General Pathology Basic Principles of Cellular and Organ

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

Pigments Definition: colored substances in the organism or environment

Pigments Classification: v endogenous hemoproteins derived – autogenous exogenous – v

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

Hemoproteins Derived Pigments v v oxyhemoglobin hematin (Fe 3+) methemoglobin (globin + hematin) carboxyhemoglobin

Blood Pigment Breakdown extravascular v intravascular v

Extravascular Blood Pigment Breakdown Hemoglobin biliverdin + globin + Fe biliverdin bilirubin

Extravascular Blood Pigment Breakdown Globin aminoacids Fe hemosiderin Fe(OH)3 + protein carrier hematoidin = tissue bilirubin (+ceroid)

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

Hemochromatosis – autosom. recessive 6 th chromosome – mutation of transferin. receptor ass. protein prevalence 0, 3– 0, 8 % (!!!) – deblocation of Iron intake (Iron need = cca 1– 2 mg/day) – deposits of HEMOSIDERIN: pancreas (diabetes bronze), myocardium, pituitary, joints, liver PHLEBOTOMY THERAPY

Blood Pigment Breakdown extravascular v intravascular v

Intravascular Blood Pigment Breakdown Hemoglobin bound to haptoglobin ( 2 – globulin) + Fe biliverdin bilirubin urobilinogen enterohepatal stercobilinogen circulation urobilin stercobilin

Bilirubin Processing v transport to the liver v v hepatocyte entry – hepatocyte blood pole glucuronylation v output to bile - hepatocyte bile pole

Icterus –Jaundice Definition: a condition in which the tissues are yellowish due to the increase of bilirubin concentration (normal plasma: 1 mg% unconj. bilirubin bound to albumin)

Bilirubin Processing v transport to the liver v v hepatocyte entry – hepatocyte blood pole glucuronylation v output to bile - hepatocyte bile pole

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

Icterus v hemolytical (dynamic) v hepatocellular (dissociated) v obstructive (resorptive) v mixed

Icterus v hemolytical (dynamic) – corpuscular (hered. spherocytosis - def. G 6 Pdehydrogenase, thalassaemia) – extracorpuscular (icterus neonati simplex, icterus neonati gravis)

Hemolytic Disease of the Newborn Morbus hemolyticus neonati – erythroblastosis fetalis v Rh- mother with an Rh+ fetus v anti Rh Ig. G crossing the placenta barrier – anaemia neonati – icterus neonati gravis – hydrops fetus universalis – abortus

Ceroid v prevalence – erythrocytes breakdown places – fatty tissue necroses – avitaminosis E – melanosis coli – Dubin - Johnson syndrome

Icterus v hepatocellular (dissociated) – hepatotoxic – acquired CCl 4, amanitin, hepatitis epidemica, febris flava, leptospirosis, bact. sepsis. . . – enzymopathies – inborn (Crigler–Najjar, Gilbert, glucuronyltransferase defect Dubin–Johnson, Rotor)

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

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

Icterus v hemolytical (dynamic) v hepatocellular (dissociated) v obstructive (resorptive) v mixed

Icterus Hemolytic Hepatocellular Obstructive Cause Bilirubin Input, conjug. , production output Bile flow block Serum bilirubin Unconj. Conj & unconj. Conj. Urine -urobilin, stercobilin 0 + +++ Urine urobilinogen +++ ++ - Feces stercobilinogen +++ +- 0 - Cholesterol +++ Bile acids +++