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 (NH 3 ) 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 From

Figure 9.20 Reverse transcriptase required 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 16 Nodular cirrhotic liver with ascitesNormal liver

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of all fulminant liver failure cases are caused by drug induced hepatotoxicity It is the most common reason a drug is withdrawn from approval Damage to liver can be hepatocellular or cholestatic Drug-Induced Hepatotoxicity from

Viral Hepatitis Treatment Symptomatic support – diuretics, meds to decrease N load, Vit. K Antivirals: Interferons Ribavirin Surgery