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Transcript
Chapter
40
Structure and Function of the Digestive System
Alexa K. Doig and Sue E. Huether
http://evolve.elsevier.com/McCance/
• Review Questions and Answers
• Animations
CHAPTER OUTLINE
The Gastrointestinal Tract, 1393
Mouth and Esophagus, 1395
Stomach, 1396
Small Intestine, 1400
Large Intestine, 1407
Intestinal Bacteria, 1408
Accessory Organs of Digestion, 1409
Liver, 1409
Gallbladder, 1413
Exocrine Pancreas, 1413
Tests of Digestive Function, 1415
Gastrointestinal Tract, 1415
Liver, 1416
Gallbladder, 1416
Exocrine Pancreas, 1416
AGING and the Gastrointestinal System, 1417
The digestive system breaks down ingested food, prepares it for
uptake by the body’s cells, provides body water, and eliminates
wastes. This system consists of the gastrointestinal tract and
accessory organs of digestion: the liver, gallbladder, and exocrine pancreas.
Food breakdown begins in the mouth with chewing and continues in the stomach, where food is churned and mixed with
acid, mucus, enzymes, and other secretions. From the stomach,
the fluid and partially digested food pass into the small intestine, where biochemicals and enzymes secreted by the liver,
exocrine pancreas, and small intestinal epithelium break it
down into absorbable components of proteins, carbohydrates,
and fats. These nutrients pass through the small intestinal epithelium into underlying blood vessels and lymphatics that carry
them to the liver via the hepatic portal circulation for further
processing and storage.
Ingested substances and secretions that are not absorbed
in the small intestine pass into the large intestine, where fluid
continues to be absorbed. Solid wastes pass into the rectum and
are eliminated from the body through the anus.
Except for chewing, swallowing, and defecation of solid
wastes, the activities of the digestive system are controlled by
hormones and the autonomic nervous system. As ingested
substances move through the gastrointestinal tract, they trigger the release of hormones that stimulate or inhibit (1) the
muscular contractions (gastrointestinal motility) that mix and
propel food from the esophagus to the anus, and (2) the timely
secretion of substances that aid in digestion. The autonomic
innervation, sympathetic and parasympathetic, is controlled by
centers in the brain and by local stimuli that are mediated by
neural plexuses within the gastrointestinal walls.
The Gastrointestinal Tract
The gastrointestinal tract (alimentary canal) consists of the
mouth, esophagus, stomach, small intestine, large intestine,
1393
1394
Unit XII The Digestive System
Parotid gland
Submandibular
salivary gland
Tongue
Sublingual
salivary gland
Larynx
Pharynx
Esophagus
Trachea
Diaphragm
Liver
Transverse
colon
Stomach
Spleen
Hepatic flexure
of colon
Splenic flexure
of colon
Ascending
colon
Descending
colon
Sigmoid colon
Ileum
Cecum
Vermiform
appendix
Anal canal
Rectum
FIGURE 40-1 Structures of the Digestive System.
Mesentery
Blood
vessels
Nerve
rectum, and anus (Figure 40-1). It carries out the following
digestive processes:
1.Ingestion of food
2.Propulsion of food and wastes from the mouth to the
anus
3.Secretion of mucus, water, and enzymes
4.Mechanical digestion of food particles
5.Chemical digestion of food particles
6.Absorption of digested food
7.Elimination of waste products by defecation
Histologically, the gastrointestinal tract consists of four
layers. From the inside out, they are the mucosa, submucosa,
muscularis, and serosa or adventitia (esophagus only). These
concentric layers vary in thickness, and each layer has sublayers (Figure 40-2). Neurons forming the enteric nervous system are located solely within the gastrointestinal tract and are
controlled by local and autonomic nervous system stimuli. The
enteric nervous system comprises three nerve plexuses located
in different layers of the gastrointestinal walls. The submucosal
plexus (Meissner plexus) is located in the muscularis mucosae,
the myenteric plexus (Auerbach plexus) between the inner circular and outer longitudinal muscle layers in the muscularis,
and the subserosal plexus just beneath the serosa. The enteric
(intramural) plexus neurons regulate motility reflexes, blood
flow, absorption, secretions, and immune response.1
SEROSA
Connective tissue layer
Peritoneum
Myenteric plexus
Submucosal plexus
Intramural plexus
SUBMUCOSA
Gland in submucosa
Duct from gland
MUCOSA
Mucous epithelium
Lamina propria
Muscularis mucosae
MUSCULARIS
Lymph nodule
Circular muscle layer
Longitudinal muscle
layer
FIGURE 40-2 Wall of the Gastrointestinal (GI) Tract. The wall of the GI tract is made up of four layers with a network of
nerves between the layers. Shown here is a generalized diagram of a segment of the GI tract. Note that the serosa is continuous with a fold of serous membrane called a mesentery. Note also that digestive glands may empty their products into the
lumen of the GI tract by way of ducts. (From Patton KT, Thibodeau GA: Anatomy & physiology, ed 8, St Louis, 2013, Mosby.)
Chapter 40 Structure and Function of the Digestive System
Mouth and Esophagus
The mouth is a reservoir for the chewing and mixing of food
with saliva. As food particles become smaller and move around
in the mouth, the taste buds and olfactory nerves are continuously stimulated, adding to the satisfaction of eating. The
tongue’s surface and soft palate contains thousands of chemoreceptors, or taste buds, that can distinguish salty, sour, bitter,
umami, and sweet tastes. Tastes and food odors help initiate
salivation and the secretion of gastric juice in the stomach.
There are 32 permanent teeth in the adult mouth, and they are
important for speech and mastication.
Salivation
The three pairs of salivary glands (the submandibular, sublingual, and parotid glands) (Figure 40-3) secrete about 1 L
of saliva per day. Saliva consists mostly of water that contains
varying amounts of mucus, sodium, bicarbonate, chloride,
potassium, and salivary α-amylase (ptyalin), an enzyme that
initiates carbohydrate digestion in the mouth and stomach.
The sympathetic and parasympathetic divisions of the autonomic nervous system control salivation. Because cholinergic
parasympathetic fibers stimulate the salivary glands, atropine
(an anticholinergic agent) inhibits salivation and makes the
mouth dry. β-Adrenergic stimulation from sympathetic fibers
also increases salivary secretion. The salivary glands are not regulated by hormones, although hormones are found in saliva.1a
Parotid gland
Parotid duct
Submandibular gland
Submandibular duct
Sublingual
gland
FIGURE 40-3 Salivary Glands. (From Patton KT, Thibodeau GA: Anatomy &
physiology, ed 8, St Louis, 2013, Mosby.)
1395
The composition of saliva depends on the rate of secretion.
Aldosterone can decrease the rate of secretion by increasing an
exchange of sodium for potassium. Sodium and water are conserved and potassium is excreted. The bicarbonate concentration
of saliva sustains a pH of about 7.4, which neutralizes bacterial
acids and prevents tooth decay. Saliva also contains immunoglobulin A (IgA), which helps prevent infection. Exogenous fluoride
(e.g., fluoride in drinking water) is absorbed and then secreted
in the saliva, providing additional protection against tooth decay.
Swallowing
The esophagus is a hollow muscular tube approximately 25 cm
long that conducts substances from the oropharynx to the
stomach (see Figure 40-1). The pharynx and upper third of the
esophagus contain striated muscle that is directly innervated
by skeletal motor neurons that control swallowing. The middle
third contains a mix of striated and smooth muscle, and the
lower third is smooth muscle that is innervated by preganglionic cholinergic fibers from the vagus nerve. Peristalsis is stimulated when afferent fibers distributed along the length of the
esophagus sense changes in wall tension caused by stretching
as food passes. The greater the tension, the greater the intensity
of esophageal contraction. Occasionally, intense contractions
cause pain similar to “heartburn” or angina.
Each end of the esophagus is opened and closed by a sphincter. The upper esophageal sphincter (cricopharyngeal muscle)
prevents entry of air into the esophagus during respiration.2
The lower esophageal sphincter (cardiac sphincter) prevents
regurgitation from the stomach. The lower esophageal sphincter is located near the esophageal hiatus—the opening in the
diaphragm where the esophagus ends at the stomach.3
Swallowing is a complex event mediated by the trigeminal
nucleus, nucleus tractus solitarius, and reticular formation of
the brainstem and also involves other brain regions, including
the insula/claustrum and cerebellum.4
Swallowing occurs in two phases: the oropharyngeal (voluntary) phase and the esophageal (involuntary) phase. During the
oral and pharyngeal phases of swallowing, food is segmented
into a bolus by the tongue and forced posteriorly toward the
pharynx as the tongue pushes upward against the hard palate.
The superior constrictor muscle of the pharynx contracts, preventing movement of food into the nasopharynx. At the same
time, respiration is inhibited and the epiglottis folds downward
to prevent the bolus from entering the larynx and trachea. The
movements of the tongue and pharyngeal constrictors propel
the food into the esophagus in a series of coordinated events,
taking less than 1 or 2 seconds.
During the esophageal phase of swallowing, the bolus is
transported to the stomach by the coordinated sequential contraction and relaxation of outer longitudinal and inner circular
layers of smooth muscle. The wave of relaxation reduces resistance and allows food to pass, after which the wave of contraction pushes food farther along. The terminal 1 to 2 cm portion
of the musculature forms the lower esophageal sphincter, which
relaxes just before the arrival of a peristaltic wave. The sphincter muscles return to their resting tone after the bolus of food
passes into the stomach. The esophageal phase of swallowing
1396
Unit XII The Digestive System
takes 5 to 10 seconds, with the bolus moving 2 to 6 cm/second.
Throughout swallowing, the sphincters and esophagus work
in concert with the peristaltic wave that moves food from the
mouth to the stomach.
Peristalsis that immediately follows the oropharyngeal phase
of swallowing is called primary peristalsis. If a bolus of food
becomes stuck in the esophageal lumen, the distention of the
esophageal wall stimulates secondary peristalsis, a wave of
contraction and relaxation that is independent of voluntary
swallowing. This is in response to stretch receptors that are
stimulated by increased wall tension, causing an increase in
impulses from the swallowing center of the brain.
When it is closed, the lower esophageal sphincter serves as a
barrier between the stomach and esophagus. Cholinergic vagal
stimulation and the digestive hormone gastrin increase sphincter tone. Nonadrenergic, noncholinergic vagal impulses relax
the lower esophageal sphincter, as do the hormones progesterone, secretin, and glucagon. Relaxation during swallowing is
mediated by the vagus nerve.5
Stomach
The stomach is a hollow muscular organ that stores food during eating, secretes digestive juices, mixes food with these juices,
and propels partially digested food, called chyme, into the duodenum of the small intestine. The anatomy of the stomach is
presented in Figure 40-4. Its major anatomic boundaries are the
lower esophageal sphincter, where food passes through the cardiac orifice at the gastroduodenal junction into the stomach,
and the pyloric sphincter, which relaxes as food is propelled
into the duodenum. Functional areas of the stomach are the
fundus (upper portion), body (middle portion), and antrum
(lower portion).
The stomach has three layers of smooth muscle: an outer,
longitudinal layer; a middle, circular layer; and an inner,
oblique layer (the most prominent) (see Figure 40-4). These
layers become progressively thicker in the body and antrum,
where food is mixed, churned, and pushed into the duodenum.
The circular layer is most prominent and the oblique layer is
the least complete; the longitudinal layer is absent on the anterior and posterior surfaces. The glandular epithelium is discussed in the section about secretory functions of the stomach
(see p. 1398).
Blood is supplied to the stomach by branches of the celiac
artery. The blood supply is so abundant that nearly all arterial
vessels must be occluded before ischemic changes occur in the
stomach wall. A series of small veins (short gastric, left and right
gastric, and left and right gastro-omental) drain blood from the
stomach towards the hepatic portal vein.
The stomach is innervated by sympathetic and parasympathetic divisions of the autonomic nervous system. Some of
the autonomic nerves are extrinsic; that is, they originate in the
central nervous system and are controlled by nerve centers in
the brain. The vagus nerve provides parasympathetic innervation and branches of the celiac plexus innervate the stomach
sympathetically. Other neurons are intrinsic; that is, they originate within the stomach and respond to local stimuli and are
components of the enteric nervous system. Extrinsic sympathetic fibers reach the stomach through the celiac plexus (solar
plexus), whereas extrinsic parasympathetic fibers enter through
the gastric branch of the vagus nerve.
Few substances are absorbed in the stomach. The stomach
mucosa is impermeable to water, but the stomach can absorb
alcohol and aspirin and other nonsteroidal anti-inflammatory
agents.
Esophagus
Fundus
Gastroesophageal opening
Lower esophageal sphincter (LES)
Body of stomach
Cardia
Serosa
Longitudinal muscle layer
rv
atu
re
Pyloric
sphincter Pylorus
Lesser c
Duodenal
bulb
Circular muscle layer
u
Oblique muscle layer
Submucosa
Mucosa
Duodenum
Antrum
Rugae
r
at e
Gre
re
tu
rva
u
c
FIGURE 40-4 Stomach. A portion of the anterior wall has been cut away to reveal the muscle layers of the stomach wall.
Note that the mucosa lining the stomach forms folds called rugae. The dashed lines distinguish the fundus, body, and antrum
of the stomach. (Modified from Patton KT, Thibodeau GA: Anatomy & physiology, ed 8, St Louis, 2013, Mosby.)
Muscularis
Chapter 40 Structure and Function of the Digestive System
Gastric Motility
In its resting state the stomach is small and contains about
50 ml of fluid. There is little wall tension, and the muscle layers
in the fundus contract very little. Swallowing causes the fundus
to relax (receptive relaxation) to receive a bolus of food from
the esophagus. Relaxation is coordinated by efferent, nonadrenergic, noncholinergic vagal fibers and is facilitated by gastrin
and cholecystokinin, two polypeptide hormones secreted by the
gastrointestinal mucosa. (The actions of digestive hormones are
summarized in Table 40-1.) Food is stored in vertical or oblique
layers as it arrives in the fundus, whereas fluids flow relatively
quickly down to the antrum.
Gastric (stomach) motility increases with the initiation
of peristaltic waves, which sweep over the body of the stomach toward the antrum. The rate of peristaltic contractions is
approximately three per minute and is influenced by neural
and hormonal activity. Gastrin and motilin (small intestine
hormones) and the vagus nerve increase contraction by making the threshold potential of muscle fibers less negative. (The
neural and biochemical mechanisms of muscle contraction
are described in Chapter 43.) Sympathetic activity and secretin (another small intestine hormone) are inhibitory and make
the threshold potential more negative. The rate of peristalsis is
1397
mediated by pacemaker cells that initiate a wave of depolarization (basic electrical rhythm), which moves from the upper part
of the stomach to the pylorus.
Gastric mixing and subsequent emptying of gastric contents (chyme) from the stomach take several hours (3 to 6
hours depending on the composition and volume of food
intake). Mixing occurs as food is propelled toward the antrum.
As food approaches the pylorus, the velocity of the peristaltic
wave increases, forcing the contents back toward the body of
the stomach. This retropulsion effectively mixes food with
digestive juices, and the oscillating motion breaks down large
food particles. With each peristaltic wave a small portion of the
chyme passes through the pylorus and into the duodenum. The
pyloric sphincter is about 1.5 cm long and is always open about
2 mm. It opens wider during antral contraction. Normally there
is no regurgitation from the duodenum into the antrum.
The rate of gastric emptying (movement of gastric contents
into the duodenum) depends on the volume, osmotic pressure,
and chemical composition of the gastric contents. Larger volumes of food increase gastric pressure, peristalsis, and rate of
emptying. Solids, fats, and nonisotonic solutions delay gastric
emptying.6 (Osmotic pressure and tonicity are described in
Chapters 1 and 3.) Products of fat digestion, which are formed
TABLE 40-1 SELECTED HORMONES AND NEUROTRANSMITTERS OF THE
DIGESTIVE SYSTEM*
SOURCE
HORMONE†
STIMULUS FOR SECRETION
ACTION
Mucosa of the
stomach
Gastrin
Presence of partially digested proteins in
the stomach
Gastrin
Acid in the stomach
Vagus and local nerves in stomach
Vagus and local nerves in stomach
Stimulates gastric glands to secrete hydrochloric acid and
pepsinogen; growth of gastric mucosa; promotes gastric motility
Stimulates acid secretion
Inhibits acid and pepsinogen secretion and release of gastrin
Stimulates release of pepsinogen and acid secretion
Stimulates gastrin and release of pepsinogen and acid secretion
Presence of acid and fat in the duodenum
Increases gastrointestinal motility
Secretin
Presence of chyme (acid, partially digested
proteins, fats) in the duodenum
Cholecystokinin
Presence of chyme (acid, partially digested
proteins, fats) in the duodenum
Enteroglucagon
Intraluminal fats and carbohydrates
Entero-oxyntin
Gastric inhibitory
peptide (GIP)
Peptide YY
Presence of chyme in duodenum
Fat and glucose in small intestine
Pancreatic polypeptide
Vasoactive intestinal
peptide
Protein, fat, and glucose in small intestine
Intestinal mucosa and muscle
Stimulates pancreas to secrete alkaline pancreatic juice and liver
to secrete bile; decreases gastrointestinal motility; inhibits
gastrin and gastric acid secretion
Stimulates gallbladder to eject bile and pancreas to secrete
alkaline fluid; decreases gastric motility; constricts pyloric
sphincter; inhibits gastrin; delays gastric emptying
Weakly inhibits gastric and pancreatic secretion and enhances
insulin release, lipolysis, ketogenesis, and glycogenolysis;
delays gastric emptying
Delays gastric emptying
Inhibits gastric secretion and gastric emptying, stimulates insulin
release; inhibits intestinal motility
Inhibits postprandial gastric acid and pancreatic secretion and
delays gastric and small bowel emptying
Decreases pancreatic and enzyme secretion
Relaxes intestinal smooth muscle, increases blood flow
Mucosa of the
small intestine
Histamine
Somatostatin
Acetylcholine
Gastrin-releasing
peptide (bombesin)
Motilin
Intraluminal fat and bile acids
Modified from Johnson LR: Gastrointestinal physiology, ed 7, St Louis, 2007, Mosby.
*Data from Schubert ML, Peura DA: Gastroenterology 134(7):1842–1860, 2008; Wren AM, Bloom SR: Gastroenterology 132(6):2116–2130, 2007.
†Note: The digestive hormones are not secreted into the gastrointestinal lumen but rather into the bloodstream, in which they travel to target tissues. There are more than 30 peptide hormone genes expressed in the gastrointestinal tract and more than 100 hormonally active peptides.
1398
Unit XII The Digestive System
in the duodenum by the action of bile from the liver and
enzymes from the pancreas, stimulate the secretion of cholecystokinin.7 This hormone inhibits food intake, reduces gastric motility, and decreases gastric emptying so that fats are not
emptied into the duodenum at a rate that exceeds the rate of bile
and enzyme secretion. Osmoreceptors in the wall of the duodenum are sensitive to the osmotic pressure of duodenal contents.
The arrival of hypertonic or hypotonic gastric contents activates
the osmoreceptors, which delays gastric emptying to facilitate
formation of an isosmotic duodenal environment. The rate at
which acid enters the duodenum also influences gastric emptying. Secretions from the pancreas, liver, and duodenal mucosa
neutralize gastric hydrochloric acid in the duodenum. The rate
of emptying is adjusted to the duodenum’s ability to neutralize the incoming acidity. Peristaltic activity in the stomach is
also affected by blood glucose levels. Low blood glucose levels
stimulate the vagus nerve and gastric smooth muscles, increasing the rate of contraction.8
Gastric Secretion
Stimulated by eating, the stomach produces large volumes of
gastric secretions. Specialized cells located throughout the gastric mucosa produce mucus, acid, enzymes, hormones, intrinsic factor, and gastroferrin. Intrinsic factor is necessary for the
intestinal absorption of vitamin B12 and gastroferrin facilitates
small intestinal absorption of iron. The hormones are secreted
into the blood and travel to target tissues in the bloodstream.
The other gastric secretions are released directly into the stomach lumen under neural and hormonal regulation.9 Mucus
covering the entire mucosa, intercellular tight junctions, bicarbonate secretion, and submucosal acid sensors form a protective
barrier against acid and proteolytic enzymes, which otherwise
would damage the gastric lining.10
In the fundus and body of the stomach the gastric glands
of the mucosa are the primary secretory units (Figure 40-5).
Several of these glands (three to seven) empty into a common
duct known as the gastric pit. The parietal cells (oxyntic cells)
within the glands secrete hydrochloric acid, intrinsic factor, and
gastroferrin. The chief cells within the glands secrete pepsinogen, an enzyme precursor that is readily converted to pepsin
(a proteolytic enzyme) in the gastric fluid. The pyloric gland
mucosa in the antrum synthesizes and releases the hormone
gastrin from G cells. Enterochromaffin-like cells secrete histamine, and D cells secrete somatostatin.
The composition of gastric fluid depends on volume and
flow rate (Figure 40-6). Potassium level remains relatively constant, but its concentration is greater in gastric secretions than
in plasma. The rate of secretion varies with the time of day;
lower in the morning and higher in the afternoon and evening.
Loss of gastric secretions through vomiting, drainage, or suction may decrease body stores of sodium, potassium, hydrogen,
and chloride.
Acid. The major functions of gastric hydrochloric acid are
to dissolve food fibers, act as a bactericide against swallowed
organisms, and convert pepsinogen to pepsin. The production
of acid by the parietal cells requires the transport of hydrogen
and chloride from the parietal cells to the stomach lumen. Acid
is formed in the parietal cells, primarily through the hydrolysis
of water (Figure 40-7). At a high rate of gastric secretion,
bicarbonate moves into the plasma, producing an “alkaline
tide” in the venous blood, which also may result in a more
alkaline urine.11
Surface mucous cells
Gastric pit
Lamina propria
Gastric glands:
Mucous
neck cell
Mucosa
Chief cell
Parietal cell
Endocrine cell
Muscularis
mucosae
Submucosa
Blood vessels
Oblique
muscle layer
Muscularis
Circular
muscle layer
Serosa
Longitudinal
muscle layer
Connective tissue
Visceral peritoneum
FIGURE 40-5 Gastric Pits and Gastric Glands. Gastric pits are depressions
in the epithelial lining of the stomach. At the bottom of each pit is one or more
tubular gastric glands. Chief cells produce the enzymes of gastric juice, and parietal cells produce stomach acid. (From Patton KT, Thibodeau GA: Anatomy & physiology, ed 8, St Louis, 2013, Mosby.)
Concentration in
gastric juice
(mEq/L)
200
Cl
H
100
K
0
Low
Na
Medium
High
Secretory rate
FIGURE 40-6 Relationship Between Secretory Rate and Electrolyte
Composition of the Gastric Secretions. Sodium (Na+) concentration is lower in
the gastric secretions than in the plasma, whereas hydrogen (H+), potassium (K+),
and chloride (Cl−) concentrations are higher. Gastric secretions are close to isotonic. Secretory rate increases during the cephalic and gastric phases of digestion.
Chapter 40 Structure and Function of the Digestive System
Acid secretion by parietal cells is stimulated by acetylcholine
(ACh) (a neurotransmitter), gastrin (a hormone), and histamine (a biochemical mediator). The vagus nerve releases ACh
and stimulates the secretion of histamine and gastrin-releasing
peptide (GRP), which stimulates release of gastrin.12 Histamine
secretion is also stimulated by gastrin. Histamine is stored in
enterochromaffin cells (mast cells; see Chapter 7) in the gastric mucosa. Histamine receptors in the gastric mucosa are H2
receptors (unlike those in the bronchial mucosa, which are H1
receptors). Gastric lipase is produced by glands in the fundus
of the stomach and is most effective in an acidic environment.
Caffeine stimulates acid secretion, as does calcium. Prostaglandins, enterogastrones (such as gastric inhibitory peptide),
somatostatin, and secretin inhibit acid secretion.13
Pepsin. Acetylcholine, through vagal stimulation during
the cephalic and gastric phases, is the strongest stimulation
Blood
CO2
Parietal cell
CO2 H2O
H2CO3
HCO
3
Cl
HCO
3
Stomach
lumen
H2O
OH
H
K
K
H
H
HCl
H2O
Cl
Cl
FIGURE 40-7 Hydrochloric Acid Secretion by Parietal Cell.
Phase
Cephalic
Gastric
Intestinal
All
for pepsin secretion. The precursor pepsinogen is quickly
converted to pepsin at a pH of 2. Acid also stimulates a local
cholinergic reflex and stimulates chief cells to secrete pepsin.
Gastrin and secretin are weaker pepsinogen secretagogues.
Pepsin is a proteolytic enzyme that breaks down proteinforming polypeptides in the stomach. Once chyme has entered
the duodenum, the alkaline environment of the duodenum
inactivates pepsin.
Mucus. The gastric mucosa is protected from the digestive
actions of acid and pepsin by a coating of mucus called the
mucosal barrier. Gastric mucosal blood flow is important to
maintaining mucosal barrier function.14
The quality and quantity of mucus and the tight junctions
between epithelial cells make gastric mucosa relatively impermeable to acid. Prostaglandins and nitric oxide protect the
mucosal barrier by stimulating the secretion of mucus and
bicarbonate and by inhibiting the secretion of acid. A break in
the protective barrier may occur because of exposure to aspirin or other nonsteroidal anti-inflammatory drugs, Helicobacter
pylori, ethanol, regurgitated bile, or ischemia. Breaks cause
inflammation and ulceration.
Intrinsic factor (IF), a mucoprotein produced by parietal
cells, combines with vitamin B12 in the stomach. It is required
for the absorption of vitamin B12 by the ileum. Atrophic gastritis and failure to absorb vitamin B12 result in pernicious anemia
(see Chapter 28).
Phases of Gastric Secretion. The secretion of gastric juice
is influenced by numerous stimuli that together facilitate the
process of digestion. The phases of gastric secretion are the
cephalic phase, gastric phase, and intestinal phase (Figure 40-8).
Stimulation at
parietal cell
Stimulus
Chewing,
swallowing,
smell,
taste
Vagus
ACh
GRP
G cell
Local
reflexes
ACh
Distention
Digested
protein
G cell
Digested
protein
Intestinal G cell
Gastrin
ACh
1399
ECL cell
Gastrin
Circulating
amino acids
Histamine
FIGURE 40-8 Mechanisms for Stimulating Acid Secretion. ACh, Acetylcholine; ECL, enterochromaffin-like cell; GRP,
gastrin-releasing peptide. (From Johnson LR: Gastrointestinal physiology, ed 7, St Louis, 2007, Mosby.)
1400
Unit XII The Digestive System
Cephalic Phase. The anticipatory and sensory experiences
of smelling, seeing, tasting, chewing, and swallowing food contribute to the cephalic phase of secretion.15 The cephalic phase
of gastric secretion is mediated by the vagus nerve through the
myenteric plexus. Acetylcholine stimulates the parietal and
chief cells to secrete acid and pepsinogen, respectively. The G
cells in the antrum release gastrin, which circulates through the
bloodstream to the gastric glands and stimulates acid and pepsinogen secretion.
Insulin secretion by the endocrine pancreas, stimulated by
hyperglycemia, also is a strong stimulus for gastric secretion
and is mediated by the vagus nerve through sensors located in
the hypothalamus. Maintenance of steady serum glucose levels
suppresses the gastric response to insulin.
Gastric Phase. The gastric phase of secretion begins with
the arrival of food in the stomach. Two major stimuli have a
secretory effect: (1) distention of the stomach, and (2) the presence of digested protein. The vagus and enteric nerve plexuses
are stimulated by distention and contribute to gastric secretion through a local reflex. Both neural reflexes are mediated
by ACh and can be blocked by atropine. As digestion proceeds,
products of protein break down, stimulating the release of more
gastrin from G cells.
Intestinal Phase. The movement of chyme from the stomach
into the duodenum initiates the intestinal phase of secretion.
This phase represents a deceleration of the gastric secretory
response; however, the presence of digested protein and amino
acids in the duodenum continues to stimulate some gastric
secretion.
Concurrently, in response to low duodenal pH and the presence of lipids, inhibitory vagal and enteric reflexes decrease
gastric motility when chyme enters the duodenum. The release
of secretin and cholecystokinin stimulate pancreatic secretions
and inhibit gastric secretions.
Small Intestine
The small intestine is about 5 to 6 m long and is functionally divided into three segments: the duodenum, jejunum,
and ileum (Figure 40-9). The duodenum begins at the pylorus
and ends where it joins the jejunum at a suspensory ligament
called the Treitz ligament. The end of the jejunum and beginning of the ileum are not distinguished by an anatomic marker.
These structures are not grossly different, but the jejunum has
a slightly larger lumen. The ileocecal valve (sphincter) controls
the flow of digested material from the ileum into the large intestine and prevents reflux into the small intestine.
The peritoneum is the serous membrane surrounding the
organs of the abdomen and lining the abdominopelvic cavity.
It is analogous to the pericardium and pleura that surround
the heart and lungs, respectively. The visceral peritoneum lies
Mucosa
Villi mucosa
Lamina propria
Muscularis
mucosae
Duodenal glands
extending into
mucosa
Circular
muscle layer
Longitudinal
muscle layer
Serosa
Longitudinal section of
duodenum
Ligament
of Treitz
(Turned
to left)
Ileocecal
valve
Villus
Cecum
Appendix
Lymph
lacteal
Artery
Ileum
Cell shedding
Lymph lacteal
Goblet cell
Enterocytes
(absorptive cells)
Endocrine cell
Differentiating
cells
Intestinal stem Intestinal crypt
(of Lieberkühn)
cells
Jejunum
Muscularis Vein
mucosae
FIGURE 40-9 Small Intestine.
Paneth cell
Lymph
duct
Chapter 40 Structure and Function of the Digestive System
on the surface of the organs, and the parietal peritoneum lines
the wall of the body cavity. The space between these two layers is called the peritoneal cavity. This cavity normally contains
just enough fluid to lubricate the two layers and prevent friction during organ movement. Inflammation of the peritoneum,
called peritonitis, may occur with perforation of the intestine or
after abdominal surgery. As the inflammatory process resolves,
scar tissue adhesions may form and cause intestinal obstruction.
The duodenum lies behind the peritoneum, or retroperitoneally, and has an essential role in mixing food with digestive
juices from the liver and pancreas. The ileum and jejunum are
suspended from the posterior abdominal wall by a component
of the peritoneum called the mesentery. The loose folds of the
mesentery facilitate intestinal motility and support blood vessels, nerves, and lymphatics.
The arterial supply to the duodenum arises primarily from
the gastroduodenal artery, a small branch of the celiac artery.
The jejunum and ileum are supplied by branches of the superior mesenteric artery. Blood flow increases significantly during digestion. The superior mesenteric vein drains blood from
the entire small intestine and empties into the hepatic portal
circulation. The regional lymphatics drain into the thoracic
duct. Both divisions of the autonomic nervous system innervate
the small intestine. Secretion, motility, and intestinal reflexes
(e.g., relaxation of the lower esophageal sphincter) are mediated parasympathetically by the vagus nerve. Sympathetic activity inhibits motility and produces vasoconstriction. Intrinsic
reflexive activity is mediated by the myenteric plexus (Auerbach plexus) and the submucosal plexus (Meissner plexus) of
the enteric nervous system.
The smooth muscles of the small intestine are arranged in
two layers: a longitudinal, outer layer; and a thicker, inner circular layer (see Figure 40-9). Circular folds of the small intestine
mucosa slow the passage of food, thereby providing more time
for digestion and absorption. The folds are most numerous and
prominent in the jejunum and upper ileum.
Absorption occurs through villi, which cover the circular
folds and are the functional units of the intestine (see Figure
40-9). A villus is composed of absorptive columnar epithelial cells (enterocytes) and mucus-secreting goblet cells of the
mucosa. Each villus secretes some of the enzymes necessary for
digestion and absorbs nutrients. Near the surface, columnar
cells closely adhere to each other at sites called tight junctions.
Water and electrolytes are absorbed through these intercellular
spaces. The surface of each columnar epithelial cell on the villus contains tiny projections called microvilli (see Figure 40-9).
Together the microvilli create a mucosal surface known as the
brush border. The villi and microvilli greatly increase the surface area available for absorption. Coating the brush border is
an “unstirred” layer of fluid that is important for the absorption
of substances other than water and electrolytes. The lamina
propria (a connective tissue layer of the mucosa) lies beneath
the epithelial cells of the villi and contains lymphocytes; plasma
cells, which produce immunoglobulins; and macrophages.
Central arterioles ascend within each villus and branch into
a capillary array that extends around the base of the columnar
cells and cascades down to the venules that lead to the hepatic
1401
portal circulation. The opposing ascending and descending blood flow provides a countercurrent exchange system
for absorbed substances and blood gases. A central lacteal, or
lymphatic capillary, is also contained within each villus and is
important for the absorption and transport of fat molecules.
Contents of the lacteals flow to regional nodes and channels
that eventually drain into the thoracic duct16 (see Figure 40-9).
Between the bases of the villi are the crypts of Lieberkühn
(intestinal glands), which extend to the submucosal layer. Undifferentiated (stem cells) and secretory cells and Paneth epithelial
cells are located here. The stem cells are precursors of columnar
epithelial and goblet cells. These premature cells produce alkaline
fluids containing electrolytes, mucus, and water. These cells arise
from the base of the crypt and move toward the tip of the villus,
maturing in shape and function as they progress. After becoming columnar cells and completing their migration to the tip of
the villus, they function for a few days and then are shed into the
intestinal lumen and digested. The entire epithelial population
is replaced about every 4 to 7 days. Many factors can influence
this process of cellular proliferation. Starvation, vitamin B12 deficiency, and cytotoxic drugs or irradiation suppress cell division
and shorten the villi. The decreased absorption that results can
cause diarrhea and malnutrition. Nutrient intake and intestinal
resection stimulate cell production. The Paneth cells located at the
base of the crypts produce defensins and other antibiotic peptides
and proteins.17 Other secretory cells produce digestive enzymes.
Intestinal Digestion and Absorption
The process of intestinal digestion is initiated in the stomach by
the actions of gastric hydrochloric acid and pepsin, which break
down food fibers and proteins. The chyme that passes into the
duodenum is a liquid that contains small particles of undigested
food. Digestion is continued in the proximal portion of the small
intestine by the action of pancreatic enzymes, intestinal brushborder enzymes, and bile salts (Box 40-1). Here carbohydrates
are broken down to monosaccharides and disaccharides; proteins are degraded further to amino acids and peptides; and fats
are emulsified and reduced to fatty acids and monoglycerides
(Figure 40-10). These nutrients, along with water, vitamins, and
electrolytes, are absorbed across the intestinal mucosa and into
the blood by active transport, diffusion, or facilitated diffusion.
Products of carbohydrate and protein breakdown move into
villus capillaries and then to the liver through the hepatic portal
vein. Digested fats move into the lacteals and eventually reach
the liver through the systemic circulation. Intestinal motility
exposes nutrients to a large mucosal surface area by mixing
chyme and moving it through the lumen. Different segments of
the gastrointestinal tract absorb different nutrients. Digestion
and absorption of all major nutrients occur in the small intestine. Sites of absorption are shown in Figure 40-11.
Water and Electrolyte Transport by the Small Intestine. The
epithelial cell membranes of the small intestine are formed of
lipids and therefore are hydrophobic, or tend to repel water.
(The properties of cell membranes are described in Chapter
1.) Therefore, water and electrolytes are transported in both
directions (toward the capillary blood or toward the intestinal
lumen) through the tight junctions and intercellular spaces
1402
Unit XII The Digestive System
BOX 40-1 SOURCES OF DIGESTIVE
ENZYMES
Salivary Glands
Amylase
Lingual lipase
Stomach
Pepsin
Gastric lipase
Pancreas
Amylase
Trypsin
Chymotrypsin
Carboxypeptidase
Elastase
Lipase-colipase
Phospholipase A2
Cholesterol esterase–nonspecific lipase
Small Intestine
Enterokinase
Disaccharidases
Maltase
Sucrase
Lactase
α,α-Trehalase
Isomaltase
Peptidases
Amino-oligopeptidase
Dipeptidase
From Johnson LR: Gastrointestinal physiology, ed 7, St Louis, 2007,
Mosby.
rather than across cell membranes. Water diffuses passively
across hydrostatic pressure and osmotic gradients established
by the active transport of sodium and other substances.
Approximately 85% to 90% of the water that enters the
gastrointestinal tract each day is absorbed in the small intestine.
The remaining water and electrolytes are absorbed at a constant
rate in the large intestine.18 Sodium passes through the tight
junctions and is actively transported across cell membranes.
Sodium and glucose share a common active transport carrier
(sodium-glucose ligand transporter1 [SGLT1]) so that sodium
absorption is enhanced by glucose transport18a (Figure 40-12).
Potassium moves passively across the tight junctions with
changes in the electrochemical gradient. Chloride is actively
secreted throughout the large and small intestines.
Carbohydrates. Carbohydrate (starch, table sugar [sucrose],
milk sugar [lactose], cereal sugar [maltose]) accounts for at
least 50% of the American diet. Because only monosaccharides
(ribose, galactose, glucose, fructose) are absorbed by the
intestinal mucosa, the complex carbohydrates (polysaccharides
and oligosaccharides) must be hydrolyzed to their simplest
form (see Figure 40-10). Salivary and pancreatic amylases break
down starches to oligosaccharides by splitting α-1,4-glucosidic
linkages of long-chain molecules. The major disaccharides are
sucrose (glucose-fructose), maltose (glucose-glucose), and lactose
(glucose-galactose). Approximately half of starch hydrolysis occurs
in the stomach and about half in the duodenum. In the small
intestine, disaccharides are hydrolyzed by brush-border enzymes
(sucrase, maltase, and lactase) to their respective monosaccharides.
The sugars are absorbed primarily in the duodenum and upper
jejunum. The monosaccharides pass through the unstirred layer by
diffusion. At the cell membrane, glucose and galactose are actively
transported with a sodium carrier (SGLT1) and fructose absorption is facilitated by glucose transporter 5 (GLUT5) and GLUT7.19
Transport of all three monosaccharides from the cytosol to the
bloodstream is facilitated by GLUT220 (see Figure 40-12). Insulin
facilitates glucose transport into fat and muscle cells via glucose
transporter 4 (GLUT4).
Insulin is not required for the intestinal absorption of glucose.
Cellulose is a glucose polysaccharide found in plants. Humans
lack enzymes to digest cellulose, and the undigested fiber contributes to stool volume and stimulates large intestine motility.
Proteins. Adults require 44 to 56 g of protein per day.
Approximately 20 to 30 g of protein is derived endogenously
from shed epithelial cells and small amounts of plasma proteins.
Most ingested protein is absorbed; only 5% to 10% is eliminated
in the stool.
The site of digestion of protein depends on the source of
the protein. For example, casein from bovine milk precipitates in the stomach and is digested by gastric pepsin and acid,
whereas the soluble proteins whey and soy pass rapidly through
the stomach and are digested by pancreatic enzymes.21 Major
protein hydrolysis is accomplished in the small intestine by the
pancreatic enzymes trypsin, chymotrypsin, and carboxypeptidase (see Figure 40-10). Trypsin and chymotrypsin (endopeptidase) hydrolyze the interior bonds of the large molecules, and
carboxypeptidases cleave the end amino acids (exopeptidase).
Hydrolysis of proteins is also carried out by the brush-border
enzymes and enzymes in the epithelial cytosol (intracellular
fluid). The brush-border enzymes hydrolyze the large oligopeptides (proteins composed of three to six amino acids) into
smaller peptides, which can cross cell membranes. Enzymes in
the cytosol then break them down to amino acids. Amino acids
are actively transported from the cytosol into the bloodstream
by a sodium-dependent carrier in the basolateral membrane.
There also are free amino acids that can be absorbed directly
from the intestinal lumen using a membrane transport protein.
Like the sugars, proteins are absorbed primarily in the proximal
area of the small intestine.
Fats
Approximately 90 to 100 g of fat is consumed daily by the average
American. Fat is an important source of calories and is a primary
structural component of cell membranes and organelles. Sources
of dietary fat are reviewed in Box 40-2. Although triglycerides
are the major dietary lipids, cholesterol, phospholipids, and fatsoluble vitamins also have nutritional importance. The digestion
and absorption of fat occur in four phases: (1) emulsification
and lipolysis, (2) micelle formation, (3) fat absorption, and
(4) resynthesis of triglycerides and phospholipids.
The mechanical action of the stomach and small intestine disperses the triglyceride droplets into small particles.
Chapter 40 Structure and Function of the Digestive System
Action
Foodstuff
Enzymes/source
Site of
action
Starch
Salivary amylase
Mouth
Dextrins, oligosaccharides
Pancreatic amylase
Carbohydrate
digestion and
absorption
Lactose
Maltose
Sucrose
Galactose
Glucose
Fructose
Brush-border enzymes
(lactase, maltase, sucrase)
Small
intestine
Pepsin in presence of
hydrochloric acid
Stomach
Absorbed by capillaries
in the villi and transported
to the liver by portal vein
Proteins
Proteases, peptones
Protein
digestion and
absorption
Pancreatic enzymes
(trypsin, chymotrypsin,
carboxypeptidase)
Small
intestine
Brush-border enzymes
(aminopeptidases and
dipeptidases)
Small
intestine
Emulsifying agents (bile
acids, fatty acids, monoglycerides, lecithin,
cholesterol, and protein)
Small
intestine
Pancreatic lipases
Small
intestine
Small polypeptides, dipeptides
Amino acids
Absorbed by capillaries in
the villi and transported to
the liver by hepatic portal
vein
Unemulsified fats
Fat
digestion
Monoglycerides
and fatty acids
Glycerol and
fatty acids
Absorbed by lacteals
in the villi and transported to
the liver in the systemic circulation, which receives lymphatic
flow from the thoracic duct or via the
hepatic portal vein
Glycerol and
short-chain fatty acids
absorbed by capillaries
in the villi and transported to the liver by
the portal vein
FIGURE 40-10 Digestion and Absorption of Foodstuffs.
1403
1404
Unit XII The Digestive System
Stomach
Water
Alcohol
Duodenum
Iron
Calcium
Fats
Sugars
Water
Proteins
Vitamins
Magnesium
Sodium
Jejunum
Sugars
Proteins
Ileum
Bile salts
Vitamin B12
Chloride
Colon
Water
Electrolytes
FIGURE 40-11 Sites of Absorption of Major Nutrients.
Brush-border
membrane
Intestinal
lumen
Emulsification is the process by which emulsifying agents (fatty
acids, monoglycerides, lecithin, cholesterol, protein, bile salts)
in the small intestinal lumen cover the small fat particles and
prevent them from re-forming into fat droplets. Emulsified fat
is then ready for lipolysis (lipid hydrolysis) by pancreatic lipase,
phospholipase, and hydrolase. Lipase breaks down triglycerides
to diglycerides, monoglycerides, free fatty acids, and glycerol
(see Figure 40-10). The action of lipase requires the presence of
colipase, a pancreatic enzyme that allows lipase to penetrate the
triglyceride molecule. Phospholipase cleaves fatty acids from
phospholipids, and cholesterol esterase breaks cholesterol
esters into fatty acids and glycerol.
The products of lipid hydrolysis must be made water soluble
if they are to be absorbed efficiently from the intestinal lumen.
This is accomplished by the formation of water-soluble molecules known as micelles (Figure 40-13). Micelles are formed of
bile salts (see p. 1411), the products of fat hydrolysis, fat-soluble
vitamins, and cholesterol. The fats form the core of the micelle,
and the polar bile salts form an outer shell, with the hydrophobic (“water-hating”) side facing the interior and the hydrophilic
(“water-loving”) side facing the aqueous (water-like) content of
the intestinal lumen. Because the unstirred layer of the brush
border is aqueous, the micelles readily diffuse through it. The
micelles maintain the fat molecules in the dissolved or solubilized form, which allows them to move more rapidly from the
micelle toward the absorbing surface of the intestinal epithelium. The fat products of the micelle then readily diffuse through
the epithelial cell membrane, while the bile salts remain in the
lumen and proceed to the ileum, where they are absorbed into
Intracellular
region
Capillary
in villi
Hydrolytic enzymes
on surface of
microvilli
Fructose
Fructose
Sucrose
Maltose
Lactose
Na
(relatively high
concentration)
Glucose
Galactose
Na
SGLT1
Passive
transport
Fructose
Glucose
(high concentration)
Glucose
Galactose
Galactose
Na
(low concentration
maintained by
active extrusion)
Na
Basolateral
membrane
FIGURE 40-12 Monosaccharides and Sodium Transport. Schematic showing monosaccharides and sodium (Na+)
transport through the small intestinal epithelium. Glucose, galactose, and sodium are transported into the epithelial cell by
sodium-glucose ligand transporter 1 (SGLT1). See text for details.
Chapter 40 Structure and Function of the Digestive System
BOX 40-2 DIETARY FAT
Saturated Fatty Acid (Palmitic Acid [C16H32O2])
Each carbon atom in the chain is linked by single bonds to adjacent carbon and
hydrogen atoms; atoms are solid at room temperature and found in animal fat
and tropical oils (coconut and palm oils); they increase low-density lipoprotein
(LDL) cholesterol (“bad” cholesterol) blood levels and increase the risk of coronary artery disease.
Unsaturated Fatty Acid
Unsaturated fatty acids are soft or liquid at room temperature; omega-6 fatty
acids are found in plants and vegetables (olive, canola, and peanut oils), and
omega-3 fatty acids are found in fish and shellfish.
1.Monounsaturated fatty acids (e.g., oleic acid [C18H34O2]): Contain one
double bond in the carbon chain and are found in plants and animals;
may be beneficial in reducing blood cholesterol, glucose levels, and systolic blood pressure; do not lower high-density lipoprotein (HDL) cholesterol (“good” cholesterol) level; low HDL levels have been associated
with coronary heart disease.
2.Polyunsaturated fatty acids (e.g., linoleic acid [C18H32O2]): Contain two or
more double bonds in the carbon chain and are found in plants and fish
oils; omega-6 fatty acids lower total and LDL cholesterol blood levels;
high levels of polyunsaturated fatty acids may lower LDL level; omega-3
fatty acids lower blood triglyceride levels, reduce platelet aggregation
and blood-clotting tendency, are necessary for growth and development,
and may prevent coronary artery disease, hypertension, cancer, and
inflammatory and immune disorders.
Hydrophobic face
Hydrophilic face
OH groups
Bile salts
Peptide bonds
Carboxyl or
sulfonic acid
A
Cylindrical micelle
B
Cross section
Bile acids
Cholesterol
Phospholipids
Free fatty acids
2-Monoglycerides
FIGURE 40-13 Structure of Bile Acid and Micelle. A, A bile salt molecule
in solution. The molecule is amphipathic in that it has a hydrophilic face and a
hydrophobic face. The amphipathic structure is key in the ability of the bile salts to
emulsify lipids and form micelles. B, A model of the structure of a bile salt–lipid
mixed micelle, an emulsified fat. (From Levy MN, Koeppen BM, Stanton BA: Principles of physiology, ed 4, St Louis, 2006, Mosby.)
1405
the circulation and returned to the liver via the enterohepatic
circulation (Figure 40-14 and Figure 40-20, p. 1411). Almost all
of the bile salts are recycled in this way.
When the fat products reach the inside of the epithelial cell,
they are resynthesized into triglycerides and phospholipids. The
triglycerides are covered with phospholipids, lipoproteins, and
cholesterol to become particles called chylomicrons. The chylomicrons travel to the basolateral membrane of the columnar
epithelial cells, where they are extruded into the intercellular
spaces of the villus. From here they enter the lacteals and lymphatic channels and, eventually, the systemic circulation.
Minerals and Vitamins. The recommended intake of calcium
ranges from 1000 to 1500 mg/day. Between 500 and 600 mg is
secreted or shed into the lumen with desquamated epithelial
cells. Not all of this calcium is absorbed. Daily absorption of
calcium is approximately 600 mg. This amount increases with
increased intake. When its concentration in the lumen is greater
than 5 mmol/L, calcium is absorbed by passive diffusion. At
concentrations less than 5 mmol/L, calcium is transported actively
across cell membranes, bound to a carrier protein. The carrier
formation requires the presence of the active form of vitamin D3
(1,25-dihydroxy-vitamin D). The calcium-protein complex moves
into the epithelial cell, where the calcium binds to proteins or other
substances. Then these complexes move through the basolateral
membrane to the interstitial fluid by diffusion or active transport.
Calcium is absorbed throughout the small intestine, but primarily
in the ileum. Increased serum calcium concentration inhibits
parathyroid hormone, which in turn decreases the formation of
vitamin D3 by the kidney, thus regulating calcium absorption.
Increased demand for calcium results in increased uptake, as
evidenced by the fact that calcium is absorbed more rapidly in
children and pregnant or lactating women. Bile salts enhance
calcium absorption indirectly by facilitating the absorption of
vitamin D, which is fat soluble. In addition, bile salts promote
the absorption of free fatty acids that, at high concentrations,
bind calcium and form soaps in the intestinal lumen. In older
individuals calcium is absorbed less readily because of inadequate amounts of the active form of vitamin D.22
The recommended intake of magnesium for adults is 300
to 350 mg/day. Approximately 50% of it is absorbed by active
transport or passive diffusion in the jejunum and ileum. Phosphate is also absorbed in the small intestine by passive diffusion
and active transport.
The levels of iron in the body are regulated primarily by intestinal absorption and secretion. The average intake ranges from
15 to 30 mg/day. Of this amount, menstruating women absorb 1
to 1.5 mg and men absorb 0.15 to 1 mg. Generally the amount of
iron absorbed is equal to the amount required. Iron is absorbed
more rapidly if a deficiency exists. A primary source of iron is
heme from animal protein. This iron is rapidly absorbed by the
epithelial cells primarily in the duodenum. Inorganic iron (e.g.,
iron in fruits, cereals, eggs, vegetables) is also readily absorbed.
The presence of vitamin C reduces ferric iron to ferrous iron,
which is the form more easily absorbed. Calcium phosphate and
phosphoproteins (milk and antacids) in the intestinal lumen
bind iron and reduce absorption. Tea also binds iron and inhibits absorption by forming iron tannate complexes.
1406
Unit XII The Digestive System
Unstirred layer
Brush-border
membrane
Microvillus
Well-mixed
luminal contents
Diffusion of
micelles
through unstirred
layer
Fatty acids
Cytosol
Phospholipids
Cholesterol
Monoglycerides
FIGURE 40-14 Lipid Absorption in the Small Intestine. Micelles of bile salts and products of lipid digestion diffuse
through the unstirred layer and among the microvilli. As digestive products are absorbed from free solution by epithelial cells
of the villi, more digestive products dissociate from the micelles. (From Levy MN, Koeppen BM, Stanton BA: Principles of
physiology, ed 4, St Louis, 2006, Mosby.)
TABLE 40-2 INTESTINAL ABSORPTION OF VITAMINS
VITAMIN
MECHANISMS OF ABSORPTION
SITE OF ABSORPTION
Fat-Soluble Vitamins
A (retinal)
D3 (1,25-dihydroxy-vitamin D)
E (α-tocopherol)
K
Micelle formation with bile salts; lipid diffusion
Ileum
Active transport (sodium dependent)
Unknown
Passive diffusion
Passive diffusion; active transport (sodium dependent)
Active transport (sodium dependent)
Active transport (intrinsic factor dependent)
Passive diffusion
Passive diffusion
Unknown
Duodenum and jejunum
Duodenum and jejunum
Jejunum
Ileum
Jejunum
Terminal ileum
Jejunum
Duodenum and jejunum
Unknown
Water-Soluble Vitamins
B1 (thiamine)
B2 (riboflavin)
Niacin (nicotinic acid)
C (ascorbic acid)
Folic acid
B12 (cobalamin)
B6 (pyridoxine, pyridoxamine, pyridoxal phosphate)
Pantothenic acid
Biotin
Iron is bound to intestinal transferrin in the lumen and is
absorbed and bound to the protein ferritin and to amino acid
chelates in the cytosol of the enterocytes. Transport of iron
across the basolateral membrane is determined by the amount
of iron in the circulation. It is transported in the blood by
plasma transferrin, a glycoprotein, and is carried to body tissues. When there is less need for iron, it remains in the enterocyte as ferritin and is carried into the lumen when the cell is
sloughed from the end of the villus. Following hemorrhage,
the intestinal cells require 3 days to increase their rate of iron
absorption. This is because the need for iron is perceived by the
precursor stem cells in the crypts of Lieberkühn, and they take
3 days to mature and migrate to the tips of the villi, where they
absorb more iron. Hepcidin is a protein synthesized by the liver
that inhibits apical uptake of iron by enterocytes and modulates
iron trafficking.23
The absorption of vitamins is summarized in Table
40-2. Most of the water-soluble vitamins are absorbed passively or by sodium-dependent active transport. Most vitamin B12 (cobalamin) is bound to intrinsic factor (making it
resistant to digestion) and absorbed in the terminal ileum,
although a small amount of the vitamin is absorbed in its free
(unbound) form.
Intestinal Motility
The movements of the small intestine facilitate digestion and
absorption. Chyme coming from the stomach stimulates intestinal movements that mix in secretions from the liver, pancreas,
and intestinal glands. A churning motion brings the luminal
content into contact with the absorbing cells of the villi. Propulsive movements then advance the chyme toward the large
intestine.
Chapter 40 Structure and Function of the Digestive System
Intestinal motility is regulated by the enteric nervous system,
vagal stimulation, and hormones (see Table 40-1). Two movements promote motility: segmentation and peristalsis. Segmentation consists of localized rhythmic contractions of the circular
smooth muscles and occurs more frequently than peristalsis.24
The contraction waves occur at different rates in different parts
of the small intestine in segments of 1 to 4 cm. Frequency is
greatest (12 per minute) in the upper small intestine and least
(8 per minute) in the distal part of the ileum. Segmentation
divides and mixes the chyme, bringing it into contact with the
absorbent mucosal surface. It also helps to propel the chyme
toward the large intestine. The frequency of the segmentation
is regulated intrinsically by the frequency of the basic electrical
rhythm (BER), which arises in the myenteric plexus of longitudinal smooth muscle and is controlled by the interstitial cells
of Cajal, the pacemaker cells of the gastrointestinal (GI) tract.
Although the basic rate of contraction is controlled intrinsically, the force of contraction can be enhanced extrinsically by
vagal stimulation.25
Intestinal peristalsis involves short segments (about 10 cm)
of longitudinal smooth muscle and propels chyme through the
intestine. The wave of contraction moves slowly (1 to 2 cm/second) to allow time for digestion and absorption.
Peptide hormones, including motilin, gastrin, secretin, and
cholecystokinin, facilitate intestinal motility. Neural reflexes
along the length of the small intestine facilitate motility, digestion, and absorption. Through reflex action, receptors in one part
of the intestine transmit signals that influence the function of
another part. The ileogastric reflex inhibits gastric motility when
the ileum becomes distended. This prevents the continued movement of chyme into an already distended intestine. The intestinointestinal reflex inhibits intestinal motility when one part
of the intestine is overdistended. Both of these reflexes require
extrinsic innervation. The gastroileal reflex, which is activated
by an increase in gastric motility and secretion, stimulates an
increase in ileal motility and relaxation of the ileocecal sphincter.
This empties the ileum and prepares it to receive more chyme.
The gastroileal reflex is probably regulated by the hormones gastrin and cholecystokinin or through the autonomic nerves.
During prolonged fasting or between meals, particularly
overnight, slow waves sweep along the entire length of the
intestinal tract from the stomach to the terminal ileum. This is
known as the interdigestive myoelectric complex, and it appears
to propel residual gastric and intestinal contents, including bacteria, into the colon.
The intestinal villi move with contractions of the muscularis mucosae, a very thin layer of muscle that separates the
mucosa and submucosa. Absorption is promoted by the swaying of villi in the luminal contents. Contractile activity also
helps to empty the central lacteals, which contain products of
fat digestion.
The ileocecal valve (sphincter) marks the junction between
the terminal ileum and the large intestine. This valve is intrinsically regulated and is normally closed. The arrival of peristaltic waves from the last few centimeters of the ileum causes the
ileocecal valve to open, allowing a small amount of chyme to
pass through. Distention of the upper large intestine causes the
1407
sphincter to constrict, preventing further distention or retrograde flow of intestinal contents.
Large Intestine
The large intestine is approximately 1.5 m long and consists
of the cecum, appendix, colon, rectum, and anal canal (Figure
40-15). The cecum is a pouch that receives chyme from the
ileum. Attached to the cecum is the vermiform appendix, an
appendage having little or no physiologic function. From the
cecum, chyme enters the colon, a four-part length of intestine
that loops upward, traverses the abdominal cavity, and descends
to the anal canal. The four parts of the colon are the ascending
colon, transverse colon, descending colon, and sigmoid colon.
Two sphincters control the flow of intestinal contents through
the cecum and colon: the ileocecal valve, which admits chyme
from the ileum to the cecum, and the rectosigmoid (O’Beirne)
sphincter, which controls the movement of wastes from the
sigmoid colon into the rectum. A thick (2.5 to 3 cm) portion
of smooth muscle surrounds the anal canal, forming the internal anal sphincter. Overlapping it distally is the striated skeletal
muscle of the external anal sphincter.
In the cecum and colon the longitudinal muscle layer consists
of three longitudinal bands called teniae coli (see Figure 40-15).
The teniae coli are shorter than the colon, giving the colon its
“gathered” appearance. The circular muscles of the colon separate the gathers into outpouchings called haustra. The haustra become more or less prominent with the contractions and
relaxations of the circular muscles. The mucosal surface of the
colon has rugae (folds), particularly between the haustra, and
Lieberkühn crypts but no villi. Columnar epithelial cells and
mucus-secreting goblet cells form the mucosa throughout the
large intestine. The columnar epithelium absorbs fluid and
electrolytes, and the mucus-secreting cells lubricate the mucosa.
The enteric nervous system regulates motor and secretory
activity independently of extrinsic nervous system control.
Extrinsic parasympathetic innervation occurs through the vagus
nerve and extends from the cecum up to the first part of the transverse colon. Vagal stimulation increases rhythmic contraction
of the proximal colon. Extrinsic parasympathetic fibers reach
the distal colon through the sacral parasympathetic splanchnic
nerves. The internal anal sphincter is usually in a state of contraction, and its reflex response is to relax when the rectum is distended. The myenteric plexus provides the major innervation of
the internal anal sphincter, but responds to sympathetic stimulation to maintain contraction and parasympathetic stimulation
that facilitates relaxation when the rectum is full. Sympathetic
innervation of this sphincter arises from the celiac and superior
mesenteric ganglia and the sphincter nerve. The external anal
sphincter is innervated by the pudendal nerve arising from sacral
levels of the spinal cord. Voluntary control of the external anal
sphincter is paralyzed after injury of the lower spinal cord, but
the internal sphincter is still functional. Sympathetic activity in
the entire large intestine modulates intestinal reflexes, conveys
somatic sensations of fullness and pain, participates in the defecation reflex, and constricts blood vessels. The blood supply of
the large intestine and rectum is derived primarily from branches
of the superior and inferior mesenteric artery.26
1408
Unit XII The Digestive System
Hepatic portal vein Aorta
Transverse
Inferior vena cava
Splenic colon
vein
Superior mesenteric artery
Hepatic
(right colic)
flexure
Splenic
(left colic)
flexure
Inferior
mesenteric
artery and
vein
Teniae coli
Ascending
colon
Haustra
Descending
colon
Mesentery
Ileocecal
valve
Sigmoid
artery
and vein
Ileum
Cecum
A
Vermiform
Rectum
appendix
External anal
sphincter
muscle
Superior rectal
artery and vein
Anus
Crypt of
Lieberkühn
Lamina
propria
Lymphoid
nodule
Muscularis
mucosae
Sigmoid
colon
Submucosa
B
Circular muscle
of muscularis externa
FIGURE 40-15 Large Intestine. A, Structure of the large intestine. B, Microscopic cross section illustrating cellular
structures of the large intestine. The wall of the large intestine is lined with columnar epithelium in contrast to the villi characteristics of the small intestine. The longitudinal layer of muscularis is reduced to become the teniae coli. (A modified from
Patton KT, Thibodeau GA: Anatomy & physiology, ed 8, St Louis, 2013, Mosby; B from Gartner LP, Hiatt JL: Color textbook of
histology, Philadelphia, 2007, Saunders.)
The primary type of colonic movement is segmental. The circular muscles contract and relax at different sites, shuttling the
intestinal contents back and forth between the contracting and
relaxing haustra. The movements massage the intestinal contents, then called the fecal mass, and facilitate the absorption of
water. Propulsive movement occurs with the proximal-to-distal
contraction of several haustral units. Peristaltic movements
also occur and promote the emptying of the colon. The gastrocolic reflex initiates propulsion in the entire colon, usually
during or immediately after eating, when chyme enters from
the ileum. The gastrocolic reflex causes the fecal mass to pass
rapidly into the sigmoid colon and rectum, stimulating defecation. Gastrin and cholecystokinin participate in stimulating this
reflex. Epinephrine inhibits contractile activity.
Approximately 500 to 700 ml of chyme flows from the ileum
to the cecum per day. Most of the water is absorbed in the colon
by diffusion and active transport. The electrochemical gradient established by sodium movement enhances the diffusion of
serum potassium from the capillaries in the lumen. Aldosterone
increases colon membrane permeability to sodium, thereby
increasing both the diffusion of sodium into the cell and the
active transport of sodium across the basolateral membrane to
the interstitial fluid. (See Chapters 3, 21, and 37 for a discussion
of aldosterone secretion.) This increases the cell-to-lumen diffusion gradient for potassium. Potassium moves outward, and
chloride is absorbed with sodium as the complementary anion.
Chloride also enters the cell in exchange for bicarbonate.
By the time the fecal mass enters the sigmoid colon, the
mass consists entirely of wastes and is called the feces. Feces,
or excrement, consists of food residue, unabsorbed gastrointestinal secretions, shed epithelial cells, and bacteria. The movement of feces into the sigmoid colon and rectum stimulates
the defecation reflex (rectosphincteric reflex). The rectal wall
stretches and the tonically constricted internal anal sphincter
relaxes, creating the urge to defecate. The defecation reflex can
be overridden voluntarily by contraction of the external anal
sphincter and muscles of the pelvic floor. The rectal wall gradually relaxes, reducing tension, and the urge to defecate passes.
Retrograde contraction of the rectum may displace the feces
out of the rectal vault until a more convenient time for evacuation. Pain or fear of pain associated with defecation (e.g., rectal
fissures or hemorrhoids) can inhibit the defecation reflex. The
defecation reflex is regulated by parasympathetic and cholinergic fibers. Voluntary inhibition or facilitation of defecation is
mediated from cortical projections onto the medulla and down
to sacral segments of the cord.
Defecation is facilitated by squatting or sitting because these
positions straighten the angle between the rectum and anal
canal and increase the efficiency of straining (increasing intraabdominal pressure). Intra-abdominal pressure is increased by
initiating the Valsalva maneuver. This maneuver consists of
inhaling and forcing the diaphragm and chest muscles against
the closed glottis. This increases both intrathoracic and intraabdominal pressure, which is transmitted to the rectum.
Intestinal Bacteria
The type and number of bacterial flora vary greatly throughout
the normal gastrointestinal tract, with an increasing number
Chapter 40 Structure and Function of the Digestive System
Hepatic duct
Cystic duct
Liver
Esophagus
Pyloric sphincter
Gallbladder
Spleen
1409
digestion and absorption. Between meals bile is stored in the
gallbladder. The exocrine pancreas produces enzymes needed
for the complete digestion of carbohydrates, proteins, and fats.
The exocrine pancreas also produces an alkaline fluid that neutralizes chyme, creating a duodenal pH that supports enzymatic
action. The liver receives nutrients absorbed by the small intestine and metabolizes or synthesizes these nutrients into forms
that can be absorbed by the body’s cells. It then releases the
nutrients into the bloodstream or stores them for later use.
Liver
Stomach
Common
bile duct
Accessory
papilla
Greater duodenal
papilla (of Vater)
Pancreas
Accessory
pancreatic duct
Pancreatic duct
Duodenum
FIGURE 40-16 Locations of the Liver, Gallbladder, and Exocrine Pancreas, Which Are the Accessory Organs of Digestion.
of bacteria from the stomach to the distal colon. The stomach
is relatively sterile because of the secretion of acid that kills
ingested pathogens or inhibits bacterial growth. Bile acid secretion, intestinal motility, and antibody production suppress
bacterial growth in the duodenum, and in the duodenum and
jejunum there is a low concentration of aerobes (10−1 to 10−4/
ml), primarily streptococci, lactobacilli, staphylococci, enterobacteria, and Bacteroides. Anaerobes are only found distal to the
ileocecal valve. They constitute about 95% of the fecal flora in
the colon and contribute one third of the solid bulk of feces. Bacteroides, clostridia, anaerobic lactobacilli, and coliforms are the
most common microorganisms from the ileum to the cecum.27
The intestinal tract is sterile at birth but becomes colonized
with Escherichia coli, Clostridium welchii, and Streptococcus
within a few hours. Within 3 to 4 weeks after birth, the normal flora are established. The normal flora do not have the
virulence factors associated with pathogenic microorganisms,
thus permitting immune tolerances. The intestinal mucosal
environment also produces a broad spectrum of protective
antimicrobial agents.28 The intestinal bacteria play a role in the
metabolism of bile salts (contributing to the intestinal reabsorption of bile and the elimination of toxic bile metabolites);
the metabolism of estrogens, androgens, and lipids and conversion of unabsorbed carbohydrates to absorbable organic acids;
the synthesis of vitamin K2 and B vitamins; and the metabolism
of various nitrogenous substances and drugs.29
Accessory Organs of Digestion
The liver, gallbladder, and exocrine pancreas all secrete substances necessary for the digestion of chyme. These secretions
are delivered to the duodenum through ducts (Figure 40-16).
The liver produces bile, which contains salts necessary for fat
The liver, which weighs 1200 to 1600 g, is the largest solid
organ in the body. It is located under the right diaphragm and is
divided into right and left lobes. The larger, right lobe is divided
further into the caudate and quadrate lobes (Figure 40-17). The
falciform ligament separates the right and left lobes and attaches
the liver to the anterior abdominal wall. A fibrous cord called
the round ligament (ligamentum teres) extends along the free
edge of the falciform ligament. The round ligament is the remnant of the umbilical vein and extends from the umbilicus to
the inferior surface of the liver. The coronary ligament branches
from the falciform ligament and extends over the superior surface of the right and left lobes, adhering the liver to the inferior
surface of the diaphragm. The liver is covered by a fibroelastic capsule called the Glisson capsule. When the liver is diseased
or swollen, distention of the capsule causes pain because it is
innervated by afferent neurons.
The metabolic functions of the liver require a large amount
of blood. The liver receives blood from both arterial and venous
sources. The hepatic artery branches from the celiac artery
and provides oxygenated blood at the rate of 400 to 500 ml/
minute (about 25% of the cardiac output). The hepatic portal
vein, which receives deoxygenated blood from the inferior and
superior mesenteric veins and the splenic vein, delivers about
1000 to 1200 ml/minute of blood to the liver. The hepatic portal
vein, which carries 70% of the blood supply to the liver, is rich
in nutrients that have been absorbed from the digestive tract
(Figure 40-18).
Within the liver lobes are multiple, smaller anatomic units
called liver lobules (Figure 40-19). The lobules are formed of
cords or plates of hepatocytes, which are the functional cells
of the liver. These cells are capable of regeneration; therefore,
damaged or resected liver tissue can regrow. Hepatocytes
secrete electrolytes, lipids, lecithin, bile acids, and cholesterol
into the canaliculi. Plasma proteins are also synthesized and
released into the bloodstream. Lipocytes are star-shaped cells
that store lipids, including vitamin A. Small capillaries, or
sinusoids, are located between the plates of hepatocytes. The
sinusoids receive a mixture of venous and arterial blood from
branches of the hepatic artery and hepatic portal vein. Blood
from the sinusoids drains into a central vein in the middle of
each liver lobule. Venous blood from all the lobules then flows
into the hepatic vein, which empties into the inferior vena cava.
The sinusoids of the liver lobules are lined with highly permeable endothelium. This permeability enhances the transport of
nutrients from the sinusoids into the hepatocytes, where they
are metabolized.30 The sinusoids are also lined with phagocytic
1410
Right lobe
Unit XII The Digestive System
Gallbladder
Inferior vena cava
Quadrate lobe
Left
lobe
Falciform
ligament
Right lobe
proper
Left lobe
Common
hepatic duct
Hepatic
artery
Falciform
ligament
Hepatic
portal vein
Round ligament
Gallbladder
Inferior vena cava
A
Caudate lobe
B
FIGURE 40-17 Gross Structure of the Liver. A, Anterior view. B, Inferior view. (From Patton KT, Thibodeau GA: Anatomy
& physiology, ed 8, St Louis, 2013, Mosby.)
Inferior vena cava
Hepatic
veins
Liver
Hepatic
portal
vein
Duodenum
Pancreas
Superior
mesenteric
vein
Ascending
colon
Appendix
Stomach
Sinusoid
Plates of
hepatic cells
Central
veins
Gastric vein
Spleen
Pancreatic
veins
Splenic vein
Gastroepiploic
vein
Bile
duct
Inferior
mesenteric
vein
Descending
colon
Small
intestine
Branch
of portal
vein
Hepatocytes
Bile
canaliculi
Branch of
hepatic
artery
FIGURE 40-18 Hepatic Portal Circulation. In this unusual circulatory route,
a vein is located between two capillary beds. The hepatic portal vein collects blood
from capillaries in visceral structures located in the abdomen and empties into the
liver for distribution to the hepatic capillaries. Hepatic veins return blood to the
inferior vena cava. (Organs are not drawn to scale.) (From Patton KT, Thibodeau GA:
Anatomy & physiology, ed 8, St Louis, 2013, Mosby.)
FIGURE 40-19 Diagrammatic Representation of a Liver Lobule. A central
vein is located in the center of the lobule, with plates of hepatocytes disposed radially. Branches of the portal vein and hepatic artery are located on the periphery of
the lobule, and blood from both vessels perfuses the sinusoids. Peripherally located
bile ducts drain the bile canaliculi that run between the hepatocytes. (Modified
from Patton KT, Thibodeau GA: Anatomy & physiology, ed 8, St Louis, 2013, Mosby.)
cells, known as Kupffer cells, which are part of the mononuclear
phagocyte system (see Chapters 7 and 27) and are the largest
population of tissue macrophages in the body. They are bactericidal and central to innate immunity.31 Stellate cells contain
retinoids (vitamin A), are contractile in liver injury, regulate
sinusoidal blood flow, may proliferate into myofibroblasts, and
participate in liver fibrosis.32 They remove foreign substances
from the blood and trap bacteria. Pit cells are natural killer cells
found in the sinusoidal lumen; they produce interferon-γ and
are important in tumor defense.33 Between the endothelial lining of the sinusoid and the hepatocyte is the Disse space, which
drains interstitial fluid into the hepatic lymph system.
Chapter 40 Structure and Function of the Digestive System
Liver
Hepatocytes synthesize
cholesterol to form
primary bile acids
Bile acid pool
Amino acids (glycine or
taurine) conjugate bile
acids to form bile salts
in bile
Gallbladder
Some bile is stored
for release during
eating
Hepatic portal vein
65% to 85% of bile salts
and secondary bile acids
enter the circulation with
protein binding and are
transported to liver
Duodenum and
jejunum
Bile salts emulsify fats
and form micelles to
transport fats through
the unstirred layer
Micelles release fats at
the brush border
Free bile salts proceed
through the intestinal
lumen
Ileum and colon
Bile salts are actively
transported across the
intestinal lumen or are
deconjugated by bacteria
into secondary
bile acids
that diffuse passively
across the lumen
Rectum
15% to 35% of bile salts
are excreted in feces
FIGURE 40-20 The Enterohepatic Circulation of Bile Salts.
Secretion of Bile
The liver assists intestinal digestion by secreting 700 to 1200
ml of bile per day. Bile is an alkaline, bitter-tasting yellowish green fluid that contains bile salts (conjugated bile acids),
cholesterol, bilirubin (a pigment), electrolytes, and water. It is
formed by hepatocytes and secreted into the canaliculi, which
are small channels adjacent to hepatocytes. Bile salts, which
are conjugated bile acids, are required for the intestinal emulsification and absorption of fats. The bile canaliculi empty
into hepatic bile ducts and eventually drain into the common bile duct (see Figure 40-19). The union of the common
bile duct and pancreatic duct is at the papilla or ampulla of
Vater, which empties into the duodenum through an opening called the major duodenal papilla and is surrounded by
the sphincter of Oddi.34 Having facilitated fat emulsification and absorption in the small intestine, most bile salts are
actively absorbed in the terminal ileum and returned to the
liver through the portal circulation for resecretion. The pathway for recycling of bile salts is termed the enterohepatic circulation (Figure 40-20).35
1411
Bile has two fractional components: the acid-dependent
fraction and the acid-independent fraction. Hepatocytes secrete
the bile acid–dependent fraction of the bile. This fraction consists of bile acids, cholesterol, lecithin (a phospholipid), and
bilirubin (a bile pigment). The bile acid–independent fraction
of the bile, which is secreted by the hepatocytes and epithelial
cells of the bile canaliculi, is a bicarbonate-rich aqueous fluid
that gives bile its alkaline pH.
Bile salts are conjugated in the liver from primary and secondary bile acids. The primary bile acids are cholic acid and
chenodeoxycholic (chenic acid or chenodiol) acid. These acids
are synthesized from cholesterol by the hepatocytes. The secondary bile acids are deoxycholic acid and lithocholic acid.
These acids are formed in the small intestine by the action of
intestinal bacteria, after which they are absorbed and flow to
the liver (see Figure 40-20). Both forms of bile acids are conjugated with amino acids (glycine or taurine) in the liver to form
bile salts. Conjugation makes the bile acids more water soluble, thus restricting their diffusion from the duodenum and
ileum. The primary and secondary bile acids together form the
bile acid pool.
Bile secretion is called choleresis. A choleretic agent is a
substance that stimulates the liver to secrete bile. One strong
stimulus is a high concentration of bile salts. Other choleretics include secretin, which increases the rate of bile flow
by promoting the secretion of bicarbonate from canaliculi
and other intrahepatic bile ducts; cholecystokinin; and vagal
stimulation.
Metabolism of Bilirubin
Bilirubin is a byproduct of destruction of aged red blood cells.
It gives bile a greenish black color and produces the yellow tinge
of jaundice. Aged red blood cells are taken up and destroyed
by macrophages of the mononuclear phagocyte system, primarily in the spleen and liver. (In the liver these macrophages
are Kupffer cells.) Within these cells, hemoglobin is separated
into its component parts—heme and globin (Figure 40-21).
The globin component is further degraded into its constituent
amino acids, which are recycled to form new protein. The heme
moiety is converted to biliverdin by the enzymatic (heme oxygenase) cleavage of iron. The iron attaches to transferrin in the
plasma and can be stored in the liver or used by the bone marrow to make new red blood cells. The biliverdin is enzymatically
converted to bilirubin in the macrophage of the mononuclear
phagocytic system and then is released into the plasma. In the
plasma, bilirubin binds to albumin and is known as unconjugated bilirubin, or free bilirubin, which is lipid soluble.
Bilirubin also may have a role as an antioxidant and provide
cytoprotection.36,37
In the liver, unconjugated bilirubin moves from plasma
in the sinusoids into the hepatocyte. Within hepatocytes it
joins with glucuronic acid to form conjugated bilirubin,
which is water soluble. Conjugation transforms bilirubin
from a lipid-soluble substance that can cross biologic membranes to a water-soluble substance that can be excreted in
the bile. When conjugated bilirubin reaches the distal ileum
and colon, it is deconjugated by bacteria and converted to
1412
Unit XII The Digestive System
TABLE 40-3 PROTEINS IN THE BODY
Red blood cell
destruction
Mononuclear
phagocytes
in spleen and
liver
Hemoglobin
Globin
Heme
ROLE
EXAMPLE
Contraction
Energy
Fluid balance
Protection
Actin and myosin enable muscle contraction.
Proteins can be metabolized for energy.
Albumin is a major source of plasma oncotic pressure.
Antibodies and complement protect against infection
and foreign substances.
Enzymes control chemical reactions; hormones regulate
many physiologic processes.
Collagen fibers provide structural support to many parts
of the body; keratin strengthens skin, hair, and nails.
Hemoglobin transports oxygen and carbon dioxide
in the blood; plasma proteins serve as transport
molecules; proteins in cell membranes control
movement of materials into and out of cells.
Hemostasis is regulated by proteins that balance
coagulation and anticoagulation.
Regulation
Structure
Iron
Biliverdin
Iron pool
Unconjugated
bilirubin
(lipid soluble)
Plasma
Amino acid
pool
Coagulation
Unconjugated bilirubin
Albumin
(bilirubin/albumin complex makes
bilirubin soluble in blood)
Hepatocytes
in liver
Unconjugated bilirubin
Glucuronic acid
Bile channels
Conjugated bilirubin
(conjugated bilirubin is water soluble)
excreted with bile
Intestine
Conjugated bilirubin
excreted with stools
Bacterial
action
Liver
Kidney
Urobilinogen
Feces
Transport
Urine
FIGURE 40-21 Bilirubin Metabolism. See text for further explanation.
urobilinogen. Urobilinogen is then reabsorbed in the intestines and transported to the kidney where it is excreted in
the urine as urobilin, giving urine its yellow color. A small
amount of urobilin is recirculated back into the liver and
eliminated in feces as stercobilin, which contributes to the
stool’s brown pigmentation.
Vascular and Hematologic Functions
Because of its extensive vascular network, the liver can store
a large volume of blood. The amount stored at any one time
depends on pressure relationships in the arteries and veins. The
liver also can release blood to maintain systemic circulatory volume in the event of hemorrhage.
Kupffer cells (macrophages) in the sinusoids of the liver
remove bacteria and foreign particles from blood in the hepatic
circulation. Because the liver receives all of the venous blood
from the gut and pancreas, the Kupffer cells play an important
role in destroying intestinal bacteria and preventing infections.
The liver also has hemostatic functions. It synthesizes most
of the clotting factors (see Chapters 7 and 27). Vitamin K1
(synthesized by plants and ingested in the diet) and vitamin
K2 (synthesized by intestinal bacteria) are fat-soluble vitamins
essential for the synthesis of clotting factors (prothrombin
and factors VII, IX, and X). Because bile salts are needed for
absorption of fats, vitamin K absorption depends on adequate
bile production in the liver. Impairment of vitamin K absorption diminishes production of clotting factors and increases
risk of bleeding.
Metabolism of Nutrients
Fats. Ingested fat absorbed by lacteals in the intestinal
villi enters the liver through the lymphatics, primarily as
triglycerides. In the liver the triglycerides can be hydrolyzed
to glycerol and free fatty acids and used to produce metabolic
energy (ATP), or they can be released into the bloodstream
bound to proteins (lipoproteins). The lipoproteins are carried by
the blood to adipose cells for storage. The liver also synthesizes
phospholipids and cholesterol, which are needed for the hepatic
production of bile salts, steroid hormones, components of
plasma membranes, and other special molecules.
Proteins. Protein synthesis requires the presence of all the
essential amino acids (obtained only from food), as well as
nonessential amino acids. Proteins perform many important
roles in the body and are summarized in Table 40-3.
Within hepatocytes, amino acids are converted to carbohydrates by the removal of ammonia (NH3), a process known as
deamination. The ammonia is converted to urea by the liver
and passes into the blood to be excreted by the kidneys. The
plasma proteins, including albumins and globulins (with the
exception of gamma globulin, which is formed in lymph nodes
and lymphoid tissue), are synthesized by the liver. The liver also
Chapter 40 Structure and Function of the Digestive System
synthesizes several nonessential amino acids and serum enzymes
that become elevated with liver injury (and other diseases):
• Aspartate aminotransferase (AST) (previously called
serum glutamate-oxaloacetate transaminase [SGOT]):
also present in red blood cells and skeletal muscle; AST
transfers an α-amino group between aspartate and
glutamate.
• Alanine aminotransferase (ALT) (previously called
serum glutamate-pyruvate transaminase [SGPT]): also
present in small amounts in the kidneys, heart, skeletal
muscle, and pancreas; ALT transfers an amino group
from alanine to α-ketoglutarate to form pyruvate and
glutamate.
• Lactate dehydrogenase (LDH): catalyzes the conversion
of lactate to pyruvate; LDH is widely distributed throughout the body and different isoenzymes are found in different tissues.
• Alkaline phosphatase: removes phosphate groups, particularly in an alkaline environment.
• Gamma-glutamyltransferase: transfers the gammaglutamyl moiety of glutathione to an acceptor to form
glutamate and is a pro-oxidant.
Reference values for the above enzymes can be reviewed in
Table 40-6 and are summarized on the inside back book cover.
Carbohydrates. The liver contributes to the stability of blood
glucose levels by releasing glucose during states of hypoglycemia
(low blood glucose levels) and taking up glucose during states
of hyperglycemia (high blood glucose levels) and storing it as
glycogen (glyconeogenesis) or converting it to fat. When all
glycogen stores have been used, the liver can convert amino
acids and glycerol to glucose.
Metabolic Detoxification
The liver alters exogenous and endogenous chemicals (e.g.,
drugs), foreign molecules, and hormones to make them less
toxic or less biologically active. This process, called metabolic
detoxification (biotransformation), diminishes intestinal
or renal tubular reabsorption of potentially toxic substances
and facilitates their intestinal and renal excretion. In this way
alcohol, barbiturates, amphetamines, steroids, and hormones
(including estrogens, aldosterone, antidiuretic hormone, and
testosterone) are metabolized or detoxified, preventing excessive accumulation and adverse effects.
Although metabolic detoxification is usually protective, sometimes the end products of metabolic detoxification
become toxins. Those of alcohol metabolism, for example, are
acetaldehyde and hydrogen. Excessive intake of alcohol over a
prolonged period causes these end products to damage hepatocytes. Acetaldehyde damages cellular mitochondria, and the
excess hydrogen promotes fat accumulation. This is how alcohol impairs the liver’s ability to function (see Chapter 2).
Storage of Minerals and Vitamins
The liver stores certain vitamins and minerals, including iron and
copper, in times of excessive intake and releases them in times of
need. The liver can store vitamins B12 and D for several months
and vitamin A for several years. The liver also stores vitamins
1413
E and K. Iron is stored in the liver as ferritin, an iron-protein
complex, and is released as needed for red blood cell production.
Gallbladder
The gallbladder is a saclike organ that lies on the inferior surface of the liver (Figures 40-17 and 40-22). The wall of the gallbladder is composed of the mucous membrane, muscularis,
and serosa. The primary function of the gallbladder is to store
and concentrate bile between meals. During the interdigestive
period, bile flows from the liver through the right or left hepatic
duct into the common bile duct and meets resistance at the
closed sphincter of Oddi, which controls flow into the duodenum and prevents reflux of duodenal contents into the pancreatobiliary system. Bile then flows into the gallbladder through
the cystic duct where it is concentrated and stored. The mucosa
of the gallbladder wall readily absorbs water and electrolytes,
leaving a high concentration of bile salts, bile pigments, and
cholesterol. The gallbladder holds about 90 ml of bile.
Within 30 minutes after eating, the gallbladder begins to
contract, forcing stored bile through the cystic duct and into
the common bile duct. The sphincter of Oddi relaxes, and bile
flows into the duodenum through the major duodenal papilla.
During the cephalic and gastric phases of digestion, gallbladder contraction is mediated by cholinergic branches of the
vagus nerve. Hormonal regulation of gallbladder contraction is
derived primarily from the release of cholecystokinin secreted by
the duodenal and jejunal mucosa in the presence of fat. Vasoactive intestinal peptide, pancreatic polypeptide, and sympathetic
nerve stimulation relax the gallbladder.
Exocrine Pancreas
The pancreas is approximately 20 cm long, with its head tucked
into the curve of the duodenum and its tail touching the spleen.
The body of the pancreas lies deep in the abdomen, behind the
stomach (see Figure 40-16). The pancreas is unique in that it
has endocrine as well as exocrine functions. The endocrine pancreas secretes insulin, glucagon, somatostatin, and pancreatic
polypeptide (see Chapter 21).
The exocrine pancreas is composed of acinar cells that
secrete enzymes and networks of ducts that secrete alkaline
fluids with important digestive functions. The acinar cells are
organized into spherical lobules (acini) around small secretory
ducts (see Figure 40-22). Secretions drain into a system of ducts
that leads to the pancreatic duct (Wirsung duct), which empties into the common bile duct at the ampulla of Vater and then
through the duodenal papilla into the duodenum. In some individuals an accessory duct (the duct of Santorini) branches off
the pancreatic duct and drains directly into the duodenum at
an opening called the minor duodenal papilla (see Figure 40-22).
Arterial blood is supplied to the pancreas by branches of the
celiac and superior mesenteric arteries. Venous blood leaves the
head of the pancreas through the tributaries to the hepatic portal vein, with the body and tail being drained through the splenic
vein. All hormonal pancreatic secretions also pass through the
hepatic portal vein into the liver.
Pancreatic innervation arises from parasympathetic neurons
of the vagus nerve, which stimulate enzymatic and hormonal
1414
Unit XII The Digestive System
Neck of
gallbladder
Right and left
hepatic ducts
Body of
gallbladder
Cystic duct
Fundus of
gallbladder
Common hepatic duct
Common
bile duct
Duodenum
Accessory
Minor
pancreatic duct
duodenal
Body of pancreas
papilla
Tail of
pancreas
Ampulla
of Vater
Major
duodenal
papilla
Pancreatic duct
Jejunum
Head of pancreas
Alpha cells
(secrete glucagon)
Beta cells
(secrete insulin)
Pancreatic
islet
Acini
Duct cells
secrete
bicarbonate
Vein
Acinar cells
secrete enzymes
Pancreatic duct
(to duodenum)
Centroacinar cells secrete
electrolytes and water
FIGURE 40-22 Associated Structures of the Gallbladder, Pancreas, and Pancreatic Acinar Cells and Duct. (Modified from Patton KT, Thibodeau GA: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.)
secretion. Sympathetic postganglionic fibers from the celiac and
superior mesenteric plexuses innervate the blood vessels and
cause vasoconstriction and inhibit pancreatic secretion.38
The aqueous secretions of the exocrine pancreas are isotonic
and contain potassium, sodium, bicarbonate, magnesium,
calcium, and chloride. Sodium and potassium concentrations
are about equal to those in the plasma. The concentration of
bicarbonate in pancreatic juice varies directly with the secretory
flow rate. As bicarbonate secretion increases, chloride secretion
decreases to maintain a constant anionic concentration. The
highly alkaline pancreatic juice neutralizes the acidic chyme
that enters the duodenum from the stomach and provides the
alkaline medium needed for the actions of digestive enzymes
and the absorption of fat in the intestine.
In the pancreas, transport of water and electrolytes through
the ductal epithelium involves active and passive mechanisms.
The ductal cells actively transport hydrogen into the blood and
bicarbonate into the duct lumen. Potassium and chloride are
secreted by diffusion according to changes in electrochemical potential gradients. As the secretion flows down the duct,
water is osmotically transported into the juice until it becomes
isosmotic. At low flow rates, bicarbonate is exchanged passively
for chloride, but at higher flow rates there is less time for this
exchange and bicarbonate concentration increases. Because
Chapter 40 Structure and Function of the Digestive System
1415
TABLE 40-4 SELECTED STUDIES OF GASTROINTESTINAL STRUCTURE
TEST
DESCRIPTION
APPLICATION
Plain roentgenograms
Use of high-energy electromagnetic radiation to evaluate tissue
structure by radiopacity or radiolucency
Introduction of radiopaque substances into the upper or lower
gastrointestinal tract
Visualization of the position, size, and structure of
abdominal contents
Enhanced visualization of the contours, position,
and size of the gastrointestinal tract to detect
umbilical hernia, ulcers, diverticula, congenital
anomalies, polyps, tumors, strictures, obstructions
Visualization or biopsy of inflamed hernias, polyps,
ulcers, strictures, varices, tumors, sites of
bleeding, mucosal or neoplastic lesions and for
culture of Helicobacter pylori from stomach
Air or barium contrast
roentgenograms
Endoscopy
Esophagoscopy (esophagus)
Gastroscopy (stomach)
Duodenoscopy (duodenum)
Colonoscopy (large intestine)
Sigmoidoscopy (sigmoid colon)
Ultrasound
Passage of rigid or flexible (fiberoptic) endoscope into the
gastrointestinal tract for visualization or biopsy
Computed tomography (CT)
Use of a computer to integrate differences in absorption of a large
number of x-rays to produce a cross-sectional image; may be
done with contrast agents
Projection of differences in magnetic properties of molecules within
different cells and tissues, using the field of a large magnet
Magnetic resonance imaging (MRI)
Use of piezoelectric crystal to generate sound waves that are
reflected from tissue interfaces to provide an image
eating stimulates the flow of pancreatic juice, the juice is most
alkaline when it needs to be—during digestion. Secretion of the
aqueous and enzymatic components of pancreatic juice is controlled by hormonal and vagal stimuli.
The pancreatic enzymes hydrolyze proteins (proteases), carbohydrates (amylases), and fats (lipases). The proteases include
trypsin, chymotrypsin, carboxypeptidase, and elastase. These
enzymes are secreted in their inactive forms—that is, as trypsinogen, chymotrypsinogen, and procarboxypeptidase—to protect the pancreas from the digestive effects of its own enzymes.
For further protection the pancreas produces trypsin inhibitor, which prevents the activation of proteolytic enzymes while
they are in the pancreas. Once in the duodenum, the inactive
forms (proenzymes) are activated by enterokinase, an enzyme
secreted by the duodenal mucosa. Trypsinogen is the first proenzyme to be activated. Its conversion to trypsin stimulates the
conversion of chymotrypsinogen to chymotrypsin and procarboxypeptidase to carboxypeptidase. Each of these enzymes
cleaves specific peptide bonds to reduce polypeptides to smaller
peptides.
Pancreatic α-amylase is secreted in active form and
digests intestinal carbohydrate by cleaving interior α-1,4glucosidic bonds to yield glucose and maltose at an optimum
pH of approximately 6.9. Pancreatic lipases hydrolyze triglycerides, cholesterol, and phospholipids to free fatty acids
in the intestine. Secretin stimulates the acinar and duct cells
to secrete the bicarbonate-rich fluid that neutralizes chyme
and prepares it for enzymatic digestion. As chyme enters the
duodenum, its acidity (pH of 4.5 or less) stimulates the S cells
of the duodenum to release secretin, which is absorbed by the
intestine and delivered to the pancreas in the bloodstream. In
the pancreas, secretin causes ductal and acinar cells to release
alkaline fluid. Secretin also inhibits the actions of gastrin,
thereby decreasing gastric hydrochloric acid secretion and
Imaging of abdominal organs (gallbladder, liver,
pancreas, spleen), masses, stones, abscesses,
structural abnormalities
Imaging of gallbladder, liver, pancreas, spleen, cysts,
hematomas, abscesses, stones, extrahepatic bile
ducts, and portal vein
Same applications as CT scan; also can detect blood
flow and vessel patency
motility. The overall effect is to neutralize the contents of the
duodenum.
Enzymatic secretion follows, stimulated by cholecystokinin,
which activates ACh from the vagus nerve and release of ACh
from pancreatic stellate cells.39 Cholecystokinin is released in
the duodenum in response to the essential amino acids and
fatty acids already present in chyme. Once in the small intestine,
activated pancreatic enzymes inhibit the release of more cholecystokinin and ACh. This feedback mechanism inhibits the
secretion of more pancreatic enzymes. Pancreatic polypeptide
is released after eating and inhibits postprandial pancreatic exocrine secretion. (Table 40-1 summarizes hormonal stimulation
of pancreatic secretions.)
Tests of Digestive Function
Gastrointestinal Tract
Although important diagnostic information can be obtained
from the patient’s medical history and presenting symptoms,
numerous disease-specific tests must be performed to evaluate the structure and function of the gastrointestinal tract. A
description of selected studies is presented in Tables 40-4
and 40-5. Radiography and imaging techniques—including
radionuclide, positron emission tomography (PET), magnetic
resonance (MR), computed tomography (CT) scanning, and
ultrasound—are procedures for evaluating structure and function. Plain radiographs using contrast media such as barium- or
iodine-containing compounds can be used to outline the gastrointestinal lumen, biliary tree and pancreatic ducts, fistulae,
and arteriovenous systems. CT scanning is particularly useful
for diagnosis of intestinal lesions and pancreatic or hepatic
tumors or cysts. Ultrasonic scanning is a safe, simple, and relatively inexpensive technique used to detect gallstones and intraabdominal masses, particularly abscesses.
1416
Unit XII The Digestive System
TABLE 40-5 SELECTED TESTS OF GASTROINTESTINAL FUNCTION
TEST
NORMAL FINDINGS
CLINICAL SIGNIFICANCE OF ABNORMAL FINDINGS
Stool studies
Resident microorganisms: clostridia,
enterococci, Pseudomonas, a few
yeasts
Detection of Salmonella typhi (typhoid fever), Shigella (dysentery), Vibrio
cholerae (cholera), Yersinia (enterocolitis), Escherichia coli (gastroenteritis),
Staphylococcus aureus (food poisoning), Clostridium botulinum (food poisoning),
Clostridium perfringens (food poisoning), Aeromonas (gastroenteritis)
Steatorrhea (increased values) can result from intestinal malabsorption or
pancreatic insufficiency
Large amounts of pus are associated with chronic ulcerative colitis, abscesses,
and anorectal fistula
Positive tests associated with bleeding
Fat: 2-6 g/24 hr
Pus: none
Occult blood: none (orthotolidine or
guaiac test)
Ova and parasites: none
d-Xylose
absorption
Gastric acid stimulation
Manometry (use of water-filled
catheters connected to pressure
transducers passed into the
esophagus, stomach, colon, or
rectum to evaluate contractility)
Culture and sensitivity of duodenal
contents
Breath tests
Glucose or d-xylose breath test
Urea breath test
Lactose breath test
5-hr urinary excretion: 4.5 g/L
Peak blood level: >30 mg/dl
11-20 mEq/hr after stimulation
Values vary at different levels of the
intestine
Detection of Entamoeba histolytica (amebiasis), Giardia lamblia (giardiasis), and
worms
Differentiation of pancreatic steatorrhea (normal d-xylose absorption) from
intestinal steatorrhea (impaired d-xylose absorption)
Detection of duodenal ulcers, Zollinger-Ellison syndrome (increased values),
gastric atrophy, gastric carcinoma (decreased values)
Inadequate swallowing, motility, sphincter function
No pathogens
Detection of Salmonella typhi (typhoid fever)
Negative for hydrogen or CO2
Negative for isotopically labeled CO2
Negative for exhaled hydrogen
May indicate intestinal bacterial overgrowth
Presence of Helicobacter pylori infection
Lactose intolerance
Fiberoptic endoscopy, using flexible endoscopes, allows
direct visualization of the gastrointestinal tract. A biopsy
channel allows tissue sampling, and suction can be applied to
remove gastrointestinal secretions or blood. Analysis of stool,
gastric secretions, tissue, and plasma provides important clues
to infection, malabsorption syndromes, ulcerative lesions, and
tumor growth.
Liver
A variety of diagnostic tests can be performed to evaluate liver
function40,41 (Table 40-6). Imaging techniques similar to those
described for the gastrointestinal tract also are useful for evaluating liver structure and function. Nuclear imaging is useful
after liver transplant.42 Elevated plasma levels of liver enzymes
are associated with many liver diseases because of the release of
cytoplasmic enzymes into the circulation when there is damage
to the hepatocyte. Of particular importance are elevations of
aminotransferases and lactate dehydrogenase (LDH). Obstruction of bile canaliculi or ducts results in regurgitation of bile
back into the hepatic sinusoids and into the circulation, manifesting with elevation of conjugated bilirubin levels. Prothrombin times (a measure of clotting tendency) are often prolonged
with both hepatitis and chronic liver disease. In severe disease,
other plasma proteins, such as albumin and globulins, may be
diminished as a result of hepatocyte damage. Liver biopsies are
often performed to evaluate the extent of liver involvement or
degeneration with cirrhosis, hepatitis, or fatty liver disease.
Gallbladder
Evaluation of structural alterations in the gallbladder may be
achieved by the use of various imaging techniques. Table 40-7
summarizes these techniques. Obstruction of the bile ducts
from stones, tumors, or inflammation prevents the flow of
bile from the liver and gallbladder from reaching the gastrointestinal tract. Both the conjugated and total serum bilirubin
values are elevated, urine urobilinogen level is increased, stools
are clay colored, and jaundice develops. Fat absorption can be
impaired and the prothrombin time prolonged if vitamin K is
not absorbed. With inflammation of the gallbladder, the white
cell count is elevated.
Exocrine Pancreas
Tests of pancreatic function are summarized in Table 40-8. Evaluation of serum lipase and urinary amylase provides particularly significant measures of pancreatic injury. Inflammation or
obstruction of the pancreas results in an early increase in serum
amylase levels. Serum lipase level remains elevated after serum
amylase has returned to normal levels and provides greater
sensitivity with delayed presentation of pancreatitis. Elevation
of urine amylase level also occurs later (after 48 hours) when
serum amylase may have returned to normal levels. Urinary
trypsinogen 2 (available as dipstick) is used to diagnose acute
pancreatitis and is comparable to serum amylase and lipase.43
Increased stool fat can reflect pancreatic insufficiency caused by
decreased lipase secretion when biliary function is normal.
Chapter 40 Structure and Function of the Digestive System
1417
TABLE 40-6 COMMON LIVER FUNCTION TESTS
TEST
Serum Enzymes
Alkaline phosphatase
Gamma-glutamyltranspeptidase (GGT)
Aspartate aminotransferase (AST; previously serum
glutamate-oxaloacetate transaminase [SGOT])
Alanine aminotransferase (ALT; previously serum
glutamate-pyruvate transaminase [SGPT])
Lactate dehydrogenase (LDH)
5′-Nucleotidase
Bilirubin Metabolism
Serum bilirubin
Unconjugated (indirect)
Conjugated (direct)
total
Urine bilirubin
Urine urobilinogen
Serum Proteins
Albumin
Globulin
total
Albumin/globulin (A/G) ratio
Transferrin
Alpha fetoprotein (AFP)
Blood-Clotting Functions
Prothrombin time (PT)
Partial thromboplastin time (PTT)
Bromsulphthalein (BSP) excretion
NORMAL VALUE
INTERPRETATION
13-39 units/L
Male 12-38 units/L
Female 9-31 units/L
5-40 units/L
Increases with biliary obstruction and cholestatic hepatitis
Increases with biliary obstruction and cholestatic hepatitis
5-35 units/L
Increases with hepatocellular injury (and injury in other tissues, i.e., skeletal
and cardiac muscle)
Increases with hepatocellular injury and necrosis
90-220 units/L
2-11 units/L
Isoenzyme LD5 is elevated with hypoxic and primary liver injury
Increases with increase in alkaline phosphatase and cholestatic disorders
<0.8 mg/dl
0.2-0.4 mg/dl
<1.0 mg/dl
0
0-4 mg/24 hr
Increases with hemolysis (lysis of red blood cells)
Increases with hepatocellular injury or obstruction
Increases with biliary obstruction
Increases with biliary obstruction
Increases with hemolysis or shunting of portal blood flow
3.5-5.5 g/dl
2.5-3.5 g/dl
6-7 g/dl
1.5:1 to 2.5:1
250-300 mcg/dl
6-20 ng/ml
Reduced with hepatocellular injury
Increases with hepatitis
11.5-14 sec or 90-100% of
control
25-40 sec
<6% retention in 45 min
Increases with chronic liver disease (cirrhosis) or vitamin K deficiency
Ratio reverses with chronic hepatitis or other chronic liver disease
Liver damage with decreased values, iron deficiency with increased values
Elevated values in primary hepatocellular carcinoma
Increases with severe liver disease or heparin therapy
Increased retention with hepatocellular injury
TABLE 40-7 DIAGNOSTIC EVALUATION OF THE GALLBLADDER
TEST
APPLICATION
Plain roentgenogram of the abdomen
Oral cholecystogram (use of an oral contrast medium such as iopanoic
acid, which is excreted with bile and concentrated in the gallbladder for
visualization by radiography; may be administered as a double dose)
Intravenous cholangiography (use of intravenous contrast agents for
visualization of gallbladder and bile ducts)
Cholecystography (ultrasound imaging of gallbladder and bile ducts)
Visualization of calcified gallstones
Visualization of gallstones; evaluation of filling and emptying of gallbladder
Cholescintigraphy (radioisotope imaging of gallbladder)
Endoscopic retrograde cholangiography (instillation of contrast medium
through cannulation of ampulla of Vater with a duodenoscope)
Computed tomography (CT)
Aging and the Gastrointestinal
System
Age-related changes in gastrointestinal function can begin to
occur before 50 years of age.44 Tooth enamel and dentin wear
down, making the teeth vulnerable to cavities. Teeth are lost,
often as a result of periodontal (gum) disease, recession of
Diagnosis of acute gallbladder inflammation (cholecystitis) or disease of bile
ducts
Preferred method for detecting gallstones; differentiation of hepatic disease from
biliary obstruction; diagnosis of chronic cholecystitis
Diagnosis of cholecystitis in individuals allergic to iodine-containing contrast
agents; diagnosis of cystic duct obstruction
Differentiation of intrahepatic or extrahepatic obstructive jaundice
Diagnosis of biliary obstruction or malignancy when ultrasound is not successful
the gums, osteoporotic bone changes, and more brittle roots
that fracture easily. Taste buds decline in number, and the
sense of smell diminishes.45 Together these losses decrease the
sense of taste. Salivary secretion decreases and contributes to
dry mouth and loss of taste.46 In very old adults these oral and
sensory changes make eating less pleasurable and reduce appetite. Food may not be chewed or lubricated sufficiently, making
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Unit XII The Digestive System
TABLE 40-8 SELECTED TESTS OF PANCREATIC FUNCTION
TEST
NORMAL VALUE
CLINICAL SIGNIFICANCE
Serum amylase
Serum lipase
60-180 Somogyi units/ml
1.5 Somogyi units/ml
Urine amylase
Secretin test
35-260 Somogyi units/hr
Volume 1.8 ml/kg/hr
Bicarbonate concentration: >80 mEq/L
Bicarbonate output: >10 mEq/L/30 sec
2-5 g/24 hr
Elevated levels with pancreatic inflammation
Elevated levels with pancreatic inflammation (may be elevated with other conditions;
differentiates with amylase isoenzyme study)
Elevated levels with pancreatic inflammation
Decreased volume with pancreatic disease as secretin stimulates pancreatic secretion
Stool fat
Measures fatty acids; decreased pancreatic lipase increases stool fat
swallowing difficult. The esophagus develops decreased motility, and changes in the upper esophageal sphincter, history of
stroke, and dementia may affect swallowing and contribute to
gastroesophageal reflux.47
Age also diminishes gastric motility and volume, including
secretion of bicarbonate and gastric mucus in some individuals. Acid content of gastric juice is related to gastric atrophy,
which results in hypochlorhydria (insufficient hydrochloric
acid), delayed gastric emptying, and compromise of the gastric mucosal barrier.48 Decreased production of intrinsic factor leads to inadequate small intestinal absorption of vitamin
B12 and pernicious anemia.49 Aging may be associated with
a change in the composition of the intestinal microflora and
increased susceptibility to disease.50 The ileal villi of the small
intestine may become broader and shorter, perhaps because of
a decrease in cell turnover. Intestinal absorption, motility, and
blood flow decrease, impairing nutrient absorption.51 Proteins,
fats, minerals (including iron and calcium), and vitamins are
absorbed more slowly and in lesser amounts, and absorption
of carbohydrates is decreased. Intestinal transit time is delayed.
Constipation is often described as a condition of old age, but
it is probably caused by lifestyle factors (e.g., diet, lack of fluid
intake) rather than physiologic decline although studies demonstrate there can be alterations in intestinal innervation.52
The rate of liver regeneration decreases with advancing age
but the volume of the liver can be maintained.53 Alterations in
liver function in older individuals are usually a sign of a pathologic condition. Liver blood flow and enzyme activity decrease
with age and can influence the efficiency of drug and alcohol metabolism.54 However, liver function test results often
remain within relatively normal ranges. Alterations in liver
function in older individuals are usually a sign of a pathologic
condition. The pancreas undergoes structural changes, such as
fibrosis, fatty acid deposits, and atrophy. Pancreatic secretion
decreases, but there is usually no observable dysfunction.55
Aging does not cause apparent changes in the structure and
function of the gallbladder and bile ducts, but the incidence of
gallstones increases.56
SUMMARY REVIEW
The Gastrointestinal Tract
1.The major functions of the gastrointestinal tract are the
mechanical and chemical breakdown of food and the
absorption of digested nutrients.
2.The gastrointestinal tract is a hollow tube that extends from
the mouth to the anus.
3.The walls of the gastrointestinal tract have several layers:
mucosa, muscularis mucosa, submucosa, muscularis (circular muscle and longitudinal muscle), and serosa (adventitia in the esophagus).
4.Except for swallowing and defecation, which are controlled
voluntarily, the functions of the gastrointestinal tract are controlled by extrinsic autonomic nerves (vagus, parasympathetic
splanchnic, and sympathetic nerves) and intrinsic autonomic
nerves (enteric nervous system) and intestinal hormones.
5.Digestion begins in the mouth, with chewing and salivation. The digestive component of saliva is α-amylase, which
initiates carbohydrate digestion.
6.The esophagus is a muscular tube that transports food from
the mouth to the stomach. The muscularis in the upper part
of the esophagus is striated muscle, and that in the lower
part is smooth muscle.
7.Swallowing is controlled by the swallowing center in the
reticular formation of the brain. The two phases of swallowing are the oropharyngeal phase (voluntary swallowing)
and the esophageal phase (involuntary swallowing).
8.Food is propelled through the gastrointestinal tract by peristalsis: waves of sequential relaxations and contractions of
the muscularis.
9.The lower esophageal sphincter opens to admit swallowed
food into the stomach and then closes to prevent regurgitation of food back into the esophagus.
10.The stomach is a baglike structure that secretes digestive
juices, mixes and stores food, and propels partially digested
food (chyme) into the duodenum. The smooth muscles of
the stomach include the outer longitudinal, middle circular,
and internal oblique.
11.The vagus nerve stimulates gastric (stomach) secretion and
motility.
12.The hormones gastrin and motilin stimulate gastric emptying; the hormones secretin and cholecystokinin delay gastric emptying.
13.Gastric glands in the fundus and body of the stomach secrete
intrinsic factor, which is needed for vitamin B12 absorption,
Chapter 40 Structure and Function of the Digestive System
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S U M M A R Y R E V I E W—cont’d
and hydrochloric acid, which dissolves food fibers, kills
microorganisms, and activates the enzyme pepsin.
14.Chief cells in the stomach secrete pepsinogen, which is
converted to pepsin in the acidic environment created by
hydrochloric acid.
15.Acid secretion is stimulated by the vagus nerve, gastrin,
and histamine and inhibited by sympathetic stimulation
and cholecystokinin. Acetylcholine stimulates pepsin
secretion.
16.Mucus is secreted throughout the stomach and protects the
stomach wall from acid and digestive enzymes.
17.The three phases of acid secretion by the stomach are the
cephalic phase (anticipation and swallowing), the gastric phase (food in the stomach), and the intestinal phase
(chyme in the intestine).
18.The small intestine is 5 m long and has three segments: the
duodenum, jejunum, and ileum. Digestion and absorption
of all major nutrients and most ingested water occur in the
small intestine.
19.The peritoneum is a double layer of membranous tissue.
The visceral layer covers the abdominal organs, and the
parietal layer extends along the abdominal wall.
20.Blood flow to the small intestine is primarily provided by
the superior mesenteric artery.
21.The duodenum receives chyme from the stomach through
the pyloric valve. The presence of chyme stimulates the liver
and gallbladder to deliver bile and the pancreas to deliver
digestive enzymes and alkaline secretions. Bile and enzymes
flow through an opening guarded by the sphincter of Oddi.
22.Bile is produced by the liver and is necessary for fat digestion and absorption. Bile’s alkalinity helps neutralize
chyme, thereby creating a pH that enables the pancreatic
enzymes to digest proteins, carbohydrates, and sugars.
23.Enzymes secreted by the small intestine (maltase, sucrase,
lactase), pancreatic enzymes (proteases, amylase, and
lipase), and bile salts act in the small intestine to digest proteins, carbohydrates, and fats.
24.Digested substances are absorbed across the intestinal wall
and then transported to the liver through the hepatic portal
vein, where they are metabolized further.
25.The ileocecal valve connects the small and large intestines
and prevents reflux into the small intestine.
26.Villi are small fingerlike projections that extend from the small
intestinal mucosa and increase its absorptive surface area.
27.Carbohydrates, amino acids, and fats are absorbed primarily by the duodenum and jejunum; bile salts and vitamin B12
are absorbed by the ileum. Vitamin B12 absorption requires
the presence of intrinsic factor.
28.Bile salts emulsify and hydrolyze fats and incorporate them
into water-soluble micelles that transport them through the
unstirred layer to the brush border of the intestinal mucosa.
The fat content of the micelles readily diffuses through the
epithelium into lacteals (lymphatic ducts) in the villi. From
there fats flow into the lymphatics and into the systemic circulation, which delivers them to the liver.
29.Minerals and water-soluble vitamins are absorbed by active
and passive transport throughout the small intestine.
30.Peristaltic movements created by longitudinal muscles propel the chyme along the intestinal tract, whereas contractions of the circular muscles (segmentation) mix the chyme
and promote digestion.
31.The ileogastric reflex inhibits gastric motility when the
ileum is distended.
32.
The intestinointestinal reflex inhibits intestinal motility
when one intestinal segment is overdistended.
33.The gastroileal reflex increases intestinal motility when gastric motility increases.
34.The large intestine consists of the cecum, appendix, colon
(ascending, transverse, descending, and sigmoid), rectum,
and anal canal.
35.The teniae coli are three bands of longitudinal muscle that
extend the length of the colon.
36.Haustra are pouches of colon that are formed with alternating contraction and relaxation of the circular muscles.
37.The mucosa of the large intestine contains mucus-secreting
cells and mucosal folds, but no villi.
38.The large intestine massages the fecal mass and absorbs
water and electrolytes.
39.Distention of the ileum with chyme causes the gastrocolic
reflex, or the mass propulsion of feces to the rectum.
40.
Defecation is stimulated when the rectum is distended
with feces. The conically contracted internal anal sphincter
relaxes and, if the voluntarily regulated external sphincter
relaxes, defecation occurs.
41.The largest numbers of intestinal bacteria are in the colon.
They are anaerobes consisting of Bacteroides, clostridia,
coliforms, and lactobacilli.
42.The intestinal tract is sterile at birth and becomes totally
colonized within 3 to 4 weeks.
43.Endogenous infections of the gastrointestinal tract occur by
excessive proliferation of bacteria, perforation of the intestine, or contamination from neighboring structures.
Accessory Organs of Digestion
1.The liver is the largest organ in the body. It has digestive, metabolic, hematologic, vascular, and immunologic
functions.
2.The liver is divided into the right and left lobes and is supported by the falciform, round, and coronary ligaments.
3.Liver lobules consist of plates of hepatocytes, which are the
functional cells of the liver.
4.The hepatic artery supplies blood to the liver. The portal
vein receives blood from the inferior and superior mesenteric veins.
5.Hepatocytes synthesize 700 to 1200 ml of bile per day and
secrete it into the bile canaliculi, which are small channels between the hepatocytes. The bile canaliculi drain
bile into the common bile duct and then into the duodenum through an opening called the major duodenal papilla
(sphincter of Oddi).
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Unit XII The Digestive System
S U M M A R Y R E V I E W—cont’d
6.Sinusoids are capillaries located between the plates of hepatocytes. Blood from the hepatic portal vein and hepatic
artery flows through the sinusoids to a central vein in each
lobule and then into the hepatic vein and inferior vena cava.
7.Kupffer cells, which are part of the mononuclear phagocyte
system, line the sinusoids and destroy microorganisms in
sinusoidal blood.
8.The primary bile acids are synthesized from cholesterol by
the hepatocytes. The primary acids are then conjugated to
form bile salts. The secondary bile acids are the product of
bile salt deconjugation by bacteria in the intestinal lumen.
9.Most bile salts and acids are recycled. The absorption of bile
salts and acids from the terminal ileum and their return to
the liver are known as the enterohepatic circulation of bile.
10.Bilirubin is a pigment liberated by the lysis of aged red
blood cells in the liver and spleen. Unconjugated bilirubin
is fat soluble and can cross cell membranes. Unconjugated
bilirubin is converted to water-soluble, conjugated bilirubin by hepatocytes and is secreted with bile.
11.Fats are synthesized by the liver from protein and carbohydrates and include glycerol, free fatty acids, phospholipids,
and cholesterol. Fat absorbed by intestinal lacteals is primarily triglyceride, which is hydrolyzed to glycerol and free
fatty acid.
12.Protein synthesis by the liver requires all essential amino
acids. The liver synthesizes albumin, globulin, and several
serum enzymes and can convert amino acids to carbohydrates by removal of ammonia.
13.Carbohydrates can be released as glucose, stored as glycogen, or converted to fat.
14.The liver performs many metabolic functions including
detoxification of exogenous and endogenous chemicals and
hormones.
15.The gallbladder is a saclike organ located in the inferior surface of the liver. The gallbladder stores bile between meals
and ejects it when chyme enters the duodenum.
16.Stimulated by cholecystokinin, the gallbladder contracts and
forces bile through the cystic duct and into the common bile
duct. The sphincter of Oddi relaxes, enabling bile to flow
through the major duodenal papilla into the duodenum.
17.The pancreas is a gland located behind the stomach. The
endocrine pancreas produces hormones (glucagon and
insulin) that facilitate the formation and cellular uptake of
glucose. The exocrine pancreas secretes an alkaline solution
and the enzymes (trypsin, chymotrypsin, carboxypeptidase,
α-amylase, lipase) that digest proteins, carbohydrates, and fats.
18.Secretin stimulates pancreatic secretion of alkaline fluid, and
cholecystokinin and ACh stimulate secretion of enzymes. Pancreatic secretions originate in acini and ducts of the pancreas
and empty into the duodenum through the common bile duct
or an accessory duct that opens directly into the duodenum.
Tests of Digestive Function
1.Numerous diagnostic tests can evaluate structure and function (digestion, secretion, absorption) of the gastrointestinal
tract. Radiographs and scans are most commonly used to evaluate structure, in addition to direct observation by endoscopy.
Gastric and stool analysis and blood studies provide important information about digestion, absorption, and secretion.
2.Plasma chemistry levels and imaging procedures are commonly used to diagnose alterations in liver function. Of
particular importance are the enzymes LDH, AST, and
ALT. Plasma bilirubin levels reflect alterations in bilirubin
and bile metabolism, and prothrombin times are prolonged
in hepatitis and chronic liver disease.
3.Obstructive diseases of the gallbladder are evident by elevated serum bilirubin levels, elevated urine urobilinogen
levels, and increased stool fat. The serum leukocyte levels
become elevated with inflammation of the gallbladder.
4.The most significant indicators of pancreatic dysfunction
are serum amylase and stool fat. Both values are increased
with diseases of the pancreas.
Aging and the Gastrointestinal System
1.Advancing age is often associated with the loss or deterioration of teeth, diminished senses of taste and smell, and
diminished salivary secretions, all of which may make eating difficult and reduce appetite.
2.Aging reduces gastric motility and secretions, particularly
of hydrochloric acid. These changes slow gastric digestion
and emptying.
3.Intestinal motility and absorption of carbohydrates, proteins, fats, and minerals decrease with age.
4.Efficiency of drug and alcohol metabolism decreases with
age and can be related to decreased liver perfusion and
decreased liver enzymes.
KEY TERMS
Alanine aminotransferase (ALT), 1413
Alkaline phosphatase, 1413
Ampulla of Vater, 1411, 1413
Antrum of stomach, 1396
Ascending colon, 1407
Aspartate aminotransferase (AST), 1413
Bile, 1411
Bile acid–dependent fraction, 1411
Bile acid–independent fraction, 1411
Bile acid pool, 1411
Bile canaliculi, 1411
Bile salt, 1411
Bilirubin, 1411
Biliverdin, 1411
Body of stomach, 1396
Brush border, 1401
Calcium, 1405
Carboxypeptidase, 1402
Cardiac orifice, 1396
Cecum, 1407
Cephalic phase of secretion, 1400
Chief cell, 1398
Cholecystokinin, 1398, 1415
Choleresis, 1411
Choleretic agent, 1411
Cholesterol esterase, 1404
Chylomicron, 1405
Chyme, 1396
Chymotrypsin, 1402
Colipase, 1404
Colon, 1407
Common bile duct, 1411
Conjugated bilirubin, 1411
Chapter 40 Structure and Function of the Digestive System
1421
K E Y T E R M S —cont’d
Crypts of Lieberkühn, 1401
Cystic duct, 1413
D cell, 1398
Deamination, 1412
Defecation reflex (rectosphincteric reflex), 1408
Descending colon, 1407
Disse space, 1410
Duodenum, 1400
Emulsification, 1404
Enteric nervous system, 1394
Enterochromaffin-like cell, 1398
Enterohepatic circulation, 1411
Enterokinase, 1415
Esophageal phase of swallowing, 1395
Esophagus, 1395
Exocrine pancreas, 1413
External anal sphincter, 1407
Fat, 1402
Fecal mass, 1408
Feces, 1408
Fundus of stomach, 1396
G cell, 1398
Gallbladder, 1413
Gamma-glutamyltransferase, 1413
Gastric emptying, 1397
Gastric gland, 1398
Gastric hydrochloric acid, 1398
Gastric phase of secretion, 1400
Gastric pit, 1398
Gastrin, 1397
Gastrocolic reflex, 1408
Gastroileal reflex, 1407
Gastrointestinal tract (alimentary canal), 1393
Haustrum (pl., haustra), 1407
Hepatic artery, 1409
Hepatic portal vein, 1409
Hepatic vein, 1409
Hepatocyte, 1409
Hepcidin, 1406
Histamine, 1398
Ileocecal valve (sphincter), 1400, 1407
Ileogastric reflex, 1407
Ileum, 1400
Internal anal sphincter, 1407
Intestinal peristalsis, 1407
Intestinal phase of secretion, 1400
Intestinointestinal reflex, 1407
Intrinsic factor (IF), 1399
Iron, 1405
Jejunum, 1400
Kupffer cell, 1410
Lactate dehydrogenase (LDH), 1413
Lacteal, 1401
Lamina propria, 1401
Large intestine, 1407
Lipase, 1404
Lipocyte, 1409
Lipolysis, 1404
Liver, 1409
Liver lobule, 1409
Lower esophageal sphincter (cardiac sphincter),
1395
Magnesium, 1405
Major duodenal papilla, 1411
Mesentery, 1401
Metabolic detoxification (biotransformation), 1413
Micelle, 1404
Microvillus (pl., microvilli), 1401
Motilin, 1397
Mouth, 1395
Mucosal barrier, 1399
Myenteric plexus (Auerbach plexus), 1394
Oral phase of swallowing, 1395
Pancreas, 1413
Pancreatic α-amylase, 1415
Pancreatic duct (Wirsung duct), 1413
Pancreatic lipase, 1415
Paneth cell, 1401
Parietal cell (oxyntic cell), 1398
Pepsin, 1398, 1399
Pepsinogen, 1398
Peristaltic movement, 1408
Peritoneal cavity, 1401
Peritoneum, 1400
References
1.Furness JB: The enteric nervous system and neurogastroenterology, Nat
Rev Gastroenterol Hepatol 9(5):286–294, 2012.
1a.Gröschl M: The physiological role of hormones in saliva, Bioessays
31(8):843–852, 2009.
2.Lang IM, Shaker R: An overview of the upper esophageal sphincter, Curr
Gastroenterol Rep 2(3):185–190, 2000.
3.Hershcovici T, Mashimo H, Fass R: The lower esophageal sphincter,
Neurogastroenterol Motil 2011 23(9):819–830, 2011.
4.Lang IM: Brain stem control of the phases of swallowing, Dysphagia
24(3):333–348, 2009.
5. Goyal RK, Chaudhury A: Physiology of normal esophageal motility,
J Clin Gastroentrol 42(5):610–619, 2008.
6.Hellström PM, Grybäck P, Jacobsson H: The physiology of gastric emptying, Best Pract Res Clin Anaesthesiol 20(3):397–407, 2006.
7.Dockray GJ: Cholecystokinin, Curr Opin Endocrinol Diabetes Obes
19(1):8–12, 2012.
8.Middleton SJ, Balan K: Idiopathic accelerated gastric emptying presenting in adults with post-prandial diarrhea and reactive hypoglycemia: a
case series, J Med Case Rep 6(1):132, 2012.
9.Chu S, Schubert ML: Gastric secretion, Curr Opin Gastroenterol
28(6):587–593, 2012.
10.Palileo C, Kaunitz JD: Gastrointestinal defense mechanisms, Curr Opin
Gastroenterol 27(6):543–548, 2011.
11.Longkumer T et al: Assessment of vagotomy status with postprandial
urinary alkaline tide, Trop Gastroenterol 30(2):91–94, 2009.
12. Ramsay PT, Carr A: Gastric acid and digestive physiology, Surg Clin
North Am 91(5):977–982, 2011.
Pharyngeal phase of swallowing, 1395
Phases of gastric secretion, 1399
Phosphate, 1405
Phospholipase, 1404
Pit cell, 1410
Primary bile acid, 1411
Primary peristalsis, 1396
Pyloric sphincter, 1396
Rectosigmoid (O’Beirne) sphincter, 1407
Retropulsion, 1397
S cell, 1415
Saliva, 1395
Salivary α-amylase (ptyalin), 1395
Salivary gland, 1395
Secondary bile acid, 1411
Secondary peristalsis, 1396
Secretin, 1397
Segmentation, 1407
Sigmoid colon, 1407
Sinusoid, 1409
Small intestine, 1400
Somatostatin, 1398
Sphincter of Oddi, 1411, 1413
Stellate cell, 1410
Stem cell, 1401
Stomach, 1396
Submucosal plexus (Meissner plexus), 1394
Subserosal plexus, 1394
Swallowing, 1395
Teniae coli, 1407
Transverse colon, 1407
Trypsin, 1402
Trypsin inhibitor, 1415
Unconjugated bilirubin, 1411
Upper esophageal sphincter (cricopharyngeal
muscle), 1395
Urobilinogen, 1412
Valsalva maneuver, 1408
Vermiform appendix, 1407
Villus (pl., villi), 1401
Vitamin, 1406
13.Schubert ML: Hormonal regulation of gastric acid secretion, Curr Gastroenterol Rep 10(6):523–527, 2008.
14.Tarnawski AS, Ahluwalia A, Jones MK: The mechanisms of gastric mucosal injury: focus on microvascular endothelium as a key target, Curr Med
Chem 19(1):4–15, 2012.
15.Zafra MA, Molina F, Puerto A: The neural/cephalic phase reflexes in the
physiology of nutrition, Neurosci Biobehav Rev 30(7):1032–1044, 2006.
16.Miller MJ, McDole JR, Newberry RD: Microanatomy of the intestinal
lymphatic system, Ann N Y Acad Sci 1207(Suppl 1):E21–E28, 2010.
17. Santaolalla R, Abreu MT: Innate immunity in the small intestine, Curr
Opin Gastroenterol 28(2):124–129, 2012.
18.Ashton KA et al: Basal and meal-stimulated colonic absorption, Dis Colon
Rectum 39(8):865–870, 1996.
18a.Wright EM, Loo DD, Hirayama BA: Biology of human sodium glucose
transporters, Physiol Rev 91(2):733–794, 2011.
19.Cheeseman C: GLUT7: a new intestinal facilitated hexose transporter,
Am J Physiol Endocrinol Metab 295(2):E238–E241, 2008.
20.Leturque A, Brot-Laroche E, Le Gall M: GLUT2 mutations, translocation,
and receptor function in diet sugar managing, Am J Physiol Endocrinol
Metab 296(5):E985–E992, 2009.
21.Jahan-Mihan A et al: Dietary proteins as determinants of metabolic and physiologic functions of the gastrointestinal tract, Nutrients 3(5):574–603, 2011.
22.Christakos S et al: Vitamin D and intestinal calcium absorption, Mol Cell
Endocrinol 347(1-2):25–29, 2011.
23.Drakesmith H, Prentice AM: Hepcidin and the iron-infection axis,
Science 338(6108):768–772, 2012.
24.Husebye E: The patterns of small bowel motility: physiology and implications in organic disease and functional disorders, Neurogastroenterol
Motil 11(3):141–161, 1999.
1422
Unit XII The Digestive System
25.Lubbers T, Buurman W, Luyer M: Controlling postoperative ileus by
vagal activation, World J Gastroenterol 16(14):1683–1687, 2010.
26. Byard RW: Acute mesenteric ischaemia and unexpected death, J Forensic
Leg Med 19(4):185–190, 2012.
27.Manson JM, Rauch M, Gilmore MS: The commensal microbiology of the
gastrointestinal tract, Adv Exp Med Biol 635:15–28, 2008.
28.Abraham C, Medzhitov R: Interactions between the host innate immune
system and microbes in inflammatory bowel disease, Gastroenterology
140(6):1729–1737, 2011.
29. Resta SC: Effects of probiotics and commensals on intestinal epithelial
physiology: implications for nutrient handling, J Physiol 587(Pt 17):
4169–4174, 2009.
30.Yokomori H et al: Recent advances in liver sinusoidal endothelial ultrastructure and fine structure immunocytochemistry, Micron 43(2-3):
129–134, 2012.
31. Yang Q et al: The evolving story of macrophages in acute liver failure,
Immunol Lett 147(1-2):1–9, 2012.
32.Tacke F, Weiskirchen R: Update on hepatic stellate cells: pathogenic role
in liver fibrosis and novel isolation techniques, Expert Rev Gastroenterol
Hepatol 6(1):67–80, 2012.
33.Tian Z et al: Natural killer cells in liver disease, Hepatol 57(4):1654–1662,
2013.
34.Horiguchi S, Kamisawa T: Major duodenal papilla and its normal
anatomy, Dig Surg 27(2):90–93, 2010.
35.Hofmann AF: The enterohepatic circulation of bile acids in mammals:
form and functions, Front Biosci 14:2584–2598, 2009.
36.Jansen T et al: Conversion of biliverdin to bilirubin by biliverdin reductase contributes to endothelial cell protection by heme oxygenase-1—­
evidence for direct and indirect antioxidant actions of bilirubin, J Mol
Cell Cardiol 49(2):186–195, 2010.
37.Jirásková A et al: Association of serum bilirubin and promoter variations
in HMOX1 and UGT1A1 genes with sporadic colorectal cancer, Int J
Cancer 131(7):1549–1555, 2012.
38. Rodriguez-Diaz R et al: Innervation patterns of autonomic axons in the
human endocrine pancreas, Cell Metab 14(1):45–54, 2011.
39. Chandra R, Liddle RA: Recent advances in pancreatic endocrine and
exocrine secretion, Curr Opin Gastroenterol 27(5):439–443, 2011.
40.Aranda-Michel J, Sherman KE: Tests of the liver: use and misuse, Gastroenterologist 6(1):34–43, 1998.
41.Johnston DE: Special considerations in interpreting liver function tests,
Am Fam Physician 59(8):2223–2230, 1999.
42.Hoekstra LT et al: Physiological and biochemical basis of clinical liver
function tests: a review, Ann Surg 257(1):27–36, 2013.
43.Mayumi T et al: Validity of the urinary trypsinogen-2 test in the diagnosis
of acute pancreatitis, Pancreas 41(6):869–875, 2012.
44.Grassi M et al: Changes, functional disorders, and diseases in the gastrointestinal tract of elderly, Nutr Hosp 26(4):659–668, 2011.
45.Gaines AD: Anosmia and hyposmia, Allergy Asthma Proc 31(3):185–189,
2010.
46.Gupta A, Epstein JB, Sroussi H: Hyposalivation in elderly patients, J Can
Dent Assoc 72(9):841–846, 2006.
47.Sura L et al: Dysphagia in the elderly: management and nutritional considerations, Clin Interv Aging 7:287–298, 2012.
48.Salles N: Is stomach spontaneously ageing? Pathophysiology of the ageing
stomach, Best Pract Res Clin Gastroenterol 23(6):805–819, 2009.
49.Patel KV: Epidemiology of anemia in older adults, Semin Hematol
45(4):210–217, 2008.
50.Tiihonen K, Ouwehand AC, Rautonen N: Human intestinal microbiota
and healthy ageing, Ageing Res Rev 9(2):107–116, 2010.
51.Drozdowski L, Thomson AB: Aging and the intestine, World J Gastroenterol 12(47):7578–7584, 2006.
52. Rayner CK, Horowitz M: Physiology of the ageing gut, Curr Opin Clin
Nutr Metab Care 16(1):33–38, 2013.
53.Schmucker DL, Sanchez H: Liver regeneration and aging: a current perspective, Curr Gerontol Geriatr Res 2011:526379, 2011.
54.McLachlan AJ, Pont LG: Drug metabolism in older people—a key consideration in achieving optimal outcomes with medicines, J Gerontol A
Biol Sci Med Sci 67(2):175–180, 2012.
55.Herzig KH et al: Fecal pancreatic elastase-1 levels in older individuals
without known gastrointestinal diseases or diabetes mellitus, BMC Geriatr 11:4, 2011.
56.Stinton LM, Shaffer EA: Epidemiology of gallbladder disease: cholelithiasis and cancer, Gut Liver 6(2):172–187, 2012.