IHL I - Bilirubin Metabolism and Excretion

Question 0

senescent RBC

Answer 0

after 120 days, picked up by the phagocytes in the spleen

spleen = graveyard for RBCs

Question 1

what are the components of bile?

Answer 1

bilirubin, bile acids/salts, cholesterol

Question 2

what happens to majority of bile salts?

Answer 2

reabsorbed by the liver (95%)

Question 3

what are the breakdown products of RBCs?

Answer 3

globin and heme

globin is catabolized

heme is broken to bilirubin

iron binds to transferrin

Question 4

bilirubin

Answer 4

produced by biliverdin reductase from biliverdin

(biliverdin formed from heme by heme oxygenase)

bilirubin is water-insoluble, unconjugated

Question 5

what happens to bilirubin after it is synthesized in the macrophage?

Answer 5

travels in blood (bound to albumin) to the liver

Question 6

UDP-GT

Answer 6

combines bilirubin with 2x UDP-glucuronic acid to form bilirubin di-glucuronide

Question 7

glucuronic acid

Answer 7

combined with bilirubin by UDP-GT to form bilirubin diglucuronide

Question 8

what is the fate of bilirubin diglucuronide

Answer 8

secreted into the bile through canaliculus and goes to small intestine

Question 9

hyperbilirubinemia

Answer 9

aka jaundice or icterus

high levels of bilirubin in extracellular fluid

Question 10

stercobilinogen

Answer 10

always in the large intestine

excretion form is stercobilin

Question 11

urobilinogen

Answer 11

from stercobilinogen that leaks

goes to liver or kidney

in kidney - converted to urobilin - excreted

Question 12

heme oxygenase

Answer 12

converts heme to biliverdin

release of CO (only place where this happens) > in spleen

Question 13

kupffer cells

Answer 13

macrophage in the liver

Question 14

biliverdin reductase

Answer 14

biliverdin converted to bilirubin

requires NADPH

Question 15

where is bilirubin formed?

Answer 15

in the spleen (NOT liver)

it is water insoluble - transported by albumin to hepatocytes**

Question 16

what is bile color from?

Answer 16

bilirubin

Question 17

UDG-glucuronyl Transferase

Answer 17

converts bilirubin to bilirubin diglucuronide (conjugated or direct)

in the liver

**know this enzyme

Question 18

indirect

Answer 18

unconjugated bilirubin (water insoluble)

Question 19

direct

Answer 19

conjugated bilirubin (water soluble)

**bc can react directly

Question 20

clay colored stool

Answer 20

liver damage or bile duct obstruction

Question 21

what color stool if bilirubin metabolism pathway defective?

Answer 21

clay colored

Question 22

what color is stercobilinogen

Answer 22

colorless!

stercobilin is dark brown

Question 23

normal blood level of unconjugated, conjugated, and total bilirubin

Answer 23

unconjugated: < 1 mg/dL
conjugated: < 0.2 mg/dL
total: < 1.2 mg/dL

Question 24

jaundice bilirubin level?

Answer 24

> 2 mg/dL

Question 25

icterus bilirubin level?

Answer 25

> 2.5 mg/dL

Question 26

cholestasis

Answer 26

impaired bile flow | increased concentration of bilirubin, bile acids, and cholesterol in blood

Question 27

kernicterus

Answer 27

high concentration (15-20mg/dL) bilirubin unconjugated

Question 28

what will hemolytic diseases cause

Answer 28

increased indirect bilirubin - liver cannot handle all of it and you can't break it down - ex/ G6PD deficiency, pyruvate kinase deficiency, Vit K toxicity

Question 29

pyruvate kinase deficiency?

Answer 29

cannot produce ATP in RBCs | -results in hemolytic anemia

Question 30

crigler-najjar syndrome

Answer 30

gene for glucuronyl transferase is defective -cannot conjugate bilirubin high indirect bilirubin** bilirubin levels 30-50 mg/dL

Question 31

gilbert syndrome

Answer 31

gene for glucuronyl transferase has point mutation medical student : jaundice that goes away ** indirect bilirubin slightly elevated under stress causes jaundice

Question 32

Kernicterus

Answer 32

in newborn massive destruction of RBCs -at birth the glucuronyl transferase is induced increase in indirect bilirubin Hb F does not respond to 2,3 BPG

Question 33

increase in direct bilirubin due to?

Answer 33

intra or extrahepatic bile duct, gallstone/tumor, defective canalicular transport

Question 34

increase direct and indirect bilirubin

Answer 34

``` liver malfunction or damage cirrhosis alcoholic cirrhosis hepatitis Wilson's disease - Cu problem ```

Question 35

dubin johnson syndrome

Answer 35

black coloration of liver ** increased direct bilirubin chronic benign defective canalicular transport

Question 36

rotor syndrome

Answer 36

high levels of direct bilirubin problem with storage of bilirubin in liver cells -leakage of bilirubin into the blood multiple defects in hepatocellular uptake and excretion of bilirubin jaundice, but normal life

Question 37

type I vs. type II crigler-najjar syndrome

Answer 37

type I has highest level of unconjugated bilirubin (>20mg/dL) type I can lead to kernicterus in infancy

Question 38

what disorder results in a glossy black liver?

Answer 38

dubin-johnson syndrome high levels of conjugated bilirubin

Question 39

hereditary disorders of bilirubin metabolism?

Answer 39

all recessive

Question 40

what are the two disorders with high unconjugated bilirubin

Answer 40

crigler-najjar and gilberts

Question 41

treatment of bilirubin metabolism disorders?

Answer 41

no real treatment, but important to be aware phototherapy in infants

Question 42

what causes prehepatic jaundice?

Answer 42

hemolytic processes

Question 43

what causes hepatic jaundice?

Answer 43

abnormal liver function -cannot deal with load of iron -gilberts, crigler-najjar, dubin-johnson

Question 44

posthepatic jaundice

Answer 44

problem with excretion of bilirubin mechanical obstruction of bile to the intestines -gallstone or tumor decreased levels of stercobilin in stool (clay-colored)

Question 45

why do newborns have jaundice?

Answer 45

massive destruction Hg F after birth all this goes to liver, can't handle it lots of unconjugated bilirubin phototherapy given to newborns

Question 46

where does conjugation occur?

Answer 46

liver by UDP-GT makes it water soluble for secretion