Small intestine Flashcards
The small bowel increases in length from about
250 cm in the term newborn to about 600 to 800 cm in the adult.
The caliber of the small intestine gradually diminishes from proximal to distal, and there is a fourfold reduction in surface area from the distal duodenum to the terminal ileum.
The duodenum is the most proximal portion of the small intestine.
It begins with the duodenal bulb, travels in the retroperitoneal
space around the head of the pancreas, and ends on its return to the
peritoneal cavity at the ligament of Treitz
The biliary and pancreatic
ducts usually join together 1 to 2 cm from the outer margin
of the duodenal wall and drain into the medial wall of the second
portion of the duodenum through the ampulla of Vater.
In 5% to
10% of individuals, an accessory pancreatic duct, also known as the
duct of Santorini, enters separately through the minor papilla 1 to 2
cm proximal to the ampulla of Vater
The proximal 40% of the mobile
small intestine is the jejunum, which occupies the left upper portion
of the abdomen. The remaining 60% of small intestine is the
ileum, and it is normally situated in the right side of the abdomen
and upper part of the pelvis
There is no distinct anatomic demarcation
between the jejunum and ileum, but the jejunum tends to be
thicker, is more vascular, and has a greater diameter than the ileum.
The luminal surface of the small intestine has visible mucosal
folds called the plicae circularis or folds of Kerckring.
They are more numerous in the proximal jejunum, decrease in number
distally, and are absent in the terminal ileum.
The jejunum and ileum are freely mobile in the abdominal
cavity and are attached to the posterior abdominal wall by the
intestinal mesentery
The entire length of jejunum and ileum is
suspended in this mesentery, except for the distal terminal ileum at
the cecum, which is retroperitoneal
The mesentery is formed by
a fan-shaped anterior reflection of the posterior peritoneum that
extends from the left side of the body toward the right sacroiliac
joint.
The small bowel transitions to the colon at the ileocecal (IC) valve,
which consists of 2 semilunar lips that protrude into the cecum.
The colon is a tubular structure about 30 to 40 cm in length at
birth and measuring some 150 cm in the adult, quarter the length of the small intestine. The colon begins at the
IC valve and ends distally at the anal verge
It consists
of 4 segments: cecum and vermiform appendix, colon (ascending,
transverse, and descending portions), rectum, and anal canal
The
diameter of the colon is greatest in the cecum (7.5 cm) and narrowest
in the sigmoid (2.5 cm)
It is larger in caliber, mostly fixed in position, and
has outer longitudinal muscle fibers that coalesce into 3 discrete
bands called taeniae: the taenia liberis (free tenia), taenia omentalis
(omental tenia), and taenia mesocolica (mesenteric tenia).
Taeniae
are located at 120-degree intervals around the colonic circumference
and extend from the cecum to the proximal rectum
Outpouchings, or haustra, occur between the taeniae, and their
mucosal surface is sectioned by semilunar folds to give the serosa
a sacculated and puckered appearance
The mesentery fully suspends
the transverse colon and sigmoid colon, while the remainder of
the colon has mesentery only on its free anterior surface
The cecum is the most proximal portion of the colon. It is
about 6 to 8 cm in length and breadth and lies in the right iliac
fossa, projecting downward as a blind pouch below the entrance
of the ileum.
The cecum is normally nonmobile because it is fixed in position
by a small mesocecum; anomalous fixation, however, occurs in
10% to 20% of the population, predominantly women, predisposing
them to cecal volvulus
The IC valve passes perpendicularly through the posteromedial
wall of the cecum and consists of a superior and inferior fold
arranged in an elliptical manner at the IC orifice.
orifice is roughly 2.5 cm inferior to the IC valve, and the vermiform
appendix
The ascending colon is narrower than the cecum and extends
about 12 to 20 cm from the level of the IC valve to the inferior
surface of the posterior lobe of the liver
IC valve to the inferior
surface of the posterior lobe of the liver, where it angulates left
and forward, forming the hepatic flexure. The ascending colon is
covered with peritoneum in about 75% of individuals and thus is
usually considered to reside in the retroperitoneum
The transverse is the longest (40 to 50 cm)
and most mobile segment of the colon.
The descending colon is about 25 to 45 cm in length and travels
posteriorly and then inferiorly in the retroperitoneal compartment
to the pelvic brim.
It emerges from the retroperitoneum
into the peritoneal cavity as the sigmoid colon redundant segment of variable length, tortuosity, and mobility.
S-shaped
The mobility of the sigmoid colon renders it susceptible to volvulus, and because it is the narrowest part of the colon, tumors
and strictures of this region typically cause obstructive symptoms early in the course of disease.
The rectum is 10 to 12 cm in length and begins at the peritoneal
reflection, follows the curve of the sacrum passing down
and posteriorly, and ends at the anal canal. The rectum narrows
at its junction with the sigmoid, expanding proximal to the anus.
The anorectal junction is 2 to 3 cm anterior to the tip of the coccyx.
2 to 3 cm anterior to the tip of the coccyx. The rectum does
not have sacculation, appendices epiploicae, or mesentery. The
outer rectal wall is progressively thickened with prominent and
anterior bands of muscle as it descends toward the anus. The
luminal surface of the rectum has 3 transverse folds called the
valves of Houston.
The anal canal is 2 cm long in the infant and 4.5 to 5 cm long
in the adult. It occupies the ischiorectal fossa, passing inferiorly
and outward toward the anal opening
The external sphincter is made up of striated muscle; it
surrounds the anal canal, and its fibers blend with those of the
levator ani muscle to attach posteriorly to the coccyx and anteriorly
to the perineal body.
Distally, the anal verge represents
the transition of anoderm to true skin
. The mucosa of the distal
3 cm of the rectum and anal canal contains 6 to 12 redundant
longitudinal folds called the columns of Morgagni, which terminate
in the anal papillae.
These columns are joined together
by mucosal folds called the anal valves, which are situated at
the dentate line.
The zona alba is a white zone that demarcates
the transition to typical squamous epithelium
The proximal duodenum receives arterial blood from the right gastric artery, supraduodenal artery, right gastroepiploic artery, and superior and inferior pancreaticoduodenal arteries.
Venous drainage is via the SMV and the splenic and portal veins.
The
SMA delivers oxygenated blood to the distal duodenum, jejunum
and ileum, ascending colon, and proximal two thirds of the transverse colon.
Branches of the inferior mesenteric artery
supply the remainder of the colon. The arterial supply of the anal area is from the superior, middle, and inferior hemorrhoidal arteries, which are branches of the inferior mesenteric, hypogastric,
and internal pudendal arteries, respectively
Venous drainage of the anus is by both the systemic and portal systems.
The internal hemorrhoidal plexus drains into the superior rectal
veins and then into the inferior mesenteric vein, which, with the
SMV, joins the splenic vein to form the portal vein.
The vascularity
of the distal anus drains by the external hemorrhoidal
plexus through the middle rectal and pudendal veins into the
internal iliac vein.
Lymphatic drainage courses through the mesentery from villus
lacteals and lymphatic follicles and converges at preaortic lymph
nodes around the SMA and celiac artery.
The lymphatic drainage
of both the small intestine and colon follows their respective
blood supplies to lymph nodes in the celiac, superior preaortic,
and inferior preaortic regions. Lymphatic drainage proceeds to
the cisterna chyli and then via the thoracic duct into the left subclavian
vein`
Proximal to the dentate line, lymphatic drainage is
to the inferior mesenteric and periaortic nodes, whereas distal to
the dentate line it flows to the inguinal lymph nodes.
Therefore,
inflammatory and malignant disease of the lower anal canal can
manifest with inguinal lymphadenopathy.
The autonomic nervous system—sympathetic, parasympathetic,
and enteric—innervates the GI tract. The sympathetic and parasympathetic
nerves constitute the extrinsic nerve supply and connect
with the intrinsic nerve supply, which is composed of ganglion
cells and nerve fibers within the intestinal wall
The wall of the small intestine and colon is composed of
4 layers: mucosa (or mucous membrane), submucosa, muscularis
(or muscularis propria), and serosa
The mucosa is thick
and highly vascularized, although less so in distal portions. It has
concentric folds (plicae circulares) that are also referred to as the
valves of Kerckring. The surfaces of the mucosal folds are studded
with villus projections, and these features combine to produce a
400- to 500-fold increase in mucosal surface area. An intestinal
villus will typically project 0.5 to 1.5 mm into the lumen, and
the height of the villus decreases from proximal to distal small
intestine.
Villi are wider and more leaf-shaped in the duodenal
bulb and proximal duodenum, becoming more finger-like in the
distal duodenum, proximal jejunum, and remainder of intestine.
Mucosal
epithelial cells turn over every 5 to 7 days. Intestinal epithelial
cells are mature by the time they reach the upper third of the
villus. Paneth cells are the only cells that do not migrate. Undifferentiated
cells have fewer intracellular organelles and microvilli
than absorptive cells.
Goblet cells are mucin-producing cells that are scattered
among intestinal villi but are more common in the distal ileum
and large intestine
Goblet cells are oval or round with flattened
basal nuclei (Fig. 98.4A); their cytoplasm is basophilic, metachromatic
(see Fig. 98.4B), and PAS-positive (see Fig. 98.4C) and
consists mostly of mucin-secreting granules
Paneth cells are flask shaped with an eosinophilic granular
cytoplasm and a broad base that is positioned against the basement
membrane (Fig. 98.5). In the small intestine, Paneth cells
are located exclusively in the crypts of Lieberkühn and secrete
α-defensins, antimicrobial proteins, lysozyme, and phospholipase
A, thought to be important in protection from infectious pathogens
and function to maintain enteric homeostasis.1
Cup cells and tuft cells are 2 intestinal epithelial cell types with
unidentified functions. Cup cells are present in villi and crypts
largely limited to the ileum. Tuft cells are marked by a tuft of
long microvilli projecting from the apical surface of the cell.
neuroendocrine cells have
been divided histologically into argentaffin (i.e., their granules
are able to reduce silver nitrate) or enterochromaffin cells and
argyrophilic cells (i.e., granules reduce silver nitrate only in the
presence of a chemical reducer)
The interstitial cells of Cajal (ICC) are found in both the small
intestine and colon and are located in the myenteric plexuses
within the muscularis propria and the submucosa
intestinal peristalsis and function as the pacemaker cells
of the intestine
The ICC are
spindle-shaped or stellate cells with long, ramified processes and
express c-kit (CD117), a tyrosine kinase receptor critical for their
survival
Brunner glands are submucosal glands (see Fig. 98.9B) found
primarily in the first portion of the duodenum and in decreased
numbers in the distal duodenum
The function of Brunner glands is to secrete a bicarbonate rich
alkaline secretion that helps neutralize gastric chyme; a
mucinous secretion that helps lubricate the mucosa;
A prominent nerve fiber plexus called the myenteric or
Auerbach plexus is located in the plane between these 2 muscle
layers
The ganglia in the myenteric plexus are more
prominent than their submucosal counterpart.
The mucosa of the small intestine is characterized by folds
(plicae circulares, or valves of Kerckring) and villi. The mucosal
folds actually comprise mucosa and submucosa.
They may be broad, short, or leaf-like
in the duodenum, tongue-like in the jejunum, and finger-like
more distally
The height of the normal villus is 0.5 to 1.5 mm; villus height
should be more than half the total thickness of the mucosa and 3
to 5 times the length of the crypts.
Villi are lined by enterocytes,
goblet cells, and enteroendocrine cells
Enterocytes are tall columnar cells, each with a basally
located, clear, oval-shaped nucleus and several nucleoli.
Two types of glands are present in the small intestine: Brunner
glands (see previously) and crypts of Lieberkühn (intestinal
crypts). The crypts of Lieberkühn are tubular glands that extend
to the muscularis mucosae (see Fig. 98.5); they are occupied
mainly by undifferentiated cells and Paneth cells.
The ICC are more
abundant in the myenteric plexus of the small intestine than
in the colon.5
Colon
The colonic walls are similar to those of the small intestine. The
outer layer forms the taeniae coli, which run in parallel to the
long axis of the colon throughout its entire length. The width
of the taeniae extends from 6 to 12 mm, and thickness gradually
increases from the cecum to the sigmoid colon
The mucosa of the large intestine is characterized by the
crypts of Lieberkühn, which dip to the muscularis mucosae and
contain goblet cells, absorptive and enteroendocrine cells, and
undifferentiated cells that are restricted to the lower third of the
crypts
Microscopically, the anal canal is divided into 3 zones: proximal,
intermediate or pectinate, and distal or anal skin
The proximal
zone is lined by stratified cuboidal epithelium, and the transition
with the rectal mucosa, which is lined by high columnar
mucus-producing cells, is called the anorectal histologic junction
The intermediate or pectinate zone is lined
by stratified squamous epithelium but without adnexae (e.g.,
hair, sebaceous glands) and is also referred to as anoderm.
proximal margin, in contact with the proximal zone, is called the dentate line;
its distal margin, in contact with the anal skin,
constitutes the pectinate line, also referred to as the mucocutaneous junction
Some authors use the terms pectinate line and dentate line interchangeably.
The anal skin is lined by squamous stratified epithelium and contains hair and sebaceous glands
The lymphatics of the small intestine are called lacteals and
become filled with milky-white lymph called chyle after eating.
Each villus contains 1 central lacteal, except in the duodenum,
where 2 or more lacteals per villus may be present.
The myenteric plexus, or Auerbach plexus, is situated between the
outer and inner layers of the muscularis propria
The deep muscular plexus, or Schabadasch plexus, is situated
on the mucosal aspect of the circular muscular layer of the
muscularis propria. It does not contain ganglia; it innervates the
muscularis propria and connects with the myenteric plexus.
Ganglion cells have an
abundant basophilic cytoplasm, a large vesicular round nucleus,
and a prominent nucleolus.
The embryo is a bilaminar germ disk at 3 weeks’ gestation.
Through a process called gastrulation, this disk becomes trilaminar
and gives rise to the 3 primary germ layers: ectoderm,
mesoderm, and endoderm
The oral opening is marked by the
buccopharyngeal membrane; the future openings of the urogenital
and digestive tracts become identifiable as the cloacal membrane.
At 4 weeks’ gestation, the alimentary tract is divided into
3 parts: foregut, midgut, and hindgut, the endoderm connecting
with the yolk sac
During the 9th
week of development, the epithelium begins to differentiate from
the endoderm, with villus formation and differentiation of epithelial
cell types. Organogenesis is complete by 12 weeks’ gestation
By week 5 of
embryonic development, splanchnic mesoderm layers are fused
in the midline and form a double-layered membrane, the dorsal
mesentery, between the right and left halves of the body cavity
The duodenum originates from the terminal portion of the
foregut and cephalic part of the midgut. Early during week 4 of
gestation, the caudal foregut begins to expand to initiate formation
of the stomach
The liver and pancreas arise at the junction
of the midgut and foregut. With rotation of the stomach,
the duodenum becomes C-shaped and rotates to the right; the
fourth portion becomes fixed in the left upper abdominal cavity.
The villi appear during week 8 of gestation,
along with the microvillus enzymes. At 12 weeks’ gestation,
crypts are present and grow between the 10th and 14th week of
gestation. At 14 weeks, the intestinal enzymes are at an adult
level of activity.
Because the foregut is supplied by the celiac artery and the
midgut by the SMA, the duodenum is supplied by both arteries
and therefore is relatively protected from ischemic injury.
In a 5-week embryo, the midgut is suspended from the dorsal
abdominal wall by a short mesentery and communicates with the
yolk sac by way of the vitelline duct.
The midgut gives rise to
the duodenum distal to the ampulla, the entire small intestine,
and the cecum, appendix, ascending colon, and proximal two
thirds of the transverse colon. The midgut rapidly elongates with
formation of the primary intestinal loop
Rapid growth of the
midgut causes it to elongate, rotate, and to begin to form a loop
that protrudes into the umbilical cord.
At
7 weeks’ gestation, the small intestine begins to rotate counterclockwise
around the axis of the SMA. At 9 weeks, growth of
the intestine causes it to herniate further into the umbilical cord,
where it continues to rotate 90 degrees before it returns to the
abdominal cavity
At 11 weeks’ gestation, the intestine retracts
into the abdominal cavity and continues its counterclockwise
rotation another 180 degrees to a total of 270 degrees. The jejunum
returns first and fills the left half of the abdominal cavity
ultimately taking its position in the LUQ. The ileum returns next
and fills the right half of the abdominal cavity ultimately assuming
its final position in the RLQ.
The colon enters last, with
fixation of the cecum close to the iliac crest and the ascending
and descending colon attaching to the posterior abdominal wall.
Elongation of the bowel continues, and the jejunum and ileum
form a number of coiled loops within the peritoneal cavity.
The cecum originates as a small dilatation or bud of the caudal
limb of the primary intestinal loop by approximately 6 weeks of
development
The distal third of the transverse colon, the descending colon
and sigmoid, the rectum, and the upper part of the anal canal
originate from the hindgut. The fetal colon develops over 30
weeks in 3 stages. Primitive stratified epithelium similar to that in
the small intestine appears between 8 and 10 weeks.
Omphalocele Failure of intestine to return to the abdominal cavity after its physiologic herniation
Gastroschisis Weakening of abdominal wall
Mobile cecum Persistence of mesocolon
Volvulus Failure of fusion of mesocolon with posterior abdominal wall
Vitelline Duct
Meckel diverticulum Persistence of vitelline duct
Omphalomesenteric cyst Focal failure of vitelline duct obliteration
Patent omphalomesenteric duct Complete failure of vitelline duct obliteration
Rotation
Malrotation Failure of rotation of the proximal midgut; distal midgut rotates 90 degrees clockwise
Nonrotation Failure of stage 2 rotation
Reverse rotation Rotation of 90 degrees instead of 270 degrees
Proliferation
Duplication Abnormal proliferation of intestinal parenchyma
Intestinal Atresia and Stenosis
“Apple-peel” atresia Coiling of proximal jejunum distal to the atresia around the mesenteric remnant
Duodenum Lack of recanalization
Small and large intestine Vascular “accident”
Anorectum Disturbance in hindgut
Enteric Nervous System
Hirschsprung disease Failure of migration of ganglion cells; microenvironment changes
Intestinal neuronal dysplasia Controversial
Pseudo-obstruction Multifactorial (see Chapter 124)
The ENS originates from vagal, truncal, and sacral neural crest
cells.
Most of the ENS cells derive from the truncal and vagal neural crest, enter the foregut mesenchyma, and colonize the developing intestine in a cephalocaudal direction colonization is complete
by 13 weeks of embryonic development.
is an anti-mesenteric outpouching of the ileum that is usually
found within 2 feet of the IC junction (see Fig. 98.17B). It occurs
in 1.2% to 2% of the population and has a male-to-female ratio
of 3:1
Meckel Diverticulum
Md is a true diverticulum, containing all 3 layers of bowel wall: mucosa, muscularis, and serosa
The length of the Md varies from 1 to 10 cm. Ectopic GI mucosa—duodenal, gastric, biliary, colonic, or pancreatic tissue—is present in about 50% of Md
Painless bleeding per rectum is the most common manifestation of Md
Blood in the stool is usually maroon, even in patients
with massive bleeding and hypovolemic shock. BRBPR (hematochezia), as
might be seen with bleeding from the left colon, is almost never
encountered, but melena may be seen in patients with intermittent, less severe bleeding.
The cause of bleeding is peptic ulceration secondary to acid production by the ectopic gastric mucosa
within the Md; a “marginal” ulcer often develops at the junction
of the gastric and ileal mucosae.
Although Helicobacter pylorihas
been observed in the gastric mucosa within a Md, a relationship
between bleeding from a Md and presence of this organism is
unlikely
Intestinal obstruction is the next most common manifestation
of Md and is caused either by intussusception with the diverticulum as the lead point or by herniation through or volvulus around
a persistent fibrous cord remnant of the vestigial vitelline duct.
In
children older than age 4, intussusception is almost always secondary to a Md, although Md–related intestinal obstruction may
occur at almost any age; volvulus around a vitelline cord has been
described in the neonatal period;
Most commonly, affected patients are diagnosed as having
acute appendicitis, and the diagnosis of Meckel diverticulitis is
made at exploratory laparotomy.
Perforation occurs in about a
third of patients with Meckel diverticulitis and may result from
peptic ulceration.
37
A chronic form of Meckel diverticulitis
(Meckel ileitis) may mimic Crohn disease of the ileum
Md
should always be considered in an infant or child with significant painless rectal bleeding although standard abdominal plain films, barium contrast studies, and US are seldom helpful in making the diagnosis; rarely, an enterolith (which is often indistinguishable from an appendicolith) or dilated bowel loops with air–fluid level within the Md may be seen on these conventional studie
bleeding is almost always from ectopic gastric mucosa
within the diverticulum, a Meckel scan, which allows imaging
of the gastric mucosa, should be the initial diagnostic study
Uptake of 99m Tc-pertechnetate is by the mucussecreting cells of the gastric mucosa, not the parietal cells. The
sensitivity and specificity of Md scintigraphy can be
improved by
administration of pentagastrin, glucagon, or pretreatment with an
H2RA.
The GI tract processes 8 to 9 L of fluid daily that is derived
from oral intake and endogenous exocrine secretions. Intestinal
fluid absorption functions with 98% efficiency, allowing only
100 to 200 mL to be excreted each day.
in children under the age of 5
years, the leading pathogens with the highest mortality are rotavirus,
Cryptosporidiumspp., and Shigellaspp.
Gastric acidity is a crucial first-line host defense that ingested
pathogenic bacteria and other pathogens must survive to infect
the small or large intestine
In general, bacterial pathogens are
highly susceptible to low pH with a pH below 4.0 being rapidly
bactericidal.
reatment with PPIs, and to a lesser
degree the shorter-acting and less potent H2RAs, is a risk factor
for bacterial gastroenteritis, including Salmonella, Campylobacter,
and C. difficileinfection,
9
and viral gastroenteritis, including
norovirus
The
morbidity and mortality of infectious diarrheal diseases are highest
in children younger than 5 years of age (particularly severe in those
<2 years old
28
) and older adults.
Other
patients who also require a more aggressive approach include
those with systemic signs and evidence of inflammatory diarrhea, illnesses lasting greater than 3 to 5 days, a history or physical
examination suggesting specific pathogens that will benefit from
Hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (STEC; most common with Shigella dysenteriaeamong Shigellaspp., but S. dysenteriaeis not endemic in the USA)
Reactive arthritis* Salmonellaspp., Shigellaspp.,
Campylobacterspp., Yersiniaspp.
Bone marrow suppression Salmonellaserovars Typhi and Paratyphi Guillain-Barré syndrome Campylobacter jejuni
Toxic megacolon Shigellaspp., Clostridioides difficile, Salmonella(rarely)
RLQ tenderness Yersiniaspp
Characteristic
Inflammatory Clinical presentation Bloody, small-volume diarrhea; lower quadrant abdominal cramps; patients may be febrile and toxic
Noninflammatory Large-volume, watery diarrhea; patients may have nausea, vomiting, generalized abdominal cramps
Inflammatory Causes Shigellaspp., Salmonella spp., Entamoeba histolytica, Campylobacterspp., Yersiniaspp., invasive Escherichia coli, Clostridioides difficile
Noninflammatory Viruses, Vibriospp., Giardia lamblia, enterotoxigenic E. coli, other enterotoxinproducing bacteria
Site of
involvement
Inflammatory
Colon
Noninflammatory
Small intestine
Diagnostic
evaluation
Inflammatory
Indicated
Noninflammatory Indicated if the patient is severely volume depleted or appears ill
Fecal leukocytes
Inflammatory
Frequently present
Noninflammatory
Small numbers often
present
Proctitis syndrome is characterized by frequent painful bowel movements that contain blood, pus, and mucus. Tenesmus, often with rectal pain, usually is prominent.
ause diarrheal stools in both illnesses contain mucus
and blood. Two features of infectious dysentery that distinguish it from UC are detection of a pathogen on diagnostic studies and a self-limited course that responds to antimicrobial therapy
without relapse.
Positive diagnostic tests for a pathogen in adults
with diarrhea, however, are obtained in only about 50%
Most patients with infectious colitis present early (within 1 week)
and with fever to the physician; histopathology of the colon in
infectious colitis also is different from that of chronic colitis in
IBD (see later). In contrast, patients with IBD often have prior
abdominal symptoms upon a careful history, less fever, and present later (>1 week after symptom onset)
higher volume or frequency of diarrhea
(especially >10 stools per day) is more commonly due to an infectious pathogen than IBD
(1) Only diarrheal
stools (i.e., those that take the form of the container) should be
tested; (2) Rectal swabs are inferior to stool culture for testing in
adults (and rejected by many clinical microbiology laboratories)
but perform similarly in children
V. choleraeand ETEC is that disease primarily results from intestinal fluid loss, which is related to the action of the enterotoxin
on the small intestinal epithelial cells. These organisms usually
do not invade the mucosal surface, and thus, mucosal architecture
remains intact. The fecal effluent is watery and often voluminous,
producing clinical features of dehydration. Bacteremia is rarely a
complication of toxigenic diarrhea.
Cholera, the prototypical toxigenic diarrhea, can cause dehydration and death within a few hours of onset.
Stool output can exceed 1 L/hr, with daily fecal outputs of 15 to 20 L if parenteral fluid replacement keeps up with losses.
V. choleraeis a gram-negative, short, curved rod that looks like a comma.
It is actively motile by means of a single polar flagellum. Vibrios
are strongly aerobic and prefer alkaline and high-salt environments
The B subunit is responsible for binding to the monoganglioside GM1
receptor on intestinal epithelial cells. The A subunit is responsible for activation of adenylate cyclase located on the basolateral
cellular membrane.
The primary vehicle for spread of cholera is contaminated food and water, and a high inoculum dose (~10^8to 10^11 organisms) is typically required for infection
So-called rice water feces (see later) contains high concentrations
of V. choleraeorganisms, which are hyperinfectious for about 5 to
24 hours after passage
The most sensitive areas are the upper intestine, particularly the duodenum and upper jejunum; the ileum is
less affected, and the colon is relatively insensitive to the toxin.
Cholera vibrios (other than O139) do not invade the mucosal
surface, and bacteremia is virtually unknown in this disease. A biopsy
specimen taken from the mucosa during acute cholera largely shows
normal architecture, in sharp contrast to the inflammatory and
ulcerating lesions associated with Salmonellaand Shigella.
In clinical cholera, the initial stage is characterized
by vomiting and abdominal distention and is followed rapidly by
diarrhea that accelerates over the next few hours to frequent largevolume rice-water stools.
The stool is isotonic with plasma, although there
is an inordinate loss of potassium and bicarbonate, with resultant
hypokalemic acidosis
Particular attention is paid
to administration of bicarbonate and potassium, which are lost
excessively in choleric stool.
The CDC and
WHO recommend doxycycline as a single oral dose of 300 mg
for nonpregnant adults. A single oral dose of azithromycin 1 g
is recommended for pregnant women, and a dose of 20 mg/kg
is recommended for children, not to exceed 1 g
Zinc supplementation, through complex
actions including improvement of immune responses, has been
shown to reduce the duration and volume of diarrhea among children with cholera in Bangladesh and may be a useful adjunct to
standard therapy
Antimicrobial resistance (e.g., to fluoroquinolone antibiotics) is an increasing concern, but because of risk
of direct transmission, antibiotics are indicated for moderate and
severe cholera
The WHO has prequalified a 2-dose regimen killed oral cholera
vaccine and currently recommends its use in endemic areas and
areas at risk for outbreaks
The most common antecedent history is consumption of raw
oysters within the preceding 72 hours. Other seafood such as
clams, mollusks, and crab all have been implicated in non-O1/
O139 vibrio disease.
incubation periods that range from as short as 6 to 12 hours
to as long as 3 days
V. parahaemolyticuscauses an acute diarrheal disease after consumption of contaminated raw fish or shellfish. Strains of V. parahaemolyticusproduce a number of distinct hemolysins, the most
significant of which is responsible for the Kanagawa phenomenon
(i.e., hemolysis of human red blood cells in Wagatsuma bacteriologic medium)
V. parahaemolyticusgastroenteritis is the most common cause of
seafood-borne illness worldwide
EPEC was initially recognized as causing severe neonatal diarrhea and remains a common cause of diarrheal illness and associated morbidity in children globally.
100
EPEC induces classic
attaching and effacing lesions, in which bacteria attach to the
intestinal cell membrane and cause effacement of the microvilli
(see Fig. 110.1B). A common pathogenicity island (LEE, locus
for enterocyte effacement) is responsible for these lesions and
serves as the basis for molecular identification of EPEC
EPEC is also reported
to be the most frequent pathogen detected in mixed infections, but, importantly, can often be recovered from asymptomatic individuals
Clinical presentation is characterized by acute diarrhea with
vomiting and dehydration, but EPEC is also strongly associated with persistent diarrhea
ETEC is acquired by consuming contaminated foods and liquids.
Infection first requires adherence and then toxin production
Adherence is mediated primarily by CFs, which are carried on
plasmids. More than 25 distinct CFs
115
have been identified and
are designated as CFA (colonization factor antigen) or CS (coli
surface antigen), followed by a number
A subunit, LT acts pathophysiologically
like cholera toxin by activating adenylate cyclase, thereby causing secretion of fluid and electrolytes into the small intestinal
lumen.
117
The second ETEC toxin is heat stable (ST) and is able
to withstand heating to 100°C. ST is a family of low molecular
weight toxins with 2 primary classes, STa and STb. Only STa
has been associated with human disease;
ne ETEC, of which 55% were acquired during travel.
Indeed, ETEC is the most common cause of travelers’ diarrhea
worldwide
STEC is
typically classified as O157 and non-O157 with O157 classically
associated with the HUS, although non-O157 strains also can
trigger HUS
The leading vehicle of infection for STEC is hamburger meat,
although outbreaks have been associated with fresh-pressed apple
cider, produce, and unpasteurized milk
The most important reservoir of infection is cattle,
hence, transmission via hamburger meat, and vaccine strategies
to reduce fecal shedding continue to be studied
In order to cause infection in humans, STEC must first adhere to
the enterocytes.
Most strains responsible for human disease cause
attachment-effacement lesions as seen in EPEC and similarly
carry the LEE pathogenicity island (see EPEC section)
After an incubation period of 1 to 14 days (mean, 3 to 4 days),
watery nonbloody diarrhea begins, is associated with severe
abdominal cramping, and often progresses to frankly bloody
stools, especially if the infecting serovar is STEC O157:H7
HUS is characterized by acute renal injury, nonimmune microangiopathic hemolytic anemia, and
thrombocytopenia
Risk factors for HUS include age less than
5 years, attendance at a large day care center, presence of bloody
diarrhea, and a high WBC count
Several laboratory methods are used to diagnose STEC infections. Currently the CDC recommends a combination of culture
for O157 STEC and a nonculture Stx assay
E. coliO157:H7 do not ferment sorbitol, screening for
this pathogen usually is done with sorbitol-MacConkey agar.
The chances of obtaining a positive culture from stool depend
on the time between the onset of symptoms and collection of the
stool. Within 2 days of onset, virtually all stool specimens from
O157-infected patients are positive, whereas after 7 days, only
one third are positive.
Enteroaggregative E. coli(EAEC)
Unlike the attaching and effacing adherence to cells seen with
EPEC, some E. colistrains adhere in an aggregative motif, with the
bacteria clumping to the cell surface in a stacked-brick pattern
The diarrhea associated with EAEC is typically watery, although
mucoid and grossly bloody diarrhea has also been reported
EAEC pathogenesis is complex but seems to have 4 major
features: characteristic adherence, biofilm formation, production of enterotoxins and cytotoxins, and mucosal inflammation
All invasive pathogens can cause dysentery, a term that refers to
a diarrheal stool that contains an inflammatory exudate composed
of polymorhonuclear leukocytes (PMNs ), mucus, and blood.
Shigellaspecies are gram-negative enteric organisms included in
the family Enterobacteriaceae
Unlike E. coli, shigellae are nonmotile, do
not produce gas from glucose, and are generally lactose negative,
except for S. sonnei. Group A (S. dysenteriaetype 1), also known
as the Shiga bacillus, produces the most severe form of dysentery.
Transmission is through fecal-oral contact. An inoculum of
just 10 organisms has been shown to be capable of causing disease.
177
The ability of Shigellaspp. to survive in acidic conditions
might account for the small inoculum that can produce disease.
Person-to-person transmission, facilitated by the low infective dose, accounts for rapid
spread of Shigellain day care centers and among people living in
conditions of poor hygiene
Shigellainitially interacts little with enterocytes and instead triggers its uptake by M cells, after which it exits the basolateral side
of the M cell into the submucosa.
The bacteria then invade the enterocytes via the basolateral side by macropinocytosis. Once phagocytosed, the bacteria lyse the phagosome and are released into
the enterocyte cytoplasm. From there, enterocyte-to-enterocyte
invasion occurs.
The major site of attack of Shigellais the colon, although
scattered ulcerations can be seen in the terminal ileum as well.
The stages of Shigellapenetration of the mucosa and its cellular interactions eventuate in enterocyte death, focal ulcers,
and mucosal inflammation, with edema, formation of microabscesses (e.g., crypt abscesses), loss of goblet cells, and loss of
tissue architecture
A volunteer study found that only 28% of subjects developed the classic
symptom progression of fever (∼48 hours), abdominal pain, diarrhea (∼72 hours), and dysentery (∼120 to 144 hours).
Fever and
abdominal pain may start within 24 hours after exposure but average 1.6 and 3.6 days, respectively. Diarrhea may begin after 24
hours and continue up to 2 weeks, but average onset is at 4 days.
Dysentery may start as early as 3 days and as late as 17, but averages 7 days and may continue for more than a month
A rash (rose spots) can occur during the acute phase of shigellosis. Arthritis can develop 2 to 3 weeks after onset of dysentery. Joint pain or effusion usually is asymmetric and involves large joints.
Shigellaspp. were the third most common
cause of death attributed to diarrheal disease in children younger
than 5 years of age and the leading cause of death attributed
to diarrheal disease among adults 15 to 99 years of age in the
Global Burden of Disease study (2015)
Antimotility agents are not recommended.
Zinc supplementation (through complex actions including
improving immune responses) and green bananas (by promoting production of short-chain fatty acids that serve as a metabolic
energy source for colonocytes) have potential to decrease severity
of shigellosis and associated morbidity
Ampicillin is the drug formulation preferred for treatment of sensitive Shigellastrains
Chronic carriers of Shigellaare rare.
Postinfection carriage
generally lasts less than 3 or 4 weeks and rarely exceeds 3 to 4
months.
Nontyphoidal salmonellosis refers to disease caused by
any serotype of the genus Salmonella, with the exception of
SalmonellaTyphi and SalmonellaParatyphi. In contrast to S.
Typhi and S.Paratyphi, nontyphoidal Salmonellaoften have
animal reservoirs, encounter humans, and cause disease.
Salmonellae are a group of predominantly motile gram-negative
bacilli comprising 2 species, Salmonella bongoriand Salmonella
enterica
Children younger than 1 year of age have the highest attack rate,
a susceptibility that may be related to immunologic immaturity
Salmonellae attack the ileum and, to a lesser extent, the colon,
causing mild mucosal ulcerations.
Invasion of host enterocytes or macrophages occurs through
a mechanism shared with other members of the Enterobacteriaceae family, the T3SS
The relationship between sickle cell anemia and Salmonella
osteomyelitis is well known. Indeed, several infectious causes of
hemolytic anemia predispose to invasive Salmonellainfection,
including malaria and bartonellosis.
Neoplastic disease is
associated with an increased risk of salmonellosis, and leukemia,
lymphoma, and disseminated malignancy predispose patients to
bloodstream invasion by this organism
Enterocolitis is the most common clinical manifestation of
salmonellosis, accounts for approximately 75% of infections,
and is indistinct from that caused by other enteric pathogens.
The incubation period varies by host and inoculum size, but typically ranges from 6 to 72 hours
Clinical manifestations are the
acute onset of fever, diarrhea, and cramping, often preceded by
nausea and vomiting
Salmonellaenterocolitis may present
as dysentery, but watery diarrhea is a more common prominent
symptom and can vary from mild to cholera-like, particularly in
patients who are hypochlorhydric
The most serious complication of salmonellosis is bacteremia
and its sequelae.
Thus, antimicrobial therapy should not be used in most cases of
Salmonellaenterocolitis.
antibiotics should be used in conditions with high risk for extraintestinal spread, such as lymphoproliferative disorders, malignant disease, immunosuppressed states
(AIDS and congenital or acquired immunodeficiencie
fluoroquinolone is the drug of first
choice, with third generation cephalosporins as alternatives.
Typhoid (Greek typhos, “stupor” or “cloudy”) fever is a febrile
illness of prolonged duration, marked by hectic fever, delirium,
persistent bloodstream infection, splenic enlargement, abdominal pain, and a variety of systemic manifestations. The illness caused by typhoidal Salmonelladiffers from nontyphoidal
Salmonellainfections in several respects
ShigellaSpeCieS
Shigellainfection (nondysenteriae;
for Shigella dysenteriaetype 1,
see text)
Ciprofloxacin 500 mg twice daily (or levofloxacin 500 mg daily) × 3
days or Azithromycin 500 mg once daily × 3 day
Typhoid and enteric fevers* Ciprofloxacin 500 mg twice daily (or ofloxacin 400 mg twice daily)
× 7-10 days
Ceftriaxone 2 g IV once or twice daily x 10-14 days
SalmonellaSpeCieS
Enterocolitis, uncomplicated Not usually recommended (see text)
CampyloBaCterSpeCieS
Campylobacter jejuni Not usually required
Azithromycin 500 mg daily × 3 days
YerSinia enterocolitica
Enterocolitis, uncomplicated Not usually required
TMP/SMX 160 mg/800 mg twice daily × 5 days
eScherichia coli
†
Enterotoxigenic Endemic disease; usually self-limited; supportive care (see text)
Travelers’ diarrhea: ciprofloxacin 500 mg twice daily × 3 days (see
Table 110.9)
Rifaximin 200 mg 3 times daily × 3 days
Stx-producing Unclear if antibiotics are effective; may be harmful
VibrioSpeCieS
Vibrio cholerae Doxycycline 300 mg × 1 dose
For severe typhoid fever, consider the addition of glucocorticoids (dexamethasone 3 mg/kg × 1, then 1 mg/kg every 6 hours × 48 hours) to parenteral
antimicrobial therapy. Antimicrobial sensitivity testing is required. Fluoroquinolones (e.g., ciprofloxacin) should not be used as empiric therapy in Asia or
other areas with high fluoroquinolone resistance
All antibiotics are administered orally unless otherwise indicated. Recommendations are given for treatment of mild/moderate infections only.
Treatments for complicated infections or severely ill, bacteremic, or immunocompromised patients are not listed previously and may differ from treatments for mild disease
The polysaccharide capsule Vi antigen is one of the most
important virulence factors for S.Typhi.
S.Typhi and S.Paratyphi are adapted specifically to the human
host. Humans serve as a chronic reservoir, periodically shedding
the organisms into the environment where they subsequently are
ingested usually in contaminated food or water supplies.
In its classic form and without treatment, typhoid fever lasts about
4 weeks and evolves in a manner consistent with the pathologic
events
The
incubation period generally is 7 to 14 days, with wide variations.
During the first week, high fever, headache, and abdominal pain are common. The pulse often is slower than would be
expected for the degree of fever, a finding referred to as Faget sign.
Abdominal pain is localized to the RLQ in most cases but can be
diffuse.
Near the end of the first week,
enlargement of the spleen is noticeable, and an evanescent classic
rash (rose spots) becomes manifest, most commonly on the chest.
During the second week, the fever becomes more continuous, and the patient looks sick and withdrawn.
During the third
week, the patient’s illness evolves into the “typhoidal state,” with disordered mentation and, in some cases, extreme toxemia. It is
from this altered mental state that the term typhoidderives
In this
period there is often intestinal involvement, manifested clinically
by greenish pea soup–like diarrhea and the dire complications of
intestinal perforation and hemorrhage.
The fourth week brings
slackening of the fever and improvement in the clinical status, if
the patient survives and recovers.
Acute cholecystitis can occur during the initial 2 to 3 weeks, and
jaundice, resulting from diffuse hepatic inflammation, has been
observed in some patients
The preeminent complications are intestinal hemorrhage and
perforation.
249
These events are most likely to occur in the third
week and during convalescence and are not related to the severity of the disease; they tend to occur in the same patient, with
bleeding serving as a harbinger of possible perforation.
After 6 weeks, approximately 50% of typhoid victims still shed
organisms in their feces. This figure declines progressively with
time, and after 3 months only 5% to 10% are excreters; by 1 year
the frequency is 1% to 6%
The chronic carrier is identified
by positive stool cultures for S.Typhi at least 1 year after the
acute episode or, in some cases, positive stool cultures without
a documented history of disease.
The probability of spontaneously aborting the carrier state is highly unlikely after this time.
Chronic carriers are more common in older age groups, women
(a 3:1 ratio of women to men),
254
and persons with biliary disease.
The organism usually is harbored in the gallbladder, although
occasionally it is carried in the large intestine without involvement of the biliary tract
The diagnosis of typhoid fever is established by isolating the
organism. Blood culture is the primary diagnostic test and is positive in 60% to 80% of patients, but declines closer to 40% outside of the study setting where many patients may have received
prior antibiotic therapy
Bone marrow culture is considered the gold standard and has a yield of better than 90%, even in treated
patients
Stool cultures become positive in the second and third
weeks.
Sampling duodenal contents by a string test yields a positive culture in 70% of patients. By the third week, urine cultures
reveal the organism in approximately 25% of patients. The titer of
agglutinins against somatic (O) antigen (Widal test) rises during
the second and third weeks of illness.
Various titer thresholds for
a positive result are used in different countries, but a 4-fold rise
in convalescent titer is considered stronger evidence of typhoid
fever. Problems with the Widal test include cross-reaction with
other Salmonellastrains causing false positives, and false negatives
if the sample is collected too early in the disease course.
One clinical trial also demonstrated benefit to high-dose dexamethasone at an initial dose of 3 mg/kg, then 1 mg/kg every 6 hours for 48 hours
Quinolone antibiotics (e.g., ciprofloxacin) have become the treatment of choice in eradicating the carrier state
Cholecystectomy
eliminates the carrier state in 85% of carriers with gallstones or
chronic cholecystitis and is most clearly recommended for persons whose profession is incompatible with the typhoid carrier
state, such as food handlers and health care providers.
There are 3 available typhoid vaccines: (1) Vi-TT (tetanus toxoid)
typhoid conjugate vaccine administered parenterally; (2) Ty21a,
a live-attenuated orally administered S.Typhi strain; and (3) Vi
capsular polysaccharide vaccine, which is administered parenterally.
The typhoid conjugate vaccine is now preferred by the
WHO for all ages because of evidence of enhanced immunogenicity and sustained levels of protection
Campylobacterspecies are motile, comma-shaped, gramnegative rods with a polar flagellum
Transmission to humans appears to occur most commonly
from infected animals and their food products. The reservoir for
Campylobacteris enormous because many animals can be infected
Stool culture remains the gold standard for diagnosis of
Campylobacterduring acute gastroenteritis
The incubation period is 24 to 72 hours after organisms are ingested, but can be as long as 10 days
Mild Campylobacterenteritis is self-limiting with supportive care
and does not typically require antibiotic treatment
rotavirus is a segmented double-stranded
RNA virus with an icosahedral structure that resembles the spokes
of a wheel, hence “rota”
Rotavirus infection is now recognized as a leading cause of infectious gastroenteritis worldwide and is extremely
common in children, the majority of cases occurring in those
younger than age 5
ROtA v
In its severe form, the infection can produce denuded villi and flattening of the epithelial surface that can persist for weeks, yielding reduced
brush border levels of disaccharidases and malabsorption of carbohydrates, fats, and protein.
The infectious inoculum for rotavirus infection is small, estimated at 1 to 10 virions, and the incubation period is 1 to 3 days
Vomiting often heralds the illness and is followed
shortly by watery diarrhea, which often leads to dehydration. The average duration of illness is 5 to 7 days,
although chronic diarrhea has been noted
rapid diagnostic
tests are available for detection of rotavirus antigen in the feces
using several commercial immunoassays (e.g., EIA, latex agglutination) or NAATs
Rehydration is the mainstay of
therapy for this infection.
RotaTeq (Merck and
Co, Inc, West Point, PA) is a pentavalent rotavirus vaccine (5
human reassortment human/bovine strains [RV5]), and
Rotarix
(GlaxoSmithKline, Philadelphia, PA) is a monovalent (RV1) vaccine. Both are recommended for administration in multiple doses
beginning at 2 months of age
The definition of travelers’ diarrhea is 3 or more unformed stools
plus 1 accompanying symptom over a 24 hour period.
Diarrhea is considered the most common medical
complaint of travelers.
Bacterial enteric pathogens, identified in 60% to 80% of cases, are the primary cause of travelers’ diarrhea.
Most infections are acquired from food and drink
Most travelers’ diarrhea is watery and self-limited (1 to 5 days
Rifaximin is approved
in the USA for the treatment of noninvasive, afebrile forms of
travelers’ diarrhea in patients older than 12 years of age. This
drug has demonstrated minimal potential for development of
bacterial resistance. Azithromycin is recommended for febrile
or dysenteric travelers’ diarrhea or as a rescue medication if
failure of rifaximin or fluoroquinolones occurs.
antibiotics and loperamide to be safe and effective, although
a recent meta-analysis suggests benefit is limited to the first
24 to 48 hours of therapy
Chemoprophylaxis is not indicated for most travelers. When prescribed, it is taken only for the duration of the trip considered as high risk for acquisition of an enteric infection.
Nonantibiotic* Bismuth subsalicylate (Pepto Bismol) 525 mg (1 ounce liquid or 2 tablets chewed of regular-strength preparation) 4 times daily
Antibiotics† Antibiotic prophylaxis should be reserved for highly selected persons Rifaximin is not effective against Campylobacter.
Rifaximin 200 to 1100 mg daily divided into 1-3 doses
Loperamide 4 mg PO then 2 mg after each loose
stool, not to exceed 16 mg daily
More rapid onset of action compared with bismuth
subsalicylate. Should not be used when there is a fever (temperature >38.5°C) or gross blood in the stool.
Antibiotics¶
Ciprofloxacin 750 mg PO once or 500 mg PO twice
daily
Levofloxacin 500 mg PO once or 500 mg PO twice
daily
Azithromycin 500-1000 mg PO once or 500 mg daily
× 3 days
Rifaximin 200 mg PO 3 times daily × 3 days Can be used for the treatment of individuals ≥12 yr of age
with travelers’ diarrhea caused by noninvasive strains of
Escherichia coli
The gross appearance of intestinal TB is divided into 3 categories: (1) ulcerative lesions (60% of patients) consisting of multiple superficial lesions confined largely to the epithelial surface;
(2) hypertrophic lesions (10% of patients) manifesting as scarring,
fibrosis, and heaped-up mass lesions that can mimic carcinoma;
and (3) ulcerohypertrophic lesions (30% of patients) where mucosal ulcerations are combined with healing and scar formation
A palpable RLQ abdominal mass is found in approximately
25% to 50% of patients as the ileum is the most common site
of intestinal involvement.
The cecum is contracted with disease on
both sides of the valve, and the valve itself often is distorted and incompetent; conification of the cecum, as seen on barium enema or small bowel follow-through, is characteristic of TB
and is referred to as Stierlin sign.
Crohn disease
can manifest virtually all of the changes of intestinal TB except
for the presence of the organism.
Features of potential help in
differentiating tuberculous enteritis from Crohn disease include
an inflammatory mass centered in the ileocecum; transverse, circumferential ulcers rather than linear ulcers along the bowel axis
(the latter is seen in Crohn disease); cecal valve incompetence
with Stierlin sign; and large (>1 cm), hypodense (necrotizing/
caseous) mesenteric lymph nodes.
avoid milk and dairy products during acute diarrhea because of
the potential for secondary lactase deficiency to have developed.
Caffeine in coffee, tea, cocoa, and cola soft drinks can potentiate abdominal cramps and diarrhea. Abstinence from alcohol is
recommended.
Travelers
fluoroquinolone
or azithromycin is typically the drug of choice for adults. Some
authors consider azithromycin to be the drug of choice because
of its activity against fluoroquinolone-resistant Campylobacter
(common in Southeast Asia and Nepal/India) as well as its safety
profile, including use in children and pregnant women.
The optimal duration of antimicrobial therapy has not been
defined with precision. Antibiotic therapy for 3 to 5 days is typical
except when C. difficileis diagnosed
Loperamide is arguably the best agent for acute, nonbloody, nonfebrile diarrhea, because it does not cross the blood-brain barrier, thereby reducing the risk for habituation or other CNS side effects.
Bismuth subsalicylate may help decrease stool liquidity and
frequency and has a low incidence of side effects (see “Travelers’
Diarrhea” section). The drug possesses antimicrobial, antisecretory, and anti-inflammatory properties on the basis of its bismuth
and salicylate moieties, respectively.
Food poisoningis defined as an illness caused by the consumption of food contaminated with bacteria, bacterial toxins, parasites, viruses, or chemicals.
A foodborne disease outbreak is defined by 2 criteria: similar illness, usually GI, in 2 or more persons; and epidemiologic or laboratory investigation that implicates food as the source.
Staphylococcal enterotoxins are resistant to freezing, heating, and low acidity which enables the toxin to survive standard techniques of food preparation and pass through the stomach unaltered
Staphylococcal food poisoning has a short incubation period of about 3 hours, with a range of 1 to 6 hours, because the disease is caused by ingestion of preformed toxin
Vomiting is the dominant initial symptom and can lead to a severe metabolic alkalosis. Fever is unusual. Rarely, hypotension and marked prostration occur. Recovery usually is complete within 24 to 48 hours.
The recommended, first-line, antimicrobials for the treatment
of CDI are oral vancomycin(125 mg 4 times a day for 10 days)
and or oral fidaxomicin (200 mg 2 times daily for 10 days)
Metronidazole appears to be less effective for CDI therapy
E. histolyticahas a simple, 2-stage life cycle that consists of an
infectious cyst and a motile trophozoite. The cyst form measures
5 to 20 μm in diameter and contains 4 or fewer nuclei. The ameboid trophozoite, which is responsible for tissue invasion, measures 10 to 60 μm and contains a single nucleus with a central
karyosome (Fig. 113.1). The cysts are relatively resistant to chlorination and desiccation, and they can survive in a moist environment for several weeks
Infection occurs following ingestion of cysts in fecally contaminated food or water. Within the lumen of the small intestine,
the quadrinucleate cyst undergoes nuclear and then cytoplasmic
division, giving rise to 8 trophozoites
Amebic Colitis
Travel to or from an endemic
area
Yes
Usual duration of symptoms
>7 days
Fecal occult blood (%)
100
Weight loss Common
Fever >38°C Minority
Bacterial Dysentery*
Travel to or from an endemic
area
Sometimes
Usual duration of symptoms
2-7 days
Fecal occult blood (%)
40
Weight loss Unusual
Fever >38°C Majority
ameoba
The cecum and ascending colon are affected most commonly,
although in severe disease the entire colon may be involved.
can range from only mucosal
thickening to multiple punctate ulcers with normal intervening tissue to frank necrosis. For unknown reasons, the downward invasion of amebic trophozoites often is halted at the level of the muscularis mucosa. Subsequent lateral spread of amebae undermines the overlying epithelium, resulting in the clean-based, flask-shaped ulcers so characteristic of classic amebic colitis Early in infection, an influx of neutrophils is typical, but in well-established ulcers, few inflammatory cells are seen
Organisms may be seen ingesting red blood cells (erythrophagocytosis
More than 90% of persons colonized with E. histolytica
spontaneously clear the infection within a year
Approximately 80% to 90% of infected persons remain asymptomatic. The other 10% to 20% of infections result in invasive
amebiasis characterized by dysentery (amebic colitis) or, in a
minority of cases, extraintestinal disease (most commonly amebic
liver abscess
In contrast to bacterial dysentery, which typically begins abruptly, amebic colitis begins
gradually over one to several weeks
The most feared complication of amebic dysentery, acute necrotizing colitis with toxic megacolon, occurs in 0.5% of cases.
This complication manifests as an acute dilatation of the colon, and 40% of patients die from sepsis unless it is promptly recognized and treated surgically
The gold standard for
diagnosis of amebic colitis remains colonoscopy with biopsy, and colonoscopy should be performed whenever infectious causes of bloody diarrhea are strong considerations in the differential
diagnosis of UC
Because the cecum and ascending colon are
affected most often, colonoscopy is preferred to sigmoidoscopy.
Classically, multiple punctate ulcers measuring 2 to 10 mm are
seen with essentially normal intervening tissue
colonic epithelium might simply appear indurated
with no visible ulcerations; appear like UC with a myriad of ulcerations and granular, friable mucosa, or as a “poached egg” with
a solitary mucus-covered ulcer; in severe cases where the ulcers
have coalesced, the epithelium may appear necrotic
Histologic
examination of a biopsy specimen taken from the edge of an ulcer
reveals amebic trophozoites and a variable inflammatory infiltrate
Fecal antigen detection, when compared with the gold standard of stool culture followed by isoenzyme analysis, is more than 90% specific and more than 85% sensitive to diagnose intestinal amebiasis
The luminal amebicides include iodoquinol, diloxanide
furoate, and paromomycin.
54,55
Of these, paromomycin, a nonabsorbable aminoglycoside, is preferred because of its safety, short
duration of required treatment, and superior efficacy; its major
side effect is diarrhea
Approximately 85% of asymptomatic
patients are cured with one course of paromomycin, and, because
it is nonabsorbable and has moderate activity against trophozoites that have invaded the colonic mucosa, it also might be useful
for single-drug treatment of mild invasive disease during pregnancy
The tissue amebicides include metronidazole, tinidazole,
nitazoxanide, erythromycin, and chloroquine
Of these, metronidazole and tinidazole are the drugs of choice,
or such noninvasive disease, treatment with a luminal
agent alone is adequate (e.g., paromomycin 25 to 35 mg/kg/day in
3 divided doses for 7 days).
55
Patients with amebic colitis should
first be treated with an oral nitroimidazole (either metronidazole
[500 to 750 mg 3 times daily for 10 days] or tinidazole [2 g once
daily for 3 to 5 days]) to eliminate invasive trophozoites.
Metronidazole and tinidazole are believed to be less effective against
organisms in the colonic lumen, and subsequent treatment with a
luminal agent such as paromomycin is recommended to prevent
recurrent disease.
It is also for this reason that the familiar
tissue amebicides (e.g., metronidazole) are not recommended as
first-line agents for treatment of asymptomatic infection.
Because of severe GI side effects, simultaneous
treatment with a nitroimidazole and a luminal agent generally is
not recommended.
Most patients with amebic colitis respond promptly with resolution of diarrhea in 2 to 5 days
Paromomycin 7-day treatment course; may be useful
during pregnancy
For both invasive intestinaL anD extraintestinaL amebiasis Metronidazole Drug of choice for amebic colitis and liver abscess
Nitazoxanide Useful alternative if the patient is intolerant
of metronidazole or tinidazole
or extraintestinaL amebiasis onLy
Chloroquine Useful only for amebic liver absces
metronidazole (750 mg 3
times a day for 10 days) followed by a luminal agent is also the
treatment of choice for amebic liver abscess
E. colitrophozoites contain a
single nucleus with a prominent karyosome that usually is eccentric in location, distinguishing them from E. histolyticaand E. dispartrophozoites, which have a centrally located karyosome.
The life cycle of Giardiaconsists of an infectious cyst form
and a motile trophozoite (Fig. 113.5). The cyst is oval (8 to
12 μm long by 7 to 10 μm wide), contains 4 nuclei, and has a
rigid outer wall that protects it from dehydration, extremes of
temperature, and chlorination
Ingestion of as few as 10 to 25 cysts can result in infection. 82 After ingestion, excystation occurs following exposure to stomach acid and intestinal proteases, each cyst giving rise to 2 trophozoites
The life cycle of Giardiaconsists of an infectious cyst form and a motile trophozoite contains 4 nuclei, and has a rigid outer wall that protects it from dehydration, extremes of temperature, and chlorination. Giardiacysts can survive in cold
water for several weeks.65,82
Ingestion of as few as 10 to 25 cysts
can result in infection
Giardiatrophozoites are pearshaped (10 to 20 μm long by 7 to 10 μm wide), contain 2 nuclei,
have 8 flagella for locomotion, and replicate by binary fission
Giardiacauses malabsorptive diarrhea
Trophozoites adhere (perhaps by suction) to the epithelium of the upper small intestine using a disk structure located on their anterior ventral surface.
Clinical manifestations of Giardiainfection are highly variable,
and range from an asymptomatic state to severe, chronic diarrhea with malabsorption.
Many patients with clinically apparent giardiasis suffer from lactose intolerance, malabsorption, or both for months following
cure of infection
Examination of concentrated, iodine-stained, wet stool preparations and modified-trichrome-stained permanent smears has
been the conventional approach to identifying Giardiainfections
Metronidazole (250 mg orally 3 times a day for 5 days) is the preferred treatment for giardiasis
The most common side effects
of metronidazole are nausea, a metallic taste, and a disulfiram-like
reaction upon consuming alcohol.
Nitazoxanide appears to be at least as effective as metronidazole and has the advantage of being available in a liquid formulation for use in pediatric patients. The recommended dosage
in children is 100 mg (ages 12 to 47 months) or 200 mg (age
>4 years) twice daily, and in adults is 500 mg twice daily for 3
days
Alternative regimens include tinidazole (2 g orally for 1 dose
A. lumbricoidesis the largest of the nematode parasites that colonize humans; females can grow to 49 cm
dirt contaminated with its eggs, whereas
adults most often are infected by farming or eating raw vegetables from plants fertilized with untreated sewage.
Humans acquire the parasite by ingesting embryonated eggs that
contain third-stage larvae. Fertilized eggs are passed in stool and
incubate in the soil for 10 to 15 days while the embryo develops
and molts twice, after which the eggs become infective.
Asymptomatic colonization with A. lumbricoidesis treated easily
with a single 400-mg oral dose of albendazole.
atients with pulmonary ascariasis should be treated with
glucocorticoids to reduce the pneumonitis and be given 2 400-mg doses of albendazole one month apart.
Capillariasis is acquired by eating raw fish infested with the parasite.
protein-losing, sprue-like diarrhea with progressive emaciation
and anasarca, which ultimately leads to death, absent treatment.
Treatment is albendazole
Birds, not humans, are the natural hosts for P. philippinensis. In
the avian small intestine, the larvae mature into adults.
Adult worms mate and produced eggs are deposited in
bird droppings into ponds and rivers to be swallowed by fish to
complete the life cycle
People become infested with the worm by eating raw or undercooked freshwater or brackish-water fish that contain the parasitic larvae.
vague abdominal pain and borborygmi. Patients begin
to have diarrhea 2 to 3 weeks after infection. Initially intermittent, diarrhea becomes persistent and increasingly voluminous.
Patients rapidly waste from escalating steatorrhea and proteinlosing enteropathy.
capillaria phili
hypotension; diarrhea produces severe hypokalemia. If
untreated, patients die from cardiac failure or secondary bacterial
sepsis usually about 2 months after the initial onset of symptoms.
In autopsy
studies, the jejunal intestinal mucosa showed flattened, denuded
villi with numerous plasma cells, lymphocytes, macrophages, and
neutrophils infiltrating the lamina propria
Diagnosis is made by finding eggs and larvae in stool specimens but stool examination is insensitive.
Push or balloon endoscopy
shows jejunal mucosal scalloping and biopsies of involved mucosa
can demonstrate the helminths
Capillariasis requires extended antihelminthic treatment with
albendazole 200 mg orally twice daily for 10 days or mebendazole 200 mg orally twice daily for 20 days to prevent recurrence.
Albendazole is better tolerated than mebendazole
