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General Pathology

General Pathology. Basic Principles of Cellular and Organ Pathology Blood Derived Pigments. Jaroslava Dušková Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague http://www1.lf1.cuni.cz/~jdusk/. Pigments. Definition Classification Blood pigment breakdown extravascular

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General Pathology

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  1. General Pathology Basic Principles of Cellular and Organ Pathology Blood Derived Pigments Jaroslava Dušková Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague http://www1.lf1.cuni.cz/~jdusk/

  2. Pigments • Definition • Classification • Blood pigment breakdown • extravascular • intravascular • Hemosiderin • location • complications • Hemochromatosis • Icterus • definition • types • complications

  3. Pigments Definition: colored substances in the organism or environment

  4. Pigments Classification: • endogenous • hemoproteins derived • autogenous • exogenous

  5. Hemoproteins Derived Pigments -colour substances originating from hemoglobin modification or breakdown

  6. Iron metabolism • daily iron need on average 1mg • losses : bile, sweat …. • turnover regulated by the HEPCIDIN

  7. Hepcidin(& Ferroportin) • a 25-amino acid peptide hormone • central regulator of body iron metabolism • synthesized in the liver • secreted in plasma • binds to the cellular iron export channel ferroportin causing its internalization and degradation, thereby • decreasingiron efflux from iron exporting enterocytes and macrophages into plasma

  8. Ferroportin • a transmembrane protein that transports iron from the inside of a cell to the outside of it. • found on the surface of cells that store or transport iron, including: • Enterocytes in the duodenum • Hepatocytes • Macrophages of the reticuloendothelial system.

  9. oxyhemoglobin (Fe2+) hematin (Fe3+) methemoglobin (globin + hematin) carboxyhemoglobin Hemoproteins Derived Pigments

  10. Blood Pigment Breakdown • extravascular • intravascular

  11. ExtravascularBlood Pigment Breakdown Hemoglobin heme oxygenase biliverdinbiliverdin reductase  bilirubin (cells of MPS) + globin + Fe

  12. ExtravascularBlood Pigment Breakdown Globin  aminoacids Fe hemosiderin Fe(OH)3 + protein carrier hematoidin= tissue bilirubin (+ceroid) Etymology: Gk: haima blood + sideros, iron

  13. Hemosiderin - Features • brown • forms a deep blue product Prussian blue with acid potassium ferocyanide solution (Perls´ reaction)

  14. Hemochromatosis - life threatening complications • cirrhosis • hepatocellular carcinoma • heart failure • arrhytmia • diabetes

  15. Blood Pigment Breakdown • extravascular • intravascular

  16. IntravascularBlood Pigment Breakdown Hemoglobinbound to haptoglobin (2– globulin) + Fe biliverdin bilirubin urobilinogen enterohepatal stercobilinogen circulation urobilin stercobilin norm in blood:1,7-17,4mmol/l

  17. Bilirubin Processing • transport to the liver • hepatocyte entry – hepatocyte blood pole • glucuronylation • output to bile - hepatocyte bile pole

  18. Icterus –Jaundice Definition: a condition in which the tissues are yellowish due to the increase of bilirubin concentration (normal plasma: 1,7-17,4 mmol/l unconj. bilirubin bound to albumin)

  19. Bilirubin Processing • transport to the liver • hepatocyte entry – hepatocyte blood pole • glucuronylation • output to bile - hepatocyte bile pole

  20. generalized prehepatal flavin hepatal ruby posthepatal verdant icterus melas local surrounding hematoma Icterus – Jaundice

  21. Icterus • hemolytical (dynamic) • hepatocellular (dissociated) • obstructive (resorptive) • MIXED

  22. Icterus • hemolytical (dynamic) • corpuscular: • hered. spherocytosis, defect of G6P- dehydrogenase) • hemoglobinopathies (sickle cell anemia, thalassaemiae) • extracorpuscular (icterus neonati simplex, icterus neonati gravis…)

  23. Hemolytic Disease of the NewbornMorbus hemolyticus neonati – erythroblastosis fetalis • Rh- mother with an Rh+ fetus • anti Rh IgG crossing the placenta barrier • anaemia neonati • icterus neonati gravis • hydrops fetus universalis • abortus

  24. Ceroid • prevalence • erythrocytes breakdown places • fatty tissue necroses • avitaminosis E • melanosis coli • Dubin - Johnson syndrome

  25. Icterus • hepatocellular (dissociated) • hepatotoxic – acquired CCl4, amanitin, hepatitis epidemica, febris flava, leptospirosis, bact. sepsis... • enzymopathies – inborn (Crigler–Najjar Gilbert - glucuronyltransferase defect Dubin–Johnson, Rotor)

  26. Icterus • posthepatal – obstructive • acquired • obstruction • intraluminal • intramural, • extramural • inborn (primary billiary atresia)

  27. multiple intrahepatal both right and left hepatic ducts common hepatic duct choledochus papilla Vateri intraluminal - stone, ascaris… intramural - non-neoplastic (inflamm.), neoplastic… extramural – non-neoplastic,neoplastic combined Blockage of the Biliary Ways - causes

  28. Blockage of the Biliary Ways - complications • icterus • cholaemia • cholangiogenic sepsis • biliary cirrhosis • bleeding disorders

  29. Icterus • hemolytical (dynamic) • hepatocellular (dissociated) • obstructive (resorptive) • MIXED

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