Vt-2006 The pathology of the liver, bile ducts and pancreas Richard Palmqvist Docent, ST-läkare, Klin Pat Lab, Labcentrum The lecture in summary Introduction, histology & physiology in brief General phenomenon Specific diseases of the liver bile ducts pancreas with focus on infections autoimmune diseases congenital diseases tumours Histology 1
Functions of the liver Synthesis and secretion of bile Storage of glycogen and fat Involved in control of blood glucose levels, aminoacids and fatty acids Synthesis of cholesterol Inactivation and metabolism of toxic molecules Storage place for Fe, Cu, fat soluble vitamins etc Synthesis of proteins Phagocytosis of erythrocytes Icterus Clinically: Yellow skin, yellow sclera etc Bilirubin metabolism Unconjugated hyperbilirubinemia Conjugated hyperbilirubinemia NOTE Important picture 2
Liver steatosis Fatty upload in hepatocytes Unspecific reaction No symptoms Reversible Causes: Toxic reaction, inadequate nutriment, circulation disturbance, etc Classical example: Alcohol Liver cirrhosis Develops through prolonged destruction of liver cells followed by a chronic inflammation and increased formation of fibrosis Not reversible (not easily anyway!) Viable hepatocytes will proliferate (regeneration) Degeneration - Fibrosis - Regeneration Etiologi example: alcohol, virushepatitis, autoimmune diseases (ex PBC) Liver cirrhosis cont d 3
Liver cirrhosis cont d Liver cirrhosis gives system symptoms NOTE! Read portal hypertension by yourself! Hepatitis A (HAV) Hepatitis B (HBV) Hepatitis C (HCV) Hepatitis D Hepatitis E Virus hepatitis 4
Hepatitis virus pathogenesis Infection Viruses to the liver Virusreplication Acute liver cell damage Restitutio ad integrum Chronic hepatitis Subclinical disease Fatale fulminant liver necrosis Hepatitis C infection - what happens? Causes to Chronic Hepatitis Chronic hepatitis should be regarded as a disease with varying etiology HBV HCV HDV Autoimmune hepatitis Drog-induced hepatitis 5
Conditions sharing pathological features with classical forms of chronic hepatitis Wilsons disease α-1-antitrypsin deficiency Primär Biliär Cirrhos Primär Scleroserande Cholangitis Reasons to perform liver biopsy in chronic hepatitis Diagnosis Underlying causes Grading of inflammatory activity Staging of fibrosis Follow up of treatment Primary Biliary Cirrhosis (PBC) Kvinnor/Män 10:1 Intrahepatic bile duct destruction Granulomatous disease Mitochondrial autoantibodies Cirrhosis end stage 6
Primary Sclerosing Cholangitis Men/Women 2:1 Ulcerative colitis in 60 % Intra + extrahepatic bile ducts Endoscopic Retrograde Cholangiography (ERCP) for diagnosis or (MRCP) ERCP in PSC Alcholic hepatitis Steatohepatitis, acute Common in western countries Toxic effect Cirrhosis end stage Histology: Acute inflammation and fibrosis around central vein. Mallory bodies. Steatosis. 7
Non-alcoholic steatohepatitis (NASH) The same histological pattern as alcoholic steatohepatitis. Metabolic diseases. Overweight. Pathological laboratory tests Future common health care problem Can develop cirrhosis Many pharmaceutical drugs harms the liver Directly toxic effect or through metabolitis Examples: Paracetamol, Methotrexate, Tetracylins Drugs Congenital diseases Gilberts syndrom Crigler Najjar s disease Hemochromatosis Mb Wilson α-1-antitrypsin deficiency 8
Benign liver tumours Cysts Hemangioma Adenoma (hepatoma and bile duct adenoma) FocalNodular Hyperplasia (not neoplasia) Primary malignant tumours Hepatocellular cancer (80%) Cholangiocellular cancer Hepatoblastom Hemaangiosarkom NOTE! Liver metastases is the most common malignancy in the liver! Hepatocellular cancer Geography Livercirrhosis, hepatitis viruses, paracites, toxin exposition is predisposing Higly differentiated Satellite tumours common Vascular growth tendency 9
Cholelithiasis 1/10 Swedes Often no symptoms Increasing age Women - estrogens? Adipositas Ethnical groups Diet Metabolic conditions Cholelithiasis formation Cholecystitis Acute Chronic 10
Acute Cholecystitis Before patient has often episodes with biliary colic (=gallstensanfall) Symptoms acute cholecystitis: Abdominal pain in upper right quadrant, Mild jaundice (20%) Acute illness often subsides But in some cases persistent pain, fever, leukocytosis surgery Complications to cholelithiasis and cholecystitis Empyema Perforation peritonitis Ascending cholangitis Bile duct obstruction 11
Gall Bladder Cancer Adenocarcinoma Elderly Poor prognosis Pancreas - Malformations Pancreas annulare Heterotropic pancreas tissue, sometimes including insulae Acute Pancreatitis 12
Acute pancreatitis Chronic pancreatitis Pancreas tumours Pseudocysts Retentionscysts Congenital cysts Cystadenom Adenocarcinom Elderly Poor prognosis Men > Women 60-70 % caput pancreaticus Common type from duct epithelium. Fibrotic. 13
Pancreascancer 14