Station 39: AMYLOIDOSIS
What is meant by amyloid?
SpoilerAmyloid is an abnormal fibrillar protein that is deposited in the extracellular tissue.
The proteins are deposited in a rigid, mesh-like, sheet structure.
What is amyloidosis or amyloid degeneration?
SpoilerAmyloidosis is a life-threatening condition in which there is deposition of abnormal fibrillar proteins known as amyloid in the extracellular tissue.
Why do amyloid deposits in chronic infection not resolve?
SpoilerHumans are susceptible to the complications of the amyloid protein because they have no enzyme that can break this structure down.
What are the common sites of amyloid deposition?
SpoilerBased on the clinical features of AL and AA amyloidosis common sites of amyloid deposition include:
Kidneys (leading to proteinuria and nephrotic syndrome)
Heart (leading to restrictive cardiac disease and arrhythmias)
Liver (Hepatomegaly)
Spleen (Splenomegaly)
Nervous System (Peripheral neuropathy, carpal tunnel syndrome, autonomic neuropathy)
Gastro-intestinal tract (Macroglossia, bleeding, poor absorption)
What are the different types of amyloid protein?
SpoilerAL protein (associated with Multiple Myeloma/Immunocyte dyscrasias, i.e., Primary amyloidosis)
AA protein (associated with Chronic inflammatory conditions e.g., T.B., Rheumatoid arthritis, Secondary amyloidosis)
β₂ or microglobulin (Aβ₂m) protein (associated with Chronic renal failure or dialysis, i.e., Hemodialysis-associated amyloidosis).
Note: Familial amyloidosis is also mentioned, caused by a mutation in transthyretin.
Which type of amyloidosis occurs in chronic inflammation?
SpoilerAA amyloidosis (or Secondary amyloidosis) occurs in chronic inflammation.
Examples of chronic inflammatory conditions include:
-Rheumatoid arthritis (commonest cause of AA amyloid in the UK)
-Inflammatory bowel disease
-Tuberculosis (T.B.)
-Bronchiectasis
-Osteomyelitis
-Renal cell carcinoma
What are the main clinical findings in amyloidosis?
SpoilerThe clinical features depend on the type (AL vs. AA) and organs involved.
The patient description in your prompt suggests AL amyloidosis due to the presence of:
-Progressive ankle swelling / Pitting pedal oedema (suggests kidney/cardiac involvement)
-Frothy urine / 3+ Proteinuria (Kidney involvement: Proteinuria and nephrotic syndrome)
-Fatigue
-Numbness in his feet (Nervous system involvement: Peripheral neuropathy)
-Large, firm tongue / Macroglossia (Gastro-intestinal tract involvement)
-Hepatomegaly (Liver involvement)
How is amyloidosis classified?
SpoilerAmyloidosis is classified by the protein and the system involved.
Classification by Protein Involved (Systemic/Generalized Amyloidosis)
• AL amyloid
(Immunocyte dyscrasias with monoclonal B-cell proliferations like Multiple myeloma)
• AA amyloid
(Chronic inflammatory conditions)
• Familial amyloidosis
(Autosomal dominant disorder, commonly caused by a mutation in transthyretin)
Classification by Clinical Type
• Primary Amyloidosis:
Associated with Immunocyte dyscrasias (e.g., Multiple myeloma), involving the AL protein.
• Secondary Amyloidosis:
Associated with Chronic inflammatory conditions (e.g., T.B., bronchiectasis), involving the AA protein.
• Haemodialysis-associated amyloidosis:
Associated with Chronic renal failure or dialysis, involving the β₂-microglobulin (Aβ₂m) protein.
How to test for amyloidosis?
SpoilerBlood and urine tests may provide hints about the diagnosis, but the gold standard for detecting amyloid deposits is to perform Congo red staining on a tissue sample, which appears apple-green when viewed with a polarizing microscope. Laser microdissection followed by mass spectrometry can determine the type of amyloid in virtually 100% of cases.