Page 130 - Concise Pathology for Exam Preparation ( PDFDrive )

5 Diseases of Immunity 115

TABLE 5.13. Classification of amyloidosis—cont’d

Clinicopathological category Associated conditions Major fibril protein Precursor protein
Familial Mediterranean fever __ ATTR Transthyretin
Familial amyloidotic neuropathies __ ATTR Transthyretin
Senile systemic amyloidosis __ ATTR Transthyretin
Localized amyloidosis
Senile cerebral Alzheimer disease Ab APP
Endocrine
Medullary carcinoma thyroid __ A Cal Calcitonin
Islet of Langerhans Type II disease Islet amyloid peptide
Isolated atrial amyloidosis __ AANF Arial natriuretic factor
Prion disease Various prion diseases of Misfolded prion pro- Normal prion protein
sc
the CNS teins (PrP )

Pathogenesis of Amyloidosis (Flowchart 5.12)

Production of abnormal Production of normal
amounts of normal protein amounts of abnormal/mutant protein
Monoclonal B­cell Chronic Mutation
proliferation inflammation

Plasma cells Macrophage activation,
increased IL­1 and IL­6
Mutant transthyretin
Excess immunoglobulin ↑Synthesis of SAA protein
light chains (liver)
Aggregation & resistance
Limited to proteolysis
proteolysis
AL protein AA protein ATTR protein
FLOWCHART 5.12. Pathogenesis of amyloidosis.

There are Two Types of Amyloid Proteins:
�Misfolded proteins (production of abnormal amounts of normal protein which is unstable,
1.
self-associates to form oligomers and fibrils, called misfolded proteins).
�Mutant proteins (production of normal amounts of abnormal/mutant protein which is
2.
structurally unstable, prone to misfolding and subsequent aggregation). Abnormally
folded proteins get deposited in extracellular tissue as fibrils and disrupt normal tissue
by causing pressure atrophy of adjacent cells and vascular narrowing; the latter leading
to ischaemia.

Morphology of Amyloidosis

• Primary amyloidosis: Affects kidneys, liver, spleen, lymph nodes, adrenal and thyroid
• �Secondary amyloidosis: Affects heart, kidneys, GIT, peripheral nerves, skin and

tongue
Gross Features
• Affected organs are enlarged, firm and waxy.
• �Painting cut-surface with iodine imparts a yellow colour, which changes to bluish-violet
after application of sulphuric acid.

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