General Pathology

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General Pathology Amyloidosis Fibrinoid, Hyalin Jaroslava Dušková Inst. Pathol. ,first Med. Staff, Charles Univ. Prague http://www1.lf1.cuni.cz/~jdusk/

Amyloidosis DEF.: confusion of protein digestion went with unusual extracellular statement of proteinaceous material - amyloid

Amylo id = starch like Amyloid - history Karl Freiherr von Rokitansky (1804-1878) Rudolf Ludwig Karl Virchow (1821-1902 ).

Amyloid - history 2. Karl Freiherr von Rokitansky (1804-1878) Austrian pathologist, conceived February 19, 1804, Königgrätz, Böhmen, Austrian Empire (now Hradec Králové, East Bohemia, Czech Republic); kicked the bucket July 23, 1878, Wien. Handbuch der pathologischen Anatomie IInd Band, Wien 1842

Amyloidosis – morphology Macroscopy: small sums – imperceptible larger stores – extended, firm, waxy organs

Ultrastructure & Biochemistry of Amyloid 90-95% non fanned fibrils diam. 10-12nm 5-10% p-part - glycoprotein + fibronectin, laminin, collagen 4

Amyloidosis conformational illness (Carrell and Lomas, Lancet, 1997) „… emerges when a constituent protein experiences an adjustment in size or vacillation fit as a fiddle with resultant self - affiliation and tissue statement" creased β – sheet structure

Conformational sicknesses (Carrell and Lomas, Lancet, 1997) Amyloidosis Prionoses - transmissible spongiform encephalopathies (incl. m. CJD) m. Alzheimeri creased β – sheet structure

Amyloidosis Classification: as indicated by the source protein (more than 20 diverse distinguished) as indicated by the appropriation systemic (summed up) localised

Systemic Amyloidosis - I. AL - imunocyte dyscrasia related light chains Ig (generally ) „ essential" Distribution: tongue, heart, GIT, liver, spleen, kidney Associated maladies: Plasma cell myeloma, B cell lymphoma,

Systemic Amyloidosis - II. AA - responsive systemic amyloidosis SAA = Serum Amyloid Associated protein „secondary" Distribution: liver, kidney, spleen, GIT, lymph hubs, gut, fat tissue Associated sicknesses : rheumatoid joint inflammation, ceaseless contaminations (tb, uncleanliness, bronchiectasiae, osteomyelitis, IBD, neoplasms MLH , RCC

Systemic Amyloidosis - III. feeble systemic SSA 25% individuals beyond 80 years old years (!) typical transthyretin TTR (prealbumin) for the most part heart & vessels invilvement

Systemic Amyloidosis - IV. A 2 - hemodialysis related  2 microglobulin Hereditary AA - Familial Mediterranean Fever ATTR - Famil. polyneuropatia transthyretin (changed shape)

Systemic Amyloidosis - complexities decreased elements of a few organs, esp. KIDNEY FAILURE IIIrd organize Amyloid nephrosis

Localized Amyloidosis - I. Feeble cardial ATTR - transthyretin - (structurally ordinary) Senile cerebral A  -  - amyloid protein

Cardiac Amyloidosis – clinical indications Dilated Cardiomyopathy (prevalent systolic dysfunction) Restrictive cardiomyopathy (dominating diastolic dysfunction) Congestive heart disappointment Rhytm anomalies Coronary deficiency Valvular brokenness Pericardial tamponade Enhance affectability to digitalis glycosides Atrial thrombosis - embolisation

Localized Amyloidosis - II. Endocrine ACal - ca medullare gl. thyreoideae AIAPP - islets of Langerhans related AANF - segregated atrial amyloidosis atrial natriuretic polypeptide Nodular tumoriform amyloid stores (tongue, lung,larynx, skin, urinary bladder, orbita)

Clinical Diagnosis of Amyloid Scintigraphy (in vivo) using human serum amyloid segment marked with 123 J Echocardiography (atrial amyloid)

Clinical Diagnosis of Amyloid Biochemistry sequening DNA - hered. shapes extraction of fibrils (from a biopsy specimen) spectrometry sequening of the amyloid protein

Amyloidosis – morphology Macroscopy: small sums – undetectable larger stores – broadened, firm, waxy organs

Morphological Diagnosis of Amyloid Macroscopy response Virchow I (sol. Lugolli) Virchow II (H 2 SO 4 )

Microscopy: KONGO red (+POLARISATION!) + KMnO 4 thioflavine S,T precious stone. violet (metachromasia) IMMUNOHISTOCHEMISTRY (electron microscopy ) Morphological Diagnosis of Amyloid

Materials: GIT (stomach, duodenum rectum, gingiva) biopsy kidney sural nerve & muscle fat goal biopsy – needle with an inward diam. 0,7-1,2mm Morphological Diagnosis of Amyloid Röcken Ch. Sletten K.: Amyloid in Surgical Pathology Virchows Arch., 2003, 1-26

integrated by youthful scientific expert at Bayer comp. 1883 as the first of monetarily lucrative direct (gesture requiring a severe) material colors licensed by AGFA 1885 (Aktiengeselschaft für Anilin farbenfabrikation) 3 weeks after the finish of the West Africa Conference to Europeans in 1885, the word Congo evoked fascinating pictures of distant focal Africa known as The Dark Continent the Congo red stain was named „Congo" for advertising purposes by a German material dyestuff organization in 1885 CONGO Red Steensma DP: „Congo" Red. Out of Africa? Curve. Pathol.Lab.Med.,2001, 125, 250-2

Reversibility of Amyloid The stores are NOT irreversible. e.g. Hrncic R. et al: Antibody intervened determination of light chain – related amyloid stores. Am.J. Pathol., 2000, 157,12369-46 Progression of summed up amyloidosis can be deferred or ceased by treatment of the basic infection. Röcken Ch. Shakespeare Ann: Pathology, conclusion and pathogenesis of AA amyloidosis. Virchws Arch. , 2002, 440, 11-122

Prevention & Therapy of Amyloid Prevention & treatment of the fundamental sicknesses Vaccination against β am. protein in mice reduced feeble plaque arrangement and enhanced memory. Nature Medicine, 2001, 7, eighteenth Jan. A β –based trial treatments in view of debasing chemicals . Zlokovic et al.: Neurovascular Pathways and Alzheimer Amyloid β - peptide. Mind Pathol. , 2005, 15, 78-83

Fibrinoid & Hyalin issue of protein digestion

Fibrinoid Change of Collagen vessels and connective tissue harm plasmorrhagia (spillage of plasma) stores of Ag-AB buildings recoloring attributes fibrin - like

Hyaline change Definition (chronicled, graphic) : intra-or extracellular change of homogenous rose „ shiny" appearance in the H & E recolored histological segments

Hyaline change Extracellular : corpus albicans, scars, hyalinoses of serous layers Intracellular: Crooke cells, Mallory' hyaline, Russell bodies

Ultrastructure Fibrinoid - collagen strands encompassed by plasma proteins might be reversible Hyalin – collagen filaments expanded in thickness, changed engineering rather stable

Hyaline change Extracellular: corpus albicans, scars, hyalinoses of serous films Intracellular : Crooke cells, Mallory' hyaline, Russell bodies

Significance of Fibrinoid Change reduced nature of the collagen ( solidness, penetrability) inclination to thrombosis in the vessels, aneurysms development

Significance of Hyalin Change decreased nature of the collagen ( flexibility) ischemia in organs with thickened blood vessel dividers intracellular - work, passing