Page 129 - Concise Pathology for Exam Preparation ( PDFDrive )

114 SECTION I General Pathology

Chemical Nature of Amyloid

• �Amyloid is composed of 95% fibril proteins, 5% P (pentagonal) component and other
glycoproteins

• �There are 23 biochemically different fibril proteins, of which the most common ones are:

AL (amyloid light chain) protein
• �The precursor protein is a clonal immunoglobulin light chain or light chain frag-
ment, derived from plasma cells.
• �Most AL are composed of lambda light chains; some have kappa chains.
• �AL amyloidosis is associated with monoclonal B cell proliferations. It is labelled
‘primary amyloidosis’ because it is not associated with any primary disease and its
clinical manifestations are due to effects of amyloid deposition. A large number of
AL amyloidoses have marrow plasmacytosis.
AA (amyloid-associated) protein
• �It has a molecular weight of 8500 kDa and 76 amino acid residues
• �Derived from precursor SAA (serum amyloid-associated) protein; it is an acute
phase reactant that circulates in the serum bound to high-density lipoprotein,
HDL-3.

• �AA protein deposits are associated with ‘secondary amyloidosis’ which occurs

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secondary inflammatory conditions like tuberculosis, bronchiectasis, chronic
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osteomyelitis, autoimmune diseases and heroin abuse.

Transthyretin (TTR)
• �TTR is a normal serum protein synthesized in the liver and choroid plexus that
binds and transports thyroxine and retinal protein
• �A mutant form is deposited in familial amyloidotic polyneuropathies and in the
hearts of aged individuals (senile systemic amyloidosis)
b2 microglobulin
• �b2 microglobulin is a component of MHC Class I

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• a normal serum protein whose levels increase in patients on long-term haemo-

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s
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dialysis
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Ab protein
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• �Ab protein is a 4000 Da protein derived from amyloid

• �It constitutes cerebral plaques in Alzheimer disease and is derived by proteolysis
from a glycoprotein called amyloid precursor protein
Q. Classify amyloidosis. Describe the aetiology and clinicopathological

features f the same.
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Ans. Classification of amyloidosis (Table 5.13): The classification of amyloidosis is
based on the tissue distribution of amyloid deposits (local or systemic amyloidosis), the
absence or presence of pre-existing disease (primary or secondary amyloidosis) and the
chemical type of amyloid protein fibril.
TABL E 5.13. Classification of amyloidosis
Clinicopathological category Associated conditions Major fibril protein Precursor protein
Systemic
Primary amyloidosis Multiple myeloma and AL Ig light chains
other monoclonal B cell
proliferations
Secondary amyloidosis Chronic inflammatory AA SAA
conditions
Haemodialysis-related amyloidosis Chronic kidney disease Ab 2 m b2 microglobulin

Hereditary amyloidosis __ AA SAA
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