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CASE 31
A 23-year-old male college student presents to his primary care physician with
abdominal pain, bloating, flatulence, and diarrhea after eating ice cream. He
denies fever, sick contacts, or recent travel. His father has a history of similar
symptoms. The patient is diagnosed with lactose intolerance and is given medications to help him digest dairy products.
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◆
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What products of carbohydrate digestion are absorbed in the small
intestine?
What products of protein digestion are absorbed in the small
intestine?
What products of lipid digestion are absorbed in the small
intestine?
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CASE FILES: PHYSIOLOGY
ANSWERS TO CASE 31: GASTROINTESTINAL
DIGESTION AND ABSORPTION
Summary: A 23-year-old man has a history of abdominal pain, bloating, flatulence, and diarrhea shortly after eating ice cream.
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Carbohydrate digestion products absorbed: Glucose, galactose, and
fructose.
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Protein digestion products absorbed: Amino acids, dipeptides, and
tripeptides.
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Lipid digestion products absorbed: Fatty acids, monoglycerides,
cholesterol, and lysophospholipids.
CLINICAL CORRELATION
Lactose intolerance is a problem that results from an absence of lactase in the
brush border of the small intestine. Lactase is responsible for breaking down
lactose into glucose and galactose, which are absorbed. The undigested and
unabsorbed lactose increases the osmotic gradient of the luminal contents, preventing the absorption of water. The increased retention of fluid results in the
symptoms of diarrhea with its abdominal distention and cramping. The bacteria in the colon ferment the lactose into a variety of gases, leading to increased
flatulence. This condition may be inherited (adult lactase deficiency) or secondary (temporary) after acute infectious gastroenteritis or mucosal damage
from nonsteroidal anti-inflammatory drugs (NSAIDs) or other medications.
Chronic small intestinal disorders also may cause lactase deficiency because
of brush border mucosal damage. Patients with this condition are encouraged
to study ingredient labels on foods and avoid products that contain milk, lactose, or dry milk solids. Lactase supplements may be taken 30 minutes before
consumption of the lactose-containing products to prevent symptoms.
APPROACH TO GASTROINTESTINAL DIGESTION
AND ABSORPTION
Objectives
1.
2.
3.
4.
Describe the digestion and absorption of carbohydrates.
Describe the digestion and absorption of proteins.
Describe the digestion and absorption of lipids.
Discuss the absorption of vitamins.
CLINICAL CASES
259
Definitions
a-dextrinase: An enzyme located on enterocyte brush border membranes
that is involved in the digestion of starch.
Maltase-glucoamylase: An enzyme located on enterocyte brush border
membranes that is involved in the digestion of starch and maltose.
Sucrase-isomaltase: An enzyme located on enterocyte brush border membranes that is involved in the digestion of starch and sucrose.
Lactase: An enzyme located on enterocyte brush border membranes that is
involved in the digestion of lactose.
DISCUSSION
The complex nutrients ingested in a meal for the most part cannot be
absorbed intact from the gastrointestinal tract. They first must be broken
down, mostly by enzymatic processes, to simpler molecules. These molecules then are absorbed by a variety of passive and active mechanisms. The
major nutrients involved are carbohydrates, proteins, lipids, and vitamins.
Carbohydrates
The major carbohydrates in the diet are complex starches (amylopectin and
amylose) and the disaccharides sucrose, maltose, lactose, and trehalose,
none of which can be absorbed as such. The digestion of starch begins in the
mouth through the action of salivary amylase. This enzyme is active not only
in the mouth as the food is chewed and swallowed but also in the orad stomach until it mixes with and becomes inactivated by gastric acid. No further carbohydrate digestion takes place after that until gastric contents are emptied
into the duodenum. There, contents are mixed with pancreatic amylase,
which continues the breakdown. The products of salivary and pancreatic amylase digestion are maltose, maltotriose, and a-dextrins. Ingested disaccharides undergo no breakdown until they reach the small intestine. In the
intestine, the digestion of the oligo- and disaccharides continues through the
actions of enzymes located on enterocyte brush borders. The enzymes
a-dextrinase, maltase-glucoamylase, and sucrase-isomaltase hydrolyze
the products of starch digestion by amylase to yield glucose. Sucraseisomaltase also hydrolyzes sucrose to glucose and fructose. Lactose is
hydrolyzed entirely by lactase to yield glucose and galactose, and trehalose
is hydrolyzed entirely by trehalase to yield glucose.
The glucose and galactose liberated during digestion are absorbed
across the enterocyte apical membrane by a shared secondary active transport system (termed SGLT-1) that is driven by the coabsorption of sodium.
Fructose, in contrast, is absorbed via facilitated diffusion through the actions
of the carrier GLUT-5. After entering the enterocyte, all three monosaccharides
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CASE FILES: PHYSIOLOGY
exit from the basolateral membrane by facilitated diffusion, using the carrier
GLUT-2. Most of the enzymes involved in carbohydrate digestion are present
in relatively high amounts throughout life. Lactase, however, is high at birth
and then in most people decreases in later life. In many people, the enzyme
decreases to such low levels by the third and fourth decades that lactose intolerance develops, as described in this case.
Proteins
Dietary protein and the protein contained in gastrointestinal secretions and
from cells shed into the lumen of the gastrointestinal tract are acted on by several enzymes to yield amino acids and oligopeptides. The process of protein
digestion begins in the stomach through the action of pepsin, which itself is
an enzyme protein derived from the precursor pepsinogen, which is secreted
by chief cells of the stomach. Once activated by acid, pepsin acts as an
endopeptidase to cleave interior peptide bonds. The major digestion of protein, however, takes place in the small intestine. There, contents are mixed
with the many proteases secreted by the pancreas as proenzymes. A key
enzyme is trypsin, which is secreted as trypsinogen. The initial secreted
trypsinogen is converted to trypsin through the action of the brush border
enzyme enterokinase. This trypsin then not only attacks peptide bonds in the
ingested proteins but also converts additional trypsinogen and the precursors
chymotrypsinogen, proelastase, and the procarboxypeptidases to their active
forms. Together, these endo- and exopeptidases liberate amino acids and peptides of varying length.
In addition to this luminal digestion, there are peptidases on the brush
border that assist in the breakdown of larger peptides to di- and tripeptides
and amino acids. Unlike the situation in carbohydrate absorption, where only
monosaccharides are absorbed, di- and tripeptides are absorbed readily
across enterocyte apical membranes along with amino acids. Several
carrier-mediated transport systems are involved in peptide and amino acid
absorption, including some that are secondary active systems that require
sodium. Once in the cell, most dipeptides and tripeptides are hydrolyzed to
amino acids, which then exit with the other amino acids through transporters
on enterocyte basolateral membranes.
Lipids
Triglycerides, phospholipids, and cholesterol esters are the major lipids
contained in the diet. Their digestion and absorption are rather complicated
because of their insolubility in water. The breakdown of triglycerides begins
in the mouth through the actions of lingual lipase. However, this activity,
along with the activity of gastric lipase, accounts for only about 10% of
triglyceride breakdown. Perhaps more important is the mechanical dispersal
CLINICAL CASES
261
and emulsification of lipids that take place in the stomach as a result of gastric contractions. This prepares the lipids for further emulsification and
breakdown by chemical (bile) and enzymatic processes in the small intestine.
Once in the small intestine, the lipid is acted on by pancreatic lipase, which
is anchored to emulsified lipid droplets by colipase, which also is secreted by
the pancreas. Colipase serves to anchor lipase to the fat droplet and to facilitate the passage of fat digestion (fatty acids and monoglycerides) to adjacent
bile salt micelles.
Phospholipids present in the diet and in biliary secretions and sloughed
cells are broken down by pancreatic phospholipases, mainly phospholipase
A2, to fatty acids and lysophospholipids. Cholesterol esters are broken down
by pancreatic cholesterol ester hydrolase (nonspecific hydrolase). The products of lipid digestion, except for some of the medium-chain and short-chain
fatty acids, are taken up into micelles, which deliver them to enterocyte apical membranes. There they diffuse from the micelles and are absorbed, along
with the medium- and short-chain fatty acids, mostly by simple diffusion.
Once inside the enterocyte, triglycerides, containing mostly long-chain fatty
acids and phospholipids are resynthesized and combined with cholesterol
to form, along with apoproteins, chylomicrons. These relatively large
lipoproteins fuse with the enterocyte basolateral membrane and are secreted
by exocytosis to be taken up in the lymph. The medium- and short-chain
fatty acids pass through the enterocytes unchanged and are taken up into
the bloodstream.
Vitamins
Vitamins are contained in the complex foods that humans ingest and are liberated and absorbed through some of the same processes discussed above.
Many of the vitamins, such as thiamine (B1), riboflavin (B2), C, biotin, folic
acid, niacin, and pantothenic acid, are water soluble and enter across enterocyte apical membranes by secondary active transport coupled to
sodium. Pyridoxine (B6) is water soluble and appears to be absorbed by
restricted diffusion. The cobalamin (B12) that is released during digestion in
the stomach is bound to and protected by glycoproteins (R proteins)
secreted by salivary glands and gastric cells. The B12 released from this complex and from food during digestion in the upper small intestine is bound to
intrinsic factor, another glycoprotein secreted by gastric parietal cells. This
complex, which is protected from further digestion, is propelled to the ileum,
where it is taken up by a carrier-mediated transport mechanism. Other
vitamins, such as A, D, E, and K, are fat soluble. Once released from foods
during digestion, mainly in the small intestine, they are taken up into micelles
and delivered to enterocyte apical membranes, where they are absorbed mainly
by simple diffusion.
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CASE FILES: PHYSIOLOGY
COMPREHENSION QUESTIONS
[31.1]
Tests show that glucose is absorbed as expected by a patient if
sucrose, lactose, or glucose is ingested, but not if complex starches
are ingested. These data indicate a defect in which of the following?
A.
B.
C.
D.
E.
[31.2]
A patient is experiencing steatorrhea. Tests show that the enterohepatic circulation of bile salts is normal and that absorption of orally
administered glucose is normal. A disorder in which of the following
is most likely to be present?
A.
B.
C.
D.
E.
[31.3]
Bile acid secretion
Brush border enzyme levels
Epithelial sodium-coupled glucose transport
Pancreatic enzyme secretion
Villus surface area
Brush border enzyme levels
Gastric motility
Ileal motility
Pancreatic enzyme secretion
Villus surface area
A patient presents with signs of cystinuria. Tests indicate that when a
solution of free amino acids is infused intraduodenally, absorption of
arginine is impaired; however, if a solution of dipeptides is infused
intraduodenally, arginine absorption is almost normal. These data
indicate that the patient has a deficiency in which of the following?
A. All sodium-coupled secondary active transport pathways in intestinal
epithelia
B. Basic amino acid transporters in intestinal epithelia
C. Bile acid synthesis
D. Epithelial cell peptidase activity
E. Pancreatic enzyme secretion
Answers
[31.1]
D. The fact that free glucose is absorbed readily indicates that villus
surface area and sodium-coupled transport are normal. The fact that
glucose is absorbed when disaccharides are ingested indicates that
brush border enzymes are intact. Because complex starches must be
broken down first by enzymes secreted by salivary glands (minor)
and the pancreas, the impaired glucose absorption seen when starches
are ingested, points toward a problem with pancreatic enzyme
secretion.