Clinical Note

Abnormalities of Lipid Assimilation

Compared with carbohydrate and protein assimilation, lipid assimilation is much more complicated, and malabsorption of lipids occurs more frequently. Malabsorption of fats can occur because of a defect at any one of the steps involved in the process of lipid assimilation. Fat malabsorption is defined as the excretion of more than 7 g of fat per day in the stool. This condition is called steatorrhea. Normal individuals are able to absorb as much as 150-200 g of fat per day, and, of the 3-5 g fat excreted in the stool each day, approximately one-half is of dietary origin. The remainder comes from desquamated cells and colonic flora added to the lumen distal to the regions where pancreatic lipase is active and bile salts are present.

Luminal digestion of triglycerides is inadequate in conditions of pancreatic deficiency. In the absence of pancreatic lipase, two-thirds of dietary fat is not absorbed and appears in the stool as undigested triglyceride. Conditions resulting in decreased pancreatic lipase activity include pancreatitis, cystic fibrosis, and other pancreatic diseases. Increased acidity of the duodenal contents resulting from gastric hypersecretion (Zollinger-Ellison syndrome) or inadequate bicarbonate secretion may lower the pH significantly below the optimum for pancreatic lipase or actually denature the enzyme. Pancreatic lipase, however, is secreted in great excess, and digestion is unimpaired in the presence of only 15-20% of the normal amount of enzyme. In the absence of bile salts, approximately 50% of the dietary fat appears in the stool. Although bile salts are important in the emulsification process, the defect is not in hydrolysis, but is a failure to absorb the products of lipolysis because almost all of the stool fat is in the form of free fatty acids. All of the steps before micelle formation can occur in the absence of bile salts because fat is emulsified by protein, lecithin, lysolecithin, and, once hydrolysis begins, by monoglycerides. Once the concentration of bile salts drops below the critical micellar concentration, however, fat malabsorption occurs. Decreases in the concentration of effective bile salts may be caused by (1) liver disease; (2) interruption of the enterohepatic circulation, such as occurs after ileal resection;

(3) bacterial overgrowth of the small intestine and subsequent bile salt deconjugation by bacteria; or

(4) increased duodenal acidity, which causes the bile salts to become protonated and un-ionized, less soluble, and unable to form micelles.

Absorption of fat is also decreased by a number of conditions that affect or decrease the number of absorbing cells. These include tropical sprue and gluten enteropathy.

No disease has been associated with triglyceride resynthesis. However, as mentioned earlier, failure to synthesize apoprotein B prevents chylomicron formation and leads to a buildup of fat within the enterocyte. This condition is known as abetalipoproteinemia.

Some aspects of lipid malabsorption can be treated by altering the diet. Substitution of medium-chain triglycerides for long-chain triglycerides will eliminate steatorrhea. Medium-chain triglycerides are more water soluble and can be hydrolyzed more rapidly than long-chain triglycerides. The resulting medium-chain fatty acids are water soluble and are absorbed directly without depending on micelle formation. Medium-chain fatty acids also pass through the enterocyte without being resynthesized into triglycerides. They do not take part in chylomicron formation and are absorbed directly into the portal blood. Substitution of medium-chain triglycerides for long-chain triglycerides will not prevent malabsorption of other lipids, such as sterols, whose uptake depends on micelle formation.

range in size from 750-6000 A, with a mean diameter of 1200 A, and are made up of 90% triglycerides, 2% cholesterol (about equally divided between free and esterified), 7% phospholipids, and 1% protein (see Fig. 9). The core of the chylomicron contains most of the triglycerides and cholesterol but no phospholipids. The surface membrane of the chylomicron is a mono-layer composed of phospholipids, apoproteins, free cholesterol, and a small amount of saturated triglycerides. Phospholipids cover 80-90% of the surface area, whereas apoproteins are present in amounts sufficient to cover only 10-20%. The exact mechanism of chylomi-cron packaging is not known; however, apoproteins are essential for transporting the lipids out of the cell. Inhibition or lack of apoprotein synthesis leads to an accumulation of lipid within the enterocytes.

The many types of apoproteins are divided into A, B, C, and E classes. Intestinal cells have been shown to synthesize Apo AI, Apo AIV, Apo B, and Apo CII. The failure to synthesize Apo B results in abetalipoprotei-nemia and the inability to transport chylomicrons out of the intestinal cells. Some apoproteins are also synthesized by the liver, and the intestinal cells can make use of circulating lipoprotein remnants. Other lipoproteins exist in addition to chylomicrons and include very-low-density lipoprotein (VLDL), low-density lipopro-tein (LDL), and high-density lipoprotein (HDL). VLDL is smaller than chylomicrons and is the major lipopro-tein synthesized during fasting. The intestine synthesizes 11-40% of VLDL during fasting, and the mechanisms for synthesis are independent of those for chylomicron synthesis. LDL is believed to be derived from the hepatic breakdown of plasma VLDL. HDL can be synthesized directly by the small intestine and the liver or derived from the catabolism of chylomicrons or VLDL. The lipoproteins not only differ in size, but their apoprotein and lipid compositions differ as well.

Although the exact steps in chylomicron formation are not entirely known, their path of intracellular transport is clear. After triglyceride synthesis within the smooth endoplasmic reticulum, chylomicrons begin to appear in the Golgi apparatus. Accumulation of chylomicrons in the Golgi leads to the formation of secretory vesicles. The vesicles containing the chylomi-crons migrate to the basolateral membrane. The vesicle membrane fuses with the cell membrane and the chylomicrons are secreted by the process of exocytosis. The chylomicrons traverse the basement membrane and enter the lacteals by moving through the gaps between the endothelial cells lining the lymphatics. Chylomicrons are too large to enter the capillaries and eventually reach the bloodstream via the thoracic duct.

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