See also: blood test and high bilirubin
Bilirubin is a waste product deriving from the metabolism of hemoglobin (a protein present in red blood cells mainly responsible for transporting oxygen from the lungs to the various tissues of the body).
As anticipated, most of the circulating bilirubin is produced during the catabolism of hemoglobin, which in turn results from the destruction of aged or damaged red blood cells. Only 10-20% of the circulating share (normal serum bilirubin levels: 0.3 - 1 mg / dl) derives from the catabolism of other hemoproteins (myoglobin, cytochromes, peroxidase, catalase) and abnormal erythroblasts (precursors of red blood cells produced in the bone marrow).
The bilirubin produced by these catabolic processes is known as free bilirubin, unconjugated bilirubin, or indirect bilirubin. By virtue of its fat solubility, indirect bilirubin is transported in the bloodstream by albumin, to which it binds with a "weak" bond. Also for this characteristic it cannot be filtered by the kidney, so it is not found in the urine.
Indirect bilirubin metabolism occurs in the liver.
The liver cells, called hepatocytes, sequester indirect bilirubin dissociated from albumin, incorporate it by diffusion or active transport across the plasma membrane, and prevent its reflux into the blood by binding to a protein, called ligandin. At this point, bilirubin is conjugated with two molecules of glucuronic acid, this reaction occurs inside the smooth endoplasmic reticulum of the hepatocyte and is mediated by the enzyme bilirubin-glucuronyltransferase.
The substance resulting from the conjugation process (which occurs in two stages: bilirubin monoglicuronide → bilirubin biglicuronide) is known as conjugated or direct bilirubin. Being water-soluble, it is excreted with the bile.
Through the bile flow, the direct bilirubin is poured into the intestine and precisely into the duodenum, where it flows through the choledochus. Most of it is then eliminated with the faeces, while a small percentage is transformed by the ileum and colon bacteria into " Urobilinogen ". This colorless substance undergoes a particular metabolism, which is easier to understand by looking at the image at the bottom of the article.
- In the terminal ileum and colon direct bilirubin is transformed into urobilinogen by bacterial beta-glucuronidase, which splits it to glucuronic acid and bilirubin; the latter is further processed and converted into urobilinogen, mesobilinogen and stercobilinogen, all colorless substances.
- The urobilinogen is mostly excreted with the faeces, in the form of colored pigments (stercobilin). A 20% is instead reabsorbed by the blood and conveyed to the liver, where it is again excreted with the bile.
- A small amount of the reabsorbed urobilinogen escapes the hepatic filter and is excreted in the urine, where it is oxidized to urobilin, the substance responsible for their characteristic color.
As anticipated, in the kidney the indirect bilirubin (unconjugated, bound to albumin) is not filtered by the glomeruli; as such, it is not found in the urine. On the contrary, conjugated or direct bilirubin does not need to bind to albumin, and being water-soluble it passes the glomerular filter; therefore, it can be found in the urine.
The amount of urobilinogen that has escaped the hepatic filter is also present in the urine, either as such or in the form of urobilin.
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