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IHL Exam 1 Me > Bilirubin Metabolism and Excretion (Choudhury) > Flashcards

Bilirubin Metabolism and Excretion (Choudhury) Flashcards

1
Q

Source of bilirubin

A

Dead RBC’s broken down by macrophages of RES

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2
Q

Hemoglobin breakdown

A

First–> heme-iron complex + globin chain

Second –> Heme complex is broken down to Fe and biliverdin

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3
Q

Fate of iron after broken down from hemoglobin?

A

Binds to transferrin and recycled to be used in formation of new RBC’s

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4
Q

“bili light” phototherapy?

A

Converts unconjugated bilirubin from “trans” to “cis” form using light.

cis form is more easily excreted in the urine

Used in treatment of infants with high levels of unconjugated bilirubin

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5
Q

unconjugated bilirubin

A

Water In-soluble

Biliverdin –> unconjugated bilirubin

carried in blood with albumin

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6
Q

how does unconjugated bilirubin enter hepatocytes

A

through the sinusoids via:
Passive diffusion
Receptor mediated endocytosis

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7
Q

Where is unconjugated bilirubin converted to conjugated bilirubin

A

Liver (SER)

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8
Q

Conjugated bilirubin

A

Water-Soluble

aka Direct

made in the liver by UDPGT

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9
Q

UDPGT

A

(uridine 5’-diphosphate glucuronyl transferase in liver

adds 2 glucuronic acids to bilirubin molecule to form conjugated bilirubin (water soluble)

without this enzyme bilirubin would not be able to be excreted (b/c it would remain water insoluble)

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10
Q

Fate of globin chain after RBC breakdown

A

broken down to aa’s

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11
Q

Elevated Urinary urobilinogen

A

occurs during hyperbilirubinemia

majority of urobilinogen is reabsorbed by the gut and re-excreted by the liver with a small amount being excreted in the urine…

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12
Q

Jaundice

A

Accumulation of conjugated or unconjugated bilirubin in the serum, usually due to hepatocellular disease or biliary obstructive disease (bilirubin is not excreted normally)

> 2.0 mg/dL

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13
Q

Increased urinary bilirubin

A

occurs when there is an increase in serum conjugated bilirubin

since the conjugated bilirubin is water-soluble, it can also be filtered by the glomerulus and excreted in the urine

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14
Q

Causes of elevated serum unconjugated bilirubin

A

1) Hemolysis
2) Gilbert’s syndrome
3) Crigler-Najjar Syndrome

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15
Q

Hemolysis

A

Hemolytic anemia due to sickle cell disease, autoimmune process, drug-induced

Results in premature release of hemoglobin from RBC’s

Rate of cell destruction and release of unconjugated bilirubin overcomes rate of liver clearance –> increase in serum levels

can be due to immature liver or shitty UDPGT activity

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16
Q

Gilbert’s syndrome

A

Genetic cause of hyperbilirubinemia (total t show it)

caused by enzyme mutation
increased urinary bilirubin

point mutation. slightly defective

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17
Q

Crigler-Najjar Syndrome

A

Genetic cause of hyperbilirubinemia (unconj. bili)

gene for enzyme UDPGT defective, cannot conjugate bilirubin, increased urinary bilirubin

die 6mo - 1 year

homozygous type I–> >5mg/dL often over 30-50 mg

heterozygous type II–> less severe, can live to adulthood

use phototherapy

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18
Q

Types of hepatic jaundice

A

1) Gilbert’s syndrome
2) Crigler-Najjar Syndrome
3) Dubin-Johnson
4) Hepatitis

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19
Q

Types of prehepatic jaundice

A

1) Hemolysis (due to sickle cell disease, autoimmune disease, drug-induced, break down of red blood cells due to HbF–> HbA (23BPG))

total bili usually does not exceed 5 mg/dL
negative urine bilirubin
negative urinary urobilinogen

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20
Q

Types of posthepatic jaundice

A

1) Biliary obstruction (impaired excretion of bilirubin)

increased serum and urine conj. bilirubin
decreased level of urobilin/stercobilin (clay stools)
negative urinary urobilinogen

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21
Q

Causes of elevated serum conjugated bilirubin

A

1) Dubin Johnson

2) Biliary obstruction (inflammation of the biliary tract, bile stones)

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22
Q

Causes of elevated serum conjugated and unconjugated bilirubin

A

1) Hepatitis

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23
Q

Dubin-Johnson Syndrome

A

Impaired excretion of conjugated bilirubin from liver

Due to inborn error of metabolism (defect in ATP binding cassette) transportation problem

Conjugated bilirubin accumulates in liver and backs up into the circulation (detected in serum)

Black Liver, brown urine (due to spillage of direct bilirubin into blood and kidney)

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24
Q

Biliary obstruction

A

Type of posthepatic jaundice causing increase serum conj. bilirubin

Includes Cholelithiasis (bile stones) blocking common bile duct, or inflammation of biliary tract

since conj. bili can’t reach the intestine, not broken down to stercobilin so have clay colored stools

no urobilinogen in urine, but lots of conjugated bilirubin backs up and is secreted in urine

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25
Q

Hepatitis

A

causes increase in both conj. and unconj. bili in serum

causes:
impaired conjugation ability
blockage of excretion from liver

total bili 5-10 mg

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26
Q

Adult reference range for serum conjugated bilirubin

A

<0.2 mg/dL

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27
Q

Adult reference range for serum unconjugated bilirubin

A

0.1-1.0 mg/dL

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28
Q

Adult reference range for Total Bilirubin

A

0.1-1.2 mg/dL

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29
Q

Kernicterus

A

conc. of unconjugated bilirubin exceeds 15-20mg

condition in newborn due to massive destruction of RBC’s (Hb F does not respond to 2-3BPG) and due to UDPGT taking time to be induced/function
to actually conjugate bilirubin

bilirubin is toxic, when enters CNS it causes severe motor dysfunction and retardation

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29
Q

Albumin

A

This is what carries unconjugated bilirubin in plasma (b/c unconj. bilirubin is usually a lipid so needs protein carrier and it is water insoluble)

30
Q

Gilbert’s syndrome

A

Genetic cause of hyperbilirubinemia

type of hepatic jaundice

mild elevation of unconj. bili

“student” stressed

caused by enzyme mutation and/or transport deficit in the hepatocyte

30
Q

Gilbert’s syndrome

A

Genetic cause of hyperbilirubinemia

type of hepatic jaundice

mild elevation of unconj. bili

“student” stressed

caused by enzyme mutation and/or transport deficit in the hepatocyte

31
Q

Crigler-Najjar Syndrome

A

Genetic cause of hyperbilirubinemia (unconj. bili)

type of hepatic jaundice

homozygous type I–> >5mg/dL often over 20 mg
kernicterus, use phototherapy for treatment

heterozygous type II–> less severe, can live to adulthood

31
Q

True or false… Bilirubin is formed in the liver

A

FALSE. bilirubin is formed outside the liver

32
Q

Types of hepatic jaundice

A

1) Gilbert’s syndrome
2) Crigler-Najjar Syndrome
3) Dubin-Johnson
4) Hepatitis

32
Q

Types of hepatic jaundice

A

1) Gilbert’s syndrome
2) Crigler-Najjar Syndrome
3) Dubin-Johnson
4) Hepatitis

33
Q

Types of prehepatic jaundice

A

1) Hemolysis (due to sickle cell disease, autoimmune disease, drug-induced)

33
Q

Treatment of Kernicterus

A

Phototherapy (blue light)
changes from trans to cis form
cis is more easily excreted in urine

34
Q

Kernicterus caused by ….

A

Fetus has Hb F
Adult has Hb A

2-3 BPG binds to adult hemoglobin and kicks out oxygen in low oxygen scenario

2-3 BPG can’t bind to Hb F in baby

34
Q

Types of posthepatic jaundice

A

1) Biliary obstruction

35
Q

Alcoholic cirrhosis of the liver leads to…

A

hyperbilirubinea due to decreased excretion of bilirubin into bile (stays in the bloodstream much longer)

35
Q

Causes of elevated serum conjugated bilirubin

A

1) Dubin Johnson

2) Biliary obstruction (inflammation of the biliary tract, bile stones)

36
Q

Causes of elevated serum conjugated and unconjugated bilirubin

A

1) Hepatitis

36
Q

Causes of elevated serum conjugated and unconjugated bilirubin

A

1) Hepatitis

37
Q

Dubin-Johnson Syndrome

A

Type of hepatic jaundice

Impaired excretion of conjugated bilirubin from liver

Due to inborn error of metabolism (defect in ATP binding cassette)

Conjugated bilirubin accumulates in liver and backs up into the circulation (detected in serum)

Dark/black liver

37
Q

Dubin-Johnson Syndrome

A

Type of hepatic jaundice

Impaired excretion of conjugated bilirubin from liver

Due to inborn error of metabolism (defect in ATP binding cassette)

Conjugated bilirubin accumulates in liver and backs up into the circulation (detected in serum)

Dark/black liver

38
Q

Biliary obstruction

A

Type of posthepatic jaundice causing increase serum conj. bilirubin

Includes Cholelithiasis (bile stones) blocking common bile duct, or inflammation of biliary tract

since conj. bili can’t reach the intestine, not broken down to stercobilin so have clay colored stools

no urobilinogen in urine, but lots of conjugated bilirubin backs up and is secreted in urine

38
Q

Biliary obstruction

A

Type of posthepatic jaundice causing increase serum conj. bilirubin

Includes Cholelithiasis (bile stones) blocking common bile duct, or inflammation of biliary tract

since conj. bili can’t reach the intestine, not broken down to stercobilin so have clay colored stools

no urobilinogen in urine, but lots of conjugated bilirubin backs up and is secreted in urine

39
Q

Hepatitis

A

causes increase in both conj. and unconj. bili in serum

causes:
impaired conjugation ability
blockage of excretion from liver

39
Q

Hepatitis

A

causes increase in both conj. and unconj. bili in serum

causes:
impaired conjugation ability
blockage of excretion from liver

40
Q

Adult reference range for serum conjugated bilirubin

A

<0.2 mg/dL

40
Q

Adult reference range for serum conjugated bilirubin

A

<0.2 mg/dL

41
Q

Adult reference range for serum unconjugated bilirubin

A

0.1-1.0 mg/dL

41
Q

Adult reference range for serum unconjugated bilirubin

A

0.1-1.0 mg/dL

42
Q

Adult reference range for Total Bilirubin

A

0.1-1.2 mg/dL

42
Q

Adult reference range for Total Bilirubin

A

0.1-1.2 mg/dL

43
Q

Kernicterus

A

Often displayed in infants with severe jaundice

causes severe motor dysfunction and retardation

44
Q

Albumin

A

This is what carries unconjugated bilirubin in plasma (b/c bilirubin is usually a lipid so needs protein carrier)

45
Q

only place in the body we make CO

A

spleen

made when heme is broken down to biliverdin

46
Q

heme oxygenase

A

takes heme and makes biliverdin

also liberates Fe and CO from heme structure

47
Q

biliverdin reductase

A

biliverdin –> unconjugated bilirubin

happening in spleen/RES

48
Q

True or false… Bilirubin is formed in the liver

A

FALSE. bilirubin is formed outside the liver

49
Q

Cholestasis

A

impaired bile flow

increased conc. of bilirubin in blood

50
Q

icterus

A

bilirubin 3.0 mg or more

51
Q

Hemolytic diseases that cause increase in indirect bilirubin (b/c breaking down lots of RBC’s)

A

G6PD deficiency
Pyruvate kinase deficiency (no ATP made so cells swell, lyse)
Vit K toxicity
Sickle cell disease

52
Q

Treatment of Kernicterus

A

Phototherapy
changes from trans to cis form
cis is more easily excreted in urine

53
Q

Kernicterus caused by ….

A

Fetus has Hb F
Adult has Hb A

2-3 BPG binds to adult hemoglobin and kicks out oxygen in low oxygen scenario

2-3 BPG can’t bind to Hb F in baby

54
Q

Rotor Syndrome

A

elevated direct bilirubin due to transport and storage problem in the liver

liver normal

jaundice but normal

55
Q

Alcoholic cirrhosis of the liver leads to…

A

hyperbilirubinea due to decreased excretion of bilirubin into bile (stays in the bloodstream much longer)

56
Q

sulfonamides

A

increase unconjugated bilirubin leading to kernicterus

71
Q

why do newborns have jaundice

A

At birth massive destruction of RBC’s due to wrong type of Hb

Neonatal hyperbilirubinemia- UDPGT is induced only at birth so the enzyme expression may be lacking (so have unconjugated)

72
Q

Elevated AST or ALT or BUN

A

in laboratory studies this means that it is a hepatic type of dysfunction

73
Q

amylase and lipase

A

in laboratory studies they tell us function of the pancreas so something is wrong post-hepatic

lipase and amylase are backed up and go back to the pancreas and cause digestion of pancreas –> pain

IHL Exam 1 Me (11 decks)

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