1.  Hepatic Pathology and Respiratory System Topics in Human Pathophysiology Fall 2011 Gilead Drug Safety and Public Health

2. Outline  Hepatic Pathophysiology  Digestive System Overview  Placement and role of liver  Liver microstructure  Pathologies of liver  Respiratory Structure and Function

3. Digestive system

4. 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

5. Figure 14.11

6. Hepatic Portal System

7. Liver Functions Secretes bile – which emulsifies fats within small intestine 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

10. Hepatitis Inflammation of the liver Causes include: Viruses and other pathogens Drug and alcohol toxicity Environmental toxins Obesity, autoimmune disorders

11. Viral Hepatitis Hepatitis A (HAV) Hepatitis B (HBV)Hepatitis C (HCV) EtiologyCauses mild acute illness- hepatocyte injury Causes acute illness and chronic liver disease, can 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 VaccinationHep A vaccineHep B vaccineNo vaccine From http://www.cdc.gov/hepatitis/index.htm

12. Figure 9.20 Reverse transcriptase required

13. Pathophysiology of Hepatitis  Destruction of hepatocytes (necrosis) by inflammation  Altered blood flow through and to liver  Edema – both peripherally and in portal vessel area  Blockage of bile ducts leading to reduced bile in small intestine and problems with fat absorption  Reduction of ability to make blood proteins including albumin, clotting factors, complement  Buildup of blood toxins including urea and ammonia

14. Symptoms of Hepatic Damage  Jaundice  Dark amber colored urine  Nausea/vomiting  Abdominal pain - R upper quad  Fatigue  Also- ascites, hepatic encephalopathy, coma, death

15. Cirrhosis  Long term result of liver damage

16. 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 liver See labtestsonline for more information

17. CT Scan of the Liver 17 Nodular cirrhotic liver with ascites Normal liver www.integris-health.com

18. 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

19. Figure 10.1 Respiratory System

20.  Gas exchange  Protection  Speech  Compression of abdomen and spine stiffening  Acid-Base balance Respiratory Functions

21.  Figure 10.8

22. Respiratory Interface  Alveolar wall  Capillary wall  Surfactant  Gas Exchange occurs by diffusion