• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/15

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

15 Cards in this Set

  • Front
  • Back
Blank
Blank
Outline the steps in the degradation of heme to bilirubin in the macrophages of the reticulo-endothelial system.
In the presence of NADPH and O2, heme oxygenase oxidizes Ferrous iron (Fe2+) to Ferric iron (Fe3+).
A second oxidation cleaves the porphyrin ring to biliverdin.

Biliverdin is then reduced with another NADPH to bilirubin by biliverdin reductase.
Differentiate between Gilbert's syndrome and Crigler-Najjar syndromes
Gilberts - common, caused by mutation in gene for bilirubin glucuronyltransferase causing reduction to 30% of enzyme activity. Presents with mild unconjugated hyperbiliruinemia.

Crigler-Najjar - rare, caused by mutation in gene for bilirubin glucuronyltransferase leading to complete absence (Type I) or very low activity (Type II). Severe congenital jaundice w/high serum unconjugated BR levels. Fatal in 12-15 mo (Type I). Only cure is liver transplant (Type I), Type II responds to phototherapy and Phenobabital (causes hypertrophy of ER leading to increased synthesis of bilirubin glucuronyltransferase.
Disccus the different forms of jaundice
Pre-Hepatic - excessive production of bilirubin, generally from excessive RBC destruction. The liver makes more than can be conjugated and the excess accumulates in the plasma. Urobilinogen enters the entero-hepatic circulation and is excreted in urine.

Hepatic - Damage to liver cells from hepatitis, hepatocellular carcinomas, etc decrease functional hepatocytes. Less bilirubin can be conjugated and excess leaks into plasma. Decreased enterohepatic circulation of urobilinogen; more enters the blood and kidneys and more urobilin is excreted in urine. AST/ALT markers rise in plasma.

Post-Hepatic - Obstruction of the bile duct from stones or tumors keep conjugated bilirubin from the intestine. It passes through the hepatic veins and enters blood plasma. In the kidneys it is filtered, turning urine dark. Decreased amonts of stercobilin and stools are pale.
Explore the relationship of serum albumin and the transport of bilirubin.
Unconjugated/Indirect bilirubin is transported to the liver by non-covalent binding to albumin.

Many drugs can displace unconjugated bilirubin, allowing it to enter the nervous system and cause damage, particularly in infants.
Explain the biochemical consequence of a block in the uptake of bilirubin in the liver.
The Bilirubin-Albumin Complex must be taken up by a facilitated, carrier mediated transport system which can become saturated.

Inside the hepatocyte, bilirubin binds to ligandin, keeping it soluble until conjugation to keep it from diffusing back across the sinusoidal surface. More bilirubin will be conjugated and excreted into bile. It will then be converted to urobilinogen in the intestine and will show up directly in the urine and as stercobilin in feces.

If this system is overloaded, unconjugated bilirubin can leak into the plasma, increasing plasma levels and causing PRE-HEPATIC JAUNDICE.
Analynze the steps in the processing of conjugated bilirubin in the intestine and its excretion in feces and urine
Bilirubin diglucuronide is hydrolyzed and reduced by bacteria in the intestine to yield urobilinogen. Most of this is oxidized by bacteria to stercobilin and excreted in feces.

The rest is reabsorbed and enters portal blood. A portion of this participates in the enterohepatic urobilinogen cycle and is sent to the liver to be resecreted in bile. The remainder is transported in the blood to the kidney where it is converted to yellow urobilin and excreted in urine.
Identify the sequential steps in heme catabolism beginning with heme till the formation of urobilinogen and stercobilin; identify the various tissues/organs involved in each step
1. Formation of bilirubin in macrophages of the reticulo-endothelial system.
2. Uptake of bilirubin in the liver
3. Conjugation of bilirubin in the liver
4. Excretion of bilirubin in the bile of the liver
5. Formation of urobilins in the intestines.
Compare and contrast conjugated and unconjugated bilirubin with reference to chemical composition, water solubility, tissue deposition, excretion in urine and common clinical conditions where they are elevated.
Unconjugated (Indirect) bilirubin is NON-POLAR and is fat, rather than water, soluble, building up in fat cells, particularly in the CNS. It can not be incorporated into bile or excreted in urine. It can become toxic and appears in elevated levels pre-hepatic or hepatic jaundice and the diseases Crigler-Najjar syndrome I & II and Gilbert's syndrome.

Conjugated (Direct) bilirubin is POLAR and therefore water, not fat, soluble. It can be incorporated into bile and excreted in urine. It is elevated in post-hepatic jaundice and in the diseases Dubin Johnson syndrome and Rotor syndrome.
Distinguish conjugated and unconjugated hyperbilirubinemia theoretically using lab tests
Unconjugated Hyperbilirubinemia -
1. Elevated unconjugated bilirubin in plasma
2. Normal conjugated bilirubin in plasma
3. Normal AST/ALT
Confirm with bilirubin absent in urine and increased urobilinogen.

Conjugated Hyperbilirubinmia
1. Normal unconjugated bilirubin in plasma
2. Increased conjugated bilirubin in plasma
3. Normal AST/ALT
Confirm with bilirubin present in urine but no urobilinogen.
Explain the biochemical mechanisms involved in the development of physiological jaundice of the newborn.
If a competitor displaces bilirubin from albumin, unconjugated bilirubin will leak into the plasma where it can penetrate the blood-brain barrier and diffuse into basal ganglia .This is refered to as KERNICTERUS (toxin encephalopathy) and possibly leads to retardation..
Explain the rationale of phototherapy and phoenobarbital in the therapy for permature babies with jaundice
Light converts unconjugated bilirubin to more polar (water soluble) isomers which can be excreted in bile.

Phenobarbitol induces UDP -glucuronosyltransferase (Bilirubin Glucoronyltransferase / Bilirubin UGT) to conjugate more bilirubin.
Distinguish prehepatic, hepatic and post hepatic jaundice based on lab data
Form of Elevated bilirubin in plasma - Unconjugated = Pre & Hepatic / Conjugated = Post

Presence of AST/ALT - Pos = Hepatic / Neg = Pre & Post

Bilirubin in Urine - Pos = Post / Neg = Pre & Hepatic

Urobilogen Levels - Urine & Feces = Pre. Totally absent = Post.
Distinguish the activity of UDP-glucuronyl transferase in adults versus premature babies.
Infants, especially premature ones, do not have fully developed livers and they are therefore unable to increase unconjugated bilirubin uptake the way adults are. They will therefore suffer symptoms far earlier.
Describe a block in the conjugation of bilirubin in liver.
Bilirubin is conjugated first to bilirubin monoglucuronide and then bilirubin diglucuronide using two UDP-gucuronic acids by UDP-Glucuronyltransferase / Bilirubin glucurohyltransferase / Bilirubin - UGT.

This enzyme is easily inducible by a number of drugs including Phenobarbitol.

Varying degrees of deficiency in this enzyme result in symptoms similar to Crigler-Najjar I & II and Gilbert syndrome. These symptoms are only called Crigler-Najjar and Gilbert's in children, by definition.