Hyperbilirubinemia is by definition a disorder of the pigment bilirubin in which there is excessive amount of it in the blood above its normal value. Usually bilirubin is obtained from dead red blood cells that undergo destruction in the spleen. It is obtained as a metabolic product to the degradation of the hemoglobin molecule found in red blood cells.
The homoglobin molecule is composed of two parts that are connected to each other. These are the heme portion and the globin portion. Bilirubin molecule is obtained from the degradation or metabolism of the heme portion of the hemoglobin molecule. The heme molecule is composed of 4 pyrrole rings that are attached to iron metal ion.
Bilirubin can accumulate in the blood causing hyperbilirubinemia due to several reasons. One of them is hemolysis of red blood cells which are destroyed red blood cells that release their content of hemoglobin and other material to the blood such as potassium in which case a state of hyperkalemia can occur.
Hemolysis in turn can be caused due to several reasons. These are: the two hemolytic disorders of thalassemia and sickle cell anemia. Sickle cell disease of red blood cells cause hemolysis due to the abnormal cell wall structure in this disorder that is sickled in its form the thing that can easily destroy it in the spleen.
The other hemolytic medical condition that can cause hemolysis is called thalassemia. This disorder is simply manifested by abnormal structure of the globin chain of its hemoglobin molecule. This can affect the structure of the cell membrane in affected red blood cells other than its biconcave structure which can facilitate its destruction by macrophages in the spleen sinuses.
In addition to these two disorders lactate dehydrogenase enzyme deficiency in red blood cells is another cause to hemolysis of red blood cells. Lactate dehydrogenase usually prevent the oxidation of important molecules in red blood cells. Its deficiency can affect the cell membrane thus easying its destruction.
The other cause to hyperbilirubinemia other than hemolysis of red blood cells is an inherent dysfunction of liver cells that can impair the uptake of bilirubin by these cells for conjugation and secretion to the gallbladder. The first cause to hyperbilirubinemia due to cellular defect in the liver is an impairment of uptake of bilirubin by liver cells.
Usually intracellular proteins transport bilirubin molecules inside the liver cells where they are conjugated or added to other compounds in the cell which will make them soluble. The lack of these proteins due to a genetic defect prevents the conjugation of the bilirubin molecules thus causing a state of hyperbilirubinemia of unconjugated bilirubin in the blood. A syndorme which is called Gilbert’s syndrome is another cause to hyperbilirubinemia. It is a genetic disease of liver cells.
In addition conjugation of bilirubin to bilirubin glucuronide is done by the catalysis of the enzyme UDP glucuronyl transferase. Deficiency of this enzyme due to a genetic defect can also increase the unconjugated bilirubin level in the blood. In the newborn the accumulation of bilirubin in the blood is prominent due to the immature liver enzymes in these people. In addition, the accumulated bilirubin in the blood can penetrate the blood-brain barrier to the brain causing severe symptoms that can lead to death.
In addition, in liver failure the reduced number of functional liver cells prevent the normal metabolism of bilirubin conjugation. Thus predisposing to hyperbilirubinemia. This is more prominent in acute liver failure than in chronic liver failure.
In addition to the afore mentioned causes of hyperbilirubinemia defective excretion of bilirubin from the liver to the gallbladder ca also cause accumulation of the pigement in the blood. Failure of the transport mechanism of bile from the liver to the gallbladder can also cause hyperbilirubinemia. It can occur as an inherited disorder which is called Dubin-johnson syndrome.
In addition, obstruction to the flow of bile from the liver to the gallbladder by stones that can obstruct the biliary canals is another cause fro the development of hyperbilirubinemia. The obstruction of the flow of bile must be in the common hepatic duct in order for jaundice to develop so that the obstruction is complete. Partial obstruction usually does not cause obstruction not leading to jaundice.