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Biochemistry Exam #3 > Heme Catabolism and Jaundice > Flashcards

Heme Catabolism and Jaundice Flashcards

1
Q

Where are the three locations that RBCs are phagocytized and degraded and what percentage is done in each?

A
  • Spleen (70%)
  • Bone marrow (30%)
  • Tissues (30%)
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2
Q

What is the purpose of heme catabolism?

A

Alter the structure of heme to a non-toxic molecule, so it can be excreted from the body

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3
Q

What are the six steps of heme catabolism?

A
  1. Formation and transport of bilirubin to liver
  2. Uptake and conjugation of bilirubin in liver
  3. Secretion and catabolism of CB
  4. Auto-oxidation of urobilinogen to stercobilin
  5. Enterohepatic reabsorption of some urobilinogen from intestines (9%)
  6. Urinary excretion of reabsorbed urobilinogen (1%)
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4
Q

What is the first step of heme catabolism? Describe this step (2)

A

Step 1: Formation and transport of bilirubin to liver

  • Heme is converted to bilirubin in macrophage
  • Bilirubin is transported to the liver through circulation (bound to albumin)
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5
Q

What are the two enzymes used in the conversion of heme to bilirubin, and what is the starting substrate and end product for each?

A
  • Heme > Biliverdin via Heme Oxygenase

- Biliverdin > Bilirubin via Biliverdin Reductase

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6
Q

What is bilirubin also called and what must it be bound to before entering circulation?

A

Bilirubin aka UCB is unconjugated bilirubin

- UCB is hydrophobic so it must bind to albumin before it can be carried through circulation

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7
Q

What is the second step of heme catabolism? Describe this step (2)

A

Step 2: Uptake and conjugation of bilirubin by the liver

  • Trapping of bilirubin in liver cells
  • Conjugation of bilirubin in liver cells
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8
Q

What are the three primary structures utilized in the uptake and conjugation of bilirubin by the liver? Describe the function of each. Which is the rate limiting step?

A
  • OATP transporters: passive/facilitated transport of UCB into the hepatocyte
  • UGT: converts UCB to CB
  • MRP2: CB excreted from the hepatocyte into the bile duct - rate limiting step
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9
Q

What is bound to UCB before it is conjugated to CB to ensure it is trapped inside the cell?

A

GST

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10
Q

What is the third step of heme catabolism? Describe this step (2)

A

Step 3: Secretion and catabolism of conjugated bilirubin

  • Secretion into bile and then into intestines
  • Intestinal bacteria hydrolyze and reduce conjugated bilirubin to urobilinogen
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11
Q

What is the fourth step of heme catabolism? Describe this step (what percentage of urobilinogen is acted on in this step?)

A

Step 4: auto-oxidation of 90% of fecal urobilinogen to stercobilin
- Gives feces its brown color

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12
Q

What is the fifth step of heme catabolism? Describe this step

A

Step 5: Enterohepatic reabsorption of some urobilinogen from intestines

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13
Q

Of the 10% of urobilinogen reabsorbed into enterohepatic circulation what happens with 9% of it and what happens with the other 1%?

A
  • 9%: Reabsorbed by liver and re-excreted into bile duct

- 1%: excreted in the urine via kidneys

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14
Q

What is the sixth step of heme catabolism? Describe this step

A

Step 6: Urinary excretion of reabsorbed urobilinogen (auto-oxidation of urinary urobilinogen to urobilin)
- Gives urine its yellow color

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15
Q

What is the traditional measurement method (test) for bilirubin levels?

A

Diazo reaction (purple color change)

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16
Q

What does the first step of the diazo reaction evaluate? What happens to CB and UCB during this step?

A

The first step of the diazo reaction evaluates DBIL (direct bilirubin)

Collect serum and directly add diazo dye to measure formation of purple color

  • Fast color change: CB (unfolded and soluble)
  • Slow color change: UCB (folded and insoluble)
17
Q

What does the second step of the diazo reaction evaluate, and what is added to the tube? What happens to the UCB in this step?

A

The second step of the diazo reaction evaluated TBIL (total bilirubin)

Add methanol to the same tube
- UCB will be unfolded and solubilized by methanol so it can now react with diazo

18
Q

How do you evaluate for Indirect Bilirubin (IBIL)? Is this a measurement or calculated value?

A

Indirect bilirubin is a calculation, NOT a measurement

IBIL = TBIL - DBIL

19
Q

What causes Jaundice and what does it result in (blood)?

A

Jaundice (aka Icterus) is caused by the deposition of bilirubin
- Results in hyperbilirubinemia (high bilirubin in blood)

20
Q

What are the four types of jaundice? What is each caused by?

A
  • Neonatal: caused by low activity of liver enzymes at birth
  • Pre-hepatic: caused by hemolytic anemia
  • Hepatic: caused by viral infection/liver damage
  • Post-hepatic: caused by bile duct obstruction
21
Q

With neonatal jaundice, what does the immature liver of newborns result in (3)?

A
  • Increased bilirubin load
  • Decreased bilirubin conjugation
  • Decreased bilirubin excretion
22
Q

What is the primary treatment for neonatal jaundice? Describe how this works

A

Phototherapy (blue light therapy) treatment: blue light alters the conformation of UCB yielding photoisomers that are more soluble than UCB in its native form

23
Q

What develops clinically in a patient with excess UCB levels? (hint: it is worse in infants) How does this present symptomatically?

A

Kernicterus: bilirubin encephalopathy

  • Excess UCB in the blood can cross the blood brain barrier causing a buildup of UCB in the brain
  • Can result in neurological damage (hearing issues to mental retardation) or even death
  • Infants are more susceptible due to immature BBB
24
Q

How does hemolytic anemia cause pre-hepatic jaundice?

A

Increased hemolysis of damaged/immature RBCs leads to increased heme metabolites and elevated levels of circulating UCB

25
Q

What are the lab values associated with pre-hepatic jaundice? Explain the reasons for each of the lab values

A
  • IBIL: Increased (elevated UCB in blood due to higher heme metabolites)
  • DBIL: Normal (serum CB levels are unaffected because liver is healthy)
  • Urinary Urobilinogen: Increased (high UCB so high CB so high urobilinogen)
  • Fecal Urobilinogen: Increased (high UCB so high CB so high urobilinogen)
26
Q

How does viral infection or liver damage cause hepatic jaundice?

A

Hepatocytes are damaged by infection or liver damage and have an impaired ability to metabolize bilirubin and transport the bilirubin (normal UCB production, but UCB > CB is decreased)

27
Q

What are the lab values associated with hepatic jaundice? Explain the reasons for each of the lab values

A
  • IBIL: Increased (higher UCB in circulation due to inability of liver to absorb)
  • DBIL: Increased (CB leaks into circulation due to leaky tight junctions)
  • Urinary Urobilinogen: Increased (liver cannot reabsorb as much urobilinogen as normal so filtered to kidney and excreted as urine)
  • Fecal Urobilinogen: Decreased (low conjugation so low CB so low urobilinogen)
28
Q

How does a bile duct obstruction cause post-hepatic jaundice? What is the secondary cause of any issues?

A

CB is unable to enter the intestine so little/no urobilinogen is produced
- Secondary: hepatocytes may be damaged due to liver damage

29
Q

What are the lab values associated with post-hepatic jaundice? Explain the reasons for each of the lab values

A
  • IBIL: Normal/Increased (if increased, it is due to secondary liver damage)
  • DBIL: Increased (CB cannot exit through bile duct, causing accumulation and back flow into circulation
  • Urinary Urobilinogen: Decreased (less CB flow into intestine so less urobilinogen produced)
  • Fecal Urobilinogen: Decreased (less CB flow into intestine so less urobilinogen produced)

Biochemistry Exam #3 (8 decks)

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