SlideShare a Scribd company logo
AMYLOIDOSIS
DR. PAMELA NAYAK
(PATHOLOGY DEPT, MMCH)
TOPICS OF DISCUSSION
 Definition
 Pathogenesis
 Properties of Amyloid
- Physical
- Chemical
 Classification
 Morphology
 Clinical presentation
 Diagnosis
Amyloidosis - Introduction
 Disorder characterized by extracellular
deposition of amyloid (fibrillar proteinaceous
substance)
 Amyloid fibril – made of misfolded protein
 Amyloid = amylose (starch) like
They have staining characteristic similar to
starch but they are unrelated to starch.
 Associated with a number of inherited and
inflammatory disorder
Amyloidosis - Definition
Amyloidosis is a disorder characterized by
the extracellular deposits of misfolded
proteins that aggregate to form insoluble
fibrils leads to tissue damage and functional
compromise.
Amyloidosis - Pathogenesis
Intracellularly in
proteasomes
Extracellularly by
macrophages
Normally
degraded
Misfolded proteins
Amyloidosis – this normal control mechanism fails
Misfolded protein accumulates outside cells.
Amyloidosis - Pathogenesis
Two categories of proteins that form Amyloid
Amyloidosis:
1. Localized: involves single organ
2. Systemic: involves multiple organs or tissues
Effect: tissue damage and compromised function
Normal proteins that have
inherent tendency to misfold
(excessive production)
Mutant proteins that
are prone to
misfolding
Amyloid – chemical nature
>20 chemically distinct amyloid exist
Most common forms:
AL (Amyloid light
chain)
AA (Amyloid
associated)
(Aβ) β-amyloid
proteins
• Complete Ig
light chain or
• Amino terminal
fragments of
light chain or
both
• (λ >> κ)
• Non Ig protein
• Synthesized by
liver
• Precursor protein
SAA
• Increased
synthesis in
inflammatory state
• Found in
Alzheimer disease
• Derived from
Amyloid precursor
protein
Amyloid - chemical nature
Rare chemical forms:
1. Transthyretin (TTR) - mutant & normal
2. β2-microglobulin (Aβ2m) – long term hemodialysis
3. Misfolded prion proteins
4. Serum amyloid P component – contribute to
amyloid deposition by stabilizing the fibrils and
decreasing their clearance
Amyloid – physical nature
Electron
microscopy:
Continuous non-
branching fibril
Diameter –
7.5 – 10 nm
X-ray crystallography &
Infrared spectroscopy
Cross β-pleated sheet
conformation
Common to all amyloid
protein
Responsible for their
distinctive Congo red
staining and birefringence
Pathogenesis :
Major forms of Amyloid fibrils
Amyloidosis – classification
1. Primary amyloidosis
2. Reactive systemic amyloidosis
3. Heredofamilial amyloidosis
4. Hemodialysis associated amyloidosis
5. Localized amyloidosis
6. Endocrine amyloidosis
7. Amyloid of aging
Amyloidosis – classification
1. Primary amyloidosis:
- Plasma cell disorder associated
- AL type amyloid protein
- Ig secreted by clonal plasma cell prone to form
Amyloid (due to its intrinsic physio-chemical
properties)
5 - 15% multiple myeloma cases develop
amyloidosis (not all)
- Amyloidogenic potential of particular chain
depends upon its specific amino acid sequence.
Amyloidosis – classification
Contd…
Most of AL amyloid do not have overt
multiple myeloma or clonal B cell neoplasm
- But they are classified as primary
amyloidosis (their presentation is due to amyloid
deposition without any associated disease)
- Modest increase in plasma cell noted in
marrow without any tumor effect
(monoclonal gummopathy)
Amyloidosis – classification
2. Reactive systemic amyloidosis:
(also k/a secondary amyloidosis)
- Associated with inflammatory condition
- AA type amyloid protein
- Common association
Rheumatoid arthritis (MC) – 3%, half of them clinically significant
Ankylosing spondylitis
Inflammatory bowel disease
(previously common association – TB, bronchiectasis, chronic
osteomyelitis)
Other cause – Heroine abuse, solid tumors (RCC, HL)
Amyloidosis – classification
Reactive systemic amyloidosis:
Inflammation  IL6 & IL1  Liver  SAA
synthesis ( )
normally degrade
Soluble end products
Monocyte
derived
enzyme
SAA
Genetically derived
mutant SAA
- Resistant to
degradation
Insoluble AA molecule
Amyloidosis – classification
3. Heredofamilial Amyloidosis:
 Rare & occur in limited geographic area
 Familial Mediterranean fever (AR inheritence) – MC
- AA type amyloid protein,
- Related to the recurrent bouts of inflammation.
 Familial amyloidotic polyneuropathy –mTTR
4. Hemodialysis associated amyloidosis:
- Patients on long-term hemodialysis
- deposition of β2-microglobulin
- cannot be filtered through dialysis membranes
5. Localized Amyloidosis:
- Involves single organ
- Macroscopically normal or nodular deposits
- Lung, larynx skin, urinary bladder, tongue
- In some cases surrounded by lymphocytes
and plasma cell & AL type amyloid.
Amyloidosis – classification
6. Endocrine amyloidosis:
- Microscopic deposits of localized amyloid
 found in certain endocrine tumors, such as
- medullary carcinoma of the thyroid gland,
- islet tumors of the pancreas,
- pheochromocytomas, and
- undifferentiated carcinomas of the stomach, and
- in the islets of Langerhans in individuals with type II
diabetes mellitus.
 Amyloidogenic proteins seem to be derived either from
- polypeptide hormones (e.g., medullary carcinoma) or
- unique proteins (e.g., islet amyloid polypeptide).
Amyloidosis – classification
7. Amyloid of aging
Senile systemic amyloidosis:
- systemic deposition of amyloid
- in elderly patients (usually in their 70s and
80s).
- previously called senile cardiac amyloidosis.
(Because of the dominant involvement and
related dysfunction of the heart)
- The amyloid in this form is composed of the
normal TTR molecule.
Amyloidosis –
Organ involvement
No consistent or distinctive pattern of
amyloid deposit
Predominant organ involvement
Primary
amyloidosis
Secondary
amyloidosis
Familial Mediterranean
fever
• Heart
• G I Tract
• Respiratory
organs
• Peripheral
nerves
• Skin
• Tongue
• Kidney
• Liver
• Spleen
• Lymphnodes
• Adrenals
• Thyroid
• Kidney
• Blood vessels
• Spleen
• Respiratory tract
• Liver (rarely)
Amyloidosis – morphology
Macroscopically:
Involved organs
- Enlarged
- Grey in appearance
- Waxy, firm in
consistency
Amyloidosis - Morphology
Microscopic:
- Extracellular
deposit
- Often adjacent to
basement
membrane
- In advanced
stage, encroach,
surrounds and
destroying the
cell
Amyloidosis - kidney
Most common and
potentially most serious
form of organ
involvement
Gross – normal or
shrunken [due to ischemia
(vascular narrowing) in
advanced stage]
Microscopy – glomerular
deposit, interstitial,
peritubular, arterial wall
deposit
Amyloidosis - spleen
One of two patterns of deposition
is seen.
 Sago spleen - deposits are
largely limited to the splenic
follicles, producing tapioca-like
granules grossly.
 Lardaceous spleen – amyloid
involves the walls of the splenic
sinuses and connective tissue
framework in the red pulp.
Fusion of the early deposits
gives rise to large, map like
areas of amyloidosis.
Amyloidosis –
Clinical manifestation
Amyloidosis may be found as
 an unsuspected anatomic change,
 having produced no clinical manifestations, or
 it may cause death.
The symptoms depend on
 the magnitude of the deposits and
 on the particular sites or organs affected.
Amyloidosis –
Clinical manifestation
Clinical manifestations at first are often entirely
nonspecific, such as –
 Weakness,
 Weight loss,
 Lightheadedness, or
 Syncope
Somewhat more specific findings appear later and
most often relate to renal, cardiac, and
gastrointestinal involvement.
Amyloidosis - Diagnosis
Histologic demonstration of amyloid deposits in tissues.
The most common sites biopsied are
- The kidney, (when renal manifestations are present), or
- Rectal or gingival tissues
(in patients suspected of having systemic amyloidosis)
 Abdominal fat aspirates can also be used for the
diagnosis of systemic amyloidosis. (Congo red stain)
(The test is quite specific, but its sensitivity is low)
 Scintigraphy with radiolabelled serum amyloid P
(SAP)
- Rapid and specific test
- Also measures extent of amyloidosis
Amyloidosis - Diagnosis
Congo red stain
- Light microscopy –
pink or red color
deposit
- Polarized
microscope – Apple-
green birefringence
EM - Confirmatory
Amyloidosis - prognosis
 The prognosis for individuals with generalized amyloidosis is poor.
 Immunocyte derived amyloidosis (not including multiple myeloma) -
median survival of 2 years after diagnosis.
 Persons with myeloma-associated amyloidosis have a poorer prognosis.
 Reactive systemic amyloidosis - somewhat better and depends to
some extent on the control of the underlying condition.
 New therapeutic strategies aimed at
- Correcting protein misfolding and
- Inhibiting fibrillogenesis are being developed.
THANK YOU

More Related Content

What's hot

Acute inflammation
Acute inflammationAcute inflammation
Acute inflammation
Dr. Varughese George
 
Pathology neoplasm
Pathology  neoplasmPathology  neoplasm
Pathology neoplasmMBBS IMS MSU
 
Amyloidosis and pathological calcification
Amyloidosis and pathological calcificationAmyloidosis and pathological calcification
Amyloidosis and pathological calcification
Dr Neha Mahajan
 
Pathologic Calcification
Pathologic CalcificationPathologic Calcification
Pathologic Calcification
SADDA_HAQ
 
Megaloblastic anemia
Megaloblastic anemiaMegaloblastic anemia
Megaloblastic anemia
Naser Tadvi
 
Cell injury : Intracellular accumulations
Cell injury : Intracellular accumulationsCell injury : Intracellular accumulations
Cell injury : Intracellular accumulations
Vijay Shankar
 
Neoplasia
NeoplasiaNeoplasia
Neoplasia
Suraj Dhara
 
Pathology of Acute Inflammation
Pathology of Acute InflammationPathology of Acute Inflammation
Pathology of Acute Inflammation
Neyaz Ahmad
 
Fatty changes
Fatty changesFatty changes
Fatty changes
S ghazal
 
Pathogenesis And Morphological changes of Myocardial Infarction
Pathogenesis And Morphological changes of Myocardial InfarctionPathogenesis And Morphological changes of Myocardial Infarction
Pathogenesis And Morphological changes of Myocardial Infarction
Kapil Sharma Neupane
 
GIANT CELLS
GIANT CELLSGIANT CELLS
Aplastic anemia
Aplastic anemiaAplastic anemia
Aplastic anemia
Asif Zeb
 
Amyloidosis 3
Amyloidosis 3Amyloidosis 3
Amyloidosis 3
Vijay Shankar
 
Pathology cell injury i
Pathology   cell injury iPathology   cell injury i
Pathology cell injury i
MBBS IMS MSU
 
Spread of tumours
Spread of tumoursSpread of tumours
Spread of tumours
Sumudu Himesha Meawela
 
Infarct
InfarctInfarct
Infarct
ariva zhagan
 
Megaloblastic anemia
Megaloblastic anemiaMegaloblastic anemia
Megaloblastic anemia
Oduenyi Christian Onyeka.BMR(PT)
 

What's hot (20)

Chronic granulomatous inflammation
Chronic granulomatous inflammationChronic granulomatous inflammation
Chronic granulomatous inflammation
 
Acute inflammation
Acute inflammationAcute inflammation
Acute inflammation
 
Pathology neoplasm
Pathology  neoplasmPathology  neoplasm
Pathology neoplasm
 
Amyloidosis and pathological calcification
Amyloidosis and pathological calcificationAmyloidosis and pathological calcification
Amyloidosis and pathological calcification
 
Haemolytic anemia
Haemolytic anemia Haemolytic anemia
Haemolytic anemia
 
Pathologic Calcification
Pathologic CalcificationPathologic Calcification
Pathologic Calcification
 
Megaloblastic anemia
Megaloblastic anemiaMegaloblastic anemia
Megaloblastic anemia
 
Cell injury : Intracellular accumulations
Cell injury : Intracellular accumulationsCell injury : Intracellular accumulations
Cell injury : Intracellular accumulations
 
Neoplasia
NeoplasiaNeoplasia
Neoplasia
 
Pathology of Acute Inflammation
Pathology of Acute InflammationPathology of Acute Inflammation
Pathology of Acute Inflammation
 
Fatty changes
Fatty changesFatty changes
Fatty changes
 
Pathogenesis And Morphological changes of Myocardial Infarction
Pathogenesis And Morphological changes of Myocardial InfarctionPathogenesis And Morphological changes of Myocardial Infarction
Pathogenesis And Morphological changes of Myocardial Infarction
 
GIANT CELLS
GIANT CELLSGIANT CELLS
GIANT CELLS
 
Aplastic anemia
Aplastic anemiaAplastic anemia
Aplastic anemia
 
Amyloidosis 3
Amyloidosis 3Amyloidosis 3
Amyloidosis 3
 
Anemia And Its Classification
Anemia And Its ClassificationAnemia And Its Classification
Anemia And Its Classification
 
Pathology cell injury i
Pathology   cell injury iPathology   cell injury i
Pathology cell injury i
 
Spread of tumours
Spread of tumoursSpread of tumours
Spread of tumours
 
Infarct
InfarctInfarct
Infarct
 
Megaloblastic anemia
Megaloblastic anemiaMegaloblastic anemia
Megaloblastic anemia
 

Similar to AMYLOIDOSIS

AMYLOIDDFHGDDSCBJUUFFFVVXFTGGVVBOSIS.pdf
AMYLOIDDFHGDDSCBJUUFFFVVXFTGGVVBOSIS.pdfAMYLOIDDFHGDDSCBJUUFFFVVXFTGGVVBOSIS.pdf
AMYLOIDDFHGDDSCBJUUFFFVVXFTGGVVBOSIS.pdf
SarithaRani4
 
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
NetanielGR
 
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
maha lingam
 
7598035.ppt
7598035.ppt7598035.ppt
7598035.ppt
SitiHajar643369
 
Classification of Amyloidosis
Classification of AmyloidosisClassification of Amyloidosis
Classification of Amyloidosis
Abhineet Dey
 
Presentation1.pptx
Presentation1.pptxPresentation1.pptx
Presentation1.pptx
SitiHajar643369
 
13238207.ppt
13238207.ppt13238207.ppt
13238207.ppt
ZuhaibRaza4
 
Amyloidosis presentation
Amyloidosis presentationAmyloidosis presentation
Amyloidosis presentation
Harshit Saxena
 
5 immunology-csbrp
5 immunology-csbrp5 immunology-csbrp
5 immunology-csbrp
Prasad CSBR
 
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
Charles Ntima
 
amyloidosis 2.pdf
amyloidosis 2.pdfamyloidosis 2.pdf
amyloidosis 2.pdf
GaurishChandraRathau
 
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
Khaled Abdiaziz
 
Amylodosis
AmylodosisAmylodosis
Amylodosis
Dr ATHUL CHANDRA.M
 
Amyloidosis of kidney. Morphological characteristics, outcomes, complications
Amyloidosis of kidney. Morphological characteristics, outcomes, complicationsAmyloidosis of kidney. Morphological characteristics, outcomes, complications
Amyloidosis of kidney. Morphological characteristics, outcomes, complications
Semey State Medical University
 
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
SanjanaPalakodeti
 
Amyloid aware booklet
Amyloid aware bookletAmyloid aware booklet
Amyloid aware bookletElsa von Licy
 
Amyloidosis - pathophysiology (PHARM D)
Amyloidosis - pathophysiology (PHARM D)Amyloidosis - pathophysiology (PHARM D)
Amyloidosis - pathophysiology (PHARM D)
Juliya Susan Reji
 

Similar to AMYLOIDOSIS (20)

AMYLOIDDFHGDDSCBJUUFFFVVXFTGGVVBOSIS.pdf
AMYLOIDDFHGDDSCBJUUFFFVVXFTGGVVBOSIS.pdfAMYLOIDDFHGDDSCBJUUFFFVVXFTGGVVBOSIS.pdf
AMYLOIDDFHGDDSCBJUUFFFVVXFTGGVVBOSIS.pdf
 
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
 
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
 
7598035.ppt
7598035.ppt7598035.ppt
7598035.ppt
 
Classification of Amyloidosis
Classification of AmyloidosisClassification of Amyloidosis
Classification of Amyloidosis
 
Presentation1.pptx
Presentation1.pptxPresentation1.pptx
Presentation1.pptx
 
13238207.ppt
13238207.ppt13238207.ppt
13238207.ppt
 
Amyloidosis presentation
Amyloidosis presentationAmyloidosis presentation
Amyloidosis presentation
 
5 immunology-csbrp
5 immunology-csbrp5 immunology-csbrp
5 immunology-csbrp
 
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
 
amyloidosis 2.pdf
amyloidosis 2.pdfamyloidosis 2.pdf
amyloidosis 2.pdf
 
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
 
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
 
Immunopathology 6
Immunopathology 6Immunopathology 6
Immunopathology 6
 
Amylodosis
AmylodosisAmylodosis
Amylodosis
 
Amyloidosis of kidney. Morphological characteristics, outcomes, complications
Amyloidosis of kidney. Morphological characteristics, outcomes, complicationsAmyloidosis of kidney. Morphological characteristics, outcomes, complications
Amyloidosis of kidney. Morphological characteristics, outcomes, complications
 
Amyloidoisis
AmyloidoisisAmyloidoisis
Amyloidoisis
 
Amyloidosis
AmyloidosisAmyloidosis
Amyloidosis
 
Amyloid aware booklet
Amyloid aware bookletAmyloid aware booklet
Amyloid aware booklet
 
Amyloidosis - pathophysiology (PHARM D)
Amyloidosis - pathophysiology (PHARM D)Amyloidosis - pathophysiology (PHARM D)
Amyloidosis - pathophysiology (PHARM D)
 

More from Suraj Dhara

SHOCK
SHOCKSHOCK
ACUTE INFLAMMATION
ACUTE INFLAMMATIONACUTE INFLAMMATION
ACUTE INFLAMMATION
Suraj Dhara
 
EXAMINATION OF SWELLING
EXAMINATION OF SWELLING EXAMINATION OF SWELLING
EXAMINATION OF SWELLING
Suraj Dhara
 
PAIN : HISTORY TAKING
PAIN : HISTORY TAKINGPAIN : HISTORY TAKING
PAIN : HISTORY TAKING
Suraj Dhara
 
MANAGEMENT OF BREAST CARCINOMA
MANAGEMENT OF BREAST CARCINOMAMANAGEMENT OF BREAST CARCINOMA
MANAGEMENT OF BREAST CARCINOMA
Suraj Dhara
 
DISEASE AND DENGUE
DISEASE AND DENGUEDISEASE AND DENGUE
DISEASE AND DENGUE
Suraj Dhara
 
THE VESTIGIALS
THE VESTIGIALSTHE VESTIGIALS
THE VESTIGIALS
Suraj Dhara
 
STAPHYLOCOCCUS
STAPHYLOCOCCUSSTAPHYLOCOCCUS
STAPHYLOCOCCUS
Suraj Dhara
 
PNEUMOCOCCUS
PNEUMOCOCCUSPNEUMOCOCCUS
PNEUMOCOCCUS
Suraj Dhara
 
SALMONELLA
SALMONELLASALMONELLA
SALMONELLA
Suraj Dhara
 
PAIN : PATHOPHYSIOLOGY
PAIN : PATHOPHYSIOLOGYPAIN : PATHOPHYSIOLOGY
PAIN : PATHOPHYSIOLOGY
Suraj Dhara
 
EPISTAXIS
EPISTAXISEPISTAXIS
EPISTAXIS
Suraj Dhara
 
NASAL POLYP
NASAL POLYPNASAL POLYP
NASAL POLYP
Suraj Dhara
 
FORENSIC MEDICINE MCQS
FORENSIC MEDICINE MCQSFORENSIC MEDICINE MCQS
FORENSIC MEDICINE MCQS
Suraj Dhara
 
RABIES (RHABDOVIRUS)
RABIES (RHABDOVIRUS)RABIES (RHABDOVIRUS)
RABIES (RHABDOVIRUS)
Suraj Dhara
 
ANATOMY OF EXTERNAL EAR
ANATOMY OF EXTERNAL EARANATOMY OF EXTERNAL EAR
ANATOMY OF EXTERNAL EAR
Suraj Dhara
 
ANATOMY OF LARYNX
ANATOMY OF LARYNXANATOMY OF LARYNX
ANATOMY OF LARYNX
Suraj Dhara
 
CONCEPTS OF HEALTH AND DISEASE
CONCEPTS OF HEALTH AND DISEASECONCEPTS OF HEALTH AND DISEASE
CONCEPTS OF HEALTH AND DISEASE
Suraj Dhara
 
LOW BIRTH WEIGHT (ACTIONS TAKEN BY BMOH)
LOW BIRTH WEIGHT (ACTIONS TAKEN BY BMOH)LOW BIRTH WEIGHT (ACTIONS TAKEN BY BMOH)
LOW BIRTH WEIGHT (ACTIONS TAKEN BY BMOH)
Suraj Dhara
 
VIROLOGY
VIROLOGYVIROLOGY
VIROLOGY
Suraj Dhara
 

More from Suraj Dhara (20)

SHOCK
SHOCKSHOCK
SHOCK
 
ACUTE INFLAMMATION
ACUTE INFLAMMATIONACUTE INFLAMMATION
ACUTE INFLAMMATION
 
EXAMINATION OF SWELLING
EXAMINATION OF SWELLING EXAMINATION OF SWELLING
EXAMINATION OF SWELLING
 
PAIN : HISTORY TAKING
PAIN : HISTORY TAKINGPAIN : HISTORY TAKING
PAIN : HISTORY TAKING
 
MANAGEMENT OF BREAST CARCINOMA
MANAGEMENT OF BREAST CARCINOMAMANAGEMENT OF BREAST CARCINOMA
MANAGEMENT OF BREAST CARCINOMA
 
DISEASE AND DENGUE
DISEASE AND DENGUEDISEASE AND DENGUE
DISEASE AND DENGUE
 
THE VESTIGIALS
THE VESTIGIALSTHE VESTIGIALS
THE VESTIGIALS
 
STAPHYLOCOCCUS
STAPHYLOCOCCUSSTAPHYLOCOCCUS
STAPHYLOCOCCUS
 
PNEUMOCOCCUS
PNEUMOCOCCUSPNEUMOCOCCUS
PNEUMOCOCCUS
 
SALMONELLA
SALMONELLASALMONELLA
SALMONELLA
 
PAIN : PATHOPHYSIOLOGY
PAIN : PATHOPHYSIOLOGYPAIN : PATHOPHYSIOLOGY
PAIN : PATHOPHYSIOLOGY
 
EPISTAXIS
EPISTAXISEPISTAXIS
EPISTAXIS
 
NASAL POLYP
NASAL POLYPNASAL POLYP
NASAL POLYP
 
FORENSIC MEDICINE MCQS
FORENSIC MEDICINE MCQSFORENSIC MEDICINE MCQS
FORENSIC MEDICINE MCQS
 
RABIES (RHABDOVIRUS)
RABIES (RHABDOVIRUS)RABIES (RHABDOVIRUS)
RABIES (RHABDOVIRUS)
 
ANATOMY OF EXTERNAL EAR
ANATOMY OF EXTERNAL EARANATOMY OF EXTERNAL EAR
ANATOMY OF EXTERNAL EAR
 
ANATOMY OF LARYNX
ANATOMY OF LARYNXANATOMY OF LARYNX
ANATOMY OF LARYNX
 
CONCEPTS OF HEALTH AND DISEASE
CONCEPTS OF HEALTH AND DISEASECONCEPTS OF HEALTH AND DISEASE
CONCEPTS OF HEALTH AND DISEASE
 
LOW BIRTH WEIGHT (ACTIONS TAKEN BY BMOH)
LOW BIRTH WEIGHT (ACTIONS TAKEN BY BMOH)LOW BIRTH WEIGHT (ACTIONS TAKEN BY BMOH)
LOW BIRTH WEIGHT (ACTIONS TAKEN BY BMOH)
 
VIROLOGY
VIROLOGYVIROLOGY
VIROLOGY
 

Recently uploaded

Embracing GenAI - A Strategic Imperative
Embracing GenAI - A Strategic ImperativeEmbracing GenAI - A Strategic Imperative
Embracing GenAI - A Strategic Imperative
Peter Windle
 
Operation Blue Star - Saka Neela Tara
Operation Blue Star   -  Saka Neela TaraOperation Blue Star   -  Saka Neela Tara
Operation Blue Star - Saka Neela Tara
Balvir Singh
 
Unit 2- Research Aptitude (UGC NET Paper I).pdf
Unit 2- Research Aptitude (UGC NET Paper I).pdfUnit 2- Research Aptitude (UGC NET Paper I).pdf
Unit 2- Research Aptitude (UGC NET Paper I).pdf
Thiyagu K
 
Acetabularia Information For Class 9 .docx
Acetabularia Information For Class 9  .docxAcetabularia Information For Class 9  .docx
Acetabularia Information For Class 9 .docx
vaibhavrinwa19
 
Thesis Statement for students diagnonsed withADHD.ppt
Thesis Statement for students diagnonsed withADHD.pptThesis Statement for students diagnonsed withADHD.ppt
Thesis Statement for students diagnonsed withADHD.ppt
EverAndrsGuerraGuerr
 
A Strategic Approach: GenAI in Education
A Strategic Approach: GenAI in EducationA Strategic Approach: GenAI in Education
A Strategic Approach: GenAI in Education
Peter Windle
 
Phrasal Verbs.XXXXXXXXXXXXXXXXXXXXXXXXXX
Phrasal Verbs.XXXXXXXXXXXXXXXXXXXXXXXXXXPhrasal Verbs.XXXXXXXXXXXXXXXXXXXXXXXXXX
Phrasal Verbs.XXXXXXXXXXXXXXXXXXXXXXXXXX
MIRIAMSALINAS13
 
Honest Reviews of Tim Han LMA Course Program.pptx
Honest Reviews of Tim Han LMA Course Program.pptxHonest Reviews of Tim Han LMA Course Program.pptx
Honest Reviews of Tim Han LMA Course Program.pptx
timhan337
 
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdf
Welcome to TechSoup   New Member Orientation and Q&A (May 2024).pdfWelcome to TechSoup   New Member Orientation and Q&A (May 2024).pdf
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdf
TechSoup
 
Palestine last event orientationfvgnh .pptx
Palestine last event orientationfvgnh .pptxPalestine last event orientationfvgnh .pptx
Palestine last event orientationfvgnh .pptx
RaedMohamed3
 
TESDA TM1 REVIEWER FOR NATIONAL ASSESSMENT WRITTEN AND ORAL QUESTIONS WITH A...
TESDA TM1 REVIEWER  FOR NATIONAL ASSESSMENT WRITTEN AND ORAL QUESTIONS WITH A...TESDA TM1 REVIEWER  FOR NATIONAL ASSESSMENT WRITTEN AND ORAL QUESTIONS WITH A...
TESDA TM1 REVIEWER FOR NATIONAL ASSESSMENT WRITTEN AND ORAL QUESTIONS WITH A...
EugeneSaldivar
 
The approach at University of Liverpool.pptx
The approach at University of Liverpool.pptxThe approach at University of Liverpool.pptx
The approach at University of Liverpool.pptx
Jisc
 
Polish students' mobility in the Czech Republic
Polish students' mobility in the Czech RepublicPolish students' mobility in the Czech Republic
Polish students' mobility in the Czech Republic
Anna Sz.
 
678020731-Sumas-y-Restas-Para-Colorear.pdf
678020731-Sumas-y-Restas-Para-Colorear.pdf678020731-Sumas-y-Restas-Para-Colorear.pdf
678020731-Sumas-y-Restas-Para-Colorear.pdf
CarlosHernanMontoyab2
 
BÀI TẬP BỔ TRỢ TIẾNG ANH GLOBAL SUCCESS LỚP 3 - CẢ NĂM (CÓ FILE NGHE VÀ ĐÁP Á...
BÀI TẬP BỔ TRỢ TIẾNG ANH GLOBAL SUCCESS LỚP 3 - CẢ NĂM (CÓ FILE NGHE VÀ ĐÁP Á...BÀI TẬP BỔ TRỢ TIẾNG ANH GLOBAL SUCCESS LỚP 3 - CẢ NĂM (CÓ FILE NGHE VÀ ĐÁP Á...
BÀI TẬP BỔ TRỢ TIẾNG ANH GLOBAL SUCCESS LỚP 3 - CẢ NĂM (CÓ FILE NGHE VÀ ĐÁP Á...
Nguyen Thanh Tu Collection
 
aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa
aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa
aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa
siemaillard
 
CACJapan - GROUP Presentation 1- Wk 4.pdf
CACJapan - GROUP Presentation 1- Wk 4.pdfCACJapan - GROUP Presentation 1- Wk 4.pdf
CACJapan - GROUP Presentation 1- Wk 4.pdf
camakaiclarkmusic
 
special B.ed 2nd year old paper_20240531.pdf
special B.ed 2nd year old paper_20240531.pdfspecial B.ed 2nd year old paper_20240531.pdf
special B.ed 2nd year old paper_20240531.pdf
Special education needs
 
How libraries can support authors with open access requirements for UKRI fund...
How libraries can support authors with open access requirements for UKRI fund...How libraries can support authors with open access requirements for UKRI fund...
How libraries can support authors with open access requirements for UKRI fund...
Jisc
 
Unit 8 - Information and Communication Technology (Paper I).pdf
Unit 8 - Information and Communication Technology (Paper I).pdfUnit 8 - Information and Communication Technology (Paper I).pdf
Unit 8 - Information and Communication Technology (Paper I).pdf
Thiyagu K
 

Recently uploaded (20)

Embracing GenAI - A Strategic Imperative
Embracing GenAI - A Strategic ImperativeEmbracing GenAI - A Strategic Imperative
Embracing GenAI - A Strategic Imperative
 
Operation Blue Star - Saka Neela Tara
Operation Blue Star   -  Saka Neela TaraOperation Blue Star   -  Saka Neela Tara
Operation Blue Star - Saka Neela Tara
 
Unit 2- Research Aptitude (UGC NET Paper I).pdf
Unit 2- Research Aptitude (UGC NET Paper I).pdfUnit 2- Research Aptitude (UGC NET Paper I).pdf
Unit 2- Research Aptitude (UGC NET Paper I).pdf
 
Acetabularia Information For Class 9 .docx
Acetabularia Information For Class 9  .docxAcetabularia Information For Class 9  .docx
Acetabularia Information For Class 9 .docx
 
Thesis Statement for students diagnonsed withADHD.ppt
Thesis Statement for students diagnonsed withADHD.pptThesis Statement for students diagnonsed withADHD.ppt
Thesis Statement for students diagnonsed withADHD.ppt
 
A Strategic Approach: GenAI in Education
A Strategic Approach: GenAI in EducationA Strategic Approach: GenAI in Education
A Strategic Approach: GenAI in Education
 
Phrasal Verbs.XXXXXXXXXXXXXXXXXXXXXXXXXX
Phrasal Verbs.XXXXXXXXXXXXXXXXXXXXXXXXXXPhrasal Verbs.XXXXXXXXXXXXXXXXXXXXXXXXXX
Phrasal Verbs.XXXXXXXXXXXXXXXXXXXXXXXXXX
 
Honest Reviews of Tim Han LMA Course Program.pptx
Honest Reviews of Tim Han LMA Course Program.pptxHonest Reviews of Tim Han LMA Course Program.pptx
Honest Reviews of Tim Han LMA Course Program.pptx
 
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdf
Welcome to TechSoup   New Member Orientation and Q&A (May 2024).pdfWelcome to TechSoup   New Member Orientation and Q&A (May 2024).pdf
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdf
 
Palestine last event orientationfvgnh .pptx
Palestine last event orientationfvgnh .pptxPalestine last event orientationfvgnh .pptx
Palestine last event orientationfvgnh .pptx
 
TESDA TM1 REVIEWER FOR NATIONAL ASSESSMENT WRITTEN AND ORAL QUESTIONS WITH A...
TESDA TM1 REVIEWER  FOR NATIONAL ASSESSMENT WRITTEN AND ORAL QUESTIONS WITH A...TESDA TM1 REVIEWER  FOR NATIONAL ASSESSMENT WRITTEN AND ORAL QUESTIONS WITH A...
TESDA TM1 REVIEWER FOR NATIONAL ASSESSMENT WRITTEN AND ORAL QUESTIONS WITH A...
 
The approach at University of Liverpool.pptx
The approach at University of Liverpool.pptxThe approach at University of Liverpool.pptx
The approach at University of Liverpool.pptx
 
Polish students' mobility in the Czech Republic
Polish students' mobility in the Czech RepublicPolish students' mobility in the Czech Republic
Polish students' mobility in the Czech Republic
 
678020731-Sumas-y-Restas-Para-Colorear.pdf
678020731-Sumas-y-Restas-Para-Colorear.pdf678020731-Sumas-y-Restas-Para-Colorear.pdf
678020731-Sumas-y-Restas-Para-Colorear.pdf
 
BÀI TẬP BỔ TRỢ TIẾNG ANH GLOBAL SUCCESS LỚP 3 - CẢ NĂM (CÓ FILE NGHE VÀ ĐÁP Á...
BÀI TẬP BỔ TRỢ TIẾNG ANH GLOBAL SUCCESS LỚP 3 - CẢ NĂM (CÓ FILE NGHE VÀ ĐÁP Á...BÀI TẬP BỔ TRỢ TIẾNG ANH GLOBAL SUCCESS LỚP 3 - CẢ NĂM (CÓ FILE NGHE VÀ ĐÁP Á...
BÀI TẬP BỔ TRỢ TIẾNG ANH GLOBAL SUCCESS LỚP 3 - CẢ NĂM (CÓ FILE NGHE VÀ ĐÁP Á...
 
aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa
aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa
aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa
 
CACJapan - GROUP Presentation 1- Wk 4.pdf
CACJapan - GROUP Presentation 1- Wk 4.pdfCACJapan - GROUP Presentation 1- Wk 4.pdf
CACJapan - GROUP Presentation 1- Wk 4.pdf
 
special B.ed 2nd year old paper_20240531.pdf
special B.ed 2nd year old paper_20240531.pdfspecial B.ed 2nd year old paper_20240531.pdf
special B.ed 2nd year old paper_20240531.pdf
 
How libraries can support authors with open access requirements for UKRI fund...
How libraries can support authors with open access requirements for UKRI fund...How libraries can support authors with open access requirements for UKRI fund...
How libraries can support authors with open access requirements for UKRI fund...
 
Unit 8 - Information and Communication Technology (Paper I).pdf
Unit 8 - Information and Communication Technology (Paper I).pdfUnit 8 - Information and Communication Technology (Paper I).pdf
Unit 8 - Information and Communication Technology (Paper I).pdf
 

AMYLOIDOSIS

  • 2. TOPICS OF DISCUSSION  Definition  Pathogenesis  Properties of Amyloid - Physical - Chemical  Classification  Morphology  Clinical presentation  Diagnosis
  • 3. Amyloidosis - Introduction  Disorder characterized by extracellular deposition of amyloid (fibrillar proteinaceous substance)  Amyloid fibril – made of misfolded protein  Amyloid = amylose (starch) like They have staining characteristic similar to starch but they are unrelated to starch.  Associated with a number of inherited and inflammatory disorder
  • 4. Amyloidosis - Definition Amyloidosis is a disorder characterized by the extracellular deposits of misfolded proteins that aggregate to form insoluble fibrils leads to tissue damage and functional compromise.
  • 5. Amyloidosis - Pathogenesis Intracellularly in proteasomes Extracellularly by macrophages Normally degraded Misfolded proteins Amyloidosis – this normal control mechanism fails Misfolded protein accumulates outside cells.
  • 6. Amyloidosis - Pathogenesis Two categories of proteins that form Amyloid Amyloidosis: 1. Localized: involves single organ 2. Systemic: involves multiple organs or tissues Effect: tissue damage and compromised function Normal proteins that have inherent tendency to misfold (excessive production) Mutant proteins that are prone to misfolding
  • 7. Amyloid – chemical nature >20 chemically distinct amyloid exist Most common forms: AL (Amyloid light chain) AA (Amyloid associated) (Aβ) β-amyloid proteins • Complete Ig light chain or • Amino terminal fragments of light chain or both • (λ >> κ) • Non Ig protein • Synthesized by liver • Precursor protein SAA • Increased synthesis in inflammatory state • Found in Alzheimer disease • Derived from Amyloid precursor protein
  • 8. Amyloid - chemical nature Rare chemical forms: 1. Transthyretin (TTR) - mutant & normal 2. β2-microglobulin (Aβ2m) – long term hemodialysis 3. Misfolded prion proteins 4. Serum amyloid P component – contribute to amyloid deposition by stabilizing the fibrils and decreasing their clearance
  • 9. Amyloid – physical nature Electron microscopy: Continuous non- branching fibril Diameter – 7.5 – 10 nm X-ray crystallography & Infrared spectroscopy Cross β-pleated sheet conformation Common to all amyloid protein Responsible for their distinctive Congo red staining and birefringence
  • 10. Pathogenesis : Major forms of Amyloid fibrils
  • 11. Amyloidosis – classification 1. Primary amyloidosis 2. Reactive systemic amyloidosis 3. Heredofamilial amyloidosis 4. Hemodialysis associated amyloidosis 5. Localized amyloidosis 6. Endocrine amyloidosis 7. Amyloid of aging
  • 12. Amyloidosis – classification 1. Primary amyloidosis: - Plasma cell disorder associated - AL type amyloid protein - Ig secreted by clonal plasma cell prone to form Amyloid (due to its intrinsic physio-chemical properties) 5 - 15% multiple myeloma cases develop amyloidosis (not all) - Amyloidogenic potential of particular chain depends upon its specific amino acid sequence.
  • 13. Amyloidosis – classification Contd… Most of AL amyloid do not have overt multiple myeloma or clonal B cell neoplasm - But they are classified as primary amyloidosis (their presentation is due to amyloid deposition without any associated disease) - Modest increase in plasma cell noted in marrow without any tumor effect (monoclonal gummopathy)
  • 14. Amyloidosis – classification 2. Reactive systemic amyloidosis: (also k/a secondary amyloidosis) - Associated with inflammatory condition - AA type amyloid protein - Common association Rheumatoid arthritis (MC) – 3%, half of them clinically significant Ankylosing spondylitis Inflammatory bowel disease (previously common association – TB, bronchiectasis, chronic osteomyelitis) Other cause – Heroine abuse, solid tumors (RCC, HL)
  • 15. Amyloidosis – classification Reactive systemic amyloidosis: Inflammation  IL6 & IL1  Liver  SAA synthesis ( ) normally degrade Soluble end products Monocyte derived enzyme SAA Genetically derived mutant SAA - Resistant to degradation Insoluble AA molecule
  • 16. Amyloidosis – classification 3. Heredofamilial Amyloidosis:  Rare & occur in limited geographic area  Familial Mediterranean fever (AR inheritence) – MC - AA type amyloid protein, - Related to the recurrent bouts of inflammation.  Familial amyloidotic polyneuropathy –mTTR 4. Hemodialysis associated amyloidosis: - Patients on long-term hemodialysis - deposition of β2-microglobulin - cannot be filtered through dialysis membranes
  • 17. 5. Localized Amyloidosis: - Involves single organ - Macroscopically normal or nodular deposits - Lung, larynx skin, urinary bladder, tongue - In some cases surrounded by lymphocytes and plasma cell & AL type amyloid.
  • 18. Amyloidosis – classification 6. Endocrine amyloidosis: - Microscopic deposits of localized amyloid  found in certain endocrine tumors, such as - medullary carcinoma of the thyroid gland, - islet tumors of the pancreas, - pheochromocytomas, and - undifferentiated carcinomas of the stomach, and - in the islets of Langerhans in individuals with type II diabetes mellitus.  Amyloidogenic proteins seem to be derived either from - polypeptide hormones (e.g., medullary carcinoma) or - unique proteins (e.g., islet amyloid polypeptide).
  • 19. Amyloidosis – classification 7. Amyloid of aging Senile systemic amyloidosis: - systemic deposition of amyloid - in elderly patients (usually in their 70s and 80s). - previously called senile cardiac amyloidosis. (Because of the dominant involvement and related dysfunction of the heart) - The amyloid in this form is composed of the normal TTR molecule.
  • 20. Amyloidosis – Organ involvement No consistent or distinctive pattern of amyloid deposit Predominant organ involvement Primary amyloidosis Secondary amyloidosis Familial Mediterranean fever • Heart • G I Tract • Respiratory organs • Peripheral nerves • Skin • Tongue • Kidney • Liver • Spleen • Lymphnodes • Adrenals • Thyroid • Kidney • Blood vessels • Spleen • Respiratory tract • Liver (rarely)
  • 21. Amyloidosis – morphology Macroscopically: Involved organs - Enlarged - Grey in appearance - Waxy, firm in consistency
  • 22. Amyloidosis - Morphology Microscopic: - Extracellular deposit - Often adjacent to basement membrane - In advanced stage, encroach, surrounds and destroying the cell
  • 23. Amyloidosis - kidney Most common and potentially most serious form of organ involvement Gross – normal or shrunken [due to ischemia (vascular narrowing) in advanced stage] Microscopy – glomerular deposit, interstitial, peritubular, arterial wall deposit
  • 24. Amyloidosis - spleen One of two patterns of deposition is seen.  Sago spleen - deposits are largely limited to the splenic follicles, producing tapioca-like granules grossly.  Lardaceous spleen – amyloid involves the walls of the splenic sinuses and connective tissue framework in the red pulp. Fusion of the early deposits gives rise to large, map like areas of amyloidosis.
  • 25. Amyloidosis – Clinical manifestation Amyloidosis may be found as  an unsuspected anatomic change,  having produced no clinical manifestations, or  it may cause death. The symptoms depend on  the magnitude of the deposits and  on the particular sites or organs affected.
  • 26. Amyloidosis – Clinical manifestation Clinical manifestations at first are often entirely nonspecific, such as –  Weakness,  Weight loss,  Lightheadedness, or  Syncope Somewhat more specific findings appear later and most often relate to renal, cardiac, and gastrointestinal involvement.
  • 27. Amyloidosis - Diagnosis Histologic demonstration of amyloid deposits in tissues. The most common sites biopsied are - The kidney, (when renal manifestations are present), or - Rectal or gingival tissues (in patients suspected of having systemic amyloidosis)  Abdominal fat aspirates can also be used for the diagnosis of systemic amyloidosis. (Congo red stain) (The test is quite specific, but its sensitivity is low)  Scintigraphy with radiolabelled serum amyloid P (SAP) - Rapid and specific test - Also measures extent of amyloidosis
  • 28. Amyloidosis - Diagnosis Congo red stain - Light microscopy – pink or red color deposit - Polarized microscope – Apple- green birefringence EM - Confirmatory
  • 29. Amyloidosis - prognosis  The prognosis for individuals with generalized amyloidosis is poor.  Immunocyte derived amyloidosis (not including multiple myeloma) - median survival of 2 years after diagnosis.  Persons with myeloma-associated amyloidosis have a poorer prognosis.  Reactive systemic amyloidosis - somewhat better and depends to some extent on the control of the underlying condition.  New therapeutic strategies aimed at - Correcting protein misfolding and - Inhibiting fibrillogenesis are being developed.