What mechanism leads to the increase in serum bilirubin when cholestasis occurs?

When cholestasis occurs, there is an obstruction in the normal flow of bile, which can be caused by various factors such as liver disease, bile duct obstruction, or other conditions that impair the normal secretion of bile from the liver. In a healthy system, bilirubin is processed in the liver and then excreted into the bile, which eventually carries it to the intestines. However, during cholestasis, the obstruction impedes the normal excretion pathway.

As a result of this impaired flow, bilirubin, which is produced from the breakdown of hemoglobin in red blood cells, accumulates in the bloodstream because it cannot be efficiently excreted into the bile. The level of serum bilirubin rises due to this decreased excretion rather than an increase in its synthesis or changes in metabolism. Consequently, the most direct mechanism leading to increased serum bilirubin levels in cholestasis is the decreased excretion of bilirubin from the liver to the intestines, leading to its accumulation in the blood.

This mechanism highlights the critical role of bile flow in maintaining bilirubin levels within the normal range and outlines how cholestasis disrupts this homeostatic process.