Microbiology of the Upper GI - Zimmer Flashcards
What are the three general GI system defenses?
- epithelium
- mucus,
- peristalsis
What are the 2 major defenses in the mouth?
- saliva (lysozyme, IgA, etc)
- normal flora
What are the 2 major defenses in the stomach?
- acid
- normal flora
What are the 2 major defenses in the intestines?
- Peyer’s patches
- normal flora
When do we have a really “clean” mouth?
Before we get teeth.
What are the four major normal flora microorganisms in the Esophagus, Stomach, Small Intestine?
- Four phyla in stomach:
- Proteobacteria
- Firmicutes
- Actinobacteria
- Bacteroidetes
What does the normal flora in the large intestine consist of?
- Microbe rich, “microbiome” studied here
- Anaerobes
- Gram-negative rods (Proteobacteria, etc)
- Enterococcus – gram-postitive cocci
- facultative anaerobes can survive wide range of stressors and enviromental conditions
- Spirochetes
What are dental caries?
Infectious disease that causes tooth decay
Results in → pain, tooth loss, spread of infection
What are the risk factors for dental caries?
- Risk factors:
- high-sugar diet
- poor oral hygiene
- reduced amount of saliva
- smoking
- periodontal disease
What is the major mechanism that causes dental caries?
- Microbial proliferation and invasion – growth and spread of microbes that causes damage that is significant in illness.
- Fermentable sugars + Acid-producing bacteria => decreased pH ==>
- DEMINERALIZATION OF TEETH
What is the treatment for dental caries?
- ***Drill out decayed area of tooth and put in a filling
- Do not want to let caries grow
- Can involve the whole tooth, infection
What is Periodontal Disease?
- Infectious disease destroying supporting structures of teeth
- underlying tissues/bones
- Mild and common form: gingivitis
- Involves the gums
- Irritation
- Redness
- Swelling
What conditions are associated with Periodontal Disease?
- Heart attack
- Stroke
- Lung disease
- Premature birth or having a baby with low birth weight, in women
- Diabetes
What is the major mechanism that causes Gingivitis and Periodontitis?
- Host immune response
- response of host to microbe that causes illness
What microbial structure composes plaque?
Biofilm
What is a biofilm?
- Biofilms consist of two or more species of bacterial microcolonies that are enclosed in a glycocalyx.
- Glycocalyx is composed of polysaccharides and constitutes up to 50-95% of the biofilm
- Other components of the biofilm include proteins and DNA
- Can be hundreds of species in a biofilm
How is a biofilm formed?
- Weak adherence of cells to a surface
- Stronger adherence, likely co-adhesion mediated
- Multiplication of cells
- Polysaccharide formation
- Changing of microbial composition over time
Why is it beneficial for bacteria to live in a biofilm?
- Adherence
- Protection from the immune system
- Protection from antibiotics
- Symbiotic (but also anti-symbiotic) relationships
- Local conditions of pH, etc, in a normally inhospitable environment
Is all plaque bad?
- Some can be neutral:
- Undisturbed dental plaque exists in a relatively stable microbial homeostasis.
- Perturbations to the microbial balance are triggered by environmental or host factors:
- excessive sugar intake in the case of caries
- inflammatory response to subgingival plaque in the case of periodontitis
- Subsequently, the microbial population within dental plaque shifts toward a more pathological community => DISEASE
What species of oral streptococci play important roles in protecting against dental caries and periodontitis?
- S. sanguinis
- S. oralis
- S. gordonii
- S. mitis – the “mitis group” produce hydrogen peroxide which inhibits the growth of other oral bacteria
Where do microbes that cause dental caries live in the mouth?
- usually located in plaques on tooth surfaces
- often in crevices or between teeth
Tip: they’re often gram positive
Where do microbes that cause periodontal disease live?
- below the gumline – in the subgingival space
- Tip: they’re often gram negative
What type of Streptococci are involved in dental caries?
- Streptococcus mutans
- The “bad” oral steptococci are key players
- identification of streptococci to the species level is complicated by the fact that many oral streptococci are naturally transformable and readily exchange DNA with one another.
What virulence factors of Streptococcus mutans allow it to cause disease?
- adhesin-like surface-associated proteins (e.g. AgI/II family)
- capable of binding to receptors in the pellicle
- extracellular glucosyltransferases (Gtfs) are constituents of the pellicle
- capable of synthesizing glucans (a type of polysaccharide) in situ from sucrose
- Glucans provide additional S. mutans binding sites, as it binds avidly and in large numbers to these polymers
What are “Keystone pathogens” (aka = “red group” pathogens) in periodontal disease?
- low-abundance microbes can orchestrate destructive periodontal inflammation by remodeling a normally symbiotic microbiota into a dysbiotic state
What are some examples of “Keystone pathogens”?
- Treponema denticola – a spirochete
- Tannerella forsythia – anaerobic, gram negative
- Porphyromonas gingivalis – best studied because it can be cultured
-
Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans
- is related to the severity of the periodontal disease – gram(-) rod
How do you prevent dental caries and periodontal disease?
- Less sugar in diet – less chance of existing biofilm becoming more pathogenic
- Brush and floss frequently – removes plaque, less chance of harboring bacteria that trigger inflammatory responses
- Fluoride
- remineralization to counteract the effects of demineralization under low pH conditions
- Inhibits bacterial glycolysis and pH maintenance enzymes
- Increased Saliva flow →sugar free gum
- Introduces components of host response
- Increases buffering capacity and removes sugars
- Return biofilm pH more quickly to resting levels
Is gingivitis reversible or irreversible?
REVERSIBLE
Treatment is the same as prevention: good cleaning and oral care.
What is the treatment for periodontitis?
- Thoroughly clean all surfaces and pockets around teeth to prevent bone damage or prevent further bone damage
- Milder cases:
- Scaling to remove tartar and bacteria
- Root planing: discourage further bacterial growth
- Antibiotics
- Topical is typical
- Oral antibiotic may be necessary in cases of persistent periodontitis despite conventional treatment, when bacteria remain in tissues empirical use of antibiotics, such as a combination of amoxicillin and metronidazole
- Severe cases:
- Centers around surgical treatments to fix permanent damage
- Flap surgery
- Soft tissue grafts
- Bone grafts where underlying bone structure is affected
- New techniques on the horizon
What is the link between Diabetes and Periodontal Disease?
- Diabetes has risk of periodontitis up to 3-fold
- increased inflammatory markers/cytokines
- Periodontal Disease has a negative effect on glycemic control
What is Ludwig’s Angina?
- Skin infection on floor of the mouth, usually results from untreated dental infections.
- Swelling of infected area may block the airway or prevent swallowing of saliva.
- Symptoms include:
- Breathing difficulty
- Confusion or other mental changes
- Fever
- Neck pain
- Neck swelling
- ***Redness of the neck
- Weakness, fatigue, excess tiredness
What pathogens cause Ludwig’s Angina?
- alpha-hemolytic streptococci
- staphylococci
- bacteroides groups
What microorganism causes Hairy Leukoplakia?
caused by a virus = EBV
Patient is almost always HIV(+)
What are the morphological characteristics of EBV?
- Genome
- SS/DS structure
- Non/Enveloped
- Herpesviridae
- Double stranded Linear DNA
- enveloped
- Epstein-barr virus (human herpesvirus 4)
What is the treatment for Candidiasis?
- Must treat with prescription antifungal
- Most commonly a topical treatment:
- clotrimazole lozenge
- nystatin suspension (swish and swallow)
- Unresponsive cases:
- systemic antifungal such as fluconazole
- Worst case:
- IV administration of amphotericin B (significant side effects)
- Untreated infections can lead to an invasive candidiasis.
What is the difference between Leukoplakia and Hairy Leukoplakia?
- Leukoplakia:
- not caused by a microorganism, thought to be caused by smoking and chewing tobacco – or other irritations
- Hairy Leukoplakia:
- caused by a virus (EBV)
- Patient is almost always HIV(+).
- Fuzzy white patches on side of tongue.
- Unlike thrush, it cannot be wiped away
What is the major pathologic micoorganism of the stomach?
Helicobacter pylori
What are the morphological features of H. pylori?
- Gm +/-
- Shape
- Catalase +/-
- Oxidase +/-
- Urease +/-
- Gram (-)
- Flagellated helix-shaped rod (spirilli)
- Microaerophilic
- Catalase and oxidase (+)
- Urease (+)
What happens after Helicobacter pylori colonization in the stomach?
- Asymptomatic Gastritis first
- then can progress to any of the following:
- Symptomatic Gastritis
- Ulcer
- Carcinoma
- Lymphoma
- then can progress to any of the following:
What mechanisms of H. pylori colonization help cause disease?
- Toxin production –
- bacteria release toxin that causes illness
- Host immune response –
- response of host to microbe that causes illness
What are the symptoms of gastritis?
- Inflammation of the gastric mucosa (transient or chronic)
- Gnawing or burning ache in upper abdomen
- Pain may become either worse or better with eating
- Nausea/Vomiting
- A feeling of fullness in your upper abdomen after eating
What are the symptoms of Gastric Ulcers?
- Most common = burning abdominal pain felt anywhere from navel to breastbone
- Worse when stomach is empty
- Flare at night
- Often temporarily relieved by eating foods that buffer stomach acid
- Disappear and then return for a few days or weeks
- Less common: The vomiting of blood —
- may appear red or black
- Dark blood in stools or stools that are black or tarry
- Nausea or vomiting
- Unexplained weight loss
- Appetite changes
What are the major virulence factors that help H. pylori colonize the GI?
- Immune Evasion:
- Inhibit phagocytic uptake Inhibit adaptive immune response
- Evade killing by reactive oxygen species and nitric oxide
- Evade recognition by pattern recognition receptors (PAMPs)
- Urease +:
- Raises local pH Urea + Urease => CO2 + Ammonia (basic, raises pH)
- Helps bacteria make it through buffering mucous layer
- Flagella:
- Allows bacteria to get through the lower pH layer
- Chemotaxis:
- Can sense pH gradient to help guide motility in preferred directions
- Toxins:
- VacA = Pore forming cytotoxin that allows leakage of Ca+ from epithelial cell
- CagA = Type 4 secretion system (TFSS) is a needle through which CagA travels into the host cytosol and affects the proliferative activities, adhesion, and cytoskeletal organization of epithelial cells.
- highly proinflammatory
- known to interact with at least ten host proteins.
How does H. pylori cause an ulcer?
- Attract inflammatory cells (host cells)
- Inflammatory cells cannot kill bacteria easily
- Host damages itself by continual, ineffective immune response!
How is H. pylori diagnosed?
- Diagnosis: A variety of methods are available, know the principles behind each test
- Endoscopy + culture = GOLD STANDARD
- rapid urease testing included
- Breath Test = detects radioactive CO2
- Stool test = direct antigen test (detects active vs. latent)
- Blood test = detects H. pylori antibodies
- Endoscopy + culture = GOLD STANDARD
How is H. pylori treated?
- week of “Triple therapy” is currently used:
- Antibiotics will be necessary
- often clarithromycin and amoxicillin
- Proton pump inhibitor (3rd arm of triple therapy)
- to aid in the healing of ulcer
What type of lymphoma can be caused by H. pylori?
- Mucosa-associated lymphoid tissue (MALT lymphoma or MALToma) in the stomach is termed “gastric MALT” (Tumors of B cells)
What type of carcinoma can be caused by H. pylori?
Gastric carcinoma
What are the symptoms of Gastric MALT?
- Indigestion
- Heartburn (stomach pain)
- Long term inflammation
- Antibiotics are still part of the treatment strategy
What are the symptoms of Gastric Carcinoma?
- Indigestion
- Heartburn (stomach pain)
- Long term inflammation
- H. pylori a risk factor in only 65-80% of gastric carcinoma
