7. Hepatobiliary Function Flashcards

1
Q

What is the cause of Gilbert’s syndrome?

A

Mutation in UDP glucuronyl transferase.

Usually results in UDP glucuronyl transferase activity to about 30% of normal.

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2
Q

What is usually indicated by elevated serum aminotransferases (ALT/AST)?

A

Damage to hepatocytes.

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3
Q

What is the effect of liver damage on prothrombin time?

A

Prothrombin time increases due to a lack of hepatic coagulation factors.

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4
Q

What five things, discussed in class, can lead to pigment or cholesterol gallstones?

A

Too much absorption of water from bile.

Too much absorption of bile acids from bile.

Too much cholesterol in bile.

Too much bilirubin in bile (hemolytic anemia).

Inflammation of epithelium.

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5
Q

What are the sodium dependent and sodium independent transporters for bile salts on the basolateral side of hepatocytes?

A

Sodium dependent: sodium taurocholate cotransporting polypeptide (NTCP).

Sodium independent: organic anionic transport proteins (OATPs)

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6
Q

Which two transporters of the enterohepatic circulation are sodium dependent, and what spaces do they move bile acids between?

A

Sodium dependent taurocholate cotransporting polypeptide (NTCP) – from the portal circulation into the hepatocytes.

Apical sodium dependent bile acid transporter (ASBT) – from the intestinal lumen into the enterocytes.

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7
Q

What serum aminotransferases are tested as liver function enzymes?

A

Alanine aminotransferase.

Aspartate aminotransferase.

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8
Q

When bilirubin is produced by the reticular endothelial system, it is not water soluble. How does it get to the liver?

A

Through attachment to albumin.

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9
Q

What is the main issue in Dubin-Johnson syndrome?

A

Increase in serum conjugated bilirubin due to a malfunctioning multidrug-resistant protein 2 (MRP2).

This prevents hepatocytes from being able to secrete bilirubin into the bile canaliculi.

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10
Q

What is the primary issue in Rotor syndrome?

A

Defective OATPs, resulting in an inability to transfer conjugated bilirubin into the hepatocytes from the blood

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11
Q

What are the five given treatments for Crigler-Najjar syndrome?

A

Phototherapy.

Blood transfusions.

Oral calcium phosphate and carbonate.

Liver transplant (some type I patients).

Phenobarbital (type II patients only).

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12
Q

How is unconjugated bilirubin neurotoxic?

A

It upregulates apoptotic events in the neurons, astrocytes, microglia, and oligodendrocytes.

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13
Q

How does the amount of bile acid in the portal system regulate the amount of bile acid produced by the liver?

A

Bile acids inhibit the action of cholesterol 7alpha-hydroxylase – the rate limiting step in bile acid synthesis.

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14
Q

What four things, discussed in class, can occur as sequelae to cirrhosis of the liver?

What dysfunction of the liver causes the symptoms?

A

Ascites – lack of albumin, decreased oncotic pressure.

Hepatic encephalopathy – lack of urea processing.

Bruising – lack of coagulation factors.

Portal hypertension – due to the fibrotic liver.

(Portal hypertension causes caput medusae and esophageal varices)

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15
Q

How does conjugated bilirubin get to the small intestine?

A

Via the common bile duct with the bile.

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16
Q

Conjugated bilirubin that passes into the small intestine will undergo a series of steps before it is excreted into the feces. What is responsible for the occurrence of these steps, and what are the intermediates?

A

The bacteria of the small intestine are responsible for the steps, they unconjugate the bilirubin into urobilinogen.

Conjugated bilirubin -> Urobilinogen -> urobilin + stercobilin -> excretion through the feces.

17
Q

When urobilinogen arrives in the kidneys to be excreted through the urine, what intermediate does it become before it is excreted?

A

Urobilin.

18
Q

How is phototherapy effective for reducing serum bilirubin in neonates?

A

Exposure of light with a wavelength of approximately 459 nm causes trans-bilirubin to isomerized into the water-soluble form cis-bilirubin.

19
Q

If urobilinogen does not continue along its path to be excreted into the feces, what other options does it have to leave the small intestine?

A

Enter the enterohepatic circulation and be returned to the liver.

20
Q

What transporter transports bile acids from the enterocytes into the portal circulation?

A

Organic solute transporter alpha/beta (OSTalpha/OSTbeta)

21
Q

Where are bile acids reabsorbed in enterohepatic recirculation?

A

In the distal ileum.

22
Q

What are the two main causes for physiological neonatal jaundice?

A

Increased bilirubin production, due to the shortened life span of fetal erythrocytes.

Decreased UDP glucuronyl transferase activity as it ramps up slowly after birth.

23
Q

What are the two bile acid transporters that move bile acids from the hepatocytes into the bile canaliculi?

A

Bile salt excretory pump (BSEP).

Multidrug-resistant protein 2 (MRP2).

24
Q

What are the “bile acid -dependent” portions of bile?

What are the “bile acid-independent” portions of bile?

A

Bile acid -dependent: bile acids, cations, water from the liver.

Bile acid-independent: bicarbonate from the pancreas, water from the pancreas.

25
Q

Do Gilbert’s syndrome and Crigler-Najjar syndrome cause conjugated or unconjugated jaundice?

A

Both cause unconjugated jaundice due to dysfunction of UDP glucuronyl transferase.

26
Q

What is the basic issue in Crigler-Najjar syndrome type II?

When do symptoms typically present?

A

<20% function of UDP glucuronyl transferase.

Much later in life.

27
Q

What diseases discussed can lead to conjugated bilirubinemia?

A

Dubin-Johnson syndrome.

Rotor syndrome.

Biliary tree obstruction.

28
Q

In which disease discussed does the liver have a black pigmentation?

A

Dubin-Johnson syndrome.

29
Q

What is the main transporter that moves bile salts from the lumen of the intestine into the enterocytes?

A

Apical sodium-dependent bile transporter (ASBT)

30
Q

Once bilirubin gets to the liver, it needs to be conjugated. What enzyme performs this function?

A

UDP glucuronyl transferase.

31
Q

What is the pathological cause of symptoms from Crigler-Najjar syndrome type I?

When do symptoms typically present?

A

Complete loss of function of UDP glucuronyl transferase.

Immediately after birth.

32
Q

What is usually indicated by elevated alkaline phosphatase?

A

Bile duct injury.

33
Q

What is the intermediate between hemoglobin and bilirubin?

A

Biliverdin

34
Q

What are the two types of gallstones?

A

Pigment gallstones.

Cholesterol gallstones.

35
Q

What is kernicterus?

A

Kernicterus is a neurologic sequelae of bilirubin-induced neurologic dysfunction.

Clinical features include cerebral palsy, sensorineural hearing loss, and gaze abnormalities.