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3. amyloidosis

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3.  amyloidosis Powered By Docstoc
					Amyloidosis

Amyloid
• “Amyloid” means “starch like” • Pathologic proteinaceous substance • Deposited b/t cells in various tissues and organs of the body • Amorphous, eosinophilic, hyaline & extracellular protein • Progressive accumulation - pressure atrophy of adjacent cells.

Amyloidosis
• A group of diseases having in common the deposition of similar appearing proteins

Physical Nature
• EM: Non-branching fibrils of indefinite length ; Diameter 7.5 – 10nm • X-ray crystallography & Infrared spectroscopy: cross-β-pleated sheet

Chemical nature
• 95% - fibril proteins • 5% - P component & other glycoproteins • 15 biochemically distinct forms

Chemical nature
• i. 3 most common types AL (amyloid light chain): complete Ig light chain, produced by plasma cells ii. AA (amyloid associated): from precursor SAA (serum amyloid-associated) synthesized in liver iii. Aβ amyloid: cerebral plaques in Alzheimer’s disease

Chemical nature
iii. β2-microglobulin: structurally similar to normal β2-m, complicates course of longterm hemodialysis patients iv. ATTR: mutant form of Transthyretin deposited in familial amyloid neuropathies

Staining Characteristics
• H&E : homogenous pink

Staining Characteristics
• Congo red : red; apple green birefringence on polarising microscope

Staining Characteristics
• Fluorescence stain : Thioflavin T

Staining Characteristics
• • • • Crystal violet : metachromatically red Van gieson : khakhi colour PAS : pink Gross: I2 + H2SO4

Classification
1. Systemic Localized 2. Primary: associated with immunocyte dyscrasia Secondary: complication of chronic inflammation 3. Hereditary or familial

Primary Amyloidosis
• Most common • AL • Plasma cell dyscrasias – M spike on IEP – Bence Jones protein • Urine test : appears on heating to 60 deg; disappears on further boiling (90-100 deg) ; reappears on cooling

Reactive Systemic Amyloidosis
• Chronic inflammation; AA

• TB, bronchiectasis, osteomyelitis, RA, IBD, Tumors : RCC, HD

Hemodialysis Associated Amyloidosis
• ß2 microglobulin cannot be filtered through dialysis membranes • Synovium, joints, tendon sheaths

Heredofamilial Amyloidosis
• AR – Familial mediterranean fever

• TTR

Localized Amyloidosis
• Single organ or tissue • Lung, larynx, skin, bladder, tongue • Some AL

Endocrine Amyloidosis
• Medullary ca of thyroid • Islet cell tumors of pancreas • Pheochromocytomas

Senile Amyloidosis
• Senile systemic amyloidosis – Senile cardiac amyloidosis – TTR

Pathogenesis
Abnormal folding of proteins → deposited in extracellular tissues → disrupt normal function 1. Normal proteins with inherent tendency to fold improperly 2. Mutant proteins, unstable & prone to misfolding, subsequent aggregation & resistant to proteolysis

Morphology
• No consistent or distinctive patterns of organ or tissue distribution of amyloid • Various organs involved – kidneys, liver, spleen, lymph nodes, adrenals, thyroid, heart, GIT, peripheral nerves, skin & tongue

Kidney
• Most common & most serious • Major cause of death • Gross
– Normal in size & colour – May be enlarged or shrunken & contracted – Waxy appearance on cut section

Kidney
• Microscopy
– Amyloid deposition in glomeruli, interstitial peritubular tissue, arteries & arterioles – Widening of basement membrane of capillaries – Capillary lumens are obliterated

Spleen
• Moderate to marked splenomegaly • 2 patterns
– Deposit limited to splenic follicles, tapioca like granules – SAGO SPLEEN – Deposits involving walls of sinuses & connective tissue in red pulp, large map like areas – LARDACEOUS SPLEEN

Spleen
• Microscopy
– Replacement of follicles & walls of splenic sinuses

Liver
• Moderate to marked hepatomegaly • Microscopy
– Starts in Space of Disse – Parenchymal cells & sinusoids – Pressure atrophy & disappearance of hepatocytes – Deposits in vessels & Kupffer cells

Heart
• More common in immunocyte dyscrasias & senile systemic amyloidosis • Gross
– Enlarged – Firm

Heart
• Microscopy
– Focal subendocardial accumulations – Within myocardium b/w muscle fibres – Pressure atrophy of myocardial fibers

Other Organs
• Adrenals
– Adjacent to basement membrane of cortical cells

• Thyroid • Pitutary

Other Organs
• GIT
– Around vessels – Submucosa, muscularis & subserosa

• Tongue
– Nodular deposition – tumor forming amyloid of the tongue

• Nerves & tendons

Clinical Correlation
• Renal : proteinuria, Nephrotic Syndrome, failure • Heart : CCF, arrhythmias, cardiomyopathy • GIT : malabsorption, diarrhea, slurring of speech

Diagnosis
• • • • • Renal / rectal / gingival biopsies Abdominal fat aspirates Serum & Urine protein electrophoresis Immuno electrophoresis Scintigraphy with radio labeled serum amyloid P (SAP) component is a rapid & specific test


				
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posted:9/29/2008
language:English
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