PMBC25 - Heme degradation: Jaundice

Created by lcoghill 

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1. Outline heme degradation starting in macrophages and ending in feces and urine

heme and globin are separated in the macrophages after 120 days, globin gets converted into amino acids, heme gets converted to bilirubin, CO and Fe3+, bilirubin gets complexed to albumin in the blood which takes it to the liver where it becomes conjugated and water soluble bilirubin diglucuronide (using 2 molecules of UDP-gluconurate) which gets excreted into the bile and released as stercobilin in the feces and urobilinogen in the urine

2. Discuss the reaction catalyzed by heme oxygenase

Heme + O2 + NADPH --> Fe3+, CO, NADP, biliverdin

3. Describe the activity of UDP glucuronyl transferase in adults and premature babies

In fetal life, bilirubin is sent back to the mother to be conjugated. Premature babies have low UDPGT activity which will increase over time - need phototherapy (blue light - forms lumirubin)

4. Gilbert's syndrome

UDPGT is at half its normal activity - common in young men, mild temporary increase in bilirubin sometimes triggered by fasting or infection

Crigler Najjar type I

UDPGT activity is absent, early onset, very high bilirubin - can cause death - phototherapy treatment becomes less effective as skin thickens

Crigler Najjar type II (Arias syndrome)

UDPGT is less than 10% of normal - later onset, high bilirubin - severe may need phototherapy, phenobarbitol is used to induce the enzyme - no severe liver damage or changes in thinking during childhood

Aspirin in newborns

can cause fatal kernicterus - bilirubin can be displaced from albumin by high doses of aspirin or sulfonamides in infants. Bilirubin can cross the blood brain barrier and can cause neurological problems

5. Explain why phototherapy is used as therapy for premature babies with jaundice

blue light forms lumirubin - analog of bilirubin - can reduce jaundice

6. Hemolytic, pre-hepatic jaundice

excessive hemolysis leads to high levels of unconjugated bilirubin in the blood, increase of urobilinogen in the intestines - urine contains more urobilinogen than normal but NO BILIRUBIN (unconjugated bilirubin cannot be released by the kidney into urine)

Hepatocellular, intra-hepatic jaundice

found in patients with hepatitis, cirrhosis or liver tumors - unconjugated and conjugated bilirubin levels are high and the urine contains bilirubin - deep orange, brown urine

Obstructive, post-hepatic jaundice

release of bile into intestines is obstructed by gallstones or pancreatic tumor. Unconjugated bilirubin is normal, conjugated bilirubin cannot reach the intestines and is released from liver into blood. Urine contains conjugated bilirubin, less urobilinogen in the intestines

How do you test for bilirubin in the blood

colorimetrically using the van den Bergh reaction - conjugated bilirubin reacts immediately (direct-reacting), unconjugated bilirubin needs more than one minute. Test for total using solvent methanol - both react fast

7. High blood unconjugated bilirubin, measurable urobilinogen, undetectable urine bilirubin

Hemolytic pre-hepatic jaundice

High ALT/AST, High blood unconjugated bilirubin, high blood conjugated bilirubin, measurable urine bilirubin

heptatocellular intra-hepatic jaundice

High blood ALP, high blood conjugated bilirubin, measurable urine bilirubin

Obstructive, post-hepatic jaundice

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