710
U N I T 8
Gastrointestinal and Hepatobiliary Function
have infection rates second only to the common cold.
Most infections are spread by the oral–fecal route, often
through contaminated water or food.
Viral Infections
Most viral infections affect the superficial epithelium of
the small intestine, destroying these cells and disrupt-
ing their absorptive function. Repopulation of the small
intestinal villi with immature enterocytes and preserva-
tion of crypt secretory cells leads to net secretion of water
and electrolytes compounded by incomplete absorption
of nutrients and osmotic diarrhea. Symptomatic disease
is caused by several distinct viruses, including the rota-
virus, which most commonly affects children 6 to 24
months of age; the norovirus (previously known as the
Norwalk virus), which is responsible for the majority
of cases of nonbacterial food-borne epidemic gastroen-
teritis in all age groups: and enteric adenoviruses, which
primarily affect children.
6
Rotavirus.
Worldwide, rotavirus is estimated to cause
more than 111 million cases of diarrhea in children
younger than 5 years of age. In the United States, the
disease causes 3 million cases of diarrhea, 80,000 hospi-
talizations, and 20 to 40 deaths per year.
31
The disease
tends to be most severe in children 3 to 24 months of
age. Infants younger than 3 months of age are relatively
protected by transplacental antibodies and possibly by
breast-feeding. The virus is spread by a fecal–oral route
and outbreaks are common in children in day care cen-
ters. The virus is shed before and for days after clinical
illness. Very few infectious virions are needed to cause
disease in a susceptible host.
Rotavirus infection typically begins after an incuba-
tion period of less than 24 hours, with mild to moder-
ate fever and vomiting, followed by onset of frequent
watery stools. The fever and vomiting usually disappear
on about the second day, but the diarrhea may continue
for 5 to 7 days. Dehydration may develop rapidly, par-
ticularly in infants. Treatment is largely supportive.
Currently, there are two licensed vaccines that protect
infants from rotavirus infection: a live, oral, pentavalent
vaccine (RotaTeq) containing five reassortment rota-
viruses isolated from human and bovine hosts, and a
monvalent vaccine (Rotarix) that is effective against all
of the serotypes that cause infection in children.
31
Bacterial Infections
Infectious enterocolitis can be caused by a number of
bacteria. There are several pathogenic mechanisms for
development of bacterial enterocolitis: ingestion of pre-
formed toxins that are present in contaminated food,
infection by toxigenic organisms that proliferate in the
gut lumen and produce an enterotoxin, and infection by
enteroinvasive organisms that proliferate in the lumen
and invade and destroy mucosal epithelial cells. The
pathogenic effects of bacterial infections depend on the
ability of the organism to adhere to the mucosal epi-
thelial cells, elaborate enterotoxins, and then invade the
mucosal epithelial cells.
In general, bacterial infections produce more severe
effects than viral infections. The complications of bacte-
rial enterocolitis result frommassive fluid loss or destruc-
tion of intestinal mucosa and include dehydration, sepsis,
and perforation. Among the organisms that cause bacte-
rial enterocolitis are
Staphylococcus aureus
(toxins asso-
ciated with “food poisoning”), Shiga toxin-producing
Escherichia coli, Shigella
species, nontyphoid salmo-
nella, and campylobacter.
32
Two particularly serious
forms of bacterial enterocolitis are caused by
C. difficile
and
E. coli
O157:H7.
Clostridium difficile Colitis.
C. difficile
(so named
because it is difficult to culture) is a gram-positive, spore-
forming bacillus that is part of the normal flora in some
healthy people. The spores are resistant to the acid envi-
ronment of the stomach and convert to vegetative forms
in the colon.
33
In general,
C. difficile
is noninvasive and
development of
C. difficile
colitis requires disruption of
normal intestinal flora, acquisition and germination of
the spores, overgrowth of the bacillus, and toxin pro-
duction. The toxins bind to and damage the intestinal
mucosa, causing hemorrhage, inflammation, and necro-
sis. The toxins also interfere with protein synthesis,
attract inflammatory cells, increase capillary permeabil-
ity, and stimulate intestinal peristalsis. Treatment with
broad-spectrum antibiotics predisposes to disruption of
the normal protective bacterial flora of the colon. After
antibiotic therapy has made the bowel susceptible to
infection, colonization by
C. difficile
occurs by the oral–
fecal route.
34
C. difficile
infection usually is acquired in
the hospital, where the organism is commonly encoun-
tered. Nearly all antibiotics have been implicated in the
disease.
A new and hypervirulent fluoroquinolone-resistant
strain of
Clostridium difficile
(NAP1/B1/027) has been
implicated in
C. difficile
outbreaks since the early
2000s.
34,35
This epidemic form has caused more severe
and refractory disease leading to complications that
include intensive care unit admission, colectomies, and
death. Before 2002,
C. difficile–
associated colitis was
rare, but its prevalence has increased significantly.
35
The
risk of
C. difficile
-associated diarrhea is increased not
only by factors, such as antibiotic exposure, but also
by gastrointestinal surgery/manipulation, prolonged
stay at a health care facility, serious underlying disease,
immune-compromising conditions, and aging. Persons
on proton pump inhibitors are at elevated risk, as are
peripartum women and heart transplant recipients.
However,
C. difficile
infection has emerged in popula-
tions not previously considered at risk.
34,35
These include
young and previously healthy persons who have not
received antimicrobial therapy or been exposed to the
hospital environment. In these cases the only risk fac-
tor was close contact with someone who had C.
difficile
infection.
35
C. difficile
colitis commonly manifests with diarrhea
that is mild to moderate and sometimes is accompanied
by lower abdominal cramping. Typically, symptoms
begin within 1 to 2 weeks after antibiotic treatment
has been initiated, although it can vary from 1 day to
