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The syndrome cannot cause severe indirect hyperbilirubinemia in neonates by itself, but it may have a summative effect on rising bilirubin when combined with other factors, [10] for example in the presence of increased red blood cell destruction due to diseases such as G6PD deficiency.
Hyperbilirubinemia may refer to increased levels of conjugated, unconjugated or both conjugated and unconjugated bilirubin. The causes of hyperbilirubinemia can also be classified into prehepatic, intrahepatic, and posthepatic. [21] Prehepatic causes are associated mostly with an increase of unconjugated (indirect) bilirubin. [21] They include:
In Dubin–Johnson syndrome, a mutation in multiple drug-resistance protein 2 (MRP2) causes a rise in conjugated bilirubin. [6] In acute appendicitis, total bilirubin can rise from 20.52 μmol/L to 143 μmol/L. In pregnant women, the total bilirubin level is low in all three trimesters. [6]
Sickle cell disease, in which a mutation in the globin gene causes the formation of sickle hemoglobin. [2] This disease is marked by the manifestation of chronic compensated hemolytic anemia, with laboratory findings not limited to unconjugated hyperbilirubinemia but also elevated serum lactate dehydrogenase and low serum haptoglobin. [2]
The varied causes of hyperbilirubinemia are best understood from bilirubin metabolism. The total average daily production of bilirubin in humans is 4 mg/kg. 80% of which is derived from haemoglobin (Hb) produced by erythrocyte breakdown, with the remaining from heme proteins , like myoglobin and cytochrome , turnover. [ 5 ]
Signs of hemolysis that are present in AIHA include low hemoglobin (blood count), alterations in levels of cell markers of hemolysis; including elevated lactate dehydrogenase (LDH), decreased haptoglobin and elevated unconjugated bilirubin. [4] Reticulocytosis, or an increase in circulating immature red blood cells, may be seen. [4]
Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. [3] [6] Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metabolism, liver dysfunction, or biliary-tract obstruction. [7]
In biliary obstruction, below-normal amounts of conjugated bilirubin reach the intestine for conversion to urobilinogen. With limited urobilinogen available for reabsorption and excretion, the amount of urobilin found in the urine is low. High amounts of the soluble conjugated bilirubin enter the circulation where they are excreted via the kidneys.
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