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Gilead -Topics in Human Pathophysiology Fall 2009 Drug Safety and Public Health Digestive system The Liver Part of digestive system Located in upper right abdominal quadrant Is served by two blood vessels: the hepatic portal vein, the hepatic artery Has one duct that carries bile away from it to the gall bladder for storage Composed of lobules that contain hepatocytes Blood moves easily from the external vessels, in porous capillaries past the hepatocytes to a central vein Hepatocytes do the work of the liver Figure 14.11 Liver Functions Secretes bile Metabolizes bilirubin - a breakdown product of hemoglobin Produces albumin, and clotting factors Metabolizes fats, proteins, carbohydrates, stores glycogen, makes HDLs and LDLs Inactivates many biologically active chemicals including alcohol, medicinal and recreational drugs, hormones, poisons Stores fat soluble vitamins and iron Converts ammonia (NH3) into soluble urea to be excreted by kidneys Figure 26.19b Hepatitis •Inflammation of the liver •Causes include: • Viruses • Drug toxicity • Wild mushroom • poisoning Viral Hepatitis Hepatitis A (HAV) Hepatitis B (HBV) Hepatitis C (HCV) Etiology Causes mild acute Causes acute illness and illnesschronic liver disease, can hepatocyte injury lead to liver cancer May cause acute illness, acts long term leading to chronic liver disease and risk of liver cancer Mode of transmission Fecal-oral primarily in children, young adults Contact with infected body fluids – blood, semen; contaminated needles, mother to newborn Contact with infected blood, mostly through contaminated needles Vaccination Hep A vaccine Hep B vaccine No vaccine From http://www.cdc.gov/hepatitis/index.htm Figure 9.20 Reverse transcriptase required Pathophysiology of Hepatitis • Destruction of hepatocytes by inflammation with edema and altered blood flow Symptoms of Hepatic Damage • • • • Jaundice Dark amber colored urine Nausea/vomiting Abdominal pain - R upper quad • Fatigue • Also- ascites, hepatic encephalopathy, coma, death Cirrhosis • Long term result of liver damage Liver Tests – Liver Panel • AST– liver enzyme, elevated with damage to cells • ALT - liver enzyme, elevated with damage to cells • ALP – enzyme related to bile ducts, levels elevate if there is a blockage • total bilirubin (blood)– may be elevated with liver damage or excessive RBC destruction • Albumin (blood) – checks on synthetic ability of liver cells • prothrombin time - decreased synthesis of clotting factors by kidneys See labtestsonline for more information Additional Liver Tests • Diagnostic tests for viral hepatitis – either serum tests for viral antigens, or serum tests for antibodies to the virus(indicating exposure) • Imaging – CT scan, ultrasound, MRI • Biopsy CT Scan of the Liver Normal liver Nodular cirrhotic liver with ascites www.integris-health.com 16 Drug Induced Hepatotoxicity • More than 900 drugs, toxins and herbs cause drug induced hepatotoxicity, • 20-40% of all fulminant liver failure cases are caused by drug induced hepatotoxicity • It is the most common reason a drug is withdrawn from approval • Damage to liver can be hepatocellular or cholestatic Drug-Induced Hepatotoxicity from http://www.emedicine.com/Med/topic3718 .htm Viral Hepatitis Treatment • Symptomatic support – diuretics, meds to decrease N load, Vit. K • Antivirals: • Interferons • Ribavirin • Surgery