GI 4 Diseases of the Liver PDF

GENERAL PATHOLOGY Diseases of the liver Dr. Antonio Barrasa  Intended learning objectives To introduce to the clinical presentation of the patient with diseases of the liver – Introduction to pathophysiology of jaundice – Introduction to pathophysiolog...

GENERAL PATHOLOGY Diseases of the liver Dr. Antonio Barrasa  Intended learning objectives To introduce to the clinical presentation of the patient with diseases of the liver – Introduction to pathophysiology of jaundice – Introduction to pathophysiology of hepatitis – Introduction to pathophysiology of alcoholic steatohepatitis – Introduction to pathophysiology of non alcoholic steatohepatitis – Introduction to pathophysiology of cirrhosis – Clinical exploration of the patient with liver disease Dr. Antonio Barrasa Liver’s functional anatomy 3  Hematologic functions of the liver food and drugs are proceced in the liver central vein or bile space or lymph haem ( from hb myoglobin cytochrome) capilars on liver and = same type of pressure iron carbon dioxxide haem oxygenase biliverdin biliverdine reductase bilirubin glucoronyl transferase add 2 glucoronic ac biluribin = lipophylic = bind albumin (bile) conjugated bilirubin attach salts (aliphatics) glucuronic ac for soluble of the bilirubin glucuronization = unsoluble to soluble conjugated bilirubin = soluble (bile and blood) unconjugated bilirubin = unsoluble colorimetry = mesure of the color = bilirubin you mesure the amount of yellow plasma = both type of bilirubin let clotting that blood = no cells and no proteins = only ions and ac mesure the yellow in the serum = only the conjugated bilirubin (soluble) unconjugated bilirubin in the stools = bleeding or loss of direct way to mesure conjugated bilirubin = direct bilirubin (in the stool = brown) proteins undirect way to mesurere unconjugated bilirubin = undirect bilirubin (soustraction) 4  Jaundice Refers to the yellowish tainting of skin and mucosas due to a deposit of bilirubin. Normally, it becomes evident with total bilirubin concentrations higher than 2,5 mg/dl. – Pre-hepatic jaundice – Hepatocellular jaundice – Obstructive (cholestatic) jaundice Dr. Antonio Barrasa  Pre-hepatic jaundice Haemolysis – Newborn’s Congenital hyperbilirubinemia Sabinston’s chart 22.17 Dr. Antonio Barrasa  Hepatocellular jaundice Inability to transport bilirubin into the bile DUE TO A PARENCHIMAL DISEASE – Acute – Chronic Dr. Antonio Barrasa  Obstructive jaundice Blockade of the transit of bile to duodenum – Intrahepatic – Extrahepatic Dr. Antonio Barrasa  Investigations in jaundice History – Pain, itching, choluria, acholia, risk factors Clinical exploration – Signs of anemia, liver disease, liver palpation Laboratory – Bilirubin levels, liver function tests, hemoglobin,… Ultrasound and other image tests Biopsy ERCP Dr. Antonio Barrasa Investigations in jaundice Sabinston’s Fig 22.15 Dr. Antonio Barrasa  Hepatitis Inflammation of the liver tissue – Infectious Pain Viral Jaundice Bacterial Anorexia and weight loss Eukaryotic Healing – Toxic Progressive Alcoholic Cirrhosis NASH Liver failure Other – Autoimmune – Ischemic Dr. Antonio Barrasa Hepatitis Dr. Antonio Barrasa  Alcoholic Steatohepatitis Risk factors. Consumption > 30 g/d – Drinking pattern – Gender – Genetics – Nutrition Pathophysiology – 80% alcohol – Alcohol dehydrogenaseàAcetaldehyde Cell death – Aldehyde dehydrogenaseàAcetate & Acetyl CoA & NADH Inflammation – 20 % alcohol Fribrosis – Microsomal etanol-oxydising system (MEOS) Cytochrome CYP2E1 – Acetate+free radicals Alcoholic fatty liver disease Alcoholic hepatitis Alcoholic cirrhosis Dr. Antonio Barrasa  Nonalcoholic Steatohepatitis (NASH) Liver inflammation due to accumulation of fat in the absence of alcohol intake – Part of the Non-alcoholic fatty liver disease (NAFLD) – Part of the metabolic syndrome – Progresses to cirrhosis Pathophysiology – Obesity + insuline resistance – Hepatocellular injury Radicals during fatty acid oxidation Toxicity by fatty acids and other metabolites Endoplasmic reticulum stress Inflammatory hepatocellular injury Cell death Inflammation Fibrosis Cirrhosis Dr. Antonio Barrasa Liver Cirrhosis Davidson’s Fig 22.26 Types Consequences Micronodular Liver insufficiency Macronodular Portal hypertension Dr. Antonio Barrasa  Liver Cirrhosis Clinical manifestations Liver insufficiency Portal hypertension – Jaundice and itching – Ascites – Protein deficiency – Varices & bleeding Albumin – Hepatorenal syndrome Clotting – Splenomegaly – Hypoglycemia Hepatomegaly – Endocrine changes – Confusion and coma Dr. Antonio Barrasa Clinical exploration Davidson´s pg 843 Dr. Antonio Barrasa Many thanks [email protected] Dr. Antonio Barrasa