Amyloidosis Flashcards
What is amyloidosis?
Tissue damage due to abnormal protein aggregation and deposition (Amyloid fibrils deposits)
Explain the pathophysiology of amyloidosis
- Normal protein in execive amounts
- Small proportion of abnormal proteins produced
- Abnormal proteins produced
Leading to: Misfolded proteins (Amyloids form) –> too many for being broken down by proteases, that deposit into tissues
Why might multiple myeloma lead to amyloidosis?
E.g. Multiple myelomas in B-cells:
- hughe amounts of antibodies produced
- Small proportion will be misfolded
- these might not be broken down, and can deposit in the tissues
AL (L= light chain) amyloidosis
What is the association between chronic liver inflammation and Amyloidosis?
Serum Amyloid A in an acute phase protein produced in the liver
- In chronic inflammation (of the liver)
- and also other e.g. cancers, RA, IBD etc. it might lead to misfolding of Serum Amyloid A (AA Amyloids) due to huge amoutns produced
- AA (Amyloidosis A)
What are the hallmarks of nephrotic syndromes?
- Proteinuria
- Hypoalbuminea
- leading to oedema
- Hyperlipidaemia (due to low concentrations of proteins in the blood that could inhibit protein synthesis)
What is the association between amyloidosis and nephrotic syndrome?
Amyloids can deposit in podocytes leading to nephrotic syndrome
What happens to the heart in cardiac amyloidosis?
Protein deposits…
- Make heart walls stiffer
- restrictive cardiomyopathy
- Interfere with electic conduction
- Arrythmias
What are the manifestations of Amyloisis in the GI tract?
Might lead to
- Malabsorbtion of nutrients
- bleeding and
- dysmotility
Enlargement of
- liver (Hepatomegaly)
- spleen (Splenomegaly)
- Tongue (Macroglossia) –> Expecially AL
What are the effects of Amyloidosis on the Nervous system
- Sensory and Motor Neuropathy
- autonomic neuropathy, carpal tunnel syndrome
Which organ systems can be affected in systemic Amyloidosis?
- kidney
- heart
- GI
- nervous system
- Skin
- Joints
- Haematological
What is a well-known example of localised amyloidosis?
Alzheimers Disease
- Aß amyloidosis
Localised Amyloidosis can also be seen in DMT2
Explain the relationship between amyloidosis and DMT2
ß-cells in pancreas produce more Insulin
- also produce more of a protein called Amylin
- accumulates and causes ß-cell death over time
What are symptoms of Amyloidosis?
Dependant on systemic site involved:
- Swelling in Face, ankles and legs
- Palpitations and SOB
- Malabsorbtion + weight loss
- Numbmness, Pain in fingers and toes
- Diarroeah and Constipation
- Orthostatic hypotension
- alzehimers
- Large tongue: interference w. speech and noisy breathing during sleep
What are signs of Amyloidosis on physical examination?
- oedema
- glossitis, hepato and splenomegaly
- Loss of sensation in fingers/toes
- Vascular: purpura, especially periorbital—a characteristic feature (AL)
+ Many more, depending of site involved
What are investigations you should untertake when suspecting Amyloidosis ?
- Biopsy of affected tissue
- positive Congo Red stain- ing with (red stiaining after Congo red stain)
- red-green birefringence under polarized light microscopy (apple green under polarized light
Other: no treatment available
What are indicators of cutaneous involvement of Amyloidosis?
- Waxy skin,
- easy bruising
- Purpura around eyes (AL)
- plaques and nodules
