Chapter 24

Gastrointestinal tract

Normal microbiota of the GI system contains archaea, bacteria, fungi, protists, and even viruses.
-Antibiotics and diet can alter the microbiota, which is harmful
-Harsh environment of the GI tract contributes to immunity
-low pH of the stomach, peristalsis of the intestines
-Mucous produced by goblet cells, and normal microbiota provide a barrier to help prevent pathogens from establishing
-Peyer’s patches – lymphoid tissues in the ileum; M cells here are able to detect pathogens

Gastrointestinal disease

Wide range of GI diseases are caused by microbial
pathogens
-Many enter the body through contaminated food and water
-Foodborne diseases are by infection or intoxication
Infection occur two ways –
1.Microbe is ingested, colonizes the gut, produces toxins that
damage host cells
2.Intoxication – bacteria produce toxins in the food; toxins are
ingested which damage cells
- Both can cause symptoms such as nausea, vomiting,
diarrhea, aches, and fever.
-Severe cases - vomiting and diarrhea may cause severe
dehydration; complications can be fatal.

Terms

Gastritis - inflammation of stomach lining
Enteritis - inflammation of the intestinal mucosa.
Gastroenteritis - inflammation involves both the stomach lining
and the intestinal lining
Hepatitis - Inflammation of the liver
 Colitis - Inflammation of the colon (often w/food intoxication)
 Dysentery – damage to the epithelial cells of the colon; causes
bleeding and excess mucus, watery stools.

Gastritis

inflammation of stomach lining

Enteritis

inflammation of the intestinal mucosa

Gastroenteritis

inflammation involves both the stomach lining
and the intestinal lining

Diarrhea, cramps, nausea

“stomach flu” not influenza

Hepatitis

inflammation of the liver

Colitis

inflammation of the colon

Dysentery

 damage to the epithelial cells of the colon; causes bleeding and excess mucus, watery stools

severe diarrhea with blood and mucus in feces

infection of the intestines

Food poisoning by Staphylococcus

- Food can become contaminated with Staph during preparation
-Associated with raw or undercooked foods
-ingestion of exotoxins cause symptoms
     -21 Staphylococcal enterotoxins
-Able to withstand the low pH of stomach
- Symptoms occur within a couple hours of ingestion
-Most of the time symptoms resolve within 24 hours

-Food kept at temperatures below 60oC are problematic

Foods: creamy salads, deli meats, pastries

Pathogens that cause food poisoning

Many gastrointestinal diseases are caused by bacterial contamination of food.
-May be due to either infection or intoxication
- toxins often responsible in both cases
- Toxins cause damage to cells lining the GIl tract, (usually colon).
-Results in symptoms - diarrhea, watery stool, abdominal cramps, or more severe
dysentery.
-Symptoms often include nausea and vomiting
- Most bacterial GI illness is short-lived/ self-limiting
- Complications: loss of fluids; severe dehydration can be fatal if untreated.
-Treat with oral rehydration therapy with electrolyte solutions

Lower Digestive Tract in Infection

gastroenteritis, Dysentery

Signs and symptoms: diarrhea, loss of appetite, nausea, incubation period 1 to 2 days

Many different intestinal pathogens can cause similar infections
- Virulence genes may be acquired by horizontal transfer
-infectious dose related to acid tolerance; organism must survive passage through stomach
-Mechanisms include alteration of intestinal epithelial cells, cell invasion, exotoxin production
 Enterotoxins cause water and electrolyte loss
 Cytotoxins cause cell death

Lower Digestive Tract - Diarrheal Diseases

1. Salmonellosis 

2. E.coli

3. Shigellosis

Epidemiology Lower Digestive Tract - Diarrheal Diseases

-Hundreds of thousands of children die of diarrheal disease every year; most are infants
-Transmitted by fecal-oral route
-ingestion of contaminated food, water
-Pathogens with low infectious dose can be transmitted by person- to-person contact
- Control measures - Sewage treatment, handwashing,chlorination of drinking water

Salmonellosis

Salmonella species

• Motile; Gram-negative rod; Enteric bacteria
            -2 species recognized

• S. enterica most common in humans, are generally short-lived and mild
  people (cases likely underreported

•  Serotypes Enteritidis and Typhi

• Sources: Eggs, raw poultry

• Symptoms (last a few days - few weeks)
   Diarrhea, Abdominal pain, Nausea, Vomiting, Fever

• -Symptoms vary depending on virulence of strain and number of infecting organisms

• S. Typhi causes typhoid fever; more severe
            -Carries more virulence genes, produces toxins and capsule

Pathogenesis of Salmonellosis 

• Stomach acid normally kills bacteria, so a large number of Salmonella are needed to cause infection.

• The bacteria that survive travel to the lower small intestine, where they attach to specific receptors on the epithelial (lining) cells.

• The intestinal cells take in the bacteria, which then multiply inside the cells and trigger an inflammatory response.

• This inflammation causes the intestine to secrete extra fluid, leading to diarrhea.

• Some special strains—such as Salmonella Typhi—are harder for the body to remove.

• These strains can cross the intestinal lining and survive inside macrophages (immune cells that normally kill bacteria).

• When the macrophages eventually die, they release the bacteria, which then spread to other tissues in the body

Salmonellosis Epidemiology

• Most common source: Water that has been contaminated with human feces.

• Other sources:

  • Crabs and other seafood from contaminated waters

  • Vegetables grown using fertilizer made from human waste

• Infected individuals:

  • Their feces can contain up to 1 million bacteria per milliliter, making the infection easy to spread if proper hygiene is not followed.

Treatment and prevention Salmonellosis

• Adequate cooking kills bacterium

• Vaccine available for prevention of typhoid fever

• Most recover without antibiotics; many strains antibiotic resistant

• Some patients experience complications (Irritable bowel syndrome, reactive arthritis)

• Prevent by sanitary handling of food; cooking to 160 degrees Fahrenheit

Escherichia coli Gastroenteritis

Part of the normal microbiota of the colon; most are helpful commensals

• Gram-negative rod closely related to Shigella

• Unlike Shigella, most E. coli strains ferment lactose

• Strains differ in virulence
  - vomiting, loose stools. profuse watery diarrhea, severe cramps and bloody diarrhea

• Recovery usually occurs within 10 days

Pathogenesis of E.coli 

Pathogenic strains have virulence factors

• Enterotoxins

•  Adhesion molecules (Type 1 fimbrae); adherence to cells of small intestine

Epidemiology of E.coli

• Person-to-person spread;

• Contaminated food and water;

• Unpasteurized milk and juices

• Sources of pathogenic strains include; Humans, domestic and wild animals

Prevention and Treatment of E.coli

Prevention 

• Hand washing; Pasteurization of drinks; Proper food preparation

• Treatment includes
   Replacement of fluids and electrolytes
   Infants may require antibiotics
  Antibiotics tend to prolong disease in adults
  Traveler’s diarrhea can be controlled with bismuth preparations

Shigellosis

• Four species of Shigella; all cause shigellosis;
  - S. flexneri, S. boydii. S. sonnei, S. dysenteriae

• Spread by oral-fecal route

• Dysentery (severe form of diarrhea)
  -Headache, vomiting, fever, stiff neck, convulsions (rare), joint pain
  -Often fatal for infants in developing countries
  

• Strict sanitary measures for food and water
  - No vaccine available
  -Treatment is fluid and electrolyte replacement
  -Antibiotics may shorten duration of symptoms (20% of species are antibiotic resistant

S. dysenteriae

S. dysenteriae (not that common in the U.S.)
Shiga Toxin – potent enterotoxin that damages cells by interfering with
protein synthesis or inducing apoptosis

• Funnctions by the A-B mechanism
  -Toxin associated with fatal hemolytic uremic syndrome (HUS)
  -Most often in S. dysenteriae (serotype 1) and Shiga-toxin producing E. coli

Shigellosis in dept.

Bacteria invade intestinal epithelial cells
- M cells in the Peyer’s patches take up the bacteria, allowing them to enter macrophages, where they multiply. The bacteria then escape from the macrophages and invade the intestinal epithelial cells, causing tissue damage.
-This invasion leads to symptoms such as stomach cramps, fever, and watery diarrhea. The diarrhea may contain pus, mucus, or blood. In more severe cases, the infection can cause ulceration of the intestinal lining, dehydration, and rectal bleeding.

• Complications (Shiga-toxin producing strains)–

• Hemolytic Uremic syndrome – damaged blood cells accumulate in the kidneys; may lead to kidney failure or reactive arthritis. Also, some patients may develop irritable bowel syndrome

Helicobacter pylori Gastritis

Symptom

• Gastritis - inflammation of stomach lining

• Symptoms occur when infection is complicated with ulcers or cancer

• Abdominal pain, Tenderness, Bleeding , May be asymptomatic
  

• Short, Gram-negative spiral, Microaerophile, Multiple polar flagella

Pathogenesis of pylori gastritis

Bacteria survive extreme acidity of the stomach

• Produces urease which breaks down urea;neutralizes environment

• Organism uses flagella to corkscrew through mucosal lining

• Stimulates inflammatory response

•  Mucus production decreases

• Without mucus stomach lining not protected rom acidic environment
  -Infection persists for years
  -Possibly for a lifetime

Helicobacter infection decreases mucus production which contributes to the development of peptic ulcers.

Clostridium difficile infection

Antibiotic-associated diarrhea

• The use of antibiotics can disrupt the normal microbial flora of the large intestine, making it more susceptible to infection by Clostridium difficile,

• Is a common cause of hospital-acquired (nosocomial) infections in the United States, particularly in elderly or immunocompromised patients

• most common infectious cause of diarrhea in hospital settings (nosocomial)

• Responsible for approximately 10–35% of all cases of antibiotic-associated diarrhea

Treatment/Prevention of C.difficile

Primarily in hospitalized patients on antibiotic therapy

• C. difficile can grow to high numbers when normal microbiota is disrupted

• Patients acquire infection in hospital or have C. diff in normal microbiota
   Treatment and prevention

•  If possible, stop antibiotics; symptoms often disappear

•  Electrolytes replacement, fluids. Sometimes fecal transplant to restore gut microbiota

• Metranidazole, vancomycin

• Preventive measures include minimizing use of antibiotics, handwashing, wearing gloves, disinfectants

• Infectious endospores shed in feces

differentiate C.difficile

• Gram-positive, obligate anaerobic rod

• Forms endospores that are highly resistant to disinfectants and harsh environmental conditions

• Spores survive stomach acid

• Spores germinate in the small intestine

• Ingested endospores become vegetative cells that colonize the large intestine

• Many strains exist, and they vary in how pathogenic they are

• Pathogenicity is mainly due to two exotoxins:

  • Toxin A (TcdA)

  • Toxin B (TcdB)

C.difficile enterotoxin,cytoxin

• Produces two major exotoxins:

  • Toxin A (TcdA): an enterotoxin

  • Toxin B (TcdB): a cytotoxin

• These toxins act on the colonic epithelium and immune cells, triggering a series of events that lead to: Increased fluid secretion, Inflammation, Damage to intestinal tissue

• Can cause pseudomembranous colitis (PMC) over time , a severe inflammatory disease of the colon

• PMC is characterized by the formation of pseudomembranes, which are made of:

  • Necrotic (dead) epithelial cells

  • Fibrin

  • Mucus

  • Leukocytes (white blood cells)

• Overall, pseudomembranous colitis involves colon inflammation and the development of a fibrin-rich pseudomembrane containing dead epithelial cells and leukocytes.

Cholera

Vibrio cholerae

• Gram-negative, curved rods

•  Salt tolerant

• Tolerates high alkaline environment

• Severe watery diarrhea
  -Can amount to loss of 20 liters of fluid per day

•  Vomiting at the onset of disease

• Muscles cramps
  -Caused by loss of fluid and electrolytes

Pathogenesis of cholera

• High infectious dose required because bacteria are sensitive to stomach acid.

• In the small intestine, bacteria adhere to the epithelial lining and multiply.

• Bacteria produce a toxin called cholera toxin.

• Cholera toxin is an A-B type toxin.

• The toxin’s action causes excess fluid secretion, leading to profuse watery diarrhea

epidemiology/ treatment and prevention of cholera

Epidemiology

• Fecal contamination of water most common source of transmission

• Also crabs and other seafood, vegetables fertilized with human feces
   Treatment and prevention

• Replacement of fluids and electrolytes before organ damage occurs

• Clean water and good sanitation measures for control

• Travelers should cook food immediately before eating and avoid fruit and ice contaminated with localwater

• Vaccines available in many parts of world

Hepaatitis virus

Hepatitis means inflammation of the liver

• Five main hepatitis viruses

• All infect hepatocytes - Cause similar symptoms
  -include malaise, anorexia, loss of appetite, dark urine, pain in the upper
  right quadrant of the abdomen, vomiting, nausea, diarrhea, joint pain, and
  gray stool, jaundice.

• Inflammation due to continued viral replication

Hepatitis A-E

• Hepatitis A – Acquired through ingestion; fecal-oral route; often mild and self-limiting after a few months; more severe strains exist but are rare. Vaccine available for at risk individuals

• Hepatitis B - acquired via exposure to contaminated blood or body fluids through mucosal contact, puncture or through placenta 9drug-use, sexual activity, etc).
  - Infection is chronic; can lead to cirrhosis of the liver; liver cancer
  - Vaccine is available; healthcare agencies offer HBV to all workers due to risk of exposure

• Hepatitic C – often undiagnosed; exposure through contaminated blood

• Hepatitic D – uncommon in the U.S.

• Hepatitis E – uncommon in the U.S.

Viral gastroenteritis

Rotavirus – common diarrheal illness; spread by oral-fecal route

• Common in children (esp. daycare centers)

• Acquired immunity is protective

• Vaccine available

• Can cause dehydration; malnutrition in developing countries
  

• Noroviruses (Norwalk viruses)
   Several strains cause gasteroenteritis
   Highly contagious; esp. in enclosed spaces (like cruiseships)
   Illness is usually mild dehydration can occur
   Illness is self-limiting