AMYLOIDOSIS

Senior Talk
Collins Okolie PGY3
 OBJECTIVES
 Definition
 Mechanism of formation
 Characteristics common to all amyloid
subtypes
 Classification
 Clinical Importance/Symptoms
 Diagnosis and Treatment
 Take home message
 Definition
 A medical condition resulting from
aggregation of extracellularly
deposited abnormal proteins called
amyloid fibrils that cause damage to
organs and tissues.

 These fibrils are insoluble, linear,

rigid and measures approximately
7.5 to 10mm in width
 Mechanism of formation
 Amyloid fibrils arise from misfolded
proteins. Alpha helix to beta pleated sheet
 Proteins are deposited extracellularly

 Proteins aggregate and form fibrils called

amyloid fibrils.
 Misfolded proteins may result from point
mutations.
 Deposited as localized vs systemic

-localized; close to cells producing it.

-Systemic; distant sites from these cells
producing these abnormal proteins.
 In 1854 Rudolph Virchow named it
amyloid based on color after staining
these proteins with iodine and
sulfuric acid. Meaning cellulose or
starch
 Characteristics common to all
amyloid subtypes
 Hematoxylin and Eosin (HE) staining
results in amorphous eosinophilic
appearance when viewed on light
microscopy.
 Amorphous eosinophilic interstitial amyloid observed on renal biopsy
 Picture was adapted from Bruce A Baethge. Amyloidosis Overview.
www.emedicine.medscape.com
 Congo red staining results in bright
green fluorescence/birefringe
apple green color when viewed
under polarized light.
 Congo red staining of a cardiac biopsy specimen containing
amyloid, viewed under polarized light
 Picture was adapted from Bruce A Baethge. Amyloidosis Overview.
www.emedicine.medscape.com
 Electron microscopy shows regular
fibrillar structure

 X-ray diffraction shows beta

pleated sheet structure
 Classification:
Historical vs Modern
 Historical (Clinical): Primary, Secondary,
multiple myeloma associated, Familial.
 Modern (Biochemical): Since 1960’s based
on ability to solubilize fibrils and
immunostain for protein subtypes.
 23 different human subtypes named based
on A for amyloid followed the precursor
protein e.g AL, AH.
Table was adapted from Harrison's principles of internal medicine 16th edition vol II, chapter 310-Amyloidosis
 Further Clinical Manifestations
 CNS/Neuro: Neuropathy both autonomic and peripheral,
dementia. Corneal deposits also.
 Cardiac:
-Cardiomyopathy typically restrictive
-Heart failure predominantly right sided
-Angina
-Sudden death
-Syncope/pre-syncope
-ECG Abnormalities and Conduction disease
-Arrhythmia
-Cardiac tamponade occasionally, though uncommon.
-Hypotension
 CARDIAC AMYLOID

Adapted from K. Shah et al, Archives of internal medicine 2006.

 Pulmonary:
-Pleural effusions
-Parenchymal nodules
-Tracheal and bronchial infiltration causing
hoarseness, airway obstruction and
dysphagia.

 Renal: Proteinuria, nephrotic syndrome,

renal failure leading to kidney transplant
or dialysis.
 Heme: Bleeding abnormalities
 Musc: Hypertrophy of muscles,
macroglossia
 Skin: Nodules, plaques, easy bruising
 GI: Organomegaly (Hepatomegaly,
splenomegaly), gastroparesis, abnormal
bowel movement usually constipation,
malabsorption
 Liver amyloid

Adapted from www.google.com/liver amyloid images

 Diagnosis
 Unexplained medical disorder and
you suspect amyloidosis: e.g heart
failure, proteinuria, hepatic
dysfunction
 Check ECG, TTE, BNP, UPEP, SPEP
 Ultimately, you need Tissue biopsy:
Abd fat pad, rectal, salivary gland,
endomyocardium.
 Bone marrow biopsy
 Treatment
 Treatment of this medical disorder is limited and
research is still in progress.
 Treatment differs depending on subtype.

 AL and AH

-High dose mephalan plus

dexamethasone/prednisone
-In selected candidates autologous stem cell
transplant is an option.
- The goal with treatment is to get rid of clonal
plasma cells that lead to immunoglobulin protein
 AA: Treat the infection or chronic
inflammatory condition causing apo serum
A protein elevation.
 Familial Mediterranean fever: Colchicine
 Other conditions are treated
conservatively or require organ transplant
 Prognosis is poor with this medical
disorder.
 TAKE HOME MESSAGE
 Can affect any organ system
 Hematoxylin and Eosin (HE) and Congo
stain only tells you these are amyloid
fibrils
 Need to immunostain to determine
subtype
 Different subtypes are treated differently.
 A lot still have to be known about the
therapy as prognosis is poor for this
disease.
 References
 Rajkumar, S. V. and M. A. Gertz. “Advances in the Treatment of
Amyloidosis.” NEJM. 2007. 356: 2413-2415
 Merlini G and V Bellotti. Molecular Mechanisms of Amyloidosis. New
England Journal of Medicine 2003, August: 349:583
 Baethge B. Amyloidosis Overview. www.emedicine.medscape.com
 Bogov B, Lubomirova M and Kiperova B. Biopsy of subcutaneous fatty
tissue for diagnosis of systemic amyloidosis. Hippokratia. 2008
Oct;12(4):236-9.
 Dember LM. Modern Treatment of Amyloidosis: Unresolved questions. J
Am Soc Nephrol. 2008 Dec 10.
 Gorevic, Shah, K. B., et al. Amyloidosis and the Heart. Archives of Internal
Medicine. 2006. 166: 1805-1813.
 P. D. An overview of amyloidosis. UpToDate.com
 J D Sipe and Alan Cohen. Amyloidosis. Harrison’s Principles of Internal
Medicine. Chapter 30, page 2024
 Images and tables were obtained from Harrison’s, Archives of internal
medicine, emedicine and google as sited on each image.