Respiratory pathophysiology Flashcards
IL-1β major cellular functions
- Increases E-selectin
- Increases vascular permeability and dilation
* Increases tissue factor release from macrophages and endothelial cells - Increases mucus production in goblet cells
Results in fever
Which increases vascular permeability more, IL-1β or TNF-α?
TNF-α
Which IL increases acute response proteins in the liver?
IL-6
Human adenovirus
What virus is implicated in a viral infection causing both bronchitis and conjuctivitis concurrently in the same Pt?
Adenovirus
Human Rhinovirus
Influenza viral attachement protein (VAP)
Hemmagluttinin (HA protein)
Binds sialic acid
Target for neutralizing Abs
Target of baloxavir
Cap-dependent endonuclease of influenza virus
What influenza type is only found in humans?
Influenza B
Where is influenza’s viral RNA replicated in the infected host cell?
Host cell nucleus - influenza = (-)ssRNA genome
How does influenza promote PNA and secondary bacterial infections?
Infecting respiratory epithelium and disabling the mucociliary escalator - also cleaving sialic acid and thinning mucus - causes mucus to fall back into lower respiratory tract
Which influenza type causes epidemic outbreaks only (not pandemic)?
Influenza B
Ag drift only
How does influenza A cause pandemics?
Antigenic shift of HA or NA gene(s)
Most virulent type of Haemophilus influenzae
Serotype B - polysaccharide capsule made from polyribitol-ribosyl-phosphate
What type of H. influenzae is responsible for sinusitis and otitis media?
Non-typable - unencapsulated
What factors does H. influenzae require to grow on agar?
X and V factors
Boiled BAP - chocolate agar
X factor = hemin
V factor = NAD+
Tx of H. influenzae PNA
-Ceftriaxone/cefotaxime
Moraxella catarrhalis
General features
Grame (-) diplococci
Strictly aerobic
Oxidase and catalase (+)
Normal flora (28-100% of humans within first year of life)
Differentiated from Neisseria by its ready growth on BAP culture
Also “Hockey Puck sign”
Tx for PNA caused by Moraxella catarrhalis
Augmentin
Bordatella pertussis
General features
Gram (-) coccobacilli in singles and paire
Aerobic
Fastidious growth requirements
Oxidase (+)
Pertussis toxin
AB subunit toxin
ADP-ribosylates GTP-binding (G) proteins that alter inhibitory regulation adenylate cyclase activity
Wide range of effects on immune cells (typically supresses immune response and migration)
Clinical progression of whooping cough
- Prodromal stage (common cold sxs)
- Paroxysmal: cough first appears (2-3 weeks)
- Convalescent: bacteria gone, cough remains for several weeks
Growth requirements of B. pertussis in laboratory
Bordet-Gengou aka charcoal horse blood agar
Provides nicotinamide
Can also be detected by PCR
Tx for whooping cough
Macrolide (azithromycin)
Pseudomonas aeroginosa
General characteristics
Gram (-) rods
Grows in wide temperature range
Oxidase (+) - differentiates from Enterobacteriaceae
What Gram (-) bacteria has an alginate capsule?
Pseudomonas aeruginosa
What bacteria produces pyocyanin pigment?
How does this function in its pathenogenesis?
P. aeruginosa
Fuctions to impair ciliary function and stimulates inflammatory response
Virulence factors of P. aeruginosa
Virulence factor that ADP-ribosylates host EF2 protein
Also list responsible organism
Exotoxin A secreted by Pseudomonas aeruginosa
Disrupts host protein synthesis leading to host cell death
Klebsiella pneumoniae
General characteristics
Gram (-) rod
Extracellular pathogen
Implicated in aspiration PNA
Hallmark organism that produces “currant jelly sputum”
Klebsiella pneumoniae
What biochemical test can differentiate M. tuberculosis from other Mycobacterium species?
Niacin +
First-line Tx of TB
Isoniazid, rifampin, ehtambutol, and pyrazinamide
Which is the MOST LIKELY cause of croup (larnyngeotrachiobronchitis) in the US?
Human parainfluenza virus
RSV causes the most severe presentation of croup
Particular significant in children < 5 y/o - swelling of upper respiratory tract compromising airway
A 4-year-old patient dies from primary influenza pneumonia after treatment with oseltamivir. You suspect that the infant was infected with a drug resistant virus. Viral genome sequencing would MOST LIKELY reveal mutations in which viral gene?
Neuraminindase (NA)
A virus causes a large outbreak in humans in rural Thailand. Within two months, it has spread to 42 different countries on 5 continents. Genetic analysis indicates that it has a segmented (-) ss RNA genome and replicates in the host cell nucleus. Which genetic process and virus is MOST LIKELY responsible?
C) Reassortment of the hemagglutinin (HA)-encoding gene segment between influenza A virus subtypes
What is the best explanation for why human rhinoviruses infections are primarily limited to the upper respiratory tract?
Rhinoviruses replicate most efficiently at 33ºC
Human adenovirus
A) Steeple sign
A clinical researcher is trying to develop a neutralizing monoclonal antibody therapy that will REDUCE airway narrowing and mucus production in respiratory syncytial virus infected infants. Which inflammatory mediator would be BEST to inactivate?
A) IL-6
B) IL-8
C) TNF-α
D) IL-4
C) TNF-α
TNF-α causes bronchial vasoconstriction by the secondary release of ET-1
Tumor Necrosis Factor-α Triggers Mucus Production in Airway Epithelium through an IκB Kinase β-dependent Mechanism
D) Neuraminidase
What is the host cell receptor for influenza attachement?
Sialic acid
A. Prophylaxis of Pt w/ anti-F protein monoclonal Ab
Prevention of RSV
C) Coronavirus and Rhinovirus
Adenovirus occurs typically in the summer
When do adenovirus infections spike (time of year) and why?
Summer - transmitted in water (i.e. swimming pools)
Sin Nombre virus clinical presentation
Severe lower respiratory infection that escalates very quickly
Typically seen W of the Missisippi
B. Direct viral invasion of airway epithelium leading to disruption of the mucociliary clearance system
Viruses w/ segmented genomes can undergo _______?
Genetic reassortment and antigenic shift (leading to zooncotic crossover events)
C. SARS-CoV-2
RSV has a linear (-) ssRNA genome
Influenza is also (-) ssRNA genome
Adenovirus is dsDNA genome
What protein on RSV mediates fusion with host cell plasma membrane?
F-protein
D. Sin nombre
The virus was discovered in 1993 during an outbreak of acute respiratory distress syndrome (ARDS). It was the first confirmed instance of hantaviruses in the Americas. The disease caused by the virus is called Hantavirus Pulmonary Syndrome (HPS)
What factors in chocolate agar are required for growth of Haemophilus influenzae?
NAD and Hemin
Factors X and V
Describe the MOA of Pseudomonas aeruginosa Exotoxin A?
An A/B subunit toxin that ADP-ribosylates host EF2 disrupting protein synthesis of host
A 65-year-old man presented with a 2-day history of high fever, cough with rusty sputum and pleuritic left-sided chest pain. His history was remarkable for treatment for congestive heart failure; he was otherwise healthy. Chest radiograph was remarkable for consolidation in the left lower lobe. Sputum Gram-stain revealed many PMNs and a Gram-positive pathogen. Sputum culture produced α-hemolytic colonies on BAP that were sensitive to optochin. Which of the following is the most likely pathogen?
Streptococcus pneumoniae
Which Haemophilus influenzae serotype is the current vaccine most effective against?
Serotype B
What is the most common source of bacterial otitis media?
The microbiota of the nasopharynx (espcecially in children)
A 61-year-old homeless alcoholic male was brought to the emergency department with a fever and cough producing a gelatinous bloody sputum. While in the ED he vomited his gastric contents and had a foul smelling sputum. Laboratory analysis of his sputum indicated that the pathogen was a Gram-negative rod. Which of the following is the most likely way he acquired this infection?
A. Aspiration of gastrointestinal contents
B. Complication of following a viral infection
C. Contact w/ another sick individual
D. IV drug use
A. Aspiration of GI contents
A 9-week-old baby presented with a 5-day history of choking spells and repetitive coughing, progressing to his turning red and gasping for breath. Two weeks before, a routine vaccination had been postponed because the child had a cold. Culture of a nasopharyngeal swab revealed a Gram-negative coccobacilli that grew on Bordet-Gengou agar but not blood agar. What pathogen is most likely responsible for the baby’s illness?
Bordetella pertussis
Delayed vaccination
(T/F) Hypoxic conditions created by the immune response inside a granuloma inhibit Mycobacteria tuberculosis growth during latent tuberculosis infections.
True
Three most common bacterial pathogens responsible for otitis media infections:
Nontypeable H. influenzae
Streptococcus
pneumoniae
Moraxella
catarrhalis
E. The pathogen is catalase and coagulase positive and produces beta-hemolytic colonies on BAP
D. Pseudomonas aueruginosa
E. Acid-fast rod
Kenyoun stain is an acid-fast staining procedure
E. Streptococcus pneumoniae
Most common cause of lobar PNA
A. Bacterial translocation from alveoli into pleural space
Potential organisms: S. aureus, aneaerobes
Legionella pneumophila
General characteristics
- Slender, pleomorphic rods with polar flagella - Gram (-) but do not stain well from sputum
- Obligate aerobesd
- Require L-cys and Fe (grown on buffered charcoal yeast extract agar)
- Catalse and gelatinase (+)
Notoriously resistant to high temp and Cl based disinfectants
What type of human host cells does Legionella invade?
- Macrophages
- Monocytes
- Alveolar epithelial cells
Legionella secretion system
Type IV during host cell invasion
Type II to escape host cell (when nutrients run out)
Legionnaires disease
Pontiac fever less severe form of Legionella infection
Most common serotype of community-acquired Legionella infections
Serotype 1
Has a urinary Ag detection
Pathogens responsible for walking PNA
- Mycoplasma pneumoniae
- Chlamydia pneumoniea
Attachment organelle of Mycoplasma
Virulence factors of Mycoplasma pneumoniae
ROS prodcued by Mycoplasma damages the respiratory epithelium and compromises the mucociliary escalator
Chlamydia pneumoniae
General characteristics
Vegatative, replicating form of Chlamydia pneumoniae
Infectious stage of Chlamydia pneumoniae life cycle
Elementary bodies
Need to form elementary bodies to leave and reinfect neighboring cells
What damages resp. epithelium of Chlamydia pneumoniae infection?
The cellular immune response
Cold serum agglutination test
Helps to distinguish between Mycoplasma and Chlamydia
Cold serum agglutination + = Mycoplasma
Tx of atypical PNA
Macrolides
Transmission and responsible pathogen of Psittacosis (ornithosis)
Zoonotic transmission from birds - Chlamydia psittaci
Can also be associated with pets and livestock (most commonly from birds)
What is transmission and responsible pathogen for Tularemia?
Tularemia aka rabbit fever is transmitted by the Dermacentor tick and deer fly
Caused by Francisella tularensis
Francisella tularensis
General characteristics
Pathogenesis of F. tularensis
PNA caused by tularemia
Tx of tularemia
Streptomycin or gentamicin
Coxiella burnetti
General characteristics
Coxiella burnetti pathogenesis
Coxiella Ag variation
Q fever
Tx for acute: doxy
Tx for chronic: doxy + hydroxychloriquine
Bacillus antracis
General characteristics
Virulence plasmids of B. antracis
What B. antracis toxin causes high intracellular levels of cAMP in its host cell?
Edema factor
B. antracis capsule
Pathogenesis of inhaled B. antracis spores
Initial sxs are nonspecific, followed by pseudo-improvement and then rapid deterioration
-Widened mediatstinal lymph nodes (seen as widening of mediastinum on CXR)
Meningitis in ~50%
B. antracis Tx
Abx:
- Quinolone (cipro)
- Tetracycline (doxy)
mAbs:
- Raxibacumab (mAb against protective Ag)
Chlamydia pneumoniae mechanism of persistence
What growth media would be best for isolating Legionella pneumophila?
Buffered charcoal yeast extract agar
Which of the following bacterial species DOES NOT stain well with either the Gram stain or the Acid-fast stain?
A. Haemophilus influenza
B. Mycobacterium tuberculosis
C. Staphylococcus aureus
D. Chlamydia pneumoniae
D. Chlamydia pneumoniae
Which of the following are obligate intracellular pathogens? (select all that apply)
A. Influenza A Virus
B. Chlamydia pneumoniae
C. Mycoplasma pneumoniae
D. Coxiella burnetii
E. Mycobacterium tuberculosis
A. Influenza A Virus
B. Chlamydia pneumoniae
D. Coxiella burnetii
Which of the following are the 3 most common bacterial atypical pneumonia pathogens?
A. Chlamydia pneumoniae
B. Coxiella burnetii
C. Haemophilus influenzae
D. Legionella pneumophila
E. Mycoplasma pneumoniae
F. Streptococcus pneumoniae
A. Chlamydia pneumoniae
D. Legionella pneumophila
E. Mycoplasma pneumoniae
A rancher named Earl presents to the physician’s office with a fever, headache and myalgia. His chief complaint is a persistent cough with scant sputum production. Characterization of Earl’s pathogen would indicate that it has distinct extracellular and intracellular morphological forms. The pathogen proliferates in macrophages and requires the acidic environment of the phagolysosome to stimulate metabolism and growth. Which of the following is the most likely pathogen?
E. Coxiella burnetti
(T/F) Legionella is readily transmitted from person-to-person
False
Must be an exposure event (water tower/hot tub/AC…etc.)
How does Legionella infect macrophages?
Upon entry into the human host, Legionella PAMPS (LPS) stimulate complementproteins. These proteins (C3b and i3b) bind to the Major Outer Membrane Protein of Legionella (MOMP). The complement proteins bind to receptors on the surface of macrophages allowing for phagocytosis of Legionella bacteria.
Bacterial pili facilitate attachment to respiratory epithelial cells.) Entry of Legionella may be through regular phagocytosis or a specialized coiling phagocytosis.
D.
B. Mycobacterium avium intracellulare
Mycobacterium tuberculosis is niacin +
C. Overwhelming systemic inflammation in response to endotoxin
LPS = endotoxin
Gram (-) pleomoprhic rod that grows on chocolate agar
Haemophilus influenzae
C. Inhibitor of bacterial protein synthesis (specifically the 50s subunit)
Macrolides are first-line Tx of atypical PNA
E. = Isoniazid (TB tx)
E. Cell-free product that contains the protective Ag
Mediastinal widening
“Medussa head” colonies
Gamma hemolysis
