Hepatobiliary Function

Question 1

What two mechanisms stimulate bile secretion?

Answer 1

1. Bile acid - dependent (MAJOR)

Movement of cations into the canaliculus

(canalicular bile is an ultrafiltrate of plasma)

2. Secretin (Bile acid - independent)

Question 2

What causes gallstones (cholelithiasis)?

Answer 2

Excess of either bilirubin or cholesterol breakdown

Too much absorption of water or bile acids or cholesterol in bile.

Question 3

What are the functions of the liver?

Answer 3

1. Detoxifies drugs/toxins
2. Bile production/secretion
3. Metabolizes carbs, proteins, lipids
4. Bilirubin production/excretion
5. Recieves absorbed nutrients

Question 5

What is the most common cause of cirrhosis? This leads to what?

Answer 5

Excessive alcohol intake

Leads to fatty liver (steatohepatitis)

Question 6

What 2 diseases have increased conjugated bilirubin?

Answer 6

1. Dubin Johnson
2. Gilberts

(Dustin Golub)

Question 7

If the ileum is resected and enterohepatic circulation is interrupted what happens?

Answer 7

Bile synthesis will be way higher than normal

Question 8

When a patient has liver failure, what symptom can they exhibit?

Answer 8

Edema from hypoalbumnemia

Question 9

When the function of the liver (ammonia –> urea) is damaged via cirrhosis & portosystemic shunting this leads to what?

Answer 9

Hepatic encephalopathy

Urea cycle impairment –> Increased ammonia in systemic circulation —> Damage brain

Question 10

What is cirrhosis?

Answer 10

Chronic liver disease where normal liver cells are damaged and replaced by scar tissue.

Question 11

What is the enzyme that turns bilirubin into its conjugated form?

Answer 11

UDP glucuronyl transferase

Question 12

What % of bile acids are excreted into feces? This means?

Answer 12

5%

This means that 90% of bile acids are recycled via portal blood and only 5% of bile needs to be synthesized by the liver.

Question 13

Decreased albumin means?

Answer 13

Severe impairment of hepatocyte function

Ex. cirrhosis

Question 14

Bile salts are recirculated to the liver via _______.

Answer 14

Enterohepatic circulation

Question 15

What 2 changes are associated w/ portal hypertension?

Answer 15

1. Esohageal varices ( veins get swollen between systemic + portal systems @ inferior end of esophagus)
2. Caput medusae (swollen connections between systemic + portal systems around umbilicus)

Question 16

What is the cause of physiologic neonatal jaundice?

Answer 16

Increased RBC destruction

Question 17

What is a symptom of Crigler-Najjar syndrome Type 1?

Answer 17

Kernicterus: brain damage caused by accumulation of unconjugated bilirubin

Question 18

What mutation causes Dubin Johnson?

Answer 18

MRP2

Liver is black

Question 19

Somatostatin, atropine, cimetidine, and omeprazole do what to gastric secretion?

Answer 19

Decrease it

Question 20

List the compostion (+ %’s of bile)

Answer 20

50% = bile salts

40% = phospholipids

Rest = cholesterol, bile pigments (bilirubin), ions, h20

Question 21

If there is a lot of bile return and no need for synthesis what hormone is inhibited?

Answer 21

cholesterol 7 alpha - hydroxylase

Question 22

Elevated alkaline phosphatase means?

Answer 22

Bile duct injury (ex. gallstones)

Question 23

PT (prothromibin time) liver test means?

Answer 23

Reflects the degree of hepatic synthetic dysfunction

As PT increases chirrhosis in the liver is getting worse

Higher the PT the worse off you are

Question 24

Remember the liver sees all drugs or toxic substances first through “first pass metabolism”

Question 25

What membrane are bile salts actively secreted across?

Answer 25

The canalicular membrane

Question 26

What can cirrhosis cause? (besides steatohepatitis)

Answer 26

Portal hypertension (resistance to portal blood flow from scarring)

Question 27

What increases saliva secretion? What decreses saliva secretion?

Answer 27

PNS Sleep, dehydration, atropine

Question 28

When you are not eating is bile released?

Answer 28

No

Question 29

What 3 diseases have increased **unconjugated** bilirubin?

Answer 29

1. Crigler Najar Syndrome 2. Physiologic Juandice 3. Hemolytic Anemia (Cunts pull hair)

Question 30

Gastrin, ACh, and histamine do what to gastric secretin?

Answer 30

Increase it

Question 31

What is the primary treatment in neonates w/ unconjugated hyperbilirubinemia?

Answer 31

Phototherapy makes bilirubin soluble

Question 32

Bilirubin is made in the body when the hemoglobin protein in old red blood cells is broken down.

Question 33

What syndrome has both increased conjugated and unconjugated bilirubin?

Answer 33

Rotors Syndrome | (Majority = conjugated)

Question 34

Hemolytic anemia results in _________ and is from what?

Answer 34

Increased **unconjugated** bilirubin Due to hemolysis.

Question 35

What mutations cause Rotor Syndrome?

Answer 35

OATP1B1 and OATP1B3 which transport bilirubin

Question 36

What are the metabolic functions of the liver?

Answer 36

carbs --\> gluconeogenesis, store + release glucose proteins --\> synthesize non - AA's + plasma proteins and convert ammonia to urea lipids --\> fatty acid oxidation, synthesis of phospholipids, cholesterol

Question 37

List the steps of bile secretion + absorption

Answer 37

1. Sinthesis + secretion of bile salts 2. Bile salts are stored + concentrated in the gallbladder 3. CCK - induced gallbladder contraction + sphincter of Oddi relaxation 4. Absorption of bile salts into the portal circulation 5. Delivery of bile slats to the liver

Question 38

What mutation causes Gilbert syndome?

Answer 38

UDP glucuronyltransferase

Question 39

What is jaundice a sign of?

Answer 39

Hyperbilirubinemia

Question 40

What is the function of bile?

Answer 40

To emulsify fat It makes lipids soluble (via micelles) so that they can be eliminated from the body

Question 41

What does bilirubin test measure?

Answer 41

Livers ability to detoxify metabolities and transport organic acids into bile

Question 42

Enterohepatic Circulation

Answer 42

Question 43

In enterohepatic circulation, what 2 systems transport bile salts across the **basolateral** membrane of hepatocytes?

Answer 43

1. NTCP (Na+ - dependent transport protein, sodium taurocholate cotransporting polypeptide) 2. OATPs (Na+ - independent transport protein, organic anaion transport proteins)

Question 44

What mutation causes Crigler - Najjar syndrome?

Answer 44

UDP gluccuronyltransferase Type 1: NO function Type 2: Partial function

Question 45

Elevated aminotransferase (AST/ALT) means?

Answer 45

liver damage