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L3, Heme catabolism

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 L3, Heme catabolism




Catabolism of Heme Heme catabolism is classified into several stages: Stage 1: formation of bilirubin in reticuloendothelial system (RES). Stage II: This stage occurs in liver. Stage III: This is produced by the action of intestinal bacteria.

StageI : formation of bilirubin in reticuloendothelial system (RES). Hemoglobin is degraded into heme and globin. Globin is degraded into amino acids. Heme is converted into biliverdin (green) then to bilirubin (yellow). Bilirubin is transported to liver bound with plasma albumin(indirect or unconjugated bilirubin (

Stage II: This stage occurs in liver: 1.Uptake of bilirubin by liver parenchymal cells: This is followed by removal of albumin. 2.Conjugation of bilirubin with glucuronic acid is catalyzed by the enzyme glucuronyltransferase leading to formation of bilirubin diglucuronide (termed direct bilirubin,conjugated bilirubin or chole bilirubin). 3.Bilirubin - diglucuronide is secreted into bile by active transport system.

Stage III: This is produced by the action of intestinal bacteria. bilirubin is released from glucuronic acid then reduced to urobilinogen(colorless) alsoknown as stercobilinogen.Urobilinogen (stercobilinogen): a. Most of them are excreted in feces and oxidized to the colored brownpigments(stercobilin) by oxygen of air. This explains darkening of feces upon standing in air. b.Small amounts of urobilinogens are reabsorpbed by portal blood and excreted by liver cells into bile (enterohepatic circulation). c.Traces escape and excreted in urine.

Van den Bergh Test for Bilirubin • Bilirubin reacts with diazo reagent (diazotized sulphanilic acid) to produce colored azo pigment. At pH 5, the pigment is purple in color. Conjugated bilirubin, being water soluble gives the color immediately (direct reaction) . Free bilirubin is water insoluble. It has to be extracted first with alcohol, when the reaction becomes positive (indirect reaction)

Hyperbilirubinemia

• Hyperbilirubinemia exists when bilirubin levels exceeds

1 mg/dl.

• Jaundice (yellow discoloration of skin and sclera of eyes) is

manifested usually at levels above 2mg/dl.

Depending on type of bilirubin present in plasma,

hyperbilirubinemias include 3 main types:

A- Unconjugated hyperbilirubinemia

(mainlyhemolyticjaundice).

B- Conjugated hyperbilirubinemia

(mainlyobstructivejaundice)

C- Mixed hyperbilirubinemia or

toxichyperbilirubinemia (hepatocellular

jaundice).

A- Unconjugated hyperbilirubinemia

It is due to :

Over production of bilirubin over the capacity of liver to uptake and

conjugate it.Or when liver fails to uptake and conjugate bilirubin.

Leading to :Increase level of unconjugated bilirubin. Unconjugated

bilirubin is water insoluble and not excreted in urine---alcholuric

jaundice.If concentration of unconjugated bilirubin exceeds that

which can be tightly bound with albumin (20 25mg/dl), it can

penetrate blood brain barrier (BBB) and produce hyperbilirubinemic

toxic encephalopathy (kertictrus) which may cause mental

retardation.


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