Hepatobiliary Function

Question 1

Cirrhosis

Answer 1

Chronic liver disease in which normal liver cells are damaged and replaced by scar tissue
Mostly caused by excessive alcohol use- leads to accumulation of fat in hepatocytes causing steatohepatitis (fatty liver w/inflammation) - scarring occurs and causes cirrhosis

Question 2

Cirrhosis and portal hypertension

Answer 2

Develops when there is resistance to portal blood flow, which most often occurs in the liver - can be caused by cirrhosis - it increases sinusoidal pressure and blood flows backward through portal collaterals

Question 3

Esophageal varices and caput medusae

Answer 3

Cirrhosis clinical manifestation
Occlusion of portal vein can cause build up of fluid in GI tract and can extend to esophagus causing esophageal varices and open new collateral vessels such as the umbilical vein that used to be closed (causes caput medusae)

Question 4

What causes bruising in cirrhosis

Answer 4

Loss of clotting factors

Question 5

What causes hepatic encephalopathy in cirrhosis

Answer 5

Ammonia metabolism is effected and there is excess ammonia which can be toxic to brain and cause osmotic changes

Question 6

What causes ascites in cirrhosis

Answer 6

Loss of (mainly) albumin production can change blood osmolarity and cause fluid buildup in interstitium
Portal hypertension contributes as well

Question 7

Which bile acids have highest/lowest concentrations

Answer 7

Highest- cholic acid

Lowest- lithocholic acid

Question 8

Duodenum, jejunum, ileum and colon functions in relation to bile salts/acids

Answer 8

Duodenum-emulsification and digestion of fats
Jejunum- micelle formation and fat absorption - passive transport
Ileum- ACTIVE* (only area with active reabsorption of bile) and passive reabsorption of bile acids
Colon- passive transport of bile acids

Question 9

Bile acid composition in the canaliculi

Answer 9

Secretin stimulates the secretion of HCO3 and H20 from the ductile cells, resulting in a increase in bile volume and pH, and decrease in bile salt concentration (bile acid independent)
Passive cation flow into canaliculus accompanies bile acid secretion from liver
Most bile formation is driven by bile acids (bile acid dependent)

Question 10

CCK

Answer 10

Released when eating, causing contraction of the gallbladder and relaxation of the sphincter of oddi; allowing bile to flow into duodenum

Question 11

Reuptake of bile salts into the liver is mediated by

Answer 11

Na dependent transport protein - NTCP

Na independent transport protein- OATP

Question 12

Excretion of bile acid into canaliculi - transporters involved

Answer 12

BSEP bile salt excretory pump

MRP2 multidrug resistance protein 2

Question 13

Transport of bile acid into enterocyte from ileum is mediated by

Answer 13

ASBT apical sodium dependent bile acid transporter

Question 14

Ion movement in gallbladder

Answer 14

Na, Cl, HCO3 and H20 move out of the gallbladder into the liver, concentrating bile acids in the gallbladder

Question 15

Relationship b/w rates of bile acid synthesis and secretion

Answer 15

Increased bile secretion increases rate of return of bile acids to liver via portal blood - exerting a negative feedback on synthesis
Interruption of enterohepatic circulation (such as in an ileal resection) can increases synthesis values significantly

Question 16

UDP glucoronyl transferase

Answer 16

Conjugates bilirubin in the liver, making it more soluble

Question 17

Urobilinogen/stercobilin

Answer 17

Conjugated bilirubin is converted to these and excreted in urine/feces

Question 18

Hemolytic anemia and bilirubin

Answer 18

Causes increased bilirubin and liver production of conjugated bilirubin is overwhelmed, causing increased levels of unconjugated bilirubin

Question 19

Gilberts syndrome

Answer 19

Increased unconjugated bilirubin
Mutation in UDP glucuronyltransferase gene causes this (enzyme is still made but less functional)
Also can be caused by interference with movement of bilirubin into liver where it is glucoronidated
Mild disease

Question 20

Crigler-Najjar syndrome

Answer 20

Increased unconjugated bilirubin in blood
Mutation in UDP glucuronyltransferase gene causes
Type 1 is very severe - starts earlier- no function of enzyme. Can cause kernicterus - brain damage caused by accumulation of unconjugated bilirubin
Typer 2 is less severe - less than 20% function

Question 21

Dubin Johnson

Answer 21

Increased conjugated bilirubin
MRP2 gene mutation (transport bilirubin out of liver cells into bile)
Liver has black pigmentation

Question 22

Rotor syndrome

Answer 22

Increased conjugated and unconjugated - mostly conjugated bilirubin
Gene mutation in OATP gene (transport bilirubin from blood into liver to be cleared)

Question 23

Causes of gallstones

Answer 23

Too much absorption of water from bile
Too much absorption of bile acids from bile
Too much cholesterol in bile
Inflammation of epithelium

Question 24

Choledocholithiasis

Answer 24

Gallstones occluding the common bile duct - causes conjugated hyperbilirubinemia

Question 25

Elevated ALTs

Answer 25

Primarily result of hepatocyte injury

Question 26

Elevated alkaline phosphatase

Answer 26

Primarily result of bile duct injury e.g. cholestasis

Question 27

Albumin test

Answer 27

Severe hepatocyte impairment is likely to reduce albumin levels - such as in cirrhosis
Hypoalbuminemia is not specific for liver disease, could also be seen in kidney glomerular disease

Question 28

PT

Answer 28

Reflects degree of hepatic synthetic dysfunction

Increases as the ability of a cirrhotic liver to synthesize clotting factors diminishes