Amyloidosis 2
•
7 likes•893 views
This document discusses amyloidosis, including its pathogenesis, classification, and specific entities. The basic mechanism involves the abnormal folding and accumulation of proteins into fibrils, which can damage tissues through pressure effects, vessel wall infiltration, and cytotoxicity. Amyloidosis is classified as either generalized/systemic, involving multiple organs, or localized, affecting a single tissue. Specific entities discussed include reactive systemic amyloidosis associated with chronic inflammation; hemodialysis-associated amyloidosis involving beta-2 microglobulin; and hereditary forms like familial Mediterranean fever and familial amyloidotic neuropathy.
More Related Content
What's hot
What's hot (20)
Similar to Amyloidosis 2
Similar to Amyloidosis 2 (20)
More from Vijay Shankar
More from Vijay Shankar (20)
Recently uploaded
Recently uploaded (20)
Amyloidosis 2
- 1. AMYLOIDOSIS : PART 2
- 2. LEARNING OUTCOMES • Pathogenesis • Basic mechanism • Specific entities • Classification • Discussion of few entities
- 3. PATHOGENESIS
- 4. Basic Mechanism Abnormal folding of proteins/ Misfolded proteins Normal circumstances Misfolded proteins are degraded Intracellularly Extracellularly Proteasome pathway Macrophages Amyloidosis Control mechanism fail Mutations which favor misfolding Accumulation and Aggregation to form fibrils
- 5. PATHOGENESIS Normal proteins, when produced in abnormal numbers Production of normal amounts of mutant proteins Acquired mutation Monoclonal B lymphocyte proliferation Immunoglobulin light chains AL protein Incomplete proteolysis Chronic Inflammation IL1 &IL6 Increased SAA protein AA protein Incomplete proteolysis Macrophages activation Eg : Transthyretin (TTR) Mutation Mutant TTR Aggregation ATTR protein AMYLOIDOSIS
- 6. Mechanism of damage to the tissues 1. Pressure effect: leading to atrophy 2. Accumulation in vessel wall : Leading to ischemia and also increased permeability 3. Direct cytotoxicity: eg, Amyloidogenic light chain accumulation n cardiac cells 4. Prefibrillar oligomers: are found be more injurious than actual fibrils. In Alzheimer's and ATTR Amyloidosis
- 7. Classification Based on the clinicopathologic features GENERALISED/SYSTEMIC AMYLOIDOSIS Primary Amyloidosis ( immunocyte dyscrasias with amyloidosis Ig Light chains AL Multiple myeloma & other plasma cell dyscrasias Secondary Amyloidosis ( Reactive systemic amyloidosis SAA AA Chronic inflammation Hemodialysis associated Amyloidosis β2- microglobulin Aβ2-m Chronic renal failure LOCALISED AMYLOIDOSIS Senile cerebral APP Aβ Alzheimer disease Endocrine: Thyroid Calcitonin Acal Medullary Ca Thyroid Islet of Langerhans Islet Amyloid Peptide AIAPP Type 2 Diabetes HEREDITARY AMYOIDOSIS Familial Mediterranean fever SAA AA Familial Amyloidotic Neuropathy Transthyretin ATTR Systemic senile amyloidosis Transthyretin ATTR CATEGORY PRECURSOR PROTEIN FIBRIL PROTEIN ASSOCIATED DISEASES
- 9. Reactive Systemic Amyloidosis Secondary Amyloidosis Previously, Tuberculosis, bronchiectasis and chronic osteomyelitis were the most important conditions Presently, Rheumatoid arthritis, Ankylosing spondylosis, inflammatory bowel diseases Drug abusers: Heroin injections… due to chronic skin infections Solid tumors : Renal cell carcinoma, Hodgkin lymphoma. Non immunocyte tumors!
- 10. Hemodialysis associated Amyloidosis β2-microglobulin is increased in the serum of these patients Chronic renal failure β2-microglobulin could not be filtered by dialysis In the Past Deposition of A β2- microglobulin Present Era Good dialysis filters Decreased incidence
- 11. Heredofamilial amyloidosis Familial Amyloidotic NeuropathyFamilial Mediterranean fever Autosomal recessive Autoinflammatory syndrome Excessive production of IL1 in response to inflammation Characterized by attacks of fever with serosal inflammation Wide spread amyloidosis AA proteins Autosomal dominant Deposition of amyloid in peripheral and autonomic nerves Fibrils are made up of mutant TTRs
- 12. Localised amyloidosis Limited to a single tissue or organ Can be only microscopic foci or may be evident grossly as nodular masses The common sites: lung, larynx, skin, bladder, tongue etc. Microscopic findings: Lymphocytes and plasma cells can be seen in the periphery of amyloid deposits. Some cases , the amyloid consists of AL protein
- 13. SUMMARY • Pathogenesis • Basic mechanism • Specific entities • Classification • Discussion of few entities