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51 Cards in this Set

  • Front
  • Back
300-400 mg of heme is degraded to ________every day.
bilirubin
80% of it comes from _____, the rest from the liver enzyme _______.
hemoglobin
cytochrome P450
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.
heme
bilirubin
“unconjugated bilirubin”
Bilirubin then leaves the spleen in a tight complex with blood serum ______ and is thus carried to the ______.
albumin
liver
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 ______ .
toxic
In the liver hepatocytes, specifically in the ERs of those cells, bilirubin is converted to a ________ form that is _______.
conjugated
water-soluble
The conjugated bilirubin is actively secreted by the hepatocytes into the ______. The ________is an important rate-limiting step in bilirubin metabolism.
bile duct
secretion step
The conjugated bilirubin then reaches the small intestine where it is _____ in the intestinal bacteria and reduced to uncolored urobilinogens.
deconjugated
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 _____.
feces
returns to the liver
urine
In spleen & bone marrow:
Heme is converted to green pigment ________ by heme oxygenase
biliverdin
Biliverdin is converted to yellow ________ by biliverdin reductase (reduction with NADPH).
bilirubin
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.
liver
In liver:
Bilirubin enters ________ via a high-capacity facilitated diffusion carrier
hepatocytes
Bilirubin is conjugated to bilirubin diglucoronide (conjugated bilirubin, also yellow) in two successive reactions with________ , catalyzed by the same enzyme.
UDP-glucoronic acid
the water-soluble conjugated bilirubin is actively secreted into the ________ against a steep concentration gradient. This is the rate limiting step in bilirubin metabolism
bile canaliculi
In intestine:
bacteria deconjugate bilirubin diglucoronide and reduce it to________ .
urobilinogen
Some urobilinogen oxidized to brown urobilins and stercobilins, goes to ______.
stool
Some is absorbed in terminal ileum of small intestine and sent back to ____.
liver
Some goes to _____.
kidneys
Bilirubin is conjugated in the ________ of hepatic cells
endoplasmic reticulum
Hyperbilirubinemia is associated with increased plasma levels of either _______ or ______ bilirubin.
unconjugated or conjugated
only ________ bilirubin is lipid-soluble and can cross to the brain and cause damage.
Unconjugated
only _______ bilirubin is water soluble and can be secreted into the bile and excreted by kidneys.
conjugated
Normal bilirubin level in blood plasma 1 mg/dL, most of it ________ and on its way to liver.
Unconjugated
At 2-3 mg/dL -> ________
hyperbilirubinemia.
At >4 mg/dL-> ________ visible to naked eye.
jaundice
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.
Jaundice
unconjugated hyperbilirubinemia: increase in plasma level of unconjugated bilirubin -> _______ .
jaundice
pre-hepatic hyperbilirubinemia
too many red blood cells are broken down
conjugated hyperbilirubinemia: increase in plasma level of conjugated bilirubin -> _______
cholestasis
Intrahepatic hyperbilirubinemia
processing of bilirubin in the liver does not function correctly
Posthepatic/extrahepatic hyperbilirubinemia
removal of bile is disturbed
Types of unconjugated hyperbilirubinemia:
Dangerous in neonates as in hemolysis induced by rhesus incompatibility.
Hemolytic jaundice
Types of unconjugated hyperbilirubinemia:

Immaturity of the bilirubin metabolizing system of the liver in newborns.
Physiological jaundice
Types of unconjugated hyperbilirubinemia:

Caused by genetic deficiency of liver conjugating enzyme UDP-glucuronyl transferase.
Crigler-Najjar syndrome / Gilbert syndrome
risk of kernicterus (brain damage) >>> treated with _________(photpchemical isomerization of bilirubin to more soluble isomer, exctreted in urine without need for conjugation).
phototherapy
severe cases of hyperbilirubinemia is treated with _______-> induces synthesis of bilirubin-conjugating enzyme.
phenobarbital
________ is any condition in which the flow of bile from the liver is blocked.
Cholestasis
Unconjugated hyperbilirubinemia:
Bilirubin is not conjugated by ______.
Unconjugated bilirubin stays in blood.
liver
Types of unconjugated hyperbilirubinemia
Hemolytic jaundice

Physiological jaundice

Crigler-Najjar syndrome / Gilbert syndrome
Liver conjugates bilirubin but flow of bile obstructed. Conjugated bilirubin flows to blood.
Conjugated hyperbilirubinemia
types of Conjugated hyperbilirubinemia
Intrahepatic biliary obstruction
Extrahepatic biliary obstruction
Dubin-Johnson syndrome
Liver disease from alcoholism in which bile canaliculi are blocked.
Intrahepatic biliary obstruction
Caused by gallstones of carcinoma of pancreas.
Extrahepatic biliary obstruction
Caused by defect in liver cell membrane carrier that pumps conjugated bilirubin into bile.
Dubin-Johnson syndrome
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 ___________
Direct bilirubin
Cholestasis
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 ___________
Indirect bilirubin
Jaundice
Increased blood indirect bilirubin. No urinary bilirubin. Increased urinary urobilinogen. Increased fecal urobilinogen.
Hemolytic Jaundice
Increased blood direct bilirubin. Bilirubin in urine. No urinary urobilinogen. No fecal urobilinogen.
Cholestasis
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
Hemolytic Jaundice
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
Cholestasis