Amyloidosis. PPT.X its pathophysiological and its properties and features

Amyloidosis is a condition in which their is deposition of amyloid protein in extracellular space. It lead to pressure atrophy of cell.

1. AMYLOIDOSIS PRESENTED BY – ANJALI GOND ROLL NO. – 30

2. INDEX INTRODUCTION PHYSICAL & CHEMICAL NATURE OF AMYLOID CLASSIFICATION PATHOGENESIS CLINICAL FEATURES MORPHOLOGICAL FEATURES ORGAN INVOLVEMENT DIAGNOSIS PROGNOSIS

3. INTRODUCTION Amyloidosis is a condition associated with number of inherited and inflammatory disorder in which extracellular deposits of fibrillar proteins are responsible for tissue damage and functional compromise. The abnormal fibrils are produced by aggregation of misfolded proteins.

4. PHYSICAL NATURE OF AMYLOID PROTEIN ELECTRON MICROSCOPY Continuous and non branching fibrils Indefinite length 7.5- 10 nm in diameter X-ray crystallography & Infrared spectroscopy Cross β-pleated sheet conformation Common to all amyloid protein Responsible for their distinctive Congo red staining and birefringence Fig1 . Showing str of amyloid protein

5. CHEMICAL NATURE The main component of Amyloid are – A fibrillary protein (95%) which is characteristic for each different type of disease. Amyloid P component (5%) consists of stacks of doughnut-shaped proteins. All different types of amyloid possess this protein. A glycosoamynoglycan . This is the part of the molecule responsible for the positive reaction with iodine .

6. TYPES OF FIBRILLAR PROTEIN Amyloid light chain(AL) - made up of complete immunoglobulin light chain, derived from the lambda light chain. Amyloid associated(AA)- derived from a unique non-Ig protein made by the liver, derived from larger precursor protein SAA(serum amyloid associated protein) others A β2 Microglobulin (A β M)- seen in patients on long term hemodialysis . Transthyretin (TTR) – serum protein synthesized in liver & transports thyroxine and retinol. Amyloid β- peptide(A β)- seen in Alzheimers disease. Prion proteins ( APrP ) Precursor of AA =SAA(Serum Amyloid Associated Protein )

7. TYPES OF NON FIBRILLAR PROTEIN Amyloid P(AP) component-found in all forms of amyloid. Apolipoprotein-E ( apoE ) Sulfated glycosaminoglycans(GAGs)

8. PATHOGENESIS Normally in human body abnormal misfolded protein are degraded – INTRACELLULAR by protesomes EXTRACELLULAR by macrophage In Amyloidosis , this degradation mechnasism fail and lead to accumulation of misfolded protein in extracellular matrix

9. CLASSIFICATION Classification of amyloidosis The classification of amyloidosis goes like this: Systemic (generalized) amyloidosis Primary amyloidosis (AL type) Secondary amyloidosis (AA type) Familial Mediterranean fever (AA type) Senile systemic amyloidosis (ATTR type) Haemodialysis-associated amyloidosis Localized amyloidosis Endocrine amyloids in Langerhans islets in type 2 diabetes Alzheimer’s disease (A β type)

10. CLINICAL FEATURES manifestations at first are often entirely nonspecific, such as – Weakness Weight loss Lightheadedness Syncope Somewhat more specific findings appear later and most often relate to renal, cardiac, and gastrointestinal involvement.

11. MORPHOLOGY Macroscopically Enlarged Grey in appearance Waxy, firm in consistency   Microscopically Extracellular deposit Often adjacent to basement membrane In advanced stage, encroach, surrounds and destroying the cell Fig showing macroscopical changes in spleen

12. ORGAN INVOVEMENT IN AMLYOIDOSIS No consistent or distinctive pattern of amyloid deposit Predominant organ involvement

13. ORGAN INVOLVEMENT - KIDNEY Most common and potentially most serious form of organ involvement Gross – normal or shrunken [due to ischemia (vascular narrowing) in advanced stage] Microscopy – glomerular deposit, interstitial , peritubular, arterial wall deposit Fig showing gross and microscopy of kidney in amyloidosis

14. SPLEEN One of two patterns of deposition is seen. Sago spleen - deposits are largely limited to the splenic follicles, producing tapioca-like granules grossly. Lardaceous spleen – amyloid involves the walls of the splenic sinuses and connective tissue framework in the red pulp. Fusion of the early deposits gives rise to large, map like areas of amyloidosis. Fig showing sago and lardaceous spleen

15. LIVER Earliest part affected is space of disse . Produces pressure atrophy of hepatocytes cirrhosis. HEART Earliest part affected is subendocardium . Leads to : Arrhythmia , Heart failure ,Restrictive Cardiomyopathy Normal ATTR deposited

16. DIAGNOSIS The diagnosis of amyloidosis depend on the histologic demonstration of amyloid deposits in tissues. Biopsy If localized : taken from localized tissue If systemic : Abdomen fat pad aspirate Rectal Gingival

17. 2. STAIN USED : Congo stain PAS stain Thioflavin S Thioflavin T 3. GROSS STAIN : Paint the cut surface of organ with lugol iodine Giving a mahogany brown color Add sulphuric acid it turn blue – Amyloid present remain brown – No Amyloid Fig showing congo red stain

18. PROGNOSIS The prognosis for individuals with generalized amyloidosis is poor. Immunocyte derived amyloidosis (not including multiple myeloma) - median survival of 2 years after diagnosis. Persons with myeloma-associated amyloidosis have a poorer prognosis. Reactive systemic amyloidosis - somewhat better and depends to some extent on the control of the underlying condition. New therapeutic strategies aimed at - Correcting protein misfolding and - Inhibiting fibrillogenesis are being developed .

19. REFERENCES Robbins & Cotran Pathologic Basis of Disease - 10th Edition general-characterisation-of-amyloidosis-physico-chemical-ultrastructural-and-histochemical-nature-of-amyloid-types-of-amyloid pathology.com/amyloidosis-part-2-pathogenesis-classification/

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