Bacterial invasion of the lamina propria: 10-15% of cases of infectious esophagitis;

*necrosis of squamous epithelium, may occur in patients with systemic and upper respiratory tract infections

Etiology: immunocompromised patients;

Key features include - Shallow sharply punched out ulcers, surrounded by relatively normal mucosa;

Multinucleated giant cells with intranuclear cowdry type A inclusions at the margin of the ulcer and inclusions in the *squamous epithelial cells with characteristic ground glass nuclei or nuclear molding

Etiology: relatively common in AIDS patients, rare in immunocompetent pts.

Characteristic Ulcers: Multiple *well circumscribed ulcers, intranuclear nnd cytoplasmic inclusions found in the capillary endothelium* and stromal cells at the base of the ulcer.

Aancillary IHC stains and/or in situ hybridization may be useful for diagnosis

Etiology: mostly Candida albicans and tropicalis;

Occurs in immunosuppresed patients, may be found in otherwise healthy individuals;

Seen in AIDS pts when T cells are very low;

At endoscopy of esophagus: white plaques of fibrinopurulent exudate*

This fungus is a normal part of GI tract flora.

Need to ID pseudohyphae with invasion and not just budding yeasts

Use this stain on candida albicans to visualize the fungal growths as dark black spots on a blue background;

In general, silver stains are used to visualize fungi and Legionella

Less common causes of this disease:

Mycobacterium tuberculosis, MAC, Histoplasma caapsulatum, toxoplasma gondii, EBV, idiopathic esophageal ulceration, and HIV retrovirus

Possible etiology of inflammation of the stomach include: systemic viral or bacterial infections

(salmonella and CMV)

Gross: punctuate erosions on the stomach surface,

Histo: Mucosal disruption with normal adjacent mucosa

Etiology: Chronic mucosal inflammatory changes in the stomach -> mucosal atrophy and intestinal metaplasia, usually in the absence of erosions:

H. Pylori* is the most important etiologic agent

Microscopic features:

Neutrophils: more abundant in the *antrum and cardia* than corpus, only inflammatory cells in the gastric epithelium.

Acute cryptitis, and mixed with macrophages and eosinophils in lamina propria.

Lymphoid follicles are almost always present

Initial phase includes acute inflammatory response;

Endoscopically: hemorrhagic lesion, and multiple antral erosions and ulcers

Characteristics: non-sporulating, curvilinear gram - rods, that flourish in gastric mucosa.

Flagella allow it to swim through the gastric mucous.

Elaborates urease, expresses bacterial adhesions and toxins;

Patients usually improve whne treated with antibiotics, relapsese are associated with re-infection

Gross: No distinct endoscopic pattern; Hyperemia, erosions, hypertrophy and atrophy may coexist in varying combinations depending on the stage/type of gastritis;

Histology: Mucous layer covering the gastric mucosa is colonized by H. pylori, the organisms attach to the mucous cell

Proton Pump Inhibitors;

In H. pylori gastritis, patients on this drug may show histology with intracellular invasion by H. pylori

Inflammation of the colon;

Histology: Diffuse, regional or focal active colitis with prominent cryptitis, without crypt architectural distortion or crypt abscess formation;

Use clinical questioning to separate this from IBD

Rotatavirus (MCC diarrhea in 6-24 m.o. worldwide),

Calcivirus = Norwalk virus (very common cause of nonbacterial food-borne epidermics (gastroenteritis) in all age groups,

Enteric adenovirus (diarrhea in infants)

Pathology: viruses selectively infect and destroy mature enterocytes and cause villous atrophy and cryptal hyperplasia.

Viral particles may be present within villous enterocytes in EM

aka Norwalk virus;

ssRNA;

Common cause of nonbacterial infecitous gasteroenteritis in all age groups;

Oral-fecal route of transmission;

Vomiting in children, diarrhea in adults; spreads in hospitals, nursing homes, and cruise ships

dsDNA virus;

Most common cause of severe diarrhea in infants and young children and a leading cause of diarrheal mortality in the world;

Only 10 virions required to inoculate (very virulent);

6-24 yr old individuals are most susceptible

Causes diarrhea by viral infection and destruction of mature enterocytes of the small bowel resulting in loss of absorptive surface → watery diarrhea.

There are vaccines now available

dsDNA (linear) genome, iscohedral capsule;

Second most common cause of pediatric diarrhea;

Biopsy is nonspecific;

Shows villous atrophy, crypt hyperplasia;

Incubation: 1 week;

Symptoms: diarrhea, vomiting, abdominal pain, fever, and weitght loss, recovery within 10 days (self limited)

Histologically: Stomach has increased presence of lymphocytes and crypt hypertrophy;

Common causes include norovirus, rotavirus and adenovirus

Characteristic giant cells surrounded by epitheloid cells in stomach;

Often secondary to other conditions;

May be able to identify TB or Fungi based on special stains/cultures

A rare, systemic disease caused by the bacterium Tropheryma whipplei;

Typically presents in middle age white males;

Sx: chronic weight loss, arthritis/joint pain, malabsorption and lymphadenopathy;

Small bowel is MC affected;

Endoscopically mucosal folds are thickened with yellow-white plaques;

Microscopically there is a massive infiltration of the lamina propria and submucosa with foamy macrophages**

Tx: Antibiotics = Penicillin, ampicillin or tetracycline;

Stains glycogen and mucopolysaccrides;

Used to visualize foamy macrophages in the lamina propria and submucosa of pts with in Whipple's disease

Etiology:

Ingestion of preformed toxins (S. aureus, Vibrio cholerae, C. perfrinigins, C. botulinium);

OR

Infection by toxigenic organisms (traveler's diarrhea, may cause diarrhea and dehydration, or dysentery),

OR

Infection by enteroinvasive organisms (dysentery)

These two bacteria have secretory toxins involved in bacterial enterocolitis;

V. cholerae: (G-, comma shaped, oxidase+) produces a toxin that permanetly activates the Gs subunit of a GPCR in the intestines causing ↑ cAMP levels causing profuse diarrhea with "rice water" stools;

EnteroToxogenic E. coli: causes Traveler's diarrhea (watery)

These two bacteria have cytotoxins and are involved in bacterial enterocolitis;

Shigella: (non-lactose fermenter that invades the intestinal mucosa and causes bloody diarrhea, no flagella).  Shiga toxin (inhibits protein synthesis) produces severe and potentially deadly dysentery;

EHEC: includes O157:H7 (produces shiga-like toxin);

Both are associated with the development of Hemolytic Uremic Syndrome, HUS (anemia, thrombocytopenia, renal failure)

G(+) cocci in clusters;

Has a bacteiral endotoxin that binds to antigen receptors in lymphocytes; found in bacterial enterocolitis

EIEC,

Shigella,

Salmonella,

Yersinia enterocolitica species

all do this in bacterial enterocolitis

Comma shaped gram - bacteira;

Causes secretory (rice-water) diarrhea,

01 and 0139 serotypes are the most important

MOA: Vibrios never invade the gut epithelium, but when cholera toxin is secreted, it induces dilute "rice water" diarrhea up to 14 L/ day, causing dehydraiton and electrolyte imbalance.

Cholera toxin is an AB toxin that is endocytosed and the A subunit carries out ADP ribosylation of the Gs subunit of the GPCR causing ↑↑ cAMP which causes massive excretion of water and electrolytes into the intestinal lumen;

The bacteria affect the proximal small intestine, but the intestinal mucosa is left intact.

Flagellated (key difference from Shigella), gram -, non-lactose fermenting bacteria;

Invades the colonic mucosa to cause bloody diarrhea;

Responsible for self-limited food an water borne illness; major source is feces- contaminated chicken and beef;

Abx may make it worse!

Salmonella typhi;

Humans are the only host for this bacteirum, which is shed in feces, urine, vomitus, and oral secretions;

Causes Typhoid Fever (Rose spots on the abdomen, fever, HA, diarrhea - can remain in the gallbladder of some pts (carriers)

Salmonella (flagellated, G -, lactose - ) species;

Cause self-limited food-water borne gastroenteritis (may be from chicken ingestion)

Symptoms of S. typhi at this point include: bacteriemia, fever and chills

Note that Typhoid fever (caused by S. typhi) is not the same as Typhus (caused by Rickettsia prowazekii (epidemic) or R. typhi (endemic), or in the form of scrub typhis by Rickettsia tasutsugamushi.

Symptoms of S. typhi at this point include:

Widespread mononuclear phagocytic involvement with rash, abdominal pain and prostration

Symptoms of S. typhi at this point include:

Ulceraiton of peyer patches with intestinal bleeding (remember that salmonella is invasive) and shock.

Salmonella affects the Ileum and colon, causing Peyer patches to become plateau-like elevations followed by oval ulceration.

It proliferates within macrophages and damages lymphoid tissue.

Spleen, liver and gallbladder are involved (remember the gallbladder is the reservoir for carriers)

Non-motile, G-, lactose- bacteria;

One of the most common causes of bloody diarrhea; Humans are the only reservoir;

Produces Shiga Toxin;

Low infectious dose (doesn't take many to infect) and large # in stool = highly transmissible via fecal/oral route;

A self-limited colitis with diarrhea (bloody), fever, abdominal pain;

Shiga toxin it secretes inhbits eukaryotic protein synthesis leading to cell damage and death

Bacterial infection leads to the following

Histo: Mucosa is hemorrhagic and ulcerated, pseudomembranes may be present;

Apthous-appearing ulcers may be present, need to differentiate from IBD

Presents with either

1) watery diarrhea, leading to dysentery with constitutional symptoms persisting for a month, or 

2) Subacute presentaiton: waxing and waning diarrhea persisting for several months (need to r/o ulcerative colitis)

Manifestation: shorter duration but greater severity in children than in adults, in the subacute presentation may mimic ulcerative colitis.

Caused by bacterium with Shiga toxin

Complicaitons: uncommon;

Include Reiter Syndrome (reactive arthritis) and hemolytic uremic syndrome (HUS)

Shigella can be treated with antibiotics which will ↓ the course and ↓ the duration of organism seeding;

Do not use antidiarrheal medications as they can prolong symptoms and delay organism clearance;

Note that the usefulness of Abx is another key difference between Shigella and Salmonella (abx with salmonella may prolong the duration of infx)

Most commonly related to previous abx therapy (especially orally admin abx);

Most common nosocomial related pathogen;

Endoscopically: Yellow-white pseudomembranes, patchy distribution, rectum may be spared

Intercrypt necrosis and balloned crypts give rise to the laminated pseudomembrane composed of fibrin, mucin, and neutrophils;

Severe and prolonged necrosis may lead to full thickness mucosal necrosis;

Remember: pseudomembranis colitis is not definitively diagnosis for this condition but is highly suggestive

G - rod;

Sx: Bloody diarrhea with severe cramps (watery diarrhea can occur also) mild or no fever;

Endoscopically: colonic edema, erosison, ulcers, and hemorrhage;

Right colon is usually more severely affected. Surgery may be necessary to control bleeding or relieve edema-caused obstruciton;

Microthrombi may be seen in small vessels.

This bug may cause HUS or TTP, severe illness in children and elderly.

Think jack in the box and contaminated beef.

Principal cause "Travelers diarrhea";

Spread via contaminated food and water: common in children under 2 years of age;

Produces LT and ST toxins which inhibit intestinal absorption and induce chloride and water secretion;

Clinical symptoms include: secreteory, noninflammatory diarrhea, dehydration and, in severe cases, shock

Large outbreaks in developed countries have been traced to inadequately cooked contaminated ground beef, vegetables and milk;

Etiology: shiga-like toxin which inhibits protein synthesis: 0157:H7 serotypes most likely to cause bloody diarrhea and HUS*

Similar to Shigella;

Transmitted via food, water and person-to-person contact;

No toxins*;

Invades epithelial cells and causes histologic features of acute self-limited colitis (Invasive necrosis and inflammation, dysentery);

Age: young children

Organisms can adhere to epithelial enterocytes via adherence fimbriae;

Dispersin, a bacterial surface protein, neutralizes the negative surface charge of lipopolysaccharide;

Produces an enterotoxin, but damage from it is minimal Symptoms: Diarrhea in children and adults

Strongyloides and hookworms enter and cause parasitic enterocolitis by this mode;

Larvae penetrate the skin of the feet and migrate through the bloodstream, cause intestinal infections;

Fish tapeworm (Cestode);

Causes B12 deficiency;

Protozoan;

Causes amebiasis by fecal-oral transmission;

Can cause dysentery and liver abscesses;

Ingested quadrinucleate cysts colonize in the colon and release trophozoites;

Clinical presentation: Abdominal pain, bloody diarrhea, weight loss;

Acute necrotizing colitis and megacolon may occur - both are associated with increased mortality;

Treat with Metronidazole

Antibiotic treatment for Entamoeba histolytica;

This drug is used to treat amoeba because they are obligate fermenters of glucose - the drug inhibits pyruvate oxidoreductase which is required for fermentation

Histology: cysts are resistant to stomach acid;

Most frequently found in cecum and ascending colon. Sigmoid, rectum and appendix may be involved;

May penetrate splanchnic vessel and embolize to liver;

Abscesses in about 40% of patients (liver), rarely but can spread to lung and heart (directly), or to the brain and kidney (hematogenously.)

Common parasite of the appendix;

Common in ages 5-15;

Worm is found in appendiceal lumen with no mucosal inflammatory response;

Inverse relationship bw this worm and inflammation;

Infects via oral-fecal method;

Does not invade, lives within lumen of the intestine;

Rarely causes serious disease;

Adults worms migrate to the anal opening at night and lay eggs on the peri-rectal tissue. Eggs cause pruritis;

Scratching → contamination of hte hands → human-to-human transmission. Worms and eggs are viable outside the body.... reinfection is common;

Caused by bacteroides fragilis (Frequent anaerobe), E. coli (frequent aerobe), Streptococcus milleri: common aerobe;

Linked to 7x ↑ risk of abscess formation

Most common symptomatic primary immune deficiency, heterogenous clinical and immunologic features;

Patients present at any age;

Pt present with reccurent bacterial infections;

Are at risk for chronic inflammatory disorders and malignancies of the GI tract

Common Variable ImmunoDeficiency;

Small bowel abnormalities may include: villous blunting, ↑ intraepithelial lymphocytes, and nodular lymphoid hyperplasia;

The trophzoite form of the organism can be identified on small bowel biopsy;

Common immunodeficiency of the small bowel

Protozoan, ferments glucose, lacks mitochondria;

2 forms: dormant but infectious cyst (oral-fecal), and trophozoites that multiply in the intestine;

As this bug moves from duodenum to jejunum, ↓ in availablity in cholestrol induces transition from trophozoites into cysts;

These adhere to but do not invade the intestinal epithelial cells;

Causes diarrhea but not dystentery*

Think in cases of watery diarrhea in pts who spend time outdoors!

MC pathogenic parasite infection in humans*;

Histo: ranges from normal SI mucosa to marked blunting of villi with mixed inflammatory infiltrate in lamina propria;

Immunity is limited by the parasite's ability to vary its major surface proteins to antigenicallly distinct forms

HBV damaging liver cells,

TB causes tissue damage when the body attempts to sequester it,

Post-streptococcal GN (IC deposition),

Sepsis

Subacute, sclerosisng panencephalitis,

Inclusion body encephalitis

Warthink-Finkeldy Cells

(Multinucleated giant cells with eosinophilic, nuclear inclusion bodies);

Found in the lymphoid organs, lungs and sputum of measles patients.