Now, let’s go over some physiology. Bilirubin is a yellowish pigment that’s normally found in bile, and is produced in the liver by breaking down hemoglobin from red blood cells.
Normally, red blood cells have an average lifespan of 120 days. When red blood cells get old or damaged, they travel to the spleen, where they are broken down to release hemoglobin. The hemoglobin is degraded into unconjugated or indirect bilirubin, which is then released into the bloodstream.
Unconjugated bilirubin then travels to the liver, where it gets taken up by hepatocytes. These cells bind a molecule called glucuronic acid to the unconjugated bilirubin, forming conjugated or direct bilirubin. Then, the hepatocytes use this conjugated bilirubin, as well as cholesterol and phospholipids, to produce bile. Then, bile is secreted by the liver through the hepatic bile ducts towards the gallbladder, where it’s stored.
Now, when food reaches the stomach, the gallbladder secretes bile through the cystic and common bile duct into the duodenum. The bile then mixes with the food to help digestion while traveling along the intestines.
Ultimately, upon reaching the colon, the colonizing bacteria convert bile’s conjugated bilirubin into urobilinogen. Most of that urobilinogen gets reabsorbed into the blood and travels to the kidneys, where it gets excreted into the urine, giving it its distinct yellow color.
Alright, now the causes of jaundice can be classified as hemolytic or prehepatic, hepatocellular or intrahepatic, and obstructive or posthepatic. Hemolytic jaundice is caused by hemolysis or breakdown of red blood cells; which occurs in conditions like hemolytic anemia, sickle cell disease, spherocytosis, thalassemia, G6PD deficiency, or blood transfusion reactions, as well as with reabsorption of large hematomas. On the other hand, hepatocellular jaundice can be caused by conditions that damage the liver, such as hepatitis, cirrhosis, liver failure, or liver cancer, and certain medications that may cause hepatotoxicity, such as acetaminophen or rifampin; as well as inherited disorders that affect the liver function, such as Gilbert syndrome, Crigler Najjar syndrome, or Dubin Johnson syndrome. Lastly, obstructive jaundice is caused by conditions that block the bile ducts, causing cholestasis or obstructed bile flow. These conditions include gallstones, pancreatitis, and pancreatic cancer, as well as congenital defects, and pregnancy.
Now, let’s discuss the pathology of each type of jaundice. First is hemolytic jaundice, in which there’s excessive breakdown of red blood cells, releasing all their hemoglobin into the blood. The excess hemoglobin is then degraded into unconjugated bilirubin, but the high amount of this bilirubin exceeds the liver’s ability to conjugate it. As a result, the excess unconjugated bilirubin will start to build up in blood. Similarly, in hepatocellular jaundice, the liver damage decreases its ability to conjugate the unconjugated bilirubin, causing unconjugated bilirubin to build up in blood. In addition, the liver damage also impairs its ability to secrete the little conjugated bile that’s produced into bile, thus also causing a build up of conjugated bilirubin in blood. Finally, obstructive jaundice results from cholestasis, which causes bile to build up in the gallbladder, and ultimately, the conjugated bilirubin in it leaks into the blood. Now, regardless of the underlying cause, the excess bilirubin in blood can’t be processed and removed from the body, so it ends up depositing in tissues like the skin, mucous membranes, and sclera.