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Gilead -Topics in Human Pathophysiology Fall 2010 Drug Safety and Public Health •Inflammation of the liver •Causes include: • Viruses • Drug toxicity • Wild mushroom poisoning Hepatitis A (HAV) Hepatitis B (HBV) Hepatitis C (HCV) Causes mild acute illnesshepatocyte 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 Fecal-oral transmission 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 B vaccine No vaccine Etiology Hep A vaccine From http://www.cdc.gov/hepatitis/index.htm Reverse transcriptase required Destruction of hepatocytes by inflammation with edema and altered blood flow Jaundice Dark amber colored urine Nausea/vomiting Abdominal pain - R upper quad Fatigue Also- ascites, hepatic encephalopathy, coma, death Long term result of liver damage 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 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 Normal liver Nodular cirrhotic liver with ascites www.integris-health.com 11 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of all fulminant liver failure cases are caused by drug induced hepatotoxicity It is the most common reason a drug is withdrawn from approval Damage to liver can be hepatocellular or cholestatic Drug-Induced Hepatotoxicity from http://www.emedicine.com/Med/topic3718 .htm Symptomatic support – diuretics, meds to decrease N load, Vit. K Antivirals: Interferons Ribavirin Surgery Respiratory system and Disease • Respiratory System structures – Airways – Respiratory interface – Gas transport – Lungs and ventilation • Selected Respiratory Disorders Unlabeled Figure 10.1 Figure 10.1 Respiratory Interface • • • • Alveolar wall Capillary wall Surfactant Gas Exchange occurs by diffusion Figure 10.8 Gas Transport • Oxygen • Carbon dioxide Figure 10.7 Respiratory Disorders • • • • • Flu (example H1N1) Asthma Cystic fibrosis (and accompanying infections) Pulmonary aspergillosis Pneumonia H1N1 • Cause – Influenza A virus • Symptoms – – – – – – – – Fever Sore throat Cough Body aches Headache Chills Fatigue Vomiting and diarrhea H1N1 H1N1 • Susceptible populations • Antivirals for influenza – Tamiflu (oseltamivir), Relenza (zanamivir), peramivir • Complications – Pneumonia and respiratory failure – Bronchitis – Ear infections – Sinus infections Asthma Cystic fibrosis • Inherited disorder causing a defect in a cell membrane Cl- channel • Causes thick sticky mucus buildup in airways and ducts of pancreas, etc. • Shortens lifespan because of pneumonia, malnutrition, etc. Pulmonary aspergillosis • Fungal lung infection • Common with AIDs patients and cystic fibrosis patients • Treated with Ambisome (amphoterocin B), one of several antifungals, alters fungal cell permeability Pulmonary Aspergillosis from an AIDS patient during autopsy http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijid/vol 6n1/aspergillosis.xml Pneumonia • Fluid buildup in lung alveoli • Thickens respiratory interface, interrupting diffusion of gases • Caused by a wide variety of microorganisms including bacteria, aspergillus and pneumocystis fungi, influenza virus (Tamiflu), cytomegalovirus (Vistide) Pneumonia Gilead treatments for lung infections • Cayston® (aztreonam) for Pseudomonas aeruginosa • Tamiflu for influenza viruses • Ambisome for aspergillus fungus • Vistide for cytomegalovirus Tests for Lung Function • • • • • Chest X-ray (CXR) Pulmonary function tests Sputum cultures Pulse oximetry Arterial Blood Gases (ABGs) Pneumonia X-ray http://www.med-ed.virginia.edu/courses/rad/cxr/pathology3chest.html Pulmonary Function Tests Figure 22.16a (VC) FEV1 Should be at least 80% of VC Figure 22.16a Sputum Culture •Patient donates a sputum sample •It is cultured with various media to determine causative agent of lung infection Pulse Oximetry •Measures arterial hemoglobin oxygen saturation •Normal is > 95% •Indicator of effectiveness of respiratory interface and gas diffusion Arterial Blood Gases • • • • • pH PCO2 PO2 O2 Saturation HCO3-