Вы находитесь на странице: 1из 9

Intern Emerg Med (2012) 7 (Suppl 3):S255S262

DOI 10.1007/s11739-012-0827-4

SELECTED PAPER CHRONIC DIARRHOEA

Clinical approach to diarrhea


Roberto Corinaldesi Vincenzo Stanghellini

Giovanni Barbara Paola Tomassetti


Roberto De Giorgio

SIMI 2012

Abstract Diarrhea is defined as reduced stool consis- clinical features are expected to reduce costs for patients
tency, increased water content and number of evacuations with chronic diarrhea.
per day. A wide array of causes and pathophysiological
mechanisms underlie acute and chronic forms of diarrhea. Keywords Chronic diarrhea  Osmotic diarrhea 
This review focuses on the major clinical aspects which Secretory diarrhea  Steatorrhea
should aid clinicians to diagnose chronic diarrhea. Clinical
history, physical examination and stool evaluation and the Abbreviations
predominant stool characteristic, i.e., bloody, watery, and EMA Endomysial antibodies
fatty diarrhea, may narrow the differential diagnosis. FD Functional diarrhea
Although mainly involved in acute diarrhea, many different IBD Inflammatory bowel disease
infectious agents, including bacteria, viruses and protozoa, IBS Irritable bowel syndrome
can be identified in chronic bloody/inflammatory diarrhea IBS-C Constipation predominant irritable bowel
by appropriate microbiological tests and colonoscopic syndrome
biopsy analysis. Osmotic diarrhea can be the result of IBS-D Diarrhea predominant irritable bowel
malabsorption or maldigestion, with a subsequent passage syndrome
of fat in the stool leading to steatorrhea. Secretory diarrhea MRI Magnetic resonance imaging
75
is due to an increase of fluid secretion in the small bowel SeHCAT 75-Seleniumhomotaurocholic acid
lumen, a mechanism often identified in gastroenteropan- tTG Tissue transglutaminase
creatic neuroendocrine tumors. The evaluation of the fecal VIP Vasoactive intestinal polypeptide
osmotic gap may help to characterize whether a chronic
diarrhea is osmotic or secretory. Fatty diarrhea (steator-
rhea) occurs if fecal fat output exceeds the absorptive/
digestive capacity of the intestine. Steatorrhea results from General features of diarrhea
malabsorption or maldigestion states and tests should dif-
ferentiate between these two conditions. Individualized Diarrhea (a term derived from the ancient Greek words dia,
diagnostic work ups tailored on pathophysiological and through and qeim, to go or to flow) is one of the most
common complaints reported by patients seen in primary
care up to tertiary referral centers. It is the cause of relevant
morbidity and social costs in developed countries and one
R. Corinaldesi (&)  V. Stanghellini  G. Barbara 
of the most frequent causes of mortality particularly in the
P. Tomassetti  R. De Giorgio pediatric population in developing countries. Overall,
Department of Clinical Medicine, Digestive Diseases diarrhea is characterized by a reduced stool consistency (or
and Internal Medicine, University of Bologna, loose stools) essentially due to an incomplete absorption
St. Orsola-Malpighi Hospital, Bldg #5, Nuove Patologie,
Via Massarenti 9, 40138 Bologna, Italy
of water and electrolyte by the intestine [1, 2]. This is the
e-mail: roberto.corinaldesi@unibo.it result of an altered electrolyte absorption/secretion or

123
S256 Intern Emerg Med (2012) 7 (Suppl 3):S255S262

non-absorbable/osmotically active substances introduced difficile toxin A can be the result of a combination of
with foods, which accumulate in the intestinal lumen. inflammatory, secretory and motor abnormalities [5, 6].
Understanding the ending balance of fluids, i.e., the oral Acute diarrhea represents the most common subtype of all
intake in addition to gastrointestinal secretions versus the diarrheas in terms of frequency, incidence and mortality ([2.5
amount that is adsorbed, is of crucial importance as it bears million deaths/year) and cause of vast direct and indirect costs
major implications for the complex pathophysiological to national health care agencies. Acute forms of diarrheal ill-
mechanisms underlying most forms of diarrhea. nesses are usually of short duration (i.e.,\4 weeks) and mainly
A detailed analysis of physiological mechanisms of related to infectious agents (usually \1 week if viruses or
daily fluid fluxes throughout the gastrointestinal tract is bacteria are involved; up to 4 weeks if protozoa play a path-
beyond the purpose of the present review. Nonetheless, a ogenetic role), ingestion of intoxicated foods or food allergy
brief account of intestinal fluid absorption/secretion in [7]. Although mainly self-limiting, acute diarrheas may also
physiological condition is relevant to the categorization of represent the start of chronic diarrheal disorders [8]. Chronic
diarrhea and therefore of its clinical approach. Studies have diarrhea can be defined as the production of loose stools (a
established that the daily amount of fluid flowing through conventional quantitative criterion being set at [200 g/day)
the small bowel is about 78 L. This fluid includes oral for more than 4 weeks. A further definition indicates more than
intake and saliva (1.5 L), gastric acid secretion and pepsin 3 bowel movements/day for more than 3 weeks. According to
(1.5 L), bile and pancreatic secretions (1 L each) and published data, its prevalence varies from 1 to 5 % of the
enteric secretion (3 L). In the small bowel, much general population [9, 10]. Nonetheless, similar to acute diar-
(approximately 90 %) of the water and electrolytes are rhea, also chronic diarrheal disorders may undergo underesti-
reabsorbed with a net amount of 8001,000 mL of fluid mated as patients do not seek for medical care until other
entering the colon. Finally, colonic reabsorption leads to symptoms occur such as weight loss, rectal bleeding, abdom-
80100 mL of water excreted with feces daily. It is enough inal pain, and urgency of defecation/incontinence. Patients
that the daily fecal water output increases by a minimal with chronic diarrhea have a poor quality of life especially if it
amount (5060 mL) to get loose stools, while a water is associated to fecal incontinence. As a result, the economic
excretion of 100 mL results in an increased stool weight impact of chronic diarrhea is enormous exceeding several
above 200 g/day, which is considered the upper normal hundred million dollars/year, which is ascribed to both direct
limit (see below) [3]. On the other hand, a decreased water costs related to diagnostic procedures and hospitalization and
absorption by only 12 % of the total amount is sufficient indirect costs related to reduced productivity [11]. The main
to cause diarrhea in many disorders characterized by an characteristics of acute and chronic diarrheas are reported in
impaired fluid and electrolyte absorption. Nonetheless, it Table 2.
should be emphasized that the small bowel and colon Diarrheal disorders often represent a challenge for cli-
possess a huge fluid and electrolyte reabsorption capacity, nicians, particularly when the symptoms are long-standing.
thus providing a powerful salvage mechanism limiting the Indeed, a myriad of possible causative factors should be
occurrence of diarrhea [4]. carefully considered until a diagnosis is established.
Various causes (some of them listed in Table 1) may Making an accurate diagnosis is central as the patient may
evoke inflammatory, osmotic, secretory, iatrogenic, and benefit of an effective management. The next paragraphs
motility/functional pathophysiological mechanisms under- will highlight the principal aspects of the clinical approach
lying acute or chronic diarrhea [3]. Notably, causative to patients with chronic diarrhea.
factors involved in chronic diarrhea are multifactorial as
they usually activate different pathogenetic mechanisms.
An example in line with this conceptual framework is Clinical history, physical examination, and principal
represented by cholera, which is the prototype of secretory laboratory tests
diarrhea but may also be associated with altered intestinal
motility leading to rapid bowel transit and reduced intes- A careful and detailed history taking is a fundamental step
tinal absorption. Likewise, diarrhea related to Clostridium in the diagnostic process of any patients with a chronic
diarrhea [3]. First of all, it is necessary to establish whether
the patient suffers a true diarrheal disorder (i.e., loose
Table 1 Main features characterizing acute versus chronic diarrhea
stools, [200 g and increased number of evacuations per
Acute Chronic day) or is affected by pseudo-diarrhea (frequent evacua-
Duration 14 weeks C4 weeks
tions of small amounts of feces with tenesmus) or just
incontinence that can be caused by an underlying fecaloma
Etiology Mainly toxic/infections Heterogeneous
(a rather common complication of chronic constipation in
Outcome Usually self-limiting Variable
elderly patients) [12]. A reduced stool consistency or, in

123
S256 Intern Emerg Med (2012) 7 (Suppl 3):S255S262

non-absorbable/osmotically active substances introduced difficile toxin A can be the result of a combination of
with foods, which accumulate in the intestinal lumen. inflammatory, secretory and motor abnormalities [5, 6].
Understanding the ending balance of fluids, i.e., the oral Acute diarrhea represents the most common subtype of all
intake in addition to gastrointestinal secretions versus the diarrheas in terms of frequency, incidence and mortality ([2.5
amount that is adsorbed, is of crucial importance as it bears million deaths/year) and cause of vast direct and indirect costs
major implications for the complex pathophysiological to national health care agencies. Acute forms of diarrheal ill-
mechanisms underlying most forms of diarrhea. nesses are usually of short duration (i.e.,\4 weeks) and mainly
A detailed analysis of physiological mechanisms of related to infectious agents (usually \1 week if viruses or
daily fluid fluxes throughout the gastrointestinal tract is bacteria are involved; up to 4 weeks if protozoa play a path-
beyond the purpose of the present review. Nonetheless, a ogenetic role), ingestion of intoxicated foods or food allergy
brief account of intestinal fluid absorption/secretion in [7]. Although mainly self-limiting, acute diarrheas may also
physiological condition is relevant to the categorization of represent the start of chronic diarrheal disorders [8]. Chronic
diarrhea and therefore of its clinical approach. Studies have diarrhea can be defined as the production of loose stools (a
established that the daily amount of fluid flowing through conventional quantitative criterion being set at [200 g/day)
the small bowel is about 78 L. This fluid includes oral for more than 4 weeks. A further definition indicates more than
intake and saliva (1.5 L), gastric acid secretion and pepsin 3 bowel movements/day for more than 3 weeks. According to
(1.5 L), bile and pancreatic secretions (1 L each) and published data, its prevalence varies from 1 to 5 % of the
enteric secretion (3 L). In the small bowel, much general population [9, 10]. Nonetheless, similar to acute diar-
(approximately 90 %) of the water and electrolytes are rhea, also chronic diarrheal disorders may undergo underesti-
reabsorbed with a net amount of 8001,000 mL of fluid mated as patients do not seek for medical care until other
entering the colon. Finally, colonic reabsorption leads to symptoms occur such as weight loss, rectal bleeding, abdom-
80100 mL of water excreted with feces daily. It is enough inal pain, and urgency of defecation/incontinence. Patients
that the daily fecal water output increases by a minimal with chronic diarrhea have a poor quality of life especially if it
amount (5060 mL) to get loose stools, while a water is associated to fecal incontinence. As a result, the economic
excretion of 100 mL results in an increased stool weight impact of chronic diarrhea is enormous exceeding several
above 200 g/day, which is considered the upper normal hundred million dollars/year, which is ascribed to both direct
limit (see below) [3]. On the other hand, a decreased water costs related to diagnostic procedures and hospitalization and
absorption by only 12 % of the total amount is sufficient indirect costs related to reduced productivity [11]. The main
to cause diarrhea in many disorders characterized by an characteristics of acute and chronic diarrheas are reported in
impaired fluid and electrolyte absorption. Nonetheless, it Table 2.
should be emphasized that the small bowel and colon Diarrheal disorders often represent a challenge for cli-
possess a huge fluid and electrolyte reabsorption capacity, nicians, particularly when the symptoms are long-standing.
thus providing a powerful salvage mechanism limiting the Indeed, a myriad of possible causative factors should be
occurrence of diarrhea [4]. carefully considered until a diagnosis is established.
Various causes (some of them listed in Table 1) may Making an accurate diagnosis is central as the patient may
evoke inflammatory, osmotic, secretory, iatrogenic, and benefit of an effective management. The next paragraphs
motility/functional pathophysiological mechanisms under- will highlight the principal aspects of the clinical approach
lying acute or chronic diarrhea [3]. Notably, causative to patients with chronic diarrhea.
factors involved in chronic diarrhea are multifactorial as
they usually activate different pathogenetic mechanisms.
An example in line with this conceptual framework is Clinical history, physical examination, and principal
represented by cholera, which is the prototype of secretory laboratory tests
diarrhea but may also be associated with altered intestinal
motility leading to rapid bowel transit and reduced intes- A careful and detailed history taking is a fundamental step
tinal absorption. Likewise, diarrhea related to Clostridium in the diagnostic process of any patients with a chronic
diarrhea [3]. First of all, it is necessary to establish whether
the patient suffers a true diarrheal disorder (i.e., loose
Table 1 Main features characterizing acute versus chronic diarrhea
stools, [200 g and increased number of evacuations per
Acute Chronic day) or is affected by pseudo-diarrhea (frequent evacua-
Duration 14 weeks C4 weeks
tions of small amounts of feces with tenesmus) or just
incontinence that can be caused by an underlying fecaloma
Etiology Mainly toxic/infections Heterogeneous
(a rather common complication of chronic constipation in
Outcome Usually self-limiting Variable
elderly patients) [12]. A reduced stool consistency or, in

123
Intern Emerg Med (2012) 7 (Suppl 3):S255S262 S257

Table 2 List of possible etiological factors and related pathogenetic mechanisms responsible for bloody, watery, and fatty diarrhea
Type Pathogenetic mechanisms Causes

Bloody Inflammatory or exudative Inflammatory diseases: Crohns disease, ulcerative colitis, diverticulitis, ulcerative
(with elevated white blood cell jejunoileitis;
count, occult or frank blood Invasive infectious diseases: Clostridium difficile (pseudomembranous colitis), invasive
or pus in stool) bacterial infections (e.g., tuberculosis, yersiniosis), invasive parasitic infections (e.g.,
Entamoeba, Giardia, Cryptosporidia, Cyclospora), ulcerating viral infections (e.g.,
cytomegalovirus, herpes simplex virus);
Neoplastic diseaases: Colon carcinoma, lymphoma, villous adenocarcinoma;
Radiation colitis
Watery Secretory (often nocturnal; Alcoholism, bacterial endotoxins (e.g., cholera), bile acid malabsorption, Brainerd
unrelated to food intake; fecal diarrhea (epidemic secretory diarrhea), congenital syndromes, Crohns disease (early
osmotic gap B50 mOsm/kg) ileocolitis), endocrine disorders (e.g., hyperthyroidism), medications (e.g., antibiotics,
antineoplastics), microscopic colitis (lymphocytic and collagenous subtypes),
neuroendocrine tumors (e.g., gastrinoma, VIPoma, carcinoid tumors), nonosmotic, irritant
laxatives (e.g., senna, cascara), postsurgical (e.g., cholecystectomy, gastrectomy,
vagotomy, intestinal resection), and vasculitis
Osmotic (fecal osmotic Carbohydrate (e.g., lactose, fructose) malabsorption syndromes, celiac disease, osmotic
gap C125 mOsm/kg) laxatives and antiacids (e.g., magnesium phosphate, sulfate), sugar alcohols (e.g.,
mannitol, sorbitol, xylitol)
Functional (distinguished from Irritable bowel syndrome
secretory types by hypermotility/
rapid gut transit, smaller
volumes and improvement at
night with fasting)
Fatty Malabsorption syndrome Amyloidosis, carbohydrate (e.g., lactose intolerance) malabsorption (late phase), celiac
(steatorrhea (damage to or loss disease (late phase), gastric bypass, lymphatic damage (e.g., congestive heart failure,
in many of absorptive ability) lymphomas), medications (e.g., orlistat, acarbose), mesenteric ischemia, noninvasive
but not small bowel parasite (e.g., Giardia), post-resection diarrhea, short bowel syndrome, small
all cases) bowel bacterial overgrowth (C105 bacteria/mL), tropical sprue, Whipples disease
(Trophoeryma whippelii)
Maldigestion (loss of digestive Hepatobiliary disorders, inadequate luminal bile acid, exocrine pancreatic insufficiency
function)
VIPoma vasoactive intestinal polypeptide secreting tumor

contrast, frequent passage of nut-like stools, abdominal example, the presence of edema, overt malnutrition and
pain and/or discomfort, is associated with a change in stool signs ascribable to fat soluble vitamin D, K, A and E
form or frequency, eventually relieved by defecation; the deficiency can altogether suggest either malabsorption or
presence of bloating, sensation of incomplete evacuation or maldigestion diseases. Cramping diarrhea associated with
urge to defecate are all symptoms suggestive of a func- skin flushing and hepatomegaly can be part of the clinical
tional intestinal disorder, such as irritable bowel syndrome spectrum secondary to a metastatic carcinoid. Exoph-
(IBS). Nocturnal diarrhea has long been thought to be thalmia suggests a diarrhea related to hyperthyroidism,
associated with organic diseases (e.g., diabetes and bacte- while an episcleritis may indicate an underlying inflam-
rial overgrowth), although recent data challenged this matory bowel disease (IBD). Dermatitis herpetiformis is a
concept. Furthermore, a thorough review of dietary habits condition associated in about 1525 % of celiac patients
(e.g., consumption of sugarless candies), drugs used by the [13].
patient (recent antibiotic therapy which may lead to Clos- Finally, rectal examination is important to verify pos-
tridium difficile related diarrhea or inadvertent/surreptitious sible perianal fistulas (Crohns disease), mucosal altera-
use of laxatives) and recent traveling (increased risk of tions as well as anal continence, structural abnormalities
bacterial and parasitic infections in developing Countries) (rectocele) and perineal descent which may result in
should be considered along with the presence of food pudendal neuropathy leading to incontinence.
allergy, previous surgeries and any other disorder contrib- Fecal examination has diagnostic implications by
uting to chronic diarrhea [3, 10]. revealing: (a) the presence of blood that can be due to a
Physical examination provides further support to variety of conditions ranging from hemorrhoids, divertic-
establish the underlying cause of a chronic diarrhea. For ulosis to IBD and cancer (see below for more details);

123
S258 Intern Emerg Med (2012) 7 (Suppl 3):S255S262

(b) large volume, pale and oily stools in patients with Types of chronic diarrhea
classic steatorrhea; (c) floating stools that can be the result
of increased methane or gas content. The distinction of diarrhea into the three categories
Based on the stool characteristics, chronic diarrhea can (bloody, watery, and fatty) may help to focus on the
be classified into three major types, i.e., bloody (inflam- diagnostic process and possibly limit the number of tests.
matory), watery (secretory/osmotic/functional or increased Proposed algorithms for acute and chronic diarrhea are
gut motility), and fatty (steatorrhea). illustrated in Figs. 1 and 2, respectively.

Fig. 1 A proposed algorithm for patients presenting with acute diarrhea

Fig. 2 A proposed algorithm for patients with chronic diarrhea

123
Intern Emerg Med (2012) 7 (Suppl 3):S255S262 S259

Bloody (inflammatory) diarrhea anti-inflammatory drugs (e.g., mesalazine, budesonide)


may stop the diarrhea related to microscopic colitis (with
This form of diarrhea is generally characterized by fre- improvement of mucosal histopathology), the evidence
quent, small volume, bowel movements. Primary causes of supports this disease as an individual entity [16]. None-
bleeding include colo-rectal cancer and polyps. Further- theless, whether bile acid malabsorption or non-steroidal
more, the presence of blood (with/without mucus and pus) anti-inflammatory medications may have a role in micro-
in stools is highly indicative of either ulcerative colitis or scopic colitis still remains an unsolved question.
Crohns disease [14]. Tenesmus is frequently associated
with inflammatory involvement of the rectum. Physical Watery diarrhea
examination, revealing abdominal tenderness at palpation,
and cutaneous, ocular and joint involvement, also provides This type of chronic diarrhea can be due to a heterogeneous
further evidence for an IBD. Other conditions that should group of conditions characterized by osmotic, functional/
be taken into account for a differential diagnosis with IBD dysmotility, and secretory mechanisms. Osmotic diarrheas
are ischemic and radiation colitis. The former is usually can occur quite commonly in daily practice and are due to
acute, while the latter can be both acute and chronic. A the presence of osmotically active substances which trigger
colonoscopic exam with histopathological analysis of the passage of water from the plasma to the small bowel
mucosal biopsies is mandatory for all these diseases. through the highly permeable epithelial lining. This
Infections are rarely responsible for chronic bloody/ osmotic mechanism contributes to chronic diarrhea
inflammatory diarrhea. However, when an infection is observed in patients with either malabsorption conditions
suspected, Campylobacter and Salmonella, particularly in such as celiac disease, bacterial overgrowth, use of laxa-
immunocompromized patients [15], as well as other tives (i.e., lactulose, polyethylene glycol and salts), or
bacteria, i.e., Shigella, E. coli 0157:H7, Yersinia, and maldigestion states, i.e., disaccharidase deficiency and
Mycobaterium tuberculosis should be sought in stool cul- exocrine pancreatic insufficiency.
tures. Notably, some bacteria require special culture media, With a steadily increasing prevalence (estimated to be
as for E. coli 0157:H7 and Yersinia, otherwise they may around 1:100 individuals worldwide), celiac disease is one
yield false-negative results. Viruses, such as Cytomegalo- of the most common conditions causing chronic diarrhea. It
virus and Herpes simplex, along with few parasites, namely is the result of an immunologic reaction of the mucosa to
Entameba, Trichuris, and Schistosoma, may also cause gluten and therefore disease-related autoantibodies repre-
bloody diarrhea. Parasitic infestations may be accompanied sent a good screening test to identify patients with chronic
by peripheral blood eosinophilia. If stool cultures are diarrhea. Specifically, IgA anti-tissue transglutaminase
negative, again colonoscopy (with mucosal biopsy sam- (tTG) and IgA anti-endomysial antibodies (EMA) are
ples) can be an important diagnostic adjunct. The fecal known to have a very high sensitivity ([95 %) and spec-
recovery of Giardia Lamblia is associated with high false- ificity (up to 98 %), provided that total IgA levels are
negative results and in the suspect of this type of infection a normal (about 3 % of celiac patients may have IgA defi-
duodenal aspirate should be obtained during upper gas- ciency) [17, 18]. In this context, anti-deamidated gliadin
trointestinal endoscopy. Detection of leukocytes in stools is antibodies should be tested and they proved to be partic-
indicative of infectious/inflammatory processes altering the ularly useful in young (\2 years) celiac patients. The final
gut mucosa [9]. Further exams to be considered in patients diagnosis must be confirmed by esophago-gastro-duode-
with a suspected inflammatory disease as a cause of bloody noscopy with duodenal biopsy showing Marsh-Oberhuber
diarrhea include abdominal CT-scan or magnetic resonance grade 3 villous atrophy in florid cases. About 3040 % of
imaging (MRI) often disclosing a bowel wall thickening. celiac patients can have increased liver transaminases
Ultrasonography, more commonly used in Europe rather which normalize following gluten-free diet [19]. Nonre-
than the US, may yield similar results in expert hands. sponsive celiac disease may be associated with complica-
However, the reliability of bowel wall thickening in the tions (intestinal lymphoma) or associated microscopic
differential diagnosis of patients with an inflammatory colitis with persistence of a chronic diarrhea [20]. Other
diarrhea is still unsettled. Finally, although rarely present- causes of osmotic diarrhea include the use of laxatives such
ing with blood in the stools, microscopic colitis (more as magnesium salts (direct osmotic effect), carbohydrate
broadly being part of collagenous/lymphocytic colitis) can malabsorption (the classic example being lactulose, an
be the cause of an otherwise undetermined chronic diarrhea effective osmotic laxative in patients with chronic consti-
[16]. Colonic biopsies (even in the presence of a normal pation) and consumption of poorly absorbable carbohy-
mucosa) are fundamental for posing the diagnosis. Eosin- drates (e.g., sugarless candies or chewing gums). All these
ophilic gastroenteritis and systemic mastocytosis represent possible causes of diarrhea should be excluded by
other rare cause of chronic diarrhea. Since intestinal reviewing carefully the patients medical history. If a

123
S260 Intern Emerg Med (2012) 7 (Suppl 3):S255S262

disaccharidase (lactase) deficiency is suspected, patients Finally, bile acid malabsorption may cause watery
may undergo H2 breath test to confirm that condition [21, diarrhea usually occurring in patients subjected to ileal
22]. Notably, the osmotic diarrhea observed in patients resection (up to 100 cm) due to complicated Crohns dis-
with the aforementioned disorders may result in passage of ease. To substantiate the existence of a bile acid malab-
nitrogenous substances (azotorrhea) and fat with stools sorption, several tests can be attempted, including assay of
(steatorrhea) (see below), thus changing its categorization bile salts in the feces ([250 g per day in disease state) [27]
from watery to fatty diarrhea. Patients with osmotic diar- and scintigraphic assessment measuring the degree of
rhea respond to fasting with a reduced fecal excretion. retention and excretion of 75SeHCAT (75-seleniumhomot-
A peculiar dysmotility/functional type of chronic diar- aurocholic acid) at 30 min and 7 days following the
rhea is detectable in patients with the so-called functional examination (normally the retention is [15 %) [28]. These
diarrhea (FD) and diarrhea-predominant IBS (IBS-D) examinations, however, cannot be considered for routine
which affects up to 5 % of the Western population. screening. A therapeutic trial with the bile salt sequestering
Although the etiologic factors underlying both FD and IBS- drug cholestyramine may be advisable and if effective, it
D remain unknown, the pathophysiological determinants can be used as ex-iuvantibus diagnostic criteria. In contrast
are increasingly recognized. Both FD and IBS-D tend to to osmotic, secretory diarrheas are not modified by fasting.
overlap in the same patients over time and the diagnosis is The assessment of osmotic gap in stool water (the for-
now made possible through a positive symptom-based mula being 290 - 2[Na?] ? [K?]) may suggest the
approach (e.g., Rome criteria) after exclusion of alarm underlying pathophysiology of a chronic diarrhea. Specif-
symptoms/signs [23]. A peculiar form of IBS-D is the ically, the osmotic gap formula measures the contribution
adverse long-term outcome of an acute episode of infec- of electrolytes and non-electrolytes to water retention in the
tious diarrhea, occurring in about 10 % of all acute, severe small bowel lumen. Values of osmotic gap[125 mOsm/kg
infectious gastroenteritis, the so-called post-infectious IBS. are highly suggestive of a pure osmotic diarrhea (with
The infectious agents involved include pathogenic bacteria nonelectrolytes being responsible for most of the fecal
(e.g., Salmonella, Shigella, Campylobacter), parasites, and osmolality), while, in contrast, \50 mOsm/kg occur in
viruses. Abdominal pain and diarrhea are the most common pure secretory diarrheas (in that circumstances most of the
symptoms of this syndrome. Risk factors for the develop- fecal osmolality is due to electrolytes); finally mixed
ment of post-infectious IBS include the virulence of the osmotic and secretory diarrheas are characterized by
pathogen, the severity, and duration of the acute enteritis, osmotic gap values ranging from 50 to 125 mOsm/kg [29].
younger age, female sex, and psychological disturbances
[24]. Fatty diarrhea
Secretory diarrhea is characterized by an active secre-
tion of iso-osmolar fluid by the intestinal epithelium into This type of diarrhea or steatorrhea occurs when the
the lumen with possible electrolyte abnormalities (e.g., daily fecal fat output exceeds the normal upper limit, i.e.,
hypokalemia and acidosis in patients with VernerMorri- 7 g/24 h, which corresponds to 9 % of fats ingested with
son syndrome due to a vasoactive intestinal polypeptide meals. However, induced diarrhea in healthy volunteers
(VIP)-oma, a rare pancreatic neuroendocrine tumor. Diar- evoked a high fecal fat output (up to 13.6 g/24 h) in 35 %
rhea with increased intestinal secretion can be either con- of subjects, thus indicating that steatorrhea can be sec-
genital (i.e., congenital chloridorrhea) or acquired, classic ondary to diarrhea per se in the absence of any abnormality
examples being gastroenteropancreatic neuroendocrine impairing digestion or absorption of dietary fat [30]. As a
tumors such as gastrinoma (ZollingerEllison syndrome), result, fecal fat values ranging from 7 to 14 g/24 h have
ileal carcinoid (carcinoid syndrome), VIPoma (Verner low specificity for the diagnosis of diseases characterized
Morrison syndrome), and glucagonoma. In addition to by defective digestion or absorption. Only fecal fat output
classic clinical features (peptic ulcers, esophagitis, secre- [14 g/24 h can be predictive of maldigestion or malab-
tory diarrhea, flushing, wheezing, and many more), the sorption states.
measurement of a variety of tumor-related bioactive mes- Fatty diarrhea can be due to two main conditions:
sengers (e.g., amines or peptides) can prove the existence (a) small bowel malabsorption (e.g., celiac disease,
of a neuroendocrine neoplasm. Imaging, including mag- Whipples disease); (b) maldigestion related to exocrine
netic resonance, CT-scan, positron emission tomography, pancreatic insufficiency. In addition to celiac disease (see
and endoscopic ultrasound, is needed to localize and stage above) and tropical sprue, a rare cause of intestinal mal-
the tumor [25]. Some neuroendocrine tumors, e.g., carci- absorption is Whipples disease. This is characterized by
noids evoking the carcinoid syndrome, may release bio- weight loss, diarrhea, arthralgias, pericarditis, and con-
active substances, such as serotonin and substance P, which gestive hearth failure. Duodenal biopsy taken during upper
can also affect gut motility [26]. digestive endoscopy is the best way to demonstrate

123
Intern Emerg Med (2012) 7 (Suppl 3):S255S262 S261

Trophoeryma whippelii (the etiopathogenetic agent) in and other peptide-secreting tumors, as well as dumping
Periodic Acid-Schiff-positive macrophages infiltrating the syndrome, and chemotherapy-induced diarrhea. Octreo-
lamina propria [31]. Steatorrhea may occur as a result of tide does not seem to have any advantage over opiates in
extensive ileal ([1 m) resection because of a diminished the treatment of chronic idiopathic diarrhea and should be
bile acid reabsorption leading to increased passage of fat a second-line agent for this indication because of the need
with stools. Mild forms of steatorrhea can be identified in for administration by injection and costs. Intraluminal
patients with intestinal infections, including Giardia, agents include adsorbents, such as clays, activated char-
Cryptosporidium, and Cyclospora detectable with appro- coal, and binding resins, medicinal fiber but their thera-
priate microbiological cultures or serological tests. peutic efficacy in the treatment of diarrhea has received
Pancreatic insufficiency, related to an underlying negligible and controversial scientific validation. Chole-
chronic pancreatitis or previous pancreatectomy (either styramine and other similar binding resins have reduced
partial or sub-total) may be identified by clinical features stool weight [33]. Bismuth subsalicylate has been shown
(abdominal pain, weight loss) and the use of fecal elastase to be effective in acute travelers diarrhea, but its effec-
which is not routinely used. Thus, steatorrhea related to tiveness in chronic diarrhea is unproven.
exocrine pancreatic insufficiency can be best proven by an
ex-iuvantibus treatment with pancreatic enzymes.
Conclusions

Therapy A reliable definition of diarrhea is based on three major


features, i.e., increasing water content, volume, and fre-
Treatment of chronic diarrhea is aimed at replacing the loss quency of stool passage. Acute diarrhea is very common
of fluids and electrolytes and targeting specific diseases (high prevalence and incidence) in the clinical practice and
responsible for the intestinal disorder [32]. Oral rehydra- is mainly due to infections. Although less frequent than
tion solutions that include glucose or other nutrients and acute forms, chronic diarrhea represents a clinical chal-
salt are useful for repletion of body fluids. They can be life- lenge because of the vast array of causes and involved
saving therapy for dehydrating, acute secretory diarrheas, pathophysiological mechanisms. Thus, an accurate history
such as cholera, but have limited application in most taking, physical and rectal examination as well as stool
chronic diarrheal states and have not been well studied in evaluation are fundamental to establish a diagnosis. Fur-
these situations. Although these solutions increase net salt thermore, categorization of chronic diarrheas based on
and water absorption, they are not designed to reduce stool stool characteristics (i.e., bloody, watery, and fatty) may
weight, and diarrhea may even worsen with their use. narrow differential diagnosis and guide appropriate tests. A
Empirical therapy is used either as initial treatment targeted strategy based on individualized diagnostic work
before diagnostic testing, or after diagnostic testing has up is expected to reduce costs for managing patients with
failed to confirm a diagnosis, or even when a diagnosis has chronic diarrhea.
been made, but no specific treatment is available or specific
treatment fails to effect a cure. Conflict of interest None.
Antibiotic therapy could be considered as an initial
therapy if the prevalence of bacterial or protozoal infec-
tion is high in a community or in a specific situation. A References
successful trial would eliminate the need for a more
extensive evaluation. Natural and synthetic opiates are 1. Wenzl HH, Fine KD, Schiller LR, Fordtran JS (1995) Determi-
widely used, but other agents, such as bile acid-binding nants of decreased fecal consistency in patients with diarrhea.
Gastroenterology 108:17291738
agents, bismuth, and medicinal fiber, can also be suc- 2. Field M (2003) Intestinal ion transport and the pathophysiology
cessfully prescribed. However, only the most modern of diarrhea. J Clin Invest 111:931943
drugs have been studied properly and their use is based on 3. Camilleri M (2004) Chronic diarrhea: a review on pathophysi-
a considerable body of experience. Most cases of diarrhea, ology and management for the clinical gastroenterologist. Clin
Gastroenterol Hepatol 2:198206
except for high-volume secretory states, respond to a 4. Palma R, Vidon N, Bernier JJ (1981) Maximal capacity for fluid
sufficiently high dose of opiates. Codeine is less potent absorption in human bowel. Dig Dis Sci 26:929934
compared to morphine as an anti-diarrheal drug, and the 5. Kurose I, Pothoulakis C, LaMont JT, Anderson DC, Paulson JC,
synthetic opiates, e.g., diphenoxylate and loperamide, are Miyasaka M, Wolf R, Granger DN (1994) Clostridium difficile
toxin A-induced microvascular dysfunction. Role of histamine.
also less potent but devoid of central effects. The J Clin Invest 94:19191926
somatostatin analog octreotide has proven effectiveness in 6. Castagliuolo I, LaMont JT, Letourneau R, Kelly C, OKeane JC,
a variety of neuroendocrine tumors including carcinoid Jaffer A, Theoharides TC, Pothoulakis C (1994) Neuronal

123
S262 Intern Emerg Med (2012) 7 (Suppl 3):S255S262

involvement in the intestinal effects of Clostridium difficile toxin breath testing in gastrointestinal diseases: the Rome Consensus
A and Vibrio cholerae enterotoxin in rat ileum. Gastroenterology Conference. Aliment Pharmacol Ther 29(Suppl 1):149
107:657665 22. Ridolo E, Baiardini I, Meschi T, Peveri S, Nouvenne A, Dalla-
7. Baldi F, Bianco MA, Nardone G, Pilotto A, Zamparo E (2009) Focus glio P, Borghi L. (2012) HRQoL questionnaire evaluation in
on acute diarrhoeal disease. World J Gastroenterol 15:33413348 lactose intolerant patients with adverse reactions to foods. Intern
8. Gadewar S, Fasano A (2005) Current concepts in the evaluation, Emerg Med (Epub ahead of print)
diagnosis and management of acute infectious diarrhea. Curr 23. Quigley EM, Abdel-Hamid H, Barbara G, Bhatia SJ, Boeckx-
Opin Pharmacol 5:559565 staens G, De Giorgio R, Delvaux M, Drossman DA, Foxx-Or-
9. Fine KD, Schiller LR (1999) AGA technical review on the enstein AE, Guarner F, Gwee KA, Harris LA, Hungin AP, Hunt
evaluation and management of chronic diarrhea. Gastroenterol- RH, Kellow JE, Khalif IL, Kruis W, Lindberg G, Olano C,
ogy 116:14641486 Moraes-Filho JP, Schiller LR, Schmulson M, Simren M, Tzeuton
10. Headstrom PD, Surawicz CM (2005) Chronic diarrhea. Clin C (2012) A global perspective on irritable bowel syndrome: a
Gastroenterol Hepatol 3:734737 consensus statement of the World Gastroenterology Organisation
11. Schiller LR (2004) Chronic diarrhea. Gastroenterology Summit Task Force on irritable bowel syndrome. J Clin Gastro-
127:287293 enterol 46:356366
12. Wrenn K (1989) Fecal impaction. N Engl J Med 321:658662 24. Barbara G, Cremon C, Pallotti F, De Giorgio R, Stanghellini V,
13. Juckett G, Trivedi R (2011) Evaluation of chronic diarrhea. Am Corinaldesi R (2009) Postinfectious irritable bowel syndrome.
Fam Physician 84:11191126 J Pediatr Gastroenterol Nutr 48(Suppl 2):S95S97
14. Di Sabatino A, Biancheri P, Rovedatti L, Macdonald TT, Corazza 25. Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW,
GR (2012) Recent advances in understanding ulcerative colitis. Thakker RV, Caplin M, Delle Fave G, Kaltsas GA, Krenning EP,
Int Emerg Med 7:103111 Moss SF, Nilsson O, Rindi G, Salazar R, Ruszniewski P, Sundin
15. Paulet P, Coffernils M (1990) Very long term diarrhoea due to A (2008) Gastroenteropancreatic neuroendocrine tumours. Lancet
Campylobacter jejuni. Postgrad Med J 66:410411 Oncol 9:6172
16. Chetty R, Govender D (2012) Lymphocytic and collagenous 26. Von der Ohe MR, Camilleri M, Kvols LK, Thomforde GM
colitis: an overview of so-called microscopic colitis. Nat Rev (1993) Motor dysfunction of the small bowel and colon in
Gastroenterol Hepatol 9:209218 patients with the carcinoid syndrome and diarrhea. N Engl J Med
17. Volta U, Villanacci V (2011) Celiac disease: diagnostic criteria in 329:10731078
progress. Cell Mol Immunol 8:96102 27. Aldini R, Roda A, Festi D et al (1982) Bile acid malabsorption and
18. Volta U, De Giorgio R (2012) New understanding of gluten bile acid diarrhea in intestinal resection. Dig Dis Sci 27:495502
sensitivity. Nat Rev Gastroenterol Hepatol 9:295299 28. Sciarretta G, Fagioli G, Furno A et al (1987) 75Se HCAT test in
19. Volta U, Granito A, Parisi C, Fabbri A, Fiorini E, Piscaglia M, the detection of bile acid malabsorption in functional diarrhoea
Tovoli F, Grasso V, Muratori P, Pappas G, De Giorgio R (2010) and its correlation with small bowel transit. Gut 28:970975
Deamidated gliadin peptide antibodies as a routine test for celiac 29. Eherer AJ, Fordtran JS (1992) Fecal osmotic gap and pH in experi-
disease: a prospective analysis. J Clin Gastroenterol 44:186190 mental diarrhea of various causes. Gastroenterology 103:545551
20. Di Sabatino A, Corazza GR (2009) Coeliac disease. Lancet 30. Fine KD, Fordtran JS (1992) The effect of diarrhea on fecal fat
373:14801493 excretion. Gastroenterology 102:19361939
21. Gasbarrini A, Corazza GR, Gasbarrini G, Montalto M, Di Stefano 31. Afshar P, Redfield DC, Higginbottom PA (2010) Whipples dis-
M, Basilisco G, Parodi A, Usai-Satta P, Vernia P, Anania C, ease: a rare disease revisited. Curr Gastroenterol Rep 12:263269
Astegiano M, Barbara G, Benini L, Bonazzi P, Capurso G, Certo 32. Schiller LR (1995) Review article: anti-diarrhoeal pharmacology
M, Colecchia A, Cuoco L, Di Sario A, Festi D, Lauritano C, and therapeutics. Aliment Pharmacol Ther 9:87106
Miceli E, Nardone G, Perri F, Portincasa P, Risicato R, Sorge M, 33. Scaldaferri F, Pizzoferrato M, Ponziani FR, Gasbarrini G, Gas-
Tursi A, 1st Rome H2-Breath Testing Consensus Conference barrini A. (2011) Use and indications of cholestyramine and bile
Working Group (2009) Methodology and indications of H2- acid sequestrants. Intern Emerg Med (Epub ahead of print)

123