2. AMYLOIDS
• Misfolded proteins that deposit in extracellular spaces.
• Can be associated with inherited/inflammatory disorders.
• Deposits cause tissue damage.
• “Amyloids” because staining characteristics resemble amylose
• With progressive accumulation, amyloids can encroach & cause pressure
necrosis on adjacent cells.
3. CHARACTERISTICS
• Multiple proteins can aggregate to form amyloid. (It doesn’t have to be only 1
type of protein)
• Aggregated proteins usually have cross ß pleated sheath configuration.
• This makes them pick up Congo Red stain.
• Have Apple Green birefringence under polarized light.
4. Source: Pathoma – Fundamentals of
Pathology
CONGO RED STAIN
Amyloid
deposits
Blood
vessel
5. Source: Pathoma – Fundamentals of
Pathology
APPLE GREEN BIREFRINGENCE
6. PATHOGENESIS
• Generally, misfolded proteins are degraded
Intracellularly: in proteosomes
Extracellularly: in macrophages
• In amyloidosis, these degradation mechanisms fail.
7. CLASSIFICATION
Amyloidosis
Systemic Localized
Primary Secondary
Involving multiple organ
systems
Involving only 1 organ
Ex: Immunoglobulin
light chain
amyloidosis
Ex: Reactive
systemic
amyloidosis
Ex:
• Medullary carcinoma
of thyroid
• Senile cardiac
amyloidosis
Hemodialysis
associated
amyloidosis
8. IMMUNOGLOBULIN LIGHT CHAIN AMYLOIDOSIS
(PRIMARY)
• Deposition of AL amyloids.
• Derived from Ig light chains.
• Plasma cell abnormalities Abnormal overproduction of light chains
Deposition
• Not all free chains produce amyloids. Amyloidogenic potential of a light chain is
determined by its specific amino acid sequence.
9. REACTIVE SYSTEMIC AMYLOIDOSIS (SECONDARY)
• Deposition of AA protein
• Derived from SAA protein
• SAA is an acute phase reactant, i.e., its levels rise in chronic inflammation
• Ex: Rheumatoid arthritis, Ankylosing spondylitis, Crohn’s disease, Ulcerative colitis,
etc.
• Infections associated with pricking of skin in narcotic use can inc. risk of
amyloidosis.
AA levels rise
10. FAMILIAL MEDITERRANEAN FEVER
• Autoinflammatory syndrome
• Inc. cytokine IL-1 production
• Attacks of fever along with inflammation of serosal surfaces is seen. Rashes can also
be present.
Inc. IL-1
Inc. SAA
Inc. AA
Amyloidosis
11. HAEMODIALYSIS ASSOCIATED AMYLOIDOSIS
Long term hemodialysis
• In the past, B2- microglobulin could not be filtered through dialysis membranes, and
was retained in circulation. With new dialysis filters, this complication has been
reduced.
B2 microglobulin
deposition
Joints, muscles,
tendons/ligaments
affected
Common
presentation:
Carpal Tunnel
Syndrome
12. LOCALIZED AMYLOIDOSIS
1. Senile cardiac amyloidosis – non-mutated serum transthyretin deposited
2. Medullary carcinoma of thyroid – Procalcitonin deposited
3. Alzheimers – Aß protein gets deposited. Precursor: Amyloid precursor protein
4. Other endocrine amyloids – seen in Islets of Langerhans in Type 2 DM,
pheochromocytoma.
15. TESTS
• Tissue biopsy
• Abdominal fat pad and rectum are easily accessible
• Biopsy of bone marrow/affected organ can also be taken
• Echocardiogram (for heart related)
16. TREATMENT
MEDICATIONS:
• Chemotherapy and blood thinners
SURGICAL:
• Autologous blood stem cell transplant
• Dialysis – If kidney is affected
• Organ transplant – in cases of severe damage
