Download GI System

Digestive System
Function
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Secretion
o Both endocrine and exocrine substances aid in digestion
Digestion
o This is the processing of ingested foods into molecular forms that can be
transferred, along with salts and water, from the external environment to
the body’s internal environment, where they can be distributed to cells by
the circulatory system.
Absorption
o The average adult consumes about 800g of food and 1200ml of water. An
additional 7000ml of fluid from salivary glands, gastric glands, the
pancreas, liver, and intestinal glands is secreted in the tract each day. Only
about 100ml of water is lost in the feces. The rest is absorbed into the
blood.
General Anatomy
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There are two divisions of the GI system
o GI Tract
 This is the tube that begins at the mouth and ends at the anus.
o Accessory glands
 Salivary glands secrete saliva to aid in the digestive process.
 The liver, pancreas, and gall bladder provide hormonal and/or
enzymatic support to the entire process.
Food Pathway
o Mouth  Esophagus  Stomach  Small Intestine (Duodenum 
Jejunum  Ileum)  Large Intestine (Ascending  Traverse 
Descending  Sigmoid Colon)  Rectum  Anus
o Once food enters the mouth, it is termed, “bolus.”
Movement of food through the gastrointestinal (GI) tract, from the mouth to the
anus involves
o Ingestion- Taking food through the mouth
o Mastication- Chewing
o Deglutition- Swallowing the food
o Peristalsis- The process of moving the food through the GI tract via
smooth muscle contraction.
The entire GI tract presents certain common structural characteristics. It is a
hollow tube composed of a lumen of variable diameter surrounded by a wall
mode of four principle layers. Structures within the GI tract are considered to be
on the outside of the body since the lumen of the tract is continuous with the
external environment, and many layers must be crossed for the GI contents to
reach the blood.
o Cross section of a typical portion of the GI tract
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Adventitia/ Serosa
 This is the outmost layer. It is a thin layer of loose
connective tissue containing various vessels and nerves,
simple squamous mesothelium, and visceral peritoneum. It
may be surrounded by mesentery.
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Muscularis Muscle
 Here there is a layer of longitudinal smooth muscle just
inside the serosa that produces a shortening movement. A
layer of circular muscle runs concentrically around the
tube, producing a narrowing of the lumen. Contractions of
these muscles provide the forces for moving and mixing the
GI contents.
 Auerbach’s (myenteric) nerve plexus is contained between
the two muscle layers.
 Submucosa
 This consists of loose connective tissue containing mucous
glands, blood and lymph vessels, and a variety of nerves
including Meissner’s (mucosal) nerves.
 Mucosa
 This is composed of ciliated columnar epithelium, lamina
propia (connective tissue containing small blood vessels,
nerve fibers, and lymphatic ducts), and muscularis mucosa
(smooth muscle).
The enteric system is composed of two different nerve plexuses.
o The submucosal plexus is located in the submucosa layer, and the
myenteric plexus is located between the circular and longitudinal smooth
muscle layer.
o These are both innervated by both the sympathetic and parasympathetic
nervous systems. Sympathetic stimulation is inhibitory, and
parasympathetic is excitatory. A patient with an overactive digestive
system would require a sympathomimetic drug to decrease its activity.
Both alpha and beta receptors are the targets. Parasympathomimetics are
required for patients with an underactive GI system.
The muscles in the GI system are single unit types. They have oscillating
membrane potentials. When the muscle fibers are stimulated by the
parasympathetic nervous system, the degree to which they depolarize is increased,
resulting in action potentials that lead to smooth muscle contraction.
Gastrointestinal Components
Oral Cavity
 Function
o Chewing, production of saliva, and swallowing
 Histology
o The oral mucosa consists of stratified squamous epithelium over a dense
layer of connective tissue. The epithelium is usually not keratinized, but
may become keratinized under adverse conditions.
 Anatomy
o Lips
 This is keratinized stratified squamous epithelium which turns into
a mucous membrane upon entering the mouth.
o Cheeks
 The cheeks contain considerable fat and are lined with a mucous
membrane consisting of non-kertinized squamous epithelium.
o Tongue
 The tongue functions to keep food inside of the mouth as it is
being chewed. After mastication, it then assists food by moving it
to the back of the throat for degluttination.
 It is a mass of striated muscle covered with a mucous membrane.
 The dorsal surface is covered with papillae which contain taste
buds, which are specialized sensory structures.
 These are gustatory receptors and are a type of epithelial
cell that is clustered with other cells called supporting and
basal cells. The taste buds are somewhat barrel shaped.
They have microvilli at the area of the taste pore.
 The four types of taste buds include salty, sweet, bitter and
sour. There is possibly a fifth type, termed “umami,” which
is an earthy taste.
 The taste buds are a good example of intensity coding. The
more receptors affected, the stronger the stimulus.
o Salivary glands
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These function to secrete saliva.
 Functions of Saliva
o Saliva lubricates food, making it easier to swallow.
o Saliva also helps dissolve some food molecules.
 It contains amylase, which is an enzyme that
can begin the process of digestion. Amylase
probably has to do more with freeing up
molecules that participate in the actual taste
phenomenon, more than it does in the actual
digestion.
 As soon as the food bolus enters the
stomach, HCl denatures amylase,
terminating any digestive activity of that
enzyme. All enzymes are proteins and the
low pH of the stomach is going to denature
them, except the few that are designed to
specifically function in that environment.
o Saliva also contains an important antibacterial
secretion.
Anatomy/ Histology
 The compound tubuloalveolar glands contain acinar cells
that secrete between 1-2 liters of saliva every day. These
terminate in an alveolus which may empty into intercalated
ducts, forming larger striated ducts. The resting rate of
secretion is about 0.5 ml per minute.
 Basket cells (myoepithelial cells) are involved in the
discharge of secretions. Cuboidal cells predominate in the
alveoli and secrete saliva containing enzymes, mucous,
immunoglobulins (IgA), etc.
Types
 The parotid gland is located in front of and under the ear.
This is the largest of the glands and is a branched acinar
gland. It contains mostly serous cells which secrete a
watery solution containing inorganic ions, IgA, and
amylase.
 The submandibular gland is located in the jaw, below the
mandible and mylohyoid muscle. This is a branched
tubuloacinar gland that contains mucous cells which secrete
mucin and lysozyme. It is mucin that gives a thick viscous
characteristic to saliva.
 The sublingual gland is located under the tongue, in the
floor of the mouth. This also a branched tubuloacinar gland
that contains mucous cells.
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Control
 Both parasympathetic and sympathetic controls exist, with
the parasympathetic producing a greater response.
 In the absence of ingested material, a low rate of salivary
secretion keeps the mouth moist. In the presence of food,
salivary secretion increases markedly. The response is
initiated by chemoreceptors and pressure receptors in the
walls of the mouth and on the tongue.
 CN 7 controls both the sublingual and submandibular
glands.
 CN 9 controls the parotid gland.
o Teeth
 These function to cut food into smaller pieces prior to
degluttination.
 Anatomy
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The crown is the part of the tooth that extends above the
gum or gingiva.
The outer part of the tooth is the enamel. It is the hardest
substance that our body produces. It is extremely hard,
translucent, non-replaceable, and is secreted by the
ameloblast during tooth development.
Just inside the enamel is a calcified matrix called the
dentin, which makes up the bulk of the tooth and surrounds
the dental pulp containing the nerves and blood vessels that
supply the tooth.
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The root canal is the central canal in the tooth where blood
vessels and nerves run.
 The dental alveolus is the part of the tooth that is embedded
in the bone. Cementum surrounds the root of the tooth and
attaches the tooth in its socket via periodontal ligaments to
the alveolar bone.
 Gingiva (gum) is a continuation of the oral mucosa,
covering the bone in which the teeth are embedded.
Organization
 On each upper and lower half of the mouth there are
normally four incisors, two canines, four premolars, and
eight molars.
o Accessory Structures
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Frenulum
 This is a tissue that attaches the lip to the gumline. There
are two, one upper and one lower.
 The lingual frenulum attaches the tongue to the floor of the
mouth.
Uvula
 This structure hangs down in the back center of the mouth.
Soft palate
 This contains receptors to activate deglutination.
Palatine tonsils
 These contain lymphatic aggregates within the submucosa,
but are not directly in the lymphatic circulation. They are
covered with an invaginating stratified squamous
epithelium.
Lingual tonsils
 These are located on the posterior 1/3 of the tongue. The
mucous membrane is thick and moves freely. Its
submucosa contains an aggregate of lymph nodules.
Oral pharynx
 Behind the teeth is the oral cavity, which leads to the oral
pharynx. Food travels this path into the esophagus while air
goes through the glottis in the nasal pharynx into the
respiratory system.
Pathology
o Apthous Ulcer (Chancre Sore)
 These lesions are very common and take the form of a shallow,
painful ulcer. They are self-limited, and although the cause
remains unknown, they are clearly affected by trauma (stress, viral,
fungal, bacterial, and autoimmune).
 Treatment is not very effective. Topical steroids, antibiotics, and
oral hygiene are possible solutions.
o Herpes Cold Sores
 80% are HSV Type I, and 20% are HSV Type II. This is the
opposite of genital cold sores. Greater than 75% of the population
has these by middle age.
 Treatment includes antivirals.
o Leukoplakia and cancer
 Leukoplakia is a whitish patch on the mucosa caused by epidermal
thickening or hyperkeratosis. This is a dysplastic condition, so it is
proliferative, but it is not a neoplastic disorder. It can be potentially
cancerous. There is a 5-15% chance of transformation to squamous
cell carcinoma. There is an association with tobacco use, chronic
friction (i.e., with ill-fitting dentures), and alcohol abuse.
 Most oral cancers are squamous cell variety, and these have a 50%
five-year mortality rate due to metastasis at time of diagnosis.
 Treatment includes local excision and radiation.
o Oral Cancer
 The lips and tongue are the most frequent sites of involvement.
Squamous cell carcinoma is the most common. The cause is
unknown, but risk increases with tobacco and alcohol.
o Thrush (Candida)
 This is a fungal infection in the oral cavity related to many other
diseases, such as those that are immunocompromised.
Esophagus
 Function
o It functions to conduct food and fluids from the pharynx to the stomach
and to prevent reflux of gastric contents.
o It also secretes mucous to aid in lubrication of the food.
o There is no enzymatic contribution towards the digestion of food.
 Anatomy
o This is a soft, hollow, highly distensible muscular tube, about 25cm long,
which extends from the pharynx to the gastroesophageal junction of the
stomach. Through the course of its travels, the esophagus goes through the
mediastenum, piercing the diaphragm at the esophageal hiatus.
o It is located in three body regions; the neck, thorax, and abdomen. It is
anterior to the vertebrae and posterior to the trachea. It adheres to the
trachea via fibroelastic membranes and muscle.
o The epithelium is stratified squamous. Its walls consist of mucosa,
submucosa, muscular propia, and adventitia.
 The superficial and deep esophageal glands transverse the mucosa
which serves as a lubricant as food is pushed down towards the
stomach.
 Lymphatic tissue and mucous glands are often present within the
lamina propia.
o The upper 1/3 of the esophagus contains skeletal muscle in the muscularis.
The lower 1/3 is involuntary muscle. In the middle, there is a mixed
muscularis area of both smooth and skeletal muscle.
o There is both an upper and lower esophageal sphincter that keep both ends
of the esophagus closed in normal conditions.
 Physiology
o The food bolus is pushed into the back of the mouth by the tongue,
pushing the food against the soft palate, activating the reflex swallowing
activity. Once the food bolus gets to the back of the throat, swallowing is
pretty difficult to prevent. The swallowing center is located in the medulla
oblongata.
o The food bolus goes to the oral pharynx, and the process of swallowing
elicits an inhibition of respiration for a period of time. This is designed to
prevent the process of swallowing and inspiration simultaneously. When
these two activities occur at the same time, it can cause violent eruptions
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of the diaphragm and abdominal muscles in a choking process trying to
expel the food particle.
 Swallowing causes the soft palate to rise and lodge against the
back wall of the pharynx, preventing food from entering the nasal
cavity.
 Swallowing also causes the epiglottis, a flap of tissue, to lie across
the glottis, the opening of the trachea. The epiglottis closes the
trachea, preventing food from entering the trachea and pushing the
food into the esophagus.
As the food enters the esophagus, the upper esophageal sphincter relaxes
and opens, closing immediately after.
The food bolus is going to be moved down the esophagus by peristaltic
action. One peristaltic wave can take nine seconds to reach the stomach.
There are two components to this.
 Segmenting action
 This is a constriction of the tube, narrowing the orifice. It is
accomplished primarily by the circular smooth muscles that
run circumferentially around the esophagus. So that when
they contract, the esophagus essentially pinches.
 Shortening action
 The longitudinal muscles contract, shortening the
esophagus, which pulls part of it up and essentially helps to
move the food bolus down.
At the end of the esophagus, there is a thickening of the muscle forming
the gastroesophageal sphincter. This is not a true sphincter, however it acts
as a sphincter.
 In infants, the gastroesophageal sphincter sometimes has not
descended into the abdominal cavity and still resides within the
thoracic cavity. The pressure in the thoracic cavity is subatmospheric which tends to allow substances to very easily ascend
up the esophagus. Consequently, there is a tendency to empty the
stomach contents very simply. Some animals like mice and rats
have a much stronger gastrointestinal sphincter than humans. They
are incapable of throwing up. This is why they are so easily killed
when ingesting toxic substances.
Swallowing is generally accomplished via both somatic nerves to skeletal
muscle and autonomic nerves to the smooth muscle.
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Pathology
o Terms
 Reflux- This is the spilling of the acidic stomach contents into the
esophagus.
 GERD- Gastro Esophageal Reflux Disorder
o When the stomach, or part of the stomach, is above
the diaphragm, it causes reflow of stomach contents
into the esophagus, causing heartburn, burping, etc.
o The symptoms are generally from the reflux, not the
mechanics.
 Dysphagia- Difficulty swallowing due to neurological spasms,
mechanics, etc.
 Hematemesis- Vomiting blood, either fresh or digested
o Hiatal Hernia
 This is a very common problem in the US. Only a small percentage
of patients have symptoms.
 A common problem exists in which the esophageal hiatus is
expanded, allowing part of the stomach to protrude through it. This
causes problems, particularly when the individual is reclining. It
tends to cause acidic stomach juices to move up through the
esophagus, producing significant distress, particularly heart burn.
Anything that causes reflux from the stomach up the esophagus
can significantly irritate the end of the esophageal area and cause a
lot of pain.
 Drugs can decrease hydrochloric acid secretion, decreasing the
irritation. Treatments include antacids, prokinetic drugs
(cytoprotective, promotility, H2 blockers, and proton pump
inhibitors) and antireflux measures. Patients with this problem
should not eat at night or eat while lying down. Antispasmodics
(Levsin or nitroglycerin) can also be used.
o Mallory Weiss Tear
 This is a tear in the mucosa at the GI junction due to severe
retching or vomiting, typically seen in alcoholics. This tear causes
blood to be present in the vomit.
o Varices
 These are dilated lower esophageal veins occurring secondary to
portal hypertension. This dilation leads to collateral bypass
channels and therefore engorged esophageal veins. Dilation of the
rectal, umbilical, and lower esophageal veins can all occur.
 This most commonly occurs due to alcoholic cirrhosis. These are
serious, because these vessels can rupture and bleed extensively,
which if severe enough can lead to death. This can also be seen in
the liver.
 Treatment includes endoscopy and injection of a sclerosing agent
or cauterization. Surgery is sometimes required. Tamponades
(balloons) are also used.
o Esophagitis and Barrett’s Esophagus
 Inflammation of the esophagus can occur for many different
reasons. In the US it is usually due to reflux. Males are affected
more than females. Symptoms include pain and a “burning”
sensation in the chest. Treatment includes antacids and antireflux
measures.
 Chronic esophagitis can lead to Barrett’s Esophagus, which is the
replacement of normal stratified squamous epithelium with
abnormal metaplastic columnar epithelium. This leads to a 30-40%
increased risk of developing adenocarcinoma of the esophagus. If
Barrett’s esophagus is not developed in 5 years, it probably will
not.
o Cancer
 Most cases of esophageal cancer are of the squamous cell variety.
Risk factors include smoking, alcohol, esophagitis, etc. It can also
spread from the stomach. Men are three times more likely than
women to get it, especially over the age of 50. This is less common
in the US vs. China and Iran, where there is a female
predominance.
Stomach
 Functions
o Primarily to temporarily store food
o Initiate the digestion of proteins
o Move the food into the small intestine as a pasty material called chyme.
 Anatomy
o This is a complex glandular digestive and endocrine organ. It is located on
the left side of the abdomen and is relatively fixed at the esophagus and
small intestine, but movable in between these structures.
o Divisions
 Cardia
 This is the part of the stomach adjacent to the esophagus. It
contains mainly mucous secreting cells, and the glands are
comparatively short in length and depth. There is no
sphincter here.
 Fundus
 This is the rounded part of the stomach above the
gastroesophageal junction. This contains the majority of the
chief and parietal cells, along with the body.
 Body
 This is the large middle portion.
 Antrum
 This is the floor of the stomach. It has a thick layer of
smooth muscle.
 Pylorus
 This is the narrow lower connection of the stomach to the
small intestine. This contains the branched glands with very
deep irregular pits that produce gastrin and mucous.
 The pyloric sphincter is the true sphincter between the
stomach and the intestine. It is a ring of smooth muscle that
controls the amount of food entering the small intestine.
o The adult stomach is about 25cm long. An empty stomach has the capacity
of 50ml, but can hold as much as 4L (1 gallon).
 The stomach can increase to as much as 1.5L without any increase
in pressure, due to receptive relaxation. This is mediated by
parasympathetic nerves with coordination by the swallowing
center in the brain.
o The stomach is innervated by the submucosal plexus and myenteric
plexus. These have both parasympathetic and sympathetic innervation,
with sympathetic innervation possessing inhibitory functions.
o The mucosa has simple columnar cells and is folded into rugae when
empty. The submucosa has circular and longitudinal muscles, while the
muscularis is smooth muscle serosa. The muscle arrangement allows food
to be moved, churned, mixed, and broken down into smaller pieces. The
rugae contain openings called gastric pits, where a variety of substances
are secreted by the cells here. These cells secrete about 2500ml of gastric
juices daily. Most of this juice is produced by exocrine glands located in
the body and fundus of the stomach. Contents of the normal gastric juice
(fasting state) include cations (Na+, K+, Mg2+, H+), anions (Cl-, HPO3-,
SO4-), pepsins, gelatinase, mucus, intrinsic factor, and water.
o Parietal (Oxyntic) cells
 Secretes hydrochloric acid (HCl)
 The stomach secretes about 2L of HCl per day, with the
majority occurring at the time of meals. The neuronal
pathways and duodenal hormones involved act directly on
the parietal cells and/or indirectly by influencing gastrin
secretion, which in turn directly influences parietal cells.
 HCl acts by converting pepsinogen secreted by the chief
cells into pepsin. Pepsin is a proteolytic enzyme which will
begin the digestion of the proteins by cleaving larger chains
of polypeptides into smaller chains. This is done most
effectively at a pH of 1.4. Between 1 and 4, there is less
digestion, and around 6-7, there is no digestion. This is an
autocatalytic, positive-feedback process.
 HCl also plays an important role against bacteria or other
ingested organisms. The extremely low pH (1-3) kills an
enormous amount of organisms. Those that get past the
stomach will cause significant intestinal distress.
 This also stimulates the flow of bile and pancreatic juices,
as well as breaking down muscle fibers and connective
tissue.
 Secretes intrinsic factor
 This is required for the absorption of vitamin B12 which
occurs in the small intestine. In fact, it is the only hormone
that is absolutely required in the process of digestion.
o Chief (Zymogenic/Peptic) cells
 These are located in the basal glands of the antrum. They secrete
pepsinogen, along with endorphins, serotonin, and cholecytokinin
in response to nerve plexuses. Its secretion parallels that of HCl.
 Pepsinogen is an example of a zymogen that refers to any enzyme
that is synthesized in an inactive form. This is done so that the
enzymes are not digested in the process of digestion. They only act
once inside a cell.
o Goblet cells (Mucous Neck Cells)
 These cells are located in the glands of the antrum and scattered
throughout the gastric epithelial lining. They have irregular shapes
and produce a less viscous, more acidic mucous secretion than
mucous secreting cells.
o Surface mucosa cells
 These secrete HCO3 and mucus to form an unstirred layer that has
a pH of about 7.0. This layer, along with the surface membranes of
the mucosal cells and the tight junctions between them, constitute
the mucosal bicarbonate barrier that coats the gastric wall and
protects the mucosal surface from damage by gastric acid and HCl.
Substances that tend to disrupt the barrier and cause gastric
irritation include ethanol, vinegar, bile salts, aspirin, and other
NSAIDs. Prostaglandins stimulate mucus secretion while aspirin
and related drugs inhibit prostaglandin synthesis. The fluid also
protects against mechanical injury by acting as a lubricant.
o G-cells (Enteroendocrine cells)
 These are found in the pits of the pylorus and secrete the hormone
gastrin into the portal blood, which is necessary for protein
digestion.
 Gastrin secretion can be stimulated by the vagus nerve via
acetylcholine, as well as being stimulated by many of the same
components that stimulate HCl. It is inhibited by the high acidity
of duodenal chyme, distension, hypertonic solutions, and solutions
containing amino acids, fatty acids, and monosaccharides. The
hormones that inhibit gastric activity are collectively known as
enterogastrones, and include secretin, CCK, and additional
unidentified hormones.
o Enterochromofin-like cells
 These cells are stimulated by gastrin to secrete histamine which
directly stimulates the parietal cells to release HCl.
 Tagamet, zantac, and pepsid AC specifically blocks the histamine
receptors, causing decreased acidity in the gastric juice.
o D-cells
 These secrete the hormone somatostatin which inhibits parietal,
chief and G cells.
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Physiology
o Gastric motility
 As with the esophagus, the stomach utilizes peristaltic waves to
move food. These waves begin higher in the body as weak
movements so that the contents are not mixed too much with acid
and pepsin. The waves become stronger towards the antrum, where
they mix the contents and close the pyloric sphincter.
 The waves are produced by pacemaker cells in the longitudinal
smooth muscle layer that undergo spontaneous depolarizationrepolarization cycles known as the basic electrical rhythm of the
stomach. This determines the frequency of the contractions, which
is about three per minute. The force is determined by the neural
and hormonal input to the antral smooth muscle, which depends on
the contents of the stomach.
 Decreased parasympathetic or increased sympathetic activity
inhibits motility.
Pathology
o Gastritis
 This is an inflammation of the stomach mucosa. It is a vague term
for a self-limiting illness characterized by nausea, anorexia,
epigastric distress with or without vomiting, as well as some
systemic symptoms. There is also the presence of inflammatory
cells, acute or chronic, in the gastric mucosa.
 Risk factors include the use of NSAIDs, prescription medications,
alcohol, physical stress, smoking, stress, aging, idiopathic,
postgastrectomy, bile reflux, and infections.
o Vomiting
 This is the forceful expulsion of the contents of the stomach and
upper intestinal tract through the mouth. It is regulated in the
medulla oblongata in an area known as the vomiting center and can
be caused by neural input via extensive distension of the stomach
or small intestine, substances acting on chemoreceptors, increased
pressure in the skull, rotating movements of the head as in motion
sickness, intense pain, or tactile stimuli of the back of the throat.
 Vomiting is generally preceded by increased salivation, sweating,
increased heart rate, pallor, and feelings of nausea. During
vomiting, the abdominal muscles contract, raising the abdominal
pressure, forcing the stomach contents into the esophagus. When
this all occurs without the expulsion of stomach contents, it is
called retching.
 Excessive vomiting can lead to large losses of the water and salts,
which could result in severe dehydration, disruption of the body’s
salt balance, and create circulatory problems because of the
decrease in plasma volume.
o Ulcers
 These are sores or erosions in the mucosa that extend through the
muscularis mucosa into the submucosa or deeper. There is a strong
association with H. pylori infection. Ulcers can also arise from
stress, NSAIDs, steroids, spicy foods, etc.
 An acute or chronic benign ulceration occurs in a portion of the
digestive tract that is accessible to gastric secretions. It does not
occur in the absence of peptic gastric secretions. A penetrating
ulcer refers to an ulcer that has gone to another organ.
 Diagnosis is done via biopsy or “breath test.” Antibiotic tests are
not as good, because there are many false positives.
 Symptoms include pain, nausea, bloating, weight loss, and other
symptoms due to blood loss. Blood in the stomach quickly
congeals and turns brown and when vomited, looks like coffee
grounds.
 Treatment
 Proton pump inhibitors inhibit HCl secretion.
 Same as GERD, but treat the H. Pylori with antibiotics as
well.
o Gastric Ulcer
 This is an ulcer due to decreased tissue resistance more than
hypersecretion.
 This is demonstrated by x-ray or gastroscopy.
 Symptoms include epigastric distress on an empty stomach,
epigastric tenderness and voluntary muscle guarding.
o Zollinger-Ellison Syndrome (Gastrinoma)
 This is the increased production of stomach acid, causing increased
ulcers. The major cause is a gastrin secreting tumor in the
pancreas, while few have tumors in the submucosa of the
duodenum and stomach, the hilum of the spleen, and the regional
lymph nodes. This is a metabolic condition, and there is no
association with H. pylori.
 Symptoms include epigastric pain, hematemesis, difficulty eating,
diarrhea and steatorrhea (fat in stool).
 Signs include severe peptic ulcer disease, gastric hypersecretion,
and elevated serum gastrin.
 Treatment includes that similar to ulcers.
o Cancer
 This cancer has a survival rate of <10%, due to a high rate of
metastasis. It is decreasing in incidence in the US. It is seen more
in patients over 40.
 A favorite location is the lesser curvature of the stomach, and
therefore any ulcer seen here on an upper GI x-ray deserves further
investigation by endoscopy. Lesions are irregular with raised
borders.
 Symptoms mimic sores or ulcers and include upper GI symptoms
with weight loss including a palpable abdominal mass, anemia, and
blood in stool.
Small Intestine (Bowel)
 Function
o This is the major digestive organ of the body. Almost all absorption occurs
here, except for water and ethyl alcohol, which is absorbed in the stomach.
o Secretions including water and mineral ions.
 Anatomy
o This extends from the pyloric sphincter of the stomach to the ileocecal
valve. It is the longest part of the alimentary canal.
o Dimensions
 1 inch in diameter.
 2m in length in situ due to muscle tone.
 6m in length in a cadaver.
o This is held in place by the mesentery, which contains arteries and veins.
The mesentery is very movable, so it allows for a lot of movement of the
intestine while at the same time not allowing for twists or folds. The
lamina propia is usually loose reticular connective tissue.
o The inner wall of the intestine tract is folded into plica circularis, which
are deep mucosal folds involving the mucosa and submucosa villi. These
are fingerlike projections in the intestinal walls. Further microscopic folds
of the entire mucosa of the intestine are called microvilli or a brushborder.
This serves to increase the small intestine’s surface area for absorption
about 600-fold.
o Structure of the Villi
 The epithelium is simple columnar with a brush border. The
epithelial cells have a large rate of mitosis, so there is a large
turnover. They are released into the intestinal lumen, contributing
to the digestive process. It is because of this rapid cell turnover that
the lining of the intestinal tract is so susceptible to damage by
agents that inhibit cell division, such as radiation and anticancer
drugs.
 In the interior of the villus there is a lymphatic vessel called a
lacteal. The lacteals are very thin-walled structures and are very
difficult to see except when they are full of lymph, particularly
when that lymph is full of fat. This is the only mechanism in which
fat can be absorbed into the body. Near the lacteals are arteries and
veins that participate in absorption.
 The villi also contain
 Goblet cells that secrete mucous.
 Intestinal crypts
 Brunner’s glands that secrete alkaline mucus, protecting the
duodenal mucus membrane against damage from the acidic
gastric juice.
 Lymphoid aggregation known as Peyer’s patches in the
lamina propia.
 Paneth cells are serous cells in the basal portion of the
intestinal glands and may play a role in controlling
intestinal flora.
o Segments of the Small Intestine
 Duodenum
 This is 10-12 inches in length. It is the shortest and widest
segment in the upper abdominal cavity. It is located mostly
to the right and is retroperitoneal, i.e., not suspended by the
peritoneum. It curves around the head of the pancreas and
terminates at the duodenojejunal flexure.
 The sphincter of Oddi (hepatopancreatic sphincter), a ring
of smooth muscle at the duodenum, controls entry of bile
and pancreatic juice.
 Glands in the submucosa of the duodenum (Brunner’s
glands) secrete an alkaline mucous that protects the
duodenal mucosa from the very acidic chyme as it comes
from the stomach.
 There are some enzymes that are secreted by the duodenum
that participate in the digestion of sugars.
o Sucrase digests glucose and fructose.
o Maltase digests maltose to glucose.
o Lactase digests lactose to glucose and galactose.
 85% of the adult population lacks lactase
and is therefore lactose intolerant.




The three classes of enzymes synthesized by the duodenal
mucosa include peptidases, enterokinase, and phosphatase.
o Aminopeptidase cleaves proteins into amino acids,
dipeptides, and tripeptides.
o Enterokinase primarily acts to activate trypsin.
o Phosphatase is an enzyme that participates in the
absorption of calcium by removing phosphate
groups, along with magnesium, ATPase, and
alkaline phosphatase.
Jejunum
 This is 3 feet and is intraperitoneal. It connects the
duodenum to the ileum.
Ileum
 This is 7 feet. This is also intraperitoneal and terminates at
the ileocecal valve which serves as a sphincter and
connects it to the large intestine. The sphincter is normally
closed, but after a meal when the gastroileal reflex
increases ileal contractions, it relaxes each time the
terminal portion of the ileum contracts allowing chyme to
enter the large intestine. A reflex contraction prevents fecal
material from moving back into the small intestine.
Physiology
o In the small intestines, the most common action is a stationary contraction
and relaxation of intestinal segments, with little apparent net movement
toward the large intestine. This is called segmentation, and its purpose is
to mix the chyme, bringing it into contact with the intestinal wall. These
movements are generated via pacemaker cells in the longitudinal smoothmuscle layer. More contractions are seen in the upper segments than the
lower, forcing chyme along its path. The “Law of Intestine” states that the
mild distention of the intestine produces a contraction of the smooth
muscle on the oral side of the distension and relaxation of the smooth
muscle on the anal side, producing movement.
 The intensity of the segmentation can be altered by hormones, the
enteric nervous system, and autonomic nerves. Parasympathetic
activity increases the force of contraction, and sympathetic
stimulation decreases it.
 After meals, the contractions cease and are replaced by a pattern of
peristaltic activity known as the migrating motility complex. This
moves in to the large intestine any undigested material still
remaining in the small intestine and prevents bacteria from
remaining in the small intestine long enough to grow and multiply.
This process is thought to be due to an intestinal hormone called
motilin.
o Gastroileal reflex
 Segmentation intensity in the ileum increases during periods of
gastric emptying.
o Intestinointestinal reflex
 Large distension of the intestine, injury to the intestinal wall, and
various bacterial infections in the intestine lead to a complete
cessation of motility.
o As much as 500ml of air may be swallowed during a meal. Most of this air
travels no further than the esophagus, from which it is eventually expelled
by belching. Some of the air reaches the stomach however, and is passed
on to the intestines where its percolation through the chyme as the
intestinal contents are mixed produces gargling sounds that can often be
quite loud.
o In the small intestine, monosaccharides and amino acids are absorbed by
specific carrier-mediated transport processes in the plasma membranes of
the intestinal epithelial cells, whereas fatty acids enter these cells by
diffusion. Most mineral ions are actively absorbed, and water diffuses
passively down osmotic gradients. Digestion and absorption have been
largely completed by the middle portion of the small intestine. The small
intestine is very permeable to water, so most of this is absorbed here.
o Digestion of Fats



Fat intake ranges from 25-160g/day in the typical American diet.
Most of this is in the form of triglycerides.
Lipids are hydrolyzed by the pancreatic lipase at the surface of the
fat droplets. These droplets need to be small, increasing their
surface area, to be digested quicker. This process is called
emulsification. Emulsification requires mechanical disruption of
the larger droplets provided by contractile activity, as well as an
emulsifying agent in the form of phospholipids and bile salts.
The bile salts also form micelles from triglycerides, which are
similar in structure to emulsion droplets, but are much smaller.
These consist of bile salts, fatty acids, monoglycerides, and
phospholipids. These increase absorption by keeping most of the
insoluble fat digestion products in solution, while at the same time
replenishing the small amount of products that are free in solution
as they diffuse into the intestinal epithelium. These can flow into
the capillaries.

Fatty acids can move across the epithelium into the columnar
epithelial cell where they are combined with other monoglycerides
back into triglycerides and moved into chylomicrons, which are
packages of triglycerides. The chylomicrons are moved by
exocytosis out of the epithelial cell and into the lacteal. The lacteal
conducts the lymph back into the circulatory system. Most of the
lymph empties back into the circulatory system via the thoracic
duct, which empties into the subclavian vein.
 Dietary triglycerides can be taken up into adipose or liver cells by
action of lipoprotein lipase (LPL). It is stored in adipose and used
in the liver for energy.
 Fat essentially delays the digestive process, and so the chyme stays
in the small intestine for a longer period of time as digestion of fat
requires additional time. Carbohydrates are digested much more
quickly than are fats. Carbohydrates do not have this inhibitory
effect on the digestive process.
o Digestion of Proteins
 40-50g of protein are required by a normal adult to supply essential
amino acids and replace the amino acids converted to urea. A
typical American diet contains about 125g of protein per day.
 Digestion is performed by the class of enzymes called proteases.
This includes pepsin in the stomach, trypsin and chymotrypsin in
the small intestine and pancreas, as well as by carboxypeptidase
secreted by the pancreas and aminopeptidase in the membrane of
the small intestine. These all cleave off amino acids allowing
shorter chains of two or three amino acids to be actively absorbed.
 Small amounts of intact proteins can cross the membrane via
endocytosis and exocytosis.
o Digestion of Carbohydrates
 This ranges from about 250-800g in the typical American diet. 2/3
consists of the plant polysaccharide starch, with the remaining
being sucrose and lactose.
 Starch digestion begins in the mouth with the salivary amylase and
continues though the small intestine with pancreatic amylase.
These are broken down to the monosaccharides glucose, galactose,
and fructose which are later transported across the intestinal
epithelium into the blood. Fructose crosses the epithelium by
facilitated diffusion, while glucose and galactose undergo
secondary active transport coupled with sodium.
 Much of these enzymes come from glands named the
Crypts of Lieberkuhn.
 Large polysaccharides, like cellulose referred to as fiber, are not
digested by the small intestine, but passed onto the large intestine
where it is partially metabolized by the bacteria.
Large Intestine, aka Large Bowel


Function
o Water absorption from indigestible food particles and it’s elimination as
semisolid feces.
 This is the area in which constipation and diarrhea occur. If water
is absorbed excessively constipation occurs, and if not, diarrhea is
the result.
o Vitamin absorption
 Potassium, folic acid, and several B complex vitamins
o Storage and concentration of undigested matter.
o 4% of absorption
Anatomy
o The large intestine surrounds the small intestine on three sides. It extends
from the ileocecal valve of the small intestine to the anus. It is about 4 feet
long and 2.5inches in diameter. Even though it has a larger diameter than
the small intestine, the surface area is decreased, since there are no villi.
o The mucosa is arranged as a series of densely packed parallel straight
tubular glands which are continuations of the Crypts of Lieberkuhn of the
small intestine. This is a reduced lamina propia. It is composed of tall
columnar epithelium with absorptive cells, goblet cells, and lymph nodes.
o Parts



Cecum
 This is sac-like structure lying below the ileocecal valve
covered by peritoneum. It is the first part of the large
intestine. Humans have a very poorly developed cecum
compared to animals that eat plants to digest that material.
Colon
 Consisting of, in order,
o Ascending Colon
 This is against the right abdominal wall. It is
usually retroperitoneal, not suspended by the
peritoneum.
o Hepatic Flexure
o Transverse Colon
 This is between the right and left colic
flexures, crossing in front of the duodenum.
o Splenic Flexure
o Descending Colon
 This extends downward from the left colic
flexure, usually retroperitoneal.
o Sigmoid Colon
 This is an S-shaped segment.
Appendix
 This is a blind sac that has no functional significance in the
body. It is located at the junction of the small and large
intestine, coming off of the cecum.
 The epithelium is columnar. It has a greatly increased
proportion of lymphoid tissue in the lamina propia. The
lumen of the appendix often appears as triangular in cross
section.
 Enteric bacteria tend to enter this and accumulate, causing
inflammation. This leads to acute appendicitis in about
10% of all people in the US. The swelling leads to
compromised blood flow and further swelling that may
rupture if left unchecked. If the appendix ruptures, it can
spill large quantities of bacteria into the peritoneum leading
to peritonitis which is an extremely dangerous kind of
infection. Symptoms are anorexia and pain that starts in the
periumbilical area and travels to the right lower quadrant
over McBurney’s point (between the pubic bone and
superior ileac crest). Treatment is surgical and should be
performed immediately.



Rectum
 This extends from the sigmoid colon to a point in front of
the tip of the coccyx within the pelvis.
 There are extensive goblet cells here with a thick, highly
vascular mucosa.
Anal Canal
 This is about 3cm long. It opens to the body exterior at the
anus.
 This is a transition to stratified squamous epithelium from
simple columnar. The outer areas contain apocrine and
sebaceous glands, which are large sweat glands
 Sphincters
o Internal anal sphincter
 This is involuntary and composed of smooth
muscle.
o External anal sphincter (lower 2/3)
 This is voluntary and composed of skeletal
muscle.
 Pathology
o Hematochezia
 Fresh rectal bleeding
o Melena
 Digested blood in the stool which is tarry
and smelly.
Physiology
o Absorption is done via active transport of sodium. If fecal material
remains in the large intestine for a long time, almost all the water is
absorbed, leaving behind hard fecal pellets.
o Some bacterial products include gas (flatus), which is a mixture of
nitrogen and carbon dioxide, with small amounts of hydrogen, methane,
and hydrogen sulfide. This rate of gas formation rises when consumed
food cannot be digested by intestinal enzymes, but is readily metabolized
by bacteria in the large intestine.
o Motility
 The contractions of the smooth muscle here are considerably
slower than the small intestine, generally occurring once every 30
minutes. This means that the material here stays for longer periods
of time. Three to four times a day, generally following a meal, a
wave of intense contractions known as a mass movement spreads
rapidly over the colon toward the rectum, coinciding with the
gastroileal reflex. With this, the muscle stays contracted for some
time.
o Defecation
 This mass movement initiates the defecation reflex, relaxing the
internal anal sphincter. The conscious urge to defecate is mediated
by stretched mechanoreceptors. The brain centers allow the


defecation to be delayed, and the smooth muscles relax. The urge
to defecate subsides until the next mass movement.
Defecation is completed by contraction of the abdominal and
thoracic muscles. This produces an increase in abdominal pressure
that is transmitted to the contents of the large intestine and rectum,
causing a rise in intrathoracic pressure. This leads to a transient
rise in blood pressure as the venous return to the heart is decreased.
About 150g of feces is eliminated each day. This includes 100g of
water and 50g of solid material, which normally contains bacteria,
undigested polysaccharides, bile pigments, cholesterol, and small
amounts of electrolytes, mainly potassium.
Pathology of the Large and Small Intestines
 Diverticulum
o This is a weak spot in the colon that bulges out. This can collect debris and
become inflamed if foreign material is caught.
o Diverticulosis is the status of having directiculi. These do not go away.
o Diverticulitis is the inflammation of the diverticula, which is seen mostly
in the sigmoid colon. It can lead to an obstruction or perforation which can
rupture. The inflammation comes and goes, and it may behave like
appendicitis. There may be pain or localized tenderness. A palpable mass
is often present. Treatment includes antibiotics and a liquid diet. Surgery
is required if bad, but much of the colon needs to be removed.
 Duodenal Ulcer
o These are about 10 times more likely to occur than gastric ulcers. They
affect about 10% of the US population. Symptoms include epigastric
distress 45-60 minutes after meals, nocturnal pain, epigastric tenderness
and guarding. Acid is seen in all cases and hypersecretion in some. An
ulcer crater or deformity of the duodenal bulb is seen on x-ray or with
endoscopy.
 Stromal (Marginal) Ulcer/ Jejunal Ulcer
o This is suspected when there is a history of operation for an ulcer followed
by recurrence of abdominal symptoms after a symptom-free interval of
months to years. Symptoms include burning, abdominal pain, nausea,
vomiting, weight loss, hematemesis (ejection of blood by vomiting),
anemia, and occult blood in stool. Pain occurs sooner because of faster
emptying time.
 Gastroenteritis
o This is the term used commonly to describe a diarrheal illness (sometimes
vomiting). There are roughly 76 million food poisonings/year, with
325,000 hospitalizations and 5,000 deaths. Refrigeration and the proper
handing of food are essential.



o There are many causes.
 Viral
 This is seen more in kids with poor hygiene. It is rare in the
US, but it is the #1 killer for kids in the world. The most
common agent is rotavirus.
 Bacterial
 Ingestion of toxins such as Staph aureus produces toxins
before ingestion. Infection with toxigenic organisms such
as E. coli or cholera produces toxins after ingestion. This is
seen in travelers in Mexico.
 Infection by enteroinvasive organisms like Salmonella or
Shigella invades the mucosa. Symptoms are seen 24-48
hours after the invasion and can last for weeks.
 This infection can also be due to an imbalance of bacteria
due to antibiotics destroying all of the “good bacteria.” This
leads to an overgrowth of clostridium dificile. There is also
antibiotic-associated colitis and pseudomembranous colitis.
 Protozoa (Giardia and Entamoeba)
 This is common in the water systems of other countries.
Regional Enteritis
o This is a chronic inflammatory disease that may involve the alimentary
tract anywhere from the mouth to the anus. The ileum is the principal site
of the disease, whether alone or in conjunction with the colon and
jejunum. It usually occurs in young adults and has a variable course with
exacerbations and remissions.
o Symptoms include insidious onset, nausea and vomiting which occurs 4560 minutes after eating, intermittent bouts of diarrhea, low-grade fever,
right quadrant pain, and fistula formation.
Constipation
o This is the retention of fecal material in the GI tract. The primary factor is
due to decreased motility.
o Symptoms include headache, loss of appetite, nausea, and abdominal
distention. The longer the fecal material remains in the large intestine, the
more water gets reabsorbed into the body, and the harder and drier the
fecal matter becomes.
o Treatment includes dietary fiber or laxatives.
Diarrhea
o This is increased fecal water content and weight, generally greater than
200 g/day. This is due to decreased fluid absorption, increased fluid
secretion, or both. It is generally caused by bacteria, protozoans, or
viruses.
o This can lead to decreased blood volume, potassium depletion, and
metabolic acidosis resulting from the loss of sodium, potassium, and
bicarbonate ions. Untreated diarrhea can result in death in underdeveloped
countries. Prevention in children is generally via ingestion of solutions
containing salt and glucose.


Inflammatory Bowel Disease
o Includes Ulcerative Colitis and Crohn’s Disease.
 These are similar clinically. Both are systemic diseases and may be
accompanied by abdominal pain, diarrhea which may be bloody,
fever, joint pains, etc. The symptoms are variable between patients,
but both are long-term and wax and wane.
o Ulcerative Colitis
 This is a non-granulomatous, chronic inflammatory disease that
affects mainly the left colon, and carries an increased risk for
developing cancer of the colon. It is of unknown etiology and is
seen mainly in adolescents and young adults.
 Symptoms include mild abdominal tenderness, weight loss, fever,
anemia, and no stool pathogens.
 Surgery is the best option, because it is definitive.
o Crohn’s Disease
 This is a granulomatous colitis that may affect any part of the GI
tract, but has a predilection for the terminal ileum and the colon. .
It is a transmural colitis, meaning that it affects all layers of the
bowel wall. It is difficult to distinguish from idiopathic ulcerative
colitis, which is purely mucosal. Fistulas can form.
 Symptoms include abdominal cramping, diarrhea and weight loss,
erythema nodosum, spondylitis, polyarthritis, and perirectal
disease.
 Treatment includes systemic steroids, enemas, and chemotherapy
agents
Ischemic Colitis
o This is due to interference of blood flow to the colon. Severe ischemia can
lead to gangrene.
o Symptoms include lower abdominal pain, fever, vomiting, blood and clots
in the rectum.

Polyps and Cancer
o A polyp is a tumorous mass that protrudes into the lumen of the gut. Some
polyps have an abnormal epithelial lining and are termed adenomatous
polyps. These are precancerous lesions and should be removed.
 Both benign and malignant tumors may show no symptoms, but
bleeding and obstruction may occur. Bleeding may cause
weakness, lassitude, and lightheadedness. Obstruction causes
nausea, vomiting, and abdominal pain. Malignant lesions produce
weight loss and extraintestinal manifestations.
o Colon cancer is very common. It accounts for about 15% of all cancer
related deaths in the US every year. Early in the course of the disease there
are usually no symptoms. Later there may be fatigue, weakness, and
anemia. If one is lucky, there is rectal bleeding early-on. Survival is
related to the extent of spread at the time of diagnosis.
 Males are affected more. Symptoms include altered bowel
function, blood in feces, unexplained anemia, weight loss, and a
palpable mass involving the colon or rectum.
 The classifications of this cancer include the Astler-Coller and
Dukes classification systems.
 Dukes Classification
A
B
C
D

Just mucosa
Muscularis/submucosa without lymph involvement
Lymph involvement
Metastasis
o Stages A and B have far better prognosis than
stages C or D.
 5 year survival
o A 98%
o B 90%
o D 0%
 Because of this major difference in prognosis, it is standard to
screen aggressively for colon cancer, and to treat any rectal
bleeding in an adult very seriously. Any anemia in an older male
should be considered GI cancer until proven otherwise.
Squamous Cell Carcinoma of the Anus
o These lesions are often confused with hemorrhoids, another common anal
disorder. Tumors tend to be annular, invade the sphincter, and spread
upward into the rectum.
Accessory Structures
Liver
 Functions
o Detoxification of blood via sinusoids
 Many of the toxic substances that enter our bodies will have
methyl groups (-CH3) attached to them, causing them to be polar.
These are filtered by the kidney and not reabsorbed, so they are
eliminated efficiently in the urine. The liver has the ability to
change some ingested, accumulated chemicals to be more polar so
that they are removed by the kidney. If not secreted, they would
lead to liver damage.
 Often the byproducts of protein metabolism produce ammonia,
which is an extremely toxic substance. The ammonia is converted
by the liver into urea to be less toxic. The liver also converts
purines into uric acid.
 It also serves as a blood reservoir.
o Carbohydrate metabolism
 The liver is one of the two areas in the body that store
carbohydrates in the form of glycogen.
 Excess glucose in the blood can be converted by the liver to
glycogen or glucose can also be converted to fat. Under situations
where glucose is required, the liver can release glucose by
glycogenolysis, the breaking down of glycogen into glucose. The
liver is the primary site of gluconeogenesis, the production of
glucose from non-carbohydrate precursors, primarily amino acids.
o Lipid metabolism
 Triglycerides and cholesterol are synthesized in the liver. The liver
excretes cholesterol into the bile.
 The liver is also the site of ketone body production during fat
metabolism.
o Protein synthesis and metabolism
 Albumins are synthesized in the liver.
 Plasma transport proteins are synthesized in the liver. These are
proteins that transport steroid hormones in particular, along with
other hormones and iron.
 Clotting factors such as fibrinogen, prothrombin, and all of the
various other proteins that will contribute to the clotting process
are synthesized in the liver.
o Formation and secretion of bile
 The liver secretes one pint of bile a day. Bile contains cholesterol
and bile salts, which are important for fat absorption.
 Bile salts are synthesized in the liver, then transferred and stored in
the gall bladder.
o Makes and stores vitamin A
o Stores iron and copper, along with vitamins B12 and D

o Produces blood cells in the embryo
Anatomy
o This is the largest gland in the body. It is located against the right, inferior
surface of the diaphragm.
o It consists of two lobes separated by the falciform ligament.
 The right lobe is larger and contains two smaller lobes, the
interiorly placed quadrate lobe and the posterior caudate lobe.
o The gall bladder is located on the inferior surface of the liver.
o The secretory unit is divided into lobules in which hepatocytes are the
functional cells. These are epithelial cells grouped together in
interconnected plates.
 Hepatocytes are radially disposed in the liver lobule forming a
layer 1-2 cells thick. These cellular plates are directed from the
periphery of the lobule to its center, forming a spongelike
structure. The space between these cellular plates contains liver
sinusoids (aka discontinuous capillaries), which are lined with a
fenestrated layer of endothelium. These are little passage ways in
which blood travels. It is almost like the blood is sieved. This
exposes the blood to a lot of tissue.
 Wherever two hepatocytes abut, they delimit a tubular space
between them called the bile canaliculus.
o Ducts
 Bile is secreted into the bile canaliculi, draining into collecting
ducts which drain ultimately into the common bile duct.
 The blood supply includes the right and left hepatic arteries.
o Kupffer cells, found within the wall of the sinusoiods, are separated from
the underlying hepatocytes by the Space of Disse. They are phagocytic
cells that contain microvilli of the hepatocytes. Blood fluids readily
percolate through the endothelial wall and make intimate contact with the
hepatocyte surface.
 The removal of RBCs by Kupffer cells results in the production of
bilirubin from the hemoglobin that is in the RBCs.
o The Portal System
 Unlike other parts of the systemic circulation, in a portal system
the blood passes through two sets of capillaries before it returns to
the heart. In the portal system, the first set of capillaries is in the
walls of the organs of the digestive tract, and the second set (the
sinusoids) are in the liver.
 The hepatic-portal system consists of veins that drain the blood
from the abdominal part of the digestive tract, pancreas, spleen,
and gallbladder. These veins go to the portal vein which distributes
blood to the capillary-like sinusoids of the liver. The blood then
dumps into the central veins, which lead to the hepatic vein, later
emptying into the inferior vena cava.
 The hepatic portal triad consists of the hepatic artery proper, portal
vein, and the common hepatic duct. These are present in the
corners of the lobules.


The blood flow to the liver is about 25% of the cardiac output. The
flow is derived from the portal vein (¾) and the hepatic artery. The
position of the liver is optimal for gathering, transforming, and
accumulating metabolites and for neutralizing and eliminating
toxic substances.
The significance of this vascular organization is that blood
supplied by the hepatic portal vein is rich in amino acids, simple
sugars, and other products of digestion, but relatively poor in
oxygen. The oxygen required to support the metabolic activity of
the liver is supplied by a separate pathway, arterial blood supplied
by the hepatic artery. The liver is unusual in that it has a dual blood
supply, both arterial and venous.

Pathology
o Hepatic dysfunction typically leads to stasis of the bile, and therefore
jaundice. Liver enzymes are generally looked at to assess liver status,
although liver function is better assessed by serum albumin levels. The
protime level, which is the bleeding time due to clotting factors not
producing properly, is also assessed.
 Jaundice is a yellow discoloration of the skin and sclera (icterus)
that occurs when systemic bilirubin levels rise above normal.
 Cholestasis is the systemic retention of bilirubin and other solutes
(mainly bile salts) that are normally excreted by the liver.
o Cirrhosis
 This is the end stage of chronic liver disease. Once cirrhosis
develops, it is irreversible. In western countries, cirrhosis is among
the top ten causes of death.
 Anatomically, the liver becomes hard, shrunken, and nodular due
to diffuse fibrous bands replacing normal liver lobules. It displays
impaired functions and diminished reserve due to a decreased
amount of functioning liver tissue. The hepatic portal vein is
diverted around rather than passing through the liver.
 The most common cause of cirrhosis is alcoholic liver disease
which accounts for 66-70% of cases. Viral hepatitis is responsible
for another 10% of cases. Cirrhosis leads to portal hypertension
and all clinical consequences, including hemmorrhoidal bleeding,
ammonia build-up in the blood, leading to an abnormal mental
state.
o Hepatitis
 This is an inflammation/infection of the liver. Elevated liver
enzymes damage liver cells in the bloodstream. It is usually nonsymptomatic (subacute) and recovery is 100%. If symptomatic,
90% of patients experience full recovery and 10% develop chronic
hepatitis, leading to inflammation, cirrhosis, and cancer. This
needs to be treated.
 Differentiation
 Acute vs. chronic
o Acute hepatitis causes liver cell necrosis and
inflammation. It can occur with resolution of an
illness and lifelong immunity. Symptoms include
malaise, anorexia, nausea, abdominal pain,
jaundice, dark urine, fever, rash, arthritis, and
itching.
o Fulminant or subacute hepatitis is the cause of acute
liver injury. It occurs in an overwhelming manner
with massive liver cell death due to hepatic necrosis
and decreased liver function. There is a high
mortality rate, but if the patient survives, liver
function is retuned to normal and there is no
residual evidence of liver disease.
o Chronic hepatitis is liver injury beyond the initial
acute stage. This can either be chronic active
hepatitis or chronic persistent hepatitis.
o The silent carrier state can have little or no liver
damage. 2/3 of these patients are unaware that they
have it.

Types
 Each different type is encapsulated with different protein
coats. They all present with different clinical symptoms.
 A- Enteric virus (Enterovirus 72)
o The incubation period is about 25 days (2-6 weeks).
Since this is so long, it is hard to track the origin. A
chronic carrier state does not occur, and many
infected individuals have an asymptomatic
infection. It is rarely fatal, unless it affects another
organ.
o Epidemiology
 In developing countries, asymptomatic
children are the reservoir. With improved
sanitation, the disease is seen more in adults.
 There were 7,600 official cases in 2003.
61,000 are estimated. It accounts for 30% of
the acute hepatitis cases. The annual
incidence in the US is 3.8-32.6/100,000,
with the average being 11.
 The seroprevalence in the US military is 1525%, 30% in homosexual men and 12% in
heterosexuals.
o Transmission
 Fecal-oral spread (rare parenteral cases). It
is an infectious hepatitis and is very
contagious.
 The virus is transmitted via contaminated
water and food from infected individuals.
 Hepatitis A may be found in daycare
facilities. Young children do not become
symptomatic, but they shed high titers. The
virus is transmitted through contaminated
diapers.


Common source outbreaks in food handlers,
health care workers, and other institutional
settings represent only a small number of
total cases.
o Prevention
 Handwashing
 Safer sexual practices
 Immune Serum Globulin
 This is highly efficacious (80-90%)
when administered at exposure.
 Recommended for sexual contacts,
household contacts, those exposed in
daycare facilities, custodial
institutions, and travelers.
 For common source outbreaks, it is
usually too late.
 Hepatitis A Vaccines
 Types: two inactivated vaccines
o Havrix (SKB)
o Vaqta (Merck)
 Very highly immunogenic and
efficacious (>95% after two doses).
 Adverse reactions are very mild.
 The CDC recommends routine
childhood immunizations.
o Diagnosis
 Elevated liver enzymes
 Acute hepatitis with positive IgM for HAV.
B- Hepadnavirus
o This is the most common cause of acute hepatitis in
the world.
o Epidemiology
 200,000-300,000 cases/year in the US
through the 1980s. Only 73,000 in 2003.
Cases in gay men have dropped in recent
years, but are now increasing.
Concomitantly, the proportion in
heterosexual men is also increasing.
 In highly endemic areas, the carrier rate can
exceed 10% with past evidence of infection
in 80-90% of the population.
 1-1.25 million are chronic carriers in the US.
300-350 million have chronic HBV
infections, and these are the major reservoirs
of HBV. 20-25% of persons with chronic
HBV infection will die prematurely of
cirrhosis or liver cancer. HBV may cause up
to 80% of all cases of liver cancer and is
second only to tobacco among known
human carcinogens.
 No medical treatment is currently available
to reliably eliminate or treat chronic
infection.
o Transmission
 Humans are the only reservoir for HBV.
 Perinatal
 Child to child through skin lesions, bites,
and contaminated medical equipment (IV).
 Adults through sexual encounters,
occupational hazards, and pericutaneous via
needle sharing and contaminated medical
equipment (IV).
 Incubation period is 2-6 months. Patients
with hepatitis B are at significant risk for
primary liver cancer.
o Laboratory Diagnosis of HBV
 Serologic markers
 Antigen (viral proteins)
o Immunized patients will not
have a positive result. This
tells us of active viruses.
o HBsAg- surface protein
excreted in the serum.
o HBeAg- component of the
viral core protein.
o Surface protein, central core,
nucleocapsid gives
information about the acute
infection, DNA/RNA, and
viral load (PCR) to see if the
treatment is working.
 Antibodies
o IgM responds to the core
protein of HBV.
 Histology of liver
 HBV cannot be cultured in standard
laboratory tissue culture

Found
 Surface Ab: have had immunization
(passive) or have had an infection
(active)
 Core Ab: had prior infection- not
possible with immunization
 Core Ab without Ab: window period.
Takes time to develop surface Abs.
 Surface Ag in blood: has an infection
now.
 IgE is chronic and IgM is acute.
o Prevention
 Post exposure prophylaxis consists of
 HBIG (0.06mg/kg) within 24-48
hours of exposure in adults and
within 7 days of birth of newborns
 This is the first dose of HBV
vaccine.
 Immune Serum Globulin is not very
effective. The asymptomatic conversion rate
is 22% vs. 4% for HBIG.
 Vaccines
 Heptivax is no longer available in the
US. Recombivax (MSD) and
Engerix B (S-KB) are. All are 8090% effective in clinical trials. They
are available in three doses. The
protection duration is not known (14
years). Currently, no booster is
recommended.
 It is safe in pregnant and lactating
women. Efficacy in HIV infection is
around 50%.
 Those recommended are all
neonates, and high risk groups,
including health care workers,
institutionalized patients, dialysis
patients, homosexual males,
hemophiliacs and blood product
recipients, and sexual contact of
carriers.
o Treatment
 Interferon/ riboviran


C- Flavivirus
o This is the most common cause of chronic hepatitis,
cirrhosis, and hepatocellular carcinoma. About 80%
develop chronic infection. 20% show signs of
cirrhosis within 10 years. Predictors are currently
unknown regarding which will progress. There is a
low spontaneous remission. Long-term sequelae are
similar to HBV.
o At least 6 different genotypes have been recognized
with type 1 being the most common (72%)
o Epidemiology
 It is difficult to determine, because the
screening tests are poorly available. There is
also a long lag time before seroconversion
(4-32 weeks, with an average of 15).
Seroconversion can occur up to a year after
the acute illness. The immune response is
variable.
 An estimated 150,000 cases/year in the US
through the 1990s, and 30,000 in 2003.
There is also an estimated 3,500,000 carriers
in the US.
 HCV infections account for >90% of non-A
and non-B hepatitis secondary to blood
transfusions, IV, etc. The incidence of HCV
infection due to blood transfusions has
declined by >95% since 1989. >50% of all
cases are community acquired with no
known risk factors.
o Diagnosis is made by antibodies discovered in
serology, PCR, viral RNA titers and liver biopsies.
There is no test for the antigen itself. The cloned
virus was used to develop the immunoassay for
anti-HCV antibody detection.
o No vaccine is available.
D- Defective/Incomplete virus (delta agent)
o This is an incomplete virus that requires HBV
surface antigen for packaging. It exclusively occurs
either simultaneously with HBV (co-infection) or
following an HBV infection (superinfection).
Superinfection of a HBV carrier with HDV
increases the severity of the chronic disease.


Virus
A
B
C
D
E
E- Possibly Calcivirus
o This is an enteric virus transmitted by the fecal/oral
route. It is mostly water-borne and is spread much
like HAV. It is isolated in epidemics from
underdeveloped countries like Asia, Africa, and
Mexico and is rare in the US. The mortality rate is
1-2%, except in pregnant patients where the rate is
>20%.
o Incubation is 3-6 weeks. Onset is acute, and there is
no chronic carrier state.
o Serology is the diagnostic test of choice.
Summary
Size
(nm)
27
42
30-60
40
32
Acute
Hep
Yes
Yes
Yes
Yes
Yes
Acute
Mortality
0.2%
0.2-1%
0.2%
2-20%
0.2%
Chronic Hep
No
Yes (2-7%)
Yes (85%)
Yes (2-70%)
No
Viral
type
RNA
DNA
RNA
RNA
RNA
Spread
Fecal/oral
Blood
Blood
Blood
Fecal/oral
 There are probably other viruses yet to be found.
o Alcoholic Liver Disease
 Fatty infiltration from chronic alcohol consumption leads to
hepatitis, then cirrhosis. This is a very large public health issue.
o Wilson’s Disease
 This is an inherited disorder of copper metabolism that leads to
liver, brain, and eye damage. Copper deposits are the problem
here, leaving characteristic Kayser-Fleischer rings in the eyes.
o Tumors
 The liver and lungs are the most common organs involved in
metastatic cancer. The most common cancers in the liver are
metastatic from the colon, lung, and breast.
 Primary liver cancer is very rare in the US, but common in Asian
countries due to an increased rate of hepatitis B carrier states.
Prognosis is grim with death usually within 6 months of the
diagnosis.
Gallbladder
 Function
o The gallbladder stores bile that is produced by the liver and concentrates it
5-10 fold. As digestion occurs, the gallbladder ejects this concentrated bile
into the duodenum to aid in the digestion and absorption of fats.
o The gallbladder can be surgically removed without impairing bile
secretion by the liver into the intestinal tract.
 Anatomy
o This is a pear-shaped sac 3-4” long located on the under surface of the
liver. It has a capacity of 30-35ml.
o The walls of the gall bladder have three coats
 Mucous coat- Tall columnar epithelium
 Fibromuscular coat- Smooth muscle
 Serous coat
o Ducts


The cystic duct from the gall bladder and right and left common
hepatic ducts combine to form the common bile duct. This enters
the duodenum in the area of the pancreatic duct. The point of entry
into the duodenum is called the major duodenal papilla of Vater.
Occasionally the pancreatic duct enters the common bile duct
before entering the pancreas, forming an ampulla of Vater.

Bile
o Bile is secreted by the cells of the liver into bile ducts, which drain into the
duodenum. Between meals, the duodenal orifice of this duct is closed and
bile flows into the gallbladder, where it is stored. When food enters the
mouth, the sphincter around the orifice relaxes. As the gastric contents
enter the duodenum, the hormone cholecystokinin (CCK) from the
intestinal mucosa causes the gallbladder to contract, emptying the
concentrated bile into the small intestine.
o Bile strongly resembles pancreatic juice. About 500ml is secreted per day.
o Ingredients
 Human hepatic duct bile is 97% water, 0.7% bile salts, 0.2% bile
pigments, 0.06% cholesterol, 0.7% inorganic salts, 0.15% fatty
acids, 0.1% lecithin (a phospholipid), 0.1% fat, and trace amounts
of alkaline phosphatase to neutralize the acid from the stomach.
Small amounts of other metabolic end products and trace metals
are also found.
 Bile salts, cholesterol, lecithin, and bile pigments are
secreted by hepatocytes. The bicarbonate is secreted by the
epithelial cells lining the bile ducts.
 Bile salts are the most important. These help participate in
enterohepatic circulation. The salts are absorbed into the ileum and
are returned via the portal vein to the liver, where they are once
again secreted into the bile.
 Bile salts, which are cholesterol derivatives, emulsify fat
due to their detergent qualities. They are amphipathic,
meaning they have both polar and nonpolar parts, allowing
the fat to be more water soluble. This is required for the
process of the fat absorption.
 Bile salts are synthesized in the liver, then transported to
the gall bladder, and stored there until the CCK stimulates
its contraction to dump the bile salts into the duodenum.
 Bile pigments
 These are formed when the heme portions of hemoglobin
are broken down during the destruction of old or damaged
erythrocytes in the spleen and liver.
 The predominant bile pigment is bilirubin. This gives bile
its yellowish color. After entering the intestinal tract via the
bile, it is modified by bacterial enzymes to form the brown
pigments that give feces its characteristic color. Some are
actually excreted in the urine, giving it a yellow color.

Pathology
o Gall Stones
 This occurs in 10-20% of adults, generally in females, families,
40s/50s, fat, and fertile.
 Typically these are cholesterol stones. Most patients with smaller
gall stones are asymptomatic, but symptoms of painful cramping
and squeezing can occur when a stone obstructs bile flow from the
gall bladder. Pain is in the right upper quadrant into the right
shoulder blade. Inflammation often occurs with stones trying to
pass. This is called cholecystitis, and treatment is mainly surgical.
 The complications that arise generally appear where the gallstone
gets stuck.
 The gall bladder and pancreas share a duct, so a small gall stone
can obstruct pancreatic flow as well leading to pancreatitis.
 Acute Pancreatitis and biliary tract disease
 In patients who do not drink alcohol, about 50% of cases of
acute pancreatitis are associated with biliary tract disease.
In such cases, the cause is obstruction of the common bile
duct and the main pancreatic duct when a gallstone
becomes lodged at the ampulla of Vater. Reflux of bile or
duodenal contents into the pancreatic duct leads to
parenchymal injury.
 Others have proposed that bacterial toxins or free bile acids
travel via lymphatics from the gallbladder to the pancreas,
giving rise to inflammation. In either case, acute
pancreatitis associated with biliary tract disease is more
common in women.
 Chronic Pancreatitis and biliary tract disease
 Chronic pancreatitis results from recurrent attacks of acute
pancreatitis. The two major causes of chronic pancreatitis
are chronic alcoholism and biliary tract calculi.
o HIV Infection and biliary tract disease
 The protozoan Cryptosporidium is frequently implicated as the
cause of the biliary disease typical of HIV. Cryptosporidial
cholangitis may present clinically as cholecystitis, sclerosing
cholangitis, or papillary stenosis.
Spleen
 Function
o Defense
 This is part of the lymphatic system. It hypertrophies during
infectious disease and atrophies with age. As blood passes through
the spleen, macrophages remove microorganisms, old red blood
cells, and debris from the blood and destroy them by phagocytosis.
While lymph nodes serve as the immunologic filters of lymph, the
spleen is the immunologic filter for the blood.
 Promotes antibodies
o Serves as a blood reservoir
o Hemopoesis- Makes lymphocytes, monocytes, and plasma cells
 During fetal life, it makes all blood cell types.
 Anatomy
o The spleen is located between the fundus of the stomach and left inferior
surface of the diaphragm, above the left kidney. It is approximately 12cm
in length. The hilus contains the splenic artery and splenic vein.
o This is a large fibrovascular encapsulated organ with an inner connective
tissue trabecular framework supporting a reticular connective tissue
meshwork. The trabecular meshwork consists of white and red pulp.
 White pulp is an aggregate of lymphoid tissue containing T and B
lymphocytes. It contains lymphatic nodules called splenic
corpuscles or Malpighian bodies. Lymphocytes are formed here.
Diffuse lymphoid tissue forms a cuff around the arterial branches
composing the periarterial lymphocyte sheath (PALS).
 Red pulp contains monocytes, free macrophages, granulocytes
(neutrophils, basophils, eosinophils), and erythrocytes (red color of
red pulp). It acts as a filtration system for damaged or old red
blood cells and microorganisms. It is more abundant than white
pulp. It is surrounded by anastomizing venous sinuses. The
parenchyma of red pulp is composed of diffuse lymphoid tissue,
which is highly infiltrated with blood cells.
General Physiology
Motility
 Movements
o Movement of food from the mouth into the pharynx is a voluntary act.
o Movement of food from the pharynx into the esophagus is a reflex act.
o Movement of the food through the esophagus is accomplished via
peristalsis. Emptying of the stomach is accomplished by gastric peristalsis.
Peristalsis then occurs throughout the colon.
o The defecation reflex is initiated by stimulation of the rectal mucosa.
 Types of motility
o Tonus contraction
 These are continual low grade contractions of smooth muscle.
o Rhythmic contractions
 These are elicited by spike potentials.
 Two types
 Segmentation- major mixing movement
 Peristalsis- major propulsive movement
Regulation
 Neural Control
o Motility is regulated by the autonomic nervous system via the enteric
nervous system, which is the intestinal muscle pacemaker.
 This is completely independent of the central nervous system. The
enteric brain is an integrated system of nervous plexi in the wall of
the digestive tract, containing both the myenteric and submucosal
plexus.
 The neurons either synapse with other neurons or end near smooth
muscles or glands. Impulses can be sent either up or down the
tracts. This contains both adrenergic and cholinergic neurons, as
well as neurons that release other neurotransmitters.
 Serotonin is the chemical transmitter used by the myenteric plexus,
a local network of nerve cells in the walls of the esophagus,
stomach, and intestine.
 The GI reflexes are initiated by
 Distention of the wall of by the luminal contents
 Chyme osmolarity (total solute concentration)
 Chyme acidity
 Chyme concentration of certain digestion products, such as
monosaccharides, fatty acids, peptides, and amino acids.
o The parasympathetic autonomic nervous system enters via CN X and
innervates most of the upper gut, including the esophagus, stomach,
pancreas, and upper large intestine. Constant stimulation on the gut muscle
creates the “tonus” of the intestinal muscle. The PANS enhances motility
and digestive secretions and relaxes muscle sphincters so food can pass.
Acetylcholine is the neurotransmitter that stimulates the gut wall.

o The sympathetic nervous system supplies the entire GI tract.
Norepinephrine inhibits the enteric nervous system, therefore inhibiting
contractions of the smooth muscle. The SANS thus slows and blocks
passage of food, decreases contraction and motility, causes loss of tonus,
constriction of sphincters, and decreases secretion of digestive juices.
Hormonal Control
o Endocrine hormones, which last longer than neurotransmitters, reach their
target through the circulation. They are produced in the epithelium of the
stomach and small intestine.
 Paracrine hormones are vasoactive intestinal polypeptides, such as
somatostatin. Somatostatin reaches target cells by diffusing
through intercellular spaces after traveling from the blood.
 Gut hormones
 Gastrin
o The introduction of a food bolus from the
esophagus into the stomach stimulates gastrin,
which produces many events, eventually leading to
the release of chyme into the small intestine. This is
secreted by the stomach and stimulates HCl
secretion.
o There are three phases of gastric secretion. These do
not necessarily occur in this order, nor one at a time.
 Cephalic Phase
 The sight, smell, and taste of food
stimulate the PNS, which activates
the initial stage of the whole
digestive process. Here, some gastrin
is secreted.
 Gastric Phase
 As the food bolus accumulates in the
stomach, the distention of the
stomach is going to have a
stimulatory effect on the PNS.
 As the peptides are digested, the
amino acids that are liberated are
going to have stimulatory effects on
acid secretion. When the secretion of
acid results in a pH of less than 2.5
in the stomach, further gastrin
secretion is inhibited to prevent
further HCl secretion.




Intestinal Phase
 Arrival of chyme causes intestinal
distension, which inhibits the
parasympathetic stimulation of
motility, which is further inhibited
by the presence of fat in the intestine.
The gastric motility inhibition allows
the chyme to remain in the small
intestine so that it can be fully
digested and absorption can take
place. Here CCK and GIP are
involved.
Secretin
o This is secreted by the small intestine and stimulates
water and bicarbonate secretion in the pancreatic
juice. It also potentiates the action of
cholecystokinin, which acts on the pancreas. This is
stimulated by increased duodenal acidity and
gastrin.
 Cholecystokinin (CCK)
o This is secreted by the small intestine in the
presence of fatty acids and amino acids.
o Its most important action is to stimulate contraction
of the gall bladder, but it also stimulates the
secretion of pancreatic juice enzymes and inhibits
gastric motility.
 Gastric inhibitory peptide
o Glucose-dependent Insulinotropic Peptide (GIP)
o This is an inhibitory hormone that inhibits gastric
motility and stimulates secretion of insulin from the
endocrine portion of the pancreas. This is to prevent
additional chyme from being released into the small
intestine too quickly. It is stimulated by chyme.
 Glucagon-like-peptide
o This is an inhibitory enzyme in the ileum and colon.
It is also stimulated by chyme and inhibits gastric
motility and the secretion/ stimulation of insulin.
Thyroid hormone increases both the rate of secretion of the
digestive juices and the motility of the GI tract.
Stimulation of the lateral hypothalamic area causes a tremendous
increase in appetite.

Digestive Enzymes
Absorption
 This is the passage of substances, such as digested foods, water, salts, and
vitamins through the intestinal mucosa into the blood or lymph. Most absorption
occurs in the small intestine.
 Absorption may occur though diffusion, osmosis, filtration, or active transport.
Absorption of lipids occurs passively as these substances pass through the lipid
bilayer of a cell membrane. Water soluble substances like sugars and amino acids
use carriers to enter cells. Some absorptive processes require energy (active
transport) while others do not (facilitated diffusion).
Pancreatic Secretions




The exocrine pancreas is the source of an enormous number of digestive enzymes.
These secretions go into the pancreatic duct which later joins the common bile
duct that enters the duodenum. The pancreatic juice is alkaline and has a high
HCO3 content (about 113 meq/L vs. 24 meq/L in the plasma). About 1400ml of
pancreatic juice is secreted per day.
The composition of normal pancreatic juices includes cations (Na+, K+, Mg2+,
H+), anions (HCO3-, Cl-, HPO3-, SO42-), albumin, globulin, and digestive enzymes.
o The bicarbonate released from the pancreas will neutralize the HCl being
released from the stomach. Its release is analogous to the release of HCl,
with the directions being reversed.
o Digestive Enzymes
 Amylase digests starch to maltose and glucose
 Trypsinogen, a precursor to trypsin, is activated by enterokinase. It
is present in the brush border of the epithelium, and it acts to
cleave peptide bonds to digest protein.
 Once trypsin is activated, it is going to activate chymotrypsin and
elastase. These cleave only internal peptide bonds.
Carboxypeptidase cleaves off the carboxyl end of a peptide.
Phospholipase cleaves the fatty acids from phospholipids.
 Lipase cleaves fatty acids from glycerol to digest triglycerides.
Cholesterolesterase releases cholesterol from other molecules.
 Ribonuclease cleaves RNA into shorter chains. Deoxyribonuclease
cleaves DNA into shorter chains.
Pancreatic juice is the most versatile of the digestive secretions, because its
enzymes are capable of nearly completing the digestion of food in the absence of
all other digestive secretions. These enzymes require a pH close to neutral for
optimal activity, and this is provided by the alkaline secretion of the pancreatic
intercalated duct cells.
Its secretion increases directly after a meal, mainly as a result of stimulation by
the hormones secretin and CCK. An additional 25% of secretions are controlled
by parasympathetic nerves in response to such things as the taste of food and
distention of the stomach.

The secretory units are compound tubuloacinar glands. Serous cells surround a
central lumen which goes on to form an intercalated duct. These are lined with
cuboidal epithelial cells. The digestive enzymes secreted are discharged into the
intercalated duct which eventually joins to form the pancreatic duct. The
pancreatic duct receives branches from lobules and joins the common bile duct to
empty into the duodenum.
o The blood supply is from the lineal (splenic) artery.
Gastrointestinal Drugs

Agents Useful in Treating Peptic Ulcers
o H2 Blockers/ Receptor Antagonists
 These can be purchased over the counter.
 Agents
 Cimetidine (Tagamet)
o This is a short-acting agent that attaches to
histamine receptors in parietal cells.
o Adverse effects include blockade of testosterone
receptors
 Famotidine (Pepcid)
 Nizatidine (Axid)
 Ranitidine (Zantac)- Longer acting
 Mechanism
 Decreased gastric acid and pepsin secretion, as well as
decreased vasodilation via H+,K+ ATPase decreasing the
H+ in the lumen.
 Therapeutic Uses
 Treat peptic ulcer disease
 Treat gastroesophageal reflux disease (GERD)
 Treat immediate hypersensitivity response
o Proton Pump Inhibitors
 This is the most effective method of preventing acid secretion. It is
converted to the active form by acid.
 Agents
 Omeprazole (Prilosec)
 Lansoprazole
 Esomeprazole (Nexium)
 Mechanism- Inhibits H+, K+-ATPase
 Therapeutic Use- Treats GERD
o Antacids
 These neutralize stomach acids that can cause heartburn in the
lower esophagus.
 Systemic
 These are highly soluble and are rapidly absorbed in the
gut.
 Sodium bicarbonate (Baking Soda)
o This causes bloating, hypertension, and acid
rebound. This should not be used with deep ulcers,
because it causes perforation and inflammation.
 These may produce systemic alkalosis, making
nonsystemic antacids more desirable.
 Nonsystemic
 Constipating agents constrict the sphincter.
o Calcium carbonate (Tums, etc)

o Aluminum hydroxide gel (Amphogel)
o Aluminum phosphate (Alternagel)
 Laxatives
o Magnesium hydroxide (Milk of magnesia)
 This works via an osmotic mechanism
o Magnesium trisilicate gel
 Mixtures
o Maalox (magnesium and aluminum oxides)
o Creamalin
o Mylanta
o Beano
o Cholinergic blockers
 Pirenzapine
 Block M1 receptors on paracrine cells
 Block M3 receptors on parietal cells
 Dicyclomine (Bentyl)- Relaxes GI muscles to treat GI spasm.
 Atropine, Methantheline, Propantheline, Tricyclics
o Misoprostol (Cytotec)
 Mechanisms
 This is a prostaglandin analog that inhibits cAMP, thus
decreasing acid secretion. It also stimulates secretion of
mucous. It is used in conjunction with NSAIDs.
 Adverse effects- Diarrhea and abortion
o Sucralfate (Carafate)
 Mechanism- This coats the ulcer crater by binding to necrotic ulcer
tissue, acting as a barrier to HCl and pepsin.
o Colloidal bismuth
 Mechanism- These preparations coat and bind to both gastric and
duodenal ulcer tissue. They protect the ulcer from acid and pepsin.
o Carbenoxolone and Bismuth subcitrate
o Antimicrobials (Penicillin, Tetracycline)
Prokinetic Drugs
o These stimulate gut activity and are used to treat pathologies such as
diabetic gastroparesis (no churning due to diabetes mellitus) and GERD.
o Cholinergic agonists
 Types
 Bethanechol
 Metoclopramide (Reglan)
o This is the most widely used antiemetic that blocks
D2 receptors.
o It increases the tone of the lower esophageal
sphincter, increases the force of gastric contractions,
improves gastro-duodenal coordination, enhances
gastric emptying, as well as sensitizing receptors in
the gastric muscles to acetylcholine to increase
stomach activity.



o Adverse Effect- can develop extrapyramidal
syndrome, EPS.
 Mechanism- Stimulate muscarinic receptors in the stomach.
 Adverse effects- Increased salivation, lacrimation, sweating.
o Cholinesterase inhibitors act in a similar manner to cholinergic agonists.
o Motilin receptors agonists (GI hormones)
 Erythromycin (E-mycin) and derivatives enhance GI contractions
and increase the rate of gastric emptying.
Emetics
o These induce vomiting by irritating the stomach lining. They can use used
with accidental ingestion of poisons.
o Types
 Apomorphine
 Syrup of Ipecac
Antiemetics
o These suppress vomiting.
o Types
 Metoclopramide (Reglan)
 This is a prokinetic drug that treats gastric hypomotility.
 Ondansetron (Zofran)
 This blocks the serotonin receptors that increases the tone
of the lower esophageal sphincter, increases the force of
gastric contractions, improves gastro-duodenal
coordination, and increases stomach emptying.
 Prochlorperazine (Compazine)- most effective
 This is a major tranquilizer, along with chlorpromazine. It
comes in the form of a suppository.
 Dronabinal (Marinol) and Nabilone are used for cancer patients.
 H-1 Blockers such as diphenhydramine, dimenhydrinate, and
promethazine.
 Scopolamine- These patches can be used behind the ears.
Laxatives (Cathartics)
o These are used to treat constipation when other measures such as
increased water, fiber, and exercise fail or cannot be used. Other uses
include preparation for surgery, acute poisoning, and severe cardiac
problems.
 A condition called “The Laxative Habit” can be encountered in
which the taking of laxatives everyday can make the gut hypotonic
and lose tone. This is common with seniors.
o Irritants
 Agents
 Emodin
 Castor oil
 Phenolphthalein (Ex-Lax)
 Bisacodyl (Dulcolax)
 Ducosate sodium (Colace)
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Mechanisms
 Stimulates the accumulation of electrolytes and water in the
lumen of the muscles of the large intestine, increasing
intestinal motility.
 Adverse effects
 Cramping
 Intestinal atony
o Emollients
 Agents
 Mineral oil (Liquid petrolatum)
 Insoluble dietary fiber (vegetables)
 Hydrophilic colloids
o Agar
o Psyllium seed (Metamucil)
o Methylcellulose (Citrucel)
 Mechanisms
 Decreases fluid absorption, therefore decreasing motility.
o Osmotic agents
 Agents
 Magnesium sulfate (Epsom salt)
 Magnesium hydroxide (Milk of magnesia)
 Lactulose (Cephulac)
 Glycerin suppositories
 PEG Electrolyte Solution (GoLYTELY, CoLYTE)
o Polyethylene glycol
o Cleans out gut pre-surgery
 Mechanism
 Increases osmotic pressure in the intestine, thereby
increasing the bulk and stimulating the muscles.
Antidiarrheal Agents
o Opium derivatives (Morphine)
 Diphenoxylate (Lomotil)- contains some atropine
 Codeine
 Loperamide (Imodium)
o Bismuth subsalicylate (Pepto-Bismol)
o Clonidine (Catapres)
o Kaolin
o Pectin
o Activated charcoal- absorbs poison
o Major tranquilizers, such as trifluoperazine and chlorpromazine.
o Antimicrobials
Diagnostic Agents- Barium salts
Heimlich Maneuver
 Common factors in choking
o Large piece of food (aka café coronary)
o Alcohol
o Dentures
o Other foreign objects
 This is the most common form of cardiac arrest in children.
 Three levels of Air Exchange
o Good- the victim can cough forcibly.
 Just watch. Do not interfere.
 This can proceed to poor.
o Poor- the victim can barely breathe. There is a weak cough or whistle.
 Treat this as a complete obstruction.
o Complete Obstruction- no air can pass through.
 The patient cannot cough.
 Ask, “Are you OK?” See if there is a response.
 Universal Sign- Grabbing Throat.
 Heimlich Maneuver
o Have the patient stand and stand behind them.
o Make a fist with the thumb out. Reach around the victim with both hands.
Place the thumb in the navel, avoiding the xyphoid.
o Give five in and up thrusts, trying to “pop” out the obstruction with each
thrust.
o This is done in the same manner for a child.
o With someone pregnant or obese, do the procedure against the chest in the
same manner as CPR. This is not as effective.
 Auto-Heimlich
o The same procedure as above can be performed. One could also make a
fist and fall over a chair.