Amyloid

Question 1

Structure of amyloid

Answer 1

• non-branching fibrils w Beta-pleated sheets
• non-fibrillary component (P-component) is smaller component of amyloid, strong afffinity for amyloid fibrils, comprised of normally occuring serum alpha1-glycoprotein, similar to C-reactive protein
• Histopath:
• Kidney: H&E appearance of amyloid; capillaries are empty, thick-walled, or occluded -> amyloid causing hypoxic changes
• Congo-red -> Apple-red birerfrigence w/ polarized light
• Heart muscle: H&E: cardiac muscle squished w/ tiny nuclei due to atrophy from the amyloidosis -> confirm w/ Congo Red stain
• EM: non-branching fibrils + P component.

Question 2

AL & AA amyloid proteins and other types

Answer 2

AL amyloid

• complete light chains, lambda type
• seen in Pt w Beta-cell dyscrasias

AA amyloid

• AA derived from larged protein called SAA, which is in high quantities during chronic inflammation.

Beta-amyloid

• Alzheimer’s disease

Beta2-microglobulin

• renal dialysis

Question 3

Systemic amyloidosis examples (best known)

Answer 3

Immunocyte dyscrasias w amyloidosis

• excess of Ig and light chains (BJ) by abnormal B cells (multiple myeloma; MM).
• AL type most common
• Most Pt who have AL amyloidosis do not have MM
• most common type of amyloidosis in N. America
• formerly known as primary amyloidosis

Reactive systemic amyloidosis:

• AA protien depositiion of most organs/systems
• formerly known as secondary amyloidosis bc it was associated w inflammatory processes including:
  
  • N. America: autoimmune disease, Hodgkin’s lymphoma, chronic skin infections.
  • Poorer countries: TB, chronic osteomyelitis, and bronchiectasis.

Dialysis

• catch-22

Heredofamilial amyloidosis:

• AA or transthyretin deposition
• Familial Mediterranean fever: defect in PMN function (AR); AA deposits
• Familial amyloidotic neuropathies: 60 mutations, most common subtype has transthyretin deposits

Question 4

Localised or isolated amyloidosis

Answer 4

• usually a single organ/system involved
• deposits of various chemical compositions
• often associated w plasma cell infiltration
• Ex. Islets of Langerhans amyloidosis
• Ex2. Senile cardiac amyloidosis: Transthyretin deposit, asymptomatic
• Ex3. Senile cerebral amyloidosis: Alzheimer’s, chromosome 21, Down’s syndrome develop similar plaques

Question 5

Organs affected by amyloidosis

Answer 5

Kidney

• seen mainly in glomeruli as diffuse nodular deposits in mesangial matrix and basement membrane -> deposits replace glomeruli
• also seen in interstitium (peritubular areas) and blood vessels of all sizes w marked luminal narrowing

Spleen

• tapioca-like granules (sago spleen)
• deposits seen around sinuses and bv

Liver

• pale, waxy, firm
• deposits seen in space of Disse’s, sinusoids, and vessels

Heart

• both systemic and localised amyloidosis affect heart
• systemic = AL type w congestive cardiac failure

Tongue, GI tract