2. What is
AMYLOIDOSIS?
?
Amyloidosis refers to a
group of protein misfolding
diseases characterized by
deposition of a particular
amyloid protein in various
organs and tissues of
animals and humans.
-University of Georgia, 43 Brighton Road, Tifton, GA 31793, USA
Amyloidosis in
kidney
3. Deposition of protein but the term
‘AMYLOID’ – Why??
It is the generic term used.
Amyloid is not a specific term but used
for variety of proteinaceous substances.
“At one time Amyloid was thought to be a
starch-like hence the name Amyloid
given”
Amylum- Starch Amyloid- Starch like
4. Amyloid and Starch
Amyloid resembles starch in some of
its chemical reactions
Reaction with Iodine
When cut surfaces of affected organ
painted with Iodine Amyloid stains
yellow red.
This colour changes to blue or violet
on application of dil. H2SO4.
Amyloid in kidney
painted with Iodine
“This technique was first used by Rudolf Virchow and
he interpreted the substance as Amyloid”
5. Histological Pathology
With H&E stain
Amyloid appear as a:
Amorphous(shapeless)
Eosinophillic
Hyaline- homogenous and
translucent
Extracellular substance
6.
7. Difference between Hyaline and Amyloid
Hyaline and Amyloid as both substances are
undifferentiated visually thus histochemical
technique is used to differentiate them.
CONGO RED STAIN used which impart
Amyloid a ‘pink’ or ‘red’ colour
YELLOW GREEN BIREFRINGENSE of
Congo red stained amyloid is observed under
POLARIZING MICROSCOPY
8. Congo red staining shows apple
green birefringence under
Polarizing Microscopy
9. Is Amyloid a single entity??
No amyloid is not a single entity
Two major and several biochemical forms exist
all deposited by different pathogenic
mechanisms.
“Amyloidosis is not single disease but a group of
diseases that share deposition of similar
looking proteins”
Uniform morphological appearance and staining
characteristics are due to remarkable constant
physical organisation of amyloid protein.
10. Physical nature of
AMYLOIDAmyloid occur to be made up of non branching
fibrils of indefinite length and 7.5 to 10nm
width
About 95% of any deposition consists of fibril
proteins and rest 5% being the non fibrillated
glycoprotein (P component) and proteoglycans
The characteristic pattern of these fibrils is
typically “beta pleated sheet structure”
11. Any fibrillar protein
deposited in tissues that
yields a beta pleated sheet
will be seen as Amyloid
This conformation is always
seen regardless of the
clinical disorder or the
chemical composition
“The structure is responsible for
characteristics staining& optical properties of
amyloid”
12. Chemical nature of Amyloid
15 different biochemical forms of Amyloid is
identified of them two are more common
1.AL (Amyloid light chains): Derived from plasma
cells and contains immunoglobulin light chains
2.AA(Amyloid associated): Non immunoglobulin
synthesized by the liver
Both of them are antigenically distinct and found in
different clinical conditions
13. Amyloid light chain proteins
Made of complete
immunoglobulin light chains or
their fragments or both
Its deposition is associated
with some form of
‘MONOCLONAL B-cell
proliferation
14. Amyloid associated (AA) proteins
Composed of protein that does not have structural
similarity with immunoglobulin
Deposited during ‘CHRONIC INFLAMMATORY
DISEASE’
Derived from larger serum precursor protein
synthesized in the liver called SAA (serum amyloid
associated proteins)
18. Occurence
1.Most common in humans but also
occur in all domestic animals
2.Common in
Dog Cattle Horse &Chicken
3.It may occur in a particular area or
all over body i.e,
Local & Generalised respectively
4.Most common in
Spleen Liver & Kidney
23. Primary Amyloidosis
• Associated with Immunological dyscrasia
•It occur in patients that do not have any
underlying detectable disease
•Occur due to deposition of Ig light chains their
fragments or both
•Associated with monoclonal proliferation
•Most common form Multiple myeloma a
malignant neoplasm of plasma cells due to
Monoclonal Gammopathy
25. Bence Jones Proteins
•In addition to whole Ig molecule plasma cells
also secrete only lambda or kappa light chains
•The two light chains are called as Bence Jones
proteins
•Presence of Bence jones proteins is not only
enough to produce amyloidosis
• Amyloidogenic potential and their subsequent
degradation influence the Bence Jones Proteins
26. Secondary Amyloidosis
•Called secondary as It occurs as an complication of
any underlying chronic inflammatory or tissue
destructive processes
•The deposits are composed of AA proteins
•Examples: seen in Tuberculosis, Bronchiectasis,
Chronic osteomyelitis.
•Also in AUTOIMMUNE DISORDRES like ‘Rheumatoid
Arthritis’
31. ProgressiveDeposition of Amyloid occurs in perivascular
space between blood vessels and in other cells cause
1. Extracellular amyloid encroaches and produce
Atrophy of adjacent cells
2. Degeneration and necrosis of surrounding cells due
to improper or no gaseous exchange
3. Pressure of Amyloid increasing cause Stenosis
4. Ischaemia in the portion involved
32. Amyloidosis in Spleen
1. Amyloid forms a cuff around central artery of spleenic
follicle
2. Amyloid increases in spleenic pulp and cause
‘LARDACEOUS SPLEEN’
3. Progressively accumulation around central artery
causes ‘SAGO SPLEEN’
4. When diffused, spleen get swollen, firm, greyish in
colour and waxy at cut surface
35. Amyloidosis in Liver
The organ get :
1. Very enlarged
2. Edges get rounded
3. Doughy Consistency
4. Pits on pressure
5. ‘Cyanotic yellow’ in colour
6. Friable rupture easily and capsule is under strain
7. Death due to hepatic rupture and Haemorrhage into
peritoneal cavity
8. Fatty change
9. Hepatic rupture usually observed in HORSE
38. Amyloidosis in Kidney
1. Occur in glomeruli of kidney between capillary
endothelium and that of glomeruli
2. Most damage due to obliteration of blood circulation
3. The Ischaemia occurred cause Atrophy, Fatty change,
and necrosis
4. Kidney bulged & mottled red and yellow appearance
5. Kidney become large in cattle
6. Uraemia and death occur before fibrosis and scaring
40. Amyloidosis in other organs
1. Occur in Islets of Langerhans
2. Amyloid deposited between capillaries and
islets
3. Commonly occur in conjunctiva of HORSE and
cause blindness
4. Amyloidosis of Respiratory passage and skin
also observed in Horses
41. Significance and results
Amyloidosis can remain unidentified in Necropsy
findings
Amyloid deposition is a ‘permanent change’ and
remain persist for life of life of individual
Stop depositing if the inciting cause is removed
However what is already deposited remain in tissues
for ever
Effect vital organs seriously like
Kidney – Uraemia
Pancreas - diabetes
Liver – Hepatic rupture
