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Normal structure of liver. Normal function of liver. Metabolic (glucose homeostasis…) Synthetic (albumin, coagulation factors) Storage (glycogen, triglycerides, Fe, Cu, vitamins soluble in fat) Catabolic (endogenous substances – hormones…, exogenous substances – drugs, alcohol…)
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Normal function of liver • Metabolic (glucose homeostasis…) • Synthetic (albumin, coagulation factors) • Storage (glycogen, triglycerides, Fe, Cu, vitamins soluble in fat) • Catabolic (endogenous substances – hormones…, exogenous substances – drugs, alcohol…) • Excretoric (bile)
Histologic examination • Necropsy • Excision during laparotomy • Fine needle punction • Percutaneous punction biopsy • unguided • laparoscopic • guided (Sono, CT) • transjugular
Representativeness • Biopsy represents approx. 1/500 000 of organ • Ideal biopsy (Scheuer, MacSween) • 2 cm length • more than 4 (8) portal tracts • Borderline representativeness • contact CLINICIAN!! • Non-representative
QualityClinical data • Clear and sufficient • clinical outcome, history • etiology • biochemical findings, other markers (oncomarkers, markers of autoimmunity…) • treatment • previous histology • preliminary diagnosis! • Unclear • contact CLINICIAN!! • Insufficient and confusing
Quality Diagnosis • Diagnosis • recent diagnostic praxis (grading and staging of chronic hepatitis…) • recent diagnostic textbooks - contact CLINICIAN!! • Methods • biopsy - contact CLINICIAN!! • immunohistochemistry, ELMI -contact CLINICIAN!! • experimental
Histologic examination – special stains and methods • Haematoxylin/eosin • Fouchet – bile (green), collagen (red) • Fe, Cu – Fe pigment, Cu pigment • Gömori – reticulin mesh • Orcein – HBsAg • PAS, Müller – mucopolysaccharides • Immunohistochemistry (HBsAg, HBcAg, a1 fetoprotein, CEA, hepatocytes – OCH1E5) • ELMI (metabolic diseases) • PCR (HBV DNA, HCV RNA,…)
Damage of hepatocytes • Type (ischemic-coagulation necrosis, piecemal necrosis, apoptosis) • Extent (monocellular, focal, submassive, massive, bridging: C-C; C-P) • Localization (centrolobular, periportal, midzonal) • Course • regeneration, healing ad integrum • regeneration + fibrosis: cirrhosis • acute liver failure: coma and death
Liver failure • Jaundice • Hypoalbuminemia • Coagulopathy • Hyperamonemia • Increase of levels of cytosolic enzymes • Endocrine complications • Hepatoencephalopathy • Hepatorenal syndrome • Coma
Cirrhosis • Nodular rearrangement • Morphology • micronodular • macronodular
Cirrhosis: etiology • Alcohol (60-70%) • Chronic hepatitis (10%) • Cryptogenic (10-15%) • Biliary (primary, secondary) • Haemochromatosis (primary, secondary) • Metabolic diseases (tyrosinemia, galactosemia) -very rare
Cirrhosis: complications • Portal hypertension • Liver failure • Hepatocellular carcinoma
Portal hypertension • Prehepatic (tumor, infection, pancreatitis, pregnancy, peroral contraceptives) • Intrahepatic – most frequent (cirrhosis, fibrosis) • Posthepatic (congestive cardiac failure, Budd-Chiari syndrome, venoocclusive disease) • Signs: • portosystemic shunts • splenomegaly • ascites
Hepatitis: etiology • Infectious (acute, chronic) • viruses (most often) • bacteria (TBC, malaria, salmonelosis, leptospirosis,…) • parazites (ecchinococcus) • protozoal (amebiasis) • Non-infectious (acute, chronic) • autoimmune • metabolic • drug induced • cryptogenic
Viral hepatitis: course • Acute (HAV, HBV, HCV, HDV, HEV) • Chronic (HBV, HBV + HDV, HCV) • risk of cirrhosis development • risk of hepatocellular carcinoma development • Fulminant (HBV, HCV)
Acute hepatitis • Gross finding – oedematous, red liver • Microscopic finding • focal necrosis • bridging necrosis • panacinar/multiacinar necrosis • periportal necrosis • Hepatocytes • polymorphism • balooning degeneration
Acute hepatitis • Inflammation • polynuclear/mononuclear infiltration • activation of Kupfer’s cells • Other changes • cholestasis • damage of bile ducts • Regeneration
Fulminant hepatitis • Gross finding - softconsistency • Microscopic finding – complete necrosis of parenchyma • Course • liver failure-coma - death • regeneration – postnecrotic cirrhosis
Chronic hepatitis: etiology • HBV, HBV+HDV, HCV • Autoimmune • Drug induced • Wilson’sdisease • a1 anti-trypsin deficiency • Cryptogenic
Chronichepatitis: clinical definition Clinical symptoms of hepatitis more than: • 6 months • 12 months in HCV
Chronic hepatitis: morphology • Inflammation • portal • periportal • lobular • Necrosis/apoptosis • piecemal • bridging • focal • Fibrosis • Deposits (Cu, PAS globules,…)