hepatobiliary function

Question 1

how does liver failure cause edema and ascites

Answer 1

loss of albumin making function of the liver decreases oncontic pressure of the capillaries which pushes more water out into interstitial space

Question 2

how does hepatic encephalopathy occur due to liver disease

Answer 2

loss of liver function leads to loss of urea cycle. accumulation of ammonia which can cross the BBB to enter the brain and alters brain function

Question 3

how does liver disease cause bruising

Answer 3

loss of clotting factor production causes increase in ability to bruise

Question 4

how does alcohol abuse affect the liver

Answer 4

• alcohol abuse is number one cause of cirrhosis
• alcohol abuse leads to fat accumulation in hepatocytes
• fatty liver leads to steatohepatitis (inflammation of liver leading to scarring and cirrhosis of liver)
• cirrohsis of liver leads to portal HTN and splenomegaly

Question 5

where does the pigmentation of bile come from

Answer 5

bile pigments such as bilirubin

Question 6

where are primary bile acids made? secondary? and where does conjugation into bile salts occur?

Answer 6

primary: in liver
secondary: in SI by intestinal bacteria
conjugation: in liver

Question 7

what are the functions of the biliary systems organs?

Answer 7

1. liver: synthesizes bile and secretes into cannaliculi
2. gallbladder: storage and concentration of bile
3. duodenum: emulisification/digestion of fat
4. jejunum: micelle formation and fat absorption
5. ileum: active absorption of bile acids to portal circulation for recycling back to liver via enterohepatic circulation

Question 8

where is ions/H20 absorbed into bile and then secrete out of bile?

Answer 8

• between liver and gallbladder, ions and H20 are secreted into bile duct by action of secretin.
• in the gallbladder, ions and H20 are secreted out of bile and it is concentrated

Question 9

what are the two transporters responsible for bringing in bile salts back from enterohepatic circulation into the hepatocyte

Answer 9

1. NTCP (Na dependent)

2. OATP (Na independent)

Question 10

what are the names of the 2 transporter responsible for moving recycled bile and synthesized bile into the bile cannaliculi inside the liver

Answer 10

BSEP and MRP2

Question 11

which transporter is responsible for bringing bile into the enterocyte from biliary excretion

Answer 11

ASBT

Question 12

which transporter is responsible for moving bile from the enterocyte into the enterohepatic circulation for recycling

Answer 12

OST-alpha / or beta

Question 13

where is passive transport or bile back to liver occur? active?

Answer 13

passive: jejunum, ileum, colon
active: ileum
* *ileum brings more than 90% back

Question 14

what effect will ileal resection have on bile synthesis

Answer 14

you will increase hepatic bile synthesis bc less is being recycled back to the liver.

*increased bile secretion increases return of bile acids and therefore decreases biosynthesis of bile in liver by inhibition of 7-alpha hydroxylase

Question 15

what are the 2 mechanisms of bile (NOT BILE ACID) secretion

Answer 15

1. bile-acid dependent
   - bile formation driven by bile acids
2. bile acid Independent or ductular secretion
   - small amount of bile is stimulated by secretin and is secreted from the ducts
   - secretin stimulates the secretion of H20 and HCO3- from ductile cells into bile in order to raise the volume and pH (lower its concentration) for neutralization in the duodenum

Question 16

what is the function of CCK on the gallbladdr

Answer 16

• contraction of gallbladder
• relaxation of the Sphincter of Oddi
• release of bile from gallbladder into duodenum during the presence of food in GI tract

Question 17

where does bilirubin come from

Answer 17

hemolysis of RBCs

Question 18

describe the bilirubin excretion/ recycling pathway

Answer 18

1. bilirubin + albumin enters liver
2. glucuronic acid and UDP glucuronyl transferase conjugate bilirubin into direct bilirubin in the liver
3. conjugated bilirubin enter SI and unconjugates to become urobilinogen
4. urobilinogen can be recycled back to the liver via enterohepatic circulation or made into urobilin/stercobilin which is excreted

Question 19

what branch of the ANS will increase bile secretion

Answer 19

PNS

Question 20

what causes jaundice

Answer 20

accumulation of bilirubin in blood

-signs: yellow discoloration of eyes, skin, and mucous membranes

Question 21

what are causes of unconjugated (indirect) jaundice

Answer 21

1. hemolytic anemia (increase in RBC breakdown)
2. heart failure (decreased delivery of bilirubin for conjugation by liver)
3. Gilberts syndrome
4. Crigler-Najjar syndrome

Question 22

what are causes of conjugated (direct) jaundice

Answer 22

1. Dubin-Johnson syndrome
2. Rotor syndrome
3. biliary tree obstruction (by gallstones)

Question 23

what do we see physiological neonatal jaundice in new borns ?

Answer 23

• *increase unconjugated bilirubin
  1. increased production of bilirubin (short lifespan of fetal RBCs)
  2. low active UDP glucuronyl transferase

Question 24

Describe Gilbert Syndrome

Answer 24

• unconjugated jaundice
• mild disease
• mutation in gene for UDP glucuronyl transferase (30% active)
• problem up taking bilirubin into liver, and conjugating it in the liver

Question 25

describe Crigler-Najjar syndrome

Answer 25

*unconjugated jaundice by mutation of UDP glucuronyl transferase

Type 1

• severe disease; starts early infancy
• no function of transferase
• causes kernicterus

Type 2

• less severe; starts later in life
• 20% function of transferase
• less likely to develop kernicterus

Question 26

what is kernicterus

Answer 26

• permanent nuerologic damage by build up of unconjugated bilirubin in brain and nerve tissue
• causes: cerebral palsy, hearing loss, gaze abnormalities
• leaves yellow spots in brain

Question 27

what are the treatments for Crigler-Najjar syndrome

Answer 27

1. phototherapy (to solubilize bilirubin)
2. blood transfusion
3. oral calcium phosphate and carbonate (complexes bilirubin in gut)
4. liver transplant for type 1
5. phenobarbitol for type 2 (aids conjugation)

Question 28

describe Dubin-Johnson syndrome

Answer 28

• conjugated jaundice (no elevation of liver enzymes)
• mutated MRP2 (so defective transport of direct bilirubin into bile canalicuili to mix with bile)
• causes mild jaundice throughout lifespan
• also causes black pigmentation in liver

Question 29

describe Rotor syndrom

Answer 29

• conjugated jaundice (some unconjugated buildup)

- mutated and or absent OATP (so defective transport of bilirubin and bile acids into liver from blood)

Question 30

difference in consequences of small vs large gallstones

Answer 30

large
-stay in gallbladder; usually asymptomatic

small

• intermittently block cystic duct –biliary pain
• impact cystic duct – acute cholecystitis
• impact distal bile duct–jaundice, biliary pain, and risk of gallbladder or pancreatic infection/inflammation

Question 31

what are measured in the biochemical liver function tests, and what are abnormal findings indicative of

Answer 31

1. ALT/AST (aminotransferases)
   - elevated due to hepatocyte injury
2. alkaline phosphatase
   - elevated due to bile duct injury

Question 32

hat are measured in the function liver function tests, and what are abnormal findings indicative of

Answer 32

1. bilirubin levels (determine direct/indirect hyperbilirubinemia)
2. serum albumin levels
   - low levels due to hepatocyte impairment
3. PT time
   - elevated PT time due to cirrhotic liver

Question 33

what are the two phases of drug metabolism in the liver

Answer 33

1. first pass
   - processed via cytochrome P450 enzymes
2. conjugation step
   - after for further detoxification of the drug