Liver pathology Liver functions Protein synthesis • albumin, clotting factors, acute-phase proteins and others Excretion of bile • bilirubin, bile acids, cholesterol, phospholipids Destruction of hormones • estrogens Metabolism of xenobiotics • drugs, toxic substances, metabolic products of intestinal microflora Deposition • glycogen, triglycerides, iron, copper and Vitamin A vv. hepaticae v. cava inf. portal tract bile v. portae blood central vien a. hepatica truncus coeliacus aortae Liver diseases Hepatosis Hepatitis Cirrhosis Obstructive diseases of biliary tract Hepatocellular carcinoma Hepatosis degeneration and / or necrosis of hepatocytes without inflammation • acute acute liver failure – microvesicular steatosis – Massive necrosis (mainly centrilobular necrosis) • chronic – macrovesicular steatosis do not have significant clinical implications – Alcoholic fatty liver disease – Nonalcoholic fatty liver disease Steatosis (fatty hepatosis) Micro- Мacro- Pathogenesis Violation of β- Metabolic disorders oxidation of fats lipoproteins Localization of fat In the mitochondria In the cytoplasm Nucleus In the center of the Shifted to the cell periphery, misshapen liver function Acute failure Has almost no effect Steatosis: micro-vs. macrovesicular Microvesicular steatosis • Reye's syndrome • Acute hepatosis of pregnancy • Alcoholic liver disease Macrovesicular steatosis • Alcoholic liver disease • Nonalcoholic fatty liver disease • Hepatitis C • etc. Necrosis of hepatocytes • Coagulation (coagulative) necrosis ischemia or toxins • Colliquation (liquefative) necrosis osmotic lysis Balloon (hydropic) degeneration active inflammation Necrosis Centrilobular (around the central vein) ischemia, toxins Piecemeal (on the border of portal tract) Bridging • porto-central • center-center • porto-portal hepatitis (necrosis + apoptosis + inflammation) Submassive (necrosis whole lobule) Massive (necrosis of several lobules) Centrilobular Piecemeal Bridging porto-central porto-portal center-center Massive liver necrosis viruses (Hepatitis B, C) exotoxins (mushrooms, arsenic, phosphorous) drugs (acetaminophen, carbon tetrachloride, halothane, isoniazid, rifampin) acute fatty liver of pregnancy hepatic vein obstruction hyperthermia ischemia tumors Wilson’s disease Massive liver necrosis Massive necrosis of hepatocytes in all zones (possible periportal sparing) with reticulin collapse, often with minimal inflammatory reaction May be bile duct proliferation, lymphocytic infiltration of central veins Alcoholic liver disease is a set of clinical syndromes and pathological changes in the liver due to alcohol (ethanol) The main forms of ALD: • steatosis • hepatitis • cirrhosis • Alcohol is a direct hepatotoxic agent • ALD develops if alcohol abuse for 10-12 years: • 40-80 g alcohol / day - men • 20-30 g alcohol / day – women • ALD development does not depend on the type of alcohol drink Steatosis Macrovesicular steatosis Hepatitis Cirrhosis Micronodular cirrhosis mixed Nonalcoholic fatty liver disease is a spectrum of conditions characterized by histological features similar to alcoholic liver disease, and are manifested in individuals who do not consume alcohol in quantities that have a damaging effect on the liver Nonalcoholic fatty liver disease steatosis steatohepatitis cirrhosis The most important epidemiological features of NASH female 60-83% obesity 40-100% Type 2 diabetes, hyperglycemia, impaired 20-75% glucose tolerance hyperlipidemia 20-81% Morphology NASH Indistinguishable from the ALD Liver diseases Hepatosis Hepatitis Cirrhosis Obstructive diseases of the biliary tract Hepatocellular carcinoma Hepatitis on the etiology • viral – hepatotrophic viruses (A, B, C, B + D, E, G) – non-hepatotrophic viruses (Ebstein-Barr virus, CMV, HSV, yellow fever, etc.) • autoimmune • metabolic – Wilson's disease – α1-antitrypsin deficiency – hemochromatosis • nonalcoholic • toxic – drug – alcoholic on the duration • acute (up to 6 months) • chronic Morphological differences of some hepatitis Hepatitis В Hepatitis С Nonalcoholic Alcoholic steatohepatitis hepatitis hydropic hydropic hydropic +macroves./mic Dystrophy hydropic +macroves. +macroves. roves steatosis steatosis steatosis Ground-glass Features of hepatocytes, No Mallory bodies cells "sanded" nuclei Councilman Apoptosis No bodies Hepatic lobules by neutrophils Portal tracts and adjacent areas of Inflammation (esp. around hepatic lobules by lymphocytes Mallory bodies) Fibrosis All types, except the central vein fibrosis All types Macrovesicular steatosis Hydropic swelling Mallory bodies “Ground-glass” hepatocytes Concilman bodies Outcomes of viral hepatitis Acute • recovery • chronic hepatitis (for A & E undescribed) • acute liver failure (fulminant form) Chronic • cirrhosis • hepatocellular carcinoma Fibrosis – excessive accumulation of extracellular matrix molecules (ECM) in tissue ECM in normal liver less than 3% of the cross-sectional area located in – portal tracts – the walls of the sinusoids – around the central veins synthesized by – fibroblasts of portal tracts – fibroblasts around the central veins – stellate cells (Ito) ECM in fibrosis of the liver content of 6 times above normal forms sept – porto-central – center-center – porto-portal synthesized by – periductal myofibroblasts – stellate cells (Ito), transformed into myofibroblasts – septa myofibroblasts – myofibroblasts around the central veins Fibrosis of the portal tract Perisinusoidal fibrosis Fibrosis of the central vein Porto-central septum Porto-portal septum Center-center septum Liver diseases Hepatosis Hepatitis Cirrhosis Obstructive diseases of the biliary tract Hepatocellular carcinoma Cirrhosis Cirrhosis - is a diffuse process characterized by fibrosis and the transformation of the normal architecture of the liver in structurally abnormal nodes Anthony PP, Ishak KG, Nayak NC, Poulsen H, Scheuer PJ, Sobin LH. The morphology of cirrhosis: definition, nomenclature and classification. Bull World Health Organ 1977;55:521–540. Criteria cirrhosis Diffuse fibrosis Nodes regenerates (false lobules), which does not have the typical structure of the hepatic lobules Сlassification of cirrhosis Havana classification of 1952 • Postnecrotic • Portal • Biliary According to the size of false nodules • Micronodular - <3 mm • Macronodular -> 3 mm • Mixed portal tract porto-central septum central vein Portal Necrosis Porto-central bridging Porto-central septa Perisinusoidal fibrosis Chronic ischemia Activation of hepatic stellate cells in the space of Disse Chronic inflammation Postnecrotic Complications of cirrhosis Chronic liver failure Portal hypertension Hepatocellular carcinoma Major complications of liver disease Liver failure (acute or chronic) massive necrosis of the liver, microvesicular steatosis, cirrhosis of the liver • hepatic encephalopathy • hypocoagulation, hypoproteinemia • hepatorenal syndrome (acute renal failure) Portal hypertension cirrhosis • bleeding from varices of esophagus • ascites-peritonitis • splenomegaly hypersplenism anemia and thrombocytopenia hypocoagulation • Hepatocellular carcinoma cirrhosis, chronic hepatitis Obstructive diseases of the biliary tract Obstructive diseases of the biliary tract Secondary biliary cirrhosis Primary biliary cirrhosis Primary sclerosing cholangitis Secondary biliary cirrhosis Causes • Obstruction of extrahepatic bile ducts gallstone disease stricture of bile duct cancer of the pancreatic head or major duodenal papilla atresia of bile ducts (congenital malformation) Morphology • pronounced chronic cholestasis (bile lakes) • neutrophils around the bile ducts • swelling of the portal tracts • cirrhosis, portal fibrosis Primary biliary cirrhosis is a chronic, progressive, often lethal disease characterized by: • destruction of intrahepatic bile ducts, • inflammatory infiltration of portal tracts, • fibrosis with a possible outcome to cirrhosis and liver failure Primary biliary cirrhosis Causes • Autoimmune destruction of intrahepatic bile ducts (possible association with other autoimmune diseases) Morphology • cholangitis - infiltration of portal tracts by lymphocytes with the destruction of the bile ducts • chronic cholestasis Cirrhosis - the final stage of the disease Primary sclerosing cholangitis is a chronic, progressive disease characterized by inflammation, fibrosis, obliteration and segmental dilatation of intra- and extrahepatic bile ducts by retrograde cholecysto-pancreatography - beaded change the bile ducts Primary sclerosing cholangitis Primary sclerosing cholangitis Causes • Autoimmune destruction (in 70% of cases associated with ulcerative colitis) Morphology • periductal onion-like fibrosis of portal tracts with segmental stenosis • chronic cholestasis Outcome • cirrhosis .