Introduction to Amyloidosis - Introduction to General Medicine - Lecture Slides, Slides of Medicine

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AMYLOIDOSIS

OBJECTIVES

 Definition

 Mechanism of formation

 Characteristics common to all amyloid subtypes

 Classification

 Clinical Importance/Symptoms

 Diagnosis and Treatment

 Take home message

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

 Amorphous eosinophilic interstitial amyloid observed on renal biopsy  Picture was adapted from Bruce A Baethge. Amyloidosis Overview.

 Congo red staining results in bright

green fluorescence/birefringe

apple green color when viewed

under polarized light.

 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.

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.

 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

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 Docsity.com

 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.