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DIARRHEA
Diarrhea is a common symptom that
can range in severity from an acute,
self-limited annoyance to a severe,
life-threatening illness. Patients may
use the term "diarrhea" to refer to
increased frequency of bowel
movements, increased stool liquidity,
a sense of fecal urgency, or fecal
incontinence
Definition
• In the normal state, approximately 10 L of
fluid enter the duodenum daily, of which all
but 1.5 L are absorbed by the small
intestine. The colon absorbs most of the
remaining fluid, with only 100 mL lost in
the stool. From a medical standpoint,
diarrhea is defined as a stool weight of more
than 250 g/24 h
• The causes of diarrhea are myriad.
In clinical practice, it is helpful to
distinguish acute from chronic
diarrhea, as the evaluation and
treatment are entirely different
Causes of acute infectious
diarrhea
•
1.
2.
3.
Noninflammatory Diarrhea
Viral - Norwalk virus, Norwalk-like virus, Rotavirus
Protozoal - Giardia lamblia, Cryptosporidium
Bacterial - Preformed enterotoxin production
Staphylococcus aureus, Bacillus
cereus, Clostridium perfringens
Enterotoxin production; Enterotoxigenic E coli
(ETEC), Vibrio cholerae
Inflammatory Diarrhea
• Viral – Cytomegalovirus
• Protozoal - Entamoeba histolytica
• Bacterial - Cytotoxin productio;
Enterohemorrhagic E coli, Vibrio
parahaemolyticus, Clostridium difficile.
Mucosal invasion; Shigella, Campylobacter jejuni
Salmonella, Enteroinvasive E coli ,Aeromonas
Plesiomonas,Yersinia enterocolitica,Chlamydia
Neisseria gonorrhoeae, Listeria monocytogenes
Causes of chronic diarrhea
• Osmotic diarrhea
Stool volume decreases with fasting;
increased stool osmotic gap
1. Medications: antacids, lactulose, sorbitol
2. Disaccharidase deficiency: lactose
intolerance
3. Factitious diarrhea: magnesium (antacids,
laxatives)
CLUES:
Secretory diarrhea
• Large volume ( >1 L/d); little change with fasting;
normal stool osmotic gap
1. Hormonally mediated: VIPoma, carcinoid,
medullary carcinoma of thyroid (calcitonin),
Zollinger-Ellison syndrome (gastrin)
2. Factitious diarrhea (laxative abuse):
phenolphthalein, cascara, senna
3. Villous adenoma
4. Bile salt malabsorption (ileal resection; Crohn's
ileitis; postcholecystectomy)
5. Medications
Inflammatory conditions
• Fever, hematochezia, abdominal pain
1. Ulcerative colitis
2. Crohn's disease
3. Microscopic colitis
4. Malignancy: lymphoma, adenocarcinoma
(with obstruction and pseudodiarrhea)
5. Radiation enteritis
Malabsorption syndromes
• Weight loss, abnormal laboratory values; fecal fat
> 7-10 g/24 h, tropical sprue, Whipple's disease,
eosinophilic gastroenteritis, Crohn's disease, small
bowel resection (short bowel syndrome)
2. Lymphatic obstruction: lymphoma, carcinoid,
infectious (TB, MAI), Kaposi's sarcoma,
sarcoidosis, retroperitoneal fibrosis
3. Pancreatic disease: chronic pancreatitis, pancreatic
carcinoma
4. Bacterial overgrowth: motility disorders (diabetes,
vagotomy, scleroderma), fistulas, small intestinal
diverticula
Motility disorders
• Systemic disease or prior abdominal surgery
1. Postsurgical: vagotomy, partial
gastrectomy, blind loop with bacterial
overgrowth
2. Systemic disorders: scleroderma, diabetes
mellitus, hyperthyroidism
3. Irritable bowel syndrome
Chronic infections
• Parasites: Giardia lamblia, Entamoeba
histolytica, Cyclospora
• AIDS-related:
• Viral: Cytomegalovirus, HIV infection (?)
• Bacterial: Clostridium difficile,
Mycobacterium avium complex
• Protozoal: Microsporida (Enterocytozoon
bieneusi ), Cryptosporidium, Isospora belli
ACUTE DIARRHEA
• Diarrhea that is acute in onset and
persists for less than 3 weeks is most
commonly caused by infectious agents,
bacterial toxins (either ingested
preformed in food or produced in the
gut), or drugs
• Recent ingestion of improperly stored or
prepared food implicates food poisoning,
especially if other people were similarly
affected. Exposure to unpurified water
(camping, swimming) may result in
infection with Giardia or Cryptosporidium
TRAVELER'S DIARRHEA
• Whenever a person travels from one
country to another—particularly if the
change involves a marked difference in
climate, social conditions, or sanitation
standards and facilities—diarrhea is likely
to develop within 2–10 days
• There may be up to ten or even more loose stools
per day, often accompanied by abdominal cramps,
nausea, occasionally vomiting, and rarely fever.
The stools do not usually contain mucus or blood,
and aside from weakness, dehydration, and
occasionally acidosis, there are no systemic
manifestations of infection. The illness usually
subsides spontaneously within 1–5 days, although
10% remain symptomatic for a week or longer,
and in 2% symptoms persist for longer than a
month
• Bacteria cause 80% of cases of traveler's diarrhea,
with enterotoxigenic E coli, Shigella species, and
Campylobacter jejuni being the most common
pathogens. Less common causative agents include
Aeromonas, Salmonella, noncholera vibrios,
Entamoeba histolytica, and Giardia lamblia.
Contributory causes may at times include unusual
food and drink, change in living habits, occasional
viral infections (adenoviruses or rotaviruses), and
change in bowel flora
• For most individuals, the affliction is short-lived,
and symptomatic therapy with opiates or
diphenoxylate with atropine is all that is required
provided the patient is not systemically ill (fever ł
39 °C) and does not have dysentery (bloody
stools), in which case antimotility agents should
be avoided. Packages of oral rehydration salts to
treat dehydration are available over the counter in
the USA and in many foreign countries
• Avoidance of fresh foods and water sources
that are likely to be contaminated is
recommended for travelers to developing
countries, where infectious diarrheal
illnesses are endemic. Prophylaxis is
recommended for those with significant
underlying disease (inflammatory bowel
disease, AIDS, diabetes, heart disease in the
elderly
• Prophylaxis is started upon entry into the destination
country and is continued for 1 or 2 days after leaving. For
stays of more than 3 weeks, prophylaxis is not
recommended because of the cost and increased toxicity.
For prophylaxis, bismuth subsalicylate is effective but
turns the tongue and the stools blue and can interfere with
doxycycline absorption, which may be needed for malaria
prophylaxis. Numerous antimicrobial regimens for oncedaily prophylaxis also are effective, such as norfloxacin
400 mg, ciprofloxacin 500 mg, ofloxacin 300 mg, or
trimethoprim-sulfamethoxazole 160/800 mg. daily for 5
days
• Because not all travelers will have diarrhea and because
most episodes are brief and self-limited, an alternative
approach that is currently recommended is to provide the
traveler with a 3- to 5-day supply of antimicrobials to be
taken if significant diarrhea occurs during the trip.
Commonly used regimens include ciprofloxacin 500 mg
twice daily, ofloxacin 300 mg twice daily, or norfloxacin
400 mg twice daily. Trimethoprim-sulfamethoxazole
160/800 mg twice daily can be used as an alternative
(especially in children), but resistance is common in many
areas. Aztreonam, a poorly absorbed monobactam with
activity against most bacterial enteropathogens, also is
efficacious when given orally in a dose of 100 mg three
times
Noninflammatory Diarrhea
• Watery, nonbloody diarrhea associated with
periumbilical cramps, bloating, nausea, or
vomiting (singly or in any combination) suggests
small bowel enteritis caused by either a toxinproducing bacterium (enterotoxigenic E coli
[ETEC], Staphylococcus aureus, Bacillus cereus,
C perfringens) or other agents (viruses, Giardia)
that disrupt the normal absorption and secretory
process in the small intestine.
• Prominent vomiting suggests viral enteritis or S
aureus food poisoning. Though typically mild, the
diarrhea (which originates in the small intestine)
may be voluminous (ranging from 10 to 200
mL/kg/24 h) and result in dehydration with
hypokalemia and metabolic acidosis due to loss of
HCO3– in the stool (eg, cholera). Because tissue
invasion does not occur, fecal leukocytes are not
present.
Inflammatory Diarrhea
• The presence of fever and bloody diarrhea
(dysentery) indicates colonic tissue damage caused
by invasion (shigellosis, salmonellosis,
Campylobacter or Yersinia infection, amebiasis) or
a toxin (C difficile, E coli O157:H7). Because
these organisms involve predominantly the colon,
the diarrhea is small in volume (< 1 L/d) and
associated with left lower quadrant cramps,
urgency, and tenesmus.
• Fecal leukocytes are present in infections with
invasive organisms. E coli O157:H7 is a toxigenic,
noninvasive organisms that may be acquired from
contaminated meat or unpasteurized juice and has
resulted in several outbreaks of an acute, often
severe hemorrhagic colitis. In
immunocompromised and HIV-infected patients,
cytomegalovirus may result in intestinal ulceration
with watery or bloody diarrhea
Enteric Fever
• A severe systemic illness manifested
initially by prolonged high fevers,
prostration, confusion, respiratory
symptoms followed by abdominal
tenderness, diarrhea, and a rash is due to
infection with Salmonella typhi or
Salmonella paratyphi, which causes
bacteremia and multiorgan dysfunction
Evaluation
• In over 90% of patients with acute diarrhea, the
illness is mild and self-limited and responds
within 5 days to simple rehydration therapy or
antidiarrheal agents
• Patients with signs of inflammatory diarrhea
manifested by any of the following require prompt
medical attention: high fever (> 38.5 °C), bloody
diarrhea, abdominal pain, or diarrhea not
subsiding after 4–5 days. Similarly, patients with
symptoms of dehydration must be evaluated
(excessive thirst, dry mouth, decreased urination,
weakness, lethargy)
• Physical examination should note the patient's
general appearance, mental status, volume status,
and the presence of abdominal tenderness or
peritonitis
• Peritoneal findings may be present in C difficile
and enterohemorrhagic E coli. Hospitalization is
required in patients with severe dehydration,
toxicity, or marked abdominal pain. Stool
specimens should be sent in all cases for
examination for fecal leukocytes and bacterial
cultures
• The rate of positive bacterial cultures in patients with
dysentery is 60–75%. A wet mount examination of the
stool for amebiasis should also be performed in patients
with dysentery who have a history of recent travel to
endemic areas or those who are homosexuals. In patients
with a history of antibiotic exposure, a stool sample should
be sent for C difficile toxin. If E coli O157:H7 is
suspected, the laboratory must be alerted to do specific
serotyping. In patients with diarrhea that persists for more
than 10 days, three stool examinations for ova and
parasites also should be performed. Rectal swabs may be
sent for Chlamydia, Neisseria gonorrhoeae, and herpes
simplex virus in sexually active patients with severe
proctitis
Treatment
• Diet :The overwhelming majority of adults have
mild diarrhea that will not lead to dehydration
provided the patient takes adequate oral fluids
containing carbohydrates and electrolytes. Patients
will find it more comfortable to rest the bowel by
avoiding high-fiber foods, fats, milk products,
caffeine, and alcohol. Frequent feedings of fruit
drinks, tea, "flat" carbonated beverages, and soft,
easily digested foods (eg, soups, crackers) are
encouraged
Rehydration
• In more severe diarrhea, dehydration can
occur quickly, especially in children. Oral
rehydration with fluids containing glucose,
Na+, K+, Cl–, and bicarbonate or citrate is
preferred in most cases to intravenous fluids
because it is inexpensive, safe, and highly
effective in almost all awake patients
• An easy mixture is ˝ tsp salt (3.5 g), 1 tsp baking
soda (2.5 g NaHCO3), 8 tsp sugar (40 g), and 8 oz
orange juice (1.5 g KCl), diluted to 1 L with water.
Alternatively, oral electrolyte solutions (eg,
Pedialyte) are readily available. Fluids should be
given at rates of 50–200 mL/kg/24 h depending on
the hydration status. Intravenous fluids (lactated
Ringer's solution) are preferred acutely in patients
with severe dehydration.
Antidiarrheal Agents
• Loperamide is the preferred drug in a dosage of 4 mg
initially, followed by 2 mg after each loose stool
(maximum:16 mg/24 h
• Bismuth subsalicylate (Pepto-Bismol), two tablets or
30 mL four times daily, reduces symptoms in patients
with traveler's diarrhea by virtue of its antiinflammatory and antibacterial properties
• Anticholinergic agents are contraindicated in acute
diarrhea
Antibiotic Therapy
• Empiric treatment-fluoroquinolones (eg,
ciprofloxacin, 500 mg twice daily) for 5–7 days.
These agents provide good antibiotic coverage
against most invasive bacterial pathogens,
including Shigella, Salmonella, Campylobacter,
Yersinia, and Aeromonas. Alternative agents are
trimethoprim-sulfamethoxazole, 160/800 mg twice
daily, or erythromycin, 250–500 mg four times
daily
• Specific antimicrobial treatment- Antibiotics are
not generally recommended in patients with
nontyphoid Salmonella, Campylobacter, or
Yersinia infection except in severe or prolonged
disease because they have not been shown to
hasten recovery or reduce the period of fecal
bacterial excretion. The infectious diarrheas for
which treatment is clearly recommended are
shigellosis, cholera, extraintestinal salmonellosis,
"traveler's" diarrhea, C difficile infection,
giardiasis, amebiasis, and the sexually transmitted
infections (gonorrhea, syphilis, chlamydiosis, and
herpes simplex infection)
CHRONIC DIARRHEA
• Etiology
The causes of chronic diarrhea may
be grouped into six major
pathophysiologic categories
Osmotic Diarrheas
• As stool leaves the colon, fecal osmolality
is equal to the serum osmolality, ie,
approximately 290 mosm/kg. Under normal
circumstances, the major osmoles are Na+,
K+, Cl–, and HCO3–. The stool osmolality
may be estimated by multiplying the stool
(Na+ + K+) × 2 (multiplied by 2 to account
for the anions)
• The osmotic gap is the difference between
the measured osmolality of the stool (or
serum) and the estimated stool osmolality
and is normally less than 50 mosm/kg
• An increased osmotic gap implies that the
diarrhea is caused by ingestion or
malabsorption of an osmotically active
substance
• The most common causes of osmotic diarrhea are
disaccharidase deficiency (lactase deficiency),
laxative abuse, and malabsorption syndromes (see
below). Osmotic diarrheas resolve during fasting.
Osmotic diarrheas caused by malabsorbed
carbohydrates are characterized by abdominal
distention, bloating, and flatulence due to
increased colonic gas production.
Malabsorptive Conditions
• The major causes of malabsorption are
small mucosal intestinal diseases, intestinal
resections, lymphatic obstruction, small
intestinal bacterial overgrowth, and
pancreatic insufficiency
• In patients with suspected malabsorption,
quantification of fecal fat should be
performed
Secretory Conditions
• Increased intestinal secretion or decreased
absorption results in a watery diarrhea that may be
large in volume (1–10 L/d) but with a normal
osmotic gap
• here is little change in stool output during the
fasting state. In serious conditions, significant
dehydration and electrolyte imbalance may
develop. Major causes include endocrine tumors
(stimulating intestinal or pancreatic secretion), bile
salt malabsorption (stimulating colonic secretion),
and laxative abuse
Inflammatory Conditions
• Diarrhea is present in most patients with
inflammatory bowel disease (ulcerative
colitis, Crohn's disease, microscopic colitis).
A variety of other symptoms may be
present, including abdominal pain, fever,
weight loss, and hematochezia
Motility Disorders
• Abnormal intestinal motility secondary to
systemic disorders or surgery may result in
diarrhea due to rapid transit or to stasis of
intestinal contents with bacterial overgrowth
resulting in malabsorption
Chronic Infections
• Chronic parasitic infections may cause diarrhea through a
number of mechanisms. Although the list of parasitic
organisms is a long one, agents most commonly
associated with diarrhea include the protozoans Giardia,
E histolytica, Cyclospora, and the intestinal nematodes
• Immunocompromised patients, especially those with
AIDS, are susceptible to a number of infectious agents
that can cause acute or chronic diarrhea
Chronic diarrhea in AIDS is commonly caused by
Microsporida, Cryptosporidium, cytomegalovirus, Isospora
belli, Cyclospora, and Mycobacterium avium complex.
Factitial Diarrhea
• Approximately 15% of patients with
chronic diarrhea have factitial diarrhea
caused by surreptitious laxative abuse or
factitious dilution of stool
Evaluation
• Stool Analysis - Twenty-four-hour stool
collection for weight and quantitative fecal
fat–A stool weight of more than 300 g/24 h
confirms the presence of diarrhea, justifying
further workup. A weight greater than
1000–1500 g suggests a secretory process.
A fecal fat in excess of 10 g/24 h indicates a
malabsorptive process
• 2. Stool osmolality–An osmotic gap confirms
osmotic diarrhea. A stool osmolality less than the
serum osmolality implies that water or urine has
been added to the specimen (factitious diarrhea).
• 3. Stool laxative screen–In cases of suspected
laxative abuse, stool magnesium, phosphate, and
sulfate levels may be measured. Phenolphthalein,
senna, and cascara are indicated by the presence of
a bright-red color after alkalinization of the stool
or urine. Bisacodyl can be detected in the urine
4. Fecal leukocytes–The presence of
leukocytes in a stool sample implies an
underlying inflammatory diarrhea.
• 5. Stool for ova and parasites–The presence
of Giardia and E histolytica is detected in
routine wet mounts. Cryptosporidium and
Cyclospora are detected with modified acidfast staining.
Blood Tests
• Routine laboratory tests–CBC, serum electrolytes, liver
function tests, calcium, phosphorus, albumin, TSH,
total T4, beta-carotene, and prothrombin time should
be obtained. Anemia occurs in malabsorption
syndromes (vitamin B12, folate, iron) and
inflammatory conditions. Hypoalbuminemia is present
in malabsorption, protein-losing enteropathies, and
inflammatory diseases. Hyponatremia and non–anion
gap metabolic acidosis may occur in profound secretory
diarrheas. Malabsorption of fat-soluble vitamins may
result in an abnormal prothrombin time, low serum
calcium, low carotene, or abnormal serum alkaline
phosphatase
Other laboratory tests
• In patients with suspected secretory diarrhea,
serum VIP (VIPoma), gastrin (Zollinger-Ellison
syndrome), calcitonin (medullary thyroid
carcinoma), cortisol (Addison's disease), and
urinary 5-HIAA (carcinoid syndrome) levels
should be obtained
• Proctosigmoidoscopy With Mucosal Biopsy:
Examination may be helpful in detecting
inflammatory bowel disease (including
microscopic colitis) and melanosis coli, indicative
of chronic use of anthraquinone laxatives.
Imaging
• Calcification on a plain abdominal radiograph
confirms the diagnosis of chronic pancreatitis. An upper
gastrointestinal series or enteroclysis study is helpful in
evaluating Crohn's disease, lymphoma, or carcinoid
syndrome. Colonoscopy is helpful in evaluating colonic
inflammation due to inflammatory bowel disease. Upper
endoscopy with small bowel biopsy is useful in suspected
malabsorption due to mucosal diseases. Upper endoscopy
with a duodenal aspirate and small bowel biopsy is also
useful in patients with AIDS and to document
Cryptosporidium, Microsporida, and M aviumintracellulare infection. Abdominal CT is helpful to
detect chronic pancreatitis or pancreatic endocrine tumors.
Treatment
• A. Loperamide: 4 mg initially, then 2 mg after
each loose stool (maximum: 16 mg/d)
• Diphenoxylate With Atropine: One tablet three or
four times daily
• Codeine, Paregoric: Because of their addictive
potential, these drugs are generally avoided except
in cases of chronic, intractable diarrhea. Codeine
may be given in a dosage of 15–60 mg every 4
hours as needed; the dosage of paregoric is 4–8
mL after each liquid bowel movement
• Clonidine: a2-Adrenergic agonists inhibit
intestinal electrolyte secretion. A clonidine patch
that delivers 0.1–0.2 mg/d for 7 days may be
useful in some patients with secretory diarrheas,
cryptosporidiosis, and diabetes.
. Octreotide: This somatostatin analog stimulates
intestinal fluid and electrolyte absorption and
inhibits secretion. Furthermore, it inhibits the
release of gastrointestinal peptides. It is very
useful in treating secretory diarrheas due to
VIPomas and carcinoid tumors and in some cases
of diarrhea associated with AIDS. Effective doses
range from 50 mg to 250 mg subcutaneously three
times daily. A dosage of 4 g one to three times
daily is recommended
• Cholestyramine: This bile salt binding resin
may be useful in patients with bile saltinduced diarrhea secondary to intestinal
resection or ileal disease