Micro Chapter 60
Barriers to Infection
 Mucosal epithelium lining alimentary system – intracellular junctional complexes maintain integrity of lining
o Disruption of mucosa by ionizing radiation or cytotoxic chemotherapy can lead to mucositis (superficial
ulcerations of mucosa of entire GI tract) and penetration of normal flora into deep tissues (bacteremia)
 Mucus formation and gut motility hinder adhesion of microorganisms to epithelial wall
 In GI mucous are mucins (complex glycoproteins in secreted and membrane-complexed forms)
o Commensal organisms can reside in mucous layer using complex carbs as energy
o Enteric pathogens must pass barrier to adhere to intestinal epithelial cells
o Clostridium difficile toxin decreases production of intestinal mucin, disrupting barrier of mucous
o Glycocalyx – mucin-rich layer covering filamentous brush border surface of epithelial cells; has decoy
binding sites that trap certain invading organisms, facilitating elimination in feces
o Some GI mucins possess natural antimicrobial activity
o In some instances, mucus triggers virulence factors
 Bile – organisms that survive intestinal lumen resistant to detergent action of bile salts
o Most enteric viruses (hep A, polio) lack lipid-containing envelope that would make them sensitive to bile
o Bacteria (Gram - typhoid bacillus, Gram + enterococci) so resistant to bile, they can grow in gallbladder
 Intestinal epithelial cells secrete antimicrobial peptides that kill bacteria by forming pores in membrane
o E. coli secretes toxins (i.e., heat-labile toxin) that suppress production of antimicrobial peptides
 M cells – in intestinal epithelium; sample antigens and microbes for delivery to subepithelial collections of
dendritic cells and lymphoid cells (Peyer’s patches)
o Some dendritic cells extend processes between tight junctions of epithelial cells to directly sample
luminal antigens
o Pattern recognition receptors on dendritic cells or epithelial cells may activate production of
antimicrobial peptides or elicit expression cytokines that recruit PMN cells and other inflammatory cells
to neutralize microbes
o Lymphocytes respond by production of secretory IgA that neutralize microorganisms or their products
Establishment of Infectious Disease in the Digestive System
 Pathogen can invade when normal defenses altered in favor of microbe
o Anatomic alterations – obstructions to flow of secretions (gall stones, intestinal blind loops caused by
surgery); overgrowth occurs in disrupted area and results in malabsorption
o Changes in stomach acidity – alteration of acid barrier of stomach by disease, surgery, or drugs
 Creates more likelihood of infection by smaller numbers of pathogens and acid-sensitive
bacteria (Vibrio cholera or Salmonella)
o Alterations to normal flora – most frequent cause is use of broad-spectrum antibiotics
o Encounter w/specific pathogenic agents; certain microbes cause disease even in absence of predisposing
host factors; possess different attributes to help them infect specific sites
 Signs and symptoms of infections caused by
o Pharmacologic action – toxins that alter normal intestinal function w/o causing lasting damage to target
cells (i.e., enterotoxins secreted by V. cholera or some strains of E. coli that provoke copious watery
diarrhea); alter absorption of small intestine, allowing excess fluid to go to colon; leads to dehydration,
electrolyte loss, depletion of intravascular volume, and shock
o Local inflammation – periodontitis (infections of anaerobic bacteria in gingival pocket) or in large
intestine w/Shigella infection (infection of lamina propria, can result in bloody diarrhea (dysentery))
o Deep tissue invasion – organisms able to invade GI tract and enter circulation (Entamoeba histolytica,
Strongyloides, and Salmonella)
 Strongyloides itself often colonized by gut bactiera, so invasion by worm causes polymicrobial
bacteremia
o Perforation – when mucosal wall necrotic, it perforates, normal flora spill into usually sterile peritoneal
cavity (peritonitis) and invade bloodstream; rupture of esophagus causes mediastinitis
Infections of the Mouth
 Specific defenses of mouth include
o
Nonpathogenic resident flora – bacteria, fungi (Candida), and protozoa (Entamoeba gingivalis); occupy
suitable sites and repel other organisms by production of acids and other metabolic inhibitors
o Mechanical actions of saliva and tongue
o Antimicrobial constituents of saliva – secretory IgA (selectively inhibits adherence of certain bacteria to
mucosal cells or tooth surfaces) and lysozyme (effective against Gram+ bacteria
 Bacteria that stick to teeth adhere to coating of sticky macromolecules (mainly proteins) called dental pellicle
o Bacteria produce polysaccharides that help in adherence
o Streptococcus mutans transforms sucrose into polysaccharides that are particularly sticky; layer on
pellicle to form matrix that allows adherence of other organisms; dental plaque
 Microbial metabolism in plaque transforms dietary sugar into acids (lactic acid) responsible for
dental caries
o Strict anaerobes reside in gingival crevices between tooth and gum
 Normal flora not virulent, but when break occurs in mucosal barrier (i.e., advanced gingivitis), organisms may
invade surrounding healthy tissue
 Mouth is portal of entry of α-hemolytic streptococci that cause subacute bacterial endocarditis in those
w/rheumatic heart disease
 Ludwig angina – polymicrobial infection of sublingual and submandibular spaces arises from tooth; cellulitis
(inflammation of submucosal or subcutaneous CT) that can progress rapidly, press against airway, and
compromise respiration airway
Candidiasis
 White patches adhering to oral mucosa consist of pseudomembranes made of Candida mixed w/desquamated
epithelial cells, WBCs, oral bacteria, necrotic tissue, and food debris
 Candida albicans found in environment and establishes in alimentary tract early in life (adult vagina commonly
colonized w/organisms that may be acquired by infant during delivery)
o Small numbers live harmlessly in alimentary tract until balance between indigenous bacterial flora and
host defenses upset (antibiotic therapy)
o Exploits changes in normal host flora to multiply locally; if defects in cellular immunity or neutrophils
exist, they may invade beyond mucosal surface
o Predisposing conditions include diabetes, malnutrition, malignancy, immunosuppressive drugs, genetic
abnormalities of immune system, and HIV
o Prolonged use of inhaled steroids for asthma can predispose to candida overgrowth in mouth
 In more severe forms of immunodeficiency, organism can disseminate through bloodstream and infect virtually
any organ system (most commonly liver, lung, and kidney)
 Can invade esophagus; candidal esophagitis seen in persons w/specific T-cell abnormalities (chronic
mucocutaneous candidiasis or AIDS); differential diagnosis includes CMV and HSV-1
o CMV and HSV-1 can cause mucosal ulcerations w/severe pain and difficulty swallowing
 Diagnose by examination of exudate because culture can have Candida even in healthy person
 Candidiasis of mouth usually superficial and responds to oral antifungal agents (nystatin); if infection extends
below mucosa, use absorbed oral antifungal agent (fluconazole) or IV amphotericin B
Stomach Infections
 Predominant bacteria in stomach are acid-resistant Gram+ organisms (Lactobacillus, Peptostreptococcus, Staph,
and Strep); normal stomach contains very few Gram- rods, Bacteroides, or Clostridium (usually associated
w/lower GI tract)
 Helicobacter pylori – expression of multiple virulence genes (urease production to neutralize stomach acid,
motility via flagella to penetrate mucous layer of stomach lining)
 Survival of pathogens through stomach into small intestine depend on buffering effects of food or may be
favored in those who don’t produce normal amounts of gastric HCl because of disease, gastrectomy, drug
therapy (H2 receptor blockers) or antacid consumption
o Peanut butter and chocolate can protect Salmonella through high fat content
o Hypochlorhydria (low stomach production of acid) or achlorhydria (no acid production) leads to
colonization of stomach and upper small intestine by enteric Gram- rods; leads to
 Development of bacterial overgrowth syndrome

Regurgitation of abnormal gastric flora, which become source of nosocomial (hospital-acquired)
aspiration pneumonia
Infections of the Biliary Tree and Liver
 Presentation of biliary obstruction often sudden and dramatic; leads to increased pressure and distention
o Mechanical, chemical, and bacterial inflammation caused by enterococci, E. coli, Klebsiella pneumonia,
Staphylococcus aureus, or Clostridium perfringens can result
o Biliary colic – pain in RUQ that may build to crescendo, subside, and recur rapidly
o Majority of patients w/common bile duct obstruction have shaking chills, high spiking fever, jaundice,
and tenderness over gall bladder
o Charcot triad – biliary colic, jaundice, and chills & spiking fever; characteristic of acute cholecystitis
 Inflammation and infection can cause ischemia of gallbladder wall, sometimes progressing to gangrene and
perforation, which can lead to peritonitis and abscess formation
o Complete obstruction  combo of pus and increased pressure leads to abscess formation, bacteremia,
and symptoms of sepsis
 Ascending cholangitis – spread of infection from biliary ducts to liver; common w/perforation
 Primary bacterial infections of liver parenchyma not common because of defensive capacity of Kupffer cells
o Liver abscesses develop from portal vein bacteremia from infected intra-abdominal site, systemic
bacteremia via hepatic artery, ascending cholangitis, and contiguous infections
o Intracellular pathogens that survive macrophages can cause granulomatous infections (typhoid fever, Q
fever, brucellosis, and TB)
 Cholangitis – infection of the bile duct; caused by obstruction and distention, resulting in inflammation of
gallbladder wall; increases risk of infection caused by bacteria normally present in bile
o Once bacterial infection established, tissue damage may be accelerated by resulting inflammation
o Healing unlikely to occur w/o surgical or spontaneous relief of obstruction and specific antimicrobials
 Emphysematous cholecystitis – rapid clinical onset, extensive gangrene, presence of gas in gallbladder wall
(when gas-forming species such as clostridia or E. coli present), and high mortality rate
o Cholecystectomy required because of frequent occurrence of gangrene, perforation, and extensive
peritonitis
 Usual presentation of cholangitis similar to cholecystitis but often accompanied by high spiking fever, chills,
jaundice, and constant pain; requires considerable pressure in duct to forminfection
o Microscopic tears or ischemic damage help bacterial infasion of duct wall
 Organisms that infect gallbladder and bile duct usually derived from GI tract (E. coli most frequent)
o 40% of infections in gallbladder and bile duct caused by mixed facultative and strictly anaerobic flora
that ascends form duodenum
o Typhoid bacilli have predilection for gallbladder; may persist for prolonged period in gallstones
(protected from effects of antibiotics); produce little or no inflammation
 All carriers, cognizant or not, shed typhoid bacteria into environment and can infect others
 Cholecystitis often presents in atypical form; abdominal ultrasound useful to establish diagnosis
o Antibiotics chosen empirically on basis of expected flora
 Patients w/suspected cholangitis should receive antibiotics for expected mixed bacterial species typically
present, even before diagnosis confirmed; then correct underlying obstruction
Bacterial Overgrowth Syndrome
 Presence of large microbial biomass in small intestine leads to competition for certain vitamins and
malabsorption of fats
 Can occur from stasis of intestinal contents in blind loop, motor abnormalities that depress peristalsis (diabetic
neuropathy, scleroderma, or gastric atony) or gastric achlorhydria (permits large bacterial inocula to reach
proximal small intestine)
 Most numerous bacteria are strict anaerobes, mainly Bacteroides species
 May cause
o Increased fecal fat (steatorrhea) – malabsorption of fat resulting from depletion of bile acid pool
 Bile acids (cholic acid) normally conjugated w/glycine or taurine in liver, secreted in bile, and
reabsorbed in terminal ileum in conjugated form; bacterial overgrowth flora can deconjugate
these, making them unavailable for reabsorption and depleting bile salts needed to form fat
micelles necessary for fat absorption in proximal gut
o Deficiency of vitamin B12; normally bound to intrinsic factor from stomach and complex absorbed from
terminal ileum; w/bacterial overgrowth, dietary B12 used by bacteria
 Cellular systems w/high rate of turnover and DNA synthesis (bone marrow, CNS, and gut
epithelium) severely impaired, leading to megaloblastic anemia or structural gut abnormalities
 Epithelial villi shortened w/decreased enterocyte turnover and atrophy
 B12 also required for myelin synthesis; deficiency results in degeneration of myelin sheaths,
producing classic neurological syndrome of pernicious anemia
o Diarrhea – usually results from degradation of malabsorbed oligosaccharides reaching colon because of
degradation by normal flora
 Osmotic diarrhea – concentration of osmotically active solutes increases and water moves
across mucosa to maintain iso-osmolarity; can also be caused by deconjugated bile salts in colon
o Malabsorption of vitamins A and D – causes severe visual disturbance and softening of bones
 Vitamin K deficiency rare; reduced absorption of fat-soluble vitamin offset by increased vitamin
production by plentiful bacteria
 Usually diagnosed when malabsorption and nutritional deficiencies present together w/predisposing anatomic
or physiological conditions (intestinal blind loops)
o Breath tests document presence of overgrowth flora in proximal small bowel
o Treatment requires correction of predisposing condition in conjunction w/careful nutritional repletion
and broad-spectrum antibiotic therapy
o Relapse can occur and repeated courses of therapy can be necessary
Diarrhea and Dysentery
 Dysentery – distinctive syndrome involving colon; inflammatory response results in abdominal pain and smallvolume stools consisting of blood, pus, and mucus
o Association w/specific microorganisms (usually Shigella)
o Therapy directed toward elimination of pathogen using antibiotics (multiple antibiotic resistance)
 Foodborne outbreaks of bloody diarrhea due to E. coli that produce toxins related to Shiga toxin (STX) from
Shigella dysenteriae type I; these E. coli called enterohemorrhagic E. coli (EHEC)
o Constitute variety of serotypes w/O157 being most common
o 10-15% of infections result in more systemic complications such as hemolytic-uremic syndrome (HUS)
o HUS results from toxin-mediated damage to endothelial cells, leading to thrombus formation in multiple
organs including kidneys and brain
 Campylobacter jejuni – usually transmitted by poultry, which are almost always colonized by the organism
 Aeromonas hydrophila and Plesiomonas species cause waterborne or shellfish-associated outbreaks
 Cyclospora cayetanensis – transmitted by contaminated imported raspberries
 Microsporidia – Enterocytozoon bieneusi, Septata intestinalis, and others cause chronic diarrhea in AIDS pts
 Agents of viral diarrhea include enteric adenovirus, astrovirus, norovirus, and rotavirus, among others
 Segment of DNA that encodes cholera toxin contained on filamentous bacteriophage (CTX) that infects bacteria
o V. cholera (O139) – new strain; resulted from deletion of O1 lipopolysaccharide synthesis genes and
insertion of new LPS synthesis genes into current pandemic serogroup O1 cholera strain
 Shigella infection – causes shigellosis (bacillary dysentery)
o In U.S., most common species is S. sonnei; causes self-limited watery diarrhea in infants and children in
child-care centers
o S. flexneri – important cause of infection in developing countries where S. sonnei rare
 Yersinia enterocolitica – often zoonotic and may be transmitted by drinking raw milk or consuming undercooked
meat such as pork
 Diarrhea affecting children younger than 2 years most likely viral (rotavirus is most common)
o In temperate regions, rotavirus diarrhea seasonal (winter vomiting disease)
o In tropical zones, it occurs year-round
o Adults may be infected, but often don’t experience symptoms
 Severe diarrhea associated w/measles

Distinct group of enteric infections seen in MSM; anal intercourse permits infection of distal bowel w/pathogens
typically associated w/STDs
o Protocolitis due to Chlamydia trachomatis, HSV, Neisseria gonorrhoeae, or Treponema pallidum
o MSM at increased risk for E. histolytica infections due to fecal-oral transmission
Infections of Small Intestine
 Viruses that cause death or dysfunction of intestinal epithelial cells – main agents rotaviruses and noroviruses
o Cause diarrhea by destroying or altering function of enterocytes at villi; don’t affect those in crypts
o Villus cells are Na+-absorbing cells; crypt cells secrete Clo Damage of villus cells leads to decreased sodium and water absorption, which results in net
accumulation of fluid in lumen and damage to disaccharidases-containing microvillus membranes,
leading to sugar malabsorption
 Sugars enter colon, where they are metabolized by bacterial flora to osmotically more active
products, drawing more fluid into lumen – partially responsible for postenteritic syndrome seen
in children (mild diarrhea persists after infection resolved)
 Bacteria that colonize small intestine – enterotoxigenic E. coli and V. cholera; diarrhea secondary to production
of toxins by organisms; toxins activate enzymes responsible for synthesis of cAMP and cGMP, which stimulate
net Cl- secretion and inhibit Na+ uptake, resulting in fluid loss
 Protozoa (Giardia and Cryptosporidium) – surface-expressed or secreted molecules that participate in host
interactions and pathogenesis
o Individuals w/hypogammaglobulinemia at increased risk for giardiasis
o Giardia express variety of surface proteins to avoid neutralization by secretory IgA
 Bacteria that cause true food poisoning – toxigenic bacteria (Bacillus cereus and Staph aureus) multiply in food
before it is eaten; toxins accumulate and are ingested along w/food
o Effects often felt w/in few hours after tainted meal consumed
 Y. enterocolitica infects primarily terminal ileum and colon in all patients; in children younger than 5 years,
infection manifests as watery diarrhea; in older children, bacteria from intestine invade mesenteric lymph nodes
and cause focal inflammatory responses (may mimic acute appendicitis)
o Many adults develop reactive arthritis w/in weeks after onset of diarrhea; same symptoms occur after C.
jejuni, S. flexneri, and nontypoidal Salmonella gastroenteritis
 Reactive arthritis immunological phenomenon driven by molecular mimicry because organisms
not found in joint fluid
 Individuals affected most severely by arthritis often possess major histocompatibility antigen
HLA-B27
Infections of Large Intestine
 Bacterial pathogens tend to produce epithelial damage, mucosal inflammation, and bloody diarrhea (dysentery
syndrome); major pathogens are Shigella species and E. histolyica (ameba)
o Because inflammation in shigellosis prominent and usually located in distal large bowel, pain worsens
w/bowel movements (tenesmus)
o Mucosa easily damaged and looks ulcerated on proctoscopy
o Stools watery and initially substantial but decrease in volume later and consist of blood, mucus, and pus
o WBCs usually scarce in amebic dysentery because they are lysed by toxin produced by amebic
trophozoites present in lesions
o Some species of Campylobacter, Salmonella, and Yersinia produce inflammatory pathology in terminal
ileum; inflammation associated w/bloody diarrhea containing leukocytes and occasionally extends to
colon, resulting in dysentery
 EHEC colonize intestine of ruminants; cattle don’t get ill from infection because they lack critical receptor for STX
molecules; contaminated beef products common source of infection by E. coli O157:H7 and other serotypes
o Following infection of large bowel, EHEC adhere to colonic epithelial cells, causing characteristic lesion
where brush border effaced by dramatic change in cytoskeletal structures beneath attached organism
o Bloody diarrhea develops in 2-3 days of onset (hemorrhagic colitis); results from action of STX on colonic
endothelium or mesenteric ischemia from circulating toxin
 C. difficile infection usually arises after administration of antibiotics, which deplete or alter resident flora
o
Infection characterized by adherent pseudomembrane w/considerable mucosal inflammation and
damage w/o tissue invasion
 Shigellosis associated w/severe malnutrition, leading to protein deficiency syndrome (kwashiorkor); sometimes
results in rectal prolapse or toxic megacolon w/complete cessation of colonic peristalsis
o Systemic complications lead to HUS, leukemoid reactions w/high WBC counts, encephalopathy
 Amebiasis may cause intestinal perforation or obstruction; organisms may spread to produce abscesses in other
organs, especially liver
 EHEC infections associated w/production of STXs; 2 main types (STX1 and STX2)
o STXs cross mucosa and injure endothelium of intestinal lamina propria, glomeruli, and brain
o Cause HUS in children and more prominent neurological disease in older adults (thrombotic
thrombocytopenic purpura (TTP))
Infections of Gut-Associated Lymph Tissue
 Typhoid fever – Salmonella typhi invasion of GALT of small bowel; organisms disseminate to liver and spleen
where they proliferate
o When number sufficient, they enter bloodstream, causing persistent bacteremia and enteric fever
o Diarrhea may be absent or transient; patients may complain of constipation
o Low WBC count in relation to fever
o Hepatosplenomegaly
o w/sustained bacteremia, organisms invade lymphatic tissue of Peyer’s patches and may cause severe
inflammatory lesions, bleeding, and perforation
o Early use of effective antibiotics curtails acute illness but predisposes to relapse (interferes w/protective
immune response)
Surgical Complications of Intestinal Infections
 Severity of peritonitis from bowel perforation related to volume of spill, spread in abdomen, and capacity of
omentum to contain abscess
 Peritoneal infections most often caused by mixture of strict anaerobes (Bacteroides fragilis) and facultative
Gram- bacteria of Enterobacteriaceae family
 In large percentage, it is sufficient to replenish fluids and electrolytes, usually by oral rehydration, and avoid use
of IV fluids unless patient in hypovolemic shock
 Symptoms that suggest specific therapy (i.e., antimicrobials) include fever, tenesmus, persistent or severe
abdominal pain, weight loss, blood in stool, recent antibiotic use, raw seafood meals, MSM practices, foreign
travel, and prolonged duration of symptoms
 Identification and diagnosis of different kinds of organisms that cause diarrhea require very different techniques
o If cholera suspected, inoculate thiosulfate-citrate-bile salt-sucrose agar
o If E. coli suspected, inoculate sorbitol-containing MacConkey agar (SMAC) because serotype of E. coli
that doesn’t ferment sorbitol and stands out causes diarrhea
 Doesn’t distinguish between non-O157:H7 STX-producing E. coli; enzyme immunoassay required
to detect STXs in stool
o If nonbloody diarrhea persists or remains unexplained, test for Cyclospora and Giardia
o If HIV patient, check for Cryptosporidium parvum, Isospora belli, and microsporidia species
o Immunoassays to detect antigens of Cryptosporidium and Giardia
o Cryptosporidium, Cyclospora, and Isospora infections diagnosed in stool or biopsy specimens (acid-fast)
 In general, infections caused by toxigenic and invasive E. coli, Shigella, and V. cholera improved w/antibiotics
o Infections often resolve before diagnosis made
 Use of antibiotics for treatment of EHEC can increase risk for developing HUS
 Antibiotic treatment could increase risk of inducing carrier state (Salmonella)
 Cryptosporidium species defy truly effective therapy
 Antidiarrheal agents reduce stool frequency and improve their consistency, but don’t shorten course of illness or
(w/exception of loperamide) reduce volume of fluid lost
o By decreasing gut transit time, antimotility agents may impair pathogen clearance, prolonging infection
and enhancing severity
 Anticholinergics or opiates can produce toxic megacolon, esp. in children and those w/inflammatory diarrhea

Oral administration of glucose w/essential electrolytes dramatically accelerates absorption of Na w/water
following passively to maintain osmolality