Digestion and Absorption in the

Gastrointestinal Tract
The major foods on which the body lives (with the exception of small quantities of substances
such as vitamins and minerals) can be classified as carbohydrates, fats, and proteins. They
generally cannot be absorbed in their natural forms through the gastrointestinal mucosa, and for
this reason, they are useless as nutrients without preliminary digestion.
Almost all the carbohydrates of the diet are either large polysaccharides or disaccharides, which are
combinations of monosaccharides bound to one another by condensation.

This phenomenon means that a hydrogen ion (H+) has been removed from one of the
monosaccharides, and a hydroxyl ion (OH−) has been removed from the next one.

The two monosaccharides then combine with each other at these sites of removal, and the
hydrogen and hydroxyl ions combine to form water (H2O). When carbohydrates are digested, this
process is reversed and the carbohydrates are converted into monosaccharides.
Hydrolysis of Carbohydrates
Proteins are formed from multiple amino acids that are bound together by peptide linkages.

At each linkage, a hydroxyl ion has been removed from one amino acid and a hydrogen ion has

been removed from the succeeding one; thus, the successive amino acids in the protein chain are

also bound together by condensation, and digestion occurs by the reverse effect: hydrolysis. That

is, the proteolytic enzymes return hydrogen and hydroxyl ions from water molecules to the

protein molecules to split them into their constituent amino acids.

Hydrolysis of Proteins
Almost the entire fat portion of the diet consists of triglycerides (neutral fats), which are combinations

of three fatty acid molecules condensed with a single glycerol molecule. During condensation, three

molecules of water are removed.

Hydrolysis (digestion) of the triglycerides consists of the reverse process: the fat-digesting enzymes

return three molecules of water to the triglyceride molecule and thereby split the fatty acid molecules

away from the glycerol.

Hydrolysisi of Fats
DIGESTION OF CARBOHYDRATES
Carbohydrate Foods of the Diet
Only three major sources of carbohydrates exist in the normal human diet.

They are sucrose, which is the disaccharide known popularly as cane sugar;

lactose, which is a disaccharide found in milk;

and starches, which are large polysaccharides present in almost all non-animal foods, particularly in
potatoes and different types of grains.
Other carbohydrates ingested to a slight extent are amylose, glycogen, alcohol, lactic acid, pyruvic
acid, pectins, dextrins, and minor quantities of carbohydrate derivatives in meats.

The diet also contains a large amount of cellulose, which is a carbohydrate.

However, enzymes capable of hydrolyzing cellulose are not secreted in the human digestive tract.
Consequently, cellulose cannot be considered a food for humans.
Digestion of Carbohydrates Begins in the Mouth and Stomach
When food is chewed, it is mixed with saliva, which contains the digestive enzyme ptyalin (an α-amylase)
secreted mainly by the parotid glands. This enzyme hydrolyzes starch into the disaccharide maltose
and other small polymers of glucose that contain three to nine glucose molecules. However, the food
remains in the mouth only a short time, so probably not more than 5 percent of all the starches will have
become hydrolyzed by the time the food is swallowed
Starch digestion sometimes continues in the body and fundus of the stomach for as long as 1 hour
before the food becomes mixed with the stomach secretions.

Activity of the salivary amylase is then blocked by acid of the gastric secretions because the amylase is
essentially inactive as an enzyme once the pH of the medium falls below about 4.0.

Nevertheless, on average, before food and its accompanying saliva become completely mixed with the
gastric secretions, as much as 30 to 40 percent of the starches will have been hydrolyzed, mainly to form
maltose.
Digestion by Pancreatic Amylase
Pancreatic secretion, like saliva, contains a
large quantity of α-amylase that is almost
identical in its function to the α-amylase
of saliva but is several times as powerful.
Therefore, within 15 to 30 minutes after
the chyme empties from the stomach into
the duodenum and mixes with pancreatic
juice, virtually all the carbohydrates will
have become digested.
In general, the carbohydrates are almost totally
converted into maltose and/or other small glucose
polymers before passing beyond the duodenum or
upper jejunum.
Hydrolysis of Disaccharides and Small
Glucose Polymers Into
Monosaccharides by Intestinal
Epithelial Enzymes
The enterocytes lining the villi of the
small intestines contain four enzymes
(lactase, sucrase, maltase, and α-
dextrinase), which are capable of
splitting the disaccharides lactose,
sucrose, and maltose, plus other small
glucose polymers, into their
constituent monosaccharides.
These enzymes are located in the enterocytes
covering the intestinal microvilli brush border,
so the disaccharides are digested as they come
in contact with these enterocytes
Lactose splits into a molecule of galactose and a molecule of glucose. Sucrose splits into a molecule

of fructose and a molecule of glucose. Maltose and other small glucose polymers all split into

multiple molecules of glucose. Thus, the final products of carbohydrate digestion are all

monosaccharides.

They are all water soluble and are absorbed immediately into the portal blood.

In the ordinary diet, which contains far more starches than all other carbohydrates combined,

glucose represents more than 80 percent of the final products of carbohydrate digestion, and

galactose and fructose each seldom represent more than 10 percent.

DIGESTION OF PROTEINS
Proteins of the Diet
Dietary proteins are chemically long chains of
amino acids bound together by peptide
linkages. The characteristics of each protein are
determined by the types of amino acids in the
protein molecule and by the sequential
arrangements of these amino acids.
Pepsin, an important peptic enzyme of the
stomach, is most active at a pH of 2.0 to 3.0 and is
inactive at a pH above about 5.0. Consequently,
for this enzyme to cause digestion of protein, the
stomach juices must be acidic.
One of the important features of pepsin digestion
is its ability to digest the protein collagen, an
albuminoid type of protein that is affected little by
other digestive enzymes. Collagen is a major
constituent of the intercellular connective tissue of
meats; therefore, for the digestive enzymes to
penetrate meats and digest the other meat
proteins, it is necessary that the collagen fibers be
digested. Consequently, in persons who lack
pepsin in the stomach juices, the ingested meats
are less well penetrated by the other digestive
enzymes and, therefore, may be poorly digested.
Both trypsin and chymotrypsin split protein
molecules into small polypeptides;
carboxypolypeptidase then cleaves individual amino
acids from the carboxyl ends of the polypeptides.
Proelastase, in turn, is converted into elastase, which
then digests elastin fibers that partially
hold meats together.
Only a small percentage of the proteins are digested
all the way to their constituent amino acids by the
pancreatic juices. Most remain as dipeptides and
tripeptides.
The last digestive stage of the proteins in
the intestinal lumen is achieved
by the enterocytes that line the villi of
the small intestine, mainly in the
duodenum and jejunum. These cells
have a brush border that consists of
hundreds of microvilli projecting
from the surface of each cell.
In the membrane of each of these microvilli are
multiple peptidases that protrude
through the membranes to the exterior, where
they come in contact with the intestinal fluids.
Two types of peptidase enzymes are especially
important, aminopolypeptidase and several
dipeptidases.
They split the remaining larger polypeptides
into tripeptides and dipeptides and a few
into amino acids. The amino acids,
dipeptides, and tripeptides are easily
transported through the microvillar
membrane to the interior of the
enterocyte.
Finally, inside the cytosol of the enterocyte are
multiple other peptidases that are specific for the
remaining types of linkages between amino acids.

Within minutes, virtually all the last dipeptides and

tripeptides are digested to the final stage to form
single amino acids, which then pass on through to
the other side of the enterocyte and thence into the
blood.
More than 99 percent of the final protein
digestive products that are absorbed are
individual amino acids, with only rare
absorption of peptides and very rare
absorption of whole protein molecules. Even
these few absorbed molecules of whole
protein can sometimes cause serious allergic
or immunologic disturbances.
Fats of the Diet. By far the most abundant fats
of the diet are the neutral fats, also known as
triglycerides, each molecule of which is
composed of a glycerol nucleus and three fatty
acid side chains.
Neutral fat is a major constituent in food of
animal origin but much less so in food of plant
origin. Small quantities of phospholipids,
cholesterol, and cholesterol esters are also
present in the usual diet.
The phospholipids and cholesterol esters contain
fatty acid and therefore can be considered fats.
Cholesterol is a sterol compound that contains no
fatty acid, but it does exhibit some of the physical
and chemical characteristics of fats; in addition, it is
derived from fats and is metabolized similarly to
fats. Therefore, cholesterol is considered, from a
dietary point of view, to be a fat.
The first step in fat digestion is to physically break
the fat globules into small sizes so that the water-
soluble digestive enzymes can act on the globule
surfaces. This process is called emulsification of
the fat, and it begins by agitation in the stomach
to mix the fat with the products of stomach
digestion.
Most of the emulsification then occurs in the
duodenum under the influence of bile, the secretion
from the liver that does not contain any digestive
enzymes.
However, bile does contain a large quantity of bile
salts, as well as the phospholipid lecithin. Both of these
substances, but especially the lecithin, are extremely
important for emulsification of the fat
The polar parts (i.e., the points where ionization occurs in water) of the bile salts and lecithin
molecules are highly soluble in water, whereas most of the remaining portions of their molecules
are highly soluble in fat. Therefore, the fat-soluble portions of these liver secretions dissolve
in the surface layer of the fat globules, with the polar portions projecting.

The polar projections, in turn, are soluble in the surrounding watery fluids, which greatly decreases
the interfacial tension of the fat and makes it soluble as well.
When the interfacial tension of
a globule of nonmiscible fluid is
low, this non-miscible fluid,
upon agitation, can be broken
up into many tiny particles far
more easily than it can when
the interfacial tension is great.
Consequently, a major function of the bile salts and lecithin (especially the lecithin) in the bile is to
make the fat globules readily fragmentable by agitation with the water in the small bowel. This
action is the same as that of many detergents that are widely used in household cleaners for
removing grease.
Each time the diameters of the fat globules are significantly decreased as a result of agitation in the
small intestine, the total surface area of the fat increases manyfold.
Because the average diameter of the fat particles in the intestine after emulsification has occurred is less
than 1 micrometer, this represents an increase of as much as 1000-fold in total surface areas of the fats
caused by the emulsification process. The lipase enzymes are water-soluble compounds and can attack
the fat globules only on their surfaces.
Triglycerides Are Digested by Pancreatic Lipase
By far the most important enzyme for digestion of the triglycerides is pancreatic lipase, present in enormous
quantities in pancreatic juice, enough to digest within 1 minute all triglycerides that it can reach. The
enterocytes of the small intestine contain additional lipase, known as enteric lipase, but it is usually not
needed.
End Products of Fat Digestion Are Free Fatty Acids
Most of the triglycerides of the diet are split by pancreatic lipase into free fatty acids and 2-monoglycerides,
Bile Salts Form Micelles That
Accelerate Fat Digestion
The hydrolysis of triglycerides is a
highly reversible process; therefore,
accumulation of monoglycerides and
free fatty acids in the vicinity of
digesting fats quickly blocks further
digestion. However, the bile salts play
the additional important role of
removing the monoglycerides and
free fatty acids from the vicinity of
the digesting fat globules almost as
rapidly as these end products of
digestion are formed.
BASIC PRINCIPLES OF GASTROINTESTINAL ABSORPTION

The total quantity of fluid that must be absorbed each day by the intestines is equal to the
ingested fluid (about 1.5 liters) plus that secreted in the various gastrointestinal secretions (about
7 liters), which comes to a total of 8 to 9 liters. All but about 7.5 liters of this fluid is absorbed in
the small intestine, leaving only 1.5 liters to pass through the ileocecal valve into the colon each
day.
The stomach is a poor absorptive area of the gastrointestinal tract because it lacks the typical
villus type of absorptive membrane and also because the junctions between the epithelial cells
are tight junctions. Only a few highly lipid-soluble substances, such as alcohol and some
drugs like aspirin, can be absorbed in small quantities.
Folds of Kerckring, Villi, and Microvilli Increase the
Mucosal Absorptive Area by Nearly 1000-Fold.
Figure demonstrates the absorptive surface of
the small intestinal mucosa, showing many folds
called valvulae conniventes (or folds of
Kerckring), which increase the surface area of
the absorptive mucosa about threefold.
These folds extend circularly most of the way
around the intestine and are especially well
developed in the duodenum and jejunum,
where they often protrude up to 8
millimeters into the lumen.
Also located on the epithelial surface of the small
intestine all the way down to the ileocecal valve
are millions of small villi. These villi project about 1
millimeter from the surface of the mucosa, as
shown on the surfaces of the valvulae conniventes.
The villi lie so close to one another in the upper
small intestine that they touch in most areas, but
their distribution is less profuse in the distal small
intestine. The presence of villi on the mucosal
surface enhances the total absorptive area
another 10-fold.
Finally, each intestinal epithelial
cell on each villus is characterized
by a brush border, consisting of as
many as 1000 microvilli that are 1
micrometer in length and 0.1
micrometer in diameter and
protrude into the intestinal chyme.
These microvilli are shown in the
electron micrograph Figure. This
brush border increases the surface
area exposed to the intestinal
materials at least another 20-fold.
ABSORPTION OF SODIUM IONS
Twenty to 30 grams of sodium are secreted in the intestinal secretions each day. In addition,
the average person eats 5 to 8 grams of sodium each day. Therefore, to prevent net loss of sodium into
the feces, the intestines must absorb 25 to 35 grams of sodium each day, which is equal to about one
seventh of all the sodium present in the body.
Whenever significant amounts of intestinal secretions are lost to the exterior, as in extreme diarrhea, the
sodium reserves of the body can sometimes be depleted to lethal levels within hours. Normally,
however, less than 0.5 percent of the intestinal sodium is lost in the feces each day because it is rapidly
absorbed through the intestinal mucosa. Sodium also plays an important role in helping to absorb sugars
and amino acids.
When a person becomes dehydrated, large amounts
of aldosterone are secreted by the cortices of the
adrenal glands.

Within 1 to 3 hours this aldosterone causes increased

activation of the enzyme and transport mechanisms
for all aspects of sodium absorption by the intestinal
epithelium.
The increased sodium absorption in turn causes
secondary increases in absorption of chloride ions,
water, and some other substances.
This effect of aldosterone is especially
important in the colon because it allows
virtually no loss of sodium chloride in the feces
and also little water loss.

Thus, the function of aldosterone in the

intestinal tract is the same as that achieved by
aldosterone in the renal tubules, which also
serves to conserve sodium chloride and water
in the body when a person becomes depleted
of sodium chloride and dehydrated.
Absorption of Chloride Ions in the Small Intestine
In the upper part of the small intestine, chloride ion
absorption is rapid and occurs mainly by diffusion (i.e.,
absorption of sodium ions through the epithelium creates
electronegativity in the chyme and electropositivity in
the paracellular spaces between the epithelial cells).
Chloride ions then move along this electrical gradient to
“follow” the sodium ions. Chloride is also absorbed across
the brush border membrane of parts of the ileum and
large intestine by a brush border membrane chloride-
bicarbonate exchanger. Chloride exits the cell on the
basolateral membrane through chloride channels.
Absorption of Bicarbonate Ions in the Duodenum and Jejunum
Often large quantities of bicarbonate ions must be reabsorbed from the upper small intestine
because large amounts of bicarbonate ions have been secreted into the duodenum in both
pancreatic secretion and bile.

The bicarbonate ion is absorbed in an indirect way as follows: When sodium ions are absorbed,
moderate amounts of hydrogen ions are secreted into the lumen of the gut in exchange for
some of the sodium. These hydrogen ions, in turn, combine with the bicarbonate ions to form
carbonic acid (H2CO3), which then dissociates to form water and carbon dioxide.
The water remains as part of the chyme in the intestines, but the carbon dioxide is readily absorbed
into the blood and subsequently expired through the lungs. This process is the so-called “active
absorption of bicarbonate ions.” It is the same mechanism
that occurs in the tubules of the kidneys.

Secretion of Bicarbonate and Absorption of Chloride Ions in the Ileum and Large Intestine
The epithelial cells on the surfaces of the villi in the ileum, as well as on all surfaces of the large
intestine, have a special capability of secreting bicarbonate ions in exchange for absorption
of chloride ions. This capability is important because it provides alkaline bicarbonate ions that
neutralize acid products formed by bacteria in the large intestine.
Immature epithelial cells that continually divide to form new epithelial cells are found deep in the spaces
between the intestinal epithelial folds. These new epithelial cells spread outward over the luminal surfaces
of the intestines. While still in the deep folds, the epithelial cells secrete sodium chloride and water into the
intestinal lumen. This secretion, in turn, is reabsorbed by the older epithelial cells outside the folds, thus
providing flow of water for absorbing intestinal digestates.

The toxins of cholera and of some other types of diarrheal bacteria can stimulate the epithelial fold
secretion so greatly that this secretion often becomes much greater than can be reabsorbed, thus
sometimes causing a loss of 5 to 10 liters of water and sodium chloride as diarrhea each day. Within 1 to 5
days, many severely affected patients die of this loss of fluid alone
Active Absorption of Calcium, Iron, Potassium, Magnesium, and Phosphate
Calcium ions are actively absorbed into the blood, especially from the duodenum, and the amount of
calcium ion absorption is exactly controlled to supply the daily need of the body for calcium.

One important factor controlling calcium absorption is parathyroid hormone secreted by the
parathyroid glands, and another is vitamin D. Parathyroid hormone activates vitamin D, and the
activated vitamin D in turn greatly enhances calcium absorption.
Potassium, magnesium, phosphate, and probably still other ions can also be actively absorbed
through the intestinal mucosa.
In general, the monovalent ions are absorbed with ease and in great quantities. Bivalent ions are
normally absorbed in only small amounts; for example, maximum absorption of calcium ions is
only 1/50 as great as the normal absorption of sodium ions.

Fortunately, only small quantities of the bivalent ions are normally required daily by the body.
Cellular mechanisms of K+ secretion and
absorption. A, This mechanism pertains only to
the small intestine, which is a net absorber of K+
through solvent drag across tight junctions. The
thickness of the arrows in the inset indicates the
relative magnitude of the K+ flux through this
pathway.
B, The colon is a net secretor of K+ . The primary
mechanism is passive K+ secretion through tight
junctions, which occurs throughout the colon. The
driving force is a lumen-negative transepithelial
voltage
C, Another mechanism of K+ secretion
throughout the colon is a transcellular process
that involves the basolateral uptake of K+
through the Na-K pump and the Na/K/Cl
cotransporter, followed by the efflux of K+
through apical K+ channels.

D, Confined to the distal colon is a transcellular

mechanism of K+ absorption that is mediated
by an apical H-K pump.
The Ca2+ load presented to the small intestine comprises dietary sources and digestive
secretions. Most of the dietary Ca2+ (~1000 mg/day) comes from milk and milk products but not
all of it is bioavailable.

For example, only very little of the Ca2+ present in leafy vegetables is absorbed because of the
concomitant presence of oxalate, a salt that binds Ca2+ and reduces its availability for absorption.
The small intestine absorbs ~500 mg/day of Ca2+ , but it also secretes ~325 mg/day of Ca2+ . Thus
the net uptake is ~175 mg/day. Active, transcellular uptake of Ca2+ occurs only in the epithelial
cells of the duodenum, but Ca2+ is absorbed by passive, paracellular diffusion throughout the
small intestine.

More Ca2+ is absorbed in the jejunum and ileum by diffusion than in the duodenum by active
transport; this difference arises largely because the duodenum has a smaller total surface area and
because the flow of Ca2+ -containing fluid through the duodenum is faster.
The active transport of Ca2+ across the villous epithelial
cells of the duodenum is transcellular and is under the
control of vitamin D—primarily through genomic effects.
Transcellular Ca2+ absorption involves three steps. The
uptake of Ca2+ across the apical membrane occurs
through Ca2+ channels, driven by the electrochemical
gradient between the lumen and the cell. Cytosolic Ca2+
then binds to a protein called calbindin, which buffers
intracellular Ca2+ . This step is important because it
allows unbound (i.e., free) intracellular Ca2+ to remain
rather low despite large transcellular fluxes of Ca2+ .
A Ca2+ pump and an Na-Ca exchanger on the
basolateral membrane then extrude the Ca2+
from the cell into the interstitial fluid.

The active form of vitamin D—1,25-

dihydroxyvitamin D—stimulates all three
steps of the transcellular pathway, but its
most important effect is to enhance the
second step by increasing the synthesis of
calbindin.
Vitamin D itself is a fat-soluble vitamin that is absorbed mainly in the jejunum.

Of course, the skin synthesizes vitamin D3 from cholesterol in a process that requires
ultraviolet light. Thus, dietary vitamin D (both vitamin D2 and D3) is most important in
regions of the world that do not receive much sunlight and during long, dark winters.
Mg2+ absorption by the gastrointestinal tract is not yet well understood, but it appears to differ
substantially from the absorption of the other key divalent cation, Ca2+ , in three important respects.

First, an active transport process for Mg2+ absorption appears to exist in the ileum, rather than in the
duodenum, as is the case for Ca2+ .

Second, 1,25-dihydroxyvitamin D does not consistently increase Mg2+ absorption.

Third, patients with increased intestinal Ca2+ absorption (e.g., absorptive hypercalciuria) have normal
Mg2+ absorption. Along with active Mg2+ absorption in the ileum, the rest of the small intestine
absorbs Mg2+ passively.
Mg2+ absorption by the gastrointestinal tract is not yet well understood, but it appears to differ
substantially from the absorption of the other key divalent cation, Ca2+ , in three important
respects.

First, an active transport process for Mg2+ absorption appears to exist in the ileum, rather than in
the duodenum, as is the case for Ca2+ .

Second, 1,25-dihydroxyvitamin D does not consistently increase Mg2+ absorption.

Third, patients with increased intestinal Ca2+ absorption (e.g., absorptive hypercalciuria) have
normal Mg2+ absorption. Along with active Mg2+ absorption in the ileum, the rest of the small
intestine absorbs Mg2+ passively.
 Iron
Absorption
Heme and nonheme iron are absorbed in the duodenum by distinct cellular mechanisms Iron
plays several critical roles in human physiology, both in the heme groups of the cytochromes
and as a key component of the oxygen-carrying heme moieties of hemoglobin and myoglobin.

The most important complication of iron depletion is anemia. Iron overload produces
hemochromatosis, a not uncommon genetic disease.

Overall iron absorption is low; 10% to 20% of ingested iron is absorbed. Heme iron is absorbed
more efficiently than nonheme iron.
Nonheme Iron may be either ferric
(Fe3+ ) or ferrous (Fe2+ ). Ferric iron
tends to form salt complexes with
anions quite easily and thus is not
readily absorbed; it is not soluble at
pH values higher than 3. Ferrous iron
does not complex easily and is
soluble at pH values as high as 8.
Ascorbic acid (vitamin C) forms soluble complexes with iron and reduces iron from the ferric to the
ferrous state, thereby enhancing iron absorption. Tannins, present in tea, form insoluble complexes with
iron and lower its absorption.

The absorption of nonheme iron is restricted to the duodenum. The enterocyte takes up nonheme iron
across the apical membrane through the divalent metal transporter DMT1 (SLC11A2), which
cotransports Fe2+ and H+ into the cell.
DMT1, as well as the oligopeptide
cotransporter is unusual in being energized by
the inwardly directed H+ gradient. DMT1 also
efficiently absorbs a host of other divalent
metals, including several that are highly toxic
(e.g., Cd2+, Pb2+ ).

In the case of dietary ferric iron, the ferric

reductase Dcytb—which is related to
cytochrome b—presumably reduces Fe3+ to
Fe2+ at the extracellular surface of the apical
membrane before uptake through DMT1.
Fe2+ moves into the cytoplasm of the enterocyte,
where it binds to mobilferrin, an intracellular
protein that ferries the Fe2+ to the basolateral
membrane. The enterocyte then translocates the
Fe2+ across the basolateral membrane, possibly
through ferroportin transporter (FP1, also known
as IREG1). The mRNA encoding FP1 has an iron-
responsive element in its 5′ untranslated region;
thus, an increase in intracellular iron levels would
be expected to decrease FP1 synthesis.
Following the exit of Fe2+ from the enterocyte
through FP1, the ferroxidase hephaestin—a
homologue of the plasma protein ceruloplasmin,
which carries copper—apparently oxidizes the Fe2+
to Fe3+ , which then binds to plasma transferrin for
carriage in the blood.

Once in the circulation, nonheme iron bound to

transferrin is ultimately deposited in all the tissues of
the body, but it has a particular predilection for the
liver and reticuloendothelial system. Inside these
cells, it binds to the protein apoferritin to form
ferritin, the major storage form of iron. Smaller
amounts of storage iron exist in an insoluble form
called hemosiderin.
Heme Iron Derived from myoglobin and
hemoglobin, heme iron is also absorbed by
duodenal epithelial cells. Heme iron enters the
cells either by binding to a brush border protein or
through an endocytotic mechanism. Inside the
cell, heme oxygenase enzymatically splits the
heme iron, thus releasing free Fe3+ , CO, and
biliverdin. The cell reduces the biliverdin to
bilirubin, which the liver eventually excretes in
bile. The enterocyte reduces the Fe3+ to Fe2+ ,
which it then handles in the same manner as
nonheme iron.
Iron absorption is tightly regulated by the size of existing body iron stores. In physiologically normal
subjects, iron absorption is limited but is markedly increased in states of iron deficiency, caused most
often by gastrointestinal bleeding or excessive menstrual flow.

For example, the expressions of DMT1 and FP1 increase in iron deficiency. Conversely, an increase in
iron stores modestly reduces iron absorption.

Recent attention has focused on a 25–amino acid peptide secreted by hepatic Kupffer’s cells, hepcidin,
which appears to downregulate duodenal iron absorption by regulating DMT1 activity as well as other
proteins in the iron-responsive pathways (e.g., FP1).

Hepcidin likely is a negative regulator of iron absorption because mice that fail to express hepcidin
have elevated body iron stores, whereas mice with enhanced hepcidin expression have profound iron
deficiency.
B12(Cobalamin)
Absorption
Cobalamin reaches the stomach bound to
proteins in ingested food. In the stomach,
pepsin and the low gastric pH release the
cobalamin from the ingested proteins. The
now-free cobalamin binds to haptocorrin
(formerly known as “R” type binder), a
glycoprotein secreted by the salivary and
gastric glands. The parietal cells of the stomach
secrete a second protein, intrinsic factor (IF),
crucial for the absorption of cobalamin.
However cobalamin and IF do not interact in the
acidic milieu of the stomach. Rather, gastric acidity
enhances the binding of cobalamin to haptocorrin.
When this cobalamin-haptocorrin complex reaches
the duodenum, the haptocorrin is degraded by
pancreatic proteases.

After the release of cobalamin from the cobalamin-

haptocorrin complex in the proximal small
intestine—made alkaline by the secretion of HCO3 −
from the pancreas and duodenum—both dietary
cobalamin and cobalamin derived from bile bind to
IF. The cobalamin-IF complex is highly resistant to
enzyme degradation.
Similar to pepsinogen secretion, histamine triggers an IF release that peaks within minutes and
then continues at a reduced rate. This secretory pattern is related to the secretion of preformed
IF; histamine has no effect on IF synthesis.

H2 histamine-receptor antagonists block IF secretion, but omeprazole, an inhibitor of the

parietal cell H-K pump, does not affect IF secretion.
Tetrahydrofolate has three parts: the biologically active
pteridine moiety, a p-aminobenzoate, and a glutamate.
PteGlu1 is the oxidized form of folate and is biologically
inactive.

B, Dietary folate is similar to medicinal folate but has

Folat Emilimi
several glutamate residues. PteGlu7 is also oxidized and
inactive.
C, In the proximal small intestine, a brush
border peptidase sequentially removes all
but the last of the glutamate residues from
dietary folate. The enterocyte then absorbs
the resulting PteGlu1 using a folate-OH
exchanger. Once inside the enterocyte, the
PteGlu1 exists across the basolateral
membrane through an unknown transporter.

The enterocyte may reduce some of the

PteGlu1 to DHF and then to THF, the
biologically active form of folate. The
enterocyte may then methylate some of the
THF to form N5 -methyl-THF.
ABSORPTION IN THE LARGE INTESTINE: FORMATION OF FECES
About 1500 milliliters of chyme normally pass through the ileocecal valve into the large intestine
each day. Most of the water and electrolytes in this chyme are absorbed in the colon, usually leaving
less than 100 milliliters of fluid to be excreted in the feces. Also, essentially all the ions are absorbed,
leaving only 1 to 5 mEq each of sodium and chloride ions to be lost in the feces. Most of the
absorption in the large intestine occurs in the proximal one half of the colon, giving this portion
the name absorbing colon, whereas the distal colon functions principally for feces storage until a
propitious time for feces excretion and is therefore called the storage colon.
Absorption and Secretion of Electrolytes and Water
The mucosa of the large intestine, like that of the small intestine, has a high capability for active absorption of
sodium, and the electrical potential gradient created by sodium absorption causes chloride absorption as well.
The tight junctions between the epithelial cells of the large intestinal epithelium are much tighter than those
of the small intestine. This characteristic prevents significant amounts of back-diffusion of ions through these
junctions, thus allowing the large intestinal mucosa to absorb sodium ions far more completely—that is,
against a much higher concentration gradient—than can occur in the small intestine. This is especially true
when large quantities of aldosterone are available because aldosterone greatly enhances sodium transport
capability.
In addition, as occurs in the distal portion of the small intestine, the mucosa of the large intestine
secretes bicarbonate ions while it simultaneously absorbs an equal number of chloride ions in an
exchange transport process. The bicarbonate helps neutralize the acidic end products of bacterial
action in the large intestine.

Absorption of sodium and chloride ions creates an osmotic gradient across the large intestinal
mucosa, which in turn causes absorption of water.

Maximum Absorption Capacity of the Large Intestine

The large intestine can absorb a maximum of 5 to 8 liters of fluid and electrolytes each day. When
the total quantity entering the large intestine through the ileocecal valve or by way of large
intestine secretion exceeds this amount, the excess appears in the feces as diarrhea.
Bacterial Action in the Colon
Numerous bacteria, especially colon bacilli, are present even normally in the absorbing colon. They are
capable of digesting small amounts of cellulose, in this way providing a few calories of extra nutrition for
the body. In herbivorous animals, this source of energy is significant, although it is of negligible importance
in human beings.
Other substances formed as a result of bacterial activity are vitamin K, vitamin B12, thiamine, riboflavin,
and various gases that contribute to flatus in the colon, especially carbon dioxide, hydrogen gas, and
methane. The bacteria-formed vitamin K is especially important because the amount of this vitamin in the
daily ingested foods is normally insufficient to maintain adequate blood coagulation.
Composition of the Feces
The feces normally are about three-fourths water and one-fourth solid matter that is composed of
about 30 percent dead bacteria, 10 to 20 percent fat, 10 to 20 percent inorganic matter, 2 to 3
percent protein, and 30 percent undigested roughage from the food and dried constituents of
digestive juices, such as bile pigment and sloughed epithelial cells. The brown color of feces is caused
by stercobilin and urobilin, derivatives of bilirubin. The odor is caused principally by products of
bacterial action; these products vary from one person to another, depending on each person’s
colonic bacterial flora and on the type of food eaten. The actual odoriferous products include indole,
skatole, mercaptans, and hydrogen sulfide.