SlideShare a Scribd company logo
1 of 74
Download to read offline
AMYLOIDOSIS
PRESENTOR-Dr.Navleen Kaur
Department of Pathology
AIMSR Bathinda
MODERATOR-
Dr.ShaffyThukral
LESSON PLAN
• HISTORY
• INTRODUCTION
• PHYSICAL & CHEMICAL NATURE
OF AMYLOID
• CLASSIFICATION
• PATHOGENESIS
• CLINICAL FEATURES
• STAINING CHARACTERISTICS
• MORPHOLOGICAL FEATURES
• DIAGNOSIS
• PROGNOSIS
History
• First described by
Rokitansky in 1842.
• Term first used by
Rudolf Virchow in
1854 based on the
color after staining it
with crude iodine-
staining techniques.
• Later recognized as
Protein by Friedreich
and Kekule 5 years
later.
INTRODUCTION
◎It is derived from the word-amylum in
Latin, amylon in Greek; means cellulose or
starch like.
◎Definition : Amyloid refers to an abnormal
deposit of insoluble polymeric protein
fibrils in tissues and organs.This
condition of deposition of amyloid in
tissues is known as Amyloidosis.
• The fibrils are formed by the aggregation
of misfolded, normally soluble proteins .
• Deposition of amyloid fibrils is usualy
extracellular.
• Amyloidosis or “protein aggregation
diseases” should not be considered as
single disease entity its rather a group of
inherited & inflammatory disorders which
are resposible for tissue damage and
functional compromise.
PHYSICAL NATURE OF AMYLOID
On Electron Microscopy
• These fibrils are
continous, non-
branching,insoluble
, linear, rigid and
measures 7.5 - 10
mm in diameter .
On X-Ray Crystallography
& Infrared spectroscopy
• Characteristic
Beta pleated
sheet
confirmation.
Amyloidosis ppt
• A fibrillary protein (95%) which is
characteristic for each different type of
disease.
• Amyloid P component (5%) consists of
stacks of doughnut-shaped proteins. All
different types of amyloid possess this
protein.
• A glycosoamynoglycan. This is the part
of the molecule responsible for the
positive reaction with iodine.
Chemical nature of amyloid
The main components of amyloid
are:
The most common forms of amyloid fibril
proteins are:
1.Amyloid light chain(AL)-made up of
complete immunoglobulin light chain,
derived from the lambda light chain.
2.Amyloid associated(AA)-derived from a
unique non-Ig protein made by the liver,
derived from larger precursor protein
SAA(serum amyloid associated protein)
others
3.Aβ2 Microglobulin(AβM)-seen in patients
on long term hemodialysis.
4.Transthyretin(TTR) - serum protein
synthesized in liver & transports thyroxine
and retinol.
5.Amyloid β-peptide(Aβ)- seen in
Alzheimers disease.
6.Prion proteins(APrP)
7.Precursor of AA=SAA(Serum Amyloid
Associated Protein)
NON FIBRILLAR AMYLOID PROTEINS
ARE
• 1.Amyloid P(AP) component-found in all
forms of amyloid.
• 2.Apolipoprotein-E (apoE)
• 3.Sulfated glycosaminoglycans(GAGs)
classification
•
Biochemical Structure-based classification
SYSTEMIC VARIANTS
AA (SAA): chronic inflammatory diseases;
periodical fever; Mediterranean fever
AL (Systemic monoclonal light chains Ig):
multiple myeloma, Waldenstroms
macroglobulinemia, B cell lymphoma
Transthyretrin
Normal TTR: senile systemic amyloidosis with
gradual heart involvement
Met30: Familial amyloid polyneuropathy
Met111: Familial amyloid cardiopathy
Aβ2M (β2-microglobulin): haemodialysis-
associated systemic amyloidosis
Local Variants
AL (Locally produced
monoclonal Ig): urogenital;
skin, eyes, respiratory
AANF (abnormal atrial
natriuretic factor): atria
Medin :Aortic amyloidosis in
elderly
Insular amyloid polypeptide/
Amylin Insulinoma, type 2
diabetes
Calcitonin :Medullary thyroid
carcinoma
Prolactin : Pituitary amyloid
Keratin : Cutaneous
amyloidosis
Ocular
Gelsolin :Familial amyloidosis;
Finnish type
Lactoferrin :Familial corneal
amyloidosis
Keratoepithelin: Familial
corneal dystrophies
Hereditary
(Familial systemic
amyloidosis/ Familial
Renal)
Fibrinogen alpha chain
Apolipoprotein AI
Apolipoprotein AII
Lysozyme
Other variants
CNS amyloidosis
Beta protein precursor
:Alzheimer’s disease,
Down syndrome
Prion protein : Creutzfeldt-
Jakob disease,
fatal familial insomnia
Cystatin C :hereditary cerebral
hemorrhage with amyloidosis -
Icelandic type
ABri precursor protein : Familial
dementia British type
ADan precursor protein
:Familial dementia Danish type
PATHOGENESIS
• Amyloidosis results from abnormal folding
of proteins, which become insoluble,
aggregate, and deposit as fibrils in
extracellular tissue.
• Normally, misfolded proteins are degraded
intracellularly by proteasomes or
extracellularly by macrophages.
• In amyloidosis the quality control
mechanism fail so,
there is rise in level of precursor of
fibrillary protein(AL in primary and SAA
in secondary form) followed by partial
degradation by reticuloendothelial cells.
• Non-fibrillary proteins facilitate
aggregation and protection against
solubilisation.
• So all these factors result in deposition of
misfolded protein outside the cells.
Amyloidosis ppt
• The proteins that form amyloid falls in 2
categories:
1.Normal proteins- that have inherent
tendency to fold improperly and form fibrils
when increased in number.
2.Mutant proteins- that are prone to
misfolding and aggregation.
Amyloidosis ppt
Clinical features
• May produce no clinical manifestations or
may cause serious problems & even
death.
• At first features are non specific like
weakness, weight loss, light headedness
or syncope.
Amyloidosis ppt
• Liver-hepatomegaly, ↑ alkaline
phosphatase.
• Spleen-splenomegaly & splenic
dysfunction.
• Heart-congestive heart failure, restrictive
cardiomyopathy, constrictive pericarditis &
amyloid deposits in valves.
KIDNEYS
stage phase course
initial Proteinuria Slowly progressing
Clinical
manifestations
Nephrotic syndrome
Oedema,proteinuria
Hypertensive (rare)
Rapidly
progressing
terminal course Chronic renal failure Relapsing
• Central Nervous System
Dementia(Alzheimers disease)
Hemorrhagic strokes
• Peripheral nervous system
Peripheral neuropathy
• Endocrine organs
hypothyroidism due to infiltration.
• Musculoskeletal
"Shoulder pad sign"
- enlargement of the
anterior shoulder
due to amyloid
deposition in
periarticular soft
tissue.
• Carpal tunnel
syndrome.
Blood vessels
• Increase
susceptibility to
bruising-typical
Raccoon eyes
• Gastrointestinal
amyloidosis-
macrglossia which may
hamper speech.
• In stomach and intestine
may lead to
malabsorption.
Staining chararcteristics of
Amyloid
1.Stain on Gross-
oldest method used
by Virchow on cut
section of gross
specimen is Lugols
Iodine which imparts
mahogany brown
colour to the amyloid
deposit which on
addition of sulfuric
acid turns blue.
2.In routine histological
sections
(hematoxylin and
eosin stains) amyloid
appears amorphous,
eosinophilic, hyaline,
extracellular
substance.
• However all proteins
are stained pink by
eosin and thus this
stain is not specific.
• 3.All amyloids stain pink-red with the Congo
Red stain.
But when these
sections are
viewed with
polarized light
they exhibit a
apple green
birefrigence. This
feature of
amyloid can be
used to identify it
in tissue
sections.
• Loss of Congo Red
staining caused by
pretreatment of the
tissue with
potassium
permanganate is a
useful tool for the
diagnosis of
amyloidosis AA.
4.Metachromatic
stains(rosaniline
dyes) i.e dye
reacts with
amyloid and
undergoes color
change-methyl
voilet/crystal
voilet imparts
rose pink color.
5.Flourescent
stains-
Thioflavin-
T/Thioflavin S-
on ultravoilet
light imparts
yellow
flourescence.
.
• 6.Immunohistochemistry stains-positive with
anti-AA stain
DIAGNOSIS
• Presence of amyloid:
- Evaluation of organ involvement (In-vivo
tests & Imaging )
- Tissue Biopsy and its histology
- Congo red staining
• Type of amyloid:
Immunohistochemistry.
• Mutation type: amino acid sequence
analysis.
INDICATIONS FOR TESTS
• Nephrotic range proteinuria with or without renal
insufficiency
• Unexplained kidney failure
• Non-dilated cardiomyopathy
• Peripheral or autonomic neuropathy
• Hepatomegaly or splenomegaly
• Malabsorption
Particular vigilance should be maintained in
patients with multiple myeloma.
IN VIVO CONGO RED TEST
Intravenous injection of Congo red dye of a known
quantity
↓
Dye gets bound to the amyloid deposits
↓
Serum levels of the dye are decreased.
Disadvantage : risk of anaphylaxis
Imaging techniques
• Technetium scan: Tc 99m pyrophosphate binds
avidly to many types of amyloid.
-strongly positive in pt’s with severe disease.
• Technetium labeled aprotinin more sensitive.
• Quantitative scintigraphy
-Done with iodine-123- labeled serum amyloid P
component (sensitive for AL, ATTR and AA )
• Cardiovascular magnetic resonance imaging
(CMR)
• Research:
- Magnetic Resonance Microimaging
- Near infrared imaging using an oxazine-
derivative probe
• Scintigraphy with radiolabeled serum
amyloid(SAP-SERUM AMYLOID P
component) -component is rapid &
specific test since SAP binds to amyloid, it
gives measure of extent of amyloidosis.
SAP SCANNING
•Iodine-123-labelled
SAP injected.
•Visualize the
scintigraphy
•24hr whole-body
retention of I-123 is
visualised.
•SAP is higher in pts
with Amyloidosis
•Distribution of organ
involvement is seen.
TISSUE DIAGNOSIS
Tissues for biopsy
Subcutaneous fat aspiration (provides enough
material for all investigations) – 60%
Rectal biopsy
Gums
Bone marrow
Others: kidneys, nerves, heart, liver
Organ biopsy: if subcutaneous fat investigation did
not provide diagnosis
Kidney biopsy to determine the cause of nephrotic
syndrome (informativity is 100%)
ABDOMINAL FAT ASPIRATION
• Technique used : FNAC
• ( fine needle aspiration
cytology)
Morphlogical features of
amyloidosis of organs
Amyloidosis of different organs show
variation in morphologic patterns, general
features are:
Grossly-affected organ is large, grey,
waxy and rubbery(firm consistency).
Microscopically,deposits are always
extracellular,begins between the cells
close to the basement membrane and are
amorphous,eosinophilic.
Amyloidosis of KIDNEY
• Most common and serious form.
• Grossly,kidneys may be normal-sized,
enlarged or shrunken in advance cases
because of ischemia.
• C/S is pale, waxy,translucent.
• Microscopically, amyloid deposit
primarily in glomeruli, but arteries,
arterioles and peritubular tissues are also
affected.
Amyloidosis ppt
Glomeruli:
-Begins in mesangium
extending into
capillary walls
glomerulus is flooded by
confluent masses or
interlacing ribbons of
amyloid.
• Homogenous
amorphous
eosinophilic deposits:
H&E
Amyloidosis of spleen
• Amyloidosis of the spleen has two
different anatomical patterns.
• Most commonly, the amyloid deposition is
limited to the splenic follicles, resulting in
the gross appearance of a moderately
enlarged spleen dotted with gray nodules
(so called "sago" spleen). .
Amyloidosis ppt
Alternatively, the
amyloid deposits
may spare the
follicles and
mainly infiltrate
the red pulp
sinuses,
producing a large,
firm spleen
mottled with waxy
discolorations
showing map like
areas
("lardaceous"
spleen)
Microscopicaly
-deposits
involve the red
pulp in the wall
of splenic
sinuses,
small arteries
and
connective
tissue.
Amyloidosis of liver
Grossly, liver is enlarged, pale, waxy & firm.
Microscopically-
Amyloid initially appears in space of
disse(space b/w the hepatocytes &
sinusoidal endothelial cells).
Later,disappearence of hepatocytes occur
due to pressure atrophy.
Vascular involvement & deposits in
kupffer cells are frequent.
Amyloidosis ppt
Amyloidosis of heart
• It may occur in any form of systemic
amyloidosis.
• Grossly,heart is enlarged and firm.
• Epi/endocardium and valves show tiny
nodular deposits.
• Microscopically-focal subendocardial
accumulations,in primary form,deposits
are seen around myocardial fibres in ring
forms also known as ring fibres,
• In localized,deposits seen in left atrium.
Amyloidosis ppt
Brain
Alzheimers disease.
• AD and many other neurodegenerative
disorders belong to the family of protein
misfolding diseases, characterized by
protein self-aggregation and deposition.
• In vivo detection of amyloid plaques &
neurofibrilary tangles in the brain enables
early identification of AD.
• Molecular PET imaging using beta-sheet
binding agents has the potential to be
extended to these wide spectrums of
protein misfolding diseases.
Neurofibrilary Tangles-Alzheimers
disease
Other organs
• Alimentary tract-may occur at any level
from oral cavity to anus, deposits initially
in vessel wall and then adjacent layers of
bowel wall.In tongue can cause
macroglossia.
• Respiratory tract- involved focally or
diffuse from larynx to bronchioles.
LASER Micro-dissection system
Histological examination of tissue section
identifying amyloid deposits
• Identify amyloid deposit
• Laser cut around amyloid deposit
• Tissue drops into microfuge cap
• Tissue is fragmented into peptide
strands and electrophoresed; nature of
protein studied.
Laser Micro-dissection equipment
Instrumental methods
• Ultrasonography: kidney’s size (non-
specific)
• CT scanning: with technetium which
binds to soft-tissue amyloid deposits (to
monitor progression)
• Radiolabeled P-component gamma
scanning: total body burden of amyloid
√ Most useful in AA amyloidosis because
the major sites of deposition are
accessible to the imaging agent
Beta-2-microglobulin
• Carpal tunnel syndrome – most common
(deposits in hands ligaments compress
the nerves).
• Reference range of serum beta-2-
microglobulin concentration of is 1.5-3
mg/L.
• Can be elevated to values of 50-100
mg/L.
• Beta-2-microglobulin levels correlate
with elevated serum creatinine levels
and are inversely related to the glomerular
filtration rate.
OTHER TESTS
• AL-Diagnosis-protein electrophoresis
immunoelectrophoresis of serum and
urine.
• bone marrow aspiration.
• Serum immunoglobulins (to exclude AL)
• In AA amyloidosis : polyclonal
hypergammaglobulinemia
• IL-1,6 levels
• SAA as an exquisitely sensitive acute phase
protein (more sensitive than CRP)
• Immunohistochemistry- to know the type of
amyloid.
Example-anti-AA stain.
Amyloidosis ppt
APPROACH TO
AMYLOIDOSIS
Amyloidosis ppt
PROGNOSIS
• Prognosis with generalized amyloidosis is
poor.
• those with AL amyloidosis have a median
survival rate of 2 years after diagnosis.
KEY CONCEPTS
◎Amyloidosis is a disorder characterized by
extrecellular deposits of misfolded proteins
that aggregates to form insoluble proteins.
◎3 factors causing misfolding-
a)normal proteins-excessive production
b)mutant proteins
c)defective proteolytic degradation
◎Characteristical features
√Fibrillar appearance(Electron microscopy)
√β pleated sheet structure(X-ray diffraction)
√Amorphous eosinophilic appearance(H &
E)
√Apple green bifringence(Congo red
staining)
◎Amyloidosis may be systemic or localized.
AL is the most common type in western
countries and AA is the most common
worldwide.
References
• Immunopathology including Amyloidosis .
In: Mohan H ed. Text book of pathology.
6th ed. Jaypee publication: India, 2010:82-
92
• Amyloid. In Vowles G H, Bancroft J D eds.
Theory and Practice of Histological
Techniques. 6th ed. Churchill Livingstone
Elsevier; 2002: 261-281
• Martin Hintersteiner1, Albert Enz2, Peter
Frey2, Anne-Lise Jaton2, Willy Kinzy1,
Rainer . In vivo detection of amyloid-
deposits by near-infrared imaging using an
oxazine-derivative probe. Nature
Biotechnology 23, 577 - 583 (2005)
• Celeste A, Veera A, Kulkarni
VP,.Nanoparticulate Radiolabelled
Quinolines Detect Amyloid Plaques in
Mouse Models of Alzheimer's Disease.
International Journal of Alzheimer's
Disease. 2009 ;31:32
Amyloidosis ppt

More Related Content

What's hot

Aplastic anemia
Aplastic anemiaAplastic anemia
Aplastic anemiaAsif Zeb
 
Megaloblastic Anaemia: Symptoms, causes, diagnosis, treatment and preventions.
Megaloblastic Anaemia: Symptoms, causes, diagnosis, treatment and preventions.Megaloblastic Anaemia: Symptoms, causes, diagnosis, treatment and preventions.
Megaloblastic Anaemia: Symptoms, causes, diagnosis, treatment and preventions.Lazoi Lifecare Private Limited
 
Autoimmune Hemolytic Anemia (AIHA)
Autoimmune Hemolytic Anemia (AIHA)Autoimmune Hemolytic Anemia (AIHA)
Autoimmune Hemolytic Anemia (AIHA)RGCL
 
Leukemoid and lekoerythroblastic reaction
Leukemoid and lekoerythroblastic reactionLeukemoid and lekoerythroblastic reaction
Leukemoid and lekoerythroblastic reactionSindhuja Yella
 
Pernicious anemia
Pernicious anemia Pernicious anemia
Pernicious anemia Sijo A
 

What's hot (20)

Hemolytic anemia ppt presentation
Hemolytic anemia ppt presentationHemolytic anemia ppt presentation
Hemolytic anemia ppt presentation
 
Aplastic anemia
Aplastic anemiaAplastic anemia
Aplastic anemia
 
Acute leukemias
Acute leukemiasAcute leukemias
Acute leukemias
 
Macrocytic anemia
Macrocytic anemiaMacrocytic anemia
Macrocytic anemia
 
Haemolytic anemia
Haemolytic anemia Haemolytic anemia
Haemolytic anemia
 
Pernicious Anemia
Pernicious  AnemiaPernicious  Anemia
Pernicious Anemia
 
Pathology of WBC Disorders
Pathology of WBC DisordersPathology of WBC Disorders
Pathology of WBC Disorders
 
GIANT CELLS
GIANT CELLSGIANT CELLS
GIANT CELLS
 
Megaloblastic Anaemia: Symptoms, causes, diagnosis, treatment and preventions.
Megaloblastic Anaemia: Symptoms, causes, diagnosis, treatment and preventions.Megaloblastic Anaemia: Symptoms, causes, diagnosis, treatment and preventions.
Megaloblastic Anaemia: Symptoms, causes, diagnosis, treatment and preventions.
 
sideroblastic anemia
sideroblastic anemiasideroblastic anemia
sideroblastic anemia
 
Amyloidosis
 Amyloidosis  Amyloidosis
Amyloidosis
 
Autoimmune Hemolytic Anemia (AIHA)
Autoimmune Hemolytic Anemia (AIHA)Autoimmune Hemolytic Anemia (AIHA)
Autoimmune Hemolytic Anemia (AIHA)
 
Laboratory diagnosis of anemia
Laboratory diagnosis of anemiaLaboratory diagnosis of anemia
Laboratory diagnosis of anemia
 
Chronic myeloid leukemia (CML)
Chronic myeloid leukemia (CML)Chronic myeloid leukemia (CML)
Chronic myeloid leukemia (CML)
 
Leukemoid and lekoerythroblastic reaction
Leukemoid and lekoerythroblastic reactionLeukemoid and lekoerythroblastic reaction
Leukemoid and lekoerythroblastic reaction
 
Microcytic hypochromic anemia
Microcytic hypochromic anemiaMicrocytic hypochromic anemia
Microcytic hypochromic anemia
 
Chronic granulomatous inflammation
Chronic granulomatous inflammationChronic granulomatous inflammation
Chronic granulomatous inflammation
 
Pernicious anemia
Pernicious anemia Pernicious anemia
Pernicious anemia
 
Multiple myeloma
Multiple myelomaMultiple myeloma
Multiple myeloma
 
Multiple myeloma
Multiple myelomaMultiple myeloma
Multiple myeloma
 

Viewers also liked

Viewers also liked (10)

Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
 
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
 
Pulmonary Tuberculosis
Pulmonary TuberculosisPulmonary Tuberculosis
Pulmonary Tuberculosis
 
Infarction
InfarctionInfarction
Infarction
 
Pulmonary tuberculosis (tb)
Pulmonary tuberculosis (tb)Pulmonary tuberculosis (tb)
Pulmonary tuberculosis (tb)
 
Amyloidosis  
Amyloidosis  Amyloidosis  
Amyloidosis  
 
Abdominal Tuberculosis
Abdominal TuberculosisAbdominal Tuberculosis
Abdominal Tuberculosis
 
Abdominal tuberculosis
Abdominal tuberculosisAbdominal tuberculosis
Abdominal tuberculosis
 
Pulmonary tuberculosis ppt
Pulmonary tuberculosis pptPulmonary tuberculosis ppt
Pulmonary tuberculosis ppt
 
Pulmonary tuberculosis..ptt
Pulmonary tuberculosis..pttPulmonary tuberculosis..ptt
Pulmonary tuberculosis..ptt
 

Similar to Amyloidosis ppt

Similar to Amyloidosis ppt (20)

Amylodosis
AmylodosisAmylodosis
Amylodosis
 
Amyloidosis
Amyloidosis Amyloidosis
Amyloidosis
 
Recent advances in amyloidosis
Recent advances in amyloidosis   Recent advances in amyloidosis
Recent advances in amyloidosis
 
CARDIAC AMYLOIDOSIS a brief review – sameer.pptx
CARDIAC AMYLOIDOSIS a brief review – sameer.pptxCARDIAC AMYLOIDOSIS a brief review – sameer.pptx
CARDIAC AMYLOIDOSIS a brief review – sameer.pptx
 
5 immunology-csbrp
5 immunology-csbrp5 immunology-csbrp
5 immunology-csbrp
 
Amyloidoisis
AmyloidoisisAmyloidoisis
Amyloidoisis
 
amyloidosis 2.pdf
amyloidosis 2.pdfamyloidosis 2.pdf
amyloidosis 2.pdf
 
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
 
Amyloidosis BY DR.MULLAPUDI RAMAKRISHNA
Amyloidosis BY DR.MULLAPUDI RAMAKRISHNAAmyloidosis BY DR.MULLAPUDI RAMAKRISHNA
Amyloidosis BY DR.MULLAPUDI RAMAKRISHNA
 
APPROACH TO A CHILD WITH IEM DR GRK.pptx
APPROACH TO A CHILD WITH IEM DR GRK.pptxAPPROACH TO A CHILD WITH IEM DR GRK.pptx
APPROACH TO A CHILD WITH IEM DR GRK.pptx
 
Raynaud's phenomenon.pptx
Raynaud's phenomenon.pptxRaynaud's phenomenon.pptx
Raynaud's phenomenon.pptx
 
AMYLOIDOSIS
AMYLOIDOSISAMYLOIDOSIS
AMYLOIDOSIS
 
Alpha-1 Anti-Trypsin Deficiency (AATD)
Alpha-1 Anti-Trypsin Deficiency (AATD)Alpha-1 Anti-Trypsin Deficiency (AATD)
Alpha-1 Anti-Trypsin Deficiency (AATD)
 
Malakoplakia and amayloidosis of kidney
Malakoplakia and amayloidosis of kidneyMalakoplakia and amayloidosis of kidney
Malakoplakia and amayloidosis of kidney
 
Fri 4 45 pm Weiss Witteles.pdf
Fri 4 45 pm Weiss Witteles.pdfFri 4 45 pm Weiss Witteles.pdf
Fri 4 45 pm Weiss Witteles.pdf
 
Maneesha.pptx
Maneesha.pptxManeesha.pptx
Maneesha.pptx
 
Adrenal Pathology
Adrenal PathologyAdrenal Pathology
Adrenal Pathology
 
Malaria
MalariaMalaria
Malaria
 
Renal amyloidosis
Renal amyloidosisRenal amyloidosis
Renal amyloidosis
 
hemolytic anemia (cell membrane defect)
hemolytic anemia (cell membrane defect)hemolytic anemia (cell membrane defect)
hemolytic anemia (cell membrane defect)
 

Recently uploaded

How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17Celine George
 
Drug Information Services- DIC and Sources.
Drug Information Services- DIC and Sources.Drug Information Services- DIC and Sources.
Drug Information Services- DIC and Sources.raviapr7
 
Vani Magazine - Quarterly Magazine of Seshadripuram Educational Trust
Vani Magazine - Quarterly Magazine of Seshadripuram Educational TrustVani Magazine - Quarterly Magazine of Seshadripuram Educational Trust
Vani Magazine - Quarterly Magazine of Seshadripuram Educational TrustSavipriya Raghavendra
 
Slides CapTechTalks Webinar March 2024 Joshua Sinai.pptx
Slides CapTechTalks Webinar March 2024 Joshua Sinai.pptxSlides CapTechTalks Webinar March 2024 Joshua Sinai.pptx
Slides CapTechTalks Webinar March 2024 Joshua Sinai.pptxCapitolTechU
 
Prescribed medication order and communication skills.pptx
Prescribed medication order and communication skills.pptxPrescribed medication order and communication skills.pptx
Prescribed medication order and communication skills.pptxraviapr7
 
How to Create a Toggle Button in Odoo 17
How to Create a Toggle Button in Odoo 17How to Create a Toggle Button in Odoo 17
How to Create a Toggle Button in Odoo 17Celine George
 
Protein Structure - threading Protein modelling pptx
Protein Structure - threading Protein modelling pptxProtein Structure - threading Protein modelling pptx
Protein Structure - threading Protein modelling pptxvidhisharma994099
 
How to Manage Cross-Selling in Odoo 17 Sales
How to Manage Cross-Selling in Odoo 17 SalesHow to Manage Cross-Selling in Odoo 17 Sales
How to Manage Cross-Selling in Odoo 17 SalesCeline George
 
EBUS5423 Data Analytics and Reporting Bl
EBUS5423 Data Analytics and Reporting BlEBUS5423 Data Analytics and Reporting Bl
EBUS5423 Data Analytics and Reporting BlDr. Bruce A. Johnson
 
Diploma in Nursing Admission Test Question Solution 2023.pdf
Diploma in Nursing Admission Test Question Solution 2023.pdfDiploma in Nursing Admission Test Question Solution 2023.pdf
Diploma in Nursing Admission Test Question Solution 2023.pdfMohonDas
 
3.26.24 Race, the Draft, and the Vietnam War.pptx
3.26.24 Race, the Draft, and the Vietnam War.pptx3.26.24 Race, the Draft, and the Vietnam War.pptx
3.26.24 Race, the Draft, and the Vietnam War.pptxmary850239
 
How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17Celine George
 
P4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdf
P4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdfP4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdf
P4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdfYu Kanazawa / Osaka University
 
In - Vivo and In - Vitro Correlation.pptx
In - Vivo and In - Vitro Correlation.pptxIn - Vivo and In - Vitro Correlation.pptx
In - Vivo and In - Vitro Correlation.pptxAditiChauhan701637
 
Ultra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxUltra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxDr. Asif Anas
 
The Stolen Bacillus by Herbert George Wells
The Stolen Bacillus by Herbert George WellsThe Stolen Bacillus by Herbert George Wells
The Stolen Bacillus by Herbert George WellsEugene Lysak
 
2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx
2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx
2024.03.23 What do successful readers do - Sandy Millin for PARK.pptxSandy Millin
 

Recently uploaded (20)

How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17
 
Drug Information Services- DIC and Sources.
Drug Information Services- DIC and Sources.Drug Information Services- DIC and Sources.
Drug Information Services- DIC and Sources.
 
Vani Magazine - Quarterly Magazine of Seshadripuram Educational Trust
Vani Magazine - Quarterly Magazine of Seshadripuram Educational TrustVani Magazine - Quarterly Magazine of Seshadripuram Educational Trust
Vani Magazine - Quarterly Magazine of Seshadripuram Educational Trust
 
Prelims of Kant get Marx 2.0: a general politics quiz
Prelims of Kant get Marx 2.0: a general politics quizPrelims of Kant get Marx 2.0: a general politics quiz
Prelims of Kant get Marx 2.0: a general politics quiz
 
Slides CapTechTalks Webinar March 2024 Joshua Sinai.pptx
Slides CapTechTalks Webinar March 2024 Joshua Sinai.pptxSlides CapTechTalks Webinar March 2024 Joshua Sinai.pptx
Slides CapTechTalks Webinar March 2024 Joshua Sinai.pptx
 
Prescribed medication order and communication skills.pptx
Prescribed medication order and communication skills.pptxPrescribed medication order and communication skills.pptx
Prescribed medication order and communication skills.pptx
 
How to Create a Toggle Button in Odoo 17
How to Create a Toggle Button in Odoo 17How to Create a Toggle Button in Odoo 17
How to Create a Toggle Button in Odoo 17
 
Protein Structure - threading Protein modelling pptx
Protein Structure - threading Protein modelling pptxProtein Structure - threading Protein modelling pptx
Protein Structure - threading Protein modelling pptx
 
How to Manage Cross-Selling in Odoo 17 Sales
How to Manage Cross-Selling in Odoo 17 SalesHow to Manage Cross-Selling in Odoo 17 Sales
How to Manage Cross-Selling in Odoo 17 Sales
 
EBUS5423 Data Analytics and Reporting Bl
EBUS5423 Data Analytics and Reporting BlEBUS5423 Data Analytics and Reporting Bl
EBUS5423 Data Analytics and Reporting Bl
 
Diploma in Nursing Admission Test Question Solution 2023.pdf
Diploma in Nursing Admission Test Question Solution 2023.pdfDiploma in Nursing Admission Test Question Solution 2023.pdf
Diploma in Nursing Admission Test Question Solution 2023.pdf
 
3.26.24 Race, the Draft, and the Vietnam War.pptx
3.26.24 Race, the Draft, and the Vietnam War.pptx3.26.24 Race, the Draft, and the Vietnam War.pptx
3.26.24 Race, the Draft, and the Vietnam War.pptx
 
How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17
 
March 2024 Directors Meeting, Division of Student Affairs and Academic Support
March 2024 Directors Meeting, Division of Student Affairs and Academic SupportMarch 2024 Directors Meeting, Division of Student Affairs and Academic Support
March 2024 Directors Meeting, Division of Student Affairs and Academic Support
 
Finals of Kant get Marx 2.0 : a general politics quiz
Finals of Kant get Marx 2.0 : a general politics quizFinals of Kant get Marx 2.0 : a general politics quiz
Finals of Kant get Marx 2.0 : a general politics quiz
 
P4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdf
P4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdfP4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdf
P4C x ELT = P4ELT: Its Theoretical Background (Kanazawa, 2024 March).pdf
 
In - Vivo and In - Vitro Correlation.pptx
In - Vivo and In - Vitro Correlation.pptxIn - Vivo and In - Vitro Correlation.pptx
In - Vivo and In - Vitro Correlation.pptx
 
Ultra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxUltra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptx
 
The Stolen Bacillus by Herbert George Wells
The Stolen Bacillus by Herbert George WellsThe Stolen Bacillus by Herbert George Wells
The Stolen Bacillus by Herbert George Wells
 
2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx
2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx
2024.03.23 What do successful readers do - Sandy Millin for PARK.pptx
 

Amyloidosis ppt

  • 1. AMYLOIDOSIS PRESENTOR-Dr.Navleen Kaur Department of Pathology AIMSR Bathinda MODERATOR- Dr.ShaffyThukral
  • 2. LESSON PLAN • HISTORY • INTRODUCTION • PHYSICAL & CHEMICAL NATURE OF AMYLOID • CLASSIFICATION • PATHOGENESIS • CLINICAL FEATURES • STAINING CHARACTERISTICS • MORPHOLOGICAL FEATURES • DIAGNOSIS • PROGNOSIS
  • 3. History • First described by Rokitansky in 1842. • Term first used by Rudolf Virchow in 1854 based on the color after staining it with crude iodine- staining techniques. • Later recognized as Protein by Friedreich and Kekule 5 years later.
  • 4. INTRODUCTION ◎It is derived from the word-amylum in Latin, amylon in Greek; means cellulose or starch like. ◎Definition : Amyloid refers to an abnormal deposit of insoluble polymeric protein fibrils in tissues and organs.This condition of deposition of amyloid in tissues is known as Amyloidosis.
  • 5. • The fibrils are formed by the aggregation of misfolded, normally soluble proteins . • Deposition of amyloid fibrils is usualy extracellular. • Amyloidosis or “protein aggregation diseases” should not be considered as single disease entity its rather a group of inherited & inflammatory disorders which are resposible for tissue damage and functional compromise.
  • 6. PHYSICAL NATURE OF AMYLOID On Electron Microscopy • These fibrils are continous, non- branching,insoluble , linear, rigid and measures 7.5 - 10 mm in diameter .
  • 7. On X-Ray Crystallography & Infrared spectroscopy • Characteristic Beta pleated sheet confirmation.
  • 9. • A fibrillary protein (95%) which is characteristic for each different type of disease. • Amyloid P component (5%) consists of stacks of doughnut-shaped proteins. All different types of amyloid possess this protein. • A glycosoamynoglycan. This is the part of the molecule responsible for the positive reaction with iodine. Chemical nature of amyloid The main components of amyloid are:
  • 10. The most common forms of amyloid fibril proteins are: 1.Amyloid light chain(AL)-made up of complete immunoglobulin light chain, derived from the lambda light chain. 2.Amyloid associated(AA)-derived from a unique non-Ig protein made by the liver, derived from larger precursor protein SAA(serum amyloid associated protein) others 3.Aβ2 Microglobulin(AβM)-seen in patients on long term hemodialysis.
  • 11. 4.Transthyretin(TTR) - serum protein synthesized in liver & transports thyroxine and retinol. 5.Amyloid β-peptide(Aβ)- seen in Alzheimers disease. 6.Prion proteins(APrP) 7.Precursor of AA=SAA(Serum Amyloid Associated Protein)
  • 12. NON FIBRILLAR AMYLOID PROTEINS ARE • 1.Amyloid P(AP) component-found in all forms of amyloid. • 2.Apolipoprotein-E (apoE) • 3.Sulfated glycosaminoglycans(GAGs)
  • 14. Biochemical Structure-based classification SYSTEMIC VARIANTS AA (SAA): chronic inflammatory diseases; periodical fever; Mediterranean fever AL (Systemic monoclonal light chains Ig): multiple myeloma, Waldenstroms macroglobulinemia, B cell lymphoma Transthyretrin Normal TTR: senile systemic amyloidosis with gradual heart involvement Met30: Familial amyloid polyneuropathy Met111: Familial amyloid cardiopathy Aβ2M (β2-microglobulin): haemodialysis- associated systemic amyloidosis
  • 15. Local Variants AL (Locally produced monoclonal Ig): urogenital; skin, eyes, respiratory AANF (abnormal atrial natriuretic factor): atria Medin :Aortic amyloidosis in elderly Insular amyloid polypeptide/ Amylin Insulinoma, type 2 diabetes Calcitonin :Medullary thyroid carcinoma Prolactin : Pituitary amyloid Keratin : Cutaneous amyloidosis Ocular Gelsolin :Familial amyloidosis; Finnish type Lactoferrin :Familial corneal amyloidosis Keratoepithelin: Familial corneal dystrophies
  • 16. Hereditary (Familial systemic amyloidosis/ Familial Renal) Fibrinogen alpha chain Apolipoprotein AI Apolipoprotein AII Lysozyme Other variants CNS amyloidosis Beta protein precursor :Alzheimer’s disease, Down syndrome Prion protein : Creutzfeldt- Jakob disease, fatal familial insomnia Cystatin C :hereditary cerebral hemorrhage with amyloidosis - Icelandic type ABri precursor protein : Familial dementia British type ADan precursor protein :Familial dementia Danish type
  • 17. PATHOGENESIS • Amyloidosis results from abnormal folding of proteins, which become insoluble, aggregate, and deposit as fibrils in extracellular tissue. • Normally, misfolded proteins are degraded intracellularly by proteasomes or extracellularly by macrophages. • In amyloidosis the quality control mechanism fail so,
  • 18. there is rise in level of precursor of fibrillary protein(AL in primary and SAA in secondary form) followed by partial degradation by reticuloendothelial cells. • Non-fibrillary proteins facilitate aggregation and protection against solubilisation. • So all these factors result in deposition of misfolded protein outside the cells.
  • 20. • The proteins that form amyloid falls in 2 categories: 1.Normal proteins- that have inherent tendency to fold improperly and form fibrils when increased in number. 2.Mutant proteins- that are prone to misfolding and aggregation.
  • 22. Clinical features • May produce no clinical manifestations or may cause serious problems & even death. • At first features are non specific like weakness, weight loss, light headedness or syncope.
  • 24. • Liver-hepatomegaly, ↑ alkaline phosphatase. • Spleen-splenomegaly & splenic dysfunction. • Heart-congestive heart failure, restrictive cardiomyopathy, constrictive pericarditis & amyloid deposits in valves.
  • 25. KIDNEYS stage phase course initial Proteinuria Slowly progressing Clinical manifestations Nephrotic syndrome Oedema,proteinuria Hypertensive (rare) Rapidly progressing terminal course Chronic renal failure Relapsing
  • 26. • Central Nervous System Dementia(Alzheimers disease) Hemorrhagic strokes • Peripheral nervous system Peripheral neuropathy • Endocrine organs hypothyroidism due to infiltration.
  • 27. • Musculoskeletal "Shoulder pad sign" - enlargement of the anterior shoulder due to amyloid deposition in periarticular soft tissue. • Carpal tunnel syndrome.
  • 28. Blood vessels • Increase susceptibility to bruising-typical Raccoon eyes
  • 29. • Gastrointestinal amyloidosis- macrglossia which may hamper speech. • In stomach and intestine may lead to malabsorption.
  • 30. Staining chararcteristics of Amyloid 1.Stain on Gross- oldest method used by Virchow on cut section of gross specimen is Lugols Iodine which imparts mahogany brown colour to the amyloid deposit which on addition of sulfuric acid turns blue.
  • 31. 2.In routine histological sections (hematoxylin and eosin stains) amyloid appears amorphous, eosinophilic, hyaline, extracellular substance. • However all proteins are stained pink by eosin and thus this stain is not specific.
  • 32. • 3.All amyloids stain pink-red with the Congo Red stain.
  • 33. But when these sections are viewed with polarized light they exhibit a apple green birefrigence. This feature of amyloid can be used to identify it in tissue sections.
  • 34. • Loss of Congo Red staining caused by pretreatment of the tissue with potassium permanganate is a useful tool for the diagnosis of amyloidosis AA.
  • 35. 4.Metachromatic stains(rosaniline dyes) i.e dye reacts with amyloid and undergoes color change-methyl voilet/crystal voilet imparts rose pink color.
  • 38. DIAGNOSIS • Presence of amyloid: - Evaluation of organ involvement (In-vivo tests & Imaging ) - Tissue Biopsy and its histology - Congo red staining • Type of amyloid: Immunohistochemistry. • Mutation type: amino acid sequence analysis.
  • 39. INDICATIONS FOR TESTS • Nephrotic range proteinuria with or without renal insufficiency • Unexplained kidney failure • Non-dilated cardiomyopathy • Peripheral or autonomic neuropathy • Hepatomegaly or splenomegaly • Malabsorption Particular vigilance should be maintained in patients with multiple myeloma.
  • 40. IN VIVO CONGO RED TEST Intravenous injection of Congo red dye of a known quantity ↓ Dye gets bound to the amyloid deposits ↓ Serum levels of the dye are decreased. Disadvantage : risk of anaphylaxis
  • 41. Imaging techniques • Technetium scan: Tc 99m pyrophosphate binds avidly to many types of amyloid. -strongly positive in pt’s with severe disease. • Technetium labeled aprotinin more sensitive. • Quantitative scintigraphy -Done with iodine-123- labeled serum amyloid P component (sensitive for AL, ATTR and AA ) • Cardiovascular magnetic resonance imaging (CMR) • Research: - Magnetic Resonance Microimaging - Near infrared imaging using an oxazine- derivative probe
  • 42. • Scintigraphy with radiolabeled serum amyloid(SAP-SERUM AMYLOID P component) -component is rapid & specific test since SAP binds to amyloid, it gives measure of extent of amyloidosis.
  • 43. SAP SCANNING •Iodine-123-labelled SAP injected. •Visualize the scintigraphy •24hr whole-body retention of I-123 is visualised. •SAP is higher in pts with Amyloidosis •Distribution of organ involvement is seen.
  • 44. TISSUE DIAGNOSIS Tissues for biopsy Subcutaneous fat aspiration (provides enough material for all investigations) – 60% Rectal biopsy Gums Bone marrow Others: kidneys, nerves, heart, liver Organ biopsy: if subcutaneous fat investigation did not provide diagnosis Kidney biopsy to determine the cause of nephrotic syndrome (informativity is 100%)
  • 45. ABDOMINAL FAT ASPIRATION • Technique used : FNAC • ( fine needle aspiration cytology)
  • 46. Morphlogical features of amyloidosis of organs Amyloidosis of different organs show variation in morphologic patterns, general features are: Grossly-affected organ is large, grey, waxy and rubbery(firm consistency). Microscopically,deposits are always extracellular,begins between the cells close to the basement membrane and are amorphous,eosinophilic.
  • 47. Amyloidosis of KIDNEY • Most common and serious form. • Grossly,kidneys may be normal-sized, enlarged or shrunken in advance cases because of ischemia. • C/S is pale, waxy,translucent. • Microscopically, amyloid deposit primarily in glomeruli, but arteries, arterioles and peritubular tissues are also affected.
  • 49. Glomeruli: -Begins in mesangium extending into capillary walls glomerulus is flooded by confluent masses or interlacing ribbons of amyloid. • Homogenous amorphous eosinophilic deposits: H&E
  • 50. Amyloidosis of spleen • Amyloidosis of the spleen has two different anatomical patterns. • Most commonly, the amyloid deposition is limited to the splenic follicles, resulting in the gross appearance of a moderately enlarged spleen dotted with gray nodules (so called "sago" spleen). .
  • 52. Alternatively, the amyloid deposits may spare the follicles and mainly infiltrate the red pulp sinuses, producing a large, firm spleen mottled with waxy discolorations showing map like areas ("lardaceous" spleen)
  • 53. Microscopicaly -deposits involve the red pulp in the wall of splenic sinuses, small arteries and connective tissue.
  • 54. Amyloidosis of liver Grossly, liver is enlarged, pale, waxy & firm. Microscopically- Amyloid initially appears in space of disse(space b/w the hepatocytes & sinusoidal endothelial cells). Later,disappearence of hepatocytes occur due to pressure atrophy. Vascular involvement & deposits in kupffer cells are frequent.
  • 56. Amyloidosis of heart • It may occur in any form of systemic amyloidosis. • Grossly,heart is enlarged and firm. • Epi/endocardium and valves show tiny nodular deposits. • Microscopically-focal subendocardial accumulations,in primary form,deposits are seen around myocardial fibres in ring forms also known as ring fibres, • In localized,deposits seen in left atrium.
  • 58. Brain Alzheimers disease. • AD and many other neurodegenerative disorders belong to the family of protein misfolding diseases, characterized by protein self-aggregation and deposition. • In vivo detection of amyloid plaques & neurofibrilary tangles in the brain enables early identification of AD. • Molecular PET imaging using beta-sheet binding agents has the potential to be extended to these wide spectrums of protein misfolding diseases.
  • 60. Other organs • Alimentary tract-may occur at any level from oral cavity to anus, deposits initially in vessel wall and then adjacent layers of bowel wall.In tongue can cause macroglossia. • Respiratory tract- involved focally or diffuse from larynx to bronchioles.
  • 61. LASER Micro-dissection system Histological examination of tissue section identifying amyloid deposits • Identify amyloid deposit • Laser cut around amyloid deposit • Tissue drops into microfuge cap • Tissue is fragmented into peptide strands and electrophoresed; nature of protein studied.
  • 63. Instrumental methods • Ultrasonography: kidney’s size (non- specific) • CT scanning: with technetium which binds to soft-tissue amyloid deposits (to monitor progression) • Radiolabeled P-component gamma scanning: total body burden of amyloid √ Most useful in AA amyloidosis because the major sites of deposition are accessible to the imaging agent
  • 64. Beta-2-microglobulin • Carpal tunnel syndrome – most common (deposits in hands ligaments compress the nerves). • Reference range of serum beta-2- microglobulin concentration of is 1.5-3 mg/L. • Can be elevated to values of 50-100 mg/L. • Beta-2-microglobulin levels correlate with elevated serum creatinine levels and are inversely related to the glomerular filtration rate.
  • 65. OTHER TESTS • AL-Diagnosis-protein electrophoresis immunoelectrophoresis of serum and urine. • bone marrow aspiration. • Serum immunoglobulins (to exclude AL) • In AA amyloidosis : polyclonal hypergammaglobulinemia • IL-1,6 levels • SAA as an exquisitely sensitive acute phase protein (more sensitive than CRP) • Immunohistochemistry- to know the type of amyloid. Example-anti-AA stain.
  • 69. PROGNOSIS • Prognosis with generalized amyloidosis is poor. • those with AL amyloidosis have a median survival rate of 2 years after diagnosis.
  • 70. KEY CONCEPTS ◎Amyloidosis is a disorder characterized by extrecellular deposits of misfolded proteins that aggregates to form insoluble proteins. ◎3 factors causing misfolding- a)normal proteins-excessive production b)mutant proteins c)defective proteolytic degradation
  • 71. ◎Characteristical features √Fibrillar appearance(Electron microscopy) √β pleated sheet structure(X-ray diffraction) √Amorphous eosinophilic appearance(H & E) √Apple green bifringence(Congo red staining) ◎Amyloidosis may be systemic or localized. AL is the most common type in western countries and AA is the most common worldwide.
  • 72. References • Immunopathology including Amyloidosis . In: Mohan H ed. Text book of pathology. 6th ed. Jaypee publication: India, 2010:82- 92 • Amyloid. In Vowles G H, Bancroft J D eds. Theory and Practice of Histological Techniques. 6th ed. Churchill Livingstone Elsevier; 2002: 261-281
  • 73. • Martin Hintersteiner1, Albert Enz2, Peter Frey2, Anne-Lise Jaton2, Willy Kinzy1, Rainer . In vivo detection of amyloid- deposits by near-infrared imaging using an oxazine-derivative probe. Nature Biotechnology 23, 577 - 583 (2005) • Celeste A, Veera A, Kulkarni VP,.Nanoparticulate Radiolabelled Quinolines Detect Amyloid Plaques in Mouse Models of Alzheimer's Disease. International Journal of Alzheimer's Disease. 2009 ;31:32