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Amyloidosis (Overview (formed of B-sheet pleated polypeptide chains that…
Amyloidosis
Overview
formed of B-sheet pleated polypeptide chains that are wound together
non-branching fibrils, 7.5-10 nm, cannot be removed
definition: extracellular deposits of insoluble fibrillar proteins that can lead to tissue damage & dysfunction
Factors contribute to amyloidosis
presence of mutated protein (hereditary amyloidosis)
limited proteolysis (amyloidosis associated with Alzheimer)
abnormally high [proteins] may lead to misfolding & aggregation can happen in
increased production (chronic inflammation)
impaired excretion (chronic renal failure)
aging (senile amyloidosis)
Classification of Amyloidosis
Localized
occurs in lung, larynx, skin, urinary bladder, tongue, region of eye
limited to single organ/tissue without involvement of any other site in the body
consist of AL protein, therefore may represent immunocyte-derived amyloid
Hereditary (familial)
Familial Amyloidotic Neuropathies (TTR type) - peripheral & autonomic nerve, autosomal dominant
Familial Mediterranean Fever (AA type) - rare & limited to ppl of Armenian, Jewish & Arabic, autosomal recessive, unknown cause of fever with inflammation of serosal surfaces (pleura, peritoneum, synovial membrane)
Systemic (generalized)
Haemodialysis associated Amyloidosis - pts on long term haemodialysis for renal failure, AB protein, occur in synovium, joint, tendon sheath, eg: carpal tunnel syndrome
Amyloidosis of Aging - systemic deposition of amyloid in elder (70s & 80s), amyloid composed of normal TTR, typically involves heart which then leads to cardiac dysfunction
Secondary Amyloidosis - secondary to associated inflammatory condition (chronic inflammation, infection, inflammatory bowel disease, neoplasia), AA protein, occur in liver, spleen, lymph node, kidney, adrenal, thyroid
Primary Amyloidosis - clinical features from effect of amyloid without other associated disease, have some immunocyte dyscrasia, AL protein, occur in skin, GIT, tongue, heart
Types of amyloid proteins
others
B2-microglobulin - component of MHC Class I mol. Present at high conc in serum of patients with renal disease, retained in circulation because not filtered by dialysis membranes
Transthyretin (TTR) - normal serum protein which binds and transports thyroxine & retinol. Deposited as amyloid under 2 conditions; mutations in gene coding for transthyretin & normal transthyretin deposited in heart of old ppl (protein normal but accumulates)
most common
AB amyloid - derived from much larger transmembrane glycoprotein called amyloid precursor protein (APP). Found in cerebral lesions of Alzheimer
AA (amyloid associated) - non Ig protein derived from larger serum precursor called SAA (serum AA) synthesized in liver and increased in inflammatory states. Associated with chronic inflammatory disorders
AL (amyloid light chain) protein - made up of complete Ig light chains, amino-terminal fragments of light chains or both. Its deposition is associated with monoclonal B-cell proliferation