Bile and Bilirubin
Bile is a watery mixture of organic and inorganic compounds that is synthesized by the liver and stored in the gall bladder.
Bile contains water, bile salts, bilirubin, cholesterol, bile pigments, and phosphatidylcholine (lecithin). Phosphatidylcholine and bile salts are quantitatively the most important organic components of bile.
The liver secretes 500-1500 ml/day of bile, a combination of bile salts, phospholipids, and cholesterol. The bile ducts also secrete bicarbonate. Bile secretion is under control of CCK, while bicarbonate secretion is induced by secretin.
Bilirubin
Normally, 4 mg/kg body weight of bilirubin is produced daily. Most of this comes from the breakdown of old red blood cells in the spleeen and liver, with the remainder coming from ineffective erythropoiesis or the catabolism of hepatic hemeproteins such as cytochromes P-450.
The heme ring is cleaved by microsomal heme oxygenase, forming biliverdin. This is converted to unconjugated bilirubin by biliverdin reductase. Unconjugated bilirubin is released into the plasma and travels to the liver bound to albumin. Because it is insoluble, it cannot be excreted in urine or bile, but can cross into the brain or the placenta.
Bilirubin Conjugation
Bilirubin is transported across hepatocyte membranes and conjugated with glucouronic acid by the enzyme UDP glucuronyltransferase. Conjugated bilirubin is excreted into the bile by active transport. When biliary excretion is impaired, pigment regurgitates into the plasma. As conjugated bilirubin is water soluble, it is readily filtered by the kidneys and gives urine a dark color.
Once in the bile, bilirubin enters the intestine, where bacteria convert it into urobilinogens, 20% of which is reabsorbed.
Between 15-30 g of bile salts are secreted from the bile duct daily in response to the need for lipid digestion and release of the hormone CCK from intestinal I cells.
Ninety five percent of bile is reabsorbed in the terminal ileum, setting up the enterohepatic circulation. Normally only 600 mg of bile is lost in the stool daily, with this amount being synthesized in the liver. Problems in ileum absorption can lead to increased bile in the colon, causing diarrhea.
Bile acids
Bile acids - cholic acid and chenodeoxycholic acid - are synthesized in the liver from cholesterol. They contain two or three -OH groups and a carboxyl group. The carboxyl group has a pKa of ~6 and is therefore not fully ionized at physiologic pH. Bile acids are amphipathic therefore acting as emulsifying agents, or detergents.
Bile Salts
Before bile acids leave the liver, they are congugated with either glycine or taurine. The carboxyl of glycine or the sufate of taurine are fully ionized at physiologic pH, leading to lower pKa values, and are more effective detergents than bile acids. Bile salts, not acids, are found in the bile.
Bacteria in the gut can remove glycine or taurine from bile salts, regenerating bile acids. These can be modified to produce secondary bile acids. If this decongugation occurs in the upper SI, this can seriously inhibit lipid absorption.
More than 95% of bile salts are reabsorbed in the ileum as a mixture of bile salts and primary and secondary bile acids are returned to the liver via the portal circulation. Bile acids are transported in the blood by albumin in a noncovalent complex. In the liver, bile acids are reconverted to bile salts are re-secreted, creating the enterohepatic circulation.
Dietary fibre or drugs such as cholestyramine sequester bile acids in the gut and prevent their reabsorption, diverting cholesterol to be used in bile acid synthesis.