SMALL BOWEL AND

LARGE BOWEL
DISORDERS
Jaba Zarkua
What is your opinion?
A student fails to use proper disinfection techniques in carrying out his
microbiology experiment. Two weeks later, he has spiking fevers and cramping
abdominal pain with diarrhea. On physical examination his temperature is 38.3C,
pulse 100/minute, respiratory rate 19/minute, and blood pressure 100/60 mm Hg.
He has a palpable spleen tip and diffuse abdominal pain without masses.
Laboratory studies show a WBC count of 2330/microliter, Hgb 13.8 g/dL, and
platelet count 282,000/microliter. Which of the following organisms was he most
likely using in his experiment?
Entameba histolytica
Clostridium difficile
Rotavirus
Salmonella typhi
What is your opinion?
While on vacation in Mexico, a medical student develops severe watery diarrhea
without blood, abdominal pain, and nausea. He becomes increasingly dehydrated
and weak. Immediately after returning home, he seeks medical attention. Stool
examination is negative for fecal leukocytes, fat, or blood, and sigmoidoscopy
reveals normal mucosa. What is probable cause of this illness?

Entameba histolytica
Clostridium difficile
ETEC
Salmonella typhi
Signs and symptoms of small bowel
disease
1. Colicky pain
Pain followed by a pain-free interval (accompanied by constipation and inability to pass
gas).
Symptom of bowel obstruction (e.g. adhesions from previous surgery).

2. Diarrhea
Could be a sign of infection, malabsorption, osmotic diarrhea.
If bloody, it may be a sign of Infarction, volvulus, dysentery.

3. Anemia
Could be due to malabsorption of Iron, folic acid, vitamin B12.
Signs and symptoms of large bowel
disease
1. Diarrhea (Infection, laxative abuse, inflammatory bowel disease; Bloody - infarction or
dysentery).
2. Dysentery (bloody diarrhea with mucus; sign of infection).
3. Pain (Inflammatory bowel disease, ischemic colitis, diverticulitis, appendicitis,
peritonitis).
4. Tenesmus (Painful, ineffective straining at stool; ulcerative colitis).
5. Iron deficiency (polyps, colorectal cancer).
6. Hematochezia (Massive loss of whole blood per rectum; sigmoid diverticulosis,
angiodysplasia).
7. Black mucosa (chronic use of laxatives of the anthranoid group - senna and rhubarb
derivatives; Bowel is black because of an increase in submucosal macrophages with
lipofuscin pigment).
Diarrheal diseases (excluding
malabsorption)
1. Diarrhea
Definition - more than 250 g of stool per day.
Acute diarrhea is defined as less than 3 weeks, chronic diarrhea over 4 weeks.
Types - osmotic, secretory.
2. Important screening tests.
Fecal smear for leukocytes (e.g., invasive diarrhea).
Osmotic gap <50 mOsm/kg from POsm is a secretory diarrhea (diarrheal fluid POsm
approximates normal Posm).
Osmotic gap >100 mOsm/kg from POsm is an osmotic diarrhea (hypotonic loss of stool
due to presence of osmotically active substances).
3. Lactase deficiency Colon anaerobes degrade undigested lactose into lactic
acid and H2 gas, leading to abdominal distention with explosive diarrhea.
Treatment is to avoid dairy products.
 Osmotic diarrhea.
Stool output is proportional to the intake of the unabsorbable substrate and is usually
not massive.
Diarrheal stools promptly regress with discontinuation of the offending nutrient, and the
stool ion gap is high, exceeding 100 mOsm/kg.
In fact, the fecal osmolality in this circumstance is accounted for not only by the
electrolytes but also by the unabsorbed nutrient(s) and their degradation products.

Secretory diarrhea.
The epithelial cells ion transport processes are turned into a state of active secretion.
The most common cause of acute-onset secretory diarrhea is a bacterial infection of the
gut. Several mechanisms may be at work (adhesion or invasion of the epithelium;
production of enterotoxins or cytotoxins; triggering release of cytokines attracting
inflammatory cells, which, in turn, contribute to the activated secretion by inducing the
release of agents such as prostaglandins or platelet-activating factor).
Features of secretory diarrhea include a high purging rate, a lack of response to fasting
and a normal stool ion gap (<50 mOsm/kg), indicating that nutrient absorption is intact.
1. Rotavirus
Most common cause of childhood diarrhea; particularly occurs in winter months.
Fecal-oral transmission.
Rotavirus vaccine highly effective in prevention; oral vaccine.
Treatment: oral hydration; nitazoxanide.

2. Norovirus (Norwalk) virus

Most common cause of adult gastroenteritis.
Nausea, vomiting, diarrhea that resolves in 1224 hours.
Occasionally can be fatal.
Fecal-oral transmission.
Treatment: supportive.
3. Campylobacter jejuni
Animal reservoirs: cattle, chicken, puppies (common source for children).
Transmission fecal-oral (animal to human) via contaminated water, poultry, or
unpasteurized milk.
Most common food-borne illness and invasive enterocolitis in the United States.
Invasive and secretory enterocolitis: dysentery (bloody diarrhea) with crypt abscesses
and ulcers resembling ulcerative colitis.
High fever and cramping abdominal pain; organisms in stool with blood and leukocytes.
Complications: Guillain-Barr syndrome (antibodies cross-react with neurons);
hemolytic uremic syndrome; HLA-B27 positive seronegative spondyloarthropathy.
Diagnosis: culture, stool antigen, serology.
Treatment: erythromycin.
4. Clostridium difficile
Associated with pseudomembranous colitis; the most common cause of nosocomial
diarrhea, antibiotic-induced diarrhea and health careassociated diarrhea; secretory
type of diarrhea.
Person-to-person induced in 30% of cases; normally present in 3% of people; carrier rate
increases to >20% in hospitalized patients (related to fecal-oral contamination and
contact with spores in environment to a lesser extent).
Antibiotic-induced in 65%90% of cases; antibiotics (e.g., ampicillin, quinolones,
clindamycin) cause overgrowth of toxin-producing C. difficile in colon; antibiotic increase
gastrointestinal reabsorption of toxins A and B from the bacterial cell membrane; toxins
release proinflammatory mediators and cytokines that attract neutrophils and stimulate
excess fluid secretion (watery diarrhea).
Cytotoxin assay of diarrheal (not solid) stool has greater specificity (75%100%) than
culture of stool (75%80%) for securing the diagnosis; glutamate dehydrogenase
antigen test is also used and has excellent sensitivity and specificity (enzyme is present
in all strains of C. difficile).
Treatment: metronidazole; vancomycin produces resistant strains.
5. Escherichia coli
ETEC: certain strains produce toxin that activate adenylate or guanylate cyclase, causing
secretory diarrhea (travelers diarrhea; no fever; no bowel inflammation; accounts for
60% of cases).
Treatment: ciprofloxacin.
STEC (O157:H7 serotype): contracted by eating undercooked beef, bean sprouts,
undercooked cookies.
Produces gastroenteritis with bloody diarrhea and hemolytic uremic syndrome (HUS; in
8% of cases).
Antibiotics not recommended; may enhance toxin release.
Diagnosis: DNA assays; enzyme immunoassays for toxin.
6. Salmonella spp.
Pathogenic Salmonella: S. typhi, S. paratyphi, S. enteritidis.
Animal reservoirs: turtles, hamsters, lizards.
S. enteritidis enterocolitis: Second most common food-borne illness in United States;
contracted by eating raw or undercooked egg products, raw milk and milk products,
drinking contaminated water, or improper washing of the hands when handling
previously mentioned animal reservoirs (animal to human).
Treatment: ciprofloxacin or levofloxacin.
Typhoid fever caused by S. typhi: Week 1: invades Peyer patches and produces sepsis
(blood culture best for diagnosis); Week 2: diarrhea (positive stool culture); classic triad
of bradycardia, neutropenia, splenomegaly.
Treatment: treat if symptomatic with fluoroquinolone; antibiotics do not shorten the
illness and may increase frequency of carrier states.
Chronic carrier state due to gallbladder disease: cholecystectomy.
7. Entamoeba histolytica
Protozoa (amoeba).
Transmitted by ingestion of cysts in food and water.
Cysts are nonmotile and are present in formed stool; trophozoites are motile and are
present in diarrhea.
Produces dysentery (bloody diarrhea); cysts excyst in the cecum and become
trophozoites in the cecum; trophozoites release powerful histolytic agents that produce
flask-shaped ulcers; trophozoites can penetrate portal vein tributaries and drain to the
liver to produce a liver abscess (anchovy paste abscess); trophozoites can penetrate
hepatic vein tributaries and produce systemic disease.
Trophozoites characteristically phagocytose red blood cells.
Diagnosis: stool antigen test (sensitivity/specificity 100%).
Treatment: metronidazole (diarrhea/dysentery; extraintestinal disease); paromomycin
(asymptomatic cyst passer).
8. Giardia lamblia
Protozoa (flagellate).
Most common protozoal cause of diarrhea in United States.
Fecal-oral transmission by ingestion of cysts in food and water; reservoirs for Giardia that
contaminate water suppliesbeavers, voles, muskrats.
Common in day care centers, mental hospitals, hikers, water supplies (chlorination does not
kill the cysts), men who have sex with men (anal-oral contact), IgA deficiency, common
variable immunodeficiency.
Produces acute and chronic diarrhea with malabsorption (cysts in formed stool; trophozoites
in loose stools).
Diagnosis: stool antigen test (sensitivity/specificity 100%).
Treatment: tinidazole or nitazoxanide.
9. Enterobius vermicularis
Intestinal nematode.
Most common helminth in the United States; most contagious round worm worldwide.
Fecal-oral transmission by ingestion of eggs (infective form).
Eggs deposited in anus by adult worms cause pruritus ani.
Other infections: urethritis in girls; acute appendicitis.
No eosinophilia because adult worms are not invasive.
Treatment: mebendazole.
Sarcastic face of Giardia don't tell it that
your life sucks!
What is your opinion?
A student fails to use proper disinfection techniques in carrying out his
microbiology experiment. Two weeks later, he has spiking fevers and cramping
abdominal pain with diarrhea. On physical examination his temperature is 38.3C,
pulse 100/minute, respiratory rate 19/minute, and blood pressure 100/60 mm Hg.
He has a palpable spleen tip and diffuse abdominal pain without masses.
Laboratory studies show a WBC count of 2330/microliter, Hgb 13.8 g/dL, and
platelet count 282,000/microliter. Which of the following organisms was he most
likely using in his experiment?
Entameba histolytica
Clostridium difficile
Rotavirus
Salmonella typhi
Right answer
Salmonella typhi - He developed typhoid fever. Even though this is an acute
bacterial infection, mononuclear inflammation and leukopenia are typical
findings. Systemic findings are frequent.
Rotavirus - Rotavirus in adults produces a limited watery diarrhea. In young
children the fluid loss can be more devastating.
Clostridium difficile - C. difficile overgrowth produces a pseudomembranous colitis
that follows broad spectrum antibiotic usage.
Entameba histolytica - Amebiasis does not usually have pronounced systemic
symptoms, though it may rarely produce hepatic abscesses weeks after the lower
GI symptoms.
What is your opinion?
While on vacation in Mexico, a medical student develops severe watery diarrhea
without blood, abdominal pain, and nausea. He becomes increasingly dehydrated
and weak. Immediately after returning to Hong Kong, he seeks medical attention.
Stool examination is negative for fecal leukocytes, fat, or blood, and
sigmoidoscopy reveals normal mucosa. What is probable cause of this illness?

Entameba histolytica
Clostridium difficile
ETEC
Salmonella typhi
Right answer
ETEC - This patient has an infectious diarrheal illness frequently experienced by
travelers visiting places where sanitation and water supply may be suboptimal.
Because of the absence of blood and fecal leukocyte and the normal appearance
of gut mucosa, the most likely pathogen in this instance is an ETEC.
What is your opinion?
A 37-year-old woman with a 20-year history of Crohn disease presents to her
primary care physician complaining of fatigue. Physical examination reveals
tachycardia (heart rate: 106/min), pale conjunctivae, angular cheilitis and a beefy
red tongue. Relevant laboratory findings include a hematocrit of 21% and an
elevated mean corpuscular volume. What is the most likely diagnosis?
Vitamin B12 deficiency.
Iron deficiency.
Copper deficiency.
Zinc deficiency.
Malabsorption
1. Definition.
Chronic diarrhea with increased fecal excretion of fat (called steatorrhea).
Concurrent deficiencies of fat-soluble vitamins, minerals, carbohydrates, and proteins
may also occur.

2. Etiology and pathogenesis of fat malabsorption.

Pancreatic insufficiency.
Bile salt/acid deficiency.
Small bowel disease.
Pancreatic insufficiency.
Most often caused by chronic pancreatitis (MC due to alcohol in adults and cystic fibrosis
(CF) in children).
Mechanism: Dietary triglyceride (TG) is hydrolyzed by pancreatic lipase. Hydrolysis
yields monoglycerides (MGs) and fatty acids (FAs). In chronic pancreatitis, pancreatic
lipase is deficient and fats are undigested producing a fatty stool (steatorrhea).
Undigested neutral fats and fat droplets are present in stool.
Maldigestion of proteins is also present due to diminished pancreatic trypsin and
undigested meat fibers are in present in stool.
Carbohydrate absorption is not affected because amylase is present in the salivary
glands and disaccharidases are present in the brush border of the intestinal epithelium.
Bile salt/acid deficiency.
Causes - Inadequate synthesis of bile salts/acids from cholesterol (e.g.,
cirrhosis); Intrahepatic/extrahepatic blockage of bile (primary biliary cirrhosis,
stone in common bile duct); Bacterial overgrowth in small bowel with
destruction of bile salts/acids (small bowel diverticula, autonomic neuropathy);
Excess binding of bile salts (cholestyramine); Terminal ileal disease (prevents
recycling of bile salts/acids e.g. crohn disease, resection of the terminal ileum).
Bile salts/acid produce micelles to enhance reabsorption of fats by the small
intestinal villi. Micelles contain MGs, FAs, fat-soluble vitamins, and cholesterol
(CH) esters. All the fat soluble vitamins (vitamins A, D, E, and K) are packaged in
micelles along with the products of fat digestion. In bile salt deficiency, micelles
are not formed, which produces a fatty stool.
Small bowel disease.
Villi increase the absorptive surface of the small intestine required to reabsorb micelles
into enterocytes. Loss of the villi leads to loss of micelles in the stool.
3. Clinical findings.
Steatorrhea (excessive, large, sticky, stools that float).
Fat-soluble vitamin deficiencies (A, D, E, K).
Water-soluble vitamin deficiencies (particularly folic acid and vitamin B12).
Combined anemias (folic acid and iron deficiency).
Ascites and pitting edema (hypoproteinemia and decrease in oncotic pressure).

4. General screening tests for fat malabsorption.

Quantitative stool for fat - best screening test; Positive test >7 g fat/24 hours.
Qualitative stool for fat - Stains are used to identify fat in stool; Lacks sensitivity.
Decreased serum beta carotene - precursor for fat-soluble retinoic acid (vitamin A).
d-Xylose screening test - Xylose does not require pancreatic enzymes for absorption; Lack
of absorption of orally administered xylose indicates small bowel disease.
5. Tests to evaluate pancreatic insufficiency.
Serum immunoreactive trypsin - trypsin is specific for the pancreas. Concentration is
decreased in chronic pancreatitis. Concentration is increased in early cystic fibrosis
CT scan of pancreas shows dystrophic calcification - sign of chronic pancreatitis.
Secretin stimulation test (requires instrumentation) -tests ability of pancreas to secrete
fluids and electrolytes.
Bentiromide test -tests ability of pancreatic chymotrypsin to cleave orally administered
bentiromide to para-aminobenzoic acid (measured in urine).

6. Tests for bile salt/acid deficiency.

Total serum bile acids are decreased in liver disease (e.g., cirrhosis).

7. Tests for bacterial overgrowth.

14C-xylose - Most sensitive/specific test; Measures 14CO2 in the breath.
Lactulose-H2 - Measures H2 in the breath.
Bile breath test (oral radioactive test) - radioactive cholylglycine is converted by bacteria
into radioactive CO2 which is increased in the breath.
What is your opinion?
A 37-year-old woman with a 20-year history of Crohn disease presents to her
primary care physician complaining of fatigue. Physical examination reveals
tachycardia (heart rate: 106/min), pale conjunctivae, angular cheilitis and a beefy
red tongue. Relevant laboratory findings include a hematocrit of 21% and an
elevated mean corpuscular volume. What is the most likely diagnosis?
Vitamin B12 deficiency.
Iron deficiency.
Copper deficiency.
Zinc deficiency.
Right answer
Vitamin B12 deficiency - The most common cause of vitamin B12 deficiency is
pernicious anemia, an autoimmune disorder in which intrinsic factorproducing
gastric parietal cells are destroyed. Intrinsic factor is necessary for vitamin B12
absorption. Other causes include malabsorption (eg, celiac sprue, enteritis, or
Diphyllobothrium latum infection) and absence of the terminal ileum (as in Crohn
disease or surgical resection). Vitamin B12 deficiency is rarely due to insufficient
dietary intake. However, after several years, strict vegetarians are at risk, because
the nutrient is found only in animal products.
What is your opinion?
A 25-year-old man complains of a low volume but chronic, foul smelling diarrhea
for the past year. He has no nausea or vomiting. On physical examination there is
no abdominal pain or masses and bowel sounds are present. His stool is negative
for occult blood. Laboratory studies include a quantitative stool fat of 10 g/day.
Upper GI endoscopy is performed with biopsies taken of the duodenum, and on
microscopic examination show absence of villi, increased surface intraepithelial
lymphocytes, and hyperplastic appearing crypts. Which of the following therapies
is most likely to be useful for this man?
Antibiotics
Gluten-free diet
Corticosteroids
Segmental duodenal resection
Aromatherapy
What is your opinion?
A 46-year-old man has had malabsorption with 5 kg weight loss for the past year
associated with a low volume diarrhea. He also has a polyarthritis and complains of
occasional visual hallucinations. On physical examination there are no joint deformities. A
stool sample is negative for occult blood. An abdominal CT scan reveals no masses, only
generalized lymphadenopathy. On upper GI endoscopy, there are no esophageal or gastric
lesions, but there are broad, flattened villi in the duodenum. Biopsies of the duodenum
reveal numerous PAS-positive macrophages in the submucosa. Which of the following
therapies is most likely to be useful for this man?
Gluten-free diet
Corticosteroids
Antibiotics
Segmental duodenal resection
Aromatherapy
Whipple disease
1. Epidemiology.
Men>Women; Peak incidence in middle age.
2. Etiology.
Tropheryma whipplei - Identified by polymerase chain reaction.
3. Morphology.
Blunting of villi.
Foamy periodic acid-Schiff (PAS) positive macrophages in lamina propria.
Macrophages obstruct lymphatics and reabsorption of chylomicrons (malabsorption of fats).

4. Clinical findings
Steatorrhea; Fever; Recurrent polyarthritis; Generalized lymphadenopathy; Increased skin
pigmentation.
5. Treatment with antibiotics.
Celiac disease
1. Epidemiology.
Inappropriate immune response to gluten in wheat products (also related proteins in rye
and barley).
Prevalence of 1% in North America.
Common in whites; uncommon in blacks and Asians.
Occurs at any age.
Highest incidence in infancy (first introduction to gluten products); third decade
(frequent association with pregnancy) and seventh decade.
Associated with dermatitis herpetiformis, autoimmune disease (hashimoto thyroiditis,
primary biliary cirrhosis), type 1 diabetes mellitus, IgA deficiency, Down syndrome,
Turner syndrome.
2. Pathogenesis.
Multiorgan autoimmune disease
Inappropriate T-cell and IgA-mediated response against gluten in genetically
predisposed persons (association with HLA-DQ2 (95% of cases) and HLA-DQ8 (5% of
cases)).
Timing and dose when gluten is introduced in the diet is important.
Tissue transglutaminase (tTG; deaminating enzyme) deaminates mucosally absorbed
gluten to produce deaminated and negatively charged gluten peptides. Deaminated
gluten peptides stimulate the immune system. They are phagocytosed by antigen-
processing cells in the lamina propria. They are presented in complex with HLA-DQ2 or
HLA-DQ8 to gluten-specific CD4 helper T cells. CD4 T cells produce cytokines that
release matrix proteases causing cell death and degradation in the epithelial cells,
resulting in the loss of the villous surface in the small intestine.
3. Diagnosis.
Antitissue transglutaminase IgA (most important), IgG antibodies - Sensitivity and
specificity 98%; Excellent screening test
Antiendomysial (EMA) IgA antibodies - Sensitivity and specificity 100%; Excellent
screening test.
Antigliadin IgA, IgG antibodies - Sensitivity 80%, specificity 85%; Moderately good
screening test.
Total IgA levels.
Endoscopic biopsy - Flattened villi, particularly in duodenum and jejunum; Hyperplastic
glands with intense lymphocytic inflammation.
4. Clinical findings.
Steatorrhea.
Weight loss.
Failure to thrive in infants and children.
Pallor due to anemia (often combined anemias).
Dermatitis herpetiformis - Considered to be a form of celiac disease; Villous atrophy in
75% of cases with or without diarrhea; Low levels of the diagnostic antibodies previously
mentioned.
Findings related to water-soluble and fat-soluble vitamin deficiencies.
Other systemic findings Bone (osteoporosis, arthritis); CNS (seizures, depression);
Reproductive (delayed puberty, miscarriages, infertility).

5. Treatment.
Gluten-free diet.
Correct nutritional deficiencies - all fat-soluble vitamins; folic acid, vitamin B ; 12

calcium.
Corticosteroids in refractory cases.
What is your opinion?
A 25-year-old man complains of a low volume but chronic, foul smelling diarrhea
for the past year. He has no nausea or vomiting. On physical examination there is
no abdominal pain or masses and bowel sounds are present. His stool is negative
for occult blood. Laboratory studies include a quantitative stool fat of 10 g/day.
Upper GI endoscopy is performed with biopsies taken of the duodenum, and on
microscopic examination show absence of villi, increased surface intraepithelial
lymphocytes, and hyperplastic appearing crypts. Which of the following therapies
is most likely to be useful for this man?
Antibiotics
Gluten-free diet
Corticosteroids
Segmental duodenal resection
Aromatherapy
Right answer
Gluten-free diet - He has celiac disease from ingestion of grains (wheat, rye,
barley, oats) that contain gluten with gliaden protein. The enzyme tissue
transglutamidase breaks down the gliaden into peptides which, when displayed to
antigen presenting cells, activate CD4 lymphocytes that produce the mucosal
inflammation.
What is your opinion?
A 46-year-old man has had malabsorption with 5 kg weight loss for the past year
associated with a low volume diarrhea. He also has a polyarthritis and complains of
occasional visual hallucinations. On physical examination there are no joint deformities. A
stool sample is negative for occult blood. An abdominal CT scan reveals no masses, only
generalized lymphadenopathy. On upper GI endoscopy, there are no esophageal or gastric
lesions, but there are broad, flattened villi in the duodenum. Biopsies of the duodenum
reveal numerous PAS-positive macrophages in the submucosa. Which of the following
therapies is most likely to be useful for this man?
Gluten-free diet
Corticosteroids
Antibiotics
Segmental duodenal resection
Aromatherapy
Right answer
Antibiotics - Whipple disease is rare. It can affect multiple organs, including the
brain. The organisms causing Whipple disease are actinomycetes (Tropheryma
whippelii). The foamy macrophages can be in the small intestinal submucosa,
adjacent lymph nodes, or at extraintestinal sites.