540
Chapter 15
be absorbed, vitamin B
12
must fi rst bind to a protein, known
as
intrinsic factor,
secreted by the acid-secreting cells in the
stomach. Intrinsic factor with bound vitamin B
12
then binds
to specifi c sites on the epithelial cells in the lower portion of
the ileum, where vitamin B
12
is absorbed by endocytosis. As
described in Chapter 12, vitamin B
12
is required for erythro-
cyte formation, and defi ciencies result in
pernicious anemia
.
This form of anemia may occur when the stomach either has
been removed (for example, to treat ulcers or gastric can-
cer) or fails to secrete intrinsic factor (often due to autoim-
mune destruction of parietal cells). Because the absorption
of vitamin B
12
occurs in the lower part of the ileum, removal
or dysfunction of this segment due to disease can also result
in pernicious anemia. Although normal individuals can
absorb oral vitamin B
12
, it is not very effective in patients
with pernicious anemia because of the absence of intrinsic
factor. Therefore, the treatment of pernicious anemia usually
requires injections of vitamin B
12
.
Water and Minerals
Water is the most abundant substance in chyme. Approximately
8000 ml of ingested and secreted water enter the small intestine
each day, but only 1500 ml pass on to the large intestine because
80 percent of the fl uid is absorbed in the small intestine. Small
amounts of water are absorbed in the stomach, but the stomach
has a much smaller surface area available for diffusion and lacks
the solute-absorbing mechanisms that create the osmotic gra-
dients necessary for net water absorption. The epithelial mem-
branes of the small intestine are very permeable to water, and net
water diffusion occurs across the epithelium whenever a water
concentration difference is established by the active absorption
of solutes. The mechanisms coupling solute and water absorp-
tion by epithelial cells were described in Chapter 4.
Sodium ions account for much of the actively transported
solute because they constitute the most abundant solute in
chyme. Sodium absorption is a primary active process, using
the Na
+
/K
+
-ATPase pumps as described in Chapter 4 and
similar to that for renal tubular sodium and water reabsorption
(Chapter 14). Chloride and bicarbonate ions are absorbed with
the sodium ions and contribute another large fraction of the
absorbed solute.
Other minerals present in smaller concentrations, such as
potassium, magnesium, and calcium, are also absorbed, as are
trace elements such as iron, zinc, and iodide. Consideration of
the transport processes associated with each of these is beyond
the scope of this book, and we shall briefl y consider as an
example the absorption of only one—iron. Calcium absorp-
tion and its regulation were described in Chapter 11.
Iron
Iron is necessary for normal health because it is the O
2
-
binding component of hemoglobin, and it is also a key com-
ponent of many enzymes. Only about 10 percent of ingested
iron is absorbed into the blood each day. Iron ions are actively
transported into intestinal epithelial cells, where most of them
are incorporated into ferritin, the protein-iron complex that
functions as an intracellular iron store (Chapter 12). The
absorbed iron that does not bind to ferritin is released on the
blood side, where it circulates throughout the body bound to
the plasma protein transferrin. Most of the iron bound to fer-
ritin in the epithelial cells is released back into the intestinal
lumen when the cells at the tips of the villi disintegrate, and
the iron is then excreted in the feces.
Iron absorption depends on the body’s iron content.
When body stores are ample, the increased concentration of
free iron in the plasma and intestinal epithelial cells leads to an
increased transcription of the gene encoding the ferritin pro-
tein and thus an increased synthesis of ferritin. This results in
the increased binding of iron in the intestinal epithelial cells
and a reduction in the amount of iron released into the blood.
When body stores of iron decrease (for example, after a loss
of blood), the production of intestinal ferritin decreases. This
leads to a decrease in the amount of iron bound to ferritin,
thereby increasing the unbound iron released into the blood.
Once iron has entered the blood, the body has very little
means of excreting it, so it accumulates in tissues. Although the
control mechanisms for iron absorption tend to maintain the
iron content of the body at a fairly constant level, a very large
ingestion of iron can overwhelm them, leading to an increased
deposition of iron in tissues and producing toxic effects such
as skin pigmentation, diabetes mellitus, liver and heart failure,
and decreased testicular function. This condition is termed
hemochromatosis
.
Some people have genetically defective con-
trol mechanisms and therefore develop hemochromatosis even
when iron ingestion is normal. They can be treated with fre-
quent blood withdrawal (
phlebotomy
), which removes iron
contained in red blood cells (hemoglobin) from the body.
Iron absorption also depends on the types of food ingested
because it binds to many negatively charged ions in food, which
can retard its absorption. For example, iron in ingested liver is
much more absorbable than iron in egg yolk because the latter
contains phosphates that bind the iron to form an insoluble
and unabsorbable complex.
The absorption of iron is typical of that of most trace
metals in several respects: (1) cellular storage proteins and
plasma carrier proteins are involved, and (2) the control of
absorption, rather than urinary excretion, is the major mecha-
nism for the homeostatic control of the body’s content of the
trace metal.
How Are Gastrointestinal
Processes Regulated?
Unlike control systems that regulate variables in the internal
environment, the control mechanisms of the gastrointestinal
system regulate conditions in the lumen of the tract. With few
exceptions, like those just discussed for iron and other trace
metals, these control mechanisms are governed by the volume
and composition of the luminal contents rather than by the
nutritional state of the body.
Basic Principles
Gastrointestinal refl exes are initiated by a relatively small num-
ber of luminal stimuli: (1) distension of the wall by the vol-
ume of the luminal contents; (2) chyme osmolarity (total solute
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