1. Gilead -Topics in Human Pathophysiology Fall 2010 Drug Safety and Public Health

2. Phagocytosis

3. Inflammation

4. Complement

6. Figure 21.5 Interferon

7.  B lymphocytes ◦ Mature in bone marrow, responsible for antibody mediated immunity ◦ When they recognize a pathogen (antigen) and are activated, develop into plasma cells and memory cells ◦ Plasma cells produce 1000s of antibodies (immunoglobulins) per second

8. B lymphocytes – Recognition Activation Attack (cloning and antibody production)

9. Figure 21.14 Antibody functions

10.  T lymphocytes ◦ 3 types: helper T cells, cytotoxic T cells, suppressor T cells ◦ When recognize a pathogen and are activated, these attack the pathogen and create a cadre of memory cells

12.  Recognize pathogen presented by other WBCs  Are activated by cytokines by other WBCs  “Clone”themselves to form active cells and memory cells  Release cytokines to activate and stimulate other WBCs, including B cells and phagocytes

13. Macrophages act as antigen presenting cells

14. Figure 21.17 Helper T cells are presented with antigen by specialized WBCs When activated these helper T cells clone themselves into memory cells and active cells

15.  AKA killer T cells  Recognize pathogen (antigens) in virally infected cell or cancer cells  Activated by cytokines from helper T cells  “Clone” themselves into attack cells and memory cells  Attack by producing proteins that open holes in infected cells

16. Figure 21.19

17.  Memory cells circulate, sometimes for a lifetime, scanning for that pathogen they recognize  A second infection by the same pathogen will yield a stronger, faster immune response that prevents illness

19. Figure 21.12

20.  A retrovirus that infects host cells macrophages and helper T cells  Its RNA is reverse transcribed into DNA, then inserted into host chromosomes  Protein synthesis of viral DNA makes components of new HIV  The components are assembled into new virus and released from host

22. Reverse transcriptase required Reverse transcriptase required Protease required

24. Reverse transcriptase Inhibitors work here Reverse transcriptase Inhibitors work here Protease inhibitor s work here

25. Gilead -Topics in Human Pathophysiology Fall 2010 Drug Safety and Public Health

26. Digestive system

27. 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

28. Figure 14.11

29. 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

31. Figure 26.19b

32. Hepatitis Inflammation of the liver Causes include: Viruses Drug toxicity Wild mushroom poisoning

33. Viral Hepatitis From http://www.cdc.gov/hepatitis/index.htm

34. Figure 9.20 Reverse transcriptase required Reverse transcriptase required

35. Pathophysiology of Hepatitis Destruction of hepatocytes by inflammation with edema and altered blood flow

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

37. Cirrhosis Long term result of liver damage

38. 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

39. 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

40. CT Scan of the Liver 40 Nodular cirrhotic liver with ascitesNormal liver www.integris-health.com

41. 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

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