposits toxic?
Oligomers are toxic because they interact with the cell membrane and many tissues, disrupting their cellular environment.
Toxicity is dictated in vivo by the number of apoptotic cells.
