7.1: Anatomy and Physiology Review
Figure 7.1 The
digestive system
and its organs
Figure
7.2 Structures and
regions of the
stomach
Figure 7.3 Liver, gallbladder, and bile ducts
The main functions of the gastrointestinal (GI) tract, (also called the alimentary canal) are to
digest food and absorb nutrients into the blood stream. The GI tract is a long, muscular tube
that extends from the mouth to the anus. The upper GI tract contains the mouth, esophagus,
and stomach. The middle GI tract contains the duodenum, jejunum, and ileum; the lower tract
contains the cecum, colon, and rectum. The accessory organs include the salivary glands, liver,
and pancreas. Figure 7.1 depicts the digestive system and its organs.
As the point of entry for food and the beginning of the digestive tract, the mouthbegins the
process of digestion. Here, food is masticated (chewed) while the tongue and salivary glands act
in concert, preparing food to be swallowed. The salivary glandsproduce saliva which both
lubricates the food to ease of swallowing and aids in the breakdown of food. Saliva contains
multiple enzymes such as salivary amylase which breaks down carbohydrates, and lipase which
breaks down fats.
The esophagus serves to pass food from the pharynx to the stomach. It contains smooth
muscle layers that use peristalsis (alternating muscular contractions) to move food through the
GI tract. The pharyngoesophageal sphincter is located in the upper esophagus and prevents air
from entering the esophagus and stomach during breathing. The gastroesophageal sphincter is
located in the lower region of the esophagus connecting it to the stomach. It prevents reflux of
gastric contents into the esophagus.
The stomach holds food in storage during the early stages of digestion. Carbohydrate and
protein digestion (by pepsin) occur here. As shown in Figure 7.2, the area where the esophagus
opens into the stomach is called the cardiac region, due to its proximity to the heart. The domeshaped portion is called the fundus, and the middle portion is the body. The region that
connects the stomach to the small intestine is called the pyloric region. The pyloric
sphincter controls the emptying of stomach contents into the small intestine and prevents the
backflow of contents into the stomach.
The small intestine is made up of the duodenum, jejunum, and ileum. The duodenum is
approximately 10 inches long. The jejunum and ileum have a combined length of approximately
9-20 feet (this can vary greatly depending on the size of the person).
The small intestine is where the majority of digestion and absorption takes place. Assisting in
the digestive process, bile and pancreatic juices enter the intestine through the common bile
duct and main pancreatic duct, respectively. For lipid digestion to occur, fat must be broken
down into smaller pieces so that the water-soluble digestive enzymes can act on the surface
molecules. This process, known as emulsification, starts in the stomach with agitation (or
mechanical digestion) and continues in the duodenum with the help of bile and pancreatic
lipase (chemical digestion). The small intestine contains a large surface area composed of villi
and circular folds, which allows for absorption of nutrients. Absorption is the process of moving
nutrients and other materials from the external environment of the GI tract into the internal
environment.
The large intestine is approximately 4.5-5 feet long and 2.4-2.7 inches in diameter. It is
comprised of the cecum, colon, rectum, and anal canal. The ileocecal valve is located at the
cecum and prevents feces from flowing back into the ileum. The colon is further divided into
the ascending, transverse, descending, and sigmoid sections. The rectum connects the sigmoid
colon to the anus. The anal canal has strong sphincter muscles that prevent incontinence. The
large intestine reabsorbs mainly water and serves as storage for waste until defecation occurs.
The liver is the largest visceral organ in the body, weighing approximately 3 lbs in an adult. It
receives 25% of the resting cardiac output. The liver is unique in that is has a venous (portal)
blood supply through the hepatic portal vein that receives about 75% of blood per minute, and
an arterial supply through the hepatic artery that receives the remaining 25% of blood. The
venous blood comes from the digestive tract, pancreas, and spleen as seen in Figure 7.3.
The hepatic vein in the liver drains into the inferior vena cava, below the level of the
diaphragm. Due to this pressure difference, the liver can store approximately 500-1000 mL of
blood. This is helpful during times of hypovolemia and shock as this blood can be moved back
into circulation. When there is an accumulation of blood in the periphery, as seen in right sided
heart failure, it accumulates in the liver.
The liver has several important functions in the body. It produces bile; metabolizes hormones
and drugs; synthesizes proteins, glucose, and clotting factors; stores vitamins and minerals and
converts them to useable material the body can utilize; changes ammonia to urea; and converts
fatty acids to ketones.
The liver can store large amounts of glucose as glycogen, through a process known as
glycogenesis. When blood glucose levels are low, glycogen is converted back to glucose. The
liver can also synthesize glucose from amino acids, glycerol, and lactic acid during times of
fasting or increased demand in a process called gluconeogenesis. Finally, it can convert excess
carbohydrates to triglycerides for storage in adipose tissue and is a major site for protein
synthesis and degradation.
The liver produces approximately 500 to 600 mL of bile daily. Bile is needed for dietary fat
digestion and absorption. The bile salts contained in bile, which are formed from cholesterol,
are the important component of digestion.
GI Wall Structure
There are 4 layers to the GI wall structure starting below the upper third of the esophagus as
seen in Figure 7.4. They are: (1) the mucosal layer, (2) the submucosal layer, (3) the muscularis
externa, and (4) the serosal layer. The mucosal layer is the first, or inner layer. It is made up of
epithelium, an underlying connective tissue called the lamina propria, and smooth muscle cells
that can contract and change the shape and surface area of the mucosal layer.
This mucosal layer has many functions:

o
o
o
o
It produces mucus that lubricates and protects the inner surface of the
alimentary canal
It secretes digestive enzymes and substances that break down food
It absorbs the breakdown products of digestion
It maintains a barrier to prevent the entry of noxious substances and
pathogenic organisms
These epithelial cells are constantly being replaced every ~5 days. As such, injury to this layer
heals rapidly.
Figure 7.4 Transverse section of the digestive system depicting the 4 layers of the GI wall
The second layer is the submucosal layer, which contains dense connective tissue and some
adipose tissue. This layer has blood vessels, nerves, and structures that secrete digestive
enzymes.
The third layer is the muscularis externa, which consists of an inner layer of circularly arranged
smooth muscle cells and an outer layer of longitudinally arranged smooth muscle layers. These
layers alternately contract to help move the contents through the GI tract (peristalsis).
The fourth layer is the serosal layer, which is a serous membrane. This is the outermost layer of
organs and is also called the visceral peritoneum. The peritoneum is the largest serous
membrane in the body. It is comprised of two continuous layers, the visceral and parietal
peritoneum. The parietal peritoneum lines the wall of the abdominopelvic cavity. Between the
two layers is the peritoneal cavity, a potential space containing fluid secreted by the serous
membranes. This serous fluid keeps a moist surface to prevent friction between the moving
abdominal organs.
The mesentery is the double layer of peritoneum that encloses some or all of the abdominal
viscera and attaches it to the abdominal wall. Included in the mesentery are blood vessels,
nerves, and lymphatic vessels that supply the intestinal wall as seen in Figure 7.5. It also holds
the organs in place and stores fat.
The omentum is a double-layered fold of peritoneum that hangs down from the stomach to
adjacent organs in the abdominal cavity. The greater omentum connects to the stomach and
covers the transverse colon and the folds of the intestine. The lesser omentum extends
between the liver and lesser curvature of the stomach. The greater omentum contains fat and
has a lot of mobility to follow the movements of the intestines. It can form adhesions (fibrous
scar tissue) adjacent to inflamed organs, such as the appendix. It also cushions the abdominal
organs against injury and provides insulation against the loss of body heat.
Figure 7.5 (A) The greater omentum and the mesentery attachments to the small and large intestines. (B) The
mesentery attachment to the small bowel, showing the blood vessels, nerves, and lymphatic vessels. (C) Sagittal
section of the female abdominopelvic cavity, showing the relationships of the peritoneal attachments and the
greater and lesser omentums.
7.2: Anatomy and Physiology Review II
Figure
7.6 Autonomic
innervation of the
GI tract (gganglion; n-nerve).
Parasympathetic
innervation is
indicated
in blue and
sympathetic in red.
GI Motility
Motility is
important in
the GI tract, as
it propels food
and fluids
forward to be
digested and
absorbed. The
movements can
be either
rhythmic or
tonic. Rhythmic
movements are
intermittent
contractions
that help to mix
and move food
along. They are
present in the
esophagus,
antrum of the
stomach, and
small
intestine. Tonic
movements have a constant level of contraction or tone without regular periods of relaxation.
They are present in the lower esophagus, the upper region of the stomach, the ileocecal valve,
and the internal anal sphincter.
The majority of contractile tissue in the GI tract is smooth muscle. This smooth muscle has lowresistance pathways called gap junctions, that electrically couple the cells. This allows the
electrical signals that initiate muscle contractions to move rapidly from one fiber to the next
within each bundle.
Like cardiac muscle in the heart, the GI tract contains specialized smooth muscle cells known
as the interstitial cells of Cajal which act as pacemaker cells. These cells give rhythmic,
spontaneous oscillations in membrane potentials, called slow waves, that range in frequency
from 3 per minute in the stomach to 12 per minute in the duodenum. The amplitude and
frequency of the slow waves is regulated by the enteric nervous system, located in the walls of
the GI tract, and by the parasympathetic and sympathetic divisions of the ANS. Notably,
peptides (neurotransmitters and GI hormones) can also help to regulate GI motility. Activation
of the SNS decreases or stops amplitude of the slow waves; whereas activation of the PNS
increases the amplitude of the slow waves.
The enteric nervous system is located in the wall of the GI tract and is made up of the
myenteric and submucosal plexuses. These two plexuses are networks of nerve fibers and
ganglion cell bodies. Interneurons connect afferent sensory fibers, efferent motor neurons, and
secretory cells to form reflex circuits. The myenteric (Auerbach) plexus is a chain of neurons that
are involved in GI motility. They are situated between the muscular layers of the GI tract.
The submucosal (Meissner) plexus plays a role in controlling secretions, absorption, and
contraction of each segment of the intestinal tract. It is situated between the mucosal and
muscular layers of the intestinal wall.
As seen in Figure 7.6, the GI system is innervated by both the sympathetic and parasympathetic
branches of the autonomic nervous systems. The vagus nerve (cranial nerve X; blue) provides
parasympathetic innervation to the stomach, small intestine, cecum, ascending colon, and
transverse colon. The remaining portions of the colon are innervated by parasympathetic fibers
exiting the sacral cord through the pelvic nerves.
Sympathetic control comes from the thoracic chain of sympathetic ganglia (Figure 7.6; red).
Activation of the sympathetic nervous system ultimately leads to decreased GI motility. This is a
result of decreased mucus secretion and the increased contraction of sphincters and blood
vessels that supply the GI tract when these nerves are stimulated.
Gastric Motility
The stomach stores food and can expand or contract in size relative to the amount of food or
gas within it. On average, the stomach can hold ~ 1 to 1.5 L of volume. As food is broken down
in the stomach it is converted into a creamy mixture called chyme.
The stomach churns and mixes food in a peristaltic fashion of 3-5 contractions per minute, each
lasting 2-20 seconds. Contraction of the antrum pushes food toward the closed pyloric
sphincter. Larger food particles are returned to the body of the stomach for further breakdown.
The other contents are emptied into the duodenum between contractions.
The pyloric sphincter regulates the flow of chyme into the duodenum and prevents backflow
back into the stomach. If this sphincter did not function properly, regurgitation of bile salts and
duodenal contents would damage the mucosa of the antrum, resulting in gastric ulcers. A rapid
influx of highly acidic gastric contents can also damage the duodenal mucosa.
Stomach emptying is regulated by hormonal and neural mechanisms. The hormones
cholecystokinin (CCK) and glucose-dependent insulinotropic polypeptide (GIP) are released in
response to the composition of the chyme (i.e. pH and/or fatty acid content). If the rate of
emptying is too slow or too fast, motility disorders will occur. For instance, gastric retention is a
result of slow emptying. This is usually caused by an obstruction or gastric atony, a decrease in
muscular tone. Dumping syndrome is the term used to describe abnormally fast emptying of
hyperosmotic gastric secretions into the duodenum and jejunum.
Small Intestinal Motility
As previously mentioned, the small intestine is the primary site of digestion and the absorption
of nutrients.
The two patterns of contractions in the small intestine are:
1. Segmentation waves are slow contractions of the circular muscle layer. They occlude the
lumen and push digestive contents forward and backward. Segmentation waves use small
portions of the intestine at a time. During this activity, chyme is mixed with the digestive
enzymes from the pancreas and all surface area is exposed to the intestinal surface for
absorption. Predictably, segmentation activity is higher after a meal. Figure 7.7A depicts this
process.
2. Peristaltic contractions are rhythmic movements designed to propel the chyme along the
small intestine toward the large intestine. Peristaltic movements contract, then relax, always in
one direction as seen in Figure 7.7B. They begin in the duodenum near the entry sites of the
common duct and main hepatic duct. When they reach the ileocecal junction, stretching of the
ileum elicits a reflex which relaxes the sphincter, allowing fluid to move into the cecum. Motility
changes in this area are common. Inflammatory diseases can increase motility, while surgery
can decrease motility.
Figure 7.7 (A) Segmentation waves, and (B) Peristaltic contractions
Colonic Motility
There are two types of movements in the colon:
1. Haustral churning occurs in compartments of the colon called haustra. These movements fill
and expel contents in the haustra, to ensure the entire surface area of the fecal mass is exposed
to the intestinal surface.
2. Propulsive mass movements involve the simultaneous contraction of a larger segment of
the colon in order to move a collective amount of fecal matter. These mass movements last
about 30 seconds, followed by a longer period of relaxation (a couple minutes) before another
contraction occurs. This process may continue for up to 30 minutes and occurs several times a
day. This is what triggers the need for a bowel movement. Normal colonic transit time is 24 to
48 hours. Normal stool is made up of 75% water and 25% solid matter. Defecation is controlled
by the involuntary internal and voluntary external anal sphincters.
GI Hormones
Although the GI tract is the largest endocrine organ in the body, it is involved in both endocrine
(distant) and paracrine (cell-to-cell) regulation. Endocrine regulation begins by releasing a
hormone (or protein) into the blood stream. Once in the circulatory system, it travels until
reaching the appropriate target cell, which then responds by releasing another hormone or
chemical messenger. For example, once stomach acid (present in chime) enters the intestine, it
stimulates the release of secretin. In contrast, paracrine regulation only occurs locally, for
example a hormone reaches a target cell by crossing a neighboring cell membrane.
Hormones produced by the GI tract include gastrin, ghrelin, secretin, CCK, and incretin
hormones (glucagon-like peptide-1 [GLP-1] and GIP). These hormones influence appetite, GI
motility, enzyme activity, electrolyte levels, and the secretion and actions of hormones like
growth hormone, insulin, and glucagon. The GI tract hormones and their functions are
summarized in Table 7.1.
Table 7.1 Gastrointestinal Hormones and Their Actions
Hormone
Site of Secretion
Stimulus for Secretion
CCK
Duodenum, jejunum
Products of protein digestion and long-chain fatty acids
Stimula
pancreatic
Gastrin
Antrum of stomach,
duodenum
Vagal stimulation; epinephrine; neutral amino acids;
calcium-containing foods (milk); alcohol. Secretion
inhibited by acid content of stomach antrum (pH<2.5)
Stimulate
gastric b
contractio
Ghrelin
Fundus of stomach
Nutritional (fasting) and hormonal (↓ levels of growth
hormone)
GLP-1
Distal small intestine
High-carbohydrate meal
GIP
Small intestine,
mainly jejunum
High-carbohydrate meal
Duodenum
Acid pH or chyme entering duodenum (pH<3)
Secretin
Stimula
appetite-
Augment
slows ga
Gastrin is produced by the G cells in the antrum region of the stomach and stimulates gastric
acid secretion. Ghrelin is made by the endocrine cells in the mucosal layer of the fundus. It has
strong growth hormone-releasing activity and stimulates food intake and digestive
function. Secretin is secreted by S cells in the mucosa of the duodenum and jejunum. It inhibits
gastric acid secretion. Secretin is released in response to duodenal pH, which causes the
pancreas to secret large amounts of bicarbonate-containing fluid. CCK is secreted by the I cells
in the intestinal mucosa. It stimulates pancreatic enzyme secretion and increases the action of
secretin. GLP-1 and GIP are the two main hormones that increase insulin release after a high
glucose intake (incretin effects). For this reason, these two hormones have been targeted in
drug therapy for diabetes mellitus.
GI Secretions
The main cells in the stomach that secrete substances necessary for digestion include the
parietal cells, chief cells, and G cells.
The parietal and chief cells are primarily located in the body and fundus of the stomach. There
are approximately 1 billion parietal cells, which secrete hydrochloric acid (HCl) and intrinsic
factor. Gastric acid is needed to chemically breakdown food, while intrinsic factor is needed for
vitamin B12 absorption. The chief cells secrete pepsinogen, which is converted to pepsin in the
stomach. Pepsin initiates the breakdown of proteins. The antrum contains the G cells, which
secrete gastrin. These cells produce and secrete approximately 20 mEq of HCl in several
hundred milliliters of gastric juices each hour.
Intestinal Secretions
The small intestine secretes its own digestive juices and also receives secretions from the liver
and pancreas. Mucus-producing glands called Brunner glands secrete large amounts of alkaline
mucus that protect the duodenum from the acidic chyme. Another type of secretion is a serous
fluid (pH 6.5-7.5) secreted by specialized cells in the intestinal mucosal layer that helps with
absorption. The last secretion consists of surface enzymes- peptidases(separates amino acids)
and disaccharidases (splits sugars), that assist with absorption.
The large intestine typically only secretes mucus. It does, however, contain a large microbial
ecosystem. Each person may have approximately 300 to 500 different species of intestinal
bacteria, with anaerobic bacteria being the most abundant. Colonization begins shortly after
birth and is increased by passage through the birth canal as well as through the ingestion of
breast milk. The main function of the microflora is the fermentation of undigestible dietary
residue and endogenous mucus produced by the epithelial cells.
The colonic microorganisms also help in vitamin synthesis (vitamin K) and the absorption of
calcium, magnesium, and iron. It is also highly protective from invading pathogens. Notably,
taking broad-spectrum antibiotics can disrupt this microbial balance and allow overgrowth of
potential pathogens, such as C. difficile. For this reason, supplementing with probiotics is
becoming a more recognized treatment of GI disorders.
7.3: Disorders of the GI Tract —
Motility/Diarrhea
Motility/Diarrhea: Disease Pathology & Clinical Presentation
Diarrhea is defined as excessively frequent passage of loose or unformed stools. The cause can
be related to many pathologic or non-pathologic factors. Diarrhea can be acute or chronic and
be caused by infectious organisms, food intolerance, drugs, or intestinal disease.
Acute diarrhea lasts for less than 2 weeks and is most often caused by infectious organisms. It
is commonly divided into noninflammatory (large-volume) and inflammatory (small-volume),
based on the stool characteristics. Organisms can cause diarrhea in different ways. Some
secrete toxins that stimulate fluid secretion. Others invade and destroy intestinal epithelial
cells, which changes fluid transport so that secretory activity continues while absorption is
stopped.
Noninflammatory diarrhea typically causes large-volume, watery, non-bloody stools, cramps,
bloating, and nausea or vomiting. Common causative organisms include S. aureus, E. coli,
Cryptosporidium parvum, Vibrio cholerae, or Giardia. Vomiting associated with this type of
diarrhea is known as viral gastroenteritis or food poisoning. Since the tissue is not invaded,
leukocytes will not be present in the stool.
Inflammatory diarrhea typically produces a fever and bloody diarrhea. It is caused by the
invasion of intestinal cells (by Shigella, Salmonella, Yersinia, or Campylobacter) or the toxins
associated with C. difficile or E. coli O157:H7 infection. These infections more often affect the
colon, causing a more frequent diarrhea, but smaller in volume. Symptoms include left lower
quadrant cramps, urgency, and tenesmus (the feeling of difficulty or being unable to empty the
bowels of stool and is often associated with cramping rectal pain).
Chronic diarrhea is when the symptoms persist for 4 weeks or greater. Chronic diarrhea can be
from inflammatory bowel disease, irritable bowel syndrome, malabsorption syndrome,
endocrine disorders (hyperthyroidism, diabetic autonomic neuropathy), or radiation colitis.
The four major causes of chronic diarrhea are the following:

o
Osmotic diarrhea is when water is pulled into the bowel from
hyperosmotic contents. The colon cannot reabsorb the excess fluid. For
instance, this occurs in individuals with lactase deficiency, as the lactose
in milk cannot be broken down and absorbed.
o
o
o
o
Secretory diarrhea occurs with increased secretions of the bowel, or
when excess bile acids remain in the intestinal contents. This occurs with
tumors and carcinoid syndrome.
Inflammatory diarrhea is associated with inflammatory diseases like
ulcerative colitis or Crohn disease.
Chronic infectious diarrhea includes the common protozoans Giardia, E.
histolytica, and Cyclospora. Immunocompromised persons are
susceptible to infectious organisms.
Factitious diarrhea is caused by overuse of laxatives or excessive intake
of laxative-type foods.
Diagnosis and Treatment
Diagnosis is made based upon symptoms of frequent stools and history of concurrent illnesses,
medication use, travel, and exposure to potential intestinal pathogens. Most instances of
diarrhea require no treatment. However, infants and small children, immunocompromised
people, or the elderly can become dehydrated and need fluid and electrolyte replacement.
Medications to treat diarrhea include diphenoxylate (Lomotil) and loperamide (Imodium),
which decrease GI motility and stimulate water and electrolyte absorption. Bismuth
subsalicylate (Pepto-Bismol) inhibits intestinal secretions and works to decrease the frequency
of unformed stools. Antidiarrheal medications should not be used with bloody diarrhea, high
fever, or signs of toxicity, as this can worsen the disease. Antibiotics should only be used when
pathogens have been identified.
Disease Pathology
Constipation is the infrequent, incomplete, or the difficult passage of stools. However, what
may be considered normal in one person (2-3 bowel movements per week), may be considered
constipation by another. Constipation can occur as a primary disorder of intestinal motility, a
result of another disease, a side effect of drugs, or as a symptom of obstructing lesions of the GI
tract.
Common causes of constipation include failure to respond to the urge to defecate, inadequate
fiber in the diet, inadequate fluid intake, weakness of the abdominal muscles, inactivity and bed
rest, and pregnancy.
Three categories of constipation are as follows:
1. Normal transit constipation (or functional constipation) is characterized by perceived
difficulty in defecation and usually responds to increased fluid and fiber intake.
2. Slow-transit constipation is characterized by infrequent bowel movements usually caused by
changes in the motor function of the colon. One example is Hirschsprung disease, in which a
defect causes absent ganglion cells in the distal bowel.
3. Defecatory disorders are typically due to a lack of muscle coordination in the pelvic floor or
anal sphincter.
Diseases associated with constipation include the following: neurologic diseases such as spinal
cord injury, Parkinson disease, and multiple sclerosis; endocrine disorders such as
hypothyroidism; and obstructive lesions in the GI tract. Constipation and a low fiber diet are a
major risk factor for developing diverticular disease. Diverticulosis refers to herniation of
mucosa and submucosa through the muscular layer of the colonic wall. When these pouches
become inflamed or infected, it is called diverticulitis, which can cause left lower abdominal
pain, fever, and GI bleeding.
Drugs known to cause constipation include narcotics, anticholinergics, calcium channel
blockers, diuretics, calcium and iron supplements, and aluminum antacids. People with longstanding constipation and straining may develop dilation of the rectum, colon, or both. This can
cause stool to accumulate with little or no sensation of the urge to defecate. Colorectal cancer
may be suspected if constipation occurs as a change from a person’s normal bowel habits.
Diagnosis and Treatment
Diagnosis is made based on a person’s history of infrequent stools, straining with defecation,
the passage of hard and lumpy stools, or the sense of incomplete evacuation with defecation.
Other disease processes should be ruled out. A rectal exam can be done to assess for fecal
impaction, anal stricture, or rectal masses, as well as to check for occult blood in the stool.
Colonic transit time tests are reserved for severe cases.
Treatment of constipation should include responding to the urge to defecate, adequate fluid
and dietary fiber intake, and moderate exercise. Laxatives and enemas should be used sparingly
because they interfere with the defecation reflex and can damage the rectal mucosa.
7.4: Disorders of the GI Tract —
Irritable Bowel Syndrome &
Inflammatory Bowel Disease
Irritable Bowel Syndrome: Disease Pathology
Irritable bowel syndrome (IBS) is the term used to describe a functional GI disorder
characterized by a variable combination of chronic and recurrent intestinal symptoms not
explained by structural or biochemical abnormalities. It affects approximately 10-15% of people
in the United States. Women are affected more so than men, and symptoms are worse during
the premenstrual period, suggesting a hormonal component. It is the most common cause for
referral to gastroenterologists.
IBS is believed to result from dysregulation of intestinal motor activity and central neural
functions controlled by the CNS. The etiology is probably multifactorial, and evidence suggests
motility, inflammatory, genetic, immune, psychological, and dietary components. Symptoms
tend to worsen in response to psychological and physiologic stresses.
Clinical Presentation
IBS symptoms include recurrent abdominal pain or discomfort that is associated with a change
in stool frequency or form. The pain or discomfort may be relieved by defecation. The pain is
usually intermittent, cramping, and in the lower abdomen. There may be varying complaints of
flatulence, bloating, nausea and anorexia, constipation or diarrhea, and anxiety or depression.
Diagnosis and Treatment
IBS may be diagnosed by the following criteria: continuous or recurrent symptoms of at least 12
weeks’ duration of abdominal discomfort or pain in the preceding 12 months, with two of three
accompanying features — relief with defecation, onset associated with a change in bowel
frequency, and onset associated with a change in form (appearance) of stool.
A history of lactose intolerance should be considered. Red flag symptoms include weight loss,
anemia, fever, occult blood in the stool, nighttime symptoms, or signs and symptoms of
malabsorption. These require further investigation.
Treatment of IBS focuses on reassurance and stress management. Increased fiber intake can
help both diarrhea and constipation symptoms. One should avoid offending foods, such as fatty
and gas-producing foods, alcohol, and caffeine-containing beverages.
Pharmacologic treatment, including antispasmodic and anticholinergic drugs, have been used
with varying success.
Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is the term used for two related inflammatory intestinal
disorders: Crohn disease and ulcerative colitis. Both diseases cause inflammation of the bowel,
have systemic symptoms, and a familial occurrence. However, their areas of involvement and
structural changes differ. The characteristics of Crohn disease and ulcerative colitis are
summarized in Table 7.2.
Table 7.2 Characteristics of Crohn Disease and Ulcerative Colitis
Characteristic
Crohn Disease
Types of inflammation
Granulomatous
Level of involvement
Primarily submucosal
Extent of involvement
Skip lesions
Areas of involvement
Primarily ileum, secondarily colon
Diarrhea
Rectal bleeding
Common
Rare
Fistulas
Common
Strictures
Common
Perianal abscesses
Common
Development of cancer
Uncommon
Etiologic factors of IBD include genetic predisposition, immune dysfunction, and environmental
factors. Although there is a genetic basis for IBD, no one gene has been identified as the key
determinant. Environmental factors include the role of gut flora. These microbes may provide
the antigen trigger for the exaggerated immune response. Smoking is also a risk factor in Crohn
disease.
Both diseases result from inflammatory cells and mediators that cause tissue damage. Both are
characterized by remissions and exacerbations of diarrhea, fecal urgency, and weight loss.
Intestinal obstruction may occur with acute disease. Other systemic manifestations that may
occur in both diseases include arthritis, inflammatory conditions of the eyes, skin lesions,
stomatitis, autoimmune anemia, hypercoagulability of blood, and sclerosing cholangitis. Figure
7.8 shows the distribution patterns of disease between Crohn and UC.
Figure 7.8 (A) Skip lesions in Crohn disease and (B) continuous involvement of the colon, beginning with the
rectum, in ulcerative colitis
Crohn Disease: Disease Pathology
Crohn disease is an inflammatory response that can affect any part of the GI tract, but mostly
the terminal ileum or cecum. It is a recurrent, slowly progressive disease that affects people in
their twenties or thirties, and women are affected slightly more than men.
Crohn disease is characterized by granulomatous lesions surrounded by normal-appearing
mucosal tissue. Multiple lesions are referred to as skip lesions as they are interspersed between
normal segments of bowel. While the submucosal layer of the bowel is affected the most, all
layers are involved. The affected bowel has a “cobblestone” appearance from the fissures and
crevices that develop around the areas of submucosal edema. Pathology of the submucosal
layer includes inflammatory and fibrotic changes; the bowel wall becomes thickened and
inflexible; the adjacent mesentery may become inflamed; and the regional lymph nodes and
channels may become enlarged. These findings are shown in Figure 7.9.
Figure 7.9 Crohn disease: (A) Thickening of the ileum wall with distortion of the ileocecal valve; (B) The mucosal
surface of the colon displaying the “cobblestone” appearance
Clinical Presentation
Crohn disease manifests with exacerbations and remissions. The main symptoms depend on
the involved locations and include diarrhea, abdominal pain, weight loss, fluid and electrolyte
disorders, malaise, and low-grade fever. Crohn disease presents with less bloody diarrhea than
ulcerative colitis due to it affecting the submucosal layer more than the mucosal layer. The
severe diarrhea often causes ulceration of the perianal skin. Nutritional deficiencies may occur
due to damage to the absorptive surface of the intestines. For this reason, Crohn disease in
childhood manifests as malnutrition and growth retardation.
Complications of Crohn disease include fistulas (tubelike passages that form connections
between different sites in the GI tract), abdominal abscesses, and intestinal obstruction.
Perineal fistulas are the most common. They can cause malabsorption, bacterial overgrowth,
diarrhea, or become infected and cause an abscess. The manifestations of Crohn disease are
summarized in Figure 7.10.
Figure 7.10 The manifestations of Crohn disease in the small intestine
Diagnosis and Treatment
To diagnose Crohn disease, one must visualize both the small and large intestine, since there
are often skip lesions. In order to visualize the small intestine, a patient may undergo a small
bowel capsule endoscopy. With this procedure the patient swallows a pill size video camera
that lets the physician visualize the small bowel lining. The patient will undergo a colonoscopy
for the physician to view the colon. Stool cultures may be taken to exclude infectious causes of
diarrhea. Finally, CT scans can detect an inflammatory mass or abscess.
Treatment of Crohn disease is a very complex process that involves experts of the disease.
Treatment includes stopping the inflammatory response, promoting healing, maintaining
adequate nutrition, and preventing and treating complications. Medications to suppress
inflammation include corticosteroids, immunosuppressants, and immunomodulators. Surgical
intervention may be needed for damaged bowel, drainage of abscesses, or repair of fistula
tracts. A nutritious diet high in calories, vitamins, and protein is recommended. In contrast,
fatty foods are often avoided because they worsen diarrhea.
Ulcerative Colitis: Disease Pathology
Ulcerative colitis, an inflammatory disease of the colon, is more common in the United States
and Western countries. The peak incidence is between the ages of 15 and 25 years. Ulcerative
colitis affects the rectum and colon only. Although it mainly affects the mucosal layer,
ulcerative colitis can extend into the submucosal layer. The inflammation is confluent and
continuous, unlike the skip lesions of Crohn disease.
The lesions of ulcerative colitis form in the crypts of Lieberkuhn, which lead to the formation of
pinpoint mucosal hemorrhages. These ultimately end in crypt abscesses, which are a notable
formation of the disease. The lesions can become necrotic and ulcerate, as seen in Figure 7.11.
The mucosal layer can develop tongue like projections that resemble polyps,
called pseudopolyps. As a result of repeated inflammation, the bowel wall thickens.
Figure 7.11 Ulcerative colitis showing ulceration of the colon
Clinical Presentation
Ulcerative colitis presents with relapsing bouts of diarrhea, usually consisting of blood and
mucus. Interestingly, the diarrhea may persist for days, weeks, or months before relenting, and
then may not recur for several months or even years. Other symptoms include mild abdominal
cramping, fecal incontinence, anorexia, weakness, and fatigue.
Severity of ulcerative colitis is defined as mild, moderate, severe, or fulminant, depending on
how much of the colon is affected and the extent of inflammation. People with fulminant
disease are at risk for developing toxic megacolon, which is the dilation of the colon with signs
of systemic toxicity, due to the vast inflammatory response. The complications of ulcerative
colitis are shown in Figure 7.12.
Figure 7.12 Complications of ulcerative colitis
Diagnosis and Treatment
Diagnosis of ulcerative colitis is made by sigmoidoscopy or colonoscopy, biopsy, and negative
stool cultures for infectious diseases. Treatment depends on the extent of the disease and
severity of symptoms and is geared to control acute manifestations and prevent recurrence.
People with mild to moderate disease may be able to control the disease by avoiding caffeine,
lactose, highly spiced foods, and gas-forming foods. Fiber supplements may be given to
decrease diarrhea. Medications, like corticosteroids, immunosuppressants, and
immunomodulators, are also used. Surgical treatment by removing the rectum and entire colon
may be required for people who do not respond to medications and conservative treatment.
People with ulcerative colitis are at higher risk of developing colon cancer and should be
screened more frequently with colonoscopies and biopsies.
7.5: Disorders of the GI Tract — GERD
& PUD
Figure 7.13 Barrett esophagus — the
presence of the tan tongues of epithelium
interlinking with the more proximal
squamous epithelium
GERD: Disease
Pathology
Gastroesophageal Reflux Disease
(GERD) is a disorder in which the
reflux, or backflow, of stomach
contents enters the esophagus. It is
typically caused by the transient
relaxation of a weak or incompetent
lower esophageal sphincter, or a
hiatal hernia. It can also be caused
by delayed gastric emptying due to
increased gastric volume and
pressure. The acidic gastric fluids
(pH <4) can damage the mucosa of
the esophagus. The reflux is
normally neutralized by esophageal
peristalsis and salivary bicarbonate.
Clinical Presentation
Heartburn is the most frequent
symptom of GERD. It usually occurs
30 to 60 minutes after eating.
Bending at the waist and lying down
can often worsen the symptoms.
However, the severity of heartburn
does not correlate to the extent of mucosal injury. Other symptoms include belching, chest
pain, dysphagia (difficulty swallowing), bloating or early satiety, laryngitis, chronic cough, sour
taste in mouth, dental erosion, or reflux-associated asthma. Alarming symptoms that require
further testing include weight loss, persistent vomiting, dysphagia, odynophagia (painful
swallowing), or evidence of blood in stool.
Chronic reflux esophagitis can cause mucosal injury, hyperemia, and inflammation.
Complications include strictures (narrowing of the esophagus) and Barrett
esophagus (see Figure 7.13), in which the normal squamous mucosa that lines the esophagus is
gradually replaced by abnormal columnar epithelium (as seen in the stomach or intestines). As
such, Barrett esophagus is a major risk factor for developing esophageal adenocarcinoma.
Diagnosis and Treatment
Diagnosis of GERD is usually made clinically by reviewing the history of the patient’s symptoms.
A trial of proton pump inhibitors (PPIs) for 14 days can serve for both diagnosis and initial
treatment, if symptoms improve. Optional diagnostic tests include ambulatory esophageal pH
monitoring, and upper endoscopy (esophagogastroduodenoscopy [EGD]) for atypical, relapsing,
or persistent symptoms.
Alcohol use, smoking, intake of specific foods (coffee/caffeine, chocolate, mints, citrus fruits,
acidic/spicy foods, or fats) may predispose or trigger GERD and should be avoided. PPIs (e.g.
omeprazole) are the most effective drug class for treatment of GERD. They work by inhibiting
the gastric proton pump, which regulates the final pathway for acid secretion. Other options
include Histamine-2 receptor (H2)-blocking antagonists (e.g. Zantac), which inhibit gastric acid
production, or antacids (neutralizes acid) for immediate relief. People should avoid positions
that increase reflux, like lying down immediately after eating or bending. Avoiding large meals
close to bedtime and sleeping with the head elevated may help to prevent reflux at night.
Weight loss is recommended if needed. Surgery may be indicated in certain situations.
Peptic Ulcer Disease: Pathology
Peptic ulcer disease (PUD) encompasses a group of ulcerative disorders in the upper GI track
that are exposed to acid-pepsin secretions. The most common forms are duodenal and gastric
ulcers. Duodenal ulcers are five times more common than gastric ulcers. Duodenal ulcers are
commonly seen between the ages of 30 and 60 years and are more prominent in men. Gastric
ulcers occur in middle-aged and older men and women.
A peptic ulcer can affect one or all layers of the stomach or duodenum. Figure 7.14 depicts the
two ulcer sites. Remissions and exacerbations are common. If it is deep enough to erode into
the muscularis layer, it will be replaced with scar tissue.
Figure 7.14 (A) Gastric ulcer — characteristic sharp demarcation from the surrounding mucosa, with radiating
gastric folds; (B) Duodenal ulcer — there are two sharply demarcated duodenal ulcers surrounded by inflamed
duodenal mucosa
The two most common causes of PUD include H. pylori infection and the use of aspirin and
other NSAIDs. Both have been shown to impair the mechanisms that protect the gastric mucosa
from the damaging effects of acid.
H. pylori infection can cause inflammation and stimulate the release of cytokines that
contribute to mucosal damage. The pathogenesis of NSAID-induced ulcers is thought to
inhibit prostaglandin synthesis. Ulcer development is drug dose-dependent and lifethreatening complications can occur without warning.
Other risk factors include advancing age, prior history of peptic ulcer, multiple NSAID use,
concurrent use of warfarin, and corticosteroid drugs. Interestingly, although smoking, alcohol
use, and stress also contribute to risk, dietary factors do not seem to play a role. A positive
family history is most likely due to genetic factors that contribute to a positive H.
pylori infection.
Clinical Presentation
Peptic ulcers usually present as chronic, upper abdominal pain and dyspepsia. While there may
be epigastric tenderness, no other signs are usually present on the physical exam. The pain can
be described as burning, gnawing, or cramplike. Gastric ulcers are worsened by eating. In
contrast, duodenal ulcers are worsened when the stomach is empty. In fact, eating may relieve
the pain. An exacerbation may present with daily pain for weeks, then remit until the next
recurrence.
The most common complication is gastroduodenal bleeding. Hemorrhage is caused by tissue
bleeding or erosion of an ulcer into an artery or vein. Bleeding is evidenced by hematemesis or
melena (dark, tarry stools). Blood in the stool may also have an insidious onset. Up to 20% of
people taking NSAIDs may present without any symptoms of pain; instead they present with
weakness, dizziness, dehydration, cool, moist skin, dark/tarry stools or coffee-ground emesis,
evidence of acute hemorrhage.
Perforation is a less frequent but potentially life-threatening complication. Perforation occurs
when an ulcer erodes through all the layers of the stomach or duodenum wall. GI contents are
then free to enter the peritoneum and cause peritonitis. Presentation may include abdominal
pain radiating into the back, severe night distress, and inadequate pain relief from eating food
or taking antacids. Perforated ulcers appear on x-ray as air under the diaphragm and
emergency surgery is necessary to repair.
Diagnosis and Treatment
Endoscopy is used to visualize and diagnose the ulcer, take biopsies for H. pylori, and exclude
malignancies. The history should evaluate for aspirin or NSAID use. Lab studies should evaluate
for anemia and check stool for occult blood. Barium radiography is reserved for those unable to
undergo endoscopy.
Treatment for PUD is focused on eradicating the cause and healing the ulcer. NSAIDs and
aspirin should be discontinued. (Patients with CV disease may need to restart low-dose aspirin
therapy after treatment). Pharmacologic treatment of H. pylori includes a PPI plus two
antibiotics. H. pylori negative patients are still given a PPI, as they are the drug of choice for
ulcer healing. H2 antagonists are less effective but may still induce healing in most patients.
Sucralfate has similar ulcer healing rates to H2 antagonists. However, the frequent dosing
schedule and large tablet size may impact patient adherence. A prostaglandin analog such as
misoprostol should be used in patients with NSAID-associated ulcers refractory to acid
suppression therapy. Misoprostol works by stimulating mucus and bicarbonate secretion and
modestly inhibiting acid secretion. There is currently no evidence to suggest that a special diet
is beneficial. Surgery is reserved to treat complications.
7.6 Disorders of the Hepatobiliary
System- Jaundice
Jaundice: Disease Pathology
Jaundice, which is a yellowish discoloration of the skin, results from abnormally high levels of
bilirubin in the blood, usually above 2 to 2.5 mg/dL. The sclera of the eye is usually one of the
first structures examined to detect jaundice.
When red blood cells are destroyed, the final product of heme breakdown is bilirubin. This free
bilirubin, which is insoluble in plasma, is transported in the blood attached to plasma albumin.
As it goes through the liver, it is released from albumin and converted to conjugated bilirubin,
which is soluble in bile. In the intestine, conjugated bilirubin is converted into a highly
soluble urobilinogen by the intestinal flora. Approximately one fifth is absorbed into portal
circulation while the remaining amount is excreted in the feces. Normal serum bilirubin is a
small amount, less than 1.5 mg/dL. Figure 7.15 depicts this process.
The five major causes of jaundice are excessive destruction of red blood cells, impaired uptake
of bilirubin by the liver cells, decreased conjugation of bilirubin, obstruction of bile flow in the
canaliculi of the hepatic lobules or in the intrahepatic or extrahepatic bile ducts, and excessive
extrahepatic production of bilirubin.
From an anatomic standpoint, jaundice is categorized as:
1. prehepatic
2. intrahepatic
3. posthepatic
Table 7.3 summarizes common causes of jaundice.
Prehepatic jaundice is commonly caused by the excessive hemolysis of red blood cells, or when
the red blood cells are destroyed at a rate greater than the liver’s ability to remove the bilirubin
from the blood. For example, it can occur following a hemolytic blood transfusion reaction or
internal hemorrhage. Neonatal hyperbilirubinemia (0-14 days old) results from increased
production of bilirubin in newborn infants and their limited ability to excrete it. In prehepatic
jaundice, there is mild jaundice, elevated unconjugated bilirubin, normal color stools, and no
bilirubin in the urine.
Intrahepatic jaundice is caused by disorders that affect the ability of the liver to remove
bilirubin from the blood or conjugate it to be eliminated in the bile. Hepatitis and cirrhosis are
the most common causes. Certain drugs, such as oral contraceptives, estrogen, anabolic
steroids, isoniazid, or rifampin, can also cause this type of jaundice. Intrahepatic jaundice
presents with elevated conjugated and unconjugated bilirubin, dark urine (due to presence of
bilirubin), and elevated serum alkaline phosphatase.
Posthepatic jaundice, also called cholestatic jaundice, occurs when bile flow is obstructed
between the liver and intestine. Common causes are strictures of the bile duct, gallstones, and
tumors of the bile duct or pancreas. Conjugated bilirubin levels are elevated, stools are clay
colored due to lack of bilirubin in the bile, urine is dark, serum alkaline phosphatase levels are
elevated, and aminotransferase levels are also slightly increased. Blood levels of bile acids are
often elevated, causing pruritus (itchy skin).
Laboratory liver function tests are important to help diagnose liver diseases. The key enzyme
tests include alanine aminotransferase (ALT) and aspartate aminotransferase (AST), both
present in liver cells. ALT is liver specific, and AST is derived from organs other than the liver.
Typically, both ALT and AST are elevated in liver damage, especially with acute hepatocellular
injury like viral hepatitis, hypoxic or ischemic injury, acute toxic injury, or Reye syndrome.
Serum bilirubin, ɣ-glutamyltransferase (GGT), 5’-nucleotidase, and alkaline phosphatase
measure hepatic excretory function. Alkaline phosphatase and 5’-nucleotidase are present in
the membranes between liver cells and the bile duct and are released by disorders affecting the
bile duct, specifically obstruction. GGT is located in the endoplasmic reticulum of the
hepatocytes and in the bile duct epithelial cells. GGT is helpful is diagnosing alcohol abuse and
hepatobiliary disease.
Figure 7.15 Bilirubin formation, circulation, and elimination
Table 7.3 Causes of Jaundice
Click to expand each item.
Prehepatic (Excessive Red Blood Cell Destruction)





Hemolytic blood transfusion reaction
Hereditary disorders of the red blood cell
o Sickle cell disease
o Thalassemia
o Spherocytosis
Acquired hemolytic disorders
Hemolytic disease of the newborn
Autoimmune hemolytic anemias
Intrahepatic




Decreased bilirubin uptake by the liver
Decreased conjugation of bilirubin
Hepatocellular liver damage
o Hepatitis
o Cirrhosis
o Liver cancer
Drug-induced cholestasis
Posthepatic (Obstruction of bile flow)




Structural disorders of the bile duct
Cholelithiasis
Congenital atresia of the extrahepatic bile ducts
Bile duct obstruction caused by tumors
7.7: Disorders of the Hepatobiliary
System — Cirrhosis & Cholecystitis
Cirrhosis: Disease Pathology
Cirrhosis occurs when the functional liver tissue has been replaced by fibrous tissue. It occurs in
the final stages of chronic liver disease. Cirrhosis can develop from viral hepatitis, toxic
reactions to drugs and chemicals, biliary obstruction, non-alcoholic fatty liver disease, but is
most commonly associated with alcoholism. Cirrhosis can also occur from metabolic disorders
that cause deposition of minerals in the liver. Two of these disorders include hemochromatosis
(iron deposition) and Wilson disease (copper deposition).
Cirrhosis is characterized by diffuse fibrosis and nodules that cause scarring. This disrupts blood
and bile flow in the liver. Disruption of blood flow leads to portal hypertension; disruption of
bile flow causes bile stasis and a loss of liver cells, leading to liver failure. Cirrhosis is associated
with an increased incidence of hepatocellular carcinoma.
Nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver
disease in the Western world. It is associated with obesity and metabolic syndrome (type 2
diabetes, hyperlipidemia). Lifestyle modification (diet/exercise/weight loss) is the current
treatment. Approximately 10-15% of people with NAFLD will progress to cirrhosis.
Figure 7.16 Clinical
manifestations of cirrhosis
Clinical Presentation
Symptoms of cirrhosis
range from asymptomatic
hepatomegaly to hepatic
failure. These
manifestations are
summarized in Figure
7.16. Symptoms may not
occur until the disease is
advanced. The most
common symptoms are
weight loss (sometimes
masked by ascites),
weakness, anorexia, and
usually diarrhea. The most
common signs are
hepatomegaly and
jaundice, often with
abdominal pain.
Late manifestations of
cirrhosis include portal
hypertension (increased
resistance to flow in the
portal venous system) and
liver cell failure. Portal
hypertension can cause
splenomegaly, ascites
(increased amount of fluid
in the peritoneal cavity),
esophageal varices
(dilated veins),
hemorrhoids, and caput
medusae (distended and
engorged superficial
epigastric veins). Other
complications include
bleeding due to decreased
clotting factors,
thrombocytopenia due to
splenomegaly,
gynecomastia due to testicular atrophy, spider angiomas, palmar erythema, and
encephalopathy with asterixis (hand tremor with extended wrist) and neurologic signs
(associated with elevated ammonia levels).
Diagnosis and Treatment
A thorough history and physical exam, along with a full panel of blood tests and an upper GI
endoscopy should be done when evaluating for cirrhosis, as well as to rule out other causes of
the disease. Signs of advanced cirrhosis may be detected using ultrasound, CT scan, and MRI.
Liver biopsy remains the most specific and sensitive test for the diagnosis of cirrhosis.
As cirrhosis is the pathologic end-stage of any chronic liver disease, it is essential to treat the
underlying causative condition, such as hepatitis B and C, or alcoholic liver disease, among
many others. One should avoid alcohol and other hepatotoxic drugs (NSAIDS) and high doses of
acetaminophen (> 2 g/day); maintain adequate nutrition and get regular exercise. Cirrhosis is
associated with serious complications, as stated under clinical manifestations, and prompt
detection and treatment of these complications is essential in order to minimize morbidity and
mortality. If ascites occurs, there should be a sodium restriction (< 2 g/day) as well as diuretic
therapy. Patients who develop complications of cirrhosis, such as hepatocellular carcinoma or
signs of decompensation should be referred for liver transplant evaluation. Liver
transplantation remains the only curative treatment option for decompensated cirrhosis.
Cholecystitis: Disease Pathology
The gallbladder is a pear-shaped muscular sac located on the ventral surface of the liver. It
functions to store and concentrate bile. Bile contains bile salts, cholesterol, bilirubin, lecithin,
fatty acids, and the water and electrolytes normally found in plasma.
When food enters the intestine, the gallbladder contracts and the sphincter of the bile duct
relaxes, so that bile can flow from the gallbladder to the duodenum. The GI hormone, CCK, is
released during food digestion and aids in stimulating gallbladder contraction.
Cholestasis is a decrease in bile flow and reduced secretion of water, bilirubin, and bile acids by
the hepatocytes. Material usually transferred to the bile, including bilirubin, cholesterol, and
bile acids, will instead accumulate in the blood. Cholestasis can be caused by intrinsic liver
disease, called intrahepatic cholestasis, or by obstruction of the large bile ducts,
called extrahepatic cholestasis.
Cholelithiasis are gallstones, primarily made of cholesterol (80%). The other 20% are black or
brown pigment stones composed of mucin glycoproteins and calcium salts. Figure 7.17 shows a
gallbladder containing multiple cholesterol gallstones.
Figure 7.17 An opened gallbladder reveals cholesterol
gallstones
The two major factors that contribute to the
formation of gallstones are abnormalities in
the composition of bile (increased
cholesterol), and the stasis of bile. Risk factors
for gallstone formation include age (40s),
obesity, and female gender, especially those
who had multiple pregnancies or are taking
oral contraceptives. These factors cause the
liver to excrete more cholesterol into the bile.
Gallbladder sludge, which is thickened
gallbladder mucoprotein with trapped
cholesterol crystals, is thought to be a
precursor of gallstones. Sludge is typically
seen in instances of pregnancy, starvation,
and rapid weight loss.
Acute cholecystitis is diffuse inflammation of
the gallbladder. Eighty-five to ninety percent
of acute cholecystitis is due to obstruction of
the gallbladder outlet from gallstones. The
other cases are due to sepsis, severe trauma, or infection of the gallbladder.
Chronic cholecystitis occurs from chronic irritation by stones or multiple attacks of acute
cholecystitis. The presence of gallstones and chronic inflammation of the gallbladder are
commonplace with this condition.
When gallstones block the common bile duct (the duct shared by the gallbladder and pancreas),
acute pancreatitis can occur. Acute pancreatitis is a reversible inflammatory condition
commonly brought on by gallstones or alcohol abuse. It presents with mid-epigastric or left
upper quadrant pain that radiates to the back, with nausea and vomiting. When damaged, the
pancreas will release amylase and lipase — these lab values will be elevated during this process.
Clinical Presentation
Gallstones cause symptoms when they obstruct bile flow or cause inflammation. Small stones
(< 8 mm in diameter) pass into the common duct, producing symptoms of indigestion and
biliary colic. Larger stones are more likely to obstruct flow and cause jaundice. The pain of
biliary colic presents as right upper quadrant or epigastric pain, sometimes radiating to the back
or shoulder. Pain is acute, lasting more than 3-6 hours and is often associated with mild fever,
anorexia, nausea, and vomiting. Lab values will often show an elevated white blood cell count,
and mild elevations of AST, ALT, alkaline phosphatase, and bilirubin. With chronic cholecystitis,
the patient may have an intolerance to fatty foods, belching, and colicky pain.
Diagnosis and Treatment
Ultrasonography is the best method to diagnose cholecystitis. It can detect stones and wall
thickening, which is indicative of inflammation. It can rule out other causes of right upper
quadrant pain, such as tumors. Other modalities include cholescintigraphy (HIDA scan) (highly
accurate in diagnosing, but cannot rule other conditions out), or CT scan. Treatment of
gallbladder disease is often by surgical removal, called a laparoscopic cholecystectomy.