In order to understand how jaundice results, the pathological processes that cause jaundice to take their effect must be understood. Jaundice itself is not a disease, but rather a sign of one of many possible underlying pathological processes that occur at some point along the normal physiological pathway of the metabolism of bilirubin.
When red blood cells have completed their life span of approximately 120 days, or when they are damaged, their membranes become fragile and prone to rupture.
As each red blood cell traverses through the reticuloendothelial system, its cell membrane ruptures when its membrane is fragile enough to allow this.
Cellular contents, including hemoglobin, are subsequently released into the blood. The hemoglobin is phagocytosed by macrophages, and split into its heme and globin portions.
The globin portion, a protein, is degraded into amino acids and plays no role in jaundice.
Two reactions then take place with the heme molecule.
The first oxidation reaction is catalyzed by the microsomal enzyme heme oxygenase and results in biliverdin (green color pigment), iron and carbon monoxide.
The next step is the reduction of biliverdin to a yellow color tetrapyrol pigment called bilirubin by cytosolic enzyme biliverdin reductase.
This bilirubin is "unconjugated," "free" or "indirect" bilirubin. Approximately 4 mg per kg of bilirubin is produced each day.
The majority of this bilirubin comes from the breakdown of heme from expired red blood cells in the process just described. However approximately 20 percent comes from other heme sources, including ineffective erythropoiesis, and the breakdown of other heme-containing proteins, such as muscle myoglobin and cytochromes.
The unconjugated bilirubin then travels to the liver through the bloodstream. Because this bilirubin is not soluble, however, it is transported through the blood bound to serum albumin.
Once it arrives at the liver, it is conjugated with glucuronic acid (to form bilirubin diglucuronide, or just "conjugated bilirubin") to become more water soluble. The reaction is catalyzed by the enzyme UDP-glucuronyl transferase.
This conjugated bilirubin is excreted from the liver into the biliary and cystic ducts as part of bile. Intestinal bacteria convert the bilirubin into urobilinogen.
From here the urobilinogen can take two pathways. It can either be further converted into stercobilinogen, which is then oxidized to stercobilin and passed out in the feces, or it can be reabsorbed by the intestinal cells, transported in the blood to the kidneys, and passed out in the urine as the oxidised product urobilin. Stercobilin and urobilin are the products responsible for the coloration of faeces and urine, respectively.
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