Hepatobiliary Flashcards
Brown pigment stones typically arise secondary to what?
Infection of the biliary tract
What enzyme is typically involved in the formation of brown pigment stones?
Injured hepatocytes and bacteria release beta-glucuronidase which contributes to the hydrolysis of bilirubin glucuronides - increasing the amount of unconjugated bilirubin in bile
What class of HIV drugs have a side effect of hyperglycemia?
Protease inhibitors (e.g. idinavir)
What does gallbladder hypomotility often lead to?
Bile precipitation and the formation of biliary sludge
Normal blood sugar levels, severe cardiomegaly, glycogen accumulation in lysosomes, normal glycogen structure - disease and enzyme deficiency?
Type II: Pompe’s disease - deficiency of lysosomal acid alpha-glucosidase
Muscle glycogen phosphorylase deficiency, weakness and fatigue with exercise, little or no rise in blood lactate levels after exercise, high level of glycogen in muscles - disease and enzyme deficiency?
Type V: McArdle’s disease - deficiency of glycogen phosphorylase
Hepatomegaly, fasting hypoglycemia, lactic acidosis, hyperuricemia, hyperlipidemia, increased glycogen storage but normal structure - disease and enzyme deficiency?
Type I: von Gierke’s disease - deficiency of glucose 6 phosphatase
How is rectal drug administration different from oral drug administration in terms of bioavailability?
Rectal drug administration partially bypasses first pass metabolism - drained by superior, middle, and inferior rectal veins. While the superior goes to the liver, middle and inferior go straight to systemic circulation.
High intracellular NADH in the setting of hypoglycemia is suggestive of what?
Since NADH is a carrier of energy, it suggests that a fuel other than glucose is being metabolized (e.g. alcohol)
What blotting technique uses a double stranded DNA probe?
Southwestern - used for proteins that bind DNA
What are some examples of DNA binding proteins (i.e. what you would use a southwestern blot for)?
Transcription factors (e.g. c-Jun and c-Fos), nucleases, histones
Toxicity of what drug is treated by donation of sulfhydryl groups?
Acetaminophen - treated with N acetylcysteine
How does acute hepatitis A typically present?
Fever, dark urine, malaise, nausea, vomiting, mild abdominal pain with hepatomegaly and jaundice
What is the function of acyl CoA dehydrogenase?
First enzyme in the series of reactions that breaks down acyl CoA to ketone bodies (beta oxidation) once it is brought into the mitochondria by the carnitine shuttle
Why are pregnant women at increased risk of gallstones?
Estrogen-induced cholesterol hypersecretion and progesterone-induced gallbladder hypomotility
Which class of viruses obtain their envelope by budding through the host cell nuclear membrane rather than the plasma membrane?
Herpesviruses
Why does Hepatitis D need to coinfect with Hepatitis B?
Needs viral coat (from Hepatitis B) before it can infect hepatocytes and multiply
Why is Hepatitis C genetically unstable?
Lacks proofreading 3’ to 5’ exonuclease activity
Acute inflammation of the gallbladder is initiated 90% of the time by?
Gallbladder outflow obstruction
Cardiac arrhythmia, hepatomegaly, dark skin (hyperpigmentation) - diagnosis?
Hemochromatosis
What are the 3 ketone bodies?
Acetone, acetoacetic acid, beta-hydroxybutyric acid
What causes spider angiomata?
Hyperestrinism
How does Hepatitis B replicate?
Double stranded DNA –> Template + RNA –> Progeny double-stranded DNA
What is the significance of prokaryotic 16S rRNA sequence?
Found in the 30s ribosomal subunit and contains a sequence complementary to the Shine Dalgarno sequence on mRNA - by allowing mRNA to bind to the ribosome, it initiates protein translation for prokaryotes
The most common form of galactosemia results from deficiency of what enzyme?
Galactose-1-phosphate uridyl transferase
Why is effective immunity against infection often not conferred for Hepatitis C?
Remarkable variety in the antigen structure of the envelope protein
What is a major gallbladder complication in the hospitalized/severely ill?
Acute acalculous cholecystitis - inflammed and enlarged gallbladder without gallstones
What is the most common malignant hepatic lesion?
Metastasis from another primary
What nutritional deficiencies do we worry about with prolonged cholestasis?
Fat soluble vitamins (A, D, E, K)
Why would someone with cholestasis get osteomalacia?
Vitamin D deficiency (Vitamin D is a fat soluble vitamin)
What does an acidophilic body signify in a hepatocyte?
Apoptosis from viral hepatitis - also called Councilman bodies and apoptotic bodies
What is the inheritance pattern of classic galactosemia?
Autosomal recessive
Presentation: 3 week old infant with persistent jaundice, dark urine, acholic stools, conjugated hyperbilirubinemia - diagnosis?
Biliary atresia
Neurologic symptoms with hepatic damage (elevated liver enzyme) should make you suspicious of what?
Wilson disease
What is one of the fastest/easiest diagnostic tools for Wilson disease?
Look for Kayser-Fleischer rings with slit lamp examination
What happens to BUN in liver disease?
Typically decreased because less ammonia is converted to urea
A moderately elevated alkaline phosphatase of unknown etiology should be followed up with by what test to check for liver disease?
Gamma-glutamyl transpeptidase - more specific for hepatocytes and biliary epithelia
Describe the series of reactions by which the liver is able to use the breakdown products of triglycerides.
- Triglycerides broken down into glycerol and fatty acids (fatty acids go on to beta oxidation)
- Glycerol goes to the liver where it is converted to glycerol 3-phosphate by glycerol kinase
- Glycerol is converted to DHAP which can be broken down into energy (via glycolysis) or glucose (gluconeogenesis)
What are the 3 progressive stages of alcohol associated hepatic injury?
- Steatosis (reversible)
- Hepatitis (reversible)
- Cirrhosis (irreversible)
What lab tests are markers of cirrhosis (i.e. irreversible liver damage)?
Prolonged PT and decreased serum albumin (indicate that liver function has been impaired; not just hepatocellular damage as is marked by AST/ALT)
What is the genetic abnormality in hemochromatosis?
Hemochromatosis gene HLA-H on chromosome 6 codes for a molecule that affects iron absorption from GI tract
Homeobox genes typically code for what?
DNA-binding transcription factors that alter the expression of genes involved in morphogenesis
Where are enhancers/repressors located vs. promoters?
Enhancers/repressors can be located anywhere vs. promoters which are located 25 or 70 bases upstream of the target gene
What step of the TCA cycle is often inhibited in alcoholics? Why?
Alpha-ketoglutarate to succinyl coA because the enzyme alpha-ketoglutarate dehydrogenase requires thiamine as a cofactor (and alcoholics are often thiamine deficient)
What is the point of adding primaquine to a malaria treatment regimen?
Prevent disease relapse - primaquine kills the intrahepatic merozoites of vivax and ovale which chloroquine does not cover
Liver biopsy shows hepatic fibrosis without fat accumulation. Also shows accumulation of small chain dextrin-like material within the cytosol of the hepatocytes - what enzyme is deficient?
Debranching enzyme deficiency (Cori disease) - glycogen can’t be broken down so patients present with hypoglycemia, hypertriglyceridemia, ketoacidosis, hepatomegaly
Describe what happens in zero order kinetics.
Constant amount of drug is metabolized per unit time, independent of concentration
Intense liver damage following a seemingly successful surgery should make you suspicious of?
Fulminant hepatitis from drug reaction to inhaled anesthetic (e.g. halothane)
What would you expect to see on lab tests for a fulminant hepatitis from a drug reaction to anesthetics?
Elevated aminotransferase levels, prolonged PT time, eosinophilia
What should be you be suspicious of in a patient with progressive exertional dyspnea and elevated liver enzymes?
Alpha1 anti-trypsin deficiency
What causes the pulmonary symptoms in alpha1 anti-trypsin deficiency?
Interalveolar septa destruction
G to T mutation in p53 from eating moldy grains?
Aflatoxin causing liver cancer
What is the tumor marker for hepatocellular carcinoma?
AFP
What does anicteric mean?
No jaundice
What is the most common benign liver tumor?
Cavernous hemangioma
Liver histology showing cavernous blood-filled vascular spaces lined by a single epithelial layer - diagnosis?
Cavernous hemangioma
What is lipoic acid a cofactor for?
Pyruvate dehydrogenase, alpha ketoglutarate dehydrogenase, branched-chain ketoacid dehydrogenase
What does a deficiency in pyruvate dehydrogenase lead to?
Lactic acidosis
What does a deficiency in branched chain ketoacid dehydrogenase lead to?
Maple syrup urine disease
Which hepatitis virus has a high mortality rate in infected pregnant women?
Hepatitis E
What type of virus is hepatitis E?
Unenveloped, single stranded RNA
What kind of imaging test can be used to confirm diagnosis of acute calculous cholecystitis?
Failed gallbladder visualization on radionuclide biliary scan
Histology: hepatocytes filled with fine cytoplasmic protein granules - diagnosis?
Hepatitis B - hepatocellular cytoplasm is filled with spheres and tubules of HBsAg and take on a finely granular, eosinophilic appearance commonly described as “ground glass”
Isoniazid can directly damage which organ?
Liver
Where is transketolase located?
Cytoplasm
Where is pyruvate carboxylase located?
Mitochondria
Where is ornithine transcarbamoylase located?
Mitochondria
Where is succinate dehydrogenase located?
Mitochondria
Describe the first step of gluconeogenesis.
Since pyruvate cannot be directly converted back to phosphoenolpyruvate, it must first undergo biotin dependent carboxylation to oxaloacetate in the mitochondria (which will then become malate, shuttle out and be converted back to oxaloacetate which can become phosphoenolpyruvate)
What is the role of acetyl CoA in gluconeogenesis?
Important allosteric activator of gluconeogenesis that acts by increasing the activity of pyruvate carboxylase
Why is there a bimodal distribution for the speed of isoniazid metabolism?
Metabolized by acetylation - there are genetically fast and genetically slow acetylators in the population
What is the significance of a porcelain (calcified) gallbladder on imaging?
Increased risk of gallbladder carcinoma
What triggers neoplastic changes with HBV infection?
Viral integration into the host DNA
What metabolic enzyme deficiency is associated with the formation of cataracts?
Galactokinase because you get a build up of galactose which is converted to galactitol which can accumulate in the lens of the eye
How would you microscopically characterize a cirrhotic liver?
Diffuse hepatic fibrosis with replacement of the normal lobular architecture by fibrous-lined parenchymal nodules
What is the most likely outcome for someone infected with Hepatitis C?
Stable chronic hepatitis
What is affected in Wilson’s disease aside from the liver?
Cornea and basal ganglia
Patients with hemochromatosis are at increased risk of developing what?
Liver cirrhosis and hepatocellular carcinoma
Which Hepatitis B antigen is a non-infective glycoprotein that forms spheres and tubules?
HbSag - The surface antigen is actually part of the envelope.
The oxidative reactions of the HMP shunt are required for what?
Anabolic reactions that require NADPH as an electron donor (e.g. cholesterol and fatty acid synthesis)
question 8
come back to this
What portions of mRNA are not transcribed from a DNA template?
Post-transcriptional modifications:
- 5’ cap
- Poly A tail
Which hepatitis virus integrates itself into the host genome?
Hep B
What are the ways in which Hepatitis A can be inactivated?
Water chlorination, bleach, formalin, ultraviolet irradiation, boiling for 1 minute
What is pantothenic acid?
Coenzyme A
Decreased ceruloplasmin is associated with what disease?
Wilson’s
What is the best treatment for Wilson’s disease?
Penicillamine chelation - removes excess copper in tissues
Liver biopsy showing extensive lymphocyte infiltration and granulomatous destruction of interlobular bile ducts should make you suspicious of?
Primary biliary cirrhosis
45 year old obese female with fever and prolonged episode of severe right upper abdominal pain after fatty meal ingestion?
Acute cholecystitis
38 year old male with long history of ulcerative colitis who presents with fatigue and elevated alkaline phosphatase?
Primary sclerosing cholangitis
65 year old Caucasian female with weight loss, abdominal discomfort, jaundice, epigastric mass?
Pancreatic cancer
35 year old homeless male with fever, abdominal pain, and jaundice?
Acute cholangitis
What does liver biopsy show in children with Reye syndrome?
Microvesicular steatosis
Describe the mechanism of liver injury with Hepatitis B.
Presence of viral HBsAg and HBcAg on infected hepatocyte surface stimulate the host’s cytotoxic CD8+ T lymphocyte to destroy the infected cells
45 year old Caucasian female with long history of pruritus and fatigue who developed pale stool and xanthelasma?
Primary biliary cirrhosis
When do we convert glucose to ribulose-5-p?
HMP shunt
