Biochem--Jaundice And Cholestasis

Front 1

300-400 mg of heme is degraded to ________every day.

Back 1

bilirubin

Front 2

80% of it comes from _____, the rest from the liver enzyme _______.

Back 2

hemoglobin
cytochrome P450

Front 3

When red blood cells die, they are phagocytosed by the macrophages of the spleen and bone marrow (or other tissue as in bruises) and the _____ in their hemoglobin is converted to ________inside these macrophages. This bilirubin is called _______ and it is extremely lipophilic.

Back 3

heme
bilirubin
“unconjugated bilirubin”

Front 4

Bilirubin then leaves the spleen in a tight complex with blood serum ______ and is thus carried to the ______.

Back 4

albumin
liver

Front 5

The reason the complex is to tight is to prevent the lipid-soluble bilirubin from crossing the blood-brain barrier and reaching the brain where it is extremely ______ .

Back 5

toxic

Front 6

In the liver hepatocytes, specifically in the ERs of those cells, bilirubin is converted to a ________ form that is _______.

Back 6

conjugated
water-soluble

Front 7

The conjugated bilirubin is actively secreted by the hepatocytes into the ______. The ________is an important rate-limiting step in bilirubin metabolism.

Back 7

bile duct
secretion step

Front 8

The conjugated bilirubin then reaches the small intestine where it is _____ in the intestinal bacteria and reduced to uncolored urobilinogens.

Back 8

deconjugated

Front 9

The colorless urobilinogen goes from there in one of three directions:
1. Some is oxidized to urobilin and stercobilin, brown substances that give ______their color.
2. A small amount of urobilinogen is absorbed in the terminal ileum (the very bottom tip of the small intestine), _________ and is secreted in the bile again.
3. < 4 mg/day finds its way to the kidneys, is excreted in the _____.

Back 9

feces
returns to the liver
urine

Front 10

In spleen & bone marrow:
Heme is converted to green pigment ________ by heme oxygenase

Back 10

biliverdin

Front 11

Biliverdin is converted to yellow ________ by biliverdin reductase (reduction with NADPH).

Back 11

bilirubin

Front 12

In blood: water-insoluble bilirubin binds tightly & noncovalently to serum albumin to be transported to the _____ (25mg bilirubin / 100 mL plasma). Anything more falls off and sticks to tissues, stays for long time because it imbeds in cell membranes.

Back 12

liver

Front 13

In liver:
Bilirubin enters ________ via a high-capacity facilitated diffusion carrier

Back 13

hepatocytes

Front 14

Bilirubin is conjugated to bilirubin diglucoronide (conjugated bilirubin, also yellow) in two successive reactions with________ , catalyzed by the same enzyme.

Back 14

UDP-glucoronic acid

Front 15

the water-soluble conjugated bilirubin is actively secreted into the ________ against a steep concentration gradient. This is the rate limiting step in bilirubin metabolism

Back 15

bile canaliculi

Front 16

In intestine:
bacteria deconjugate bilirubin diglucoronide and reduce it to________ .

Back 16

urobilinogen

Front 17

Some urobilinogen oxidized to brown urobilins and stercobilins, goes to ______.

Back 17

stool

Front 18

Some is absorbed in terminal ileum of small intestine and sent back to ____.

Back 18

liver

Front 19

Some goes to _____.

Back 19

kidneys

Front 20

Bilirubin is conjugated in the ________ of hepatic cells

Back 20

endoplasmic reticulum

Front 21

Hyperbilirubinemia is associated with increased plasma levels of either _______ or ______ bilirubin.

Back 21

unconjugated or conjugated

Front 22

only ________ bilirubin is lipid-soluble and can cross to the brain and cause damage.

Back 22

Unconjugated

Front 23

only _______ bilirubin is water soluble and can be secreted into the bile and excreted by kidneys.

Back 23

conjugated

Front 24

Normal bilirubin level in blood plasma 1 mg/dL, most of it ________ and on its way to liver.

Back 24

Unconjugated

Front 25

At 2-3 mg/dL -> ________

Back 25

hyperbilirubinemia.

Front 26

At >4 mg/dL-> ________ visible to naked eye.

Back 26

jaundice

Front 27

yellowing of the skin and sclera of the eye due to increased levels of bilirubin in the blood (i.e. hyperbilirubinemia) above 2-3 mg/dL.

Back 27

Jaundice

Front 28

unconjugated hyperbilirubinemia: increase in plasma level of unconjugated bilirubin -> _______ .

Back 28

jaundice

Front 29

pre-hepatic hyperbilirubinemia

Back 29

too many red blood cells are broken down

Front 30

conjugated hyperbilirubinemia: increase in plasma level of conjugated bilirubin -> _______

Back 30

cholestasis

Front 31

Intrahepatic hyperbilirubinemia

Back 31

processing of bilirubin in the liver does not function correctly

Front 32

Posthepatic/extrahepatic hyperbilirubinemia

Back 32

removal of bile is disturbed

Front 33

Types of unconjugated hyperbilirubinemia:
Dangerous in neonates as in hemolysis induced by rhesus incompatibility.

Back 33

Hemolytic jaundice

Front 34

Types of unconjugated hyperbilirubinemia:

Immaturity of the bilirubin metabolizing system of the liver in newborns.

Back 34

Physiological jaundice

Front 35

Types of unconjugated hyperbilirubinemia:

Caused by genetic deficiency of liver conjugating enzyme UDP-glucuronyl transferase.

Back 35

Crigler-Najjar syndrome / Gilbert syndrome

Front 36

risk of kernicterus (brain damage) >>> treated with _________(photpchemical isomerization of bilirubin to more soluble isomer, exctreted in urine without need for conjugation).

Back 36

phototherapy

Front 37

severe cases of hyperbilirubinemia is treated with _______-> induces synthesis of bilirubin-conjugating enzyme.

Back 37

phenobarbital

Front 38

________ is any condition in which the flow of bile from the liver is blocked.

Back 38

Cholestasis

Front 39

Unconjugated hyperbilirubinemia:
Bilirubin is not conjugated by ______.
Unconjugated bilirubin stays in blood.

Back 39

liver

Front 40

Types of unconjugated hyperbilirubinemia

Back 40

Hemolytic jaundice

Physiological jaundice

Crigler-Najjar syndrome / Gilbert syndrome

Front 41

Liver conjugates bilirubin but flow of bile obstructed. Conjugated bilirubin flows to blood.

Back 41

Conjugated hyperbilirubinemia

Front 42

types of Conjugated hyperbilirubinemia

Back 42

Intrahepatic biliary obstruction
Extrahepatic biliary obstruction
Dubin-Johnson syndrome

Front 43

Liver disease from alcoholism in which bile canaliculi are blocked.

Back 43

Intrahepatic biliary obstruction

Front 44

Caused by gallstones of carcinoma of pancreas.

Back 44

Extrahepatic biliary obstruction

Front 45

Caused by defect in liver cell membrane carrier that pumps conjugated bilirubin into bile.

Back 45

Dubin-Johnson syndrome

Front 46

Blood bilirubin level is measured by the van den Bergh method:
Ehrlich’s reagent is added to
WATER to solubilize conjugated bilirubin to measure ________ and to indicate ___________

Back 46

Direct bilirubin
Cholestasis

Front 47

Blood bilirubin level is measured by the van den Bergh method:Ehrlich’s reagent is added to
SOLVENT to solubilize unconjugated bilirubin to measure ________ and to indicate ___________

Back 47

Indirect bilirubin
Jaundice

Front 48

Increased blood indirect bilirubin. No urinary bilirubin. Increased urinary urobilinogen. Increased fecal urobilinogen.

Back 48

Hemolytic Jaundice

Front 49

Increased blood direct bilirubin. Bilirubin in urine. No urinary urobilinogen. No fecal urobilinogen.

Back 49

Cholestasis

Front 50

serum/blood:
bilirubin (micormoles/l) 50-150; normal range 3-17.
AST I.U. < 35; normal range <35
ALP I.U. <250; normal range <250
gamma GT I.U. 15-40; normal range 15-40
albumin g/l 40-50; normal range 40-50
reticulocytes(%) 10-30; normal range <1
prothrombin time (seconds) 13-15; normal range 13-15

urinary changes:
bilirubin: absent

urobilinogen: increased or normal
faecal changes:
stercobilinogen: normal

Back 50

Hemolytic Jaundice

Front 51

serum / blood:
bilirubin (micromoles/l) 50-250; normal range 3-17
AST I.U. 300-3000; normal range <35
ALP I.U. <250-700; normal range <250
gamma GT I.U. 15-200; normal range 15-40
albumin g/l 20-50; normal range 40-50
reticulocytes(%) <1; normal range <1
prothrombin time (secs) 15-45; normal range 13-15
( " + parenteral vit. K) 15-45

urinary changes:
bilirubin: normal or increased
urobilinogen: normal or reduced

faecal changes:
stercobilinogen: normal or reduced

Back 51

Cholestasis