This document discusses amyloidosis, which is the extracellular deposition of fibrillar proteinaceous substances that have similar morphological appearances and staining properties but different chemical structures. It describes how amyloidosis was first described in 1842 and named by Virchow. The key components of amyloid fibrils are discussed as well as the mechanisms of amyloid formation and deposition. Important details on the morphology, sites of involvement like the kidney and spleen, and clinical manifestations are provided.

1. AmyloidosisAmyloidosis
Or Beta –fibrillosisOr Beta –fibrillosis
Immunologic mechanisms……Immunologic mechanisms……

2. Extra cellular deposition of fibrillarExtra cellular deposition of fibrillar
proteinaceous substanceproteinaceous substance
Similar morhological appearance , stainigSimilar morhological appearance , stainig
properties and physical structure butproperties and physical structure but
different chemical structuredifferent chemical structure

3. 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 andon cut surface turned brown with Iodine and
blue on adding dilute sulphuric acidblue on adding dilute sulphuric acid
H & EH & E  Extra cellular , homogenous ,Extra cellular , homogenous ,
structureless , eosinophilic , hyaline materialstructureless , eosinophilic , hyaline material
Shows Positive with Congo red staining andShows Positive with Congo red staining and
shows apple green birefringance on polarisingshows apple green birefringance on polarising
microscopymicroscopy

5. ComponentsComponents
1.1. Fibril proteinsFibril proteins
2.2. Non Fibrillar components ( PNon Fibrillar components ( P
Component)Component)

6. Fibril ProteinFibril 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 aOne fibril = twin filaments seperated by a
clear spaceclear space

7. Under X ray crystallography and infraredUnder X ray crystallography and infrared
spectroscopyspectroscopy  CROSS BETA PLEATEDCROSS BETA PLEATED
SHEET ConfigurationSHEET Configuration
Periodicity is 1000 APeriodicity is 1000 A  givesgives
characteristic staining properties withcharacteristic staining properties with
Congo Red and polarizing microscopyCongo Red and polarizing microscopy
Amyloid is also referred to as BetaAmyloid is also referred to as Beta
FibrillosisFibrillosis

8. Chemical composition of FibrilsChemical composition of Fibrils

9. 1.1. Light chain – amino terminal segment and part of C regionLight chain – amino terminal segment and part of C region
2.2. Acute phase reactant proteinAcute phase reactant protein
3.3. Mutated Trans ThyretinMutated Trans Thyretin
4.4. Normal Trans ThyretinNormal Trans Thyretin
5.5. Beta 2 microglobulinBeta 2 microglobulin
6.6. Transmembrane Glyco protein(AbPP)Transmembrane Glyco protein(AbPP)
7.7. Heavy ChainHeavy Chain
8.8. ProcalcitoninProcalcitonin
9.9. Islet PolypeptideIslet Polypeptide
10.10. Pro insulinPro insulin
11.11. ProlactinProlactin
12.12. ANFANF
13.13. LactoferrinLactoferrin
14.14. Prion ProteinPrion Protein
15.15. ApolipoproteinApolipoprotein
16.16. GelsolinGelsolin
17.17. LysozymeLysozyme
18.18. CystatinCystatin
19.19. Amyoid of familial dementiaAmyoid of familial dementia
20.20. Fibrinogen alpha chainFibrinogen alpha chain

10. Non fibrillar componentNon fibrillar component

11. P component –P component – glycoproteinglycoprotein resembling CRPresembling CRP
Apolipoprotein EApolipoprotein E
Sulfated GlycosaminoglycansSulfated Glycosaminoglycans
Alpha 1 anti chymotrypsinAlpha 1 anti chymotrypsin
Protein XProtein X
ComponentComponent
ProteinasesProteinases
Membrane componentsMembrane components

12. MechanismMechanism
1.1. Pool of amyloidogenic precursor proteinsPool of amyloidogenic precursor proteins
2.2. Nidus for fibrillosisNidus for fibrillosis  interactioninteraction
between basement membrane proteinsbetween basement membrane proteins
and Amyloid componentsand Amyloid components
3.3. Partial degradation by macrophages /Partial degradation by macrophages /
RESRES
4.4. ATTR , Ab2M , prionsATTR , Ab2M , prions  not degradednot degraded
5.5. Help of P component in aggregation ,Help of P component in aggregation ,
folding and protectionfolding and protection

13. In AAIn AA
An important role for AEFAn important role for AEF  AmyloidAmyloid
Enhancing FactorEnhancing Factor glyco proteinglyco protein
AEF is seen inAEF is seen in
1.1. CancersCancers
2.2. Familial Mediterranean feverFamilial Mediterranean fever
3.3. Chronic inflammationChronic inflammation

14. MorphologyMorphology
Extra cellular matrix and in the extraExtra cellular matrix and in the extra
cellular basement membranecellular basement membrane
General grossGeneral 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
MicroMicro  extra cellular depositionextra cellular deposition

15. Amyloidosis of kidneyAmyloidosis of kidney
Most commonMost common
Most seriousMost serious
Affects the renal functionAffects the renal function
Mostly SecondaryMostly Secondary
One third of primaryOne third of primary
20 % of Death from Amyloids20 % of Death from Amyloids
Increase permeabilityIncrease permeability  proteinuriaproteinuria 
nephrotic syndromenephrotic syndrome

16. Amyloid spleenAmyloid spleen
Sago spleenSago spleen
Lardaceous spleenLardaceous spleen

19. Amyloid liverAmyloid liver