AmyloidosisAmyloidosis

Or Beta –fibrillosisOr Beta –fibrillosis

Immunologic mechanisms……Immunologic mechanisms……

Extra cellular deposition of fibrillar Extra cellular deposition of fibrillar proteinaceous substanceproteinaceous substance

Similar morhological appearance , stainig Similar morhological appearance , stainig properties and physical structure but properties and physical structure but different chemical structuredifferent chemical structure

Described by Rokitansky in the year 1842Described by Rokitansky in the year 1842

Virchow named it as AmyloidVirchow named it as Amyloid

on cut surface turned brown with Iodine and on cut surface turned brown with Iodine and blue on adding dilute sulphuric acidblue on adding dilute sulphuric acid

H & E H & E Extra cellular , homogenous , Extra cellular , homogenous , structureless , eosinophilic , hyaline materialstructureless , eosinophilic , hyaline material

Shows Positive with Congo red staining and Shows Positive with Congo red staining and shows apple green birefringance on polarising shows apple green birefringance on polarising microscopymicroscopy

Components Components

1.1. Fibril proteinsFibril proteins

2.2. Non Fibrillar components ( P Non Fibrillar components ( P Component)Component)

Fibril Protein Fibril Protein

95% of Amyloid95% of Amyloid

Delicate , randomly dispersed , Delicate , randomly dispersed ,

8 – 10 nm Diameter8 – 10 nm Diameter

Indefinite lengthIndefinite length

One fibril = twin filaments seperated by a One fibril = twin filaments seperated by a clear spaceclear space

Under X ray crystallography and infrared Under X ray crystallography and infrared spectroscopy spectroscopy CROSS BETA PLEATED CROSS BETA PLEATED SHEET Configuration SHEET Configuration

Periodicity is 1000 A Periodicity is 1000 A gives gives characteristic staining properties with characteristic staining properties with Congo Red and polarizing microscopyCongo Red and polarizing microscopy

Amyloid is also referred to as Beta Amyloid is also referred to as Beta FibrillosisFibrillosis

Chemical composition of FibrilsChemical composition of Fibrils

1.1. Light chain – amino terminal segment and part of C regionLight chain – amino terminal segment and part of C region2.2. Acute phase reactant proteinAcute phase reactant protein3.3. Mutated Trans ThyretinMutated Trans Thyretin4.4. Normal Trans ThyretinNormal Trans Thyretin5.5. Beta 2 microglobulin Beta 2 microglobulin 6.6. Transmembrane Glyco protein(AbPP)Transmembrane Glyco protein(AbPP)7.7. Heavy ChainHeavy Chain8.8. ProcalcitoninProcalcitonin9.9. Islet PolypeptideIslet Polypeptide10.10. Pro insulinPro insulin11.11. Prolactin Prolactin 12.12. ANFANF13.13. LactoferrinLactoferrin14.14. Prion ProteinPrion Protein15.15. ApolipoproteinApolipoprotein16.16. GelsolinGelsolin17.17. LysozymeLysozyme18.18. CystatinCystatin19.19. Amyoid of familial dementiaAmyoid of familial dementia20.20. Fibrinogen alpha chainFibrinogen alpha chain

Non fibrillar componentNon fibrillar component

P component – P component – glycoproteinglycoprotein resembling CRP resembling CRP

Apolipoprotein EApolipoprotein E

Sulfated GlycosaminoglycansSulfated Glycosaminoglycans

Alpha 1 anti chymotrypsinAlpha 1 anti chymotrypsin

Protein XProtein X

ComponentComponent

ProteinasesProteinases

Membrane componentsMembrane components

MechanismMechanism

1.1. Pool of amyloidogenic precursor proteinsPool of amyloidogenic precursor proteins2.2. Nidus for fibrillosis Nidus for fibrillosis interaction interaction

between basement membrane proteins between basement membrane proteins and Amyloid componentsand Amyloid components

3.3. Partial degradation by macrophages / Partial degradation by macrophages / RESRES

4.4. ATTR , Ab2M , prions ATTR , Ab2M , prions not degraded not degraded 5.5. Help of P component in aggregation , Help of P component in aggregation ,

folding and protectionfolding and protection

In AA In AA

An important role for AEF An important role for AEF Amyloid Amyloid Enhancing FactorEnhancing Factor glyco protein glyco protein

AEF is seen in AEF is seen in

1.1. CancersCancers

2.2. Familial Mediterranean feverFamilial Mediterranean fever

3.3. Chronic inflammationChronic inflammation

MorphologyMorphology

Extra cellular matrix and in the extra Extra cellular matrix and in the extra cellular basement membranecellular basement membrane

General gross General gross organ is enlarged , organ is enlarged , pale , and rubbarypale , and rubbary

Cut surface is firm , waxy and translucentCut surface is firm , waxy and translucent

Micro Micro extra cellular deposition extra cellular deposition

Amyloidosis of kidneyAmyloidosis of kidney

Most commonMost common Most seriousMost seriousAffects the renal functionAffects the renal functionMostly Secondary Mostly Secondary One third of primaryOne third of primary20 % of Death from Amyloids20 % of Death from AmyloidsIncrease permeability Increase permeability proteinuria proteinuria nephrotic syndromenephrotic syndrome

Amyloid spleenAmyloid spleen

Sago spleenSago spleen

Lardaceous spleenLardaceous spleen

Amyloid liverAmyloid liver