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

Bilirubin Metabolism and Excretion (Choudhury) Flashcards

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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
Hepatitis
causes increase in both conj. and unconj. bili in serum causes: impaired conjugation ability blockage of excretion from liver total bili 5-10 mg
26
Adult reference range for serum conjugated bilirubin
<0.2 mg/dL
27
Adult reference range for serum unconjugated bilirubin
0.1-1.0 mg/dL
28
Adult reference range for Total Bilirubin
0.1-1.2 mg/dL
29
Kernicterus
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
29
Albumin
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
Gilbert's syndrome
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
Gilbert's syndrome
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
Crigler-Najjar Syndrome
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
True or false... Bilirubin is formed in the liver
FALSE. bilirubin is formed outside the liver
32
Types of hepatic jaundice
1) Gilbert's syndrome 2) Crigler-Najjar Syndrome 3) Dubin-Johnson 4) Hepatitis
32
Types of hepatic jaundice
1) Gilbert's syndrome 2) Crigler-Najjar Syndrome 3) Dubin-Johnson 4) Hepatitis
33
Types of prehepatic jaundice
1) Hemolysis (due to sickle cell disease, autoimmune disease, drug-induced)
33
Treatment of Kernicterus
Phototherapy (blue light) changes from trans to cis form cis is more easily excreted in urine
34
Kernicterus caused by ....
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
Types of posthepatic jaundice
1) Biliary obstruction
35
Alcoholic cirrhosis of the liver leads to...
hyperbilirubinea due to decreased excretion of bilirubin into bile (stays in the bloodstream much longer)
35
Causes of elevated serum conjugated bilirubin
1) Dubin Johnson | 2) Biliary obstruction (inflammation of the biliary tract, bile stones)
36
Causes of elevated serum conjugated and unconjugated bilirubin
1) Hepatitis
36
Causes of elevated serum conjugated and unconjugated bilirubin
1) Hepatitis
37
Dubin-Johnson Syndrome
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
Dubin-Johnson Syndrome
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
Biliary obstruction
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
Biliary obstruction
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
Hepatitis
causes increase in both conj. and unconj. bili in serum causes: impaired conjugation ability blockage of excretion from liver
39
Hepatitis
causes increase in both conj. and unconj. bili in serum causes: impaired conjugation ability blockage of excretion from liver
40
Adult reference range for serum conjugated bilirubin
<0.2 mg/dL
40
Adult reference range for serum conjugated bilirubin
<0.2 mg/dL
41
Adult reference range for serum unconjugated bilirubin
0.1-1.0 mg/dL
41
Adult reference range for serum unconjugated bilirubin
0.1-1.0 mg/dL
42
Adult reference range for Total Bilirubin
0.1-1.2 mg/dL
42
Adult reference range for Total Bilirubin
0.1-1.2 mg/dL
43
Kernicterus
Often displayed in infants with severe jaundice causes severe motor dysfunction and retardation
44
Albumin
This is what carries unconjugated bilirubin in plasma (b/c bilirubin is usually a lipid so needs protein carrier)
45
only place in the body we make CO
spleen made when heme is broken down to biliverdin
46
heme oxygenase
takes heme and makes biliverdin also liberates Fe and CO from heme structure
47
biliverdin reductase
biliverdin --> unconjugated bilirubin happening in spleen/RES
48
True or false... Bilirubin is formed in the liver
FALSE. bilirubin is formed outside the liver
49
Cholestasis
impaired bile flow increased conc. of bilirubin in blood
50
icterus
bilirubin 3.0 mg or more
51
Hemolytic diseases that cause increase in indirect bilirubin (b/c breaking down lots of RBC's)
G6PD deficiency Pyruvate kinase deficiency (no ATP made so cells swell, lyse) Vit K toxicity Sickle cell disease
52
Treatment of Kernicterus
Phototherapy changes from trans to cis form cis is more easily excreted in urine
53
Kernicterus caused by ....
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
Rotor Syndrome
elevated direct bilirubin due to transport and storage problem in the liver liver normal jaundice but normal
55
Alcoholic cirrhosis of the liver leads to...
hyperbilirubinea due to decreased excretion of bilirubin into bile (stays in the bloodstream much longer)
56
sulfonamides
increase unconjugated bilirubin leading to kernicterus
71
why do newborns have jaundice
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
Elevated AST or ALT or BUN
in laboratory studies this means that it is a hepatic type of dysfunction
73
amylase and lipase
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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