DIARRHEAS

CCBS- 3
 Diarrheal diseases
Diarrhea:
Passage of more than 250g of stool per day
Patients perceive this as:
Increased volume, Increased fluidity or
Increased frequency of stools
Acute diarrhea = less than 3 weeks
Chronic diarrhea = over 4 weeks
Dysentery:
Low volume, painful diarrhea with blood,
mucus and WBCs in stool
Diarrhea is divided into three subtypes:
1. Invasive diarrhea
2. Secretory diarrhea
3. Osmotic diarrhea
Invasive diarrhea
It is characterized by :

Invasion of the intestine (enterocytes) by the

pathogen
Inflammation in the bowel mucosa
A Low-volume diarrhea and
Diarrhea with blood and leukocytes (i.e., dysentery)

Causes:

Campylobacter jejuni (MC in USA)

Shigella spp.
Entamoeba histolytica
Invasive diarrhea
Screening test
1. Fecal smear for leukocytes
Positive
2. Order
1. Stool culture (gold standard) and
2. Stool for ova and parasites
Secretory diarrhea
It is characterized by :
Loss of isotonic fluid from the intestine
High-volume diarrhea
No inflammation in bowel mucosa
Causes:
Laxatives: danger of melanosis coli (black
bowel syndrome) with use of
phenanthracene laxatives
Enterotoxin Production: Vibrio cholera,
Enterotoxigenic E. coli
Increased serotonin: Carcinoid syndrome
Secretory diarrhea
Mechanisms:

Enterotoxins produced by the pathogens

stimulates Chloride channels regulated by cAMP
and cGMP causing loss of isotonic fluid (NaCl)
in stool
Laxatives
Serotonin increases bowel motility
Screening tests:

Fecal smear for leukocytes: negative

Increased 5-HIAA: carcinoid syndrome
Osmotic diarrhea
Characteristics:
An Osmotically active substance (e.g. lactose) in
the lumen of bowel is draws hypotonic salt solution
out of bowel
High-volume diarrhea
No inflammation in bowel mucosa
Causes:
Disaccharidase deficiency (Lactose intolerance)
Ingestion of poorly absorbable solutes (e.g.,
magnesium sulfate laxatives)
Screening tests:
Fecal smear for leukocytes: negative
Stool osmotic gap >100 mOsm/kg
Lactase Deficiency
Lactase: an enzyme that breaks lactose into
glucose and galactose
It is a Disaccharidase and a brush border enzyme
Lactase deficiency: results in
Inability to break lactose down.
Large amounts of lactose present in the bowel
It is osmotically active  draws fluid out of the bowel.
Anaerobic bacteria in colon act on the lactose &
produce hydrogen and other gases and acids.
Gas production would result in abdominal distension
and explosive diarrhea.
The stool would be acidic
Selected organisms causing
diarrhea
Norwalk virus
Most common cause of adult
gastroenteritis*
Patients present with vomiting and
diarrhea
Fecal oral transmission
Causes secretory diarrhea.
Rotavirus
Most common cause of childhood diarrhea*
Usually occurs in winter months*
Transmitted by fecal oral route
Infects small intestine mucosa and produces,
Watery, non-bloody diarrhea
Secretory diarrhea,
Rotazyme test on stool
establishes diagnosis
Campylobacter jejuni:

Curved or S-shaped gram-negative rods

MC invasive bacterial enterocolitis in US
Contracted by eating contaminated poultry or milk
Invades jejunum and colonic mucosa and produces
crypt abscesses and ulcers resembling ulcerative
colitis
Blood and mucus are present in the stool (dysentery)
Positive fecal leukocyte smear
Usually self limited, Invasive diarrhea
Clostridium difficile:

Gram positive rod

Associated with pseudomembranous colitis
Antibiotics (e.g., ampicillin (MCC), clindamycin)
cause overgrowth of toxin-producing C. difficile
in colon
Toxin damages the mucosa of the colon resulting
in formation of a Pseudomembrane (creamy to
greenish flat plaques) that covers colon mucosa.
Toxin assay of stool is best confirmatory test
Rx: metronidazole; vancomycin produces
resistant strains
Escherichia coli:
Enterotoxigenic EC (ETEC):
Produces heat-stable toxin that stimulates
guanylate or adenylate cyclase, causing
secretory diarrhea (traveler's diarrhea)
Enterohemorrhagic EC
O157:H7 serotype
contracted by eating undercooked beef.
Produces hemolytic uremic syndrome
Mycobacterium avium-intracellulare
complex (MAC)

Acid-fast rods
Causes diarrhea with malabsorption in AIDS
(CD4 count <50 cells/μL)
Organisms present within foamy macrophages in
lamina propria.
Simulates Whipple's disease
Morphology
Hallmark of MAC
infection:
Abundant acid fast
bacilli within
macrophages
Vibrio cholera:
Produces a powerful toxin
Enterotoxin stimulates adenylate cyclase in small
bowel resulting in secretory diarrhea (rice water
stools).
Contracted from drinking contaminated water or
eating contaminated seafood,
Rx is fluid replacement; glucose and sodium
required in oral supplements (glucose enhances
sodium uptake).
Cryptosporidium parvum:

Most common cause of diarrhea in AIDS

Contracted by ingesting oocysts (acid-fast
positive)
Attaches to brush borders of small intestine
Produces diarrhea and abdominal pain
Detected by using string test
Entamoeba histolytica:

Produces dysentery with flask-shaped ulcers in

cecum
Trophozoites phagocytose red blood cells
= erythrophagocytosis
Portal vein spread to liver  amoebic liver
abscess
Rx: metronidazole
Giardia lamblia:

MC protozoal cause of diarrhea in United States

Produces acute and chronic diarrhea with
malabsorption
Contracted by ingesting cysts (from mountain
spring)
Detected with antigen test of stool
Rx: metronidazole
Microbial Pathogens associated
with Diarrhea
Pathogen Discussion

VIRUSES

Cytomegalovirus Common cause of diarrhea in AIDS

Norwalk virus Most common cause of

adult gastroenteritis

Rotavirus Most common cause of childhood diarrhea

Rotazyme test on stool establishes diagnosis
Pathogen Discussion

BACTERIA

Bacillus cereus Gram-positive rodFood poisoning with preformed toxin

Associated with fried rice or tacos

Campylobact Curved or S-shaped gram-negative rodsContracted by eating

contaminated poultry or milkProduces dysentery with crypt
er jejuni abscesses and ulcers resembling ulcerative colitis

Clostridium Food poisoning with preformed toxin

botulinum (blocks release of acetylcholine)
Adult Causes paralysis and mydriasisFood
Infant poisoning often contracted by eating
spores in honey
Pathogen Discussion
BACTERIA
Clostridium difficile Associated with pseudomembranous
colitisAntibiotics (e.g., ampicillin)
cause overgrowth of toxin-producing
C. difficile in colonPseudomembrane
covers colon mucosaToxin assay of
stool is best confirmatory testRx:
metronidazole; vancomycin produces
resistant strains
Escherichia coli ETEC: produces heat-stable toxin that
stimulates guanylate or adenylate
cyclase, causing secretory diarrhea
(traveler's diarrhea)STEC (O157:H7
serotype): contracted by eating
undercooked beef. Produces hemolytic
uremic syndrome
Pathogen Discussion

BACTERIA

Mycobacteri Acid-fast rodsCauses diarrhea with

um avium- malabsorption in AIDS (CD4 count <50
intracellular cells/μL)Foamy macrophages in lamina
e complex propria simulate Whipple's disease
(MAC)

Mycobacterium Acid-fast organisms swallowed from

tuberculosis
primary focus in lungInvade Peyer's
patchesCircumferential spread in
lymphatics leads to stricture
formation
Pathogen Discussion
BACTERIA
Salmonella Pathogenic Salmonella: S. typhi, S.
species paratyphi, S. enteritidisAnimal
reservoirs: turtles, hamsters, lizards
Typhoid fever caused by S. typhi:
Week 1: invades Peyer's patches and
produces sepsis (blood culture best
for diagnosis) Week 2: diarrhea
(positive stool culture); classic triad of
bradycardia, neutropenia,
splenomegaly Chronic carrier state
due to gallbladder disease
Shigella No animal reservoirsMucosal
species ulceration, pseudomembranous
inflammation, dysentery
Pathogen Discussion

BACTERIA

Staphylococcus Food poisoning with preformed toxin;

aureus
culture food not stoolGastroenteritis
occurs in 1-6 hours after eating
Vibrio cholerae Enterotoxin stimulates adenylate cyclase in small bowel
Contracted from drinking contaminated water or eating
contaminated seafood, especially crustaceaRx is fluid
replacement; glucose and sodium required in oral supplements
(cotransport system for reabsorption)

Yersinia enterocolitica Dysentery, mesenteric lymphadenitis (granulomatous

microabscesses)
Pathogen Discussion

PROTOZOA

Balantidium coli Produces colonic ulcers with bloody diarrhea

Cryptosporidium Most common cause of diarrhea in AIDSContracted by ingesting

parvum oocysts (acid-fast positive)

Entamoeba Produces dysentery with flask-shaped ulcers in cecumTrophozoites

histolytica phagocytose red blood cellsRx: metronidazole

Giardia lamblia Most common protozoal cause of diarrhea in United StatesProduces

acute and chronic diarrhea with malabsorptionDetected with antigen
test of stoolRx: metronidazole

Isospora belli Oocysts (acid-fast positive)Associated with AIDS diarrhea

Pathogen Discussion

HELMINTHS

Ascaris lumbricoides Bowel obstruction in adult phase

Diphyllobothrium latum Adult worms produce vitamin B12 deficiency

Enterobius vermicularis Eggs deposited in anus cause anal

pruritusUrethritis in girls;
appendicitisNo eosinophilia
Necator americanus Adults attach to villi, resulting in blood loss and iron
deficiency

Strongyloides stercoralis Abdominal pain and diarrhea

Trichuris trichiura Abdominal pain, diarrheaRectal prolapse in children

A 55-year-old woman saw her physician because of
complaints of bloody diarrhea and malaise. She states that
she has had severe abdominal cramps and watery diarrhea
for the past 2 days. When she had a bowel movement this
morning, she said that she noticed blood in her stool. When
asked about what she may have eaten or drunk recently, she
remembered drinking unpasteurized apple juice about 4 days
ago. Her vital signs are temperature 37°C, pulse 100/min,
blood pressure 120/85 mm Hg, and respirations 19/min. Fecal
specimens grown on sorbitol containing MacConkey agar
isolated several lactose fermenting gram-negative, rod-
shaped organisms. Which of the following organisms is the
most likely cause of this patient’s condition?
A. Campylobacter duodenale
B. Shigella sonnei
C. Escherichia coli (an enterohemorrhagic strain)
D. Escherichia coli (an enterotoxigenic strain)
E. Escherichia coli (an enteropathogenic strain)
If this patient is treated with an antibiotic, more toxin is
released from the bacteria and can result in renal
failure. Which toxin causes this syndrome?
A. Endotoxin
B. Shiga toxin
C. Toxin A
D. Labile toxin
E. Exotoxin B
A 41-year-old man presented to his physician with crampy
bilateral lower quadrant pain that decreased after bowel
movements. He has a low-grade fever of 37.8°C. He states
that his bowel movements are watery but there is no blood in
them, and that he has had about 15 bowel movements in the
past 24 hours. About 1 week before he began having
diarrhea, the patient finished a 3-week course of antibiotic to
treat acute bacterial prostatitis. A complete blood count
reveals a leukocytosis of 20,000 white blood cells/L. A
colonoscope shows numerous elevated yellow-white plaques
with the intervening mucosa being hyperemic and
edematous. Which of the following is the most likely
causative organism of this patient’s condition?
A. Staphylococcus aureus
B. Shigella sonnei
C. Vibrio cholera
D. Clostridium difficile
E. Campylobacter jejuni
An 80-year-old man living in a care home presents to
the Emergency Department with a four-day history of
cramping abdominal pain and watery, non-bloody
diarrhoea. He denies vomiting and states his
diarrhoea has been worsening with five episodes of
loose stool in the past 24 hours. All of his meals are
provided by the care home. No other care home
residents are symptomatic. He has no recent travel
history. He is being treated for a catheter-associated
urinary tract infection with co-amoxyclav by his GP.
He had colon cancer, for which he had a partial
colectomy one year ago. His medication includes
aspirin and a proton pump inhibitor.
Examination
Temperature 38.1°C, oxygen saturation 95%,
respiratory rate 18, pulse 112, blood pressure
100/65 mmHg.
He has signs of mild dehydration
His abdomen is mildly distended and tender but
there are no signs of guarding or rebound
tenderness
Bowel sounds are active
There is no organomegaly.
His urinary catheter is draining straw-coloured
urine
Rectal examination reveals a large prostate and
diarrhoeal stool with no evidence of blood
Bloods
Haemoglobin 11.4 g/dL (11.4–15.0 g/dL)
White cell count 28.5 × 109/L (3.9–10.6 g/dL)
Platelets 342 × 109/L (150–440 × 109/L)
C-reactive protein 86 mg/L (<5 mg/L)
Radiology
Abdominal radiograph shows dilated and thickened
loops of bowel suggestive of colitis
Microbiology
Blood cultures were negative
Stool was sent for testing but no results are
available yet
What is his most likely cause, and the differential
diagnosis of watery diarrhoea?
What tests would you request on the stool sample?
What is the appropriate treatment?
The most likely cause of this elderly gentleman’s
watery, non-bloody diarrhoea is Clostridium
difficile bacterial gastroenteritis given the very
high peripheral white cell count and raised
inflammatory markers (C-RP) associated with the
following risk factors:
Recent hospital admission
Living in a care home
Antibiotic therapy
Bowel surgery and being on proton pump inhibitors
Important negative features of the history include
no travel, not eating-out and no illness in other
care home residents
C. difficile is an anaerobic, spore-forming
bacterium that is carried in the gut of some people
It causes disease (pseudomembranous colitis)
through production of toxins that damage the
colonic mucosa
In severe disease it can lead to toxic megacolon,
bowel perforation and death
The differential diagnosis of watery
diarrhoea includes:
Viral – enterovirus, rotavirus (usually in children) and
norovirus (in which vomiting is almost always present)
Bacterial – Campylobacter spp., C. difficile,
Yersinia enterocolitica, Salmonella sp., Shigella
sp. (usually bloody diarrhoea), Vibrio cholera
(associated with contact or travel to endemic areas)
Parasitic – Giardia lamblia (appropriate travel history
required) or cryptosporidium in the
immunocompromised or young children
Toxins (which have the shortest incubation period after
exposure) – staphylococcal food poisoning, Bacillus
cereus toxin or enterotoxogenic E. coli
Non-infectious causes – alcohol excess, lactose
intolerance or inflammatory bowel disease
Investigations of watery diarrhoea must include a
stool sample sent for:
MC&S for bacterial causes
PCR testing looking for viral causes
Ova, cysts and parasites
C. difficile toxin testing as only toxin-producing
strains cause disease
Culture methods for C. difficile are slow and
no longer used for diagnosis
Blood cultures are taken to exclude urinary sepsis
and gram-negative sepsis
The latter could indicate a perforation of the gut or
leakage of bowel contents that would indicate
severe colonic disease
Treatment is based on removing as many risk
factors as possible and treating with oral antibiotics
(metronidazole or vancomycin) depending on
severity of disease and local hospital policy
In severe or life-threatening cases, surgical
management may also be required (colectomy)
In chronic or recurrent cases, alternate therapy
includes probiotics, faecal enemas and fidoxamicin
Prevention is by eliminating risk factors thereby
reducing the likelihood of developing disease
Reduced transmission from person to person
requires hand washing with soap and water after
every contact with a patient having diarrhoea
Alcohol hand rub does not destroy the spores and
is therefore not sufficient to prevent spread
All patients with C. difficile should be isolated
because its spores are hardy and easily
contaminate the environment
This is why environmental cleaning plays an
important role in controlling outbreaks
A 25-year-old woman presents with a three-week
history of explosive, loose, watery diarrhoea that
started ten days after she returned from a
holiday in Nepal. She drank bottled water while
there, but brushed her teeth with tap water and
had ice in her drinks. She opens her bowels at
least five times a day and has increased flatulence.
Her stools are foul smelling and float in the toilet bowl.
There is no blood in the stool. The diarrhoea is
associated with cramping central abdominal pain. Her
appetite is unchanged, there is no vomiting, but she
has noticed some weight loss. Her past medical
history is unremarkable. She does not take any
regular medications.
Examination
She is haemodynamically stable and not
dehydrated
Her abdomen is slightly distended but is soft and
non-tender to palpation
There is no organomegaly and the liver is not
tender to palpation
Auscultation reveals normal bowel sounds
INVESTIGATIONS
Haematology and renal and liver function tests are
within normal range
Inflammatory markers are not raised
Radiology: Abdominal x-ray showed mildly dilated
loops of bowel but no evidence of obstruction.
Microbiology: No pathogens isolated from stool
MC&S. Stool ova, cysts and parasites (OCP)
reveal multiple cystic structures measuring 10 x 10
micrometers. These are smooth-walled and oval
 Questions
1. What are the causes of diarrhoea in a
returning traveller?
2. What is the diagnosis in this case?
3. How is this treated and can it be
prevented?
Travellers’ diarrhoea is an encompassing term of
the syndrome of diarrhoea occurring in travellers
It is the commonest health issue affecting returning
travellers
It can be caused by one (or more) of a number of
different organisms including bacteria, viruses and
parasites
Common causes include bacteria such as
Escherichia coli (ETEC), Campylobacter sp.
and Salmonella sp., protozoa such as
Cryptosporidium and Giardia sp., and viruses
such as norovirus
Less common causes of diarrhoea in travellers
include dysentery (Shigella sp.) and cholera
(Vibrio cholera)
TD is usually acquired through ingesting
contaminated food or drinking water
The travel destination and clinical symptoms will
assist in determining the likely underlying
pathogen(s)
Small bowel infection usually causes a watery
diarrhoea while large bowel invasion presents as a
dysentery (bloody diarrhoea) or colitis
Given the chronic nature of the watery diarrhoea
and the travel history in this case, the cause is
more likely parasitic
The differential diagnosis would include
giardiasis, or if immunocompromised,
cryptosporidiosis
There may be more than one pathogen associated
with TD and full investigation for bacteria, parasites
and viruses should be performed
The patient’s stool sample (Figure 4.8) contains cysts of
Giardia lamblia
Bacterial culture is negative
This microbiological diagnosis fits with the clinical picture of
watery diarrhoea, foul-smelling steatorrhoea (fatty, floating
stools) and abdominal cramps
Giardia is most prevalent in developing countries on
account of poor sanitation
However, it also occurs in developed countries where water
treatment is not adequate
G. lamblia is a protozoan parasite acquired from ingestion
of cysts in contaminated water or food, or by the fecal-oral
route
Once in the small intestine they excyst, releasing
trophozoites that bind to the small intestinal wall
Here they cause damage leading to reduced absorption of
solutes, which causes an osmotic diarrhoea, malabsorption
of fat and fat-soluble vitamins, resulting in steatorrhoea
Diagnosis is by stool microscopy looking for ova,
cysts and parasites
This should be requested on all patients with
travellers’ diarrhoea even if another pathogen is
isolated, as multiple infections may occur
The cyst and trophozoite stages are both seen in
the stool and will be detected in 90% of cases if
stool samples are collected on three separate days
Several drugs can treat giardiasis, including
albendazole, tinidazole and metronidazole
The close contacts of the patient should also be
screened for giardiasis
There is no vaccine against giardiasis
Prevention of giardiasis, and other causes of travellers’
diarrhoea, is best done using good food and water
hygiene practices
Avoid drinking tap water, or using it to brush teeth or
make ice
If this is not possible, boil or treat the water before use
Drinking bottled or tinned water and drinks is preferred
Eating hot, well-cooked food and avoiding street food,
undercooked food or food that has been left standing
will reduce the risk
Avoid raw foods such as salads or unwashed fruits
Washing your hands before eating is essential, which
can be done using soap and water or alcohol-based
hand gels