Definition, Etiology, Epidemiology, Pathophysiology, Clinical Presentation, Diagnosis and Treatment of Gastroenteritis

1. GASTROENTERITIS
Dr. Kainat Panjwani, PharmD
Assistant Professor
Pharmacotherapeutics III
MLR Institute of Pharmacy

2. Definition
 Gastroenteritis is
inflammation of the
gastrointestinal tract,
involving the stomach,
intestines, or both; usually
resulting in diarrhoea,
abdominal cramps, nausea
and possibly vomiting.
 Gastroenteritis is frequently
termed "stomach flu" or
"gastric flu" because the
most frequent cause of
gastroenteritis is viral, but
influenza viruses (flu
viruses) do not cause

3. EPIDEMIOLOGY
 Occurs worldwide
 Fecal-oral route of transmission
 Water common reservoir
 Overcrowding & poor sanitation are risk
factors
 Animals, insects may be source of infection

4. Diarrheal illnesses may be classified as
follows:
1. Osmotic diarrhoea, retention of water
in the large intestine as a result of an
accumulation of non-absorbable, water
soluble compounds. Ceases with
fasting, discontinue oral agents.
Causes – Purgatives like Magnesium
sulfate or Mg containing antacids
Especially associated with
excessive intake of Sorbitol and
Mannitol.
Generalised malabsorption

5. 2. Inflammatory (or mucosal) diarrhoea, damage to
intestinal mucosal cell leading to a loss of fluids and
blood.
Causes- Immunodeficiency
Shigella dysentery
Inflammatory conditions like UC and CD
3. Secretory diarrhoea, active intestinal secretion of fluids
and electrolytes as well as decreased absorption.
Large volume, painless, persists with fasting
Causes- Cholera enterotoxin, thermolabile E. coli
enterotoxin
Laxatives like docusate sodium

6. 4. Motility diarrhoea, increases
frequency of defecation due to
underlying diseases. Large volume,
signs of Malabsorption
Causes- DM – autonomic neuropathy
Hyperthyroid diarrhoea
IBS

7. CLASSIFICATION
 Bacterial gastroenteritis
 Viral gastroenteritis

8. ETIOLOGY
 Etiologies include bacteria, viruses,
parasites, toxins, and drugs. (eg, metals,
plant substances).
Viruses
 Four categories of viruses cause most
gastroenteritis:
rotavirus and calicivirus
(predominantly the norovirus [formerly
Norwalk virus]) cause the majority of viral
gastroenteritis, followed by astrovirus
and enteric adenovirus.

9.  Rotavirus
 is the most common cause of sporadic,
severe, dehydrating diarrhoea in young
children (peak incidence, 3 to 15 mo).
 Rotavirus is highly contagious; most
infections occur by the fecal-oral route.
 Adults may be infected after close
contact with an infected infant.
 The illness in adults is generally mild.
 Incubation is 1 to 3 days.

10. Astrovirus
 Can infect people of all ages but
usually infects infants and young
children.
 Infection is most common in winter.
 Transmission is by the fecal-oral
route.
 Incubation is 3 to 4 days.

11. Adenoviruses
 Are the 4th most common cause of
childhood viral gastroenteritis.
 Infections occur year-round, with a slight
increase in summer.
 Children < 2 yr are primarily affected.
 Transmission is by the fecal-oral route.
 Incubation is 3 to 10 days.
 In immunocompromised patients,
additional viruses (eg, cytomegalovirus,
enterovirus) can cause gastroenteritis.

12. Bacteria
The bacteria most commonly implicated
are
 Salmonella
 Campylobacter
 Shigella
 Escherichia coli (especially serotype
O157:H7)

13. Bacteria cause gastroenteritis by several mechanisms.
 Certain species (eg, Vibrio cholerae, enterotoxigenic strains
of E. coli) adhere to intestinal mucosa without invading and
produce enterotoxins.
 These toxins impair intestinal absorption and cause secretion
of electrolytes and water by stimulating adenylate cyclase,
resulting in watery diarrhoea.
 Clostridium difficile produces a similar toxin when overgrowth
follows antibiotic use.
 Some bacteria (eg, Staphylococcus aureus, Bacillus cereus,
Clostridium perfringens) produce an exotoxin that is ingested
in contaminated food. The exotoxin can cause gastroenteritis
without bacterial infection.
 These toxins generally cause acute nausea, vomiting, and
diarrhoea within 12 h of ingestion of contaminated food.
Symptoms abate within 36 h.

14.  Other bacteria (eg, Shigella, Salmonella, Campylobacter,
some E. coli subtypes) invade the mucosa of the small bowel
or colon and cause microscopic ulceration, bleeding,
exudation of protein-rich fluid, and secretion of electrolytes
and water.
 The invasive process and its results can occur whether or not
the organism produces an enterotoxin. The resulting
diarrhoea contains WBCs and RBCs and sometimes gross
blood.
 Salmonella and Campylobacter acquired through
undercooked poultry; unpasteurized milk is also a possible
source.
 Campylobacter is occasionally transmitted from dogs or cats
with diarrhea.
 Salmonella can be transmitted by undercooked eggs and by
contact with reptiles.
 Shigella dysenteriae type 1 (not present in the US) produces

15. Several different subtypes of E. coli cause
diarrhoea.
Enterohemorrhagic E. coli
 It produces Shiga toxin, which causes bloody
diarrhoea (hemorrhagic colitis).
 Undercooked ground beef, unpasteurized milk and
juice, and contaminated water are possible
sources.
 Person-to-person transmission is common in the
day care setting.
 Hemolytic-uremic syndrome is a serious
complication.

16. Enterotoxigenic E. coli
 produces two toxins (one similar to cholera toxin)
that cause watery diarrhoea.
 This subtype is the most common cause of
traveler's diarrhoea.
Enteropathogenic E. coli
 causes watery diarrhoea.
 Once a common cause of diarrhoea outbreaks
in nurseries, this subtype is now rare.

17. Enteroinvasive E. coli
 causes bloody or nonbloody diarrhoea,
 Yersinia enterocolitica can cause
gastroenteritis or a syndrome that
mimics appendicitis.
 It is transmitted by undercooked pork,
unpasteurized milk, or contaminated
water.
 Several Vibrio species (eg.
V. parahaemolyticus) cause diarrhoea
after ingestion of undercooked seafood.

18.  V. cholerae sometimes causes severe
dehydrating diarrhoea in the developing
world.
 Listeria causes food-borne gastroenteritis.
 Aeromonas is acquired from swimming in or
drinking contaminated fresh or brackish
water.
 Plesiomonas shigelloides can cause
diarrhoea in patients who have eaten raw
shellfish or traveled to tropical regions of the

19. Parasites
The parasites most commonly implicated
are
 Giardia
 Cryptosporidium

20. PATHOPHYSIOLOGY
1. Bacterial pathophysiology
 Bacteria can cause diarrhoea in three
different ways:
1. Mucosal adherence
2. Mucosal invasion
3. Toxin production

21. 1. Mucosal adherence
 Most bacteria causing diarrhoea must first adhere to specific
receptors on the gut mucosa.
 A number of different molecular adhesion mechanisms have been
elaborated; for example, adhesions at the tip of the pili or fimbriae
which protrude from the bacterial surface aid adhesion.
 For some pathogens this is merely the prelude to invasion or toxin
production but others such as enteropathogenic Escherichia coli
(EPEC) cause attachment-effacement mucosal lesions on electron
microscopy (EM) and produce a secretory diarrhoea directly as a
result of adherence.
 Adhere in an aggregative pattern with the bacteria clumping on the
cell surface and its toxin causes persistent diarrhoea.
 Diffusely adhering E. coli (DAEC) adheres in a uniform manner
and may also cause diarrhoea seen in children.

22. 2. Mucosal invasion:
 Invasive pathogens such as Shigella sp.,
enteroinvasive E. coli (EIEC) and
Campylobacter sp. penetrate into the intestinal
mucosa.
 Initial entry into the mucosal cells is facilitated
by the production of ‘invasins’, which disrupt the
host cell cytoskeleton.
 Subsequent destruction of the epithelial cells
allows further bacterial entry, which also causes
the typical symptoms of dysentery: low-volume
bloody diarrhoea, with abdominal pain.

23. 3. Toxin production :
Gastroenteritis can be caused by different types of
bacterial toxins:
 Enterotoxins, produced by the bacteria adhering to
the intestinal epithelium, induce excessive fluid
secretion into the bowel lumen, leading to watery
diarrhoea, without physically damaging the mucosa,
e.g. cholera, enterotoxigenic E. coli (ETEC).
 Some enterotoxins preformed in the food primarily
cause vomiting, e.g. Staph. aureus and Bacillus
cereus.
 A typical example of this is ‘fried rice poisoning’, in
which B. cereus toxin is present in cooked rice left
standing overnight at room temperature.
 Cytotoxins damage the intestinal mucosa and, in
some cases, vascular endothelium as well (e.g. E. coli)

25. Viral pathophysiology
 Viral spread from person to person occurs by fecal-oral
transmission of contaminated food and water.
 Some viruses, like noroviruses, may be transmitted by an
airborne route.
 Clinical manifestations are related to intestinal infection, but
the exact mechanism of the induction of diarrhoea is not
clear.
 The most extensive studies have been done with rotavirus.
 Rotaviruses attach and enter mature enterocytes at the tips of
small intestinal villi.
 They cause structural changes to the small bowel mucosa,
including villus shortening and mononuclear inflammatory
infiltrate in the lamina propria

26.  Rotavirus infections induce maldigestion of
carbohydrates, and their accumulation in the
intestinal lumen, as well as a malabsorption of
nutrients and a concomitant inhibition of water
reabsorption, can lead to a malabsorption
component of diarrhoea.
 Rotavirus secretes an enterotoxin, NSP4, which
leads to a Ca2+ -dependent Cl- secretory
mechanism.
 Morphologic abnormalities can be minimal, and
studies demonstrate that rotavirus can be
released from infected epithelial cells without
destroying them.

27. Pathophysiology of Parasite ind.
GE
 Certain intestinal parasites, notably Giardia intestinalis
adhere to or invade the intestinal mucosa, causing
nausea, vomiting, diarrhoea, and general malaise.
 The infection can become chronic and cause a
malabsorption syndrome.
 It is usually acquired via person-to-person transmission
(often in day care centers) or from contaminated water.
 Cryptosporidium parvum causes watery diarrhoea
sometimes accompanied by abdominal cramps,
nausea, and vomiting.
 In healthy people, the illness is self-limited, lasting
about 2 wk.
 In immunocompromised patients, illness may be
severe, causing substantial electrolyte and fluid loss.
 Cryptosporidium is usually acquired through
contaminated water.

28.  Other parasites that can cause
symptoms similar to those of
cryptosporidiosis include Cyclospora
cayetanensis and, in
immunocompromised patients, Isospora
belli, and a collection of organisms
referred to as microsporidia (eg,
Enterocytozoon bieneusi,
Encephalitozoon intestinalis).
 Entamoeba histolytica (amebiasis) is a
common cause of subacute bloody

29. Clinical manifestations

30. SYMPTOMS AND SIGNS
 The condition is usually of acute onset,
normally lasting 1–6 days, and is self-
limiting.
◦ Nausea and vomiting
◦ Diarrhoea
◦ Anorexia
◦ Fever
◦ Headaches
◦ Abnormal flatulence
◦ Abdominal pain
◦ Abdominal cramps
◦ Melena
◦ Fainting and Weakness
◦ Heartburn

31. DIAGNOSIS
1. Clinical evaluation (MHx, Physical
examination)
◦ Findings suggestive of gastroenteritis
include
 copious, watery diarrhoea
 ingestion of potentially contaminated food
(particularly during a known outbreak)
 untreated surface water
 known GI irritant; recent travel;
 or contact with similarly ill people.

32. 2. Stool testing in select cases
 If a rectal examination shows occult blood or if watery
diarrhoea persists > 48 h, stool examination (fecal
WBCs, ova, parasites) and culture are indicated.
 However, for the diagnosis of giardiasis or
cryptosporidiosis, stool antigen detection using an
enzyme immunoassay has a higher sensitivity.
 Rotavirus and enteric adenovirus infections can be
diagnosed using commercially available rapid assays
that detect viral antigen in the stool, but these are
usually done only to document an outbreak.
 All patients with grossly bloody diarrhoea should be
tested for E. coli O157:H7, as should patients with non
bloody diarrhoea during a known outbreak.

33.  Specific cultures must be requested
because this organism (E.coli) is not
detected on standard stool culture
media.
 Adults with grossly bloody diarrhoea
should usually have sigmoidoscopy with
cultures and biopsy.
 Appearance of the colonic mucosa may
help diagnose amebic dysentery,
shigellosis, and E. coli O157:H7
infection, although ulcerative colitis may
cause similar lesions.
 Patients with recent antibiotic use should
have a stool assay for C. difficile toxin.

34. GENERAL TESTS
 Serum electrolytes
 Blood Urea Nitrogen (BUN)
 Creatinine should be obtained to
evaluate hydration and acid-base
status in patients who appear
seriously ill.
 Complete Blood Picture (CBP) is
nonspecific, although eosinophilia may
indicate parasitic infection.

35. Treatment -
 REHYDRATION
 The treatment of cholera and other dehydrating diarrheal
diseases was revolutionized by the promotion of oral
rehydration solutions.
 The efficacy of which depends on the fact that glucose-
facilitated absorption of sodium and water in the small
intestine remains intact in the presence of cholera toxin.
 The World Health Organization recommends a solution
containing 3.5 g sodium chloride, 2.5 g sodium bicarbonate,
1.5 g potassium chloride, and 20 g glucose (or 40 g sucrose)
per liter of water.
 Oral rehydration solutions containing rice or cereal as the
carbohydrate source may be even more effective than
glucose-based solutions, and the addition of L-histidine may
reduce the frequency and volume of stool output.
 Patients who are severely dehydrated or in whom vomiting
precludes the use of oral therapy should receive IV solutions
such as Ringer's lactate.

36.  Although most secretory forms of traveler's diarrhea—
usually due to enterotoxigenic and enteroaggregative E.
coli—can be treated effectively with rehydration,
bismuth subsalicylate, or antiperistaltic agents,
antimicrobial agents can shorten the duration of illness
from 3–4 days to 24–36 h.
 Antibiotic treatment for children who present with
bloody diarrhea raises special concerns.
 Laboratory studies of enterohemorrhagic E. coli strains
have demonstrated that a number of antibiotics induce
replication of Shiga toxin–producing lambdoid
bacteriophages, significantly increasing toxin production
by these strains.
 Clinical studies have supported these laboratory results,
and antibiotics are not recommended for the
treatment of enterohemorrhagic E. coli infections in
children.

37.  Loperamide should not be used by patients with fever
or dysentery; its use may prolong diarrhea in patients
with infection due to Shigella or other invasive
organisms.
 The recommended antibacterial drugs are as follows:
Adults:
(1) A fluoroquinolone such as ciprofloxacin,
750 mg as a single dose or 500 mg bid for 3 days;
levofloxacin, 500 mg as a single dose or 500 mg qd for
3 days; or norfloxacin, 800 mg as a single dose or 400
mg bid for 3 days.
(2) Azithromycin, 1000 mg as a single dose
or 500 mg qd for 3 days.
(3) Rifaximin, 200 mg tid or 400 mg bid for 3
days (not recommended for use in dysentery).

38. Children:
Azithromycin, 10 mg/kg on day 1, 5
mg/kg on days 2 and 3 if diarrhea persists.
Alternative agent: furazolidone, 7.5
mg/kg per day in four divided doses for 5
days.
 All patients should take oral fluids
(Electrolyte sachets, or flavored mineral
water) plus saltine crackers.
 If diarrhea becomes moderate or severe, if
fever persists, or if bloody stools or
dehydration develops, the patient should
seek medical attention.