Metabolism
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Gripping abdominal pain and jaundice
Key points from this exercise:
Haem from old red blood cells is oxidised to bilirubin, which is conjugated with glucuronic acid in the liver, and excreted in the bile.
Jaundice is due to abnormally high concentrations of bilirubin in the bloodstream; the urine is dark because of excretion of bilirubin, and faeces are pale because of the lack of bilirubin.
Liver disease leads to jaundice because of failure to conjugate bilirubin, so that what is present in the bloodstream is unconjugated bilirubin.
Gall stones may obstruct the bile duct, preventing the secretion of bile. In this case it is conjugated bilirubin that is present in the bloodstream.
Bile contains bilirubin, cholesterol, phospholipids and bile salts.
Bile salts are synthesised from cholesterol by 7-alpha hydroxylation and side-chain oxidation. They are conjugated with glycine or taurine.
Bile salt conjugates are amphiphilic and can form micelles alone or together with other lipids. They are are essential for the absorption of the products of lipid digestion.
Gall stones consist mainly of cholesterol, which is very insoluble. Only a small increase in the cholesterol content of bile, or a small reduction in the concentration of bile salts, results in crystallisation of cholesterol to form gall stones.
There is considerable entero-hepatic recycling of bile salts; they are reabsorbed in the terminal ileum, commonly after deconjugation and further metabolism by intestinal bacteria, then stored in the gall bladder and resecreted. The small body pool of bile salts may undergo 6 - 10 cycles of secretion and reabsorption each day.
Cholecystectomy does not impair lipid absorption - the function of the gall bladder is to concentrate bile and store it until required for secretion. In the absence of a gall bladder the more dilute hepatic bile is secreted into the duodenum.
Impairment of the reabsorption of bile salts leads to increased synthesis from cholesterol - this can be exploited to treat familial hypercholesterolaemia by feeding ion exchange resins that bind bile salts and prevent their reabsorption.