Figure 48-7. Digestion and absorption of carbohydrates.

Short oligopeptides are further digested by enzymes in the brush border of the small intestine or

within the cell cytoplasm. Single amino acids, dipeptides, and tripeptides are able to diffuse through the

apical membrane into the cytoplasm. Single amino acids are cotransported into the cytoplasm with

sodium along an electrochemical gradient. This electrochemical gradient is maintained by the Na+-K+-

ATPase pump on the basolateral cell membrane. At least four separate transport mechanisms exist for

the various electrochemical properties of amino acids which are transported (neutral, dibasic, acidic,

and imino). Peptides greater than 3 amino acids in length are broken down into smaller peptides by

enzymes in the brush border. The resultant dipeptides and tripeptides are then moved into the

cytoplasm along with H+ by a cotransporter PepT1, where they are hydrolyzed by specific peptidase

into their component amino acids. Transport of amino acids into the cytosol provides an osmotic

gradient by which water is further absorbed from the intestinal lumen. A small portion of the processed

amino acids are utilized by the enterocyte, and the vast majority is shuttled into the portal blood flow

via amino acid transporters on the basolateral membrane.

Fat Digestion and Absorption

Forty percent of the average daily caloric intake (60 to 90 g) in a Western diet is in the form of fat.

Ninety percent of these ingested fats are triglycerides, while the remainder is comprised of cholesterol,

phospholipids, and fat-soluble vitamins. The initiation of lipid digestion occurs when CCK is stimulated

by the presence of fatty acids on the duodenal mucosa. CCK in turn stimulates pancreatic secretion of

lipase and its cofactor colipase. Lipase hydrolyzes triglycerides at the 1 and 3 positions of the glycerol

backbone, yielding two fatty acids and a monoglyceride (a fatty acid esterified to glycerol). Cholesterol

and fat-soluble vitamins are hydrolyzed by pancreatic cholesterol esterase and phospholipids by

phopholipase A2

. The products of lipolysis interact with bile salts to form water soluble micelles. Mixed

micelles are 50 to 400 Å in diameter and are a combination of fatty acids, bile salts, and

monoglycerides. The structure of a micelle is composed of an inward facing hydrophobic region and a

hydrophilic region facing outward toward the aqueous environment of the intestinal lumen. Due to the

hydrophobic core, cholesterol, phospholipids, and fat-soluble vitamins can reside within the micelle

structure. Micelles are able to interact with the mucosal cells and empty their contents into the

cytoplasm. This occurs by the process of dissolution of the micelles into the lipid bilayer of the mucosal

cell. Once this is completed, the components of the micelle are ready to reform with new lipid

components to repeat this process. There is no energy consumed directly in the transfer of lipids into

the cell cytoplasm.

Once in the cytoplasm, long-chain fatty acids and β-monoglycerides are carried by cytosolic fatty

acid–binding proteins to the smooth endoplasmic reticulum (SER). In the SER, resynthesis of

triglycerides occurs. These triglycerides are further processed in the Golgi apparatus where a

phospholipid and an apoprotein coat are added to form a chylomicron. Chylomicrons are 90%

triglyceride; the remaining 10% is composed of phospholipid, cholesterol, and protein. These large

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particles are 750 to 6,000 Å in diameter. Before exiting the Golgi apparatus, the chylomicrons are

packaged into secretory vesicles. They exit the cell membrane by exocytosis and enter the central

lacteal of the villus and the intestinal lymphatic system. In addition, enterocytes also produce smaller

lipoprotein particles, very low density lipoproteins, which contain a higher cholesterol/triglyceride ratio

and provide the major route of entry for dietary cholesterol into the lymphatic system.

Short chain fatty acids contain less than 8 carbon atoms and are water soluble. This allows these

molecules to enter and exit the enterocyte by simple diffusion independent of bile micelles or

chylomicrons. Medium chain triglycerides consist of 6 to 12 carbon atoms and can be absorbed by

simple diffusion or through the previously mentioned process of transport of long chained fatty acids

via the formation of bile micelles and chylomicrons. Both short and medium chain fatty acids may enter

the portal circulation without entering into the lymphatics. The majority of dietary fat is processed and

absorbed in the duodenum and upper jejunum.

Absorption of Bile Salts

Approximately 95% of the bile salts secreted into the intestine are reabsorbed and returned to the liver

through the portal circulation. Once in the liver, these bile salts are reprocessed and secreted and stored

in the gallbladder in preparation for the next meal. This process of recycling of bile salts is referred to

as the enterohepatic circulation. This reabsorption occurs by both passive and active means. A small

amount of bile salts are passively reabsorbed along the entire length of the small intestine. The majority

of bile salts, however, are reabsorbed though an active Na+-dependent transport mechanism in the

terminal ileum. Bile, which is not reabsorbed, passes into the colon where it is deconjugated by

bacteria. This process increases the solubility of the bile and promotes further passive absorption. High

concentrations of bile salts within the colon inhibit sodium and water reabsorption, resulting in

diarrhea. Patients who have undergone resection of their ileum may suffer from diarrhea due to this

process. These patients may be treated with the bile-binding resin, cholestyramine, to help alleviate

their symptoms.

Vitamin Absorption

Fat-soluble vitamins (A, D, E, and K) are incorporated into micelles along with fats in order to pass into

the enterocyte. These vitamins are then processed and packaged into chylomicrons so that they can exit

into the lymphatic system. Water-soluble vitamins are absorbed in the jejunum and ileum through a

variety of mechanisms. Vitamin C (ascorbic acid), biotin, and niacin are transported by Na+-dependent

mechanisms. Folate, vitamin B1

(thiamine), and vitamin B2

(riboflavin) are absorbed by Na+-

independent mechanisms and vitamin B6

is absorbed by passive diffusion.25

Vitamin B12

(cobalamin) absorption is dependent on the presence of intrinsic factor, a glycoprotein

produced by the gastric parietal cells. One molecule of intrinsic factor binds two molecules of cobalamin

to form a complex which attaches to a specific membrane receptor in the terminal ileum. Unbound

cobalamin cannot be absorbed. Cobalamin becomes unbound from its complex in the enterocyte and

exits from the cell into the portal circulation with the aid of B12

-binding proteins called transcobalamins.

Cobalamin is essential for DNA synthesis and a deficiency usually presents with megaloblastic anemia.

Inability to absorb sufficient amounts of cobalamin may be due to lack of intrinsic factor after proximal

or total gastrectomy, autoimmunity to gastric parietal cells or intrinsic factor, or atrophic gastritis. In

addition, cobalamin-intrinsic factor complexes may fail to be absorbed due to distal ileal disease or

resection, and cobalamin deficiency may occur from bacterial overgrowth due to bacterial

overconsumption of cobalamin.

Small Intestinal Microbiota

8 The importance of the microbiota of the small intestine on metabolism and its impact on health and

disease processes are increasingly being realized. The small intestine is not highly populated by bacteria

due to its relatively inhospitable environment, which is comprised of a variety of antimicrobial proteins,

immunoglobulins, and a low pH. Bacterial populations of the small intestine have been estimated at

103/g in the duodenum to 108/g in the distal ileum, but despite these relatively low populations there is

evidence that there is interplay between the microbes and the intestinal lining that may directly affect

intestinal health.26 The role of microbes and bile acid metabolism is relatively well understood, but new

findings about the regulation of bile acid conjugation are cited as possible factors in irritable bowel

disease and inflammatory bowel disease.27 Metabolism of fatty acids, dietary fiber, and amino acids

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alter the production of microbial anti-inflammatory and proinflammatory factors and is thought to play

an important role in mucosal integrity and translocation, as well as, hepatic function and may have a

role in the pathogenesis of nonalcoholic fatty liver disease.28–32 While the exact mechanisms of many of

the interactions between the gut microflora and the small intestinal microenvironment are still

speculative, it has become evident that a symbiotic environment is present which, at least in part, is

responsible for proper homeostasis of the small intestine.

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