GI&HB Week Two

  1. This is a highly hydrophobic compound that consists of 4 fused hydrocarbon rings that form a steroid nucleus
  2. Cholesterol in blood plasma is mostly found in what form?
    Esterified (with a fatty acid covalently linked the -OH at Carbon 3)
  3. What is the major site of cholesterol metabolism?
  4. What are the 3 sources of liver cholesterol?
    • Diet
    • Extrahepatic Tissue (reverse cholesterol transport)
    • De Novo Synthesis
  5. What are the three ways cholesterol leaves the liver?
    • VLDL Secretion
    • Bile Salt Synthesis & Secretion
    • Free Cholesterol Secreted in Body
  6. What are the two ways to get cholesterol out of the body?
    • Conversion to bile acids/salts
    • Fecal secretion
  7. What is cholesterol synthesized from?
    Acetyl CoA
  8. What is the first step of cholesterol synthesis, and where does it take place?
    • Synthesis of 3-hydroxy-3-methylglutaryl (HMG) CoA from Acetyl CoA
    • Takes place in the cytoplasm of the liver cell
  9. What is the second step of cholesterol synthesis? What enzyme catalyzes this reaction, and what is the reducing agent?
    • Reduction of HMG-CoA to Mevalonate
    • Catalyzed by HMG-CoA Reductase
    • Reducing Agent: NADPH
  10. What is the rate-limiting step of cholesterol synthesis?
    Reduction of HMG-CoA to Mevalonate
  11. The synthesis of cholesterol from mevalonate is carried out by a complex series of steps. This pathway requires a lot of what two molecules? What does this mean for the body?
    • ATP & Acetyl CoA
    • You cannot make this compound if the body is starving
  12. Why is it so difficult for the body to rid itself of cholesterol?
    Because the molecule is so hydrophobic
  13. HMG-CoA reductase is subject to many kinds of metabolic control. What role does SREBP-2 play?
    The precursor of SREBP-2 (SREBP-SCAP) is retained in the ER when cholesterol levels are high. If cholesterol levels are lowered, however, then the SREBP-2 precursor is trafficked to the Golgi where proteases cleave the precursor. This releases soluble SREBP-2 so that it can move to the nucleus and promote transcription of the HMG-CoA reductase gene, which promotes production of cholesterol.
  14. Regulation of HGM-CoA reductase is subject to many kinds of metabolic control. What role do sterols play?
    Degradation of HMG-CoA reductase is accelerated when sterol levels are high. This serves to eliminate excess CoA to reduce cholesterol levels in the body.
  15. Regulation of HGM-CoA reductase is subject to many kinds of metabolic control. What role does phosphorylation by the AMP kinase play?
    HMG-CoA is inactive when it is phosphorylated. AMP kinase serves to phosphorylate HMG-CoA. This phosphorylation is activated with there are low levels of ATP in the cell.
  16. Bile acids are synthesized from free cholesterol in the liver. How is this done?
    Bile acids are conjugated to molecules of glycine or taurine by an amide linkage to form bile salts.
  17. Conversion of bile acids to bile salts increases the _______ nature of the compounds, making bile salts much better "detergents" for digesting lipids.
  18. What type of circulation results in a 95% reabsorption of bile salts that are secreted into the intestine during digestion?
    Enterohepatic Circulation (between the intestine and the liver)
  19. What is the total loss of bile salts from the intestine per day?
    ~ 0.5g/day
  20. A deficiency of bile salts in the liver can cause the formation of ______ which develop when the ratio of cholesterol to bile salts is high and cholesterol precipitates out of suspension in the gallbladder.
  21. What are two ways in which bile salt deficiency occurs?
    • When there is a disruption of enterohepatic circulation and the bile salts are not reabsorbed
    • There is liver disease that is preventing new synthesis of bile acids in the liver
  22. Membrane phospholipids are specialized lipids in which a polar, ionic compound is attached by a phosphodiester bridge to _____ or _____?
    • Diacylglycerol
    • Sphingosine
  23. What are the most abundant phospholipids?
  24. Sphingomyelin is a complex membrane phospholipid based on a _______?
  25. How do Glycosphingolipids differ from Sphingomyelin?
    They are also derived from a ceramide, but they do not contain a phospate group
  26. The plasma membrane is at a steady state balanced between exocytosis of secretory vesicles and endocytosis of plasma membrane proteins. Some membrane lipids are recycled and reused, whereas others are targeted to the lysosome for degradation. Accumulation of lipid from inadequate degradation is called ______, and causes what?
    • Lipidoses
    • Lysosomal Storage Diseases
  27. Sphingomyelin degradation requires which lysosomal enzyme to cleave the phosphoryl choline?
  28. Neimann-Pick disease is caused by a deficiency in what? What does it lead to?
    • Deficiency of Sphingomyelinase
    • Leads to lipidoses in liver, spleen, and CNS (in type A)
  29. This is a deficiency in the degradation of Beta-glucosidase, an ezyme that breaks down glucocerebroside; this causes the accumulation of
    glucocerebroside in cells.
    Gaucher Disease
  30. What are the main two types of liver function tests, and what is each for?
    • AST/ALT: Hepatocellular
    • ALK Phos: Cholestatic
  31. What are located in hepatocytes and released after hepatocellular injury? What are the two forms?
    • Transaminases
    • AST & ALT
  32. What is mild transaminitis with predominant AST indicative of (3)?
    Hepatic: Alcohol, Steatosis, Cirrhosis
  33. What is non-hepatic mild Transaminitis indicative of (4)?
    • Hemolysis
    • Myopathy
    • Thyroid Disease
    • Strenuous Exercise
  34. The AST:ALT ratio is elevated 2:1 in what disease?
    Alcohol Disease
  35. What disease is characterized by these symptoms?
    Associated Conditions: Obesity, Diabetes, Hyperlipidemia

    Diagnosis: AST/ALT < 1, exclude other causes, U/S, liver bx

    Treatment: treat associated conditions
    Non-Alcoholic Steatohepatitis
  36. What is the diagnosis?
    History is Key

    Labs: AST/ALT > 2, MCV >94

    Alcoholic Hepatitis: anorexia, fever, jaundice, hepatomegaly

    Treatment: abstinence, nutrition
    Alcoholic Liver Disease
  37. What is the incubation period for hep A?
    About 1 month
  38. What is the incubation period for hep B?
    Weeks - Months
  39. What is the diagnosis of the disease characterized by:
    AR mutation of HFE gene

    One of most common genetic diseases of liver

    Clinical Manifestations: after age 40 in men, 50 in women; fatigue, arthropathy, diabetes, impotence, hyperpigmentation, cardiomyopathy

    Diagnostic Tests: transferrin saturation > 50%; ferritin >200; genetic testing C282Y/C282Y

    Treatment: phlebotomy to ferritin < 50
  40. What is the diagnosis?
    This disease has widely variable clinical presentations: asymptomatic LFT abnormality; severe hepatitis with jaundice; cirrhosis and complications of portal HTN

    It is often associated with other autoimmune dz

    Diagnostic Labs:
    compatible clinical presentation
    ANA or ASMA with titer 1:80 or greater
    IgG > 1.5 upper limits normal
    liver bx - portal lymphocytes + plasma cells
    Autoimmune Hepatitis
  41. What is the diagnosis?
    AR -- Copper Metabolism
    Chronic hepatitis or fulminant hepatitis

    Associated clinical features:
    neuropsychiatric disease, hemolytic anemia

    Physical Exam:
    Kayser-Fleischer Rings

    ceruloplasmin down
    Urinary Cu up

    Wilson's Disease
  42. What is the diagnosis related to these symptoms?
    Clinical Features:
    Lung Disease: inadequate protease inhibitor activity
    Liver Disease: accumulation of variant A1AT in hepatocytes

    Presentations: neonatal hepatitis; elevated LFTs; hepatitis; cirrhosis

    Treatment: liver transplantation
    Alpha-1 Antitrypsin Deficiency
  43. Alkaline Phosphatase is produced by biliary epithelial cells. What pathologies are indicated by an elevation in APT (6)?
    • Biliary Duct Obstruction
    • Primary Biliary Cirrhosis
    • Primary Sclerosing Cholangitis
    • Infiltrative Liver Disease
    • Hepatitis/Cirrhosis
    • Medications
  44. What is the diagnosis?
    Cholestatic Liver Disease (ALP)

    Most common symptoms:
    Pruritis, fatigue; many pts asx, and dx by abnormal LFT

    Female:Male ratio 9:1

    Compatible clinical presentation
    AMA titer 1:80 or greater
    Liver bx -- bile duct obstruction

    Treatment: Ursodeoxycholic acid 15 mg/kg
    Primary Biliary Cirrhosis
  45. What is the diagnosis?
    Cholestatic Liver Disease (ALP)

    Inflammation of large bile ducts

    90% associated with IBD

    No autoantibodies, no elevated globulins
    Biopsy -- concentric fibrosis around bile ducts

    Cholangiocarcinoma: 10-15% lifetime risk

    Treatment: liver transplantation
    Primary Sclerosing Cholangitis
  46. What kind of history if associated with abnormal LFTs?
    • Pain
    • Edema, increased abdominal girth, confusion, GI bleeding
    • PMH: DM, hyperlipidemia, autoimmune
    • Medications
    • Alcohol
    • Sex, drugs, blood transfusion pre-1990
    • Family history of liver disease
  47. What can be seen in the Physical Exam in the evaluation of abnormal LFTs?
    • Skin: spider angiomata, gynecomastia
    • Liver size, splenomegaly
    • Clubbing, palmer erythema, D-contracture
    • Ascites
    • Edema
    • Mental status, asterixis
    • Obesity
    • Hyperpigmentation, Kayser-Fleischer Rings
  48. Bilirubin is a product of hemoglobin breakdown. What are its two forms?
    • Unconjugated (indirect): insoluble; increase in hemolysis; Gilbert Syndrome, meds
    • Conjugated (direct): soluble; increase in obstruction, cholestasis, cirrhosis, hepatitis, primary biliary cirrhosis, etc; no elevation until loss of > 50% capacity
  49. What are the three classifications of Maternal Liver Disease?
    • Intrahepatic Cholestasis of Pregnancy (ICP)
    • Acute Fatty Liver of Pregnancy (AFLP)
    • HELLP
  50. What is the diagnosis?
    Pregnant Patient

    Intense pruritis, variable LFT, intact liver function

    Treatment: UDCA Cholestyramine, Hydroxyzine
    Intrahepatic Cholestasis of Pregnancy (ICP)
  51. What is the diagnosis?
    Pregnant Patient

    Presents in 3rd trimester with HA, N/V, abd pain

    Often associated with pre-eclampsia/eclampsia

    Increased ALT
    Increased bilirubin
    Increased PT

    Treatment: glucose, correct PT, delivery
    Acute Fatty Liver of Pregnancy (AFLP)
  52. What is the diagnosis?
    Hemolysis, increased LFTs, decreased platelets

    plt <100
    LDH >600
    AST > 70
  53. What is the most common cause of drug-induced liver disease?
  54. What does albumin reveal about liver disease?
    • Poor marker of liver function
    • Decreased by trauma, inflammatory conditions, malnutrition
  55. What does Prothrombin Time (PT) reveal about liver disease?
    Insensitive: no change until liver loses 80% capacity
  56. What does Ammonia reveal about liver disease?
    • No correlation between brain and serum values
    • Only one contribution to encephalopathy
  57. A diverse group of metabolic disorders from enzyme deficiencies in heme synthesis
  58. Where does synthesis of porphyrias occur?
    Liver and Bone Marrow
  59. What is the rate limiting step in hepatic synthesis?
    ALA synthase
  60. What is the predominant site of synthesis in 5/7 of the porphyrias?
  61. What disease or class of diseases is associated with these symptoms?
    Abdominal Pain


    Dark Urine

    Neuropsych Features: hysteria, depression, psychosis, confusion, hallucinations, seizures, and comas

    Periphery Sensory Deficits

    Weakness leading to ascending paralysis or quadriplegia

    Overproduction of ALA and PGB (neurotoxic)
    Acute Porphyrias
  62. Are acute porphyrias more common in males or females?
    5x F > M
  63. What is the diagnosis?
    Most common acute porphyria

    Primarily manifests as derangement in ANS or psychiatric disorder

    Partial deficiency of PBG deaminase

    AD with variable expression
    Acute Intermittent Porphyria (AIP)
  64. What is the most common ACUTE porphyria?
    Acute Intermittent Porphyria (AIP)
  65. What are the treatment options for Acute Porphyrias?
    • IVFs and glucose administration
    • IV hematin
    • Avoidance of precipitants
    • Women triggered by menses improved with OCPs
    • HCC screening/surveillance
    • Special sunscreen
  66. What is the diagnosis?
    Deficient activity of uroporphyrinogen decarboxylase (UROD)

    Most common human porphyria

    Presents mid to late life
    Porphyria Cutanea Tarda
  67. What is the most common Porphyria?
    Porphyria Cutanea Tarda
  68. What porphyria is often co-morbid with these disorders?
    Factors/Diseases contributing to iron accumulation or oxidative stress in hepatocytes

    Excessive Alcohol Consumption

    Estrogen Use

    Chronic HCV

    Hepatic Siderosis



    End Stage Renal Disease
    Porphyria Cutanea Tarda
  69. These dermatologic findings are common in what porphyria?
    Increased Fragility
    Pigment Changes
    Hirsuitism (cheeks, forearms)
    Porphyria Cutanea Tarda (PCT)
  70. What are the treatments for Porphyria Cutanea Tarda (PCT)?
    • Phlebotomy (preferred)
    • Low Dose Hydroxychloroquine or Chloroquine
    • Avoid Offending Agents
  71. What is the diagnosis/porphyria type?
    UROD Deficiency

    AR form of familiar PCT


    More severe

    Presents in childhood (<2yrs)

    Features resemble congenital erythropoietic porphyria (CEP)
    Hepatoerythropoietic Porphyria (HEP)
  72. What is the diagnosis/porphyria type?

    First yr of life

    Blisters/Disfiguring lesions in exposed areas


    Brownish discoloration of teeth

    Coombs neg. hemolytic anemia

    Congential Erythropoietic Porphyria (CEP)
  73. What is the treatment of Congential Erythropoietic Porphyria (CEP)?
    • Splenectomy
    • Transfusion/Hematin Infusions
    • BMT curative in severly affected patients
  74. What is the second most common type of Porphyria?
    Erythropoietic Protoporphyria (EPP)
  75. What is the diagnosis/porphyria type?
    Partial deficiency of FECH

    Final step in heme synthesis

    AD with variable penetrance

    Extreme Photosensitivity -- scars and lichenification

    Mild hypochromic

    Microcytic anemia

    5-10% develop liver disease
    Erythropoietic Protoporphyria (EPP)
  76. What is the treatment of Erythropoietic Protophorphyria (EPP)?
    • IV hematin
    • Charcoal
    • Cholestyramine
    • BMT
  77. What are the histological changes to the liver from Acute Porphyria (4)?
    • Elevated transaminases
    • Bile acid levels
    • Liver Biopsy shows steatosis and iron deposition
    • Increased HCC risk
  78. What are the histological changes to the liver due to PCT/HEP (6)?
    • Liver enlargement
    • Fatty infiltration
    • Inflammation
    • Granulomatous changes
    • Siderosis and Fibrosis may lead to Cirrhosis
    • Only slight increased HCC risk
  79. These are the largest lipoprotein particle. They package fat that is consumed in the diet and absorbed through the intestine. Their primary function is to deliver dietary lipid to adipose tissue and the liver.
  80. These particles are synthesized in the liver to secrete lipids that are either recycled through the liver or newly synthesized by the liver. In the blood plasma, they distribute their triacylglycerol content to peripheral tissues. These are classified as bad cholesterol.
  81. These particles are responsible for reverse cholesterol transport. They are synthesized in the intestine and liver, and are small empty particles that pick up lipid in the peripheral circulation, and return it to the liver. These particles return cholesterol from the periphery to the liver to be excreted as bile. These are classified as good cholesterol.
  82. What is the signature apoplipoprotein for the chylomicron?
    Apo B-48
  83. What is the signature apolipoprotein of VLDL/LDL?
    Apo B-100
  84. These particles consist of a hydrophilic phospholipid coat and a hydrophobic core (the lipid cargo). The apoproteins are associated with the phospholipid monolayer.
    Lipoprotein Particles
  85. This apolipoprotein family are important structural molecules that regulate the synthesis of the specific particle.
    Apolipoprotein B
  86. This apolipoprotein type is found on HDL particles and is a cofactor for the Lecithin cholesterol acyl transferase (LCAT) that converts plasma cholesterol to cholesteryl ester in that particle
    Apo A-I
  87. This apolipoprotein type plays an important role in activating lipoprotein lipase (LPL) enzymes that are linked to the endothelial cell walls of capillaries. These LPL proteins cleave the triacylglycerol content of the lipoprotein particles so that the fatty acids can be taken up by nearby tissues.
    Apo C-II
  88. This apolipoprotein type plays a role in clearance of the lipoprotein particles from the blood plasma. It serves as a ligand that binds a cell surface receptor. The ligand/receptor complex is internalized by the cell, engulfing the lipoprotein particle
    Apo E
  89. How is the identification of lipoprotein particles in the blood done?
    Electrophoretic Mobility
  90. What blood lipid would be elevated in an individual with an LPL deficiency?
  91. Identify the Helminth:
    Fluid filled cysts found mostly in the liver and lungs

    Can be asymptomatic for several years

    Cysts can lead to blood sputum and cause neurologic or hepatic disorders

    Hepatic cysts may cause abdominal pain and biliary duct obstruction

    Cyst rupture can cause fever, eosinophilia, and anaphylaxis

    How is this transmitted, diagnosed, treated, and prevented?
    • Echinococcus Granulosis
    • Transmission: Ingesting eggs from soil, water, or dog fur
    • Diagnosis: Imaging and serology (parasites in aspirates from cysts)
    • Treatment: Surgical removal of cysts followed by albendazole
    • Prevention: Prevent dogs from eating sheep entrails
  92. Identify the Helminth:
    Abdominal Pain
    Biliary Obstruction
    Multiloculated Cysts in Liver
    Can gradually invade neighboring tissues

    How is this transmitted, treated, diagnosed, and prevented?
    • Echinococcus Multilocularis
    • Transmission: Digestion of eggs in feces
    • Diagnosis: Imaging and Serology (parasites in aspirates from cysts)
    • Treatment: Albendazole is drug of choice; Surgery to remove cysts
  93. Which Schistosome spp. is found in Africa/Latin America?
  94. Which Schistosome spp. is found in Africa/Middle East?
  95. Which Schistosome spp. is found in Asia?
  96. What dictates the epidemiology for Schistosome spp.?
    It requires a snail to complete its life cycle -- the snail dictates the epidemiology
  97. Identify the Helminth:
    Acute Symptoms:
    Dermatitis, Swimmer's Itch (cercariae), Fever, Cough, Abdominal Pain, Diarrhea, Hepatosplenomegaly, Eosinophilia (mature worms)

    Chronic Symptoms:
    Tissue biopsies show large granulomas surrounding eggs, Inflammation in infected tissues due to soluble egg proteins, Portal hypertension

    How is this transmitted, diagnosed, treated, and prevented?
    • Schistosome spp.
    • Transmission: Free-swimming cercariae (larval stage) penetrate the skin
    • Diagnosis: ID of eggs in stools or urine
    • Treatment: Praziquantel
    • Prevention: Avoid swimming in endemic areas and proper disposal of human waste
  98. What chronic phase symptom of Schistosome spp. is specific to Mansoni?
    Colonic polyps with bloody diarrhea
  99. What chronic phase symptom of Shistosome spp. is specific to Haemotobium?
    • Bloody urine
    • Urinary Tract Infection
    • Cystitis
    • Bladder Neoplasms
  100. What tissues does S. Mansoni target?
    • GI Tract
    • Liver
  101. What tissues does S. Japonicum target?
    • GI Tract
    • Liver
  102. What tissue does S. Haemotobium target?
    Urinary Tract
  103. Identify the Helminth:
    Most infections of are asymptomatic.

    Heavy infections can lead to:
    Abdominal Pains
    Bile Duct Obstruction leading to Cholangitis and Cholangiohepatitis
    Rare incidence of Cholangiocarcinomas

    How is this transmitted, diagnosed, treated, and prevented?
    • Clonorchis Sinesis
    • Transmission: Ingestion of cercariae from raw or undercooked fish
    • Diagnosis: Identification of eggs in stools
    • Treatment: Prazinquantal
    • Prevention: Prevent by eating properly cooked fish and proper disposal of human waste
  104. Identify the Helminth:
    Acute Phase Symptoms:
    RUQ Abdominal Pain

    Chronic Phase Symptoms:
    Biliary Tract Obstruction

    How is this transmitted, diagnosed, treated, and prevented?
    • Fasciola Hepatica
    • Transmission: Ingestion of metacercariae larvae encysted in aquatic plants
    • Diagnosis: ID of eggs in stool
    • Treatment: Triclabendazole
    • Prevention: Prevent by not eating aquatic vegetables or raw sheep liver
  105. Identify the Helminth:
    Abdominal Pain
    Intestinal Obstruction

    How is it transmitted, diagnosed, treated, and prevented?
    • Fasciolopsis Buski
    • Transmission: Digestion of contaminated aquatic vegetables that contain cysts
    • Diagnosis: Eggs in stool
    • Treatment: Praziquantel
    • Prevention: Prevent by proper disposal of human waste
  106. Inflammation of the liver caused by viruses, chemicals, drugs, alcohol, inherited diseases, or autoimmunity.
  107. These are possible acute symptoms what viral disease?
    Loss of Appetite
    Abdominal Pain
    Dark Colored Urine
    Light Colored Stools
    Tender and Enlarged Liver
  108. These are some of the possible chronic symptoms associated with what viral disease?

    Usually presents no clinical symptoms
    Loss of Energy
    Gradually damage the liver (liver failure)
    Typically lasts for years
    Rarely resolves without treatment
  109. What is the histopathology of hepatitis?
    • Necrosis of hepatocytes
    • Framework of the reticulum is preserved
  110. What labs are associated with hepatitis?
    • AST (normal range 5-40 units/liter serum)
    • ALT (normal range 7-56 units/liter serum)
  111. What is the genome of Picornavirus?
    Is it enveloped?
    • ssRNA '+' sense
    • No
  112. Identify the Virus:
    Distinguishing Features:
    Single RNA, single polypeptide
    IRES, vpG on RNA end essential for replication
    Not Lytic (unique Hepatovirus)

    Disease Manifestations:
    Common Cold
  113. What is the treatment and/or prevention of Picornavirus?
    • Supportive
    • Vaccine for Polio
  114. What are the characteristics of Hepatitis A?
    • Picornavirus (Hepatovirus)
    • Icosahedral
    • Non-enveloped
    • ssRNA, + sense
    • Humans are the only reservoir
  115. How is Hepatitis A diagnosed?
    Detection of anit-HAV IgM

    Detection of anti-HAV IgG in the absence of IgM indicates immunity (lifelong)
  116. How is Hepatitis A transmitted?
    • HAV is shed into the GI and found in the stool of the infected person
    • Spread by fecal/oral route
    • Often found in raw shellfish which concentrate the virus
    • Blood exposure is rare but can occur
  117. What is the diagnosis?
    Abdominal Pain
    Loss of Apetite Nausea
    Dark Urine (often first indicator)
    Pale Stools
    Elevated Liver Enzymes (ALT, AST) in Sera
    Hepatitis A
  118. What is the most important determinant of severity in Hepatitis A?
    Age -- patients older than 49 have substantially greater risk of fatality (2.7%)
  119. How can Hepatitis A be prevented?
    • Vaccine -- 94-100% efficacious
    • Passive immunization with immune globulin -- up to 2 weeks after known contact or before travel to HAV-endemic area (protection will not last)
    • Hygiene and Sanitation
  120. Is Hepevirus (HEV) enveloped?
  121. What is the genome of Hepevirus (HEV)?
    ssRNA '+' sense
  122. Name the Virus:
    Distinguishing Features:
    Single RNA
    Three distinct polypeptides
    Icosahedral Symmetry

    Disease Manifestations:
    Resolving Acute Hepatitis
    More significantly pathogenic in pregs
  123. What is the treatment and/or prevention for Hepevirus (HEV)?
    Vaccine -- not licensed in US bc dont see many cases
  124. How is Hepevirus (HEV) transmitted?
    • Fecal-oral Transmission
    • Not commonly transmitted via person-to-person contact (gotta swallow)
  125. What dictates severity of Hepevirus (HEV) infection?
    • Severity of disease is related to infectious dose
    • Pregnant women are at greatest risk
  126. What is a key distinguishing feature between HAV and HEV?
    Immunity to HEV is not life-long. One can be reinfected
  127. Is Hepadnavirus (HBV) enveloped?
  128. What is the genome of Hepadnavirus (HBV)?
    • Partial dsDNA/Partial ssDNA
    • Circular, but nicked
  129. Identify the Virus:
    Distinguishing Features:
    Very small genome
    Replicates through an RNA intermediate
    Causes tumors
    Reverse transcriptase

    Disease Manifestations:
    Acute and Chronic Hepatitis
    Transmission predominantly mother-to-child
    Hepadnavirus (HBV)
  130. What is the treatment and/or prevention for Hepadnavirus (HBV)?
  131. In Hepadnavirus (HBV), what is an important antigen for replication that is derived from the same transcript as the core but has an alternate translational initiation and different structure?
    HBV e antigen
  132. What are the modes of transmission for Hepadnavirus (HBV)?
    • Blood
    • Sexual
    • Pernatal -- mother to neonate always results in chronic hepatitis
  133. True or False:
    Infection of HBV in adulthood generally results in protection.
  134. There is a high incidence of what three diseases in chronic carriers of HBV, resulting in 5,000-6,000 deaths/year?
    • Progressive Hepatitis
    • Cirrhosis
    • Hepatocellular Carcinoma (HCC)
  135. What is the most common mode of transmission of HBV in the US?
    Sexual Transmission
  136. In HBV, 90% of _______ infected individuals have chronically evolving hepatitis, whereas 90% of _____ infected individuals recover.
    • Vertically
    • Horizontally
  137. How is Hepadnavirus (HBV) diagnosed?
    • Immunoassay for HBsAg -- present during prodrome and acute disease. Present for 6+ months = carrier state
    • "Window Phase" -- HBsAg has disappeared but anti-HBsAg can not be detected. During the window one can look for anti-HBc
    • Viral Load can be measured by PCR -- important in management of drug resistance
  138. What is an important indicator of HBV virus production and transmissibility?
    HBeAg presence during prodrome and acute disease
  139. How is HBV treated and/or prevented?
    • Alpha-interferon for those already infected
    • Lamivudine (RT inhibitor) usually used after pts become sick. Resistance is a problem
    • Vaccine
    • HBlg -- for immediate protection in persons known to be exposed.
  140. Identify the Virus:
    Distinguishing Features:
    Negative sense, closed circular, ssRNA
    Satellite Virus: requires HBV to replicate
    Smallest "virus" known to infect humans
    Genome codes for no protein

    Disease Manifestations:
    More severe acute diseaseHigher risk of fulminant hepatitis
    Hepatitis D Virus
  141. What are the clinical characteristics of an HDV superinfection of HBV+ patient?
    • Usually develop chronic HDV infections
    • Greater potential for development of cirrhosis & HCC
  142. How can HDV coinfection and superinfection be prevented?
    • Co-infection: use methods to prevent initial HBV infection
    • Superinfection: Education of HBV+ patient regarding risk factors to avoid
    • Monitor for sudden changes in hepatic disease in HBV infected patients
  143. Is Hepacivirus (HCV) enveloped?
  144. Identify the Virus:
    ssRNA + sense

    Disease Manifestations:
    Yellow Fever
    West Nile Virus
    Hepacivirus (HCV)
  145. What is the most common blood-borne infection in the US?
    Hepatitis C Virus
  146. Identify the Virus:
    No clinical symptoms in 80% of infected

    When present, same as for HAV
    Long-term Effects: Chonic infection (60-80%), Chronic Liver Disease (60% of chronic infections -- HCC or Cirrhosis)

    A leading indication for Liver Transplant
    Hep C Virus
  147. How is HCV transmitted?
    • Blood or Body Fluids
    • Permucosal (perinatal, sexual -- rare)
  148. How is HCV diagnosed?
    • Detection of antibodies by anti-HCV ELISA (Test does not distinguish between acute, chronic, or resolved infection)
    • RIBA -- used after ELISA is positive due to false positives
    • RT-PCR: detects viral RNA in the blood to determine if disease is active
  149. How is HCV managed?
    • Monitor liver function of infected patients
    • Interferon alpha + ribavirin or pegylated interferon alpha are treatments of choice
    • Infected individuals should avoid alcohol
    • Viral load should be monitored by RT-PCR in symptomatic phases
  150. Viral infections are cleared by (lymphocytes or neutrophils)?
  151. What are the two leading causes of cirrhosis in the US?
    • Chronic Viral Hepatitis
    • Alcohol
  152. What is the sixth leading cause of adult deaths?
  153. What is a serious complication of cirrhosis?
    Portal Hypertension
  154. What is the difference between a compensated and a decompensated form of cirrhosis?
    • Compensated: No portal hypertension complications
    • Decompensated: Have PH complications, die 1-5 yrs
  155. What is a cirrhotic liver?
    A liver that is unable to regenerate because it is encapsulated with fibrosis
  156. What are the two clinical syndromes that cirrhosis leads to?
    • Portal Hypertension
    • Liver Insufficiency
  157. Portal hypertension in cirrhosis leads to development of what three clinical complications?
    • Variceal Hemorrhage
    • Ascites
    • Encephalopathy
  158. Liver insufficiency in cirrhosis leads to development of what two clinical complications?
    • Jaundice
    • Encephalopathy
  159. What is this method used to measure?
    Hepatic Venography

    A balloon catheter is passed into the hepatic vein
    and FHVP (free hepatic venous pressure) and WHVP (wedged hepatic venous
    pressure) are measured.

    Hepatic venous pressure gradient (HVPG) = WHVP - FHVP
    Portal Hypertension
  160. How is portal hypertension defined?
    A free portal vein pressure in excess of the normal 5-10 mmHg

    A wedged hepatic venous pressure more than 5 mmHg greater than the inferior vena cava pressure
  161. What is the threshold portal pressure necessary for varices to form?
    12 mmHg
  162. Variceal hemorrhage occurs most frequently from esophageal varices....where?
    At the gastroesophageal junction
  163. How are bleeding varices corrected?
    Variceal Band Ligation
  164. What is the diagnostic modality of choice to evaluate severe upper gastrointestinal bleeding?
    Upper Endoscopy: to determine actual source of bleeding, evaluate severity of bleeding, and determine the risk of rebleeding
  165. What is the management strategy when endoscopic treatment fails?
    • Transjugular Intrahepatic Portosystemic Shunt (TIPS)
    • Transplantation
  166. Which type of varices are most difficult to stop bleeding?
    Gastric Varices
  167. The purpose of this is to correct portal hypertension by creating a communication between the hypertensive portal system and low-pressure systemic veins, bypassing the liver. What is it?
    Transjugular Intrahepatic Portosystemic Shunt (TIPS)
  168. This is performed by advancing a catheter introduced through the jugular vein into a hepatic vein and into a main branch of the portal vein. An expandable stent is then introduced connecting hepatic and portal systems, and blood from the hypertensive portal vein and sinusoidal bed is shunted to the hepatic vein.
    Transjugular Intrahepatic Portosystemic Shunt (TIPS)
  169. What are the complications of transjugular intrahepatic portosystemic shunt (TIPS)?
    • Portal-systemic Encephalopathy
    • Liver Failure
  170. What is the main cause of Ascites?
    Chronic Liver Disease
  171. How is uncomplicated ascites managed?
    • Sodium Restriction: Goal -- negative sodium balance
    • Fluid Restriction is not necessary unless there is hyponatremia
  172. What are the indications for abdominal paracentesis?
    • New-onset ascites
    • Admission to hospital
    • Clinical deterioration
    • Fever
  173. What are the main organismal culprits of spontaneous bacterial pericarditis?
    • Escherichia (43%)
    • Klebsiella Pneumoniae
    • Streptococcus Pneumoniae
  174. Serum-Ascites Albumin Gradient (SAAG) is high in portal hypertensive causes of ascites. What SAAG score is indicative of the presence of sinusoidal hypertension as seen in cirrhotic and cardiac ascites?
    A SAAG of 1.1 g/L or above
  175. Do peritoneal causes of ascites have a low or a high SAAG value?
  176. What is the diagnosis?

    Reversible neuropsychiatric abnormalities
    Abnormal EEG
    Hepatic failure
    Portosystemic shunting
    Hepatic Encephalopathy
  177. Are measurements of ammonia necessary for diagnosis of Hepatic Encephalopathy?
    No; Ammonia levels are unreliable, and there is a poor correlation between the stage of encephalopathy and blood level of ammonia.
  178. What are the main risk factors for developing Hepatocellular Carcinoma (HCC)?
    • HCV RR
    • HBV RR
    • Hemochromatosis
  179. What is the only cure of Hepatocellular Carcinoma (HCC)?
    Liver Transplantation
  180. What does the Model for End-Stage Liver Disease (MELD) score estimate?
    Risk of 3-month mortality
  181. How is the Model for End-Stage Liver Disease (MELD) score measured (what lab values are used)?
    • Serum total bilirubin
    • Serum creatinine
    • INR
  182. What Model for End-Stage Liver Disease (MELD) score is necessary for a patient to be considered for liver transplantation?
    > 10-12
  183. The liver plays a vital role in drug metabolism by virtue of its:
    • Location b/w splanchnic & systemic circulation
    • Possession of a vast array of enzymes
    • Transforming drugs into pharmacological active compound
    • Degrading drugs for elimination
  184. 50% of cases of acute liver disease in the US are a result of what?
    Adverse Drug Reactions
  185. What is a key enzyme of phase I metabolism?
  186. What are the two categories for hepatotoxic drugs?
    • Intrinsic: has predictable toxicity
    • Idiosyncratic: nonpredictable
  187. What are the characteristics of intrinsic hepatotoxicity?
    • Experimental Reproducibility
    • Always Dose Dependent
    • High Incidence in Humans
    • Latency-short and relatively consistent
  188. What are some key dose-dependent hepatotoxins?
    • Acetaminophen
    • Cyclophosphamide, Busulfan
    • Carbon Tetrachloride
    • Alfatoxins
    • Ethanol
    • Copper, Iron, Mercury
    • Bile Salts
  189. Which type of drug reactions have these characteristics?

    Experimental reproducibility (usually only in animal models)
    No dose dependence
    Low incidence in humans
    Latency-often long and variable
    Idiosyncratic Drug Reactions
  190. Drug-induced hepatocellular jaundice is serious and specific for drug-induced liver injury. This is known as....?
    Hy's Rule
  191. What lab tests verify Drug-Induced Liver Disease (non-cholestatic)?
    ALT > 3x ULN + total biliruben > 2x ULN (alk phos < 2x ULN)
  192. What lab tests verify Cholestatic Drug-Induced Liver Disease?
    • Alk phos < 2x ULN
    • ALT < 2x ULN
    • Total biliruben > 2x ULN
  193. When diagnosing Cholestatic Drug-Induced Liver Disease, what needs to be ruled out?
    Gilbert's Syndrome
  194. What drug type is the most common cause of Cholestatic Drug-Induced Liver Disease?
    Sulfa-type Drugs
  195. Do Statin drugs cause Hepatotoxicity?
  196. An ALT < 3x ULN represents what?
    Background Noise
  197. Should Statins be used to treat fatty liver disease?
  198. What is the role of a liver biopsy in Drug-Induced Liver Disease?
    • Not required to establish diagnosis
    • Used to exclude other hepatobiliary disorders
  199. These drugs are the main causative agents of what?

    Hepatic Granulomas
  200. What is the leading cause of ACUTE liver failure in the US?
  201. What dose of Acetaminophen can cause severe liver necrosis?
    Single dose of 15-25 grams
  202. Should liver patients ever be perscribed acetominophen?
    Yes, liver patients can take in proper doses
  203. What is the antidote for acetaminophen overdose?
  204. What are the clinical variants of HAV infection?
    • Cholestatic Hepatitis
    • Relapsing Hepatitis
    • Fulimant Hepatic Failure
  205. Globally, what is the most common type of Hepatitis infection?
    Hep B
  206. In HBV infection, does the risk of chronic infection increase or decrease with age?
  207. What agents are used to treat chronic HBV?
    • Peginterferon alfa-2a
    • Entecavir
    • Tenofovir
  208. What are the stages of fibrosis in chronic hepatitis?
    • 1. Portal
    • 2. Periportal
    • 3. Septal
    • 4. Cirrhosis
  209. What disease is characterized by this pathogenesis?

    Increased intestinal iron absorption from birth
    Period of asymptomatic iron accumulation
    End-organ damage due to toxic iron effects
    Hereditary Hemochromatosis
  210. What are the classifications of Hemochromatosis?
    • Type 1: HFE
    • Type 2a: Hepcidin
    • Type 2b: Hemojuvulin
    • Type 3: Transferrin Receptor 2
    • Type 4: Ferroportin
  211. In this type of Hereditary Hemochromatosis, a mutated HFE protein impairs Tfr2-linked serum iron entry in hepatocytes and immature enterocytes causing both to falsely "sense" an iron poor state. This causes DMT1, ferroportin to be upregulated, causing hepcidin secretion to be suppressed.
    Type 1
  212. These 2 types of Hereditary Hemochromatosis, known as Juvenile Types, are characterized by mutations that lead to lack of suppression of ferroportin-mediated enterocyte iron export into serum
    • Type 2a -- Hepcidin
    • Type 2b -- Hemojuvulin
  213. What is the gene responsible for Type 1 Hereditary Hemochromatosis?
    • Homozygous: C282Y
    • Heterozygous: C282Y/H63D
  214. What does a mutation in HFE-1 protein lead to?
    An increase in intestinal iron absorption
  215. What are the main serum iron tests?
    • Ferritin
    • Iron Saturation
  216. For C282Y, penetrance variations are probably due to other "modifier" genes which interact with C282Y as well as female blood loss. The Beutler grading system is used to define penetrance. What are it's grades?
    • Grade 0: Normal Liver Tests
    • Grade 1: Increased TIBC
    • Grade 2: Plus Increased Ferritin
    • Grade 3: Plus Minor Symptoms
    • Grade 4: Plus Potentially Lethal Symptoms
  217. The "Gestalt" System is a commonly used qualitative system to grade Iron. For Hepatocellular Hemosiderin, what is the Grading Scale?
    • Trace: very little, zone 1 only
    • 1+: zone 1 only, more than a trace
    • 2+: zones 1 and 2
    • 3+: pan-zonal, but not intense
    • 4+: pan-zonal, intense
  218. What is the diagnosis?
    Can be asymptomatic

    Hepatic Presentation: fulminant hepatic failure, chronic active hepatitis, cirrhosis, fatty liver disease, massive hepatic necrosis, hemosiderosis

    Neurological Presentation: tremor, ataxia, etc

    Psychiatric Presentation: depression, psychosis, poor school performance

    Hematologic Presentation: hemolytic anemia

    Decreased hepatic excretion of copper
    Absorption remains normal
    Copper Accumulation: in liver and brain -- damage through free radical formation
    Wilson's Disease
  219. What is the age of presentation and physical exam findings associated with Wilson's Disease?
    • Mean Age at Presentation: 12-23 years; pt rarely older than 50
    • Physical Exam Findings: Kayser-Fleischer Rings (copper ring in cornea); "Sunflower" cataracts
  220. What is diagnostic of Wilson's Disease?
    • Lowered Ceruloplasm
    • Raised Urinary Copper
    • Kayser-Fleischer Rings
  221. What is the definitive test for Wilson's Disease?
    • Quantitative Copper Analysis
    • Normal < 35 mcg/g dry weight liver
  222. What is the cause of 44% of liver-related deaths?
    Alcoholic Liver Disease
  223. What are the minimum amounts of alcohol to cause cirrhosis?
    • Males -- 80 g/day X 10 years
    • Females -- 20-40 g X 10 years
  224. What are the risk factors for alcoholic liver disease (5)?
    • Quantity
    • Gender
    • Hepatitis C
    • Genetics
    • Malnutrition
  225. How is alcoholic hepatitis diagnosed (what are the associated labs)?
    • AST/ALT ratio > 2 (ETOH suppresses production of ALT)
    • ASH vs NASH -- repeat urine and blood alcohols, talk to spouse
  226. How is asymptomatic alcoholic hepatitis characterized (3)?
    • Hepatomegaly
    • Biochemistry mildly abnormal
    • Needs histology for confirmation
  227. How is liver failure in Alcoholic Hepatitis characterized (6)?
    • Bilirubin greatly increased
    • Alk Phos modest
    • PT increased
    • Albumin reduced
    • Neutrophilia
    • Ascites
  228. What are the medication recommendations for Cirrhosis?
    • Acetaminophen is ok
    • Tramadol when acetaminophen is not enough
    • No NSAIDS
    • Trazodone or Hydroxyzine for insomnia rather than benzos
  229. Should Corticosteroids be used for severe Alcoholic Hepatitis?
Card Set
GI&HB Week Two