Bilirubin total levels are determined by both conjugated and unconjugated bilirubin in bloodstream. Bilirubin circulates in blood in mainly two forms, which include the indirect or unconjugated and the direct or conjugated bilirubin. The indirect form does not readily dissolve in water and being insoluble, it needs to be made water-soluble so that it is easily excreted from the body.
For it to be converted to water-soluble, it has to pass through the liver. In the liver, it is conjugated and then released to the intestine. Both bilirubin total levels and direct bilirubin can be measured directly in blood. However, indirect bilirubin concentrations are derived by subtracting the direct bilirubin from total serum bilirubin.
Elevated levels of bilirubin cause jaundice and they are categorized based on the different anatomical sites of body pathology. Prehepatic elevated levels of serum bilirubin occur when there is increased production of bilirubin. This occurs when the rate at which old red blood cells are destroyed increased. Hepatic elevated bilirubin occurs when there is a liver dysfunction, which prevents it from conjugating or processing the unconjugated bilirubin to water-soluble form. Moreover, when there is obstruction of the bile duct, it leads to posthepatic elevated levels of bilirubin.
Unconjugated hyperbilirubinemia
Unconjugated hyperbilirubinemia is common among newborns but in adults, it can be caused by increased destruction of red blood cells in what is known as hemolysis. In addition, the elevated levels of indirect bilirubin can also be caused by ineffective erythropoiesis, where there is rapid turnover of hemoglobin and destruction of some fraction of developing erythroid cells in bone marrow.
Lead poisoning and disorders like thalassemia major can increase the unconjugated bilirubin. If there is prolonged production of unconjugated bilirubin, this situation can lead to precipitation of bilirubin salts causing gallstones to form. Moreover, impairment in the delivery of bilirubin in liver as a result of congestive heart failure or portosystemic shunts can cause the levels of indirect bilirubin to increase.
The hepatic bilirubin is delivered to the liver to be processed and broken down to make it water-soluble. The uptake by liver may be impaired by these conditions. Liver cirrhosis may also cause the levels to elevate. Medications such as rifamycin and flavaspidic acid also inhibit the uptake of bilirubin by liver. There are inherited disorders, which may affect the levels of hepatic bilirubin in blood such as Crigler-Najjar syndrome and Gilbert syndrome.
Conjugated hyperbilirubinemia
The other part, which makes up bilirubin total concentration, is conjugated bilirubin. Increased levels of conjugated bilirubin or conjugated hyperbilirubinemia may be caused by hepatitis. Viral, alcoholic, and autoimmune related hepatitis is associated with this form of elevated levels of bilirubin. Liver infiltration, which is caused by diseases like lymphoma, tuberculosis, amyloidosis, and sarcoidosis, can also increase conjugated levels of bilirubin.
Moreover, obstruction of biliary, (the tract system which forms the path where bile is released from the liver and then transported to the first part of the small intestine or duodenum) causes the levels of hepatic bilirubin to increase. The obstruction of the biliary duct may be caused by conditions like chronic pancreatitis, acute pancreatitis, pancreatic cancer, and biliary atresia.
Some drugs can cause elevated liver enzymes, which cause more conversion of unconjugated bilirubin into conjugated form. These drugs cause a liver injury, which leads to conjugated hyperbilirubinemia, and they include anabolic steroids, and erythromycin.
Managing the conditions, which cause elevated levels of both conjugated and unconjugated bilirubin, can help reduce the levels. In normal circumstances, blood contains some amount of bilirubin total concentration but in low levels. When a patient is tested of serum or total bilirubin, the tests can provide an accurate assumption of the function of liver.
In a healthy person, the liver should be able to take up the prehepatic bilirubin and make it water-soluble before sending it to the small intestine together with the bile. If there is failure or drop in the way the liver functions, then the levels of bilirubin will rise. When there is increased level of bilirubin total concentration, then it may lead to jaundice.
The jaundice condition is characterized by yellowing of the white part of the eye known as sclera. The entire skin of the body may also turn yellow in severe cases of jaundice. Bilirubin total concentrations are elevated passed the normal ranges by factors like increased production of the substance as more old red blood cells are destroyed. It may also be caused by decreased conjugation because of liver dysfunction.
When the liver is not able to secrete the bile component that contains conjugated bilirubin, then this may lead to increased levels of serum bilirubin. When blockage of bile ducts occurs, it means that the conjugated bilirubin that has been released from the liver through the bile is not able to reach the intended areas like the small intestines and therefore the levels remain high in bloodstream.