Absorption

Almost all ingested food, 80 percent of electrolytes, and 90 percent of water are absorbed in the small intestine. Although the entire small intestine is involved in the absorption of water and lipids, most absorption of carbohydrates and proteins occurs in the jejunum. Bile salts and vitamin B12 are absorbed in the terminal ileum. Iron and calcium are absorbed in the duodenum in amounts that meet the body’s current requirements. Fat-soluble vitamins (A, D, E, and K) are absorbed along with dietary lipids in micelles via simple diffusion. Most water-soluble vitamins (including most B vitamins and vitamin C) also are absorbed by simple diffusion. Intrinsic factor secreted in the stomach binds to vitamin B12, preventing its digestion and creating a complex that binds to mucosal receptors in the terminal ileum, where it is taken up by endocytosis. Water-soluble nutrients enter the capillary blood in the villi and travel to the liver via the portal vein. After absorption, lipids enter the lacteals of the villi to be transported by lymphatic vessels to the systemic circulation via the thoracic duct. All absorbed nutrients, except for long chain fatty acids and monoglycerides, enter the portal vein to be transported to the liver.

Mechanisms of absorption of various products of digestion

Both glucose and galactose are absorbed at the apical membrane of the enterocyte by secondary active transport. This process is carried out by Na+ Glucose cotransporter or SGLUT 1 against an electrochemical gradient. Energy for active transport is derived from the Na+ gradient created by Na-K ATPase in the basolateral membrane of the cell. Glucose and galactose are transported from the enterocyte into the bloodstream by facilitated diffusion carried out by GLUT 2. Fructose is absorbed at the apical membrane by GLUT 5 and enters the bloodstream from the basolateral through GLUT 2.

Trypsin and brush border proteases are the most important enzymes for protein digestion. Pepsin helps but is not essential. Trypsinogen in the pancreatic secretions is converted to active trypsin by the brush border enzyme enterokinase or enteropeptidase. Trypsin in turn activates all other enzymes and also activates more trypsinogen. The H+ cotransporter for di and tripeptides utilizes the H+ gradient created by Na±H+ exchanger in the apical membrane.

Bile salts emulsify dietary lipids which helps in digestion. Pancreatic lipase is secreted as an active enzyme but it needs colipase for its action. The products of lipid digestion form micelles which helps in lipid absorption. At the intestinal brush border, lipids are released from the micelles and enter the enterocyte where they are esterified in the smooth endoplasmic reticulum. The lipids combine with apolipoproteins which are synthesized by the enterocyte to form chylomicrons. The chylomicrons are packed into secretory vesicles by the Golgi body, which is followed by exocytosis where the chylomicrons enter the lacteals, cisterna chyli, thoracic duct and ultimately the systemic circulation.

Free vit B12 binds to R proteins or transcobalamin 1 in the saliva or stomach. Protein bound vitamin B12 has to be first released by pepsin in the stomach. R proteins are degraded by pancreatic proteases in the duodenum allowing the combination of vit B12 with intrinsic factor. Intrinsic factor protects it from degradation and helps in the absorption of vit B12. In the ileum, the vitamin B12/intrinsic factor complex is taken up into the enterocyte. The absorbed vitamin B12 then binds to transcobalamin II where approximately 50% of the vitamin B12 will be delivered to the liver and the remainder will be delivered to other tissues.

Iron absorption occurs predominantly in the duodenum and upper jejunum. Gastric acid lowers the pH in the proximal duodenum, enhancing the solubility and uptake of ferric iron. The enzyme ferric reductase on the intestinal brush border converts Fe3+ to Fe2+ (ferrous form) which can be easily absorbed. When gastric acid production is impaired (for instance by acid pump inhibitors such as the drug, prilosec), iron absorption is reduced substantially. Vitamin C and citrates aid iron absorption while tannins (tea), phytates (wheat) and antacids interfere with iron absorption. Heme is absorbed by a completely different mechanism than that of inorganic iron. The process is more efficient and is independent of duodenal pH . Consequently meats are excellent nutrient sources of iron. A protein on the apical membrane of enterocytes called divalent metal cation transporter 1 (DMT1) transports iron across the apical membrane and into the cell. Once inside the enterocyte, iron can be stored as ferritin or transported through the basolateral membrane and into circulation through ferroportin. The transmembrane protein ferroportin is the only efflux route of cellular iron and is regulated almost exclusively by hepcidin levels. High levels of iron, inflammatory cytokines and oxygen lead to increased levels of the peptide hormone hepcidin. Hepcidin binds ferroportin leading to increased cellular ferritin stores and preventing the absorption of iron into the blood. Hepcidin also potentiates the excretion of iron through sloughing of enterocytes. If hepcidin levels are low and ferroportin is not downregulated, ferrous (Fe2+) iron can be released from the enterocyte, where it is oxidized once again into ferric (Fe3+) iron for binding to transferrin, its carrier protein which is present in the plasma. Two copper-containing enzymes, ceruloplasmin in the plasma and hephaestin on the basolateral membrane of the enterocyte catalyze the oxidation of and subsequent binding of ferrous iron to transferrin in the plasma. The principal role of transferrin is to chelate iron so that it can be rendered soluble, prevent the formation of reactive oxygen species, and facilitate its transport into cells.