Cholesterol & Bile
Bile Salts
Regulation
As surfactants or detergents, bile acids are potentially toxic to cells, and their concentrations are tightly regulated. They function as a signaling molecule in the liver and the intestines by activating a nuclear hormone receptor, FXR, also known by its gene name NR1H4. Activation of FXR in the liver inhibits synthesis of bile acids, and is one mechanism of feedback control when bile acid levels are too high. FXR activation by bile acids during absorption in the intestine increases transcription and synthesis of FGF19, which will then inhibit bile acid synthesis in the liver.[7] Emerging evidence associates FXR activation with alterations in triglyceride metabolism, glucose metabolism, and liver growth.[citation needed]
Bile salts mal-absorption may be the result of radiation enteropathy
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Intestinal absorption of bile acids
bile acid transporters are all highly expressed in the ileum but not in the liver, jejunum or colon.[4] When expression of these specialized transporters is reduced, the intestine is less efficient at bile acid reabsorption (Type 1 bile acid malabsorption).If intestinal motility is affected by gastro-intestinal surgery, or bile acids are deconjugated by small intestinal bacterial overgrowth, absorption is less efficient (Type 3 bile acid malabsorption).
Overproduction of bile acids
Primary bile acid diarrhea (Type 2 bile acid "malabsorption") may be caused by an overproduction of bile acids.[7][8] Several groups of workers have failed to show any defect in ileal bile acid absorption in these patients, and they have an enlarged bile acid pool, rather than the reduced pool expected with malabsorption.[9] The synthesis of bile acids in the liver is negatively regulated by the ileal hormone fibroblast growth factor 19 (FGF19), and lower levels of this hormone result in overproduction of bile acids, which are more than the ileum can absorb.[8]
Diagnosis
Several methods have been developed to identify the disorder but there are difficulties with all of them.[10] Fecal bile acid quantification is unpleasant for both the patient and laboratory.Diagnosis of bile acid malabsorption is easily and reliably made by the SeHCAT test. This nuclear medicine test involves two scans a week apart and so measures multiple cycles of bile acid excretion and reabsorption. There is limited radiation exposure (0.3mSv). Retention of SeHCAT at 7 days is normally above 15%; values less than 15%, 10% and 5% predict respectively mild, moderate and severe abnormal retention and an increasing likelihood of response to bile acid sequestrants.[11] This test is not licensed in the USA, and is underutilized even where it is available.[12][13]Older methods such as the 14C-glycocholic breath test are no longer in routine clinical use.Measurement of 7 alpha-hydroxy-4-cholesten-3-one, a bile acid precursor, in serum, shows the increased bile acid synthesis found in bile acid malabsorption.[14] This test is an alternative diagnostic means when available. Fasting blood FGF19 values may have value in the recognition of the disease and prediction of response.[15]
Page 1: Cholesterol
Page 2: High Blood Cholesterol Level
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