The small intestine is the main site for the digestion of food and the absorption of the products of this digestion. It is a tube, 2.5 cm in diameter and approximately 4 m in length, and comprises the duodenum, jejunum and ileum.
When chyme first enters the duodenum, there is a continuation of gastric secretion thought to be due to the activation of G cells in the intestinal mucosa (see intestinal phase; Fig. 38e). This is short lived as the duodenum becomes more distended with further gastric emptying. A series of reflexes is initiated which inhibits the further release of gastric juices. A number of hormones are involved in these reflex responses. Secretin is released in response to acid stimulation; it reaches the stomach via the bloodstream and inhibits the release of gastrin. The presence of fatty acids, due to the breakdown of fats in the duodenum itself, releases two polypeptide hormones, called gastric inhibitory peptide (GIP) and cholecystokinin (CCK), which inhibit the release of both gastrin and acid. Both secretin and CCK, however, stimulate the release of pepsinogen from the chief cells, thereby aiding protein digestion. Together with mechanoreceptors in the duodenum via vagal and local reflex pathways, the release of secretin and CCK has also been implicated in the control of gastric emptying. The chyme that first enters the duodenum is acidic, hypertonic and only partly digested; at this early stage, the nutrients formed cannot be absorbed. There is an osmotic movement of water across the freely permeable wall which leads to the contents becoming isotonic. The acidity is neutralized by the addition of both bicarbonate secreted by the pancreas and bile from the liver, and further digestion of the chyme is performed by the addition of enzymes from the pancreas, liver and intestine itself.
The lining of the small intestine is folded into many small, finger- like projections called villi (Fig. 39). Between the villi lie some small glands, called crypts, which can secrete up to 3 L of hypotonic fluid per day. The surface of the villi is covered with a layer of epithelial cells which, in turn, have many small projections called microvilli (collectively called the brush border) that project towards the lumen of the intestine. The small intestine is particularly adapted for the absorption of nutrients. It has a huge surface area (about the size of a tennis court), and the chyme is forced into a circular motion as it passes through the tract, facilitating mixing and therefore digestion and absorption. There is a constant turnover of epithelial cells within the gastrointestinal (GI) tract, with the small intestine epithelium totally replacing itself approximately every 6 days.
Each villus contains a single, blind-ended lymphatic vessel, called a lacteal, and also a capillary network. Most nutrients are absorbed into the bloodstream via these vessels. The venous drainage from the small intestine, large intestine, pancreas and also from some parts of the stomach passes via the hepatic portal vein into the liver; here, it passes through a second capillary bed to be further processed before returning to the circulation.
Absorption of nutrients
The small intestine absorbs water, electrolytes, carbohydrates, amino acids, minerals, fats and vitamins. The mechanisms by which movement from the lumen to the circulation occurs are variable. Nutrients move between the GI tract and the blood by passing through and around the epithelial cells. As the contents of the intestine are isotonic with body fluids and mostly have the same concentration of the major electrolytes, their absorption is active. Water cannot be moved directly, but follows osmotic gradients set up by the transport of ions. The major contributor to this osmotic gradient is the sodium pump. Na+–K+ ATPase is located on the blood side of the epithelial cell (basolateral membrane), and hydrolysis of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) leads to the expulsion of three Na+ ions from the cell in exchange for two K+ ions. Both of these are against the concentration gradients, leading to a low concentration of Na+ and a high concentration of K+ within the cells. The low intracellular concentration of Na+ ensures a movement of Na+ from the intestinal contents into the cell by both membrane channels and transported protein mechanisms. Na+ is then rapidly transported out of the cell again by the basolateral Na+–K+ pump. K+ leaves the cell, again via the basolateral membrane, down its concentration gradient. This outward movement of K+ is linked to an outward movement of Cl−, against its concentration gradient, Cl− having entered down its concentration gradient like Na+ via the luminal membrane. These movements set up an osmotic gradient between the lumen and the blood, leading to water absorption following the movement of Na+ and Cl− from the lumen into the cell across the luminal membrane.
Carbohydrates are absorbed mostly in the form of monosaccharides (glucose, fructose and galactose). They are broken down into monosaccharides by enzymes released from the brush border (maltases, isomaltases, sucrase and lactase). The monosaccharides are transported across the epithelium into the bloodstream by means of cotransporter molecules that link their inward movement with that of Na+ down its concentration gradient. At the basolateral membrane, monosaccharides leave the cell either by simple diffusion or by facilitated diffusion down the concentration gradient.
The polypeptides produced in the stomach are broken down into oligopeptides in the small intestine by enzymes (proteases) secreted by the pancreas: trypsin and chymotrypsin. These are further broken down into amino acids by another pancreatic enzyme, carboxypeptidase, and an enzyme located on the luminal membrane epithelial cells, aminopeptidase. The free amino acids enter the epithelial cells by secondary active transport coupled to the movement of Na+ and a number of different cotransporter mechanisms.
Two very important minerals that are absorbed from the diet are calcium and iron. Intracellular calcium concentrations are low and any free calcium in the diet can cross the luminal membrane down a steep concentration gradient through channels or by a carrier mechanism. In the cell, it binds to a protein which carries it to the basolateral membrane, where it is actively transported against the concentration gradient by a Ca2+ ATPase with the hydrolysis of ATP, or by an Na+–Ca2+ antiporter linked with the movement of Na+ down its con- centration gradient into the cell and the removal of Ca2+ from it.
Most dietary iron is in the ferric (Fe3+) form which cannot be absorbed; however, in the ferrous (Fe2+) form, it forms soluble complexes with ascorbate and other substances and can be readily absorbed. These complexes are transported across the membrane by a carrier protein and, once in the cell, bind with a variety of substances including ferritin. A second carrier protein transports the iron across the basolateral membrane into the bloodstream.
Fats and lipids
Fat digestion occurs almost entirely in the small intestine. The major enzyme is a pancreatic enzyme called lipase which breaks fat down into monoglycerides and free fatty acids. However, before the fat can be broken down, it has to be emulsified, which is a process by which the larger lipid droplets are broken down into much smaller droplets (about 1 μm in diameter). The main emulsifying agents are the bile acids, cholic acid and chenodeoxycholic acid. The free fatty acids and monoglycerides form tiny particles (4–5 nm in diameter) with the bile acids, called micelles. The outer region of the micelle is hydrophilic (water-attracting), whereas the inner core contains the hydrophobic (water-repelling) part of the molecule. This arrangement allows the micelles to enter the aqueous layers surrounding the micro- villi, and the monoglycerides, free fatty acids, cholesterol and fat- soluble vitamins can then diffuse passively into the duodenal cells, leaving the bile salts within the lumen of the gut until they reach the ileum, where they are reabsorbed. Once within the epithelial cells, the fatty acids and monoglycerides are reassembled into fats by a number of different metabolic pathways. They then enter the lymphatic system via the lacteals and eventually reach the bloodstream through the thoracic duct.
The fat-soluble vitamins, A, D, E and K, essentially follow the pathways for fat absorption. The remaining water-soluble vitamins are mainly absorbed by diffusion or mediated transport. The exception is vitamin B12, which must first bind with intrinsic factor (secreted from the parietal cells in the stomach wall). When bound, vitamin B12 attaches to specific sites on the epithelial cells in the ileum where a process of endocytosis leads to absorption.