Diarrheal Diseases
Presented by Dr. Kapil Dhingra

Diarrhea
• Diarrhea is defined as passage of abnormally
liquid or unformed stools at an increased
frequency.
• For adults on a typical Western diet, stool weight
>200 g/d can generally be considered diarrheal.
• Diarrhea may be further defined
– acute if <2 weeks,
– persistent if 2–4 weeks,
– chronic if >4 weeks

Acute Diarrhea
• >90% caused by infectious agents.
• Remaining 10%
– medications,
– toxic ingestions,
– ischemia

 Infectious Agents
– feco-oral transmission
– five high-risk groups
1. Travelers - enterotoxigenic or enteroaggregative
Escherichia coli, Campylobacter, Shigella, Giardia
2. Consumers of certain foods -
– Salmonella, Campylobacter, or Shigella from chicken
– enterohemorrhagic E. coli (O157:H7) from undercooked
hamburger
– Bacillus cereus from fried rice or other reheated food
– Staphylococcus aureus or Salmonella from mayonnaise or
creams
– Salmonella from eggs
– Listeria from uncooked foods or soft cheeses
– Vibrio species, Salmonella, or acute hepatitis A from seafood,
especially if raw.

3. Immunodeficient persons
– primary immunodeficiency (e.g., IgA deficiency, common variable
hypogammaglobulinemia, chronic granulomatous disease)
– secondary immunodeficiency states
(e.g., AIDS, senescence, pharmacologic suppression)
4. Daycare attendees and their family members
5. Institutionalized persons

Pathogen Incubation Period
Bacillus cereus, Staphylococcus aureus 1-8 hr
Clostridium perfringens 8-24 hr
Vibrio cholerae, enterotoxigenic
Escherichia coli, Klebsiella pneumoniae,
Aeromonas species
8–72 h
Enteropathogenic and enteroadherent E.
coli, Giardia organisms
1-8 days
C. difficile 1–3 d
Hemorrhagic E. coli 12–72 h
Rotavirus and norovirus 1–3 d
Salmonella, Campylobacter, and
Aeromonas species, Vibrio
parahaemolyticus, Yersinia
12 h–11 d

• Infectious diarrhea may be associated with
systemic manifestations
– Reiter's syndrome - arthritis, urethritis, and
conjunctivitis may accompany or follow infections
by Salmonella, Campylobacter, Shigella, and
Yersinia.
– Hemolytic-uremic syndrome - enterohemorrhagic
E. coli (O157:H7) and Shigella

Other Causes
• Medications –
antibiotics,
cardiac antidysrhythmics,
 antihypertensives,
nonsteroidal anti-inflammatory drugs (NSAIDs),
antidepressants,
chemotherapeutic agents,
 bronchodilators,
antacids,
 laxatives

• Ischemic colitis –
– acute lower abdominal pain preceding
watery, then bloody diarrhea;
– acute inflammatory changes in the sigmoid or left
colon while sparing the rectum
• Toxins –
– organophosphate insecticides
– amanita and other mushrooms;
– arsenic

Approach to the Patient: Acute
Diarrhea

• Most episodes of acute diarrhea are mild and self-limited
and do not justify the cost and potential morbidity rate of
diagnostic or pharmacologic interventions.
• Indications for evaluation include
– profuse diarrhea with dehydration,
– grossly bloody stools,
– fever 38.5°C (101°F),
– duration >48 h without improvement,
– recent antibiotic use,
– new community outbreaks,
– associated severe abdominal pain in patients >50 years,
– elderly (70 years)
– immunocompromised patients.

Investigations
• The cornerstone of diagnosis in those
suspected of severe acute infectious diarrhea
is microbiologic analysis of the stool.
• Workup includes
a) cultures for bacterial and viral pathogens,
b) direct inspection for ova and parasites
c) immunoassays for certain bacterial toxins (C.
difficile), viral antigens (rotavirus), and protozoal
antigens (Giardia, E. histolytica).

• If stool studies are unrevealing, flexible sigmoidoscopy
with biopsies and upper endoscopy with duodenal
aspirates and biopsies may be indicated.
• Structural examination by sigmoidoscopy, colonoscopy,
or abdominal CT scanning (or other imaging
approaches) may be appropriate in patients with
uncharacterized persistent diarrhea to exclude IBD or
as an initial approach in patients with suspected
noninfectious acute diarrhea caused by ischemic colitis,
diverticulitis, or partial bowel obstruction.

Treatment: Acute Diarrhea
• Fluid and electrolyte replacement are of
central importance to all forms of acute
diarrhea.
• Profoundly dehydrated patients, especially
infants and the elderly, require IV rehydration.

• WHO ORS
Sodium chloride 2.6 gm/lt
Glucose, anhydrous 13.5 gm/lt
Potassium chloride 1.5 gm/lt
Trisodium citrate, dihydrate 2.9 gm/dl

Antibiotics
• Reduce severity and duration of diarrhea.
– Treat empirically without diagnostic evaluation
using a quinolone, such as ciprofloxacin (500 mg
bid for 3–5 d).
– Empirical treatment can also be considered for
suspected giardiasis with metronidazole (250 mg
qid for 7 d).

• Antibiotic coverage is indicated, whether or
not a causative organism is discovered, in
patients who
are immunocompromised,
have mechanical heart valves or recent vascular
grafts, or
are elderly.

• In moderately severe nonfebrile and
nonbloody diarrhea, antimotility and
antisecretory agents such as loperamide can
be useful adjuncts to control symptoms.
• Such agents should be avoided with febrile
dysentery, which may be exacerbated or
prolonged by them.

Chronic Diarrhea
• Diarrhea lasting >4 weeks
• In contrast to acute diarrhea, most of the
causes of chronic diarrhea are noninfectious.

Causes of chronic diarrhea
Secretory
causes
Osmotic
causes
Steatorrheal
causes
Inflammatory
causes
Dysmotile
causes
Factitial
causes
Iatrogenic
causes

• Secretory Causes
– due to derangements in fluid and electrolyte
transport across the enterocolonic mucosa.
– characterized clinically by watery, large-volume
fecal outputs
– typically painless
– persist with fasting

1. Medications
antibiotics,
cardiac antidysrhythmics,
 antihypertensives,
nonsteroidal anti-inflammatory drugs (NSAIDs),
antidepressants,
chemotherapeutic agents,
 bronchodilators,
antacids,
 laxatives
Chronic ethanol consumption

2. Bowel Resection, Mucosal Disease, or
Enterocolic Fistula
– inadequate surface for reabsorption of secreted
fluids and electrolytes.
– tends to worsen with eating.
– With disease (e.g., Crohn's ileitis) or resection of
<100 cm of terminal ileum, dihydroxy bile acids may
escape absorption and stimulate colonic secretion
(cholorrheic diarrhea).
– may contribute to so-called idiopathic secretory
diarrhea, in which bile acids are functionally
malabsorbed from a normal-appearing terminal
ileum.

3. Hormones
– Metastatic gastrointestinal carcinoid tumors
• watery diarrhea ,episodic
flushing, wheezing, dyspnea, and right-sided valvular
heart disease.
• Diarrhea is due to the release into the circulation of
potent intestinal secretagogues
serotonin, histamine, prostaglandins, and various
kinins.
– Gastrinoma
• diarrhea due to fat maldigestion owing to pancreatic
enzyme inactivation by low intraduodenal pH

– VIPoma
• watery diarrhea hypokalemia achlorhydria syndrome,
also called pancreatic cholera,
• due to a non- cell pancreatic adenoma, referred to as a
VIPoma,
• secretes VIP and a host of other peptide hormones
pancreatic polypeptide, secretin, gastrin, gastrin-
inhibitory polypeptide ,neurotensin, calcitonin, and
prostaglandins

– Medullary carcinoma of the thyroid
• watery diarrhea caused by calcitonin, other secretory
peptides, or prostaglandins
– colorectal villous adenomas

4. Congenital Defects in Ion Absorption
• defects in specific carriers associated with ion
absorption
• defective Cl–/HCO3
– exchange (congenital
chloridorrhea) with alkalosis (which results from a
mutated DRA [down-regulated in adenoma] gene) and
• defective Na+/H+ exchange (congential sodium
diarrhea), which results from a mutation in the NHE3
(sodium-hydrogen exchanger) gene and results in
acidosis.
• hormone deficiencies such as occurs with
adrenocortical insufficiency (Addison's disease) that
may be accompanied by skin hyperpigmentation.

• Osmotic Causes
– ingested, poorly absorbable, osmotically active
solutes draw enough fluid into the lumen to
exceed the reabsorptive capacity of the colon.
– characteristically ceases with fasting or with
discontinuation of the causative agent.

1. Osmotic Laxatives
– Ingestion of magnesium-containing antacids,
health supplements, or laxatives
2. Carbohydrate Malabsorption
– acquired or congenital defects in brush-border
disaccharidases and other enzymes
– Ex. lactase deficiency
• sugars, such as sorbitol, lactulose, or fructose, are
malabsorbed, and diarrhea ensues with ingestion of
medications, gum, or candies sweetened with these
poorly or incompletely absorbed sugars

• Steatorrheal Causes
– Fat malabsorption
– greasy, foul-smelling, difficult-to-flush diarrhea
often associated with weight loss and nutritional
deficiencies due to concomitant malabsorption of
amino acids and vitamins
– Quantitatively, defined as stool fat exceeding the
normal 7 g/d

Causes of steatorrhea
1. Intraluminal Maldigestion
– most commonly results from pancreatic exocrine
insufficiency
– Other causes include
• cystic fibrosis;
• pancreatic duct obstruction;
• somatostatinoma.
– Bacterial overgrowth in the small intestine may
deconjugate bile acids and alter micelle
formation, impairing fat digestion
• occurs with stasis from a blind-loop,
• small-bowel diverticulum or
• dysmotility

2. Mucosal Malabsorption
– most commonly occurs from celiac disease
• characterized by villous atrophy and crypt hyperplasia
• proximal small bowel
• fatty diarrhea associated with multiple nutritional
deficiencies
– Tropical sprue
• a similar histologic and clinical syndrome
• occurs in residents of or travelers to tropical climates

– Whipple's disease,
• due to the bacillus Tropheryma whipplei
• histiocytic infiltration of the small-bowel mucosa,
• typically occurs in young or middle-aged men;
• frequently associated with arthralgias, fever,
lymphadenopathy, and extreme fatigue, and it may
affect the CNS and endocardium

3. Postmucosal Lymphatic Obstruction
– congenital intestinal lymphangiectasia
– acquired lymphatic obstruction secondary to
trauma, tumor, cardiac disease or infection
– unique constellation of fat malabsorption with
enteric losses of protein (often causing edema)
and lymphocytopenia.

• Inflammatory Causes
– accompanied by pain, fever, bleeding, or other
manifestations of inflammation
– The unifying feature on stool analysis is the
presence of leukocytes or leukocyte-derived
proteins such as calprotectin
– Any middle-aged or older person with chronic
inflammatory-type diarrhea, especially with blood,
should be carefully evaluated to exclude a
colorectal tumor.

Idiopathic Inflammatory Bowel Disease
―Crohn's disease
―ulcerative colitis

Distinguishing characteristics of CD and UC
UC
CD
Feature
Only colon
SB or colon
Location
Continuous,
begins distally
Skip lesions
Anatomic
distribution
Involved in >90%
Rectal spare
Rectal
involvement
Universal
Only 25%
Gross bleeding
Rare
75%
Peri-anal disease
No
Yes
Fistulization
No
50-75%
Granulomas

Endoscopic features of CD and UC
UC
CD
Feature
Continuous
Discontinuous
Mucosal
involvement
Rare
Common
Aphthous ulcers
Abnormal
Relatively
normal
Surrounding
mucosa
Rare
Common
Longitudinal ulcer
No
In severe cases
Cobble stoning
Common
Uncommon
Mucosal friability
distorted
Normal
Vascular pattern

Pathologic features of CD and UC
UC
CD
Feature
Uncommon
Yes
Transmural inflammation
No
50-75%
Granulomas
Rare
Common
Fissures
No
Common
Fibrosis
Uncommon
Common
Submucosal inflammation

Radiologic features of CD and UC
UC
CD
Collar button
ulcers
Nodularity
granularity
cobble stoning
string sign of SB

Primary or Secondary Forms of Immunodeficiency
Eosinophilic Gastroenteritis
o Eosinophil infiltration of the mucosa, muscularis, or
serosa at any level of the GI tract may cause
diarrhea, pain, vomiting, or ascites.
o atopic history,
o Charcot-Leyden crystals due to extruded eosinophil
contents may be seen on microscopic inspection of
stool, and
o peripheral eosinophilia

• Dysmotility Causes
– Hyperthyroidism,
– carcinoid syndrome,
– drugs (e.g., prostaglandins, prokinetic agents)
– Primary visceral neuromyopathies or idiopathic acquired intestinal
pseudoobstruction may lead to stasis with secondary bacterial
overgrowth causing diarrhea.
– Diabetic diarrhea, often accompanied by peripheral and generalized
autonomic neuropathies, may occur in part because of intestinal
dysmotility.
– The exceedingly common IBS characterized by disturbed intestinal and
colonic motor and sensory responses to various stimuli. Symptoms of
• stool frequency cease at night,
• alternate with periods of constipation
• accompanied by abdominal pain relieved with defecation,
• rarely result in weight loss.

• Factitial Causes
– accounts for up to 15% of unexplained diarrheas
referred to tertiary care centers
– Hypotension and hypokalemia are common co-
presenting features

APPROACH TO THE PATIENT:
CHRONIC DIARRHEA

• History
– onset
– duration
– pattern
– aggravating (especially diet) and relieving factors
– stool characteristics
• Other features
– fecal incontinence
– Fever
– weight loss
– Pain
– exposures (travel, medications, contacts with diarrhea)
– extraintestinal manifestations (skin changes, arthralgias,
oral aphthous ulcers)
• Family history of IBD or sprue

• Physical findings
– hemodynamic status
– thyroid mass,
– wheezing,
– heart murmurs,
– edema,
– abdominal masses,
– lymphadenopathy,
– mucocutaneous abnormalities,
– perianal fistulas, or anal sphincter laxity

• Peripheral blood leukocytosis, elevated
sedimentation rate, or C-reactive protein
suggests inflammation;
• anemia reflects blood loss or nutritional
deficiencies;
• eosinophilia may occur with parasitoses,
neoplasia, collagen-vascular disease, allergy, or
eosinophilic gastroenteritis.
• Blood chemistries may demonstrate electrolyte,
hepatic, or other metabolic disturbances.
• Measuring tissue transglutaminase antibodies
may help detect celiac disease.

• Patients suspected of having IBS should be
initially evaluated with flexible sigmoidoscopy
with colorectal biopsies

• For secretory diarrheas medication-related side effects or
laxative use should be reconsidered.
• Microbiologic studies should be done including
– fecal bacterial cultures
– inspection for ova and parasites, and
– Giardia antigen assay (the most sensitive test for giardiasis).
• Small-bowel bacterial overgrowth can be excluded by intestinal
aspirates with quantitative cultures or with glucose or
lactulose breath tests

• Upper endoscopy and colonoscopy with biopsies
and small-bowel barium x-rays are helpful to rule
out structural or occult inflammatory disease.
• When suggested by history or other findings,
screens for peptide hormones should be pursued
(e.g., serum gastrin, VIP, calcitonin, and thyroid
hormone/thyroid-stimulating hormone, or
urinary 5-hydroxyindolacetic acid, and
histamine).

• osmotic diarrhea should include tests for
lactose intolerance and magnesium
ingestion, the two most common causes.
• Low fecal pH suggests carbohydrate
malabsorption;
• lactose malabsorption can be confirmed by
lactose breath testing or by a therapeutic trial
with lactose exclusion and observation of the
effect of lactose challenge (e.g., a liter of
milk).

• For those with fatty diarrhea, endoscopy with
small-bowel biopsy (including aspiration for
Giardia and quantitative cultures) should be
performed

Tests for steatorrhea
• Quantitative test
– 72hr stool fat collection – gold standard
• > 7gm/day – pathologic
• Qualitative tests
– Sudan lll stain
• Detect clinically significant steatorrhea in
>90% of cases
– Acid steatocrit – a gravimetric assay
• Sensitivity – 100%, specificity – 95% , PPV – 90%
– NIRA (near infra reflectance analysis)
• Equally accurate with 72hr stool fat test
• Allows simultaneous measurement of fecal fat, nitrogen, CHO

• Chronic inflammatory-type diarrheas should
be suspected by the presence of blood or
leukocytes in the stool.
• Such findings warrant stool cultures;
inspection for ova and parasites; C. difficile
toxin assay; colonoscopy with biopsies.

Treatment: Chronic Diarrhea
• depends on the specific etiology
• If the cause can be eradicated, treatment is
curative as with
 resection of a colorectal cancer,
 antibiotic administration for Whipple's disease or
tropical sprue, or
 discontinuation of a drug

• Suppression of the underlying mechanism
 elimination of dietary lactose for lactase deficiency
or gluten for celiac sprue,
 use of glucocorticoids or other anti-inflammatory
agents for idiopathic IBDs,
 adsorptive agents such as cholestyramine for ileal
bile acid malabsorption,
 proton pump inhibitors for the gastric
hypersecretion of gastrinomas,

 somatostatin analogues such as octreotide for
malignantcarcinoid syndrome,
 prostaglandin inhibitors such as indomethacin for
medullary carcinoma of the thyroid, and
 pancreatic enzyme replacement for pancreatic
insufficiency
• Replacement of fat-soluble vitamins may also
be necessary in patients with chronic
steatorrhea.

Thank you