Bile droplets

Morphology The morphologist uses the term cholestasis to describe the presence of bile in the hepatocytes as well as in hypertrophic Kupffer cells (= cellular bilirubino-stasis), particularly in the form of inspissated bile droplets and copper within the more or less dilated canaliculi (= canalicular bilirubinostasis). In extrahepatic cholestasis, bile is additionally found within the likewise mostly dilated interlobular bile ducts (= ductular bilirubinostasis) as well as in the parenchyma in the form of bile infarcts" or bile lakes . 

Fig. 13.5 Bilirubinostasis with bile droplets (->) in the hepatocytes and canaliculi. Clinical diagnosis extrahepatic obstructive jaundice...

Irrespective of the physical form of the carotenoid in the plant tissue it needs to be dissolved directly into the bulk lipid phase (emulsion) and then into the mixed micelles formed from the emulsion droplets by the action of lipases and bile. Alternatively it can dissolve directly into the mixed micelles. The micelles then diffuse through the unstirred water layer covering the brush border of the enterocytes and dissociate, and the components are then absorbed. Although lipid absorption at this point is essentially complete, bile salts and sterols (cholesterol) may not be fully absorbed and are not wholly recovered more distally, some being lost into the large intestine. It is not known whether carotenoids incorporated into mixed micelles are fully or only partially absorbed. 

Bicarbonate is only one of the digestive chemicals that get secreted into the small intestines. Bile acids play a role as well. Bile is made in the liver, stored in the gallbladder, and, when needed, secreted into the small intestines via the bile duct. Bile plays an essential role in the breakdown of fat by dissolving it in the small intestine, much like soap dissolves oil on a frying pan. This breaks the fat down into small droplets. These fat droplets are broken down even further by other intestinal enzymes so that they can be absorbed by the body. 

The absorption efficiency of the different carotenoids is variable. For example, (3-cryptoxanthin has been reported to have higher absorption efficiency than a-cryptoxanthin in rats (Breithaupt and others 2007). Carotenoids must be liberated from the food before they can be absorbed by intestinal cells (Faulks and Southon 2005). Mechanical disruption of the food by mastication, ingestion, and mixing leads to carotenoid liberation (Guyton and Hall 2001). The enzymatic and acid-mediated hydrolysis of carbohydrates, lipids, and proteins (chemical breaking of the food) also contributes to carotenoids liberation from the food matrix (Faulks and Southon 2005). Once released, carotenoids must be dissolved in oil droplets, which are emulsified with the aqueous components of the chyme. When these oil droplets are mixed with bile in the small intestine, their size is reduced, facilitating the hydrolytic processing of lipids by the pancreatic enzymes (Pasquier and others 1996 Furr and Clark 1997 ... 

The digestion and absorption of fat is considerably more complex than that of carbohydrate or protein because it is insoluble in water, whereas almost aU enzymes catalyse reactions in an aqueous medium. In such media, fat can form small droplets, an emulsion, which is stable in this medium. Formation of an emulsion is aided by the presence of detergents these possess hydrophobic and hydrophilic groups, so that they associate with both the fat and the aqueous phases. Such compounds are known as emulsifying agents and those involved in digestion are mainly the bile salts and phospholipids. 

During passage through the intestines, the active lipase breaks down the triacylglycerols in the interior of the droplets into free fatty acids and amphipathic monoacylglycerols. Over time, smaller micelles develop (see p. 28), in the envelope of which monoacylglycerols are present in addition to bile salts and phospholipids. Finally, the components of the micelles are resorbed by the enterocytes in ways that have not yet been explained. 

Cholesterol can be derived from two sources—food or endogenous synthesis from ace-tyl-CoA. A substantial percentage of endogenous cholesterol synthesis takes place in the liver. Some cholesterol is required for the synthesis of bile acids (see p. 314). In addition, it serves as a building block for cell membranes (see p. 216), or can be esterified with fatty acids and stored in lipid droplets. The rest is released together into the blood in the form of lipoprotein complexes (VLDLs) and supplies other tissues. The liver also contributes to the cholesterol metabolism by taking up from the blood and breaking down lipoproteins that contain cholesterol and cholesterol esters (HDLs, IDLs, LDLs see p.278). 

This process involves mixing (peristalsis) in the duodenum with bile salts, which act like detergents to dissipate lipid droplets. 

For this water concentration, the micellar region for the bile salt mixture is large for all oleyl compounds except oleic acid. Oleic acid is distinguished from the other compounds in that it does not form a lyotropic liquid crystalline phase spontaneously in water and, similarly, is present as oil droplets in bile salt solution when its micellar solubility is exceeded. Figure 1 shows also that the micellar area of an equimolar mixture of monoolein and sodium oleate is considerably greater than that of an equimolar mixture of monoolein and oleic acid, indicating that fatty acid ionization also enhances micellar solubility when monoolein is present. The equimolar mixture of sodium oleate and oleic acid has a micellar area similar in size to that of monoolein, as does the equimolar combination of all three compounds. 

Effect of Bulk pH on Behavior and Solubility of Oleic Acid in Bile Salt Solution. Figure 2 shows the effect of bulk pH on the behavior and solubility of oleic acid in 0.15M buffer (above) and in 4 mM sodium glycodeoxycholate (below). In buffer, oleic acid has an extremely low solubility, and the excess, below pH 6.8, is present as an emulsion. In micellar bile salt solution, the oleic acid is solubilized to some extent. Above pH 6.5, its solubility rises markedly, and the excess now forms a dispersed phase which probably consists of droplets of fatty acid emul-... 

Steroids are lipids found in living systems that all have the ring system shown in Figure 3.8 for cholesterol. Steroids occur in bile salts, which are produced by the liver and then secreted into the intestines. Their breakdown products give feces its characteristic color. Bile salts act on fats in the intestine. They suspend very tiny fat droplets in the form of colloidal emulsions. This enables the fats to be broken down chemically and digested. 

Figure 4-2. Photomicrograph of a portion of a hepatocyte from a cholestatic infant with PIZ phenotype.Amorphous a 1-antitrypsin (AT) is in the transitional zone between rough and smooth endoplasmic reticulum. B, bile T, triglyceride droplet.

Q9 Lipid in the diet is present mostly in the form of triglycerides, which are digested by pancreatic lipase to yield fatty acids and monoglycerides bile salts are also required for digestion and absorption of the dietary lipids. Bile salts interact with the fatty acids and monoglycerides in the gut lumen to form micelles, which can be absorbed by the epithelial cells. In the epithelial cell the triglyceride is resynthesized to form droplets, or chylomicrons, which enter the lacteals and are carried by the lymphatic system into the general circulation. 

ACAT transfers amino-acyl groups from one molecule to another. ACAT is an important enzyme in bile acid synthesis, and catalyses the intracellular esterification of cholesterol and formation of cholesteryl esters. ACAT-mediated esterification of cholesterol limits its solubility in the cell membrane and thus promotes accumulation of cholesterol ester in the fat droplets within the cytoplasm this process is important in preventing the toxic accumulation of free cholesterol that would otherwise damage ceU-membrane structure and function. Most of the cholesterol absorbed during intestinal transport undergoes ACAT-mediated esterification before incorporation into chylomicrons. In the liver, ACAT-mediated esterification of cholesterol is involved in the production and release of apo-B-containing lipoproteins. 

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