Handout Amyloidosis

Question 1

Amyloidosis Definition

Answer 1

characterized by progressive organ dysfunction due to the relentless deposition of abnormal insoluble proteins in blood vessels and interstitium.

Question 2

What are the broadest categorization of the types of amyloidosis?

Answer 2

Systemic (also called “generalized”): can be broken down into 4 major categories (primary, secondary, induced and hereditary)

Localized: heart, brain, thyroid, pancreas and skin

Question 3

Amyloidosis Epidemiology

Answer 3

uncommon, primarily in late middle-aged and elderly, may be primary (most common) or secondary to another disease

Question 4

Amyloidosis Pathogenesis

Answer 4

disease of abnormal protein folding all folded into beta-pleated sheets, immunoglobulin light chains (primary, Bence-Jones proteins up to 15% of patients with multiple myeloma, but most have just monoclonal gammopathy)

Question 5

Amyloid A

Answer 5

secondary to chronic inflammatory diseases such as RA (up to 3% of them)

Question 6

Transthyretin

Answer 6

Senile, primarily in heart, particular mutant form in 4% of AAs

Question 7

Primary amyloidosis most commonly involves which organs?

Answer 7

heart, gut, nerves, skin and tongue

Question 8

What is the most common form of amyloidosis in the US?

Answer 8

PRIMARY AMYLOIDOSIS

Question 9

What is the protein deposited in primary amyloidosis?

Answer 9

AL “amyloid light chains”

about 2/3 lambda, 1/3 kappa, the opposite of hte usal predominance of kappa in monoclonal gammopathies

Question 10

Patients with primary amyloidosis have __________ in their urine or in their serum or in both?

Answer 10

Bence-Jones proteins; but most patients with bence-jones proteins do not have amyloidosis

Question 11

What disease is primary amyloidosis associated with?

Answer 11

Multiple myeloma, but only 10% of patients with multiple myeloma have amyloidosis

Question 12

Secondary amyloidosis commonly involves which organs?

Answer 12

kidneys, liver, spleen, lymph nodes, adrenals, and thyroid

Question 13

What is secondary amyloidosis secondary to?

Answer 13

chronic inflammatory conditions

Question 14

What is secondary amyloidosis commonly associated with?

Answer 14

RA, inflammatory bowel disease, chronic injection drug abuse, renal cell carcinoma, and Hodgkin’s disease

Question 15

What is the protein deposited in secondary amyloidosis?

Answer 15

AA “amyloid A” which is though to be derived from serum amyloid A protein (SAA) which is an acute-phase reactant synthesized by the liver which circulates complexed to HDL

Question 16

Induced amyloidosis commonly involves which organs?

Answer 16

nerves (e.g. carpal tunnel), joints, bone, gut, and tongue

Question 17

What type of disease is induced amyloidosis?

Answer 17

Iatrogenic disease due to chronic HD, affecting as many as 70% of patients receiving long-term HD

Question 18

What is the protein deposited in induced amyloidosis?

Answer 18

AB2M (beta-2-microglobulin), which is the light chain of the HLA class I histocompatibility surface receptor present on all nucleated cells. It is normally present in the blood and excreted in the urine, but cannot pass through dialysis membranes

Question 19

Hereditary amyloidosis is composed of which diseases?

Answer 19

Familial Mediterranean fever

Amyloid Poly-Neuropathy

Question 20

Familial Mediterranean Fever

Answer 20

AR
Arabs, Sephardic, Jews, Armenians
Recurrent attacks of fever, peritonitis, pleuritis and synovitis, eventually leading to AA deposition in the liver, spleen, kidneys and adrenals

Question 21

Amyloid Poly-Neuropathy

Answer 21

AD
India, Portuguese, Jap, Swedish, Jew
Peripheral and autonomic neuropathy due to deposition of ATTR (amyloid transthyretin), various abnoraml versions of the pre-albumin carrier protein for thyroid hormone and retinol

Question 22

Localized (Senile) Cardiac Amyloidosis

Answer 22

ATTR deposition in the ventricles or AANF, amyloid atrial natriuretic factor, deposition in the atria.

Question 23

Localized (Senile) Cerebral Amyloidosis

Answer 23

deposition of AB (amyloid beta), an abnormally large degradation product of APP (amyloid precursor protein) in Alzhimer’s Disease and Down Syndrome.

Question 24

Localized Thyroid Amyloidosis

Answer 24

feature of medullary carcinoma and involves deposition of calcitonin

Question 25

Localized Pancreatic Amyloidosis

Answer 25

feature of Type II diabetes mellitus and involves deposition of amyloid in islets of Langerhans

Question 26

Localized Cutaneous Amyloidosis

Answer 26

deposition of AL or AA

Question 27

Amyloidosis Gross Pathology

Answer 27

enlarged firm waxy organs

Question 28

Amyloidosis Microscopic Pathology

Answer 28

amorphous hyaline eosinophilic material, first in blood vessels +/- glomeruli, then interstitium, Congo Red stain makes it red (“apple-green birefringent)

Question 29

Amyloidosis Symptoms

Answer 29

Initially nonspecific (weakness, weight loss), later dyspnea, light-headedness, syncope (heart) or edema (kidneys). 
Presentations include heart failure (d/t deposition in the heart), renal failure (d/t deposition in the glomeruli), dementia (d/t deposition in the brain), liver failure and peripheral neuropathy

Question 30

Amyloidosis Signs

Answer 30

macroglossia

Question 31

Amyloidosis Diagnosis

Answer 31

BIOPSY showing the extracellular deposition of amorphous eosinophilic hyaline material which appears pink (or red) on Congo Red stain and has an “apple-green” birefringence (a light yellow color) under polarized light