Handout Amyloidosis Flashcards
Amyloidosis Definition
characterized by progressive organ dysfunction due to the relentless deposition of abnormal insoluble proteins in blood vessels and interstitium.
What are the broadest categorization of the types of amyloidosis?
Systemic (also called “generalized”): can be broken down into 4 major categories (primary, secondary, induced and hereditary)
Localized: heart, brain, thyroid, pancreas and skin
Amyloidosis Epidemiology
uncommon, primarily in late middle-aged and elderly, may be primary (most common) or secondary to another disease
Amyloidosis Pathogenesis
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)
Amyloid A
secondary to chronic inflammatory diseases such as RA (up to 3% of them)
Transthyretin
Senile, primarily in heart, particular mutant form in 4% of AAs
Primary amyloidosis most commonly involves which organs?
heart, gut, nerves, skin and tongue
What is the most common form of amyloidosis in the US?
PRIMARY AMYLOIDOSIS
What is the protein deposited in primary amyloidosis?
AL “amyloid light chains”
about 2/3 lambda, 1/3 kappa, the opposite of hte usal predominance of kappa in monoclonal gammopathies
Patients with primary amyloidosis have __________ in their urine or in their serum or in both?
Bence-Jones proteins; but most patients with bence-jones proteins do not have amyloidosis
What disease is primary amyloidosis associated with?
Multiple myeloma, but only 10% of patients with multiple myeloma have amyloidosis
Secondary amyloidosis commonly involves which organs?
kidneys, liver, spleen, lymph nodes, adrenals, and thyroid
What is secondary amyloidosis secondary to?
chronic inflammatory conditions
What is secondary amyloidosis commonly associated with?
RA, inflammatory bowel disease, chronic injection drug abuse, renal cell carcinoma, and Hodgkin’s disease
What is the protein deposited in secondary amyloidosis?
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
Induced amyloidosis commonly involves which organs?
nerves (e.g. carpal tunnel), joints, bone, gut, and tongue
What type of disease is induced amyloidosis?
Iatrogenic disease due to chronic HD, affecting as many as 70% of patients receiving long-term HD
What is the protein deposited in induced amyloidosis?
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
Hereditary amyloidosis is composed of which diseases?
Familial Mediterranean fever
Amyloid Poly-Neuropathy
Familial Mediterranean Fever
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
Amyloid Poly-Neuropathy
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
Localized (Senile) Cardiac Amyloidosis
ATTR deposition in the ventricles or AANF, amyloid atrial natriuretic factor, deposition in the atria.
Localized (Senile) Cerebral Amyloidosis
deposition of AB (amyloid beta), an abnormally large degradation product of APP (amyloid precursor protein) in Alzhimer’s Disease and Down Syndrome.
Localized Thyroid Amyloidosis
feature of medullary carcinoma and involves deposition of calcitonin
