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The differential diagnosis of diarrhea may be approached from either an anatomic or a physiologic basis.
The anatomic approach is used in Table 22. In the stomach and duodenum, pernicious anemia and
ZollingerEllison syndrome are prominent causes. A carcinoma may form a fistula with the transverse colon
and cause diarrhea. Viral gastroenteritis, and Giardia infection may also be prominent causes.
DIARRHEA
Liver and biliary tract diseases of all types may cause diarrhea (steatorrhea) by decreasing the secretion of
bile. Ampullary carcinoma and cirrhosis are illustrated here, but one should not forget the diarrhea of chronic
cholecystitis. The pancreas is the source of important digestive enzymes; as a result, chronic pancreatitis
and pancreatic carcinomas may be associated with diarrhea (steatorrhea) in adults, whereas cystic fibrosis
should be considered in children. The pancreatic islet cell tumors may secrete gastrin or vasoactive
intestinal peptide, causing diarrhea.
Most of the lesions causing diarrhea are in the small intestine. Thus, cholera, Salmonella, Staphylococci,
typhoid, and tuberculosis attack here. The carcinoid syndrome, various polyps (especially PeutzJeghers),
and regional ileitis are also important causes. Toxins and drugs (Table 22) are common causes acting here,
as are pellagra and other vitamin deficiencies and food allergies. Systemic autoimmune diseases such as
scleroderma and Whipple disease are also important. Mesentery artery insufficiency or obstruction should
be considered both here and in the colon.
TABLE 22. DIARRHEAANATOMIC CLASSIFICATION
Degener
Vascula
Inflammat
Neopla
ory
sm
ative
Intoxication
and
and
Deficien
Idiopathic
Congen
ital
Autoimmu
ne
Allergic
Trau
ma
Endocrine
cy
Carcin
Stoma
ch and
Duode
num
oma
Surg
Viral
with
Pernicio
gastroent
fistula
us
eritis
into
anemia
Uremia
intestin
ery
Zollinger
(e.g.
Ellison
blind
syndrome
loop)
es
Iron
Parasite
deficienc
Antacid
Neopla
Liver
and
Chronic
sm
cholecystit obstruc
Biliary
is and
ting
Tract
lithiasis
bile
Cirrhosis
Cirrhosis
ducts
Pancre
as
Chronic
pancreatiti
s
Pancre
atic
carcino
ma
Radiation
Cystic
Pancreatic
fibrosis
cholera
Degener
Vascula
Inflammat
Neopla
ory
sm
ative
Intoxication
and
and
Deficien
Idiopathic
Congen
ital
Autoimmu
ne
Allergic
Trau
ma
Endocrine
cy
Islet
cell
adeno
ma
Peutz
Mesent
Small
eric
Intestin
artery
insuffici
Jehgers
Cholera
Carcin
oid
Pellagra
Sprue
divertic
Regional
Fistul
Hypoparathy
ulum
ileitis
roidism
(Meckel
ency
Pyridoxi
Botulism
Polyp
ne
deficienc
Cathartic
Whipple
Hyperthyroidi
disease
sm
Scleroder
Addison
ma
disease
Staphyloc
Sarco
occus
ma
Salmonell
Lymph
oma
Escherichi
Mercurial
Reserpine
Antibiotic
Degener
Vascula
Inflammat
Neopla
ory
sm
ative
Intoxication
and
and
Deficien
Idiopathic
Congen
ital
Autoimmu
ne
Allergic
cy
a coli
Parasites
Alcohol
Tuberculo
Other
sis
drugs
Mesent
Large
eric
Intestin
artery
insuffici
Shigella
Polyp
Mucus
colitis
Familial
polypos
is
Ulcerative
colitis
ency
Carcin
oma
Amebiasis
and
Diverticulo
other
sis
neopla
Granulom
atous
colitis
sms
Other
parasites
Antibiotic
Hypervitam
Food
allergy
Trau
ma
Endocrine
Degener
Vascula
Inflammat
Neopla
ory
sm
ative
Intoxication
and
and
Deficien
Idiopathic
Congen
ital
Autoimmu
ne
Allergic
Trau
ma
Endocrine
cy
inosis
Uremia
A wide variety of etiologic agents cause diarrhea by their action on the colon.
1.
2.
3.
4.
5.
6.
7.
8.
9.
Having considered the local causes of diarrhea, do not forget reflex diarrhea from diseases of other organs,
such as pyelonephritis, salpingo-oophoritis, and central nervous system diseases.
Using Table 23, the reader can develop the differential diagnosis of diarrhea with physiology. Diarrhea may
result from increased intake of fluids or bulk foods; hyposecretion of enzymes necessary for digestion of
food; hypersecretion of gastrointestinal fluids and enzymes; malabsorption of various substances,
particularly protein and fat; exudations of pus induced by granulomatous or ulcerative colitis and
Salmonella or Shigella infections; hypermobility from stimulation by cathartics, various hormones (e.g.,
vasoactive intestinal peptides and gastrin), and hypomobility from autonomic dysfunction as occurs in
diabetic neuropathy.
TABLE 23. DIARRHEAPHYSIOLOGIC CLASSIFICATION
Gastric
Pernicious
anemia
Hypermobility
Primary
Malabsorption
Zollinger
Ellison
Dumping syndrome
syndrome
Iron
deficiency
Gastric
resection
Duodenal
Lactase
Blind loop
deficiency
syndrome
Secretion-induced
Sucrase
deficiency
Biliary
Liver
Cholecystokinin
Cholecystokini
disease
induced
n-induced
Obstructive
Regional ileitis
jaundice
Pancreati
Cystic
Pancreatic
fibrosis
cholera (islet
cell adenoma
Gastrin
Exudative
Hypermobility
Primary
Malabsorption
Exudative
with
vasoactive
intestinal
peptide)
Small
Intestine
Chronic
Vasoactive
pancreatitis
intestinal peptide
Cholera (e.g.,
Escherichia
coli)
Diabetic
diarrhea
Drugs
Coffee
Celiac sprue
Serotonin-induced
Tropical sprue
Cathartic
Regional
ileitis
Salmonellosi
s
Whipple
disease
Parasympathomime
Intestinal
tic
lymphoma
Extensive
resection
Protein-losing
Large
enteropathy
Intestine
(e.g., villous
adenoma)
Shigella
Hypermobility
Primary
Malabsorption
Exudative
Ulcerative
colitis
Amebiasis
Diarrhea
Lonny M. Hecker, M.D., David R. Saunders, M.D., and David Losh, M.D.
1.0 Introduction
Diarrhea affects most individuals at some time during their lives. The occasional
loose or watery stool is so common that few individuals seek medical advice,
unless the diarrhea is persistent. In this chapter diarrhea is divided into acute and
chronic categories based on whether it has been present for less than or greater
than four weeks.
This chapter will present evidenced based recommendations for the evaluation
and treatment of diarrhea in adults. The information provided is not necessarily
applicable to children and should not be used to guide pediatric practice. It
includes important papers published prior to 1990 and those accessed via a
MEDLINE search, 1990 - 1998, using the MeSH headings Diarrhea, acute, and
diarrhea, chronic. Other headings searched included malabsorptive syndrome,
and Fordtran, JS, whose research group has made so many contributions to the
subject.
2.0 Physiology and Pathophysiology
Diarrhea results when the remarkable efficiency of the gut for absorbing water,
electrolyte, and nutrients is impaired. About 9-10 liters of water and electrolyte
enter the upper jejunum daily, of which one liter is delivered to the cecum, and
one-tenth of a liter is delivered to the outside world. Decreasing this efficiency
from 99% to 98% would double fecal water to produce potentially a wetter stool.
A great variety of drugs, toxins, pathogens, and food stuffs can impair the
efficiency of salt and water absorption.
The chief contribution of the stomach to digestion and absorption is metered
delivery of food and drink to the small intestine so that the absorptive capacity of
the upper small intestine is not overwhelmed.
Carbohydrate and protein in the small and large intestines are especially
important in increasing the efficiency of sodium and water absorption. Soluble
starches are digested by pancreatic amylase into small chains of glucose
molecules which, together with the ingested disaccharides (lactose and sucrose),
are hydrolyzed to monomers by brush border enzymes.
Absorption of sodium (and water) is coupled to the absorption of glucose and
galactose, especially in the duodenum and jejunum. Much of the available sugars
have been absorbed when chyme arrives in the ileum, where sodium absorption
relies on sodium/hydrogen and chloride/bicarbonate exhangers. Carbohydrate
those at risk who require urgent intervention. It is, therefore, incumbent on the
primary care provider to carefully select both diagnostic tests and therapeutic
modalities. This is one area of clinical medicine where careful history and
physical are still of paramount importance.
3.1 Background
3.1.1 Incidence
The overall incidence of acute diarrhea in adults is difficult to determine. Most
episodes are self-limited and probably do not involve the health care provider.
Epidemiologists have examined the impact of acute diarrheal disease on the
health care system by looking at the number of adult patients hospitalized with
the diagnosis of diarrhea using the International Classification of Diseases, Ninth
revision (ICD-9) codes for both infectious and presumed non-infectious
diarrhea. One study, in the southeast United States found that, of a total 4.06
million hospitalizations in 1985, 2.1% listed diarrhea among the top threedischarge diagnoses [Gangarosa, 1992]. Diarrhea was strongly associated with
9% of all hospitalizations of children and 1.5% of hospitalizations of adults.
Certain circumstances are associated with an especially high incidence of acute
diarrheal disease. Operation Desert Shield involved the deployment of 200,000
US military personnel in Saudi Arabia. The rate of diarrheal disease in this group
soared to as much as 100 cases per 1000 soldiers per week in some units
[Hyams, 1991]. 57% of surveyed troops reported at least one episode of diarrhea
and 20% reported to be temporarily disabled due to diarrhea. Enterotoxigenic
E. coli, Shigella and Norwalk virus appeared to be the most common etiological
agents.
3.1.2 Morbidity and Mortality
Diarrhea is a major cause of childhood disease in the developing world. Global
mortality estimates from diarrhea and its complications range from 1.5 to 5.1
million deaths per year for children under the age of five [Bern, 1992]. Acute
diarrheal illness is also associated with adult mortality in the United States. In
fact, age over 70 years is the most important risk factor for death related to
diarrhea.
The National Center for Health Statistics data indicates more than 25,000
persons died of diarrhea in the US between 1979 and 1987 [Lew, 1991].
Seventy-eight per cent of these individuals were 55 years of age or older. Being
white, female and residing in a nursing home were independent risk factors for
death among the elderly.
3.1.3 Foodborne Disease
Acute diarrhea occurring in travelers and persons with AIDS warrants certain
special considerations and will be discussed later.
3.2.1 Acute Watery Diarrhea with Nausea and Vomiting
Acute watery diarrhea associated with nausea and vomiting is typically called
gastroenteritis. Most cases are infectious, due to either bacteria or viruses.
3.2.1.1 Staphylococcus aureus
Staphylococcus aureus infection is characterized by the sudden onset of
abdominal pain, nausea, vomiting, and diarrhea and in a minority of cases fever
(Table 2). Symptoms are due to ingestion of preformed toxin which is usually in
foods which are cooked and then improperly stored at room temperature
[Holmberg, 1984]. Antimicrobial therapy is not recommended for S. aureus
associated diarrhea because symptoms are due to preformed toxin and are selflimited.
3.2.1.2 Viral Gastroenteritis
Acute diarrhea, vomiting and fever are the hallmarks of viral gastroenteritis,
which accounts for 30-40% of all acute diarrheal illness in the US (Table 2).
Symptoms result from reduced absorptive surface in the small intestine due to
viral mediated lysis of enterocytes. Most viral gastroenteritis is caused by one of
five viruses. Rotavirus accounts for 30-60% of all severe watery diarrhea in
infants and young children and is a major cause of morbidity and mortality
worldwide. Rotavirus, enteric Adenovirus, Calcivirus and Astrovirus are
uncommon causes of diarrhea in adults in the United States. Norwalk virus,
however, is much more common in adults and older children. It is more common
during the winter and may be found in contaminated drinking or swimming water,
poorly cooked shellfish, and contaminated foods [Kohn, 1995]. Norwalk virus has
been responsible for nearly 40% of all outbreaks of acute vomiting and diarrhea
in schools, camps, hospitals, nursing homes and on cruises [Blacklow, 1991].
The virus is spread via the fecal-oral route, though airborne transmission has
also been suggested. Norwalk virus infection causes vomiting, cramps headache
and diarrhea beginning 1-2 days after exposure and usually lasting 1-2 days.
Norwalk viral infection is associated with marked delayed gastric emptying and
small intestinal mucosal damage causing both carbohydrate and fat
malabsorption. Symptoms may persist for 2 weeks. Specific diagnostic tests
remain research tools at the present time. Symptoms are self-limited and there is
no effective or recommended anti-viral therapy.
3.2.1.3 Non-Infectious Causes of Acute Diarrhea and Vomiting
There are also non-infectious causes of watery diarrhea and vomiting. For
example, acute heavy metal poisoning due to ingestion of copper, zinc, iron or
cadmium may cause nausea, vomiting, cramps and diarrhea occurring 5 to 60
minutes after ingestion [Bishai, 1993].
3.2.2 NonInflammatory Diarrhea
The hallmark of noninflammatory diarrhea or watery nonbloody diarrhea, is large
volume stools. Upper gastrointestinal symptoms including nausea, vomiting and
cramps may occur but significant abdominal pain and fever are usually absent.
Acute noninflammatory diarrhea is usually associated with small bowel infections.
Leukocytes are typically absent from the stool. Bacterial enteric pathogens,
which cause acute nonbloody diarrhea in adults, include Vibrio cholerae,
enterotoxigenic E. coli (ETEC), Clostridium perfringens and Bacillus cereus.
Commonly implicated protozoa include Giardia lamblia, Cryptosporidium parvum,
similarly has often been presented as a cause of diarrhea when large numbers
are present in the stool. To date there is insufficient evidence to definitively
implicate either of these organisms as causes of diarrhea [Shlim, 1995].
3.2.3 Acute Inflammatory Diarrhea
Acute inflammatory diarrhea typically presents as frequent bowel movements
often accompanied by blood, left lower quadrant cramping, abdominal pain and
urgency. Fecal leukocytes are often present. The typical pathogens associated
with inflammatory diarrhea include Salmonella, Shigella, Campylobacter jejuni,
enterohemorrhagic E. coli 0157:H7 (EHEC), enteroinvasive E. coli (EIEC) and
Clostridium difficile. Less common causes include Yersinia, E. histolytica,
Aeromonas species and Plesiomonas shigelloides (Table 4).
3.2.3.1 Salmonella
Salmonella species are gram-negative rod shaped bacteria. S. typhi is the
principal cause of enteric or typhoid fever causing fever, delirium and abdominal
pain. Typhoidal salmonella is not a particularly important cause of diarrhea. The
nontyphoidal Salmonella species, however include some of the most important
causes of foodborne illness in the U.S. [Chalker, 1988]. They may account for
more than 25% of all reported cases of FBDO and 50% of all FBDO deaths in
which an organism can be identified [Bean, 1996] (Table 5). Approximately
40,000 cases of nontyphoidal Salmonella are reported to the CDC annually,
probably representing only a small fraction of the actual incidence. Most
transmissions have been traced to raw or partially cooked eggs, poultry, beef,
pork or milk. Documented sources have also included contaminated medical
equipment, marijuana, and pets. Salmonella infections cause diarrhea principally
by direct invasion of both small and large intestinal mucosa, however an
enterotoxin, which causes secretory diarrhea, has also been described.
Salmonella enteritis usually presents with watery diarrhea and abdominal pain.
Grossly bloody diarrhea is surprisingly uncommon. Constitutional symptoms
including headache, fever, chills and malaise may occur [Baird-Parker, 1990].
Salmonella enteritis is usually self-limited with resolution of diarrhea within one
week. While fecal leukocytes are common, the diagnosis is based upon
isolation of Salmonella from the stool. Antibiotic therapy has not been proven to
shorten the course of the acute illness and may prolong excretion and thereby
transmission of the organism [Neill, 1991]. Antibiotic treatment is therefore not
recommended for healthy persons with mild symptoms. Antimicrobial therapy is
reserved for patients who are bacteremic or at increased risk of the
consequences of bacteremia including extremes of age and those with sickle cell
disease, AIDS, cancer, prosthetic valves or other serious underlying disease
[DuPont, 1997].
3.2.3.2 Shigella
clinical laboratories do not test for EIEC which can be identified by culture and
specialized serogrouping, or PCR. Treatment recommendations are identical to
that proposed for Shigellosis. No controlled trials have examined the role of antimicrobial therapy though use of trimethoprim and sulfamethoxazole has been
suggested [DuPont, 1997].
3.2.3.5 Clostridium difficile
Clostridium difficile associated diarrhea accounts for only 15-20% of all
antibiotic associated diarrhea [Kelly, 1994]. In fact, most antibiotic associated
diarrhea is mild, self limited and not associated with C. difficile [Fekety, 1997]. C.
difficile is a spore forming obligate anaerobic bacillus found ubiquitously in soil,
water and health care institutions. C. difficile rarely invades intestinal mucosa.
Instead, it causes intestinal damage via the elaboration of 2 toxins which adhere
to the mucosal surface. Most strains of C. difficile elaborate both toxins A and B.
The two toxins vary in potency, however both act to cause disease.
Approximately 8% of all patients admitted to the hospital are asymptomatic
carriers of C. difficile [McFarland, 1990]. C. difficile associated diarrhea occurs
sporadically and in outbreaks. Almost every antibiotic has been associated with
C. difficile diarrhea. The most frequently involved are ampicillin, other penicillin
derivatives, cephalosporins, and clindamycin. Even metronidazole and
vancomycin have been implicated as causes of C. difficile diarrhea. C. difficile
associated diarrhea may not manifest itself until 6-8 weeks after the
discontinuation of antibiotics. It has also been associated with chemotherapeutic
agents and less frequently with underlying leukemia and lymphoma without prior
exposure to antibiotics or chemotherapy. Patients typically present with cramps
and watery diarrhea. Occult bleeding may be noted, but significant hematochezia
is rare [Kelly, 1994]. Colitis more commonly involves the left colon but isolated
right sided colitis may occur and can cause marked right sided abdominal pain
and tenderness with little diarrhea. The term "C. difficile associated diarrhea" may
be used to describe the entire spectrum of disease from a purely secretory
diarrhea to colitis with or without pseudomembranes and even fulminant colitis.
Complications may include dehydration, electrolyte disturbances, reactive
arthritis, toxic megacolon and colonic perforation. Clinical signs and symptoms
can include fever, abdominal tenderness, and profound leukocytosis. Flexible
sigmoidoscopy may reveal a nonspecific colitis. Pseudomembranes, when
present, appear as yellowish plaques which may become confluent.
Diarrhea may resolve obviating the need for specific treatment if antibiotics can
be discontinued. Similarly, mild C. difficile associated diarrhea may resolve
spontaneously and does not need to be treated. Moderate to severe diarrhea
should be treated with oral metronidazole (250mg qid for 10 days). Oral
vancomycin (125 mg qid for 10 days) is more expensive and should be reserved
for pregnant women, children under age ten and patients who are critically ill due
to pseudomembranous colitis [Fekety, 1997]. It may also be prescribed for
patients who do not respond, cannot tolerate or are infected with organisms that
are resistant to metronidazole.
Clinical relapse will occur in 10 to 20% of patients who have initially responded to
therapy. Relapse will usually occur within three weeks after completion of
therapy. Relapses should be confirmed with repeat stool C. difficile toxin assay.
Asymptomatic patients should not be retested. Positive toxin tests in patients
without symptoms do not need to be treated [Kelly, 1994]. If possible, antibiotics
should be discontinued and avoided for at least two months. Relapses are
usually due to incomplete eradication or reinfection rather than the development
of resistance. Metronidazole should also be the treatment of choice for relapses.
Though there are few randomized placebo controlled trials, treatment
approaches for patients with multiple relapses include the following: 1- 2 months
of either oral metronidazole or oral vancomycin every other day with a gradual
taper; oral vancomycin plus rifampin; oral yogurt, lactobacillus preparations,
cholestyramine or Saccharomyces boulardii [Fekety, 1997].
Prevention of C. difficile associated diarrhea depends primarily upon proper
handwashing by hospital personnel and avoidance of unnecessary and
potentially high risk antibiotics [Pear, 1994]. Saccharomyces boulardii, a
nonpathogenic yeast was evaluated in a double blind-blind placebo controlled
randomized trial for the prevention of antibiotic associated diarrhea [McFarland,
1995]. Patients receiving new -lactam antibiotic prescriptions were randomized
to placebo or S. boulardii (500 mg po bid) beginning within 72 hours of antibiotic
initiation and continuing until 3 days after the antibiotic was discontinued.
Significantly fewer patients taking S. boulardii developed antibiotic associated
diarrhea (RR = 0.29 95% CI = 0.08,0.98). S. boulardii does not appear to have
any side effects.
3.2.3.6 Amebiasis
Amebiasis is one of the most common parasitic diseases worldwide. Infection is
acquired by ingestion of protozoal cysts of Entamoeba histolytica. The
trophozoite produced in the small bowel invades the epithelium of the colon
causing ulceration.
Risk factors in the United States include sexual promiscuity and colonic irrigation.
Amebiasis is unlikely to be contracted during short-term foreign travel though
high rates of infection exist in the Indian subcontinent, southern and western
Africa, the Far East and South and Central America. The clinical presentation of
acute amebiasis includes abdominal pain, tenesmus, and frequent loose to
watery stools with blood and mucus. Rarely fulminant colitis may intervene with
rapid onset of severe bloody diarrhea, fever and abdominal tenderness
progressing to colonic perforation and death. The diagnosis is complicated by the
recent discovery of 2 distinct but morphologically identical species, E. dispar and
E. histolytica. E. dispar is noninvasive, only associated with an asymptomatic
carrier state and 10 times more common worldwide. It is nonpathogenic even in
patients with AIDS [Ravdin, 1995]. The pathogenic and nonpathogenic species
cannot be distinguished under the microscope unless one identifies E. histolytica
trophozoites, which have engulfed erythrocytes.
Virtually all patients with acute amebic colitis have fecal occult blood tests, but
fecal leukocytes are rare due to the phagocytic activity of the parasite
[Gonzalez-Ruiz, 1994]. Serum anti-amebic antibodies are usually present but
cannot distinguish between past and present infection. A negative antibody test,
however is very helpful is eliminating acute amebic colitis from the differential
diagnosis in a patient with acute bloody diarrhea [Ravdin, 1990]. Colonoscopy
with biopsy of the ulcer edge and histological demonstration of ameba remains
the definitive test for the diagnosis of amebic colitis. Recommended treatment of
invasive colitis is metronidazole 750 mg po tid for 10 days. Less severe colitis
may be treated with tetracycline 250 mg po tid for 10 days or erythromycin 500
mg po qid for 10 days. All treatments should be followed by diiodohydroxyquin
650mg po tid for 20 days to eliminate all residual cysts [Ravdin, 1995].
3.2.3.7 Aeromonas and Plesiomonas
Aeromonas hydrophilia, Aeromonas sobria and Plesiomonas shigelloides
are gram negative facultative anaerobic bacteria, which are likely but not
universally, accepted causes of acute diarrhea. The most common source of
Aeromonas is untreated drinking water and patients typically present within one
multiple biopsies should be reserved for those patients in whom a specific agent
cannot be identified, and significant symptoms persist despite nonspecific
therapy.
3.5 Diagnostic Evaluation
3.5.1 History
The initial evaluation of the adult patient presenting with acute diarrhea should
focus on the setting, nature and severity of the acute diarrheal illness as well as
the patient's age and overall health status. Early intervention is warranted for
individuals who are elderly (>70 years), debilitated or immunocompromised.
Even previously healthy adults with acute diarrhea should see their health care
provider early if they experience dehydration, fever, gastrointestinal bleeding,
abdominal pain or neurologic symptoms.
Recently published practice guidelines recommend prompt medical evaluation in
those patients who present with dehydration, bloody stools, profuse watery
diarrhea, fever greater than 38.5 C (101.3 F), severe abdominal pain, >6
unformed stools during a 24 hr period, or duration of illness of >48 hours
[DuPont, 1997]. These guidelines are derived from available scientific evidence
but in this case they are largely based upon consensus. The impact of >6
unformed stools or duration of illness >48 hours on either the likelihood of a
positive stool culture or the ultimate clinical outcome of the patient has not been
studied.
The patient should be asked if they have noted any symptoms of dehydration
including lightheadedness, dizziness, dry mouth, excessive thirst, decreased
urine output, increased heart rate or changes in mental status. Initial history
should also elicit any associated nausea, vomiting, fever, shaking chills or signs
of significant upper or lower gastrointestinal bleeding (coffee ground emesis,
hematemesis, melena, hematochezia), joint pain or a new skin rash. If this initial
assessment does not indicate anything requiring immediate intervention, the
evaluation can proceed to focus on the character of the illness, the setting in
which it began, and other factors which may point to a specific diagnosis.
In order to assess the severity the diarrhea one should ask specifically about the
frequency, consistency and volume of the stool. Patients should be asked to
quantify the number of bowel movements in a 24-hour period. It may be helpful to
stratify the severity of diarrhea. Mild diarrhea be defined as less than three
unformed bowel movements in a 24 hour period. Moderate diarrhea is three or
four per day and severe diarrhea is more than four unformed bowel movements
per day. In the absence of a specific diagnosis, the type of empiric treatment
(bismuth subsalicylate, loperamide or antimicrobials) may be predicated on this
type of stratification scheme [Gorbach, 1997]. A report of >6 stools is a sign of
severity and should prompt one to pursue further medical evaluation. Loose
consistency correlates directly with quantity of stool water. This is one area where
the patients description may be difficult to interpret. Verbal descriptors such as
"solid" and "liquid" appear to have reproducible meaning while the meaning of
"loose" and "semiformed" are variable [Mertz, 1995]. Some directed questions
may help the patient describe their current stool appearance.
Diarrhea Questionnaire
A. Stool Form Assessment
1.) Have you been having diarrhea in the past 7 days?
Yes
No
2.) In the past 7 days have your stools typically been:
Well-formed
Semi-formed (very soft but retains some form)
Loose ( no form, breaks apart)
Liquid (mushy like applesauce or watery)
3.) How often have your bowel movements looked like each of the following pictures
in the past 7 days?
All of the time
Most of the time
Some of the time
None of the time
Nonspecific antidiarrheal therapy may reduce the looseness of the stool without
The initial physical examination in the adult with acute diarrhea should focus
primarily on the assessment for any signs of significant dehydration.
Hypotension, resting tachycardia and orthostatic changes should be sought by
measuring heart rate and blood pressure in both the supine and standing
positions after 3 minutes have elapsed to allow for equilibration. Changes of 20
points or more in the pulse or blood pressure indicate significant volume
depletion. Other indications of dehydration include dry mucus membranes, poor
skin turgor and if severe, changes in mental status. Physical examination should
also include a careful abdominal and rectal examination to look for signs of
obstipation, obstruction, peritonitis, or anorectal disease.
3.5.3 Laboratory Evaluation
An otherwise healthy adult with mild acute diarrhea of less than 3 days duration
without any obvious cause may be treated symptomatically. Individuals with
significant underlying medical disease or moderate to severe diarrheal illness of
greater than 48 hours should undergo further diagnostic evaluation. This group
would include individuals with bloody diarrhea, significant dehydration, fever or
abdominal pain. Further evaluation is also indicated for individuals with recent
travel, antibiotic use, day-care exposure or nursing home workers, food handlers,
and those present during a community outbreak or following exposure to high
risk foods.
3.5.3.1 Stool Examination
The initial evaluation of the stool in the setting of acute diarrhea may include
visual examination for evidence of gross blood, testing for occult blood, and
microscopic examination of the stool for red and white blood cells. Visual
indicators of gastrointestinal hemorrhage include bright red blood, maroon or
black tarry stools. Dark stools, which are not black and tarry, do not indicate
bleeding. Though hematochezia is nonspecific, one study done in Bangladesh
demonstrated visible blood was found significantly more often in those infected
with Shigella or Entamoeba histolytica than with other pathogens [Stoll, 1983]. In
the United States, E. coli O157:H7 is the most commonly isolated organism from
stool specimens that are visibly bloody.
Testing of the stool for occult blood is problematic. A study of US citizens
studying in Mexico and presenting with acute diarrhea demonstrated the finding
of a negative fecal occult blood test was a reliable indicator of the lack of invasive
bacterial infection [McNeely, 1996]. The percentage of false positive exams,
however is likely increased in the setting of anal trauma associated with acute
diarrhea and there is insufficient positive predictive value. Newer tests for fecal
occult blood using latex agglutination of fecal hemoglobin may improve the
specificity but are currently too complicated and expensive for general use
[Beltinger, 1997].
Direct examination of the stool for fecal leukocytes has been used for decades
as an indicator of intestinal inflammation [Harris, 1972]. The methodology is
simple enough that someone with microscopy skills and a very basic laboratory
can perform the test reliably. Use of a fresh stool sample in a cup rather than one
obtained with a rectal swab is recommended. An aliquot of fresh stool on the tip
of a wooden stick is mixed on a glass slide with normal saline until it is barely
transparent. A drop of methylene blue or Grams stain may facilitate identification
of fecal leukocytes. The finding of >10 fecal leukocytes per high power field is
considered positive. One US study retrospectively examined the utility of fecal
leukocytes as an indicator of a positive stool culture. The sensitivity and
specificity were 40% and 78%, respectively. The positive predictive value was
only 20%. Several other studies have also shown fecal leukocytes are a very
poor predictor of enteric infection. Fecal leukocytes are also present in
noninfectious inflammatory disorders of the colon including inflammatory bowel
disease, ischemia and radiation proctitis.
The measurement of fecal lactoferrin by latex agglutination has been proposed
as a more sensitive test for the detection of fecal leukocytes [Guerrant, 1992].
Stool Hemoccult, fecal leukocyte and fecal lactoferrin all have poor positive
predictive value.
Routine stool culture for enteric pathogens should identify Salmonella, Shigella,
Campylobacter, E coli O157:H7, and Yersinia. Some labs have added
Aeromonas and Plesiomonas.
Clinical predictors of a positive culture include diarrhea of greater than 24 hours
duration, fever, and either blood in the stool or abdominal pain with vomiting
[Koplan, 1980]. A multicenter review of nearly 60,000 stools submitted for culture
revealed an overall positivity rate of 6.4%. Multiple specimens are frequently
submitted from the same patient, however, 96.9% of positives were found on the
first specimen and 99.0% after the second [Valenstein, 1996]. No more than 2
specimens are necessary to exclude an enteric infection.
Stool cultures are frequently sent to evaluate hospitalized patients who develop
diarrhea. At least 5 retrospective and 1 prospective study have evaluated the
likelihood of a positive stool culture in relationship to the number of days in the
hospital [Siegel, 1990], [Rohner, 1997], [Yannelli, 1988]. While the overall
positivity rate was approximately 6%, the yield of stool culture in those
developing diarrhea after the 3rd hospital day was only 0-1% in all studies
[Valenstein, 1996], [Rohner, 1997]. Similarly, specimens submitted for ova and
parasites (O&P) had an overall yield of 2.5%. This decreased to 0.7%, if
submitted from patients hospitalized for more than 4 days [Valenstein, 1996].
Guidelines have been proposed to limit the use of stool cultures to patients in the
hospital <3 days unless they are immunocompromised. Outcome studies using
this type of guideline have reduced the number of specimens submitted by 37%
[Chitkara, 1996].
The examination for ova and parasites (O&P) is recommended for individuals
with persistent diarrhea who are at risk because of foreign travel, high-risk sex,
immunocomprimised status, exposure to unfiltered water, day care aged children
or a community outbreak [DuPont, 1997]. The evaluation is time consuming and
the yield may vary considerably with the available level of expertise. Typically 3
specimens are collected on successive days. In those patients in whom a
parasite was ultimately identified by stool examination, 97.6% of specimens were
positive after 2 specimens were examined. The yield increased to 99.8% after
three specimens were examined. Stool examination for ova and parasites
identifies an organism in only 2.5% of specimens submitted. Specimens from
immunocompetent persons are seldom positive if submitted after the fourth
hospital day [Valenstein, 1996], [Mohr, 1992].
In contrast, testing for Clostridium difficile toxin in appropriate patients has a
high frequency of positivity in both outpatients and inpatients regardless of length
of stay [Barbut, 1996]. C. difficile toxin was detected more frequently from
inpatients than any other bacterial pathogen even though it was requested on
only 50% of the specimens submitted for culture [Valenstein, 1996]. Testing for C.
difficile toxin is appropriate in individuals who are receiving or have received
antibiotics within the previous 2 months.
The evaluation of an adult with watery non-bloody diarrhea and exposure to day
care aged children or unfiltered water should focus on giardiasis. The sensitivity
of the microscopic examination for Giardia lamblia, however, is only 50-70%. In
lieu of stool for O&P, one should submit a single stool specimen for Giardia
specific antigen. This commercially available ELISA has sensitivity and
specificity of 96% and 100%, respectively [Rosoff, 1989].
Routine stool studies for outpatients with mild to moderate diarrhea may not be
necessary and can in the aggregate greatly add to the cost of medical care.
(Table 10) Stool culture for enteric pathogens is indicated if the patient has any
of the alarm signals outlined in (Table 11).
3.5.4 Endoscopy
Endoscopy is generally unnecessary in the evaluation of adults with acute
diarrhea. Flexible sigmoidoscopy may be recommended in the evaluation of
patients with persistent diarrhea and one of the following:
o
o
o
o
Most adults presenting with acute diarrhea will have only mild sodium and water
depletion and will respond appropriately to oral hydration. Clear liquids such as
dilute fruit juice, carbonated beverages, and sports drinks may suffice for mild
self-limited diarrhea. These drinks however, should not be recommended for
patients with moderate to severe diarrhea because they have an inappropriate
ratio of sodium to carbohydrate [Avery, 1990]. The physiological principle
explaining the coupled transport of sodium and glucose underlies most current
recommendations. The ideal solution would contain sodium 60-90 mEq/L,
potassium 20mEq/L, citrate 30mEq/L and glucose 20g/L. Rehydration formulas
which incorporate these principles include the WHO-UNICEF oral rehydration
salt packets and commercially available products including Infalyte , Lytren,
Pedialyte and Resol. The constituents of several often utilized formulations are
presented in (Table 12). Homemade solutions may be used effectively if clean
water is available and care is taken to avoid errors in mixing (Table 13).
Continued intake of food is now considered an important part of oral therapy for
diarrhea and should not be discouraged [Avery, 1990]. Boiled starches and
cereals (potatoes, noodles, rice, wheat, and oats), crackers and bananas are
ideal. Milk is often avoided, however the development of clinically important
lactose intolerance in the setting of acute diarrhea is rare [DuPont, 1997].
3.6.2 Antidiarrheal Therapy
Nonspecific antidiarrheals are very commonly used in mild to moderate acute
diarrhea. These may include bismuth subsalicylate, diphenoxylate HCl with
atropine sulfate (Lomotil), loperamide (Imodium), attapulgite (KaoPectate) and
cholestyramine (Questran). Anticholinergics are generally ineffective and are not
recommended because of side effects.
Bismuth subsalicylate (Pepto-Bismol) may have both anti-secretory and antimicrobial activity. Salicylate absorption can occur but short term use in adults
appears to be safe [Gorbach, 1990]. In 1977 DuPont et al. published a
randomized double blind placebo controlled study of bismuth subsalicylate
suspension in the treatment of acute diarrhea in US students who had recently
arrived in Mexico [DuPont, 1977]. Bismuth subsalicylate suspension was
associated with a significant decrease in the number of unformed stools and
subjective complaints of diarrhea, nausea and abdominal cramps. There was no
significant difference in water content or total weight of the stools between the
two groups. A subsequent study of healthy volunteers who ingested
enterotoxigenic E. coli (ETEC) demonstrated bismuth subsalicylate tablets taken
four time a day caused a significant reduction in the incidence of acute diarrhea
[Graham, 1983].
ETEC was rarely recovered in the stools of subjects given bismuth subsalicylate.
A second study on US students in Mexico demonstrated bismuth subsalicylate (2
tabs four times a day in doses identical to Pepto-Bismol ) given within 48hours of
arrival was associated with a significant reduction in the incidence of travelers
diarrhea [DuPont, 1987]. This regimen accounted for a protection rate of 65%.
Side effects reported included only darkening of the tongue and stool. There was
no statistically significant increase in the development of tinnitis. Bismuth
subsalicylate may also be effective in reducing symptoms in patients with viral
gastroenteritis [Steinhoff, 1980].
Loperamide is a modified opiate that does not significantly penetrate the central
nervous system. It is available over-the-counter and exerts its antidiarrheal effect
by reducing intestinal motility. It has no demonstrated antisecretory activity.
Loperamide (Imodium A-D) has been compared to bismuth subsalicylate (Pepto
Bismol) and attapulgite (Kaopectate) in two open labeled field trials for the
treatment of acute watery nonbloody diarrhea. Loperamide was more effective
and worked faster than bismuth subsalicylate. 75% of patients achieved relief
from symptoms of diarrhea within only one day of therapy [Johnson, 1986],
[DuPont, 1990].
Diphenoxylate-HCl with atropine (Lomotil) is another opiate-like antimotility
agent. Although data is limited, diphenoxylate-HCl with atropine may be
contraindicated in patients with bloody diarrhea. In one study, diphenoxylate-HCl
with atropine prolonged fever and illness in patients with bloody diarrhea due to
Shigella [DuPont, 1973]. A subsequent study did not confirm this finding however
[Murphy, 1993].
Attapulgite (Kaopectate) is a naturally occurring purified hydrated aluminum
magnesium silicate which is not absorbed systemically. It was tested in a double
blind placebo controlled study of adults with mild to moderate acute diarrhea not
due to bacteria or protozoa. Attapulgite (600mg) two tabs after each bowel
movement for a maximum of 72 hours was associated with a significant reduction
in the frequency of diarrhea [Zaid, 1996]. Stool volume was not evaluated. These
adsorbents may add form to the stool without affecting overall fluid losses and
should therefore be used only in patients with mild diarrhea.
Cholestyramine is a nonabsorbable resin used as a cholesterol lowering agent
with the side effect of constipation. Limited studies have demonstrated
cholestyramine is effective as a nonspecific treatment for acute diarrhea [McCloy,
1971]. A specific role may exist for treatment of relapsing pseudomembranous
colitis secondary to Clostridium difficile.
3.6.3 Antibiotic Therapy
Empiric antibiotic therapy may be indicated in selected adults with acute
diarrhea. Pending culture results, empiric antibiotic therapy may be considered in
patients with fever >38.5 C (101 F), dysentery or bloody diarrhea (excluding
amebiasis), and moderate to severe travelers diarrhea. The rationale for empiric
antibiotic therapy in moderate to severe travelers diarrhea, is that most of these
patients harbor a bacterial pathogen. Few studies have evaluated the benefit of
empiric antimicrobial therapy for acute diarrhea in adults who are not recent
travelers. One such study evaluated 202 patients treated with either
ciprofloxacin, trimethoprim/sulfamethoxazole or placebo for 5 days in a
randomized double blind fashion [Goodman, 1990]. Ciprofloxacin, but not
trimethoprim/sulfamethoxazole shortened the duration of illness and had a higher
cure rate than placebo. 82% of patients who received ciprofloxacin had improved
or were cured by the third day. Despite a lack of strong scientific evidence,
empiric antibiotic therapy is also commonly used for patients over age 60 with
moderate to severe diarrhea or those with significant underlying medical
conditions [Ericsson, 1987], [Wistrom, 1992].
When indicated, the drug of choice for antimicrobial therapy of diarrhea of
unknown cause is a quinolone such as norfloxacin 400mg, ciprofloxacin 500mg
or ofloxacin 300mg bid for 3-5 days [Farthing, 1996], [DuPont, 1997].
Unfortunately, as feared, reports of quinolone resistance have begun to appear.
The decision to use antimicrobial therapy, after stool studies reveal a causative
agent, will depend on whether or not symptoms have persisted. The benefits of
antibiotics are most well demonstrated for Shigella, C. difficile and Giardiasis.
The drugs of choice for specific antimicrobial agents are listed in (Table 14).
4.0 Chronic Diarrhea
4.1 Introduction
Chronic diarrhea implies an increased frequency of passing looser stools for
more than a month.
Healthy, young Americans eating controlled diets containing 20g of dietary fiber
have stool weights of about 100 g daily [Saunders, 1988]. The stools are 70%
water by weight, but the water entrapped in fibrous residue or in bacteria
comprises 30-75% of the wet weight of stools [Stephen, 1980].
Healthy humans can have heavier stools if their diet contains food stuffs which
enhance fecal bacteria, or contribute to fecal fiber. Vegetarians may have stool
weights normally in excess of 200g. On the other hand, patients may have
abnormally loose stools whose daily weight is less than 200g. The consistency of
stools is determined by the water content and by the ability of fecal insoluble
solids to bind the fecal water [Wenzl, 1995].
The punch-line: a decreased consistency of feces should be the major
characteristic in the definition of diarrhea rather than an arbitrarily defined
excessive daily fecal weight (exceeding 200g per day, for example), or increased
frequency of defecation.
Diarrhea is said to be chronic after one month because most infectious causes of
acute diarrhea resolve within this period of time [Donowitz, 1995], except in
patients who are immunosuppressed.
We present an approach to the differential diagnosis of chronic diarrhea based
on groups of diseases, although pathophysiologic mechanisms can overlap
considerably. However, clinicians should be able to use this scheme to develop a
hypothesis and to test the hypothesis in a logical manner.
4.2 The Diarrhea History
Physicians begin to generate hypotheses as soon as a patient is greeted, and as
the presenting complaint is heard. The ensuing questioning will depend on the
initial hypotheses. The essence of this disease-oriented approach to chronic
diarrhea is the emphasis on eliminating expeditiously diseases causing
hematochezia and diseases with malabsorption, so that the difficult group of
predominantly watery diarrheas can be considered without distraction.
4.2.1 Immunocompetence
It is essential to establish that the patient with chronic diarrhea is
immunocompetent. Otherwise, an infectious etiology for the diarrhea would be of
paramount concern. Questions about blood transfusions, intravenous drug use,
occupational or recreational exposure to HIV, and immunosuppressive medical
therapy must be asked.
4.2.2 Onset
An abrupt onset may connect the symptom of chronic diarrhea to the cause such
as cyclospora (mountaineering in Nepal) or as lactose intolerance (following viral
enteritis).
4.2.3 Frequency of Defecation
4.2.3.1 Diarrhea After Meals
Diarrhea after meals suggests a heightened gastro-colic reflex. Patients with
irritable (idiopathic) bowel syndrome often voice this complaint.
4.2.3.2 Awakening from Sleep
Diarrhea which awakens a patient from sleep is an alarm signal for organic
disease. Diarrhea rarely awakens the patient with functional (idiopathic) bowel
disease.
4.2.3.3 Daily Diarrhea
Daily diarrhea suggests organic disease. Patients with irritable (idiopathic) bowel
syndrome often have good days interspersed with bad ones.
4.2.4 Volume of Diarrhea
4.2.4.1 Teaspoons or Tablespoons?
Is the patient passing teaspoons or tablespoons (small volume) of stools?
Affirmation suggests anorectal dysfunction (incontinence), or proctitis (especially
if tenesmus or hematochezia is present).
4.2.4.2 Cupfuls?
Is the patient passing cupfuls of stool (large volume)? Patients who pass more
than 1 L of stool daily have small bowel mucosal disease, or a combination of
small and large bowel mucosal disease, or a hypersecretory state; these
inferences are based on the absorptive capacity of the normal colon [Debongnie,
1978].
4.2.5 Relationship to Eating
4.2.5.1 Worsened by Eating?
Is the diarrhea worsened by eating, and, if so, is the diarrhea worsened by eating
fatty foods? An affirmation suggests steatorrhea.
4.2.5.2 Lessened by Fasting?
Is the diarrhea lessened by fasting? An affirmation suggests malabsorption, but
patients with irritable (idiopathic) bowel syndrome often give a positive response.
4.2.5.3 Unaffected by Fasting?
Is the diarrhea unaffected by fasting? A positive response suggests an exudative
enteropathy (inflammatory bowel disease), or a hypersecretory state.
4.2.6 Fecal Characteristics
4.2.6.1 Blood in Stools?
Has the patient seen blood in stools? (Inflammatory bowel disease)
4.2.6.2 Stool Consistency?
What is the consistency of the stools? The patient should be challenged to
describe the stools as semi-formed, or as mushy (like applesauce), or as loose
(like thin soup). A formal diarrhea questionnaire is offered by Mertz et al [Mertz,
1995]. Steatorrheic stools are sometimes mushy rather than loose [Bo-Linn,
1984], [Hofmann, 1985].
4.2.6.3 Color and Odor?
The color and the odor of stools are only informative if these characteristics have
changed dramatically.
4.2.6.4 Excessive Flatus?
Floating stools and excessive flatus suggest carbohydrate malabsorption. Stools
float because of their content of gas, not of fat [Levitt, 1972].
4.2.6.5 Oily Droplets?
Oily droplets in the toilet water indicate steatorrhea, and especially malabsorption
of dietary triglyceride.
4.2.6.6 Recognizable Food Stuffs?
Has the patient recognized food stuffs in the stool, and of additional importance,
is there an estimate of elapsed time between ingestion and expulsion? This head
of meal transit time can be very helpful. A HOMTT less than 12 hours has been
associated with experimentally induced diarrhea [Read, 1980]. Food stuffs such
as corn kernels, or whole beets, which color the stools red, can be used as
markers.
4.2.7 Previous Abdominal Surgery or Irradiation
observed a red discoloration of their stools after eating four whole canned beets
with a meal [Saunders, Unpublished Observations]. The clinician is interested
only in abnormally rapid transit times in the work-up of diarrhea. Diarrhea can be
induced experimentally when the HOMTT becomes less than 12 hours [Read,
1980]. Furthermore, steatorrhea (up to 14 g of fat per day) can be induced in
normal subjects by osmotic laxatives [Fine, 1992] which would be expected to
hasten transit of chyme through the small intestine. So having an idea of
intestinal transit time contributes to understanding the etiology of diarrhea, and
the interpretation of measurements of fecal fat.
4.3.2 The Sudan Test for Fecal Fat
This test can be performed on a spot specimen, or on a timed collection of stool.
A representative sample of stool is placed on a glass slide, and it is acidified with
glacial acetic acid to protonate long-chain fatty acids so that they are converted
from insoluble salts to fatty crystals. After adding an ethanolic solution of Sudan
III and applying a cover slip, the slide is gently heated to melt the fatty acids into
oily droplets [Drummery, 1961]. Up to 100 tiny (<4 microns) droplets may be seen
in normal stool at a magnification of 400x. If the number and size of the orange
fatty droplets is increased, a second fecal slurry in water should be prepared.
This specimen is not acidified; it is examined directly after adding the Sudan III
[Drummery, 1961].
The Sudan Test is very sensitive for the detection of fatty acid (Part One of the
test) and of triglyceride (Part Two of the test) [Khouri, 1989]. Therefore, if Part
Two (and Part One) of the Sudan Test is positive, the clinician should suspect
maldigestion of dietary triglyceride (pancreatic insufficiency, small bowel
resection). A negative Part Two of the Sudan Test does not exclude pancreatic
insufficiency. Mineral oil, and the unabsorbable fat substitute, sucrose polyester
(Olestra ) could cause false positive Sudan Tests (Parts One and Two).
The bottom line: If a patient is ingesting fat (> 80 g per day), the Sudan Test is
excellent for proving clinical suspicion of fat malabsorption [Drummery, 1961],
and it has the added advantage of being able to suggest maldigestion of dietary
triglyceride.
4.4.2.2 Pathophysiology
Steatorrhea should be an initial clinical suspicion. When steatorrhea is proven,
the definitive cause can be discovered by remembering the way stations along
4.4.2.2.5 Summary
In small intestinal diseases, it is not only the excessive amounts of fat which
contribute to the weight of the stools. Malabsorbed LCFA [Ammon, 1973], and
bile salts [McJunkin, 1981], if solubilized in fecal water, can block absorption of
salt and water by colonocytes.
4.4.2.3 Diagnosis
The importance of gastric, or of intestinal resection to the etiology of steatorrhea
is evidenced by surgical scars. The clinical challenge is to distinguish between
small bowel luminal defects and mucosal diseases.
4.4.2.3.1 Pancreatic Insufficiency
Pancreatic insufficiency is the chief cause of small bowel luminal defects if the
intestinal tract is intact; a history of cystic fibrosis or of recurrent attacks of
abdominal pain associated with ethanolic excesses would be pertinent. Proving
pancreatic insufficiency is more difficult. A plain abdominal film might reveal
pancreatic calcification, but the absence of calcification is unhelpful; not all
patients with calcifications have steatorrhea [Lankisch, 1986].
In our patient, triglyceride in her stool incriminated the pancreas, and the CT
scan revealed an abnormal head of the pancreas. Fecal triglyceride, however, is
an insensitive test for pancreatic insufficiency [Khouri, 1989]. The Secretin Test
involves placing a tube in the proximal duodenum to aspirate pancreatic juice
after an intravenous injection of secretin intravenously; gastric contents must be
prevented from entering the duodenum. Recent modifications [Heij, 1986] of the
Secretin Test (continuous infusion of secretion and CCK-octapeptide) make the
test even more laborious but they allow a sensitivity of 83% and a specificity of
89% for detecting exocrine pancreatic insufficiency.
The Bentiromide Test has a sensitivity of about 80% in severe chronic
pancreatitis when compared to the Secretin Test [Niederau, 1985]. Bentiromide is
benzoyl-tyrosyl-para-amino-benzoic acid which, after ingestion, is hydrolyzed by
pancreatic chymotrypsin; the released p-amino benzoic acid is absorbed, and
excreted in urine where it can be measured. False positive tests have been
reported in renal insufficiency, and in small intestinal disease [Niederau, 1985].
Pancreatic insufficiency is not reliably detected by the bentiromide test until
pancreatic chymotrypsin is less than 5% of normal.
Measuring fecal chymotrypsin has been used as an indirect test of pancreatic
insufficiency especially in cystic fibrosis [Niederau, 1985]. Like the Bentiromide
Test, it is insensitive in mild to moderate disease.
A therapeutic trial of gastric acid inhibition with supplements of pancreatic
enzymes makes good sense although it has not been rigorously tested. The
patient keeps a diarrhea diary while eating a constant diet, and omitting antidiarrheal medicines. After a baseline period of 3 days, a proton-pump inhibitor
(for example, omeprazole 20 mg twice daily) is added for another 3 days. Then
for a final 3 days, pancreatic enzymes (for example, Cotazyme capsules of 8000
lipase units) 4 capsules with meals and 2 capsules with snacks are added to the
PPI. An advantage of this trial is that a definite improvement in the PPI period
directs the clinician to consider Zollinger-Ellison syndrome.
4.4.2.3.2 Mucosal Diseases
Among mucosal diseases, celiac sprue would be suggested by a childhood
history of diarrhea, presence of diabetes, of iron-deficiency anemia that fails to
respond to oral iron, and oral ulcers.
If our patient did not have the clue of triglyceride in her stools, she might have
been screened for celiac sprue by searching for IgA endomysial antibodies. The
sensitivity and specificty of this immunofluoresent test approaches 100% in
specialized laboratories, but there are concerns about the reliability of
commercial assays [Grodzinsky, 1994]. Definitive diagnosis of celiac sprue
depends on small bowel biopsy, and a clinical response to a gluten-free diet.
A trial of a gluten-free diet has no place in the investigation of patients with
suspected celiac sprue unless the endomysial antibody test is postitive, or the
small bowel biopsy is compatible with the diagnosis. Some patients with
gastrointestinal symptoms such as flatulence and abdominal distension due to
functional (idiopathic) bowel disease can feel better when glutenous (cereals and
the attendent poorly absorbed carbohydrates) are avoided.
4.4.3 Bloody Diarrhea
Exudative diarrhea is usually obvious because of bloody stools. Sometimes,
however, Crohns disease is overlooked as a cause of chronic diarrhea if the
stools are not grossly bloody.
4.4.3.1 Profile of a Patient
For the past year an eighteen year old college student had episodes of diarrhea
(3-4 mushy to watery stools daily) which lasted 1-4 weeks. He was thought to be
lactose-deficient, and, indeed, 50 g of a lactose drink provoked abdominal
cramps, flatus, and diarrhea. The diarrhea was improved, but not eliminated by
avoiding lactose. The discovery of occult blood (Hemoccult ) in his stools led to
flexible sigmoidoscopy. The rectosigmoid mucosa was macroscopically normal,
but biopsy specimens contained granuloma typical of Crohns disease. The
patient continues to have occasional episodes of diarrhea which are helped by
loperamide.
4.4.3.2 Pathophysiology
Inflammation can cause disruption of the mucosal surface so that blood or
plasma leaks into the lumen and increases the volume of the fecal stream.
Anemia, and hypoalbuminemia can result. Inflammatory cytokines, and hastened
colonic transit impair colonic absorption of salt and water.
Malabsorption could also be a factor in the diarrhea of Crohns disease.
Involvement of ileal mucosa might impair the absorption of bile salts so that the
concentration of bile salts in fecal water becomes sufficient to block absorption of
Na+ and water by colonocytes [Hofmann, 1972]. If hepatic synthesis of bile acids
can compensate for a minor disruption of the enterohepatic circulation, the
diarrhea can be mainly watery, rather than fatty [Hofmann, 1972].
4.4.3.3 Diagnosis
Chronic bloody diarrhea would prompt investigation of idiopathic inflamatory
bowel disease, or of parasitic disease (E. histolytica, Schistosomiasis). Less
obvious is the patient who has chronic inflammation of the colonic mucosa
without gross blood. A family history of idiopathic inflammatory bowel disease can
be helpful, as well as a past history of hematochezia. Crampy abdominal pain,
and right lower quadrant tenderness or mass suggest Crohns disease.
A history of recent therapy with an antibiotic might incriminate C. difficile and its
exotoxins which should be sought in the patients stool.
The presence of fecal occult blood (or excessive leukocytes), unexplained by C.
difficle or ameba, necessitates at least a flexible sigmoidoscopy with mucosal
biopsy in a young patient, and a colonoscopy in the older patient. The
colonoscopist should try to obtain biopsies of the terminal ileum which can be
informative even if the colon is normal [Geboes, 1998].
4.4.4 Predominantly Watery Diarrhea
4.4.4.1 Diarrhea Due to Endocrinopathies
This group deserves pride of place, not because of its prevalence, but because
thyroid disease, and adrenal disease are eminently treatable.
4.4.4.1.1 Thyroid Disease
Hyperthyroidism is associated with chronic diarrhea with, and without
steatorrhea, and with a hypersecretory state [Donowitz, 1995].
4.4.4.1.2 Hypoadrenocorticalism
4.4.4.5.2 Pathophysiology
The cause of microscopic colitis is unknown. Speculations include impending
inflamatory bowel disease (ulcerative colitis, or Crohns colitis), or the sequel of
an infectious colitis. It seems certain that the abnormal mucosa is a factor in the
pathogenesis of diarrhea, because colons of patients with microscopic colitis
malabsorb salt and water infused under steady state conditions [Bo-Linn, 1985].
4.4.4.5.3 Diagnosis
Microscopic colitis should be considered in patients when malabsorption and
medication-induced diarrhea have been excluded. Irritable (idiopathic) bowel
syndrome would not be expected to present de novo in the middle-aged, or
elderly. Colonoscopy with biopsy is probably more informative than flexible
sigmoidoscopy because the right colonic mucosa can be more involved than that
in the left colon [Janda, 1991]. Multiple (>12) mucosal biopsies should be
obtained. Perhaps Subtle Colitis is a better rubric than Microscopic Colitis,
because all colitides have microscopic abnormalities.
For this phrase to have any credence, it must be carefully defined, much as is
Fever of Unknown Origin in Infectious Disease. By definition, then, patients with
DUO have an increased frequency of passing stools of decreased consistency
for more than 2 months. Thorough investigation of the groups of diseases
outlined in Sections 4.4 is unrewarded. In particular, there is no evidence for
immunosuppression. Finally, the patients diarrhea is difficult to control with
customary non-specific measures. A virtue of an appellation of DUO is that there
are a small group of diseases that can be revisited so that selected study can
establish a diagnosis [Schiller, 1991].
4.5.1 Fecal Incontinence
Incontinence is probably paramount if an elderly, parous lady admits to
involuntary passage of small amounts of stool. Corroborative evidence might be
obtained in a direct physical exam. An anal "wink" (cutaneo-anal reflex) indicates
that neural pathways are intact. Visual and digital exam can assess the tissue
mass of the pudenal body, and the strength of the external anal sphincter. A
descent of the pelvic floor of more than 1 - 2 inches during straining (in the left
lateral position) denotes muscle weakness. The toilet test (whereby the patient
strains on a toilet while the pelvic floor is viewed with a hand mirror) can highlight
abnormal descent of the pelvic floor, hemorrhoids, and rectal prolapse. A 24 hour
stool might weigh 100 - 200 g. Such a patient should be referred to a specialized
clinic for electrophysiological and manometric tests; biofeedback training can
help many patients.
4.5.2 Overlooked Malabsorption
A fat balance may give a spuriously high coefficient of absorption because the
stool collection was incomplete, or because the patient was eating insufficient
amounts of fat. Furthermore, the underlying disease may have progressed since
the initial testing so that steatorrhea is now readily detectable.
Repeating the inquiry outlined in (Table 16) involves no risk or major financial
penalty.
4.5.2.1 Profile of a Patient
A 47 year old lawyers diarrhea began one year ago at a time when his daughter
contracted diarrhea in a daycare center. He did not respond to two courses of
metronidazole based on a suspicion of giardiasis. Random stool specimens were
said to be negative for blood, fat, and leukocytes. Sigmoidoscopy with biopsy
was unremarkable. The familys pediatrician suggested a diet of bananas,
applesauce, and rice on which the diarrhea seemed to improve.
Six months after his initial work-up, he consented to the protocol in (Table 16).
The 24 hour stool weighed 1070 g, containing 21 g of fat. The Sudan Stain
revealed sudanophilic droplets after acidification only.
The hypothesis of celiac sprue was unsupported by the duodenal mucosal
biopsies which contained normal villi; however, patchy areas of inflammation and
mucosal erosions were seen. Additionally, a lesser curve gastric ulcer was
encountered by the endoscopist. The suspicion of Zollinger-Ellison symdrome
was supported by a serum gastrin of 860 pg / ml (normal 46 142 pg / ml), and
a dramatic improvement in his diarrhea with a proton pump inhibitor. Subsequent
CT-directed biopsy of a hepatic mass revealed neuroendocrine tumor.
4.5.3 Induced and Factitious Diarrheas
As emphasized in 4.4.4.3, many medications can cause diarrhea. Laxative abuse
can be especially vexatious; it should be suspected in patients who seem overly
concerned about maintaining a thin body. Phenolphthalein can be readily
detected by alkalinizing fecal supernate, or urine with a drop of 1 N NaOH. The
clinical chemistry laboratory can search for bisacodyl, Mg ++, sulfate, phosphate,
and anthraquinones.
4.5.3.1 Profile of a Patient
A 40 year old licensed practical nurse was referred with a diarrheal syndrome of
3 years duration. Multitudinous investigations had been unrewarded, and her
diarrhea continued even when she fasted. Therapy with prednisone 20 mg a day
ameliorated her diarrhea, but she was now confined to a wheelchair because of
osteopenic fractures.
While fasting, and on intravenous feeding, her 24 hour stool weight was 770 g.
The supernate of this liquid stool had an osmolality of 316 mosmols / kg; [Na +],
31 meq / L; [K+], 53 meq / L. The osmotic gap of 148 was found to consist of Mg +
+
. Bottles of milk of magnesia were uncovered in her dresser drawer and in her
suitcase; she said that she was using milk of magnesia to regulate her bowels.
4.5.3.2 Profile of a Patient
A 36 year old roofer complained of diarrhea since a laparotomy for abdominal
pain 4 years previously. A Meckels diverticulum and a small carcinoid were
resected. Extensive work-ups were unrewarded; 24 hour stools of 300 - 400 g
contained no excess fat, blood, or leukocytes. Because he was applying for
disability (as a roofer with diarrhea!) he was admitted to hospital for a 48 hour
fast. He said that beets passed through his gut within 10 minutes. A random stool
specimen had a [Na+] of 28 meg / L, [K+] of 41 meg / L, and an osmolality of 168
mosmols / kg.
Our patient had factitious diarrhea. A whole gut transit time of 10 minutes might
Three fresh stool samples have been examined for common bacterial, and
parasitic pathogens, and for unusual pathogens.
The patients diarrhea is poorly controlled by loperamide (4 mg every 6
hours), and there are alarm signals (see Glossary). Flexible
sigmoidoscopy to 40 cm and four mucosal biopsies (two from the sigmoid,
and two from the rectum) are helpful.
5.3
Overview
Definition
Diarrhea is characterized by unformed, watery stools (200 to 250
g/day) and increased bowel movement frequency, often
accompanied by fever, chills, malaise. The symptom of an
underlying condition or conditions, diarrhea is considered to be
acute at onset, and chronic after two to three weeks. Although
diarrhea is a common condition and usually self-limiting (two to
three days), complications can be serious, even fatal, in infants
and elderly patients, consequently it is important to attempt to
determine the cause(s).
Diarrhea has four primary classifications.
Etiology
Common causes include viral, bacterial, and parasitic infection
(often spread person-to-person), inflammation, drugs, and
psychogenic causes. In particular:
RELATED INFORMATION
Conditions with
Similar Symptoms
View Conditions
Drug Monographs
Antidiarrheal Drugs
Cholestyramine Resin
Herb Monographs
Barberry
Goldenseal
Licorice
Marshmallow
Slippery Elm
Supplement
Monographs
Brewer's Yeast
Glutamine
Lactobacillus Acidophilus
Quercetin
Vitamin A (Retinol)
Vitamin C (Ascorbic Acid)
Acute:
Infection (primary)
Inflammatory bowel disease (primary)
Iatrogenic causes
Poisoning
Chronic:
Malabsorption
Low sugar absorption (lactose intolerance)
Antacids
Secretory diarrhea:
Exudative diarrhea:
Western Herbalism
Laxatives
Hyperthyroidism
Risk Factors
Weight loss
Differential Diagnosis
Crohn's disease
Colitis, ulcerative colitis
Whipple's disease
Inflammatory bowel disease
Irritable bowel syndrome
Reiter's syndrome
Zollinger-Ellison syndrome
Over-the-counter medications
Various rare intestinal tumors (ganglioneuroblastoma,
Diagnosis
Physical Examination
For most patients, diarrhea is relatively benign and self-limiting. A
few patients, however, have an underlying illness that should be
diagnosed and treatedin particular, patients with diarrhea that
has persisted for longer than three days or with blood in the feces
(suggesting exudative diarrhea). Determining the mechanism
(osmotic, secretory, exudative, or motility) helps direct treatment.
Because patients will not be capable of reporting stool weight/day,
patient history plays a major role in diagnosing diarrhea.
incontinence.
Determine the volume type of diarrhea.
Determine if diarrhea is acute (generally related to
infection) or chronic.
Note signs and symptoms.
Ask patient about risk factors, lactose intolerance,
Assess:
Hydration
Abdominal tenderness
Bowel sounds
Laboratory Tests
Stool sample
CBC
Serum electrolytes
BUN
d-xylose
Pancreatic function
Urinalysis
Pathology/Pathophysiology
Blood:
Leukocytosis
Pathogens
Anemia
Biochemical deficiencies
Endoscopy:
Mucosal abnormalities
Bleeding
Ulcers
Stool:
Parasites
Imaging
Small-bowel radiography
Barium enema
Treatment Options
Treatment Strategy
Because diarrhea is a symptom, treatment should be dictated by
the cause (or causes). For acute, uncomplicated diarrhea, it may
be sufficient to reassure patients that the diarrhea is benign and
will resolve in a couple of days and simply treat the symptoms.
For some chronic diarrhea, dietary change can be sufficient
without additional evaluation.
Serious acute bloody diarrhea and chronic diarrhea will require
evaluation and treatment of underlying cause(s). Hospitalization
should be considered with dehydration; in any case, replacement
of fluids (clear fluids without caffeine and rehydration fluids) and
electrolytesparticularly with very young and very old patientsis
critical.
Drug Therapies
Because some medications prescribed for diarrhea can delay
resolution of certain infectious diarrhea conditions (as well as
other contraindications), diarrhea should be diagnosed before
drug therapy is undertaken. Common drug therapies (many OTC)
include the following.
Nutrition
Herbs
Herbs are generally a safe way to strengthen and tone the body's
systems. As with any therapy, it is important to ascertain a
diagnosis before pursuing treatment. Herbs may be used as dried
extracts (capsules, powders, teas), glycerites (glycerine extracts),
or tinctures (alcohol extracts). Unless otherwise indicated, teas
should be made with 1 tsp. herb per cup of hot water. Steep
covered 5 to 10 minutes for leaf or flowers, and 10 to 20 minutes
for roots. Drink 2 to 4 cups/day. Tinctures may be used singly or in
combination as noted.
Do not initiate antidiarrheal therapy if the diarrhea is secondary to
an infectious agent. Herbs can be used as anti-inflammatories,
antimicrobials, or antidiarrheals. Choose one or two from each
category as needed. They are best used as teas unless otherwise
noted.
Anti-inflammatory herbs:
antispasmodic.
Marshmallow root (Althea officinalis) is best prepared as
cold-water tea. Soak 2 tbsp. root in one quart of water
overnight. Strain and drink throughout the day.
Antimicrobial herbs:
Antidiarrheal herbs:
Homeopathy
Acupuncture
Patient Monitoring
Dehydrated patients and infant and elderly patients with serious
signs and symptoms should be monitored carefully. Patients with
acute diarrhea should report conditions that do not resolve in three
to five days. Follow up with chronic patients as required.
Other Considerations
Prevention
Avoid risk factors as possible.
Complications/Sequelae
Dehydration
Syncope, arrhythmias (from loss of electrolytes)
Anemia
Prognosis
Pregnancy
Dehydration can cause preterm labor. Gastrointestinal spasm may
have reflexive action on uterine muscle and induce contractions.
Goldenseal (Hydrastis canadensis) and barberry (Berberis
vulgaris) should be avoided in pregnancy as they may stimulate
contractions. High doses of vitamin A may be teratogenic and
should be avoided.
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