Gastrointestinal and Hepatobiliary Infections

Readings: F.S. Southwick. Infectious Diseases in 30 Days. pg. 240-288.

Overview

Viewed in its simplest form the gastrointestinal tract is a tube that goes through the center of the body from the mouth to the anus. The primary function of this system is digestion and nutrient uptake. The walls of this tube are lined with a diverse number of epithelial cells that are especially good at transmembrane secretion and absorption. They also maintain the barrier that protects the host from microbial pathogens and mutagens. This barrier consists of the intact mucosal surface and an extensive population of resident immune cells.

The epithelial cells have a relatively short life with most cells only lasting between 48 and 72 hours. This is good in that the constant turnover of cells makes it more difficult for pathogens to colonize the gastrointestinal tract. It also has a down side in that the high rate of mitosis makes these cells more susceptible to mutagenic compounds and tumor formation.

Through this tube passes all of the liquid and solid material we ingest. Carried with the ingested material are bacteria, which tend to colonize those parts of the tube that offer a suitable environment for growth.

In a relatively short time following birth a "normal" flora is established in each part of this tube. Each end of the tube, the oral cavity and the colon, is heavily colonized while the central part of the tube, the stomach, duodenum, jejunum and the proximal half of the ileum, are lightly colonized.

Each portion of the gastrointestinal tract has special anatomic, physiological and biochemical barriers to infection by the normal flora or pathogenic microorganisms. When microorganisms or their toxins breach these barriers we have disease.

The barriers to infection of the GI tract include:

    A. An unbroken mucosal epithelium covering all parts of this system. Under normal conditions epithelial cells are continually sloughed off and replaced. As the cells are sloughed off, microorganisms attached to these cells or within these cells enter the internal chyme and are excreted from the body. If the sloughing process is interfered with, pathogens can form foci of infection. If the normal replacement process is interfered with, as in radiation therapy or cancer chemotherapy, there is ulceration of the mucosa with the resulting clinical symptoms of nausea and vomiting. Infection of the ulcer can lead to septicemia and fever.

    B. The glycocalyx, a glycoprotein and polysaccharide layer that covers the surface of the epithelial cells. This presents a thick, relative to the size of bacteria, physical barrier as well as a chemical trap that binds microorganisms

C. Mucous. The mucous plays two roles in disease prevention; it acts as a physical barrier making it harder for the bacteria to access the epithelial cell surfaces and it coats the bacteria, making it easier to remove them via peristalsis.

D. Acidity of the stomach. The normal pH of the stomach is less than 4. This acidity spills into the small intestine establishing a pH gradient that prevents most bacteria from colonizing the stomach, duodenum, jejunum and upper half of the ileum. Because of this, the majority of ingested pathogens never reach the intestinal tract alive. Over 99.9% of ingested bacteria are killed after 30 minutes exposure to stomach acidity. Alteration of the acid barrier of the stomach by disease, surgery, drugs or antacids increases the survival of pathogens when inside this organ and can result in microbial infections. For example, the inoculum of Vibrio cholerae required to cause disease is 10⁸ organisms. If gastric acidity is neutralized by 2 gm of sodium bicarbonate, only 10⁴ ingested organisms are required to cause disease.

E. Bile. Bile solubilizes lipids. It can also inactivate organisms that have a lipid envelope. All enveloped viruses and many bacteria are prevented from growing in areas of high bile salts. Obstruction of the flow of bile by gallstones has two effects: 1. downstream from the blockage and in the intestine pathogens can proliferate and cause disease and 2. upstream from the block bile salts accumulate and initiate a cycle of inflammation and damage to the gallbladder wall which can become a site of infection (cholecystitis).

F. IgA. Secretary IgA helps prevent colonization by certain pathogens.

G. Gut motility. Peristalsis contributes to the health of the gut by: 1. Aiding in the fluid absorption process. 2. Maintaining appropriate dilution of indigenous enteric microflora. 3. Ridding the host of pathogenic microorganism by hindering adherence of micro-organisms to receptors on the epithelial cell surface.

H. Peyer's patches. These are whitish unencapsulated patches of lymph follicles in the mucosa and sub-mucosa (MALT and GALT (peyer’s patches), which provide a homing site for lymphocytes. M cells lining the intestine process antigens and present them to the lymphocytes. In addition there is non-specific lymphocyte trafficking through the Peyer's patches; about 1-2% of the lymphocyte pool recirculate each hour providing a ready source of white blood cells. The intestinal mucosa demonstrates a state of "physiologic inflammation" in the lamina propria, with neutrophils, macrophages, plasma cells and lymphocytes present - suggesting a constant battle to maintain the integrity of the mucosa.

Following invasive infections a vigorous inflammatory reaction ensues resulting in many white blood cells going into the lumen. One way to differentiate an invasive infection from a noninvasive infection or a toxin-mediated disease is by looking for the presence of white blood cells in the feces.

I. Normal flora. Of the normal microflora 99.9% are anaerobes. They are mainly members of the genera Bacteroides, Prevotella, Clostridium, and Peptostreptococcus. The remaining organisms are aerobes or facultative cells of the genera Escherichia, Proteus and Pseudomonas as well as other less numerous species. The normal non-pathogenic flora competes with pathogens for nutrients and intestinal receptor sites keeping them from causing disease.

The gastrointestinal tract is subjected to continual challenge by pathogenic microorganisms but is well protected by the various barriers discussed above. It is only when one or more of these barriers is breached that we have disease. Some of the more common factors that compromise the human are:

A. Ingestion of antacids neutralizes stomach and upper intestinal acidity and allows microorganisms to proliferate on areas that are lightly colonized (stomach).

B. Antibiotic therapy destroys the normal flora and reduces competition that pathogens are normally subjected to.

C. Glucosteroid therapy reduces the immune reaction.

D. Cancer chemotherapy reduces the normal flora and the cellular and humoral immunity as well as the intestinal epithelium integrity.

E. Radiation therapy affects immunity and can upset the balance of normal flora and intestinal epithelium integrity.

F. Ingestion of pre-formed toxins with food and/or water (Staphylococcus= enterotoxin).

G. Ingestion of microorganisms that produce toxins/enzymes/ immune suppression factors in situ (E. coli, Shigella, Salmonella).

H. Anatomic alterations. Obstructions to the flow of liquids remove one of the most powerful defensive mechanisms of the gastrointestinal tract. Stones in the gallbladder impede the flow of bile and predispose the biliary tree to infections. The presence of large diverticula (seen in 50% of people over 60 years of age) or the surgical formation of intestinal “blind loops” creates sites with reduced flow of intestinal contents, leading to bacterial overgrowth and metabolic derangements.

Diseases

As you see there are a large number of diseases associated with the gastrointestinal and hepatobiliary systems.

Mouth, teeth and jaw Dental caries Gingivitis Periodontal disease Pulpitis Dentoalveolar abscess Periodontal abscess Ludwig’s angina Osteomyelitis of the jaw Stomatitis (Gonorrhea, Syphilis, Herpes, Candida) Hand, foot and mouth disease Oral warts Oral hairy leukoplakia Salivary glands Mumps Acute and chronic parotitis Esophagus Esophagitis Stomach Gastritis Peptic ulcer Intestines Food poisoning Diarrhea and vomiting Dysentery (colitis) Pseudomembranous colitis Diverticulitis Appendicitis Liver Hepatitis Liver abscess Pancreas Pancreatic abscess Gallbladder Cholecystitis Cholangitis Peritoneum Primary and Secondary Peritonitis Intraabdominal abscess

Overview

Infections of these systems are very common. Literally millions of people are affected each year by infections of the gastrointestinal tract. Gastrointestinal diseases are the second most common reason people go to their physician.

Etiology

An enormous number of organisms cause they include bacteria, viruses, fungi, and parasites. They are too numerous to count here and will be discussed in more detail later.

Epidemiology

Nearly all persons have had dental caries sometime in their life. Most people have at least one case of diarrhea each year. Children average 2-3 episodes of diarrhea in a year. Diarrhea is the most common cause of death in the developing world. There are over 76 million cases of food poisoning each year in the U.S. Most of the time these diseases are self-limiting and people do not go to their physician unless their symptoms become severe or chronic.

Pathogenesis

Depends on the site infected or intoxicated. There are two basic mechanisms that infectious agents use in causing disease in these systems.

One is to produce a toxin that when ingested will cause symptoms. This is called intoxication. The most common cause of food poisoning in the U.S. is the result of intoxication. Staphylococcus aureus produces an enterotoxin in improperly stored food that upon ingestion causes primarily nausea and vomiting. Another example of intoxication is botulism. Symptoms occur within 2-4 hours of ingestion and usually resolve in 24-48 hours.

The other mechanism involves actual infection of and/or destruction of the host cells. Some pathogens only attach to the surface of the epithelial cells and produce toxins that then cause cell damage and/or death (ETEC E. coli, Giardia lamblia). Usually this results in a watery diarrhea without inflammatory cells or blood in the stools. Others after attaching go into the cells and damage them (Campylobacter, Shigella, Salmonella, Rotavirus, Norwalk agent). Depending on how deep the infection goes the symptoms can vary from being a watery diarrhea (viral gastroenteritis) to bloody mucus covered stool (dysentery; Shigellosis), to invasion of the bloodstream (enteric fever; Salmonella typhi). Symptoms occur 24-72 hours following ingestion and usually resolve in 2-7 days (exceptions include enteric fevers).

Some gastrointestinal pathogens can cause chronic infections that remain with the host for months to years (Helicobacter pylori, Giardia lamblia) or a lifetime (Hepatitis B virus, Herpes Simplex virus).

Manifestations

Depend on the part of the systems affected.

Mouth; various lesions, dental cavities, tooth pain/sensitivity to hot and/or cold, bleeding gums, petechia, facial pain and/or swelling, abscesses, cellulitis.

Salivary glands: jaw pain when swallowing, swelling under jaws.

Esophagus: dysphagia (difficulty in swallowing), odynophagia (painful swallowing; unique to infectious causes of esophagitis), heartburn, atypical chest pain, regurgitation.

Stomach: vomiting, epigastric pain that occurs 90 min to 3 hours after eating; eating relieves the pain; belching, indigestion, heartburn.

Small intestines: large volume watery diarrhea, sometimes fatty stools, increased bowel sounds, cramps, diffuse abdominal pain, no guarding or rebound tenderness, rarely has white blood cells in stool.

Large intestines: small volume bloody diarrhea with mucus in it (dysentery), cramps, diffuse abdominal pain, rarely any guarding or rebound tenderness, frequently has white blood cells in stool, fever.

Liver: upper right quadrant pain of the abdomen, fever, icterus, clay-colored stools, dark urine.

Gallbladder (cholecystitis and cholangitis): Jaundice, right upper quadrant pain, high fever, chills.

Peritoneum: sharp localized abdominal pain aggravated by motion, fever, chills, constipation, abdominal distension, decreased bowel sounds, guarding, rebound tenderness.

Diagnosis

Depends on the disease and where it is located in the systems.

Laboratory examination

Several different laboratory tests can be used to aid in the diagnosis of gastrointestinal diseases.

A. Stools

1. Gross examination (watery, mucoid or bloody)

2. Microscopic examination

a. Fecal leukocytes detection by methylene blue staining (non-inflammatory reaction vs. inflammatory reaction)
b. Sudan stain for fat globules (large fat globules indicates malabsorption)
c. Eosin stain (stains undigested muscle fibers, indicating pancreatic insufficiency and maldigestion)
d. pH (acidic pH indicates lactose intolerance in children) - normal pH is greater than 7.
e. Copper sulfate reaction - presence of reducing sugars indicates carbohydrate malabsorption.
f. Occult blood test
g. Culture for enteric pathogens

B. Blood culture for septicemia

C. Serological tests (e.g., typhoid fever, amebiasis)

D. Toxin assays – Fibroblast cell assay for toxin A and B produced by C. difficile.

E. ELISA tests (LT of E. coli and cholera toxin of Vibrio cholerae)

F. Endoscopy (esophagus, stomach and upper duodenum) and colonoscopy (colon) can be used to directly view the pathology, gather samples for pathological examination, and correct certain problems. It can also be used to cannulate the biliary and pancreatic ducts to inject contrast media for radiological studies.

G. Radiological studies and pathological examination

Therapy

As above.

Prevention

Maintain good oral hygiene, properly cook and store all food, drink safe water, take special precautions when traveling to other countries, avoid illegal intravenous drug use, avoid frequent sexual contacts, avoid excessive alcohol use.

All travelers to areas where diarrheal diseases are common should observe the following recommendations:

· Drink only water that you have boiled or treated with chlorine or iodine.

· Other safe beverages include tea and coffee made with boiled water and carbonated, bottled beverages with no ice.

· Eat only foods that have been thoroughly cooked and are still hot, or fruit that you have peeled yourself.

· Avoid undercooked or raw fish or shellfish, including ceviche.

· Make sure all vegetables are cooked avoid salads.

· Avoid foods and beverages from street vendors.

· Do not bring perishable seafood back to the United States.

· A simple rule of thumb is "Boil it, cook it, peel it, or forget it.