Hepatobiliary Physio

Question 1

Main Functions of Liver

Answer 1

• Bile production
• Carb/protein/lipid metabolism
• Bilirubin production/excertion
• Detox of substances

Question 2

Carbohydrate metabolism (liver)

Answer 2

• Gluconeogenesis
• Glycogen storage
• Glucose release

Question 3

Protein metabolism (liver)

Answer 3

• Nonessential AA synthesis
• Modification of AAs for biosynthetic pathways
• Plasma protein synthesis (ie. albumin)
• Conversion of ammonia to urea

Question 4

Lipid metabolism (liver)

Answer 4

• FA oxidation

- Synthesis of lipoproteins, cholesterol and phospholipids

Question 5

Portal hypertension

Answer 5

Resistance to portal blood flow (usually in liver d/t cirrhosis) and can lead to esophageal varices and caput medusae

Question 6

Esophageal Varices

Answer 6

Swollen connection between systemic and portal systems @ inferior end of esophagus

Question 7

Caput Medusae

Answer 7

Swollen connection between systemic and portal systems around umbilicus

Question 8

Hepatic Encephalopathy

Answer 8

Decreased hepatic urea cycle metabolism leading to accumulation of ammonia in systemic circulation (by crossing BBB)

Question 9

Bile composition

Answer 9

• Bile salts (50%)
• Phospholipids (40%)
• Bile pigments (ie. bilirubin) (2%)
• Cholesterol (4%)
• Ions and H2O

Question 10

Bile Function

Answer 10

• Vehicle for elimination of substances from body

- Allows lipids to become soluble

Question 11

Relative amount of bile acids

Answer 11

Cholic acid > Chenodeoxycholic acid > Deoxycholic acid > Lithocholic acid

Question 12

Primary bile acids

Answer 12

• Cholic acid
• Chenodeoxycholic acid
• Synthesized in liver hepatocytes

Question 13

Secondary bile acids

Answer 13

• Deoxycholic acid (from cholic)
• Lithocholic acid (from chenodeoxycholic)
• Lumen on SI

Question 14

Bile salts

Answer 14

• Cholic acid – deoxycholic acid – glycodeoxycholic acid/taurodeoxycholic acid
• Chenodeoxycholic acid – lithocholic acid – glycolithocholic acid/taurolithocholic acid
• Conjugated in liver

Question 15

Liver and Bile secretion

Answer 15

• Electrolytes secreted (Secretin mediated)

- Bile acids secreted

Question 16

Gallbladder and bile secretion

Answer 16

Storage and concentration of bile b/w meals (CCK mediated)

Question 17

Duodenum and bile secretion

Answer 17

Emulsification and digestion of fats

Question 18

Jejunum and bile secretion

Answer 18

Micelle formation and fat absorption

Question 19

Ileum and bile secretion

Answer 19

Active absorption of bile salts (leading to enterohepatic recirculation of bile)

Question 20

Recirculation of bile salts

Answer 20

• Uptake is across BL membrane of hepatocytes via

Na+-dependent transport protein (NTCP) and Na+-independent transport protein (OATPs)

Question 21

Bile acid synthesis/secretion relationship

Answer 21

• Increased bile secretion increases rate of return of bile acids to liver (via portal blood) – negative feedback on synthesis

Question 22

Enzyme regulating formation of bile acids/salts

Answer 22

7a- hydroxylase (cholesterol to primary bile acid)

7a-dehydroxylase (primary bile acid to secondary bile acid)

Question 23

Role of secretin in bile secretion

Answer 23

Stimulates secretion of HCO-3 and H2O from ductile cels – increased bile volume, [HCO-3], and pH and decreased [bile salts]
*Responsible for only small portion of bile secretion

Question 24

Enzyme converting unconjugated bilirubin to conjugated bilirubin

Answer 24

UDP glucuronyl transferase

Question 25

Hemolytic anemia

Answer 25

- Hemolysis -- increased unconjugated bilirubin | - Liver's capacity to produce conjugated bilirubin is overwhelmed

Question 26

Physiological neonatal jaundice

Answer 26

- Increased UC bilirubin during 1st week | - D/t increased breakdown of fetal erythrocytes and low UDP glucuronyl transferase activity

Question 27

Gilbert Syndrome

Answer 27

- increased levels of UC bilirubin - relatively mild - d/t mutation in gene coding for UDP glucuronyl transferase (30% that of normal activity)

Question 28

Crigler-Najjar syndrome (Type 1)

Answer 28

- No function of UDP glucuronyl transferase | - Can cause kernicterus

Question 29

Kernicterus

Answer 29

- Permanent neurological sequelae of bilirubin-induced neuro dysfunction - Leads to cerebral palsy, sensorineural hearing loss - Tx with immediate phototherapy

Question 30

Crigler-Najjar syndrome (Type 2)

Answer 30

- Less than 20% function of UDP glucuronyl transferase | - Less likely to develop kernicterus

Question 31

Treatments for Crigler-Najjar

Answer 31

- Phototherapy - Blood transfusions - Oral Ca and PO43- - Liver transplant - Phenobarbitol (Type 2)

Question 32

Dubin-Johnson Syndrome

Answer 32

- Increased conjugated bilirubin (w/o elevated liver enzymes) - D/t defect in ability of hepatocytes to secrete conjugated bilirubin into bile (MRP 2 mutation) * Black pigmented liver and mild jaundice

Question 33

Rotor Syndrome

Answer 33

- Buildup of UC/C bilirubin (more conjugated though) - Abnormally short/absent OATP1B1 and OATP1B3 proteins (genes related to bilirubin transport) - Similar to Dubin-Johnson... but no liver pigmentation

Question 34

Mechanism of phototherapy

Answer 34

- Process of isomerization changes trans-bilirubin into cos-bilirubin isomer (water soluble) - 459nm wavelength

Question 35

Cholelithiasis causes

Answer 35

- too much water absorption from bile - too much absorption of bile acids from bile - too much cholesterol in bile - inflammation of epithelium

Question 36

Locations of gallstones (and effects) (in order of prevalence)

Answer 36

1. Large gallstones staying in GB (asymptomatic) 2. Small stones intermittently blocking cystic duct (intermittent pain) 3. Small stones impacted in cystic duct (acute cholecystitis) 4. Small stones impacted in distal bile duct (jaundice/pain/cholangitis/pancreatitis)

Question 37

Elevated aminotransferase

Answer 37

Result of hepatocyte injury

Question 38

Elevated alkaline phosphatase

Answer 38

Result of bile duct injury (cholestasis)

Question 39

Bilirubin lab test

Answer 39

Measures liver's ability to detoxify metabolites and transport organic anions into bile

Question 40

Albumin lab test

Answer 40

Severe hepatocyte impairment will reduce albumin levesl in plasma

Question 41

PT

Answer 41

- Reflects the degree of hepatic synthetic dysfunction | - Increases as liver's clotting ability decreases

Question 42

Phase I drug metabolism

Answer 42

Drugs processed via cytochrome p450

Question 43

Phase II drug metabolism

Answer 43

Conjugation (w/ glucoronide, sulfate, AAs, glutathione) step follows, for further detox