yellowing of the skin is usually caused due to the accumulation of the pigment bilirubin in the blood. This symptom can have several causes as will be discussed in the context of this article. The causes of skin yellowing can be conveniently divided to hemolytic causes or due to hepatocellular damage and due to an obstruction to the flow of bile whether it is intrinsic to the liver or it is an obstruction in the biiary canal. All these causes will be discussed in this article.
The first cause of skin yellowing that is discussed here is the hemolytic cause. Hemolysis is the process in which red blood cells rupture releasing their contents which inculde the molecule hemoglobin in addition to potassium ions and the enzyme lactate dehydrogenase or LDH. The molecule of interest to us in this context is hemoglobin and its release to the blood causes hyperhemoglobinemia. This molecule is then metabolized in the body releasing the molecule bilirubin as a metabolic product of the heme portion of the hemoglobin molecule. This molecule in turn accumulates in the blood causing symptoms of hyperbilirubinemia and jaundice. An example of all this process occurs in the blood condition of thalassemia and sickle cell disease of red blood cells.
The other cause of skin yellowing is an intrinsic defect in the liver cells or hepatocytes. There are several causes under this heading. One of them is cellular damage in the liver whether it is chronic or acute liver failure that leads to the development of jaundice due to the impaired metabolism of bilirubin in the liver cells due to its destruction. Jaundice can appear in both cases of liver failure and is the result of the accumulation of the pigment in the blood.
Also bilirubin is entered into the liver cells where it is being conjugated (bound to proteins in the liver cells which make it water soluble) and then transported to the biliary canal and from there it is transported to the intestine. The mechanism of bilirubin entry into the liver cells involve special proteins that assist in its entry into the cell. The absence of these proteins in the case of liver disease leads to deficient uptake of bilirubin by the liver cells which lead to increased level of unconjugated bilirubin in the blood, thus causing yellowing of the skin in the body. The typical syndrome that shows this disorder is called Gilbert's syndrome which is a genetic disorder that is inherited as an autosomal dominant trait and is characterized by mild Jaundice.
Also another defect which involves the liver cells is the improper conjugation of bilirubin in the liver cells. Usually conjugation of bilirubin to bilirubin glucuronide is done with the help of the enzyme UDP glucuronyl transferase. In certain cases these liver enzymes can be absent thus leading to the accumulation of unconjugated bilirubin in the blood with subsequent development of jaundice. Also these enzyme systems for conjugation of biirubin in the liver cells can be immature in infants. Thus it can cause infantile type of jaundice that is characteristic only of children. Also drugs that are administered to treat other conditions in the body can affect the function of this enzyme, thus causing also the same symptom of jaundice. Another disorder that can cause impaired function of this enzyme also is called the crigler-najjar syndrome. This disorder a rare disease that is inherited as autosomal recessive disorder and is charcterized by the absence of this enzyme for the conjugation of bilirubin.
The last cause of skin yellowing that is discussed here is related to obstruction of the flow of bile from the liver to the biliary canal. In this case after the conjugation of bilirubin in the liver cells its transport from the liver to the biliary canal is impaired for unknow reasons. This can in turn cause hyperbilirubinemia of the conjugated type. A typical disorder that involves this type of obstruction is called Dubin-johnson syndrome and is characterized by conjugated hyperbilirubinemia in addition to the accumulation of a pigment in the liver cells which is suspected to be lipofuscin. Another disorder with the same characteristics but without involvement of the pigment is called Rotor's syndrome. Another type of obstruction to bile flow from the liver to the biliary canal occurs in the biliary canal itself. In this case it can be caused due to a cholesterol stone that can lodge in the biliary canal and obstruct the flow of bile to the intestine. The result in this case is the development of jaundice which is accompanied with severe pain due to the contraction of the muscles of the gallbladder