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GI > Bilirubin, Jaundice, and Gallstones > Flashcards

Bilirubin, Jaundice, and Gallstones Flashcards

1
Q

Where does most bilirubin come from?

A

Hemoglobin from senescent RBCs. (rest comes from heme from hepatic enzymes)

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2
Q

Uncojugated bilirubin isn’t water soluble. So how is it transported in the blood?

A

It’s bound to albumin with hydrogen bonds.

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3
Q

What enzyme conjugates glucuronide to bilirubin in the hepatocyte ER?

A

UDP glucuronosyltransferase

G transferase

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4
Q

Review: What’s the rate-limiting step in bilirubin secretion?

A

Pumping bile into the bile duct.

Requires ATP.

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5
Q

How does the body protect against uncojugated bilirubin being a neurotoxic lipid? (4 things)
In what patients can these be defective?

A

Binding to albumin.
BBB
Conjugation
Excretion in bile
(… only newly mentioned thing is the BBB)
These can all be partial defective in newborns.

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6
Q

What is delta bilirubin?

Significance?

A

Conjugated bilirubin that has covalently bound to albumin.
It’s only found in patients with prolonged cojugated bilirubinemia, and it has a long half-life because it’s too big to be peed out.
(its persistence can make it look like hyperbilirubinemia isn’t resolving)

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7
Q

What are urobilinogen and pyrroles?

A

Some bilirubin is converted to urobilinogen by gut bacteria… which can be absorbed and peed out.
Some urobilinogen is converted by bacteria to pyrroles, which give stool its color.

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8
Q

About how high must bilirubin be in order to get jaundice?

A

About twice normal levels.

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9
Q

How does urine look in a patient with unconj. hyperbili?

In conj. hyperbili.?

A

Unconjugated: Urine looks normal, as the bilirubin can’t reach the urine.
Conjugated: Urine looks dark, as the water soluble conjugated bilirubin can reach the urine.

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10
Q

3 etiologies of unconj. hyperbili.?

A

Overproduction of bili
Reduced uptake of bili by liver
Defects of bili conjugation.

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11
Q

2 ways to get reduced hepatic uptake of unconj. bili?

A

Altered circulation.. (portal shunting… right heart failure)
Effect of some drugs (eg. rifamycin)
(this is pretty uncommon)

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12
Q

3 main processes that can cause overproduction of bili?

Are these associated with altered liver histology / enzymes?

A 
Hemolysis  (e.g. sickle cell anemia).
Extravasation into tissue (e.g. bruise, hematoma).
Ineffective erythropoeisis (e.g. pernicious anemia).
These don't cause altered liver histology / enzymes.
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13
Q

What are 2 inherited forms of defects in conjugation?

A 
Crigler Najjar (types I & II) - rare, severe
Gilbert's - common, benign.
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14
Q

3 acquired causes of defective conjugation of bilirubin?

A

Drugs
Chronic hepatitis (e.g. Wilson’s)
Hyperthyroidism

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15
Q

Do newborns have relatively impaired bilirubin conjugation?

A

Yes.

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16
Q

How does phototherapy help get rid of jaundice of the newborn?

A

Breaks H bonds between bili and albumin… making bili soluble and easier to excrete.

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17
Q

What’s less functional in Gilbert’s syndrome?

A

G-transferase. Less conjugation, more serum unconj. bili.

Note that liver enzymes are normal.

18
Q

When do people with Gilbert’s syndrome actually get significantly high bilirubin?

A

During fasting.

Normally, unconj. bili rises a tiny bit when fasting, but this response is very exaggerated in Gilbert’s Syndrome.

19
Q

3 types of causes of conj. hyperbili.?

A

Inherited secretory defect (rare).
Disease of hepatocytes (hepatocellular, cholestatic, or both).
Biliary obstruction.

20
Q

2 inherited defects in secretion bili into the bile ducts?

A

Dubin-Johnson Syndrome (causes black liver, too)

Rotor Syndrome

21
Q

If you have necrotizing hepatitis causing conj hyperbili, what other biochemistries will be altered?

A

High liver enzymes, low PT (which won’t be corrected by IM Vit K)

22
Q

How can you distinguish with imaging intrahepatic from extrahepatic cholestasis?

A

Extrahepatic cholestasis will cause dilated biliary ducts.

Intrahepatic cholestasis will not.

23
Q

Biochemical findings in cholestasis?

A 
High serum alk phos.
Increased GGT (which is more specific).
24
Q

What are notable symptoms of cholestasis?

A

Pruritis

Fatigue and Anorexia

25
Q

What can be given to alleviate the pruritis of cholestasis?

A

Cholestyramine

and diphenhydramine

26
Q

Cholestasis can lead to malabsorption of Vit. ADEK. What does deficiency in each lead to?

A

Vit A: night blindness
Vit D: osteomalacia
Vit K: impaired prothrombin synth
Vit E: cerebellar and peripheral nerve disorders

27
Q

Why do people with cholestasis get xanthelasmae?

A

Cholesterol not excreted in bile builds up and deposits in the skin.

28
Q

2 types of extrahepatic causes of cholestasis?

A

Benign: stones, strictures, pancreatitis.
Malignant: pancreas, bile duct, gall bladder cancers

29
Q

What is the main medical therapy for cholestasis?

A

Ursodeoxycholic Acid (aka Ursodiol)

30
Q

What kind of lesion gets serum bilirubin the highest?

A

Complete obstruction of bile flow (… even more so if there’s hemolysis thrown in)

31
Q

What’s the most common type of gallstone?

A

Cholesterol

32
Q

3 predisposing factors for gallstones?

A

Supersaturation
Stasis
Nucleation factors

33
Q

Main way to detect gallstones?

A

Ultrasound - look for the shadows.

34
Q

What are pigment gallstones formed from?

Where do they form?

A

Mainly unconjugated bilirubin.
Black ones form in gallbladder
Brown ones form in the bile duct.

35
Q

Risk factors for cholesterol gall stones?

A

Lots…
Female, >30, multiparity, obesity, lack of exercise….
Rapid weight loss, genetics, drugs, TPN, Western diet.
(The old, not-PC mnemonic not mentioned was “Fat, Forty, Female, Fertile”)

36
Q

What determines the radiodensity of cholesterol stones?

A

The amount of calcium salts present.

37
Q

What’s “sludge”?

How can one prevent it from progressing?

A

A nice cholesterol, bilirubin, mixed mucous gel at the bottom of the gallbladder. It may progress to stones.
Weight loss and ursodiol can help prevent progression to stones.

38
Q

What are black stones formed by?

Who gets them?

A

Mostly calcium bilirubinate, but with lots of calcium salts.

Older people with hemolysis and cirrhosis.

39
Q

What are brown stones formed by?

Who gets them?

A

Calcium bilirubinate without as much calcium salts (less radiodense)… form in bile duct.
Risks: being older and s.p. cholecystectomy.

40
Q

Can gallstones be asymptomatic?

A

Yes, and most are.

GI (45 decks)

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