Amyloid PDF

Bana Define amyloid: What is the diagnosis of amyloidosis? Amyloid is a pathologic proteinaceous substance identification of amyloid deposits in biopsy specimens by deposited between cells in various tissues and organs of histopathology dia...

Bana Define amyloid: What is the diagnosis of amyloidosis? Amyloid is a pathologic proteinaceous substance identification of amyloid deposits in biopsy specimens by deposited between cells in various tissues and organs of histopathology diagnosis). the body in a wide variety of clinical settings. May be done directly on the affected organ, on an abdominal fat pad biopsy What is amyloidosis? Proteins like amyloid stain pink a group of rare, serious conditions caused by a build-up of an abnormal protein called amyloid in organs and Congo red + “Apple green” birefringence → amyloidosis tissues throughout the body. / Additional investigations that may be required: The deposition of the various types of amyloid in tissues 1. FBC, LFTs (amyloidosis) leads to organ malfunction. 2. Renal function tests – creatinine, eGFR, 24hr / proteinuria it is a group of diseases having in common the 3. Cardiac tests: Troponin, ECG, ECHO, MRI deposition of abnormal protein 4. SPEP, light chain quantification 5. Bone marrow biopsy How do u detect amyloid? 6. Skeletal imaging 7. Genetic sequencing 1. Core issue in amyloidosis is the misfolding of 8. Variable presentation – diagnosis may take time to protein reach 2. Structurally abnormal protein cannot be cleared and prevents the normal function of cells/tissues 3. A specific precursor protein pathologically misfolds from its physiological tertiary structure into a more linear shape dominated by ‘beta- pleated’ sheets 4. Resistant to proteolysis → can’t be broken down 5. Misfolded protein aggregates into oligomers, eventually forming insoluble amyloid fibrils 6. deposit extracellularly in tissues 7. Both the circulating oligomers, which are cytotoxic, and the fibrils, which cause distortion of the tissue architecture, lead to organ dysfunction. What are the three components of Amyloid? 1. Non branching fibrils in a beta pleated sheet conformation. 2. Nonfibrillar pentagonal glycoprotein (Amyloid P component), which is derived from a circulating serum protein called serum amyloid P (SAP). 3. Proteoglycans Bana What are the classifications of amyloidosis? How does the kidney look like in amyloidosis? 1- Nonhereditary: Large, pale, grey, firm. Microscopic deposits in glomeruli, a. Systemic: (several organ systems) interstitial peritubular tissue, blood vessels walls. Eventual - Primary amyloidosis → immunocyte obliteration of the glomerulus dyscrasia - Secondary amyloidosis → complication How does the spleen look like in amyloidosis? of an underlying chronic inflammatory or destructive tissue process Moderate enlargement, pale, grey, waxy. Microscopic b. Localized (a single organ) deposits in splenic follicles (‘Sago’ spleen) or splenic sinuses 2- Hereditary (separate yet distinctive pattern of organ in large sheets (‘lardaceous’ spleen) involvement, that is usually systemic) What are the most common types of major fibril protein? 1. AL (amyloid light chain)(90%): - is due to an overproduction of immunoglobulin light chains derived from plasma cells → derived from monoclonal B cell proliferation - Kidneys are heart involved - Treatment: bone marrow transplant or How does the liver look like in amyloidosis? chemotherapy 2. AA (amyloid-associated): Massive enlargement → 9000g, Microscopic deposits in - is due to continuous overproduction of acute space of Disse, hepatic parenchyma and sinusoids. Trapped phase proteins in chronic inflammation hepatocytes undergo compression-atrophy and replaced by - Derived from SAA (serum amyloid- amyloid associated) synthesized in the liver under influence of cytokines such as IL-6 and IL-1, How does the heart look like in amyloidosis? as part of the physiological acute phase response. Mild to moderate enlargement, grey-pink subendocardial - If untreated → significant mortality elevations especially in the atria. Deposits throughout 3. ATTR - transthyretin – heart, lung, tenosynovium, myocardium, first between myocardial fibres, then causing ligaments pressure atrophy 4. Aβ amyloid is found in the cerebral lesions of Alzheimer disease What are the other organs/sites that help in diagnosing amyloidosis? AL and AA amyloid tend to deposit systemically. 1. Generally encountered as part of systemic disease “Endocrine” amyloid → localised 2. Endocrine: Adrenals, thyroid, pituitary, pancreas (diabetes) Clinical features of amyloidosis: 3. GIT – may be identified on a rectal biopsy 4. Tongue – macroglossia Depends very much on the subtype 5. Synovial tissue – carpal tunnel syndrome 1. Kidneys → protein in the urine 6. Skin 2. Heart → heart failure, restrictive cardiomyopathy 3. Liver → raised LFTs, hepatomegaly 4. GIT → malabsorption 5. Spleen → dysfunction, abnormal erythrocytes