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GI Week 4 > Lecture 37: Bilirubin, Jaundice and Gallstones > Flashcards

Lecture 37: Bilirubin, Jaundice and Gallstones Flashcards

1
Q

Where does HEME come from?

A
  1. 80% from senescent RBCs
  2. 20% from heme (produced by hepatic enzymes)
    From these two sources, the enzye HEME OXYGENASE in the reticuloendothelial cells breaks down heme to
    i. Biliverdin
    ii. CO
    iii. Fe
    Biliverdin is then broken down to bilirubin
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2
Q

What are the characteristics of unconjugated bilirubin?

A

Very water INSOLUBLE

Because its proprionic acid groups (polar groups) are hidden by H-bonding…weird huh?

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3
Q

How is unconjugated bilirubin transported?

A

Bound by albumin because unconjugated bilirubin is water insoluble
At the hepatocyte membrane, they are split apart
Bilirubin is then taken up by the hepatocyte

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4
Q

What is the Space of Disse?

A

The space at which the bilirubin and albumin dissociate so that bilirubin can be transported into the hepatocyte membrane

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5
Q

Where does unconjugated bilirubin get conjugated?

A

In the hepatocyte

Gets conjugated with glucuronide in the ER by UDP Glucuronosyltransferase or UDP-GTransferase

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6
Q

Where does bilirubin get secreted?

A

Into the canaliculus against its concentration gradient

Most are secreted as diglucuronide

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7
Q

What is the transporter in the hepatocyte that carries glucuronides (hence bilirubin) into the lumen of the canaliculus?

A

MRP2

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8
Q

What are the organic components of bile?

A
  1. bilirubin (1%)
  2. bile salts (66%)
  3. phospholipid (22%)
  4. cholesterol
  5. protein
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9
Q

What is the point of glucuronidation of bilirubin?

A

It makes bilirubin water soluble
So conjugated bilirubin is water soluble
Found in bile not blood

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10
Q

What are the toxic effects of unconjugated bilirubin?

A

Neurotoxic lipid
So it is bound to albumin and inactivated by conjugation, excretion and blood brain barrier
These protective mechanisms may be defective in newborn

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11
Q

What is delta bilirubin?

A

A CONJUGATED bilirubin that is COVALENTLY BOUND to albumin (different from unconjugated albumin that is H-bond to albumin)
Only found in patients with protracted hyperbilirubinemia
Very strongly bound together

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12
Q

How is bilirubin broken down?

A

Bacteria convert bilirubin to colorless urobilinogen

Urobilinogen is then converted into pyrroles by bacteria to give stool its color

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13
Q

Where can you find urobilinogen?

A

In urine because some of it is absorbed and passed to the urine via the serum

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14
Q

What is urobilinogen?

A

Breakdown product of bilirubin

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15
Q

What is icterus?

A

Jaundice, yellowing of the eye

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16
Q

What are the different types of jaundice?

A
  1. Unconjugated (“indirect”) jaundice

2. Conjugated (“direct”) jaundice

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17
Q

What are the characteristics of indirect jaundice?

A

Unconjugated hyperbilirubinemia

H-bond of albumin prevents passage into urine

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18
Q

What are the characteristics of conjugated jaundice?

A

Direct jaundice
Mixture of conjugated and unconjugated bilirubin in serum
Water soluble conjugated bilirubin passes into urine
May have some delta bilirubin

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19
Q

If you see bilirubin in the urine, what type of

Bilirubinemia is it?

A

“direct’ hyperbilirubinemia because this is the
“conjugated” hyperbilirubinemia
Only conjugated is water soluble

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20
Q

What causes unconjugated jaundice?

A

OVERPRODUCTION of bilirubin
Reduced uptake of bilirubin by liver
Defects on bilirubin conjugation

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21
Q

What are the types of overproduction of bilirubin?

A
  1. Hemolysis
  2. Extravasation into tissue (hematoma)
  3. Ineffective EPO
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22
Q

What are the types of defects of conjugation?

A
  1. Crigler Najjar types I & II
  2. Gilbert’s (common, benign) Gil bearrrrrsssss
  3. Drugs
  4. Wilson’s
  5. Hyperthyroidism
  6. Newborn
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23
Q

What are the types of reduced hepatic uptake?

A
  1. altered circulation
  2. drug effect
    Example: RIFAMYCIN
24
Q

Why are newborns prone to unconjugated bilirubinemia?

A
  1. immature transport
  2. immature conjugation
  3. hemolysis
    Treated by phototherapy
25
Q

Why does phototherapy treat unconjugated bilirubinemia?

A

Phototherapy breaks internal H bonds of unconjugated bilirubin
Exposes proprionic acid groups to allow them to be water soluble

26
Q

What is kernicterus?

A

Bilirubin injury to CNS

27
Q

What are the characteristics of Gilbert’s Syndrome?

A

Benign, Auto Rec,
Defect in promotor gene in glucuronsyltransferase
G-transferase = ~30% of normal
Serum of unconjugated bilirubin usually slightly elevated
Bilirubin levels much higher after having food after a fast…
No G-transferase = no conjugated bilirubin
Too much UNCONJUGATED bilirubin

28
Q

How is Gilbert’s Syndrome diagnosed?

A 
Rule out hemolysis
Liver enzymes are normal
No bilirubin in the urine
NO NEED for liver biopsy
Diagnosis of exclusion
29
Q

What causes conjugated hyperbilirubinemia?

A

When an injury to the cell or biliary obstruction causes reflux into the serum

  1. inherited secretory defect
  2. disease of hepatocytes (cholestatic of necrotizing injury)
  3. Biliary obstruction (extrahepatic cholestasis)
30
Q

What are the two rare inherited secretory defect?

A
  1. Dubin-Johnson
    • liver appears black
  2. Rotor syndrome
    • liver does not appear black
31
Q

What are the common symptoms of necrotizing hepatitis?

A
  1. fatigue
  2. anorexia
    Loss of hepatocytes = release of conjugated bilirubin
32
Q

Can chronic hepatitis cause conjugated hyperbilirubinemia?

A

Yes

Due to viral, alcohol, drugs

33
Q

What is the most common cause of conjugated bilirubinemia?

A

Reduced bile flow
Intrahepatic = PBC
Extrahepatic = mass at the head of the pancreas to obstruct the bile duct

34
Q

What are the histological features of cholestasis?

A
  1. canalicular bile plugging
  2. little necrosis
  3. intrahepatic/extrahepatic similar
35
Q

What is GGT?

A

Gamma-glutamyl transpeptidase

36
Q

What are the biochemical findings of cholestasis?

A
  1. serum alkaline phosphatase (3x normal)
    • can come from bone and placental isoenzymes as well
  2. Increased GGT
  3. elevated alkaline phosphate without jaundice
37
Q

What are the symptoms of cholestasis?

A
  1. icterus
  2. pruritus
  3. fatigue
38
Q

What causes pruritus in cholestasis?

A

Accumulation of the bile salts on the skin
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924137/
page 15
This is so because the treatment for pruritus (resins that bind bile salts in intestine and cholestyramine, a bile acid sequestrant) all cure itching by decreasing serum concentration of bile salts

39
Q

What is the malabsorption seen in cholestasis?

A

The fat-soluble vitamins

Vitamin A, D, E, K

40
Q

What do you see in vitamin E deficiency?

A

Cerebellar and peripheral nerve disorder

41
Q

In cholestasis, where do the cholesterol deposits show up?

A

In the eyes and fingers

42
Q

What is Xanthelasma?

A

Deposits of cholesterol in the eye

43
Q

What are the causes of extrahepatic cholestasis?

A
  1. Benign, like gallstones or strictures

2. Malignant, like pancreas, bile duct and gallbladder cancer

44
Q

What are the intrahepatic causes of cholestasis?

A
  1. Alcohol
  2. Drugs
  3. Hep A
  4. Sepsis
  5. Intarvenous alimentation
  6. pregnancy, estrogens
  7. Granulomatous TB
  8. PBC and PSC
45
Q

What are the treatments for cholestasis?

A

Ursodeoxycholic acidtherapy

Helps secrete bile saltA

46
Q

What causes gallstones?

A

80% are from cholesterol!

Bilirubin precipitate from bile = 20%

47
Q

What are the 3 predisposing factors for gallstones?

A
  1. Supersaturation
  2. Stasis
  3. Nucleation factors
48
Q

How do you detect gallstones?

A

Ultrasound

49
Q

What are the types of gallstones?

A
  1. Cholesterol stones = white
  2. Black gallstones = formed from bilirubin in gallbladder
  3. Brown gallstones = formed in the bile duct
50
Q

What are the risk factors for cholesterol gallstones?

A
  1. Fat (lack of exercise)
  2. Fucking (multiparity)
  3. Female
  4. Forty
    The 4 F’s
51
Q

What are the characteristics of white stones?

A

50-90% cholesterol
Calcium salt concentration = x-ray
Only 15% of white stones with enough calcium salt concentraton can show up in x-ray

52
Q

What is the medical therapy for the gallstones?

A
  1. surgery
  2. Ursodeoxy and chenodeoxycholic acids (slow but still have recurrent disease)
  3. used prophylactically in rapid weight loss
53
Q

What are the characteristics of black stones?

A

Formed by calcium bilirubinate

Form only in gallbladder

54
Q

What are the characteristics of brown stones?

A

Calcium blirubinate but LITTLE calcium salts
Risk factors = INFECTION in the bile duct
Don’t show up on the x-rays because this is due to infection

55
Q

What is the significance of sludge?

A

Formed when there is stasis
Can be a risk factor for gallstones
Risk factors for sludge: pregnancy, rapid weight loss, intravenous feeding

56
Q

What is the pathophysiology of acute cholecystitis?

A
  1. Persistent blockage of cystic duct by gallstone
  2. increase in mucosal prostaglandins causes inflammation
  3. Inhibiting prostaglandins with NSAIDs in biliary colic patient decreases cholecystitis
  4. Half develop superimposed infection
57
Q

What is cholecystitis?

A

Inflammation of the GALL BLADDER!!

GI Week 4 (12 decks)

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