Exam 4 Pathophysiology Flashcards - Key Infections and Mechanisms

What are the 2 main infections caused by Vibrio cholera?

Cholera and Gastroenteritis

What virulence factors does V. cholera have?

Tolerates a wide range of pH. Susceptible to stomach acids.

How does cholera toxin work? What does it do? What is the receptor?

Complex A-B toxin. Binds to the ganglioside GM1 receptors which results in a hypersecretion of water and electrolytes.

What are the symptoms of cholera infection?

Watery stools, Vomiting, Weakness, Shock, and Dehydration.

What causes the rice water stools?

GM1 ganglioside receptor binding to Cholera toxin.

How does V. cholera adhere to the mucosal cell layer?

1. The toxin co-regulated pilus encoded by the TCP gene complex

2. Chemotaxis proteins are encoded by the CEP genes.

Epidemic vs Pandemic

An epidemic occurs when an infectious disease spreads rapidly to many people. A pandemic is a global disease outbreak

Where can V. cholera be found? How is it spread?

In estuarine and marine environments. Spread by contaminated food or water. Direct person-to-person is rare due to high dosage.

What is the reservoir for Cholera?

Man and Water

What infections does V. parahemolyticus cause? How could you catch it?

Bacterial gastroenteritis. Contaminated raw fish.

What infections does V. vulnificis cause? How could you catch it?

High mortality rate, wound exposure to the contaminated salt water of bad shellfish.

Opportunistic pathogen

Typically non-pathogenic microorganisms act as a pathogen in certain circumstances.

What 4 surface components facilitate attachment?

1. Flagella

2. Pili

3. Lipopolysaccharide

4. Alginate

Virulence factors

Exotoxin A (ETA) = Burn wounds, BLocks peptide chains, Type II secretion.

Pyocyanin = blue redox pigment, superoxide, and hydrogen peroxide.

Pyoverdin = Yellow-green pigment that binds iron for metabolism.

LasA (serine protease) and LasB (zinc metalloprotease) = degrade elastin, which damages elastin-containing tissue.

Alkaline protease = Tissue destruction and spread of P. aeruginosa.

Phospholipase C = heat labile hemolysin, breaks down lipids and lecithin. Tissue destruction.

Exoenzyme S (ExoS) and Exoenzyme T (ExoT) = toxins produced by P. aeruginosa.

What makes Pseudomonas resistant to many antibiotics?

1. Mutation of porin proteins

2. Produces B-lactamases

3. Efflux pumps can pump antibiotics out of cells

What factors predispose immunocompromised patients to Pseudomonas infection?

Previous therapy with broad-spectrum antibiotics eliminates the normal bacterial population. Use of mechanical ventilation equipment which may introduce the organism to the lower airways.

What kind of infections can Pseudomonas cause?

The lower respiratory tract can be asymptomatic or inflammation of the bronchial to severe necrotizing bronchopneumonia.

Why is the mortality rate in affected patients higher with P. aeruginosa bacteremia?

1. The predilection of the organism for immunocompromised patients

2. Difficulty in treating antibiotic-resistant strains

3. Inherent virulence of Pseudomonas

Campylobacter

Discovered in the last 20 to 30 years.

What are 3 features for members of the Campylobacter family?

(1) a low DNA guanine plus cytosine base ratio,

(2) an inability to ferment or oxidize carbohydrates, and

(3) microaerophilic growth requirements (i.e., growth only in the presence of a reduced oxygen level)

Reservoir and types of infections (symptoms) caused by C. jejuni, C. coli, and C. fetus

C. jejuni - (reservoir: Poultry, cattle, sheep), infection causes gastroenteritis, extraintestinal infections, Guillain-Barré syndrome, reactive arthritis

C. coli - (reservoir: Pigs, poultry, sheep, birds), infection causes gastroenteritis, extraintestinal infections

C. fetus - (reservoir: Cattle, sheep), infection causes vascular infections, meningoencephalitis, gastroenteritis

What is Guillain-Barré syndrome? What causes it?

Autoimmune disease is caused by antigenic crossreactivity between oligosaccharides in bacterial capsules and glycosphingolipids on the surface of tissues.

Causes damage, loss of nerve conduction, and paralysis.

Mechanism of transmission of Campylobacter

Zoonotic infection (bad poultry), can also be acquired by contaminated food, unpasteurized milk, and water.

Helicobacter

Curved gram-negative rods

H. pylori (Gastric), H. cinaedi (colon), H. fenneliae (septicemia)

Types of infection and reservoir for H. pylori

Chronic gastritis, ulcers, gastric adenocarcinoma, and mucosa lymphoid tissue lymphoma.

Developing nations

Reservoir (Humans) person to person spread through shit.

Gastric ulcers

70% to 100% of patients with gastritis are infected with H. pylori

How did Barry Marshall prove that ulcers were caused by H. pylori?

He drank H. pylori to infect himself, got an ulcer after 14 days, and took antibiotics to cure himself!

How was H. pylori discovered? Mechanism of transmission? Reservoir?

In 1983, gram negative rods resembling campylobacters were found in patients with type B gastritis.

2 factors that facilitate H. pylori colonization

(1) blockage of acid production by a bacterial acid- inhibitory protein and

(2) neutralization of gastric acids with the ammonia produced by bacterial urease activity.

Know the virulence factors of H. pylori - what are they..what do they do?

Urease = neutralizes gastric acid

Flegella = motility

Mucinase = degrades gastric mucus

Phospholipase = degradation of hydrophobic phospholipids

VacA = protein that damages the cell by producing vacuoles

cagA (cytotoics-associated gene) = ecods for a structure secretion system to inject into the host epithelial cell.

What does Bordetella pertussis cause?

Pertussis or whooping cough

What 4 things are required for B. pertussis to cause infection?

1) exposure to the B. pertussis,

2) bacterial attachment to ciliated epithelial cells

3) proliferation of the bacteria,

4) production of localized tissue damage and systemic toxicity

What do the virulence factors do

Filamentouse hemagglutinin = binding suflated glycoproteins on membranes. Highly immunogenic.

Pertussis toxin = S2 subunit binds to glycolipid on surface of ciliated respiratory cells.

Pertactin = Promotes binding to sulfated glycoprotein intergrins on the membranes of respiratory cells.

Fimbriae = Bind to mammalian cells.

Adenylated cyclase/hemolysin

toxin = increases intracellular level of adenylated cyclase.

Tracheal cytotoxin = peptidoglycan fragment that kills ciliated respiratory cells and release interleukin-1.

Demonecrotic toxin = Causes does-dependent skin lesions or fatal reactions in experimental animal moel.

Know and describe the 3 stages of whooping cough

catarrhal stage - resembles a common cold, with serous sneezing, malaise, anorexia, and low-grade fever. Patients in the catarrhal stage are highly infectious. Lasts 1 to 2 weeks

paroxysmal stage - ciliated epithelial cells are extruded from the respiratory tract, and the clearance of mucus is impaired. Classic whooping cough paroxysms (i.e., a series of repetitive coughs followed by an inspiratory whoop). Lots of mucous production. The paroxysms are frequently terminated with vomiting and exhaustion. Patients may experience as many as 40 to 50 paroxysms daily during the height of the illness

convalescent stage - Paroxysms diminish but secondary complications can arise: pneumonia, seizures, encephalopathy (disease, damage or malfunction of the brain)

What is the reservoir of B. pertussis?

humans

How is it transmitted?

Person to person by aerosols

What does the vasaccine contain?

inactivated pertussis toxin, filamentous hemagglutinin, and pertactin are highly

effective

What infections does the dTAP vaccine protect against?

diphtheria, tetanus, and whooping cough

Brucella

Initial nonspecific symptoms like chills and fitigae then can progress to gastrointestinal tract, bones/joints, respiratory tract)

Brucella is also an ______________ of the _________

intracellular parasite of the reticuloendothelial system.

What types of infection does Brucella cause?

Arthritis

Intracellular pathogen (Brucella)

Resistant to killing in serum and by phagocytes

How does smooth vs rough morphology correlate to virulence?

Smooth colonies associated with virulence

O chain of smooth LPS and virulence (marker for virulence)?

Yes it is an important marker for virulence

Reservoirs for Brucella?

Animals

How do humans get infected?

Trasmitiion from animals (cattle), consumption of contaminated unpasterurized milk or direct contact with infected animal reservoir. ITs also an occupational hazard.

How can Brucella infection be controlled?

Eradicaation of the disease in the animal reservoir through vaccination and serologic monitoring of the animals for evidence of disease.

Francisella

Small gram-negative coccobacilli, aerobe, nonfermenter

What does F. tularensis cause?

Tularemiz (rabit fever) resitant to freezing temps, sensitive to heat.

How can humans be infected/exposed to F. tularensis?

Handling contaminated animal tissues or fluids

Bites (masquitoes)

Contaminated water, food or soil

Inhalation of infective aerosols

Bioterrorist weapon potential

Low infectious dose, short incubation period, case fatality rate (Untreated 30-60%) (untreated 1-3%)

What are the 3 types of tularemia (and symptoms)?

- Ulceroglandular tularemia: painful papule develops at the site of inoculation that progresses to ulceration; localized lymphadenopathy

- Oculoglandular tularemia: after inoculation into the eye (e.g., rubbing eye with a contaminated finger), painful conjunctivitis develops with regional lymphadenopathy

- Pneumonic tularemia: pneumonitis with signs of sepsis develops rapidly after exposure to contaminated aerosols; high mortality unless promptly diagnosed and treated

Reservoir for F. tularensisi

Wild mammals

Legionella

Slender, pleomorphic, nonfermentative, gram-negative rods. Stains poorly with common reagents

Where is Legionella commonly found?

Natural bodies of water, cooling towers, condensers an water systems.

What makes a person high risk for Legionella infection?

Compromised pulmonary function and patients with decreased cellular immunity.

What factors contribute to the colonization ability of Leionella?

•The ability to multiply over the temperature range of 20° C to 43° C and survive for varying periods at 40° C to 60° C

•The capacity to adhere to pipes, rubber, plastics, and sediment and persist in piped water systems even when flushed

•The ability to survive and multiply within free-living protozoa and in the presence of

commensal bacteria and algae

What are the two main types of infection caused by Legionella?

Legionnaires' disease (severe form of pneumonia)

Pontiac fever (influenza-like illness)

Intracellular pathogen

Legionellae are facultative intracellular bacteria that multiply in free-living amoebae in nature and in alveolar macrophages, monocytes, and alveolar epithelial cells in infected hosts.

What are the 3 major patterns for clinical manifestation?

(1) sporadic cases, which are most common and usually occur in the community;

(2) epidemic outbreaks, characterized by short duration and low attack rates

(3) nosocomial clusters, occurring in compromised patient populations

About 70% of cases of legionnaires' disease are caused by L. pneumophila, and 20% to 25% of cases are associated with travel.

Ability of Clostridium to cause disease is attributed to what 3 factors?

(1) ability to survive adverse environmental conditions through spore formation;

(2) rapid growth in a nutritionally enriched, oxygen-deprived environment; and

(3) production of numerous histolytic toxins, enterotoxins, and neurotoxins.

What does Clostridium perfringens cause?

Produces many toxins and enzymes that lyse blood cells and destroy tissues, leading to diseases such as overwhelming sepsis, massive hemolysis, and myonecrosis

What does Clostridium tetani cause? 3 clinical diseases

Generalized tetanus: generalized musculature spasms and involvement of the autonomic nervous system in severe disease (e.g., cardiac arrhythmias, fluctuations in blood pressure, profound sweating, dehydration)

Localized tetanus: musculature spasms restricted to localized area of primary infection

Neonatal tetanus: neonatal infection primarily involving the umbilical stump; very high mortality

What is tetanospasmin and what does it do?

a heat-labile neurotoxin that blocks release of neurotransmitters (i.e., gamma-aminobutyric acid, glycine) for inhibitory synapses

Symptoms of C. tetani infection

. Chills

• Difficulty swallowing

• Headache

• Irritability

• Jaw and neck stiffness

• Low fever

• Restlessness

• Sore throat

• Stiff arms and legs

• These symptoms will soon progress to classic tetanus such as:Difficulty opening the jaw - which is why it is called 'lockjaw',

• Muscle spasms in the back, neck or abdomen (Spastic paralysis)

How can humans get a C. tetani infection?

Spores

How can it be prevented?

Vaccination consisting of three doses followed by a booster every 10 years

Does disease cause immunity?

No disease does not induce immunity

Clostridium botulinum - causes what 4 types of botulism

(1) classic or foodborne botulism,

(2) infant botulism,

(3) wound botulism,

(4) inhalation botulism.

How do humans get infected with foodborne botulism?

Consumption of home-canned foods and occasionally preserved fish.

>30 cases in US

What does botulinum toxin do? What is it used for cosmetically?

Blocks acetylcholine activity and results in paralysis

Diminish wrinkles by paralyzing muscles

Flaccid vs spastic paralysis

Flaccid paralysis causes your muscles to shrink and become flabby. It results in muscle weakness. Spastic paralysis involves tight and hard muscles.

C. difficile produces 2 toxins - what are they and what do they do?

Enterotoxin that attracts neutrophils and stimulates their release of cytokines

Cytotoxin that increases permeability of the intestinal wall and subsequent diarrhea

What leads to/causes C. difficile infections?

Spore formation and antibiotic resistance/exposure

What are the 2 main clinical diseases caused by C. difficile?

Antibiotic-associated diarrhea: acute diarrhea generally developing 5 to 10 days after initiation of antibiotic treatment (particularly clindamycin, penicillins, cephalosporins, fluoroquinolones); may be brief and self-limited or more protracted

Pseudomembranous colitis: most severe form of C. difficile disease with profuse diarrhea, abdominal cramping, and fever; whitish plaques (pseudomembranes) over intact colonic tissue seen on colonoscopy