1. Acute and Chronic Diarrhea
Dr.Atakan Yeşil Yeditepe University
Department of Gastroenterology

2. Definitions Acute diarrhea <14 days duration
Persistent diarrhea >14 days
Chronic diarrhea >30 days
Inflammatory diarrhea
fever, tenesmus, fecal leukocytes, colonic bleeding
Non-inflammatory diarrhea

3. Principles of Evaluation
Majority of cases resolve in 1-2 days without any sequelae
Stool culture has a low yield
Specific diagnosis is useful for antimicrobial treatment decisions but not supportive treatment

4. Acute Diarrhea Subtypes
Organik (Nonfunctional)
Noninflammatory: Norwalk, Rota, Giardia, Staf. Aureus, B. Cereus, C. Perfringens, ETEC, Vibrio cholerae
İnflammatory: CMV, EHEC, C. Difficile, Shigella, Salmonella, EIEC, Yersinia, E. Hystolytica
İnorganik (Fonctunial)

5. The Big 4 found on 233,000 stool cultures
Camphylobacter %
Salmonella %
Shigella %
E coli O157:H7 (STEC) %
Total yield from stool cultures is 5.8%

6. Other agents Norwalk virus Norovirus CMV (HIV, elderly)
Various E coli strains (traveller’s diarrhea)
Vibrio (shellfish, water)
Giardia (persistent diarrhea)
Cryptosporidium (farms)
Isosporia
Entamoeba histolytica
Cyclospora
Yersinia (lymphadenitis)
Aeromonas

8. Clostridium difficile causes antibiotic-associated colitis; it colonizes the human intestinal tract after the normal gut flora have been altered by antibiotic therapy.
It is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among elderly hospitalized patients.

9. Clinical Presentation
Asymptomatic (carrier state)
Antibiotic-associated diarrhea
Antibiotic-associated colitis +/-Pseudomembranes
profuse, watery-semi-formed stools
mucoid - heme +
systemic symptoms common
marked abdominal tenderness
hypoalbuminemia
elevated WBC
Ileus - toxic megacolon
no diarrhea
acute abdomen
shock

10. Carrier state
About 20 percent of hospitalized adults are C. difficile carriers who shed C. difficile in their stools but do not have diarrhea; in long-term care facilities, carriage rate may approach 50 percent.
Although asymptomatic, these individuals serve as a reservoir for environmental contamination.
The host immune response to C. difficile may play a role in determining an individual's carrier status.
Data on treatment of asymptomatic carriers are limited and routine treatment is not recommended

11. C. difficile–associated diarrhea
Manifestations of C. difficile–associated diarrhea with colitis include watery diarrhea up to 10 or 15 times daily with lower abdominal pain and cramping, low grade fever, and leukocytosis .
Fever (T>38.5) is a sign of severe C. difficile–associated diarrhea (CDAD); fever is associated with CDAD in about 15 percent of cases.
Leukocytosis in the setting of CDAD is common;
Infrequently, symptoms present as late as 10 weeks after cessation of therapy

12. The antibiotics most frequently implicated in predisposition to C
The antibiotics most frequently implicated in predisposition to C. difficile infection are fluoroquinolones, clindamycin, cephalosporins, and penicillins, but virtually all antibiotics, including metronidazole and vancomycin, can predispose to C. difficile

13. Physical examination generally demonstrates lower abdominal tenderness
Physical examination generally demonstrates lower abdominal tenderness. Sigmoidoscopic or colonoscopic examination may demonstrate a spectrum of findings, from patchy mild erythema and friability to severe pseudomembranous colitis
Unexplained leukocytosis in hospitalized patients (even in the absence of diarrhea) may reflect underlying C. difficile infection.

16. The diagnosis of C. difficile infection requires the presence of moderate to severe diarrhea or ileus, and either
●A stool test positive for C. difficile toxins or toxigenic C. difficile
●Endoscopic or histologic findings of pseudomembranous colitis

17. Diagnostic Tests for C. difficile
Culture -Sensitivity nearly 100%
-Specificity good if confirm toxin
Manual Cytotoxin
-Sensitivity and specificity
nearly 100%
EIA toxin test - sensitivity 90%

18. Treatment

19. What to do? Individual patient: In general
Treat with Flagyl for 10 days
Reserve Vancomycin for critically ill or allergic
In general
Try to use Flagyl instead of Clindamycin for anaerobic coverage
Limit broad spectrum antibiotics
C. difficile patients
gloves
private rooms, if possible

20. Recommended by AGA;
obtaining stool cultures on initial presentation in immunocompromised patients (HIV-infected, elderly, patients with comorbidities or with underlying inflammatory bowel disease), those with severe or bloody diarrhea.

21. The management of patients with acute diarrhea begins with general measures such as hydration and alteration of diet. AGA recommends no antibiotic therapy in most cases

22. If empiric therapy is warranted, we recommend treatment with a fluoroquinolone for three to five days in the absence of suspected EHEC infection.
If campylobacter is suspected we recommend azithromycin or erythromycin as alternative agents, given high rates of fluoroquinolone resistance.
Directed antibiotic therapy should be administered when an intestinal pathogen is identified.

23. AGA suggests the antimotility agent loperamide be used for the symptomatic treatment of patients with acute diarrhea in whom fever is absent or low grade and the stools are not blood

24. Chronic Diarrhea
Its definition has traditionally been based upon the frequency, volume, and consistency of stools.
American Gastroenterological Association suggests that chronic diarrhea should be defined as a decrease in fecal consistency lasting for four or more weeks.

25. Irritable bowel syndrome
Patients with IBS can present with a wide array of symptoms, which include both gastrointestinal and extraintestinal complaints. Patients with IBS complain of crampy lower quadrant pain with diarrhea, constipation, alternating diarrhea and constipation, or normal bowel habits alternating with either diarrhea and/or constipation. Pain may be relieved with defecation.

26. Functional diarrhea
Functional diarrhea has been classified separately from IBS in a consensus statement (Rome III), which defines it as continuous or recurrent passage of loose (mushy) or watery stools without abdominal pain or discomfort

27. Inflammatory bowel disease
Inflammatory bowel disease primarily refers to ulcerative colitis and Crohn disease.

28. Microscopic colitis
Microscopic colitis is characterized by chronic watery (secretory) diarrhea without bleeding. It usually occurs in middle-aged patients but can affect childrenTwo different types of microscopic colitis have been generally recognized:
●Lymphocytic colitis
●Collagenous colitis without lymphocytic infiltration of the surface epithelium
Collagenous and lymphocytic colitis produce a similar clinical picture characterized by nonbloody chronic watery (secretory) diarrhea of up to two liters daily. The clinical course is mainly intermittent.
The term microscopic colitis implies that the diagnosis is made by histology. Thus, colonoscopy usually reveals macroscopically normal colonic mucosa although slight edema, erythema, and friability may be seen.
Although specimens obtained by flexible sigmoidoscopy are frequently sufficient to establish the diagnosis, the severity of histologic changes declines from the proximal to the distal colon; thus, biopsies obtained from the right colon (ie, by colonoscopy) are optimal

29. Malabsorption syndromes
Lactose intolerance
Chronic pancreatitis
Celiac disease
Bacterial overgrowth of the small intestine

30. Post-Cholecystectomy
Diarrhea following cholecystectomy has been reported in 5 to 12 percent of patients

31. Chronic infections
Some persisting infections (eg, C. difficile, Aeromonas, Plesiomonas, Campylobacter, Giardia, Amebae, Cryptosporidium, Whipple's disease, and Cyclospora) can be associated with chronic diarrhea

32. Secretory diarrhea
Secretory diarrhea characteristically continues despite fasting, is associated with stool volumes >1 liter/day, and occurs day and night in contrast to osmotic diarrhea in which these characteristics are uncommon.
Although usually unnecessary, the distinction between an osmotic and a secretory diarrhea can also be established by measuring stool electrolytes and calculating an osmotic gap.
The osmotic gap is determined by subtracting the sum of the sodium and potassium concentration in stool multiplied by a factor of 2 from 290 mOsm/kg to account for unmeasured anions (ie, ({Na+} + {K+})) (calculator 1). An osmotic gap of >125 mOsm/kg suggests an osmotic diarrhea while a gap of <50 mOsm/kg suggests a secretory diarrhea .

33. Further testing in patients with secretory diarrhea may include stool cultures to exclude chronic infection, imaging of the small and large bowel, and selective testing for secretagogues, such as gastrin or vasoactive intestinal polypeptide ("Zollinger-Ellison syndrome (gastrinoma):
Secretory diarrhea occurs in 80 percent of patients with carcinoid syndrome and is often the most debilitating component of the syndrome. Stools may vary from few to more than 30 per day, are typically watery and nonbloody, and can be explosive and accompanied by abdominal cramping. The abdominal cramps may be a consequence of mesenteric fibrosis or intestinal blockage by the primary tumor. The diarrhea is usually unrelated to flushing episodes.

34. Testing for bile-acid malabsorption or empiric treatment with a bile-acid binding resin may also be helpful. An association between bile acid malabsorption and gallbladder dysmotility has been described (Habba syndrome). The diarrhea responds to cholestyramine.
Further testing in patients with osmotic diarrhea may be unnecessary if the osmotic agent can be identified based upon the history. An example is inadvertent ingestion of sorbitol (such as in sugar substitutes) or lactose in patients who have lactose intolerance. Temporary avoidance of lactose-containing foods can help establish the diagnosis of lactose intolerance in patients who were unaware of the diagnosis. As an alternative, the diagnosis can be made by specific testing for lactose intolerance (such as hydrogen breath testing)
Breath testing can also identify specific forms of carbohydrate malabsorption (such as fructose or sucrose) but is rarely required. Testing the stool for laxatives may occasionally be required if laxative abuse is suspected. Laxative abuse can be suggested by the presence of melanosis coli on sigmoidoscopy or colonoscopy.

35. Inflammatory or infectious diarrhea
Inflammatory diarrhea should be suspected in patients with clinical features suggesting inflammatory bowel disease C. difficile infection, those at risk for opportunistic infections such as tuberculosis, or those with a pertinent travel history. Diagnosis can usually be established by sigmoidoscopy or colonoscopy or by analysis of stool specimens.
Serum markers of acute inflammation (such as the sedimentation rate and C-reactive protein levels) are useful in identifying patients with suspected inflammatory diarrhea. These markers are typically normal in patients with noninflammatory chronic diarrhea such as IBS or food intolerance. However, their test characteristics have not been well validated for this purpose; thus, their role in patients presenting with chronic diarrhea is unclear.

36. Fecal leukocytes
A number of studies have evaluated the accuracy of fecal leukocytes alone or in combination with occult blood testing. The ability of these tests to predict the presence of an inflammatory diarrhea has varied greatly, with reports of sensitivity and specificity ranging from 20 to 90 percent A meta-analysis of diagnostic test accuracy estimated that at a peak sensitivity of 70 percent, the specificity of fecal leukocytes was only 50 percent . Thus, fecal leukocytes are not a good test for inflammatory diarrhea.

37. Fecal calprotectin!!!!!!
Calprotectin is a zinc and calcium binding protein that is derived mostly from neutrophils and monocytes.
It can be detected in tissue samples, body fluids, and stools, making it a potentially valuable marker of neutrophil activity .
Fecal calprotectin levels are increased in intestinal inflammation and may be useful for distinguishing inflammatory from noninflammatory causes of chronic diarrhea .
The authors note that in settings with a low prevalence of IBD (such as among patients seen for abdominal pain or diarrhea in a primary care setting) the test might be most useful to help rule out IBD while in high prevalence settings (such as a gastroenterology clinic) the test might be most useful for ruling in IBD. However, test characteristics varied considerably among the studies included in the meta-analysis. Furthermore, diagnostic evaluation (including endoscopy) is sometimes needed even if IBD is not strongly suspected. Thus, fecal calprotectin can be considered as an adjunctive test in diagnostic evaluation of patients with chronic diarrhea.
Other potential roles have also been proposed including in colorectal cancer screening and monitoring of activity in inflammatory bowel disease . However, its test characteristics are not yet sufficiently defined for routine clinical application for of these indications