SM_156b: Biliary Tract Disorders Flashcards
Cholestasis presents with ____ and ____
Cholestasis presents with hyperbilirubinemia and jaundice
Cholestasis pathology includes ____
Cholestasis pathology includes liver lobule
These are ____
These are bule infarcts
These are ____
These are bile plugs
Describe the anatomy of the biliary system
Anatomy of the biliary system
Cholestasis involves diminished ____ and ____
Cholestasis involves diminished bile flow and hepatobiliary secretion
- Bile salt-dependent bile flow: osmotic forces
- Bile salt-independent bile flow: osmotic and other factors
___ infusion stimulates bile flow, while ___ increases as bile flow increases
Bile salt infusion stimulates bile flow, while bile salt secretion increases as bile flow increases
Cholestasis involves impairment in molecular mechanisms of ____
Cholestasis involves impairment in molecular mechanisms of bile formation
Serum liver chemistry tests include ____, ____, ____, and ____
Serum liver chemistry tests include transaminases, bilirubin, alkaline phosphatase, and albumin prothrombin time
- Transaminases: ALT (SGPT), AST, (SGOT)
- Bilirubin: direct to conjugated, indirect to unconjugated
____ is the optimal imaging modality for detecting biliary obstruction
Ultrasound is the optimal imaging modality for detecting biliary obstruction
Conjugated hyperbilirubinemia is either ____ or ____
Conjugated hyperbilirubinemia is either biliary obstruction or no biliary obstruction
- Biliary obstruction: extrahepatic cholestasis
- No biliary obstruction: intrahepatic cholestasis
Initial management of the jaundiced patient involves ____ and ____
Initial management of the jaundiced patient involves ruling out extrahepatic obstruction and ruling out easily treatable causes of intrahepatic cholestasis
- Ruling out extrahepatic obstruction: treat with endoscopic, radiologic, or surgical intervention
- Alcohol, meds, herbal, or OTC meds
Primary biliary cirrhosis is ____
Primary biliary cirrhosis is slowly progressing cholestatic liver disease of unknown etiology
- Female predominance
- Often asymptomatic but fatigue, pruritis, abdominal pain, jaundice, xanthomas, portal hypertension, and liver failure develop over 5-20 years
- Alkaline phosphatase and gamma-glutamyl transpeptidase typically elevated
- AMA positive in ≥ 90% of patients
This is ____ in ____
This is bile duct inflammation in primary biliary cirrhosis
Cholestasis is ____ that presents clinically with ____ or ____
Cholestasis is diminished bile flow / hepatobiliary secretion that presents clinically with jaundice or pruritis
- Characteristic liver biopsy findings
- Impaired vectoral transport from portal blood into the bile ducts of the various components of bile
- Extrahepatic form indicates an obstructive etiology
- Intrahepatic form indicates an impairment in molecular mechanisms of bile formation
Bile salts are important for ____
Bile salts are important for fat digestion and absorption
- Important for cholesterol and lipid metabolism
- Modulate hepatocyte intracellular signaling mechanisms and transcriptionally regulate many liver-specific gnes
- Excess concentrations of bile salts disrupt hepatocyte membranes, injure hepatocytes, and induce apoptosis (especially hydrophobic)
- Can cause severe pruritis
Describe functions of bile salts
Functions of bile salts
- Detergents which are important for fat digestion and lipid absorption
- Prevent gallstone formation
- Important for cholesterol secretion, metabolism, and lipid homeostasis
- Stimulate secretion of phosphatidylcholine (lecithin) into bile
Clinical uses of bile salt (ursodeoxycholic acid) therapy are ____, ____, and ____
Clinical uses of bile salt (ursodeoxycholic acid) therapy are treatment of cholestatic liver diseases, therapy for pruritis associated with cholestasis, and gallstone dissolution therapy
Bile salts are endogenous ligands for the ___
Bile salts are endogenous ligands for the nuclear receptor farnesoid X receptor
- Farnesoid X receptor targeting can treat non-alcoholic steatohepatitis via effects on inflammation / fibrosis, lipid metabolism, and carbohydrate metabolism
Heme + bilirubin = ____
Heme + bilirubin = biliverdin
Bilirubin must be conjugated to ___ prior to secretion into bile
Bilirubin must be conjugated to bilirubin UDP-GT prior to secretion into bile
Describe hepatic transport of bile salts and bilirubin
Hepatic transport of bile salts and bilirubin
- Bile salt uptake from portal blood into cell via Ntcp and bilirubin uptake via albumin OATPs
- Bile salt secretion into bile via BSEP and bilirubin secretion into bile via MRP2
Bilirubin peaks on ____ in normal infants and ____ in premature infants
Bilirubin peaks on day 4-5 in normal infants and day 6 in premature infants
- Bilirubin UDP-GT activity is birth-related
- Increased RBC breakdown: hemolysis, hematoma
Gilbert’s disease involves ____ but no clinical consequences
Gilbert’s disease involves mild elevated unconjugated bilirubin but no clinical consequences
Bilirubin is increased in healthy individuals under conditions of ____, ____, or ____
Bilirubin is increased in healthy individuals under conditions of fasting, exertion, and infections
Gilbert’s Disease involves ____ in the TATAA box
Gilbert’s Disease involves 7 TAs in the TATAA box
Describe evaluation of Gilbert’s Disease
Evaluation of Gilbert’s Disease
- Asymptomatic patient
- Normal ALT, AST, alk phos, direct bilirubin
- Mild unconjugated hyperbilirubinemia
- Rule out hemolysis: CBC with peripheral smear, reticulocyte count, and haptoglobin
Excess metabolic capacity of the liver must obstruct ____ or ____ for jaundice to develop
Excess metabolic capacity of the liver must obstruct both left and right bile ducts or common bile duct for jaundice to develop
Intrahepatic cholestasis of sepsis results from ____
Intrahepatic cholestasis of sepsis results from down-regulation of multiple ATP-dependent canalicular hepatocyte transporters
Bile acids are ____
Bile acids are hydrophobic
Most canalicular transporters are ____-dependent
Most canalicular transporters are ATP-dependent
Intrahepatic cholestasis of pregnancy results from ____
Intrahepatic cholestasis of pregnancy results from Abcb4 mutations
- Treat with ursodeoxycholic acid (hydrophilic)
Abcb4 (MDR3) deficiency results in ____ or ____
Abcb4 (MDR3) deficiency results in intrahepatic cholestasis of pregnancy or progressive familial intrahepatic cholestasis 3
___ is the phenomenon in which the effect of one gene is dependent on the presence of ≥ 1 modifier genes
Epistasis is the phenomenon in which the effect of one gene is dependent on the presence of ≥ 1 modifier genes
- Gene-gene interactions between or within that lead to non-additive effects
