Functions of the Liver
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
The liver produces about 1 L of bile per day, and this passes into the gall bladder where it is concentrated to about one-fifth of its volume. Bile consists of electrolytes, protein, bilirubin, bile salts and lipids. Bile acids (cholic acid and chenodeoxycholic acid) are produced in the liver from cholesterol. In the gut, bacterial action on cholic and chenodeoxycholic acids produces secondary bile acids such as deoxycholic acid and lithocholic acid. The bile acids conjugate with glycine or taurine to form bile salts (Figure 37.5). Bile salts are more water soluble and less lipid soluble, which limits the passive absorption in the small intestine so that the bile salts remain within the gut. The main function of bile salts is the emulsification of dietary fat, which is essential for fat absorption. In addition, bile salts are also important for the absorption of fat-soluble vitamins, especially vitamins A, D, E and K. At the terminal ileum, bile salts are reabsorbed by the apical sodium-dependent bile transporter. The reabsorbed bile salts are carried to the liver in the portal circulation, mostly bound to plasma proteins. The recirculation of bile salts is referred to as enterohepatic circulation.
Liver physiology
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2015
The liver produces about 1 L of bile per day, and this passes into the gall bladder where it is concentrated to about one-fifth of its volume. Bile consists of electrolytes, protein, bilirubin, bile salts and lipids. Bile acids (cholic acid and chenodeoxycholic acid) are produced in the liver from cholesterol. In the gut, bacterial action on cholic and chenodeoxycholic acids produces secondary bile acids such as deoxycholic acid and lithocholic acid. The bile acids conjugate with glycine or taurine to form bile salts (Figure 6.5). Bile salts are more water soluble and less lipid soluble, which limits the passive absorption in the small intestine so that the bile salts remain within the gut. The main function of bile salts is the emulsification of dietary fat, which is essential for fat absorption. In addition, bile salts are also important for the absorption of fat-soluble vitamins, especially vitamins A, D, E and K. At the terminal ileum, bile salts are reabsorbed by the apical sodium-dependent bile transporter. The reabsorbed bile salts are carried to the liver in the portal circulation, mostly bound to plasma proteins. The recirculation of bile salts is referred to as enterohepatic circulation.
The accessory organs: Pancreas, liver and gallbladder
Paul Ong, Rachel Skittrall in Gastrointestinal Nursing, 2017
Bile salts make up one of the most important constituents of bile. They are water-soluble derivatives of cholesterol. Two important bile acids are produced in the liver: cholic acid and chenodeoxycholic acid. These are conjugated (made soluble) to an amino acid to produce the conjugated form that is released into the canaliculi (Figure 6.12). Bile acids perform two important functions. First they help to break down, or emulsify (not digest), fat globules to smaller fat droplets. This helps to increase the surface area across which the enzyme lipase can work to digest fats. When bile salts have completed their function they are released back into the lumen of the small intestine and are transported with chyme to the terminal ileum. The majority of bile acids are reabsorbed across the terminal ileum epithelium into blood and are then transported via the hepatic portal vein to the sinusoids in the liver lobules. Here the bile salts are then taken up by the hepatocytes and are effectively recycled so that they can be secreted again as an important constituent of bile. The continuous recycling of bile acids is known as the enterohepatic circulation (Figure 6.13). In early infancy the secretion of bile salts into the small intestine is much reduced. This has the effect of reducing the digestion of fats, and in particular long-chain fatty acids. This should not present a problem for breastfed infants as breast milk contains fats that are already emulsified.
Pharmacological effects of nanoencapsulation of human-based dosing of probucol on ratio of secondary to primary bile acids in gut, during induction and progression of type 1 diabetes
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Armin Mooranian, Nassim Zamani, Ryu Takechi, Hesham Al-Sallami, Momir Mikov, Svetlana Goločorbin-Kon, Bozica Kovacevic, Frank Arfuso, Hani Al-Salami
Rau et al. investigated the effects of inflammation on bile acid profile. The authors examined changes in bile acid metabolism and enterohepatic regulation processes associated with inflammatory bowel disorders. They found that there was strong association between bile acid levels in gut and liver, and inflammation, through effects on gene expression and signalling pathways including farnesoid X receptors [29]. This suggests that bile acid based feedback mechanisms take place at the genetic and molecular levels and are not confined only to the gut. Stiehl et al. investigated the effects of chenodeoxycholic acid and ursodeoxycholic acid treatments on the bile acid profile in gallstone patients. The authors explored the effects of chronic daily intake of chenodeoxycholic acid and ursodeoxycholic acids on bile acid metabolism and ratio. The authors found that treatment chenodeoxycholic acid and ursodeoxycholic acid resulted in significant changes in bile acid profile, metabolism and ratios via alteration of liver bile acid synthesis and conjugation [30]. This was not consistent with a previous study in our laboratory which showed that acute treatment of diabetic rats with a conjugated bile acid did not significantly change the concentrations of the bile acid in plasma or tissues [3].
TGR5 agonists for diabetes treatment: a patent review and clinical advancements (2012-present)
Published in Expert Opinion on Therapeutic Patents, 2022
Rachana S. Bhimanwar, Amit Mittal
In another patent, Intercept Pharmaceuticals describes different chenodeoxycholic acid derivatives to treat obesity, insulin sensitivity, and inflammation. The patent retained the general structure 2 and optimized mainly with methyl group substitution at C-23, C-6 of chenodeoxycholic acid. Representative compounds 2e-2 h are illustrated in Figure 2. An in-vitro experiment revealed that CDCA without an alkyl substitution exhibited an EC50 value of 4 µM and the inclusion of the C-6 methyl group increases activity drastically with an EC50 value of 0.37 µM (compound 2 g). The compound 2e (23(R + S)-methyl-6methyl-chenodeoxycholic acid) was found to be most potent with EC50 0.11 µM on the TGR5 receptor and 123% efficacy [27].
Early diagnosis for cerebrotendinous xanthomatosis with juvenile cataract and family history
Published in Ophthalmic Genetics, 2023
Nurşen Öncel Acır, Burcu Taskiran Kandeger
The CYP27A1 mutation encoding the enzyme involved in bile acid synthesis results in the shifting of cholesterol to the cholestanol pathway (3). Clinical problems are caused by an increase in cholestanol and bile alcohols in the blood, urine, and feces, which then cross the blood-brain barrier and accumulate in various organs (15). Although cholestanol levels increase significantly in this disease, plasma cholesterol levels remain normal. Despite deposits in multiple organs, early-onset juvenile cataracts, and symptoms such as recurrent diarrhea episodes, the presence of cerebrotendinous xanthomatosis frequently remains misdiagnosed for years. However, with an early diagnosis of the disease, the production and plasma levels of cholestanol and bile alcohols decrease following the initiation of oral chenodeoxycholic acid (6,16). Moreover, the neurological complications of the disease can be prevented or even reversed (16). At this point, the early detection of the condition and the timing of the administration of chenodeoxycholic acid are critical. For this reason, juvenile cataract, which is one of the first symptoms, the morphology of the cataract, and the patient’s family history are of vital importance.
Related Knowledge Centers
- Acetic Acid
- Bile Acid
- Carboxylic Acid
- Cholic Acid
- Deoxycholic Acid
- Ethanol
- Glycine
- Taurine
- Cholesterol
- Muricholic Acid