AMYLOIDOSIS Senior Talk Collins Okolie PGY3
OBJECTIVES <ul><li>Definition </li></ul><ul><li>Mechanism of formation </li></ul><ul><li>Characteristics common to all amy...
Definition <ul><li>A medical condition resulting from aggregation of extracellularly deposited abnormal proteins called am...
Mechanism of formation <ul><li>Amyloid fibrils arise from misfolded proteins. Alpha helix to beta pleated sheet </li></ul>...
<ul><li>In 1854 Rudolph Virchow named it amyloid based on color after staining these proteins with iodine and sulfuric aci...
Characteristics common to all amyloid subtypes <ul><li>Hematoxylin and Eosin (HE) staining results in  amorphous eosinophi...
<ul><li>Amorphous eosinophilic interstitial amyloid  observed on renal biopsy </li></ul><ul><li>Picture was adapted from B...
<ul><li>Congo red staining results in  bright green fluorescence/birefringe apple green color  when viewed under polarized...
<ul><li>Congo red staining of a cardiac biopsy specimen containing amyloid, viewed under polarized light   </li></ul><ul><...
<ul><li>Electron microscopy shows  regular fibrillar structure   </li></ul><ul><li>X-ray diffraction shows  beta pleated s...
Classification:   Historical vs Modern <ul><li>Historical (Clinical): Primary, Secondary, multiple myeloma associated,  Fa...
Table was adapted from Harrison's principles of internal medicine 16 th  edition vol II,  chapter 310-Amyloidosis
Further Clinical Manifestations <ul><li>CNS/Neuro: Neuropathy both autonomic and peripheral, dementia. Corneal deposits al...
CARDIAC AMYLOID Adapted from K. Shah et al, Archives of internal medicine 2006.
<ul><li>Pulmonary:  </li></ul><ul><li>-P leural effusions </li></ul><ul><li>-Parenchymal nodules </li></ul><ul><li>-Trache...
<ul><li>Heme: Bleeding abnormalities </li></ul><ul><li>Musc: Hypertrophy of muscles, macroglossia </li></ul><ul><li>Skin: ...
Liver amyloid Adapted from  www.google.com/liver  amyloid images
Diagnosis <ul><li>Unexplained medical disorder and you suspect amyloidosis: e.g heart failure, proteinuria, hepatic dysfun...
Treatment <ul><li>Treatment of this medical disorder is limited and research is still in progress. </li></ul><ul><li>Treat...
<ul><li>AA: Treat the infection or chronic inflammatory condition causing apo serum A protein elevation.  </li></ul><ul><l...
TAKE HOME MESSAGE <ul><li>Can affect any organ system  </li></ul><ul><li>Hematoxylin and Eosin (HE) and Congo stain only t...
References <ul><li>Rajkumar, S. V. and M. A. Gertz.  “Advances in the Treatment of Amyloidosis.”  NEJM.  2007.  356:  2413...
Upcoming SlideShare
Loading in...5
×

AMYLOIDOSIS.ppt

12,583

Published on

0 Comments
9 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
12,583
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
640
Comments
0
Likes
9
Embeds 0
No embeds

No notes for slide

AMYLOIDOSIS.ppt

  1. 1. AMYLOIDOSIS Senior Talk Collins Okolie PGY3
  2. 2. OBJECTIVES <ul><li>Definition </li></ul><ul><li>Mechanism of formation </li></ul><ul><li>Characteristics common to all amyloid subtypes </li></ul><ul><li>Classification </li></ul><ul><li>Clinical Importance/Symptoms </li></ul><ul><li>Diagnosis and Treatment </li></ul><ul><li>Take home message </li></ul>
  3. 3. Definition <ul><li>A medical condition resulting from aggregation of extracellularly deposited abnormal proteins called amyloid fibrils that cause damage to organs and tissues. </li></ul><ul><li>These fibrils are insoluble, linear, rigid and measures approximately 7.5 to 10mm in width </li></ul>
  4. 4. Mechanism of formation <ul><li>Amyloid fibrils arise from misfolded proteins. Alpha helix to beta pleated sheet </li></ul><ul><li>Proteins are deposited extracellularly </li></ul><ul><li>Proteins aggregate and form fibrils called amyloid fibrils. </li></ul><ul><li>Misfolded proteins may result from point mutations. </li></ul><ul><li>Deposited as localized vs systemic </li></ul><ul><li>-localized; close to cells producing it. </li></ul><ul><li>-Systemic; distant sites from these cells producing these abnormal proteins. </li></ul>
  5. 5. <ul><li>In 1854 Rudolph Virchow named it amyloid based on color after staining these proteins with iodine and sulfuric acid. Meaning cellulose or starch </li></ul>
  6. 6. Characteristics common to all amyloid subtypes <ul><li>Hematoxylin and Eosin (HE) staining results in amorphous eosinophilic appearance when viewed on light microscopy. </li></ul>
  7. 7. <ul><li>Amorphous eosinophilic interstitial amyloid observed on renal biopsy </li></ul><ul><li>Picture was adapted from Bruce A Baethge. Amyloidosis Overview. www.emedicine.medscape.com </li></ul>
  8. 8. <ul><li>Congo red staining results in bright green fluorescence/birefringe apple green color when viewed under polarized light. </li></ul>
  9. 9. <ul><li>Congo red staining of a cardiac biopsy specimen containing amyloid, viewed under polarized light </li></ul><ul><li>Picture was adapted from Bruce A Baethge. Amyloidosis Overview. www.emedicine.medscape.com </li></ul>
  10. 10. <ul><li>Electron microscopy shows regular fibrillar structure </li></ul><ul><li>X-ray diffraction shows beta pleated sheet structure </li></ul>
  11. 11. Classification: Historical vs Modern <ul><li>Historical (Clinical): Primary, Secondary, multiple myeloma associated, Familial. </li></ul><ul><li>Modern (Biochemical): Since 1960’s based on ability to solubilize fibrils and immunostain for protein subtypes. </li></ul><ul><li>23 different human subtypes named based on A for amyloid followed the precursor protein e.g AL, AH. </li></ul>
  12. 12. Table was adapted from Harrison's principles of internal medicine 16 th edition vol II, chapter 310-Amyloidosis
  13. 13. Further Clinical Manifestations <ul><li>CNS/Neuro: Neuropathy both autonomic and peripheral, dementia. Corneal deposits also. </li></ul><ul><li>Cardiac: </li></ul><ul><li>-Cardiomyopathy typically restrictive </li></ul><ul><li>-Heart failure predominantly right sided </li></ul><ul><li>-Angina </li></ul><ul><li>-Sudden death </li></ul><ul><li>-Syncope/pre-syncope </li></ul><ul><li>-ECG Abnormalities and Conduction disease </li></ul><ul><li>-Arrhythmia </li></ul><ul><li>-Cardiac tamponade occasionally, though uncommon. </li></ul><ul><li>-Hypotension </li></ul>
  14. 14. CARDIAC AMYLOID Adapted from K. Shah et al, Archives of internal medicine 2006.
  15. 15. <ul><li>Pulmonary: </li></ul><ul><li>-P leural effusions </li></ul><ul><li>-Parenchymal nodules </li></ul><ul><li>-Tracheal and bronchial infiltration causing hoarseness, airway obstruction and dysphagia. </li></ul><ul><li>Renal: P roteinuria, nephrotic syndrome, renal failure leading to kidney transplant or dialysis. </li></ul>
  16. 16. <ul><li>Heme: Bleeding abnormalities </li></ul><ul><li>Musc: Hypertrophy of muscles, macroglossia </li></ul><ul><li>Skin: Nodules, plaques, easy bruising </li></ul><ul><li>GI: Organomegaly ( Hepatomegaly, splenomegaly), gastroparesis, abnormal bowel movement usually constipation, malabsorption </li></ul>
  17. 17. Liver amyloid Adapted from www.google.com/liver amyloid images
  18. 18. Diagnosis <ul><li>Unexplained medical disorder and you suspect amyloidosis: e.g heart failure, proteinuria, hepatic dysfunction </li></ul><ul><li>Check ECG, TTE, BNP, UPEP, SPEP </li></ul><ul><li>Ultimately, you need Tissue biopsy: Abd fat pad, rectal, salivary gland, endomyocardium. </li></ul><ul><li>Bone marrow biopsy </li></ul>
  19. 19. Treatment <ul><li>Treatment of this medical disorder is limited and research is still in progress. </li></ul><ul><li>Treatment differs depending on subtype. </li></ul><ul><li>AL and AH </li></ul><ul><li>-High dose mephalan plus dexamethasone/prednisone </li></ul><ul><li>-In selected candidates autologous stem cell transplant is an option. </li></ul><ul><li>- The goal with treatment is to get rid of clonal plasma cells that lead to immunoglobulin protein </li></ul>
  20. 20. <ul><li>AA: Treat the infection or chronic inflammatory condition causing apo serum A protein elevation. </li></ul><ul><li>Familial Mediterranean fever: Colchicine </li></ul><ul><li>Other conditions are treated conservatively or require organ transplant </li></ul><ul><li>Prognosis is poor with this medical disorder. </li></ul>
  21. 21. TAKE HOME MESSAGE <ul><li>Can affect any organ system </li></ul><ul><li>Hematoxylin and Eosin (HE) and Congo stain only tells you these are amyloid fibrils </li></ul><ul><li>Need to immunostain to determine subtype </li></ul><ul><li>Different subtypes are treated differently. </li></ul><ul><li>A lot still have to be known about the therapy as prognosis is poor for this disease. </li></ul>
  22. 22. References <ul><li>Rajkumar, S. V. and M. A. Gertz. “Advances in the Treatment of Amyloidosis.” NEJM. 2007. 356: 2413-2415 </li></ul><ul><li>Merlini G and V Bellotti. Molecular Mechanisms of Amyloidosis. New England Journal of Medicine 2003, August: 349:583 </li></ul><ul><li>Baethge B. Amyloidosis Overview. www.emedicine.medscape.com </li></ul><ul><li>Bogov B, Lubomirova M and Kiperova B. Biopsy of subcutaneous fatty tissue for diagnosis of systemic amyloidosis. Hippokratia. 2008 Oct;12(4):236-9. </li></ul><ul><li>Dember LM. Modern Treatment of Amyloidosis: Unresolved questions. J Am Soc Nephrol. 2008 Dec 10. </li></ul><ul><li>Gorevic, Shah, K. B., et al. Amyloidosis and the Heart. Archives of Internal Medicine . 2006. 166: 1805-1813. </li></ul><ul><li>P. D. An overview of amyloidosis. UpToDate.com </li></ul><ul><li>J D Sipe and Alan Cohen. Amyloidosis . Harrison’s Principles of Internal Medicine. Chapter 30, page 2024 </li></ul><ul><li>Images and tables were obtained from Harrison’s, Archives of internal medicine, emedicine and google as sited on each image. </li></ul>
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×