Small Intestine
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.
