AmyloidosisAmyloidosis

Dr. Amitabha BasuDr. Amitabha Basu

What is amyloid (amylin : starch-What is amyloid (amylin : starch-like)?like)?

►Def : Homogeneous, Pink, extra Def : Homogeneous, Pink, extra cellular , pathologic material.cellular , pathologic material.

Nature of AmyloidNature of Amyloid

A.A. Physical NaturePhysical Nature : non branching : non branching protein fibrils 7.5 -10 nm in diameter. protein fibrils 7.5 -10 nm in diameter. Beta pleated sheet.Beta pleated sheet.

B.B. Chemical natureChemical nature : :

95% Protein Fibril 95% Protein Fibril

Beta-Pleated Sheet Beta-Pleated Sheet

Chemical natureChemical nature

►Amyloid = Amyloid = 95% Protein Fibril95% Protein Fibril + 5% + 5% Glycoprotein P component - pentagonal Glycoprotein P component - pentagonal moleculemolecule

►Many different chemical types of Many different chemical types of amyloidamyloid

►Common typesCommon typesAmyloid associate ( AA)Amyloid associate ( AA)Amyloid light chain (AL)Amyloid light chain (AL)

PathogenesisPathogenesis

►PrecursorPrecursor of AA = of AA = SAASAA ( ( SSerum erum AAmyloid myloid AAssociate protein from liver): ssociate protein from liver): chronic inflammation.chronic inflammation.

►PrecursorPrecursor of AL = Immunoglobulin from of AL = Immunoglobulin from plasma cells = ? Multiple Myeloma .plasma cells = ? Multiple Myeloma .

AmyloidosisAmyloidosis

►Def : Disease characterized by Def : Disease characterized by deposition of amyloid in the tissue.deposition of amyloid in the tissue.

Classifications of Classifications of AmyloidosisAmyloidosis

A.A. Systemic amyloidosisSystemic amyloidosis1.1. Primary amyloidosisPrimary amyloidosis2.2. Secondary amyloidosisSecondary amyloidosis

B.B. Localized amyloidosisLocalized amyloidosis1.1. Senile cerebralSenile cerebral2.2. Senile cardiacSenile cardiac3.3. Type 2 diabetes.Type 2 diabetes.

Primary systemic Primary systemic amyloidosisamyloidosis

Disease Disease namename

Type of Type of amyloid in amyloid in the tissuethe tissue

PrecursorPrecursor

Multiple Multiple MyelomaMyeloma

ALAL Ig lambdaIg lambda(or kappa (or kappa chains)chains)

Secondary systemic Secondary systemic amyloidosisamyloidosis

Disease nameDisease name Type of Type of amyloid in the amyloid in the tissuetissue

Chronic inflammatory Chronic inflammatory disease.disease.

AAAA

Hemodialysis associate Hemodialysis associate amyloidosis in chronic amyloidosis in chronic renal failure.renal failure.

A-beta 2 micro A-beta 2 micro globulin.globulin.

(A(Aββ2- 2- micro micro globulinglobulin) )

Rheumatoid arthritisRheumatoid arthritis AAAA

Localized amyloidosis : Localized amyloidosis : mainly due to agingmainly due to agingDisease nameDisease name Type of Type of

amyloid in the amyloid in the tissuetissue

Senile Senile cerebral cerebral amyloidosis:amyloidosis:Alzheimer's Alzheimer's disease disease

Amyloid beta Amyloid beta proteinprotein

(A(Aß)ß)

Type 2 Type 2 diabetesdiabetes

Islet amyloid Islet amyloid polypeptide polypeptide

( AIAPP) in ( AIAPP) in islet of islet of LangerhansLangerhans

Disease and amyloidDisease and amyloid

Multiple Myeloma Multiple Myeloma ( Primary)( Primary)

ALAL

Rheumatoid arthritis/ TB Rheumatoid arthritis/ TB

( secondary, reactive)( secondary, reactive)AAAA

Senile systemic Senile systemic amyloidosis, amyloidosis, familial familial polyneuropathiespolyneuropathies

TTRTTR

Acute Familial Acute Familial Mediterranean FeverMediterranean Fever

AA AA

Hemodialysis associatedHemodialysis associated AAββ2 micro 2 micro globulinglobulin

Alzheimer's disease Alzheimer's disease Amyloid betaAmyloid beta

Medullary CA thyroidMedullary CA thyroid calcitonincalcitonin

Special stain and amyloidSpecial stain and amyloid

►Lugals iodine: Used only on gross Lugals iodine: Used only on gross specimenspecimen

►PAS: Stain PAS: Stain PP component ( in Biopsy component ( in Biopsy specimen)specimen)

►Congored : Most important (in Biopsy Congored : Most important (in Biopsy specimen)specimen)

Special stain and amyloidSpecial stain and amyloid►Lugals iodine : Brown in gross Lugals iodine : Brown in gross

specimen of heart.specimen of heart.

Special stain and amyloidSpecial stain and amyloid

Congo red ( normal Congo red ( normal light)light)

Brick red Brick red

Congo red Congo red ( polarized light)( polarized light)

Apple green Apple green birefringencebirefringence

MorphologyMorphology

►Gross of any organ with amyloidosis : Waxy in nature.

Amyloidosis of kidney ; amyloid Amyloidosis of kidney ; amyloid deposit in the mesengeum of the deposit in the mesengeum of the

glomerular tuftglomerular tuft

Amyloid in heart : name the Amyloid in heart : name the stain and viewing light stain and viewing light

Clinical manifestationClinical manifestation

Kidney Kidney Nephrotic syndrome, Nephrotic syndrome, protenuria, renal protenuria, renal failurefailure

Tongue , GITTongue , GIT Macroglossia, Macroglossia, malabsorptonmalabsorpton

Heart Heart Cardiomegaly, heart Cardiomegaly, heart failurefailure

Bone marrow Bone marrow involvement in involvement in Multiple Multiple Myeloma.Myeloma.

Fracture/ Multiple Fracture/ Multiple myeloma myeloma

Laboratory findingsLaboratory findings

1.1. Biopsy from gingiva and rectum and Biopsy from gingiva and rectum and special stain.special stain.

2.2. Diagnosis of Multiple Myeloma Diagnosis of Multiple Myeloma associated amyloid (AL).associated amyloid (AL).

1.1. Presence of M-band in electrophoresis.Presence of M-band in electrophoresis.

2.2. Bens-Jones protein in the urine.Bens-Jones protein in the urine.

3.3. Increased light chain and monoclonal Ig.Increased light chain and monoclonal Ig.

Presence ofPresence of M-bandM-band in in

electrophoresielectrophoresiss

Disease and AmyloidDisease and Amyloid

►Primary amyloidosis: Primary amyloidosis: AL,AL, ►Secondary amyloidosis : Secondary amyloidosis : AA,AA, ►Hereditary (familial) amyloidosis: Hereditary (familial) amyloidosis: ATTRATTR

Disease and amyloidDisease and amyloid

Multiple Myeloma Multiple Myeloma ( Primary)( Primary)

ALAL

Rheumatoid arthritis/ TB Rheumatoid arthritis/ TB

( secondary, reactive)( secondary, reactive)AAAA

Senile systemic Senile systemic amyloidosis, amyloidosis, familial familial polyneuropathiespolyneuropathies

TTRTTR

Acute Familial Acute Familial Mediterranean FeverMediterranean Fever

AA AA

Hemodialysis associatedHemodialysis associated AAββ2 micro 2 micro globulinglobulin

Alzheimer's disease Alzheimer's disease Amyloid betaAmyloid beta

Medullary CA thyroidMedullary CA thyroid calcitonincalcitonin

Thank youThank you