Amyloidosis

1. “All evil comes from people whose idea of wellbeing only includes themselves, their own family, community, race, religion or nation.” -- Sadhguru Selfishness is the cause of evil…!

2. 2 CLINICAL PATHOLOGY The foundation of Clinical Medicine. Shashidhar Venkatesh Murthy A/Prof & Head of Pathology College of Medicine & Dentistry Amyloidosis

3. 3 Amyloidosis: Introduction  Group of disorders with extracellular deposition of fibrillary non digestible abnormal (misfolded) proteins waxy material (> 20 different proteins).  “Amyloid” (starch like - Virchow) due to charged sugar molecules in the protein.  Routine Microscopy shows as uniform pink deposits.  Congo red stain – specifically stains amyloid – red which apear apple green under polarized microscopy.  Primary, Secondary/Inflammatory*, Systemic / Local & Hereditary types.  Hepatosplenomegaly, restrictive cardiomyopathy & organ failure. Glomerulus - Congo Red Stain Polarized Microscopy

4. 4 Amyloidosis: Types & their Pathogenesis: Pathogenesis Primary Secondary Senile / Hereditary β pleated

5. 5 Amyloidosis: Clinical Disorders Systemic Amyloidosis: (multiorgan)  Primary: Plasma cell / Immunocyte disorders: Multiple myeloma. - AL  Secondary: Reactive, Chronic Inflam. TB, Auto.Imm dis. – AA  Hemodialysis Associated: Chronic Renal Failure – β2 microglob.  Systemic Senile Amyloidosis: Ageing Transthyretin, cardiomyopathy ATTR  Hereditary Amyloidosis: Many subtypes, familial: ATTR ATTR: Amyloid of TTR transporter of Thyroxin & Retinol (VitaminA)  Localized Amyloidosis: (Specific tissue / organ)  Senile cerebral: Alzheimer disease Aβ  Endocrine: Diabetes DM2 – AIAPP Proinsulin.  Cardiac Amyloidosis: atrial natriuretic factor. AANF  Medullary carcinoma thyroid – ACal – Calcitonin. 

6. “All evil comes from people whose idea of wellbeing only -- Sadhguru Think before thinking negative..…!

7. 7 Senile Systemic Amyloidosis – Heart, Restrictive CMP Normal  Previously known as Senile Cardiac Amyloidosis.  Restrictive Cardiomyopathy & Arrhythmias.  American Black population 4%, Transthyretin (ATTR)  Familial amyloid polyneuropathy (FAP): Sweden, Japan, common.

8. 8 Amyloidosis: Morphology  Gross: Organ enlargement, pale, rubbery firm (waxy deposits)  Microscopy: extracellular Pink deposits. Congo Red stain +ve.  Effects: Pressure atrophy of surrounding cells, Narrowing of BV. Ischemia, infarctions, dysfunction / hypofunction. Normal Kidney Liver

9. “All evil comes from people whose idea of wellbeing only -- Sadhguru

10. 10 Amyloidosis: Summary  Extracellular deposition of waxy, misfolded, non digestible proteins with β pleated fibrillary structure.  Leading to cellular damage & organ failure.  Primary, Secondary, Systemic, Localized & Hereditary types.  Secondary Amyloidosis, Commonest, chronic inflammation. SAA.  Clinical: Hepatosplenomegaly, brain, kidney & Heart failure  Gross: Firm, pale, waxy enlargement of organs.  Microscopy: Extracellular, pink protein. Congo red stain positive, apple green under polarized microscopy.  Late complication in chronic infections(TB), Inflammations, Autoimmune disorders, Ageing and B cell neoplasms like multiple myeloma. Rarely hereditary disorders.

11. “No doubt knowledge is valuable, but above it is Character” Knowledge without character is dangerous!