Lecture 1: Infections of Upper GIT PDF

Lecture 1 Infections of upper GIT Dr. Hala Tabl  Defense mechanism against GITinfections  Every day we swallow large numbers of microorganisms.  Because of the body’s defense mechanisms, however, they rarely succeed in surviving the passage to the in...

Lecture 1 Infections of upper GIT Dr. Hala Tabl  Defense mechanism against GITinfections  Every day we swallow large numbers of microorganisms.  Because of the body’s defense mechanisms, however, they rarely succeed in surviving the passage to the intestine in sufficient numbers to cause infection.  Normal Flora It's estimated that about 1,200 species of bacteria, yeast and other organisms live in the human gastrointestinal tract.  Types of Gastrointestinal Infections  Infections of upper GIT (Stomatitis, Esophagitis, Gastritis).  Microbial causes of Diarrhea (Bacterial, Viral, Parasitic).  Food poisoning.  Parasites of the gastrointestinal tract.  Microbial causes of Hepatitis. Infections of oral cavity Infections of Esophagus Infections of Stomach I- Infections of oral cavity: A) Fungal causes:  Oral candidiasis (Oral thrush): Whitish patches on the tongue and mucosa of oral cavity. B) Viral causes:  Herpes simplex virus infections (Herpetic stomatitis): Vesicular eruptions and ulcerations in the oral cavity.  Coxsackievirus A infections: Herpangina: fever, blisters and ulceration of the soft palate and back of throat. Hand, foot and mouth disease: vesicular rashes on hands, feet and ulcers in mouth. II- Esophagitis: A) Fungal causes: Esophageal candidiasis. B) Viral causes: Herpesviruses such as cytomegalovirus and herpes simplex virus. *Most cases occur in immunocompromised patients III- Gastritis  Helico/bacter/pylori = H. pylori Helix=spiral / bacteria / pylorus of the stomach It is a type of bacteria that settles in the stomach mucosa The most common chronic bacterial infection in the world Infect over 50% of world population One of the leading etiology for various gastroduodenal diseases  Morphology Gram-negative; spiral or curved bacilli. Motile with multiple unipolar flagellae (Lophotrichous flagellae). Non-capsulated, non-spore forming.  Cultural characters  They are microaerophilic, require 5% O2, 5-10% CO2 and high humidity.  They grow best at 37°C for 3-6 days.  Fresh blood or serum agar media are used for culture of H. pylori.  Skirrow's medium as a selective medium.  The colonies are translucent, pinpoint.  Biochemical reactions  Do not ferment sugars.  Oxidase positive (possess cytochrome oxidase).  Catalase positive.  Urease positive (Produces large quantities of urease).  Virulence Factors and pathogenesis Pathogenesis of H. pylori depends on its ability to colonizes the mucosa of the stomach. It has many virulence factors that enable the bacterium to survive in the extreme acidic environment of the gastric tract, to reach the more neutral environment of the mucous layer, and to resist the human immune response, resulting in persistence. Urease: Converts urea (abundant in saliva and gastric juices) into CO2 and ammonia. Ammonia cause: Neutralize the local acid environment (Facilitates colonization). Localized tissue damage.  Multiple unipolar flagellae: Corkscrew motility enables penetration into viscous environment (mucus).  Mucinase: Degrades gastric mucus; Localized tissue damage.  Adhesins & LPS: Adhesion to epithelial cells.  Vacuolating cytotoxin (VacA): *Forms pores and intracellular vacuoles. *It induce apoptosis (causes epithelial cell damage) &breakdown the tight junction between cells.  Cytotoxin-Associated Gene A (Cag A): Stimulates inflammatory responses (gastritis) through induction of pro-inflammatory mediators (IL-8) and recruiting and activating inflammatory cells (neutrophils).  Transmission of H. pylori  Direct human-to-human transmission, via either an oral-oral (by saliva) or feco-oral route or sharing objects. This person-to-person mode of transmission is supported by the higher clustering of H. pylori infection within families.  The infection is usually transmitted in childhood through close contact with the mother.  Other possible sources include fecal contamination of food or water. Clinical outcome of H.pylori infections  Clinical pictures A) Mostly Asymptomatic B) Manifestations of gastritis or peptic ulcer: Epigastric dull or burning pain (Heartburn). Nausea. Indigestion (dyspepsia). Frequent burping (eructation). Bloating (Feeling full after eating a small portion). Loss of appetite. Weight loss. Dark or tarry stools or bloody vomit. Laboratory diagnosis  Non endoscopic (non invasive tests) 1) Urea Breath Test  [13C] or [¹⁴C] labeled urea is ingested.  Urease of H. pylori hydrolyzes the ingested urea into labeled CO2, which is exhaled with breath and then detected by radioisotopes reader. 2) Stool antigen detection:  By ELISA.  By immunochromatography. 3) Serology:  Detection of H. pylori antibodies in serum.  Endoscopic (invasive) tests 1) Specimen Collection: At least two biopsies are taken from the gastric mucosa during endoscopy. 2) Rapid urea test (RUT): The gastric biopsy sample is placed onto a medium containing urea and PH indicator. Red color indicate positive result. 3) Cultivation: On Skirrow's medium and incubated in microaerophilic atmosphere, at 37°C for 3-6 days. 4) Histological assessment: H. pylori can be visualized with hematoxylin and eosin-stained sections or using special stains. 5) PCR  Invasive endoscopy with gastric tissue biopsy followed by bacterial culture, histology, or rapid urease testing: The gold standard. This approach is recommended for higher risk patients (i.e. GI bleeding, sudden weight loss, excessive vomiting, or anemia) or those over the age of 60 for which a clinician may wish to rule out malignancies.  Non-invasive methods such as the urea breath test or stool antigen test: The recommended approach for low risk patients. These methods used for diagnosis of active disease and also used to monitor response to therapy.  Serology: Not preferred, as Abs may persist for years after infection and treatment (not differentiate between past and current infection)  Treatment  Triple drug regimen: for 14 days Proton pump inhibitors (PPI) + clarithromycin + (either amoxicillin or metronidazole).  Quadruple drug regimen: for 14 days PPI + Bismuth salt + tetracycline + metronidazole.