Amyloidosis & Pathologic
Calcification
Dr. Mayank Gupta
Ack: Dr (Prof) Vishal Saxena MBBS MD
FICMR
Amyloidosis
Definition:
A group of diseases characterized by the
deposition of an extracellular protein k/a
amyloid which causes
Deposition of amyloid in extracellular
spaces which causes
a. pressure atrophy of the adjacent cells
b. organ dysfunction.
Properties of amyloid
Amyloid is a fibrillar
protein.
Individual subunits form
Twisted β- pleated sheet
Characteristics:
Amorphous eosinophilic deposits on
H & E stain
Deposits stain red with Congo Red
stain
Demonstrates Apple green
birefringence under polarized light.
Win 2009 Amyloidosis of the kidney
Congo red Stain
Win 2009
Yellow-green birefringence( polarized light)
Major types of amyloid proteins & causes
Amyloid light chain (AL)
Derived from light chains of Ig
kappa or lambda light chains (e.g Bence Jones
protein)
Amyloid associated (AA)
Derived from serum associated amyloid
An acute phase reactant
produced by liver (inflammation and neoplasia)
β-Amyloid (Aβ)
Derived from β amyloid precursor protein.
protein product of chromosome 21
Amyloidosis: types
1. Systemic
2. Localized
Systemic Amyloidosis
Primary amyloidosis:
Type of amyloid: AL amyloid
Derived from Precursor protein :
Immunoglobulin light chain (λ chain)
Associated with Multiple myeloma.
Reactive systemic amyloidosis (secondary
amyloidosis):
Type of amyloid: AA amyloid
Derived from Precursor protein : SAA
Associated with Rheumatoid arthritis, SLE,
TB, Osteomyelitis, Crohn disease, cancer.
Systemic Amyloidosis
Familial Mediterranean fever:
Type of amyloid: AA
Derived from Precursor protein : SAA
Autosomal recessive disease
Recurrent inflammation, fever, and neutrophil
dysfunction (mutant pyrin gene).
Familial amyloidotic neuropathy : Autosomal D
Type of amyloid : ATTR (mutant form of
Transthyretin)
Derived from Precursor protein: Transthyretin
Systemic Amyloidosis
Senile systemic amyloidosis: Transthyretin
Type of amyloid: ATTR
Derived from Precursor protein: Transthyretin
Men > 70 years old ;
May cause heart failure – restrictive
cardiomyopathy & arrhythmias
Hemodialysis- associated amyloidosis:
Type of amyloid: Aβ2M
Derived from β2-microglobulin
May cause carpal tunnel syndrome and joint
disease.
Localized types of amyloid
Senile cerebral amyloidosis:
Type of amyloid Aβ
Derived from Precursor protein: βAPP
Found in Alzhiemer plaques in the brain and in
cerebral vessels
The gene for βAPP is located on chromosome
21.
Isolated atrial amyloidosis
Type of amyloid AANF
Derived from Precursor protein Atrial
natriuretic factor
Localized types of amyloid
Endocrine type:
1. Type of amyloid : A cal (calcitonin)
Derived from Calcitonin : Medullary carcinoma of
thyroid
2. Type of amyloid: AIPP (amylin)
Derived from Islet amyloid peptide
Adult onset Diabetes Mellitus (TYPE II)
Prion Disease (CJD; KURU)
Pathologic infections prion – PrPsc
Amyloidosis in Multiple Myeloma
Elderly patient ; multiple osteolytic
lesion; increased serum monoclonal Ig
(M spike)
Amyloidosis in medullary carcinoma thyroid
Senile cardiac Amyloidosis
Amyloidosis in Alzhiemer’s disease
Central amyloid angiopathy
Neuritic /Senile
plaques
Amyloidosis in Prion disease - CJD
Cerebral atrophy Spongiform changes in the
brain
Distribution of disease in systemic forms
Common sites of involvement
Heart, spleen, tongue, adrenals, liver and
kidney.
Renal system: Kidney most common organ involved
Renal failure is the most common cause of death
(nephrotic syndrome)
Cardiovascular system: Restrictive cardiomyopathy
low voltage EKG, cardiac arrhythmias and CHF
Gastrointestinal system:
Macroglossia, malabsorption, hepatomegaly with
increased alkaline phosphatase.
Musculoskeletal system: Carpal tunnel syndrome
common
Techniques used to diagnose amyloidosis
Biopsy of
Rectal mucosa / gingiva / omental pad of
fat or the organ involved.
Immunoelectrophoresis
to detect light chains in primary
amyloidosis.
Prognosis:
The prognosis of systemic amyloidosis is
poor
AL (Immunoglobulin light Multiple Myeloma, other plasma cell dyscrasias,
chain) B-cell lymphoma
AA (Apo serum amyloid A) Chronic diseases (RA, Ankylosing spondylitis, SLE,
TB, Crohn disease, Chronic bronchitis,
bronchiectasis, Cancer, Familial Mediterranean
Fever)
ATTR (Transthyretin) Familial Amyloidotic polyneuropathy
Senile systemic amyloidosis
Myocardial infarction
A beta 2 microgolobulin Hemodialysis
A beta (Beta protein Alzheimer’s disease, Down’s syndrome
precursor)
AANF Isolated atrial amyloidosis
A cal (Calcitonin) Medullary carcinoma thyroid
AIPP (Amylin) DM Type II
Pathologic Calcification
Abnormal deposition of calcium in
tissues.
Two forms:
1. Dystrophic calcification
2. Metastatic calcification
Dystrophic (Dystrophic means : “seeking out
the bad”) calcification
Occurs in dead ,dying and necrotic tissues.
In the presence of normal serum calcium and phosphorus
levels.
Examples:
Calcification associated with
Enzymatic fat necrosis: visible on X rays
Damaged heart valves:
Mitral valve calcific mitral stenosis
Bicuspid aortic valve aortic stenosis
Atheroclerotic plaques
Periventricular calcification in Congenital CMV
infection
Granulomas (tuberculosis, histoplasmosis).
Dead fetus lithopedion (stone child).
Breast cancer visible on mammograph
Psammoma bodies thyroid cancer, ovarian cancer
Morphology
Gross: Calcium deposits have
White (chalky white) granular appearance
Gritty sensation while cutting.
Microscopy:
H & E stain: calcium salts have basophilic
appearance.
A single calcified cell may progressively
acquire outer layers of calcium giving rise to
lamellated calcified structures k/a Psammoma
bodies.
Ghon’s Tubercle
with
Dystrophic calcification
Nodular masses of deposited calcium
Dystrophic Calcification
A
Atherosclerotic Plaque
Dystrophic Calcification in
the wall of the stomach
B
Dystrophic Calcifications: Breast Carcinoma
Mammograph
Psammoma Body
Metastatic calcification
Deposition of calcium in normal and undamaged (healthy)
tissue.
Due to increase in serum calcium (hypercalcemia).
Examples of metastatic calcification:
Nephrocalcinosis: in hyperparathyroidism
Calcification of tubular basement membrane.
Calcification of basal ganglia: due to high phosphorous
levels.
Calcification of
alveolar wall
Gastric epithelium
Causes for hypercalcemia
Increased secretion of PTH
Primary hyperparathyroidism (most common).
Parathyroid hyperplasia or adenoma
Ectopic PTH related protein secretion (SCC of
lung).
Destruction of bone tissue
Multiple myeloma, breast cancer, Paget’s dis.
Vitamin D related disorders
Vitamin D intoxication
Milk and Antacid abuse
Cause for hyperphosphatemia:
Renal failure
Metastatic Calcification: Kidney
Metastatic Calcification: Lung
