CALCULOUS BILIARY DISEASE Risk Factors

Risk factors for gallstone disease include female sex, age greater
Method of than 40 years, white, Latin American, and Native American
Zachary L. Smith, DO; and Mick S. Meiselman, MD descent, family history, obesity, rapid weight loss, starvation, total
parenteral nutrition, bariatric surgery, diabetes mellitus, and
hypertriglyceridemia.

CURRENT DIAGNOSIS Clinical Manifestations

The typical symptomatic presentation of gallstone disease is biliary
• True biliary colic is characterized by the abrupt onset and ces- colic. This is described as severe pain located in the mid-
sation of severe mid-epigastric or, less commonly, right upper epigastrium or, less commonly, the right upper quadrant, that
quadrant pain. begins and ceases abruptly. The pain is typically constant, occur-
• Pain commonly starts 1 to 2 hours after eating and can be ring 1 to 2 hours after a meal, and can either be localized or radiate
localized or radiate to the back, right shoulder, or chest. to the back or right shoulder. Often the onset of pain occurs during
• The onset of biliary colic commonly occurs during sleep. sleep. Nausea and vomiting commonly accompany biliary pain,
• Nausea and vomiting commonly follow the onset of pain. and, as with most surgical entities, pain typically precedes the onset
• Elevations of total and conjugated bilirubin, ALP, and GGT with of these symptoms. Biliary colic can also manifest as chest pain and
modest elevations in AST and ALT support a suspected diagnosis is occasionally mistaken for cardiac angina. Prolonged episodes of
of choledocholithiasis. pain localized to the right upper quadrant often herald cholecystitis
• A normal serum biochemistry profile has a negative predictive rather than biliary colic. A clinical history containing the cardinal
value of 97% for ruling out choledocholithiasis. features of biliary colic carries a high diagnostic accuracy.
• Transabdominal ultrasonography is a useful and cost-effective
test for diagnosing cholelithiasis; however, it has significantly Diagnosis
lower utility for choledocholithiasis. Transabdominal ultrasonography is the preferred initial imaging
• For intermediate-risk patients with suspected choledocho- test for cholelithiasis. The sensitivity for detecting the presence
lithiasis, examination of the common bile duct with magnetic of gallstones within the gallbladder lumen on ultrasonography
resonance cholangiopancreatography (MRCP) or endoscopic is 97%.
ultrasonography (EUS) is warranted.
Biliary Sludge
Biliary sludge is often diagnosed on transabdominal ultrasonogra-

Calculous Biliary Disease

phy. It appears as low-amplitude nonshadowing echoes that layer
in dependent portions of the gallbladder. The clinical course of
CURRENT THERAPY
biliary sludge varies from patient to patient. Some patients remain
symptom free, and others develop overt biliary colic. A fraction of
• The treatment of choice for symptomatic cholelithiasis is lapa-
patients demonstrate resolution of biliary sludge on repeat imag-
roscopic cholecystectomy. Elective laparoscopic cholecystec- ing. Symptomatic biliary sludge should be treated the same as cho-
tomy should only be performed for true biliary colic. Vague lelithiasis. Similarly, patients with asymptomatic biliary sludge
symptoms such as bloating, dyspepsia, and atypical abdominal should be managed expectantly.
pain are not commonly related to gallstone disease and thus are
not an indication for gallbladder removal. Treatment
• Laparoscopic cholecystectomy should generally take place
In patients with symptomatic cholelithiasis, treatment should be
within 72 hours of presentation for acute cholecystitis in aimed at acute pain control and prevention of recurrent episodes.
appropriate surgical candidates. In patients without contraindications, cholecystectomy is the pre- 179
• Laparoscopic cholecystectomy is recommended in pregnant
ferred choice for treatment of symptomatic uncomplicated choleli-
patients with symptomatic cholelithiasis and acute cholecystitis. thiasis. This is preferably done via laparoscopy, which offers lower
This is best done by experienced surgeons in the second or early rates of complications and postoperative pain along with better
third trimesters. cosmetic results when compared with open cholecystectomy.
• Patients who should undergo preoperative ERCP for choledo-
Because of the high incidence of cholelithiasis, true biliary colic
cholithiasis include those with high risk stratification and those should be identified before a decision is made to proceed with
deemed intermediate risk in whom a common bile duct stone is laparoscopic cholecystectomy. Vague symptoms such as bloating
identified on MRCP or endoscopic ultrasonography. or atypical abdominal pain are not typical of gallstone disease
and thus often persist after surgery. In cases of asymptomatic
Cholelithiasis uncomplicated cholelithiasis, elective cholecystectomy is not
Epidemiology recommended unless the patient is diabetic or is undergoing an
Gallstone disease is common in Western populations, affecting operation such as gastric bypass surgery, after which there is an
10% to 15% of adults. It is estimated that 6.3 million men increased risk of gallstone formation.
and 14.2 million women in the United States have gallstones. There is a very limited role for medical management of gallstone
Although the vast majority of patients remain asymptomatic disease. Nonoperative management of symptomatic cholelithiasis
throughout their lifetime, roughly one third develop symptoms involves bile dissolution with ursodeoxycholic acid (Actigall).
or complications. The use of medical therapy is limited based on poor efficacy and
high rates of recurrence and thus should be reserved only rarely
for nonsurgical candidates.
Pathophysiology Analgesia is an important adjunct in the treatment of symptom-
Gallstones can be categorized based on their composition. Of atic cholelithiasis. In patients with severe symptoms requiring nar-
patients with gallstone disease in the Western world, 80% to cotic pain medication, meperidine (Demerol) is preferred over
90% have cholesterol stones or cholesterol-predominant stones morphine because it has less effect on the sphincter of Oddi. Non-
(mixed stones). Pigment gallstones account for the remaining 5% steroidal antiinflammatory drugs (NSAIDs) are another mainstay
to 10%. Patients with hemolytic disorders are prone to pigment of therapy. Parenterally administered ketorolac (Toradol) is per-
stone formation, and therefore the correspondence with disorders haps the most commonly used agent for biliary colic in the acute
such as sickle cell anemia, hereditary spherocytosis, and Gilbert’s care setting. Studies have shown that NSAIDs are beneficial in
syndrome is high. the management of pain due to gallstones, and at least one study

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 has suggested that early administration of NSAIDs might decrease
the progression to acute cholecystitis.

Complications
Complications that can potentially arise from cholelithiasis include
acute cholecystitis, cholangitis, pancreatitis, obstructive jaundice,
and, rarely, gallstone ileus.

Choledocholithiasis
Choledocholithiasis often manifests concomitantly with symptom-
atic gallstone disease and is a finding in 5% to 10% of patients
undergoing laparoscopic cholecystectomy for symptomatic chole-
lithiasis. The workup for suspected choledocholithiasis combines
history, physical examination, laboratory data, and various imag-
ing modalities. If the clinical history and physical examination are
suggestive, the clinician should obtain serum liver biochemistry
tests including alanine aminotransferase (ALT), aspartate amino-
transferase (AST), total and fractionated bilirubin, alkaline phos-
phatase (ALP), and γ-glutamyl transpetidase (GGT).
The typical pattern of serum biochemistry is one of cholestasis. A Figure 1 A large gallstone in the common bile duct (CBD) with dilatation
conjugated hyperbilirubinemia along with high levels of GGT and of the CBD proximally. The endoscopic ultrasound probe is visualized in
ALP are seen often in the setting of modest elevation of the trans- the top of the image, and a large cone-shaped shadow is cast distal to the
aminases. ALP is usually elevated out of proportion to the transam- gallstone.
inases; however, extreme levels of AST and ALT have been
described. Transaminase levels greater than 1000 U/L, although
rare in gallstone disease, should not dissuade the clinician from a experience the sensitivity is much lower. Other indirect indicators
diagnosis of choledocholithiasis. Serum biochemistries provide of choledocholithiasis such as common bile duct dilation (77%–
the most utility in ruling out common bile duct stones. A normal 88% sensitivity) can provide additional diagnostic clues. Based
biochemical profile has a negative predictive value of 97%. Clinical on the high false-negative rates for common bile duct stones and
predictors for assessing the likelihood of choledocholithiasis in dilation, a negative transabdominal ultrasound scan cannot rule
IV The Digestive System

patients with symptomatic cholelithiasis are listed in Box 1. out choledocholithiasis. CT scanning has a higher sensitivity for
choledocholithiasis than transabdominal ultrasound. Levels of
Diagnosis radiation and cost have limited its use as a first-line diagnostic tool.
A variety of modalities are available for diagnosing choledocho- Three nonsurgical modalities offer true visualization of the com-
lithiasis. Perhaps the least expensive and most widely available test mon bile duct with comparable sensitivities: Magnetic resonance
is transabdominal ultrasound. Although the sensitivity for choleli- cholangiopancreatography (MRCP), endoscopic retrograde cho-
thiasis is quite high with transabdominal ultrasound, identifying langiopancreatography (ERCP), and endoscopic ultrasonography
stones in the common bile duct (Figure 1) is more difficult. Prospec- (EUS). MRCP has a diagnostic sensitivity of 85% to 92% for
tive studies have reported sensitivities ranging from 22% to 55% detecting choledocholithiasis, and, although it is useful for helping
for detecting common bile duct stones; however, in our clinical determine which intermediate-risk patients would benefit from
preoperative ERCP, small and distal common bile duct stones
are often missed.
180 EUS and ERCP are both minimally invasive techniques useful in
BOX 1 Proposed Strategy to Assign Risk of
the diagnosis and management of choledocholithiasis. Owing to
Choledocholithiasis in Patients with Symptomatic
the proximity of the extrahepatic bile duct to the proximal duode-
Cholelithiasis, Based on Clinical Predictors
num, EUS provides high sensitivity (89%–94%) for detecting com-
Predictors of Choledocholithiasis
mon bile duct stones and is especially useful for detecting stones less
Very Strong
than 5 mm in diameter. ERCP provides similar diagnostic sensitiv-
Common bile duct stone on transabdominal ultrasound
ity; however, ERCP offers therapeutic capability. Because of the
Clinical ascending cholangitis reasonably high risk of complications including pancreatitis
Total bilirubin > 4 mg/dL
(1.3%–15.1%), infection (0.6%–5.0%), gastrointestinal hemor-
rhage (0.3%–2.0%), and perforation (0.1%–1.1%), ERCP as
Strong an initial modality should be reserved for patients who have a high
Dilated common bile duct on transabdominal ultrasound pretest probability for choledocholithiasis and particularly
(>6 mm with gallbladder in situ) for those with complications such as acute cholangitis or severe
Total bilirubin 1.8–4 mg/dL pancreatitis.
Moderate
Research has evaluated the use of ultrasound-guided ERCP with
Abnormal liver biochemistry test other than bilirubin
the goal of avoiding unnecessary bile duct cannulation, and reserv-
Age older than 55 years
ing its use for therapeutic purposes only. A systematic review from
Clinical gallstone pancreatitis
2009 showed that compared with ERCP alone, the use of EUS
avoided unnecessary ERCP in 67.1% of patients in whom no com-
Likelihood of Choledocholithiasis Based on Clinical mon bile duct stone was identified. As more gastroenterologists
Predictors become trained in this modality, EUS-guided ERCP might prove
Presence of any very strong predictor: High to be the preferred diagnostic modality in intermediate-risk
Presence of both strong predictors: High patients for the diagnosis and initial therapy of choledocholithiasis.
No predictors present: Low
All other patients: Intermediate Treatment
Patients with choledocholithiasis should be treated to avoid recur-
From ASGE Standards of Practice Committee, Maple JT, Ben-Menachem T, Anderson MA,
et al: The role of endoscopy in the evaluation of suspected choledocholithiasis. Gastro- rent symptoms and development of complications. Stones can be
intest Endosc 2010;71:1–9, with permission. extracted from the common bile duct via ERCP or laparoscopic
cholecystectomy with bile duct exploration. Studies have shown

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 similar efficacies without significant differences in morbidity or These abnormalities, if present, should raise suspicion for other
mortality; however, clinical expertise varies widely with the lapa- conditions such as choledocholithiasis, cholangitis, or Mirizzi’s
roscopic approach. Ultimately, cholecystectomy should be per- syndrome. Mirizzi’s syndrome is a rare cause of obstructive jaun-
formed to prevent recurrence in surgical candidates. In patients dice characterized by an impacted cystic duct stone that causes
undergoing laparoscopic cholecystectomy for suspected choledo- mass effect and compression of the common bile duct or common
cholithiasis, perioperative management differs based on the risk hepatic duct.
stratification of the patient (see Box 1). High-risk patients should The initial imaging study of choice for acute cholecystitis is trans-
proceed directly to ERCP before surgery for attempted stone abdominal ultrasound. Findings suggestive of cholecystitis include
extraction. In intermediate-risk patients, a preoperative MRCP cholelithiasis, pericholecystic fluid (Figure 2), and a sonographic
or EUS should be performed, and, if the results are positive, the Murphy’s sign (Figure 3). Thickening of the gallbladder wall sup-
patient should undergo ERCP as a prelude to surgery. For sus- ports a diagnosis of acute cholecystitis, but it is a nonspecific
pected choledocholithiasis in low-risk patients, surgery should be
performed without further imaging of the common bile duct.

Complications
The two most common adverse complications of choledocholithia-
sis are gallstone pancreatitis and acute cholangitis. Gallstone pan-
creatitis develops in 3% to 7% of patients with gallstones and is the
most common cause of acute pancreatitis in the United States. The
diagnosis and management of acute pancreatitis is discussed in a
separate chapter.
Acute cholangitis is caused by obstruction and stasis of the bil-
iary tract with complicating bacterial infection. The syndrome is
characterized by fever, jaundice, and abdominal pain, also known
as Charcot’s triad. Patients who develop hypotension and changes
in mental status (Reynold’s pentad) have a poorer prognosis.
Elderly patients often do not demonstrate the classic signs of acute
cholangitis, but they can develop a delayed-sepsis–like syndrome,
of which hypotension is the most pronounced feature. High biliary
pressures promote the translocation of bacteria from the portal cir-

Calculous Biliary Disease

culation into the biliary tree. The most common bacterial organism
seen in acute cholangitis is Escherichia coli (25%–50%), followed
by Klebsiella, Enterobacter, and Enterococcus species.
Treatment for acute cholangitis should focus on antimicrobial
therapy and biliary drainage. Empiric antibiotic regimens should
provide adequate activity against gram-negative and anaerobic Figure 2 Computed tomography (CT) scan demonstrating acute
organisms. Common regimens include monotherapy with ampicil- cholecystitis. The outline arrow indicates gallstones within the
lin and sulbactam (Unasyn) or pipercillin and tazobactam (Zosyn) gallbladder lumen. The two solid arrows highlight mural thickening of
the gallbladder wall and small amounts of pericholecystic fluid. (Image
or combination therapy with a fluoroquinolone plus metronida-
courtesy of Richard M. Gore, MD, Department of Radiology,
zole (Flagyl). NorthShore University Health System, Evanston, IL.)
Patients without hypotension or mental status changes com-
monly show initial improvement after empiric antibiotics are
administered, and thus biliary drainage can be done nonurgently. 181
In patients demonstrating signs of sepsis or severe infection, emer-
gency biliary drainage via ERCP is warranted. Patients who are not
candidates for ERCP may undergo percutaneous transhepatic bil-
iary drainage as an alternative.

Acute Cholecystitis
Acute cholecystitis is a syndrome defined by right upper quadrant
pain, fever, and leukocytosis in the setting of gallbladder inflamma- g
tion. Nausea and vomiting often occur as concurrent symptoms.
Patients commonly have a positive Murphy’s sign on physical
examination, which is defined as abrupt cessation of inspiration
on deep palpation of the gallbladder fossa, just beneath the liver
edge. Approximately 95% of patients with acute cholecystitis have
gallstones. In these instances, cholecystitis is thought to be precip-
itated by obstruction of the cystic duct and by local irritation of the
gallbladder wall. Local inflammation is followed by release of pro-
inflammatory prostaglandins. Superimposed bacterial infection
might or might not complicate acute cholecystitis. As with cholan-
gitis, the main bacteria responsible for infections during acute cho-
lecystitis are E. coli and Klebsiella, Enterobacter, and Enterococcus
species.

Diagnosis
The diagnosis of acute cholecystitis can often be made on physical
examination alone. The most common laboratory finding in acute
cholecystitis is leukocytosis. Mild elevations in AST and ALT can Figure 3 Acute cholecystits: ultrasound. Gallbladder (g) is distended, with
also be seen. Elevations of bilirubin and ALP are typical of biliary mural thickening (arrowhead) and a stone in the gallbladder neck (arrow).
obstruction and are not commonly seen in acute cholecystitis. Positive sonographic Murphy sign was present.

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 cholecystitis carries major risks of gangrene (50%) and perforation
(10%), and mortality ranges from 30% to 50%. Numerous organ-
isms have been associated with acute acalculous cholecystitis,
including bacterial, viral, fungal, and parasitic infections.
The diagnosis is difficult. Patients are often critically ill and
unable to elicit their symptoms. Transabdominal ultrasound is
the best modality to evaluate acute acalculous cholecystitis in the
critically ill patient owing to its availability, cost, and ease of per-
formance. Hepatobiliary iminodiacetic acid (HIDA) and computed
tomography (CT) scanning can have a role in difficult-to-diagnose
acute acalculous cholecystitis and should be considered if ultra-
sound is nondiagnostic. Whereas false-positive test results can
occur, a normal HIDA scan has a high negative predictive value
in evaluating acute acalculous cholecystitis.
Because of the high rate of gangrene and perforation, early cho-
lecystectomy should be performed in patients who are surgical can-
didates. In patients too ill to undergo surgery, biliary drainage with
percutaneous cholecystostomy should be considered.

Gangrenous Cholecystitis, Emphysematous

Cholecystitis, and Gallbladder Perforation
Gangrenous cholecystitis is most often seen in elderly patients and
diabetics along with patients who delay seeking medical treat-
ment for their symptoms. It is the most common complication
of acute cholecystitis and carries a high mortality. Emphysema-
Figure 4 Hepatobiliary iminodiacetic acid (HIDA) scan demonstrating tous cholecystitis is caused by gas-forming bacteria that infect
acute cholecystitis. There is nonfilling of the gallbladder (outline arrow), the gallbladder. E coli and Clostridium species are most com-
with isotope noted in the stomach and duodenum (solid arrows). (Image monly implicated. Gas in the gallbladder may be seen on imaging,
courtesy of Richard M. Gore, MD, Department of Radiology,
NorthShore University Health System, Evanston, IL.)
particularly CT or magnetic resonance imaging (MRI). Patients
with gangrenous or emphysematous cholecystitis are at an ele-
IV The Digestive System

vated risk for gallbladder perforation. Early empiric antibiotics

and cholecystectomy are crucial in the management of these
finding. Transabdominal ultrasound has a sensitivity of 88% for complications to minimize mortality and prevent perforation of
diagnosing acute cholecystitis. Hepatobiliary cholescintigraphy the gallbladder, a condition that carries a mortality rate
(HIDA scan) (Figure 4) is recommended if the suspicion of chole- of 42% to 60%.
cystitis remains after a negative transabdominal ultrasound.
MRCP and CT scan are typically not necessary for the diagnosis, Gallbladder Disease in Pregnancy
although CT scan can be useful if complications from cholecystitis Pregnancy is a major risk factor for cholesterol gallstone forma-
such as perforation are suspected. tion. Because of anatomic changes secondary to the gravid uterus,
biliary colic can be difficult to delineate from other causes of
Treatment abdominal pain. Pregnant patients often have gallstones on trans-
The treatment for acute cholecystitis involves supportive care, anal- abdominal ultrasound, and thus a detailed history and physical
182 gesia, antibiotics, and either surgery or percutaneous gallbladder examination are needed to diagnose a patient’s abdominal pain
drainage. If treatment is delayed or inadequate, numerous potential as biliary. Patients with other symptoms including bloating or dys-
complications can result. These include emphysematous or gangre- pepsia should be evaluated for other etiologies.
nous cholecystitis and gallbladder perforation. All patients with In pregnant patients with recurrent symptomatic cholelithiasis,
acute cholecystitis should be admitted to the hospital and given laparoscopic cholecystectomy remains the treatment of choice.
supportive care including intravenous fluids. NSAIDs and opioid The second and early third trimesters are the best times to perform
analgesics are typically used for pain control. cholecystectomy owing to ease and lower rates of complications.
Although bacterial etiologies complicate less than half of all epi- Nonsurgical management of gallstones is limited in pregnancy.
sodes, empiric antibiotics are commonly administered to patients NSAIDs are generally avoided late in pregnancy owing to the risk
with acute cholecystitis. Appropriate antibiotic regimens are the of premature closure of the ductus arteriosis, especially after 30 to
same as those used in the setting of acute cholangitis (see the dis- 32 weeks of gestation.
cussion of complications of choledocholithiasis). After appendicitis, acute cholecystitis is the second most com-
In patients who are adequate surgical candidates, cholecystec- mon nonobstetric surgical emergency during pregnancy. As with
tomy should be performed within 72 hours of initial presentation. nonpregnant patients, pregnant women with acute cholecystitis
Numerous prospective trials and a Cochrane Database review have should be treated with cholecystectomy in addition to medical
evaluated early versus delayed (6–12 weeks) cholecystectomy. management. Early surgery for pregnant patients with acute cho-
There is overwhelming consensus that early surgery carries no lecystitis has been found to decrease relapse rates and hospital
increase in complications or perioperative morbidity and is associ- readmissions. No differences in maternal or fetal morbidity and
ated with shorter hospital stays. Furthermore, early laparoscopic mortality have been found in patients treated conservatively versus
cholecystectomy eliminates the risk of recurrent episodes of acute surgically for acute cholecystitis during pregnancy.
cholecystitis.

Acute Acalculous Cholesystitis References

Abboud PA, Malet PF, Berlin JA, et al: Predictors of common bile duct stones prior to
An estimated 5% to 10% of cases of acute cholecystitis develop cholecystectomy: A metaanalysis, Gastrointest Endosc 44:450–455, 1996.
without the presence of gallstones. Acute acalculous cholecystitis Akriviadis EA, Hatzigavriel M, Kapnias D, et al: Treatment of biliary colic with diclo-
is often seen in the setting of serious medical illness, complicated fenac: a randomized, double-blind, placebo-controlled study, Gastroenterology
113:225–231, 1997.
surgery, severe blunt trauma, and burn injuries. Other conditions ASGE Standards of Practice Committee, Maple JT, Ben-Menachem T, Anderson MA,
such as diabetes mellitus, vasculitis, AIDS, and congestive heart et al: The role of endoscopy in the evaluation of suspected choledocholithiasis,
failure have also been implicated as risk factors. Acute acalculous Gastrointest Endosc 71:1–9, 2010.

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Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2019. Elsevier Inc. Todos los derechos reservados.
 ASGE Standards of Practice Committee, Maple JT, Ikenberry SO, Anderson MA, et al: using these markers. Therefore the American Gastroenterological
The role of endoscopy in the management of choledocholithiasis, Gastrointest Association has released a consensus statement suggesting that
Endosc 74:731–744, 2011.
Barie PS, Eachempati SR: Acute acalculous cholecystitis, Gastroenterol Clin North chronic diarrhea should be defined as a decrease in fecal consis-
Am 39:344–357, 2010. tency lasting for 4 or more weeks.
Dhupar R, Smaldone GM, Hamad GG: Is there a benefit to delaying cholecystectomy
for symptomatic gallbladder disease during pregnancy? Surg Endosc 24:108–112, Epidemiology
2010.
Everhart JE, Khare M, Hill M, Maurer KR: Prevalence and ethnic differences in gall- Chronic diarrhea is a common cause of death in developing coun-
bladder disease in the United States, Gastroenterology 117:632–639, 1999. tries, as well as the second leading cause of overall mortality in chil-
Freitas ML, Bell RL, Duffy AJ: Choledocholithiasis: Evolving standards for diagnosis dren 1 to 59 months old. The prevalence in the general population
and management, World J Gastroenterol 12:3162–3167, 2006. in developed nations and economic impact of chronic diarrhea has
Gore RM, Thakrar KH, Newmark GM, et al: Gallbladder imaging, Gastroenterol
Clin North Am 39:265–267, 2010. not been well established. This could be related to the variable
Gurusamy KS, Samraj K: Early versus late laparoscopic cholecystectomy for acute nature of the studies that have been performed with regard to def-
cholecystitis, Cochrane Database Syst Rev 18: CD005440. inition, population characteristics, and overall study design. Rough
Papi C, Catarci M, Ambrosio D, et al: Timing of cholecystectomy for acute calculous estimates based on this limited information suggest that chronic
cholecystitis: A meta-analysis, Am J Gastroenterol 99:147–155, 2004.
diarrhea can affect up to 5% of the population and can cost up
to $350,000,000 annually from work loss alone.

CHRONIC DIARRHEA Classification Based on Pathophysiology

Elucidating the exact cause of chronic diarrhea can be very chal-
Method of
lenging, because there are several hundred conditions that can be

de Leon, MD
Andre
related. It is often separated into three basic categories, including
watery, fatty (malabsorption), and inflammatory (with blood
and pus); however, these should not be strictly adhered to because
there is often considerable overlap between the categories. Watery
CURRENT DIAGNOSIS diarrhea can be further subdivided into osmotic, secretory, drug-
induced, and functional types. Osmotic diarrhea is related to water
History retention; secretory diarrhea is due to reduced absorption of water;
• Duration and frequency drug-induced is as stated in its name; and functional diarrhea is due
• Presence of fever/blood to hypermotility of the gut.
• Food/medication intake
• Travel history Watery Diarrhea
Watery diarrhea can be subdivided into four categories, including
Physical Examination
• Gastrointestinal examination
osmotic, secretory, drug-induced, and functional types. Fecal
osmotic gap can be calculated, which will help guide further

Chronic Diarrhea
• Hydration status
• Digital rectal examination
workup and diagnosis. An elevated osmotic gap (>125 mOsm/
• Other systems: endocrine, ophthalmologic, skin
kg) is suggestive of possible osmotic causes, such as lactose intoler-
ance. A normal osmotic gap can be associated with irritable bowel
Testing syndrome or may be indicative of a further workup for possible
• Fecal occult blood testing celiac disease. A decreased osmotic gap (<50 mOsm/kg) points
• Stool for ova/parasites, Clostridium difficile and other bacteria toward secretory causes, including infectious (ova, parasite, bacte-
• Stool antigen for cryptosporidium, giardia ria, giardia), endocrine (hyperthyroidism), autoimmune (Addi-
• Fecal electrolytes (Na, K, Osm) son’s), neoplastic (pheochromocytoma), and anatomic defect.
• Fecal leukocytes 183
• Erythrocyte sedimentation rate (ESR) Fatty/Malabsorptive Diarrhea
• Complete blood count (CBC) Malabsorptive diarrhea is, as the name implies, secondary to
• Other: iron panel (celiac sprue), TSH (hyperthyroidism), liver impaired absorption along the gut. This can be due to structural
function tests (LFTs) abnormalities (gastric bypass, short bowel syndrome, celiac sprue,
• Colonoscopy with biopsy pancreatic insufficiency) or structural abnormalities related to vas-
cular compromise (mesenteric ischemia). Impaired absorption can
also occur secondary to infections such as Tropheryma whipplei
(Whipple’s disease), Giardia, small bowel bacterial overgrowth,
and tropical sprue. Medications such as aminoglycoside antibi-
CURRENT THERAPY otics, orlistat (Alli, Xenical), thyroid supplementation, acarbose
(Precose), and ticlopidine (Ticlid) can also cause malabsorptive
• Supportive care and rehydration, if necessary diarrhea.
• Trial of discontinuation of possible offending medication/food
(lactose, gluten, sorbitol) Inflammatory Diarrhea
• Dietary modification with increased fiber intake (dietary or Inflammation leading to diarrhea is often due to autoimmune,
supplementation) infectious, or neoplastic processes or radiation exposure. Autoim-
• Specific therapy as directed by culture and susceptibilities or mune processes are felt to play a large role in inflammatory bowel
biopsy disease (IBD), which often manifests as Crohn’s disease or ulcera-
• Empiric therapy trial with antibiotics tive colitis. Infections such as Clostridium difficile, Mycobacterium
• Empiric trial of probiotics1 (limited evidence of efficacy in tuberculosis, Yersinia, cytomegalovirus, herpes simplex virus, ame-
healthy adults with chronic diarrhea) biasis, and Strongyloides can lead to a diarrhea with associated
inflammation of the bowel. Colon cancer (villous adenocarcinoma)
1
Not FDA approved for this indication. and lymphoma can also cause inflammatory diarrhea.

Clinical Manifestations
Chronic diarrhea has traditionally been defined based on consis- History. Thorough investigation of a patient complaining of
tency, volume, and frequency of stools. However, recent studies ongoing diarrhea-like features should always include a detailed
have found that there is considerable variability in definition when medical history. A clear understanding of the patient’s symptoms

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