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DIARRHEA
Grace L. Villa-Malayan MD, DPPS, DPAPP

OBJECTIVES
Definition of Diarrhea
Epidemiolgy
Mechanisms and Pathophysiology
Different causes of diarrhea
Diagnostics
Management
Prevention

GASTROENTERITIS
Denotes infections of the gastrointestinal tract
caused by bacterial, viral, or parasitic
pathogens
Most common manifestation is DIARRHEA

DIARRHEA
It is the an excessive loss of fluid and
electrolyte in the stool
It is a symptom of gastroenteritis with or
without vomiting, abdominal pain and fever
Acute diarrhea is a sudden onset of excessive
stools of >10 ml/kg/day in infants and
>200g/24 in older children which lasts for <14
days
Chronic or persistent diarrhea if the episode
lasts for >14 days

EPIDEMIOLOGY
Diarrheal disorders in childhood account for a
large portion (18%) of pediatric deaths
Estimated 1.5 Million deaths per year globally
WHO and UNICEF estimate that almost 2.5
Billion episodes of diarrhea occur in children
<5 years old

ETIOLOGY OF DIARRHEA
It is due infection through the fecal-oral route
or by ingestion of contaminated food or water
Associated with poverty, poor environmental
hygiene and development indices
Enteropathogens that are infectious in small
inoculums (shigella, enterohemorrhagic E. coli,
Campylobacter jejuni, noroviruses, rotavirus,
Giragia lamblia, Cryptosporidium parvum,
Entamoeba histolytica) ---- transmitted through
person-to-person contact
Cholera is a consequence of food or water
supply contamination
Food-borne outbreaks of bacterial diarrhea in
the US are commonly due to Salmonella, E.
coli, Clstridium botulinum, Clostridium
perfringens, and Staphylococcus aureus.

PATHOGENESIS OF INFECTIOUS DIARRHEA
Pathogenesis and severity of bacterial disease
depend on the presence of preformed toxins
(S.aureus, B.cereus), produce secretory
(cholera, E.coli, Salmonella, Shigella) or
cytotoxic (Shigella,S. aureus, V.
parahaemolyticus, C. difficile, EE. Coli, C.
jenuni) toxins or are invasive and on whether
they replicate in food.

PATHOPHYSIOLOGY AND MECHANISM
The basis of diarrhea is disturbed intestinal
solute transport and water absorption
Water movement across intestinal membranes
is passive and both determined by both active
and passive fluxes of solutes like sodium.
Chloride and glucose

SECRETORY and DIARRHEA
Occurs when the intestinal epithelial cell solute
transport system in an active state of secretion
It is caused by secretagogue such as cholera
toxin

Toxin binds to epithelium of the bowel


Stimulates intracellular cAMP of cGMP


Increased secretion and electrolyte transport
















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PRIMARY
MECHANISM
DEFECT STOOL
EXAMINATION
EXAMPLES COMMENT
SECRETORY Decreased
absorption
Increased
secretion
Electrolyte
transport
Watery, normal
osmolality with ion
gap <100mOsm/kg
Cholera, toxigenic E.
coli; carcinoid, VIP,
neuroblastoma,
congenital chloride
diarrhea, Clostridium
difficile,
cryptosporidiosis
(AJDS)
Persists during
fasting; bile alt
malabsorption can
also increase
intestinal water
secretion; no stool
leukocytes
OSMOTIC Maldigestion
Transport
defects
Ingestion of
unabsorbable
substances
Watery, acidic, and
reducing substances:
increased osmolality
with ion gap >100
mOsm/kg
Lactase deficiency,
glucose galactose
malabsorption,
lactulose, laxative
abuse
Stops with
fasting:increased
breth hydrogen with
carbohydrate
malabsorption; no
stool leukocytes
INCREASED
MOBILITY
Decreased
transit time
Loose to normal
appearing stool,
stimulated by
gastrocolic reflex
Irritable bowel
syndrome,
thyrotoxicosis,
postvagotomy
dumping syndrome
Infection can also
contribute to
increased motility
DECREASED
MOBILITY
Defect in
neuromuscular
unit(s) stasis
(bacterial
overgrowth)
Loose to normal
appearing stool
Pseudo-obstruction,
blind loop
Possible bacterial
overgrowth
DECREASED
SURFACE
AREA
(OSMOTIC,
MOBILITY)
Decreased
functional
capacity
Watery



Short bowel
syndrome, celiac
disease, rotavirus
enteritis
Might require
elemental diet plus
parenteral
alimentation
MUCOSAL
INVASION
Inflammation,
decreased
colonic
Reabsorption,
increased
motility
Blood and increased
WBCs in stool

Salmonella, Shigella,
Infection; Amoebiasis;
Yersinia,
Campylobacter
Infections
Dysentery evident in
blood, mucus and
WBCs

Ion gap = Stool osmolality [[stool Na + stool K] x 2]

INFECTIOUS DIARRHEA
E. coli
Rotavirus
Salmonella
Shigella
Amoebiasis







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COMPARISON OF THREE TYPES OF ENTERIC INFECTION
PARAMETER I II III
MECHANISM Noninflammatory
(enterotoxin or
adherence/superficial
invasion)
Inflammatory (invasion,
cytotoxin)

Penetrating
LOCATION Proximal small bowel Colon Distal small bowel
ILLNESS Watery diarrhea Dystentery Enteric fever
STOOL
EXAMINATION
No fecal leukocyte
Mild or no inc.
lactoferin
Fecal
polymorphonuclear
leukocytes
LActoferin
Fecal mononuclear
leukocyte
EXAMPLES Vibrio cholera
E. coli (ETEC,LT,ST)
C. perfringens
Bacillus cereus
Stphyloccoccus aureus
Also
+
:
Giardia lamblia
Rotavirus
Norwalk-like viruses
Cryptosporidium
parvum
E. coli (EPEC, EAEC)
Microsporidia
Cyclospora cayetanenis

Shigella
E. coli (EIEC, EHEC)
Salmonella enteridis
Vibrio
parahaemolyticus
Clostridium difficile
Campylobacter jejuni
Entamoeba histolytica
Salmonella typhi
Yersenia enterocolitica
?Campylobacter fetus

I. ESCHERICHIA COLI
Important causes of enteric infections
Member of the Enterobacteriaceae family
They are Facultative anaerobic, Gram negative bacilli
Most fecal E.coli do not cause diarrhea









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ENTEROTOXIGENIC E.COLI (ETEC)
Causes 10-30% of dehydrating infantile
diarrhea in developing world
Causes 20-60% of travelers diarrhea
Responsible for 3-39% of overall diarrhea
episodes in the developing world
S/S
Explosive watery, nonmucoid, nonbloody
diarrhea, abdominal pain, nausea, vomiting
With or without fever
Self limiting
Usually resolves in 3-5 days but may last >1
week

PATHOGENESIS
Diarrhea is caused by the colonization of the
small intestine and elaboration of enterotoxins
Toxins: Heat-labile enterotoxin (LT) cAMP
Heat-stable enterotoxin (ST)-cGMP
Adherence is due to fimbrial colonization
factor antigens (CFs or CFAs)

ENTEROINVASIVE E.COLI (EIEC)
Watery diarrhea or dysentery syndrome ith
blood, mucus and leukocytes in stools
Fever, systemic toxicity, crampy abdominal
pain, tenesmus and urgency
Resembles bacillary dysentery
Most seen in outbreaks
EIEC causes colonic lesions with ulcerations,
hemorrhage, mucosal and submucosal edema
and infiltration by the polymorphonuclear
leukocytes

PATHOGENESIS
They invade the gut and produce dysentery like
illness
They enter into the cells --- intracellular
multiplication---- intracellular and intercellular
spread and host-cell death
Adheres thru invasion of the plasmid antigen

ENTEROPATHOGENIC E.COLI (EPEC)
The major cause of acute and persistent
diarrhea in children less than 2 years old in
developing countries
In developed countries, they cause occasional
outbreak in daycare centers and pediatric ward
S/S
Profuse watery, nonbloody diarrhea with
mucus, vomiting and low grade fever
Persistent diarrhea (>14 days) can lead to
malnutrition

PATHOGENESIS
EPEC causes blunting of villi, inflammatory
changes and sloughing superficial mucosa of
the duodenum and colon
Has characteristics attaching and effacing
(A/E) histopathologic lesion--- intimate
attachment of bacteria to the epithelial surface
and effacement of host cell microvilli

SHIGA TOXIN-PRODUCING E.COLI (STEC)
Five to 10% of children can have STEC
hemorrhagic colitis
Severe illness occurs most often among
children from 10 months to 10 years old
Transmitted from person to person as well as
by food and water
Poorly cooked hamburger is the most common
cause
S/S
Abdominal pain with diarrhea that is initially
watery but within a few days it can become
blood-streaked or grossly blood

PATHOGENESIS
STEC can affect the colon most severely
Organism adhere to intestinal cells
Strains affect humans by attaching-effacing
lesions
The attachment mechanism has genes (intimin,
tir, Esp A-D) very closely related to EPEC
Shiga toxin in the virulence factorC

ENTEROAGGRIVATIVE E.COLI (EAEC)
Associated with acute and persistent pediatric
diarrhea in developing countries, mostly in
children less than 2 years old.
S/S
Watery mucoid, secretory diarrhea with low-
grade fever and little or no vomiting
Watery diarrhea can persist for >14 days
Associated with growth retardation and
malnutrition in infants and developing
countries

PATHOGENESIS
It forms a characteristic biofilm on the
intestinal mucosa and induce shortening of the

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villi, hemorrhagic necrosis and inflammatory
responses

PHASES OF PATHOGENESIS
1. Adherence to the intestinal mucosa by the way
of aggregative adherence fimbriae or related
adhesions
2. Enhanced production of mucus
3. Production of toxins
4. Inflammation that results in damage of the
mucosa and intestinal secretion

The intestinal inflammatory response
(increased fecal lactoferrin, interleukin-8 and
1Beta) may be related to growth impairment
and malnutrition
EAEC are recognized by adherence to Hep- 2
cells in an aggregative, stacked brick- like
pattern called aggregative adherence

DIFFUSELY ADHERENT E.COLI
? in doubt of its true pathogens
Both developed and developing countries have
associated the organisms with diarrhea
especially in children less than 2 years old

PATHOGENESIS
Two Putattive Adherence Factors:
1. Surface fimbriae responsible for the
diffuse adherence of phenotype in a
prototype strain
2. Outer membrane protein designated as
AIDA-I

DIAGNOSIS
Non-DNA dependent tests have been
developed for STEC
Serotype O157:H7 is suggested by isolation of
an E.coli that fails to ferment Sorbitol on
MacConkey Sorbitol medium
Other use tissue culture assays
Use of DNA probes for encoding various
virulence traits
EIEC there is positive fecal leukocyte
EIEC and STEC have elevated
polymorphonuclear leukocyte count with a left
shift
Fecal lactoferrin, IL8, IL-1 Beta are
inflammatory markers
Electrolytes are non specific


TREATMENT
The corner stone is still APPROPRIATE
FLUID AND ELECTROLYTE THERAPY as
specified by WHO
Oral rehydrating solutions are used to prevent
dehydration
Zinc supplementation
Antimicrobial therapy

PREVENTION
Proper hygiene
Prolonged breast-feeding
Proper food handling and disposal

ROTAVIRUS
Family : Reoviridae
Wheel-like, triple-shelled icosahedrons
containing 11 segments of double-stranded
RNA
Classified by serogroup A, B, C, D, F, G
Group A includes the common human
pathogens

PATHOGENESIS
Viruses can cause human diarrhea selectively
infect and destroy villus tip cells in the small
intestine
Biopsy showed villus blunting and round cell
infiltrate the lamina propia



Selective viral infection of intestinal villus tip
cells thus leads to:
a. Decreased absorption of salt and water
and an imbalance in the ratio of
intestinal fluid absorption to secretion

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b. Diminished disaccharidase activity and
malabsorption of complex
carbohydrates particularly lactose

CLINICAL MANIFESTATION
Rotavirus infection incubation period is within
48 hrs (range 1-7 days) with mild to moderate
fever
Vomiting
Watery stools
Stool is without gross blood or WBC
Infection occurs among 4-36 months old

DIAGNOSIS
Based on clinical epidemiologic features
ELISA with >90% specificity
Latex agglutination tests
Electron microscopy
RNA PCR

LABORATORY
Isotonic dehydration with acidosis is the most
common finding in children with severe viral
enteritis
Stools are free of blood leukocyte

DIFFERENTIAL DIAGNOSIS
Other infectious causes of enteritis such as
bacteria and protozoa
Surgical cases such appendicitis, bowel
obstruction and intussusception

TREATMENT
Avoid and treating dehydration are the main
goals
Maintenance of the nutritional status
Lactobacillus species is helpful for mild cases

PROGNOSIS
Most fatalities occur in infants with poor
access to medical care and are attributed to
dehydration
Primary infection results in a predominantly
serotype-specific immune response

PREVENTION
Proper hygiene
Vaccination



SHIGELLA PATHOGENESIS
Superficial invasion of colonic mucosa through
M cells located over Peyer patches --- after
phagocytosisapoptosis of macrophages,
multiplication of bacteria, release of
transmigration of neutrophils into the lumen of
colon, neutrophil necrosis and degranulation
epithelial barrier and mucosal destruction



DIAGNOSIS
Asses degree of dehydration


History and PE
Clinically determine the etiology of diarrhea


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Stool examination can give important data on
the etiology of diarrhea

TREATMENT
Oral rehydration therapy
Enteral feeding
Diet selection
Zinc supplementation
Probiotics?
Antibiotics?




HOME-MADE ORAL FLUID RECIPE
Preparing 1L of aral fluid using salt, sugar and water at
home. The ingredients to be mixed are:
1 tsp salt
8 leevl tsp sugar
1L (5 cupfuls) of clean drinkinf water or water
that has been boiled and then cooled.

Zinc supplementation for 10-14 days for less
than 0 months = 10 mg/day for more than 6
months = 20mg/day
Probiotics = restores good bacteria in the gut =
enhances host protective immunity such as
down-regulation of pro-inflammatory
cytokines and up-regulation of anti-
inflammatory cytokines







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Dietary Recommendations


Antimicrobial agents for the treatment of specific
causes of diarrhea



PREVENTION
Report notifiable disease such as Botulinum,
E.coli, Salmonellosis, Shigellosis, Cholera,
Cryptosporidosis, and Cyclospora
Exclusive breast-feeding
Improved complementary feeding practices
Rotavirus immunization
Improved water and sanitary facilities and
promotion of personal and domestic hygiene
Improved case management of diarrhea


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