Liver

Question 1

How do you distinguish between conjugated bilirubinemia and unconjugated bilirubinemia (a test)? What is the differential diagnosis for unconjugated bilirubinemia?

Answer 1

Conjugated bilirubinemia will end up in the urine, and you can test that shit.

DDx: Newborn (esp. if there is hemolytic dz of the newborn –> hemolysis + limited conjugation ability), Crigler-Najjar, Gilbert, hemolysis

Question 2

Does direct bilirubin measure conjugated, or unconjugated bilirubin?

Answer 2

Conjugated

Question 3

Regarding labs, how can you distinguish between the two major forms of conjugated bilirubinemia: cholestatic jaundice and hepatocellular jaundice?

Answer 3

In cholestatic jaundice, ALT and AST are only mildly elevated while ALKPhos is markedly elevated (>3x upper normal limit).

In hepatocellular jaundice, ALT and AST will be super high (>300 IU) while the ALKPhos will be <3x upper limit of normal

Question 4

What diagnostic tests are good to distinguish between intrahepatic and extrahepatic cholestasis?

Answer 4

Ultrasound or CT helps you visualize dilated ducts. If they are dilated = extrahepatic obstruction

Question 5

Hepatocytes in zone ___ of the liver acinus are most susceptible to ischemia.

Answer 5

zone 3

Question 6

What is the specific mechanism by which rifampin can cause bilirubinemia? What type of bilirubinemia is it (conjugated vs. unconjugated)?

Answer 6

Inhibition of OATP-2, which aids in uptake of UCB by hepatocytes. It leads to unconjugated bilirubinemia.

Question 7

How does Gilbert syndrome present? What is the pathophysiology behind this disease? What is the treatment?

Answer 7

Presents with jaundice/bilirubinemia during times of stress (lack of sleep, starvation, etc.). It is unconjugated because the defect is in the glucuronosyl transferase enzyme (low activity). No treatment; bouts of jaundice are self-limited.

Question 8

What specific transporter in the liver is particularly sensitive to stress (ie. infection, drugs), which can potentially lead to bilirubinemia and bilirubinuria? What is its function?

Answer 8

MRP-2 transporter - transports conjugated bili into bile canaliculi

Question 9

Which cell type in the liver mediates the fibrosis that is characteristic of cirrhosis?

Answer 9

stellate cells

Question 10

Describe the pathogenesis of ascites.

Answer 10

Increased pressure in the sinusoids -> lymphatics on the surface of the liver dilate and weep fluid into the peritoneal cavity.

Question 11

Hypertension of the portal system at which of the following locations is likely to lead to splenomegaly and hypersplenism: pre-hepatic, intrahepatic, post-hepatic?

Answer 11

Intrahepatic and pre-hepatic hypertension typically cause marked splenomegaly and hypersplenism

Question 12

What are the mechanisms by which one could get unconjugated hyperbilirubinemia?

Answer 12

1. Hemolysis
2. Impaired delivery (ex. right heart failure)
3. Impaired uptake (OATP-2)
4. Impaired storage in hepatocytes
5. UDP transferase gets messed up (Gilbert, Crigler-Najjar)

Question 13

What is the genetic defect that causes Gilbert syndrome?

Answer 13

Mutation of UGT1A1 gene on chromosome 2

Question 14

What are cholesterol stones made out of?

Answer 14

Cholesterol

Question 15

What are mixed pigment and black pigment stones made out of?

Answer 15

Black pigment stones are made out of unconjugated bilirubin and calcium and mixed stones are made out of bilirubin, calcium, and cholesterol

Question 16

What causes biliary colic?

Answer 16

Blockage of the cystic duct by a stone.

Question 17

What is a drug that you can use to treat gallstones and cholestasis? How does it work?

Answer 17

Ursodiol/ursodeoxycholic acid - decreases rate of cholesterol absorption

Question 18

Why does acute hepatitis cause an elevation of serum B12 and iron?

Answer 18

When hepatocytes die, they release B12 and ferritin

Question 19

What is the treatment for acetaminophen toxicity and how does it work?

Answer 19

Acetylcysteine replenishes reduced glutathione so toxic NAPQI can be converted to a water soluble metabolite for excretion

Question 20

What are the risk factors of NAFLD?

Answer 20

Female, fat, forty, fertile

Question 21

What is the treatment for early hepatorenal syndrome?

Answer 21

Plasma volume expansion w/ albumin

Question 22

What is the treatment for late hepatorenal syndrome?

Answer 22

Vasopressors like octreotide, midodrine. Albumin helps restore effective arterial blood volume.

Question 23

Liver and biliary tree disorders can sometimes refer pain to the _______.

Answer 23

Shoulder

Question 24

Which cell type in the liver do FFAs cause damage to? What is the mechanism by which fibrosis occurs in this case?

Answer 24

FFAs –> oxidation products –> Kuppfer cells make TNF-a –> Stellate cells make collagen

Question 25

What is the carrier protein for unconjugated bilirubin?

Answer 25

albumin

Question 26

What is the rate-limiting step of bilirubin metabolism?

Answer 26

Uptake of unconjugated bilirubin into hepatocytes

Question 27

Which step in bilirubin metabolism is most resistant to dysfunction?

Answer 27

conjugation

Question 28

What are the essential factors for gallstone formation?

Answer 28

1. Saturation (thermodynamics)
2. Stasis
3. Nucleation (kinetics)

Question 29

What enzyme is responsible for unconjugating bilirubin after it has been secreted into the bile ducts?

Answer 29

Ductal epithelial cells express beta-glucuronidase

Question 30

Explain why INR can be elevated without hypoalbuminemia in the setting of hepatitis.

Answer 30

The half life of clotting factors is shorter than albumin, so there will be a time when clotting factors are low while there is still plenty of albumin

Question 31

Right-sided heart failure may cause necrosis of zone ____ hepatocytes.

Answer 31

3

Question 32

Describe the pathogenesis of hepatorenal syndrome.

Answer 32

Cirrhosis -> increased portal venous pressure, liver endothelial cells make vasoconstrictors and have increased sensitivity to vasoconstrictors, and they also make less NO

Splanchnic circulation increases NO production to increase flow, which leaks out into into the systemic circulation -> low BP -> increased cardiac output

The splanchnic vessels act as a third space and keep the EABV low

Low BP triggers the RAAS and SNS systems –> epinephrine and a lot of angiotensin II constricts both afferent and efferent arterioles in the kidneys -> kidney failure

Question 33

Is a stone in the cystic duct likely to cause bilirubinemia?

Answer 33

No, conjubated bilirubin can still get down the common bile duct

Question 34

What are the mechanisms by which a severe GI bleed in a cirrhotic patient can cause oliguria?

Answer 34

Low BP -> RAAS activation and concentration of urine

If the patient has cirrhosis already, this can precipitate hepatorenal syndrome -> kidney failure

Question 35

What are the mechanisms by which a severe GI bleed in a cirrhotic patient can cause somnolence?

Answer 35

Hypoperfusion from blood loss

Blood in the GI tract liberates ammonia and is absorbed, then bypasses the liver from portosystemic shunts and goes to the brain (hepatic encephalopathy)