Absorption

Almost all ingested food, about 80% of electrolytes, and about 90% of water are absorbed in the small intestine. Although the entire small intestine participates in the absorption of water and lipids, most carbohydrate and protein absorption 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 match the body’s current needs.

Fat-soluble vitamins (A, D, E, and K) are absorbed along with dietary lipids in micelles by simple diffusion. Most water-soluble vitamins (including most B vitamins and vitamin C) are also absorbed by simple diffusion.

Intrinsic factor, secreted in the stomach, binds vitamin B12. This binding prevents vitamin B12 digestion and forms a complex that binds to mucosal receptors in the terminal ileum, where it is taken up by endocytosis.

After absorption:

• Water-soluble nutrients enter the capillary blood in the villi and travel to the liver via the portal vein.
• Lipids enter the lacteals of the villi and are transported by lymphatic vessels to the systemic circulation via the thoracic duct.
• All absorbed nutrients, except 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 across the apical membrane of the enterocyte by secondary active transport. This is mediated by the Na+ glucose cotransporter (SGLUT 1), which moves glucose or galactose against its electrochemical gradient.

The energy for this transport comes from the Na+ gradient, which is maintained by the Na-K ATPase in the basolateral membrane. After entering the enterocyte, glucose and galactose leave the cell across the basolateral membrane by facilitated diffusion via GLUT 2.

Fructose is absorbed at the apical membrane by GLUT 5 and exits across the basolateral membrane through GLUT 2.

Trypsin and brush border proteases are the most important enzymes for protein digestion. Pepsin contributes, but it isn’t essential. Trypsinogen in pancreatic secretions is converted to active trypsin by the brush border enzyme enterokinase (enteropeptidase). Trypsin then activates other pancreatic proteases and also activates additional trypsinogen.

The H+ cotransporter for dipeptides and tripeptides uses the H+ gradient created by the Na±H+ exchanger in the apical membrane.

Bile salts emulsify dietary lipids, which supports lipid digestion. Pancreatic lipase is secreted as an active enzyme, but it requires colipase for full activity. The products of lipid digestion form micelles, which support lipid absorption.

At the intestinal brush border:

• Lipids are released from micelles and enter the enterocyte.
• Inside the enterocyte, lipids are esterified in the smooth endoplasmic reticulum.
• Lipids combine with apolipoproteins (synthesized by the enterocyte) to form chylomicrons.
• Chylomicrons are packaged into secretory vesicles by the Golgi body and released by exocytosis.
• Chylomicrons then enter the lacteals, cisterna chyli, thoracic duct, and ultimately the systemic circulation.

Free vit B12 binds to R proteins (transcobalamin 1) in the saliva or stomach. Protein-bound vitamin B12 must first be released by pepsin in the stomach. In the duodenum, pancreatic proteases degrade the R proteins, allowing vit B12 to bind intrinsic factor. Intrinsic factor protects vit B12 from degradation and supports its absorption.

In the ileum, the vitamin B12/intrinsic factor complex is taken up into the enterocyte. Absorbed vitamin B12 then binds to transcobalamin II. Approximately 50% of the vitamin B12 is delivered to the liver, and the remainder is delivered to other tissues.

Iron absorption occurs predominantly in the duodenum and upper jejunum. Gastric acid lowers the pH in the proximal duodenum, which increases the solubility and uptake of ferric iron. Ferric reductase on the intestinal brush border converts Fe3+ to Fe2+ (the ferrous form), which is more readily absorbed.

When gastric acid production is impaired (for example, by acid pump inhibitors such as prilosec), iron absorption decreases substantially. Vitamin C and citrates aid iron absorption, while tannins (tea), phytates (wheat), and antacids interfere with iron absorption.

Heme is absorbed by a different mechanism than inorganic iron. This process is more efficient and is independent of duodenal pH, which is why 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 into the cell. Once inside the enterocyte, iron has two main fates:

• It can be stored as ferritin.
• It can be transported across the basolateral membrane into the circulation through ferroportin.

Ferroportin is the only efflux route for cellular iron and is regulated almost exclusively by hepcidin. High levels of iron, inflammatory cytokines, and oxygen increase levels of the peptide hormone hepcidin. Hepcidin binds ferroportin, which increases cellular ferritin stores and prevents iron absorption into the blood. Hepcidin also potentiates iron excretion through sloughing of enterocytes.

If hepcidin levels are low and ferroportin is not downregulated, Fe2+ can be released from the enterocyte. It is then oxidized back to Fe3+ so it can bind transferrin, its carrier protein in plasma. Two copper-containing enzymes catalyze this oxidation and support binding to transferrin:

• Ceruloplasmin (in plasma)
• Hephaestin (on the basolateral membrane of the enterocyte)

The principal role of transferrin is to chelate iron so it remains soluble, prevent the formation of reactive oxygen species, and facilitate iron transport into cells.