Lecture 32 to 37 Respiratory system Flashcards
1
Q
Single syndrome: multiple etiologies
Ex. Infectious pharyngitis
A
- Strep. pyogenes or unknown (most common)
- Rhinovirus, adenovirus, coronavirus, EBV
- HSV, HPIV, influenza virus Coxsackie virus, etc…
2
Q
Defenses of respiratory system are often defeated by:
A
- smoking
- endotracheal intubation
- pollution
- suppression of cough reflex
- predisposing infection
- disruption of homeostasis: age, malnutrition, immunosuppression, etc…
3
Q
Interplay bw a professional and secondary pathogen
Ex. flu & pneumococcal pneumonia
A
Suggested underlying mechanisms
- changes to RT
- epithelial damage
- airway function altered
- up-regulation and expsoure of receptors
- alteration of innate immune response
- not limited to flu virus; observed w multiple respiratory viruses with the top ones are:
- Strep. pneumoniae
- Staph. aureus
- Hemophilus influenza
4
Q
Microflora (URT)
A
- corynebacterium
- enterobacteriaceae
- Staph
- Strep
Haemophilus
- Moraxella
- Mycoplasma
5
Q
Tranmission & acquisition
A
Exogenous:
- inhalation of infectious droplets:
- small droples
- dried respiratory droplet nuclei w mucin
- self-inoculation of eyes, etc..
6
Q
virus persistence on dry inanimate surfaces
A
Survival times
- adenovirus: 7 d to 3 mo
- rhinovirus: 2 h to 7 d
- coronavirus: 3 h; significant w regard to fomite-mediated transmission & survival in dropletss
- RSV: up to 6 h
7
Q
Endogenous infections
A
- Endogenous infectons usually due to microflora
- situations that can predispose to RT infection
- nl flora move to unusual location, Ex. smoker, , COPD, CF, asthma, chronic bronchitis, age
- preceding infection causing damage -> secondary infection
- aspiration of URT flora, Ex. Enterobacteriaceae into lungs -> aspiration pneumonia
8
Q
Some pathogens require specialised growth media that is not standard
A
- Bordetella pertusis: Bordet-Gengou
- C. diphtheriae: Tinsdale agar
- (slide 23 for rest)
9
Q
6 major families of Viral agents of RT infections
A
- adenoviruses
- rhinoviruses
- coronaviruses
- HPIV
- RSV
- influenza viruses
- Emerging: non-polio picornaviruses
10
Q
Some respiratory viruses do NOT exert their main pathology in respiratory tract
A
major examples
- measles: both rubella & rubeola
- VZV aka HSV-3
- smallpox
- coxsackie virus
- Norwalk virus
11
Q
Taxonomy of respiratory infections
A
URT
- sinusitis
- rhinitis
- otolaryngitis
- laryngitis
- pharyngitis
LRT
- bronchitis
- bronchiolitis
- pneumonia: community-acquired (acute, subacute, & chronic) and nosocomial (acute)
12
Q
Viruses directly involved in RTI
A
- Rhinoviruses: (+) RNA, type of Picorna virus
- Adenoviruses: linear ds DNA
- Influenza virus: segmented RNA
- RSV: (-) RNA
- Corona virus: (+)
- HPIV: (-) RNA
13
Q
Infectious rhinitis: microbial causes
A
Viral agents
- rhinovirus
- adenovirus
- coronavirus
- Non-polio picorna virus Ex. EV-D 68
Bacterial agents: no significant bacteria
14
Q
Rhinoviruses
A
- Sx: common cold, fever is rare in adults
- virus family: Picornaviridiae
- Medically signifiicant: Enteroviruses, polioviruses
- Icosahedral, non-enveloped
- Pathogenesis:
- Attachment to ICAM-1 cell receptor via surface clef/canyon
- viral replication & cell to cell spead
- cell damange, cilia immoblised, viral shedding
- Antigenic drift leading to 115 serotypes
- Epi: all ages, young children more severe, humans sole reservoir
- Transmisson: direct contact, respiratory droplets, survival time 2h to 7 d
- Rx: Diversionary care to treat common cold
15
Q
Adenoviruses
A
- Sx: pharyngitis, conjunctivitis
- Family: adenoviridae
- Genus: Mastadenovirus
- Replication: Class 1 (nucleus)
- Etiopath: interference w host immune response
- E1A*: hijacks cell
- activates viral gene transcription
- binds cell growth suppressor: p105Rb promotes transformation
- deregulates cell growth
- inhibits activation of interferon response elements
- E1B: binds p53 & promotes transformation & blocks apoptosis
- E3: prevents TNF-alpha inflammation
- fibre protein: enables attachment to host cell receptor
- receptor varies w viral serotype
- Serotypes 2 & 5= Coxsackie Adenovirus Receptor (CAR)
- cell surface glycoprotein belings to IgG superfamily
- Penton base has toxic activity
- inhibition of cell mRNA synthesis
- cell rounding
- tissue damage
- E1A*: hijacks cell
- Epi: widespread, most infections occur in children
- can be associated w ocular, respiratory, or GI systems
- outcomes of adenoviral infection
- Lytic: ex. mucoepithelial cells
- Latent: ex. adenoid cells
- Transmission: swimming pools, aerosols, direct contact, fomites, fingers
- 7 d to 3 mo survival time
16
Q
Coronaviruses
A
- Sx: common cold, SARS
- Family: Coronaviridiae
- HCoV-229E, HCoV-OC43, SARS-CoV, MERS-CoV, etc…
- enveloped, helical nucleocapsid, characteristic fringe=surface/”spike” glycoproteins
- Genetic material: ss (+) linear RNA
- class IVb replication
- Coronavirus S protein: “spike” protein
- Peplomers: 20 nm projecting surface proteins, define tissue tropism, attach to proteins or carbs, site of main antigenic epitopes: neutralising Ab
- Etiopath: specifics unclear
- replication optimal @ 33-34C
- occurs in ciliated nasal epithelium
- no good animal model for major CoV types; difficult to isolate & grow
- Epi: isolated from humans and animals (no cross-infect)
- total # serotypes undetermined
- re-infection by same serotype possible
- Transmission: mostly via droplet; fecal-oral route also possible
- surival time: 3 h
17
Q
Infectious pharyngitis: microbial causes
A
Viral agents
- rhinovirus
- adenovirus
- coronavirus
Bacterial agents
- Strep. pyogenes Group A
- Strep pneumoniae
- Corynebacterium diphtheriae
Sx: strep. throat sx, fever, swelling and narrowing, etc…
18
Q
Strep. pyogenes
A
- Sx: pharyngitis, strep. throat
- Group A strep.
- Pus formation due to leukocidin production
Virulence factors
- lack catalase (facultative anaerobes)
- Growth enhanced by CO2
- nutritionally fastidious
- nl culture medium=blood agar (BA)
- yeast extract + peptone +5% blood
- Beta -> hemolysin enzyme from bacteria to lyse cell membrane so true hemolysis
- (Alpha-> reduced (not true hemolysis) so green; A disk: Bacitracin inhibits growth of Group A)
- P disk: inhibits pneumococcus
- nl culture medium=blood agar (BA)
19
Q
Corynbacterium diphtheriae
A
- Sx: severe pharyngitis (diphtheria)
- 4 biotypes: gravis, mitis, belfanti, and Gram +ve intermedium
- other non-pathogenic Corynebacteria spp. are members of nl flora in pharynx, nasopharynx, and on skin.
- other medically-important species:
- C. jeikeium: associated w bacteraemia, IV cath colonisation
- C. minutissimum: RTI, wound infections
- Etiopath:
- organism is non-invasive and does not enter into blood
- pharyngitis can be severe enough to block airway -> suffocation
- main virulence factor= diph. exotoxin
- genes for toxin acquired via lysogenic conversion.
- toxin is responsible for local and systemic sx
- inflammation & formation of pseudomembrane
- damage to organs
- Sample & Dx: throat/nasopharyngeal samples
- screen: CYS Tellurite plate
- Dx: CYS Tellurite plate + BA (CTBA) -> Tellurite inhibits the growth of most URT bacteria.
- Immunodiffusion asasy (Elek test): Gold
- growth = diagonal bands of precipitin = +ve test
- PCR for tox gene although non-toxigenic strains produce a repressor for gene -> risk of fp
- methylene blue (very non-specific)
24
Q
Human parainfluenza viruses (HPIV)
A
- Sx: croup; bronchitis
- Virus family: paramyxoviridae (-ve) ss RNA
- Subfamily: paramyxovirniae & pneumoviriniae
- Genera: HPIV 1 &3 (respirovirus), HPIV-2, HPIV-4 (Mumps), morbillivirus (measles), megamyxovirus, Hendra virus, Nipah virus
- Genus: RSV, mPV
- Enveloped, linear ss (-) sense RNA virus
- Glycoprotein with Hemagglutinin-Neuraminidase (HN)
- Fusion factor (F)
- Etiopath:
- Transmission: inhalation of large-droplet aerosols
- Fusion factor (F) involved in viral entry
- Release of nucleocapsid into cytoplasm occurs following fusion of viral and host cell envelope.
- Virulence factors (below) inhibit IFN-alpha & beta production and signaling pathways.
- Inflammation and mucosal edema can lead to narrowing of airway and stridor.
- Virulence factors
- P/F proteins: immune evasion
- F proteins (fusion proteins): role in syncytium formation
- HN protein: structural Hemagglutinin & Neuraminidase
- L protein: multifunction polymerase
- M protein: matrix structural protein
- P/F protein (non-structural protein): role in evasion of immune response by blocking IFN expression & signalling
25
Q
Influenza
A
- orthomyxo virus (-) ss RNA
- TBC sialic acid
Adults Sx:
- rapid: onset after short incubation of 1 to 4 d
- sudden: malaise and headachle lasting a few h
- abrupt: rise of fever, chills, severe muscle aches. Loss of appetite, non-productive cough lasting 3 to 8 d
- recovery: complete in 7 to 10 d
- Pt contagious before sx appear (end of 1st d) for next 7 d
- risk of secondary infection highest in time from 6 to 12 d after infection
Children’s Sx:
- same as those in adults, PLUS
- high fever
- G.I. sx: vomiting, ab pain
- earache (otitis media)
- muscle pain and sometimes swelling
- febrile convulsions (rare but occurs in children < 3 y)
Complications
- primary viral pneumonias
- secondary bacterial pneumonias
- muscle inflammation: cardiac involvement
- rare neuro syndromes: Guillain-Barre, encephalitis, Reye’s syndrome in Children (made worse by aspirin and aspirin containin drugs)
Types
- Type B: found only in humans; less severe than type A; 2 valences against B (Victoria-like & Yamagata-like)
- Type C: cause mild illness in humans & do not cause epidemics, pandemics.
- Type A: disease of birds -> all 15 H and 9 N types
Virulence factors: Matrix protein (M1), NA, HA, ion channel M2 protein (type A only), RNA segments (below)
- 8 segments: Influenza A & B
- 7 segments: Influenza C
- M1 & M2 proteins common to all A viruses
- caveat: hidden from immune system
Influenza virus increases the susceptibility of the lower respiratory tract to bacterial invasion by destroying cilated cells.
Entry of influenza into cell
- Stage 1: attachment
- Stage 2: Entry & Fusion w endosomal vesicle (not cell membrane)
- Stage 3: Uncoating
38
Q
Legionella pneumophilia
A
- Sx: Legionnaire’s disease (pneumonia), pontiac fever (self-limiting)
Family: Legionellaceae
- single genus: Legionella
- Gram -ve rods, motile, non-spore forming
- 49 species, 70 serogroups
- >80% of all infections due to L. pneumophilia sergroup 1
- can be associated w epidemics
- uptake is via phagocytosis; prevent fusion of phagosome-lysosome.
- much of damage = host inflammatory response.
- virulence factors
- intracell growth
- endotoxin
- extracell protease
- Epi: expsure = inhalation of contaminated aerosols
- person to person transmission = rare
- can survive ~50C for > 30 min.
- Does not take saffranin couterstain so is invisible under gram stain -> silver stain
- *
39
Q
Pseudomonas spp.
A
- Gram -ve rods, strictly aerobic,
- highly motile w multiple flagella, versatile metabolism
- opportunist ubiqitous in fresh water sources
- Catalase +
- Oxidase +
- encapsulated
- thrives in aquatic environment
- non-hemolytic; produces very mucoid colonies on conventional agar
- some strains produce pigments: Pyocyanin, pyoverdin/Fluorescein giving a green colour to colourles media; smells like Grapes!
Etiopath:
- Toxin inactivates E2-F by ribosylation (same as Diphtheria toxin)
Sx
- only weakly pathogenic to persons w normal innate acquired immunity; most common infection is Otitis Externa (Swimmer’s ear)
- Dangerous for persons w structural defects in body defenses.
- burn victims
- CF: causing necrotising bronchial pneumonia
- pseudomonas aeruginosa & Burkholderia cepacia are now considered CF pathogens
- often fatal nosocomial infection
- osteomyelitis in diabetics & IV drug users
- nosocomial UTI
- Eccthyma gangrenosum: black necrotic lesions on skin
Rx:
- Pipericidin
- Fluoroquinolones for UTI
- Aminoglycosides
45
Q
Coccidiodes imitidis
A
- most virulent of all human mycotic pathogs; expsoure is through inhalation of arthroconidia (endospores) from soil
- Spherule protects spores from phagocytosis (fig. below)
- mostly in desert areas of US but not exclusive (SW USA, Arizona, Cali), N. Mexico, S. & Central America
- Self-limited flu-like illnesses
