SM_156b: Biliary Tract Disorders

Question 1

Cholestasis presents with ____ and ____

Answer 1

Cholestasis presents with hyperbilirubinemia and jaundice

Question 2

Cholestasis pathology includes ____

Answer 2

Cholestasis pathology includes liver lobule

Question 3

These are ____

Answer 3

These are bule infarcts

Question 4

These are ____

Answer 4

These are bile plugs

Question 5

Describe the anatomy of the biliary system

Answer 5

Anatomy of the biliary system

Question 6

Cholestasis involves diminished ____ and ____

Answer 6

Cholestasis involves diminished bile flow and hepatobiliary secretion

• Bile salt-dependent bile flow: osmotic forces
• Bile salt-independent bile flow: osmotic and other factors

Question 7

___ infusion stimulates bile flow, while ___ increases as bile flow increases

Answer 7

Bile salt infusion stimulates bile flow, while bile salt secretion increases as bile flow increases

Question 8

Cholestasis involves impairment in molecular mechanisms of ____

Answer 8

Cholestasis involves impairment in molecular mechanisms of bile formation

Question 9

Serum liver chemistry tests include ____, ____, ____, and ____

Answer 9

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

Question 10

____ is the optimal imaging modality for detecting biliary obstruction

Answer 10

Ultrasound is the optimal imaging modality for detecting biliary obstruction

Question 11

Conjugated hyperbilirubinemia is either ____ or ____

Answer 11

Conjugated hyperbilirubinemia is either biliary obstruction or no biliary obstruction

• Biliary obstruction: extrahepatic cholestasis
• No biliary obstruction: intrahepatic cholestasis

Question 12

Initial management of the jaundiced patient involves ____ and ____

Answer 12

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

Question 13

Primary biliary cirrhosis is ____

Answer 13

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

Question 14

This is ____ in ____

Answer 14

This is bile duct inflammation in primary biliary cirrhosis

Question 15

Cholestasis is ____ that presents clinically with ____ or ____

Answer 15

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

Question 16

Bile salts are important for ____

Answer 16

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

Question 17

Describe functions of bile salts

Answer 17

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

Question 18

Clinical uses of bile salt (ursodeoxycholic acid) therapy are ____, ____, and ____

Answer 18

Clinical uses of bile salt (ursodeoxycholic acid) therapy are treatment of cholestatic liver diseases, therapy for pruritis associated with cholestasis, and gallstone dissolution therapy

Question 19

Bile salts are endogenous ligands for the ___

Answer 19

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

Question 20

Heme + bilirubin = ____

Answer 20

Heme + bilirubin = biliverdin

Question 21

Bilirubin must be conjugated to ___ prior to secretion into bile

Answer 21

Bilirubin must be conjugated to bilirubin UDP-GT prior to secretion into bile

Question 22

Describe hepatic transport of bile salts and bilirubin

Answer 22

Hepatic transport of bile salts and bilirubin

1. Bile salt uptake from portal blood into cell via Ntcp and bilirubin uptake via albumin OATPs
2. Bile salt secretion into bile via BSEP and bilirubin secretion into bile via MRP2

Question 23

Bilirubin peaks on ____ in normal infants and ____ in premature infants

Answer 23

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

Question 24

Gilbert’s disease involves ____ but no clinical consequences

Answer 24

Gilbert’s disease involves mild elevated unconjugated bilirubin but no clinical consequences

Question 25

Bilirubin is increased in healthy individuals under conditions of ____, ____, or ____

Answer 25

Bilirubin is increased in healthy individuals under conditions of fasting, exertion, and infections

Question 26

Gilbert’s Disease involves ____ in the TATAA box

Answer 26

Gilbert’s Disease involves 7 TAs in the TATAA box

Question 27

Describe evaluation of Gilbert’s Disease

Answer 27

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

Question 28

Excess metabolic capacity of the liver must obstruct ____ or ____ for jaundice to develop

Answer 28

Excess metabolic capacity of the liver must obstruct both left and right bile ducts or common bile duct for jaundice to develop

Question 29

Intrahepatic cholestasis of sepsis results from ____

Answer 29

Intrahepatic cholestasis of sepsis results from down-regulation of multiple ATP-dependent canalicular hepatocyte transporters

Question 30

Bile acids are ____

Answer 30

Bile acids are hydrophobic

Question 31

Most canalicular transporters are ____-dependent

Answer 31

Most canalicular transporters are ATP-dependent

Question 32

Intrahepatic cholestasis of pregnancy results from ____

Answer 32

Intrahepatic cholestasis of pregnancy results from Abcb4 mutations

• Treat with ursodeoxycholic acid (hydrophilic)

Question 33

Abcb4 (MDR3) deficiency results in ____ or ____

Answer 33

Abcb4 (MDR3) deficiency results in intrahepatic cholestasis of pregnancy or progressive familial intrahepatic cholestasis 3

Question 34

___ is the phenomenon in which the effect of one gene is dependent on the presence of ≥ 1 modifier genes

Answer 34

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