The Lung Part 8 Flashcards
1
Q
Common viral causes of community acquired viral pneumonia
A
- Influenza virus types A and B
- Respiratory syncytial virus
- Human metapneumovirus
- Adenovirus
- Rhinovirus
- Rubeola
- Varicella
- All can cause URI (common cold) or a more severe LRI; factors that vapor extension include extremes of ages, malnutrition, alcoholism, debilitating illnesses
2
Q
How viruses cause pneumonia–mechanism
A
- have tropisms that allow them to attach to and enter respiratory lining cells
- Viral replication and gene expression leads to cytopathic changes including cell death and secondary inflammation
- damage and impairment of pulm defenses like mucociliary clearance predisposes to bacterial superinfection which are more serious than viral
3
Q
Influenza viruses of type A infect who??
A
-humans, pigs, horses and birds and are the major cause of pandemic and epidemic influenza infections!!
4
Q
Influenza genome encodes
A
- hemagglutinin and neuraminidase proteins
- Hemagglutinin has 3 major subtypes (H1-H3); neuraminidase has two (N1, N2)–both parts of virus envelope which is made up lipid bilayer
- Hemagglutinin attaches virus to its cellular target via silica acid residues on surface polysaccharides
5
Q
How does hemagglutinin allow viral envelope to fuse with host cell membrane?
A
- After uptake of virus into endosomal vesicles, acidification of endosome triggers conformational change allowing viral envelope to fuse with host cell membrane, releasing viral RNAs into cytoplasm of cell
- Neurominidase helps w/release of newly formed visions that are budding from infected cells by cleaving sialic acid residues
6
Q
Neutralizing host Abs against viral hemagglutinin and neuraminidase
A
-prevent and ameliorate (respectively) infection with influenza
7
Q
Influenza viral genome composition
A
- eight single stranded RNA, each coding protein/s
- RNAs packaged into helices by nucleoproteins that determine the influenza virus type (A, B or C)
- influenza virus A predominates
8
Q
Antigenic DRIFT
A
- spontaneous mutations that alter antigenic epitopes on viral hemagglutinin and neuraminidase proteins causing influenza EPIDEMICS
- these antigenic changes are sufficient to elude Abs
- usually though, these new strains bear resemblance to prior strains that some members are at least partially resistant to infection
9
Q
Antigenic SHIFT
A
- -occurs when BOTH hemagglutinin and neuraminidase genes are REPLACED through recombination animal influenza viruses
- causes PANDEMICS–more widespread and longer
- EVERYONE is susceptible to new influenza virus
- Viral assembly involves packaging of each of the 8 viral RNAs into single virions and infection of animal w/2 diff flu strains can lead to swapping genetic material creating new strain
10
Q
Influenza–affect on pneumocytes in those who lack protective Abs
A
- After entry into pneumocytes, virus inhibits sodium channels, producing electrolyte and water shifts leading to accumulation in alveolar lumen
- leads to death of infected cells via inhibition of host cell mRNA translation and activation of caspases leading to apoptosis
- Death of epithelial cells exacerbates fluid accumulation and releases danger signals that activate resident macrophages
- Epithelial cells also release inflammatory mediators prior to death adding even more inflammation
- Mediators from epithelial cells and macrophages activate nearby pulm endothelium allowing neutrophils to attach and extravasate into interstitium within first day or two of infection
11
Q
Influenza virus–how severe infection happens
A
- sometimes, viral infection causes enough lung injury to produce ARDS
- More often, however, severe/fatal pulm dz results from a superimposed BACTERIAL pneumonia, ESP STAPH AUREUS!
12
Q
How influenza virus is controlled–host mechanisms
A
- viral products induces innate immune response to produce a and B-interferon which up regulate expression of MX1 gene which encodes a GTPase that interferes with influenza gene transcription and viral replication
- Natural killer cells and cytotoxic T cells recognize and kill infected host cells, limiting viral replication and viral spread to adjacent pneumocytes
- augmented by development of Ab response to viral hemagglutininin and neuraminidase proteins
13
Q
Comorbidities associated with higher risk of severe infection by influenza
A
-Diabetes, heart disease, lung disease, immunosuppression
14
Q
Future influenza pandemic
A
- avian influenza which normally infects birds
- H5N1–in birds
- Human death cases–all acquired by close contact with domestic birds; most death from pneumonia
- Luckily, H5N1 transmission is inefficient but if it combines with an influenza that is highly infectious for humans, it might result in human-to-human transmission
15
Q
Human metapneumovirus
A
- Paramyxovirus associated with upper and lower respiratory tract infections
- can affect any age, but mostly young children, elderly, and immunocompromised
- can cause bronchiolitis and pneumonia
- clinically indistinguishable from RSV and mistaken for influenza
- First infection occurs in early childhood but reinfections are common throughout life, esp in elderly
16
Q
Diagnostic methods and treatment for Human MPV
A
- PCR tests for viral RNA and direct IF for Dx
- Tx: Ribavirin–used mostly in immunocompromised w/severe disease
- still need to develop safe vaccine–currently working on it
17
Q
Severe Acute Respiratory Syndrome (SARS)
A
- first in China, then Hong Kong, Taiwan, Singapore, Vietnam, Toronto
- cause: new coronavirus
- coronavirus causes URI but SARS different bc it infected Lower resp tract and spread throughout body
- virus has disappeared
18
Q
Community acquired viral pneumonia morphology
A
- URI: mucosal hyperemia and swelling, lymphomonocytic and plasmacytic infiltration of submucosa and overproduction of mucus
- swollen mucosa and viscous exudate can plug nasal channels, sinuses, or Eustachian tubes leading to suppurative bacterial infection
- tonsillitis causing hyperplasia of lymphoid tissue in Waldeyer ring common in children
19
Q
Viral Laryngotracheobronchitis and Bronchiolitis
A
- vocal cord swelling and abundant mucus production
- Impairment of bronchociliary fnx invites bacterial superinfection with more suppuration
- plugging of small airways leads to lung atelectasis
- if bronchiolar involvement more severe, secondary and terminal airways are plugged by cell debris, fibrin and inflammatory exudate leading to organization and fibrosis–results in bronchiolitis and permanent lung damage
20
Q
Lung involvement in viral infections
A
- may be patchy or involve whole lobe b/l or u/l
- affected areas are red-blue and congested
- pleuritis/pleural effusions infrequent
21
Q
Histologic pattern of viral infections
A
- INTERSTITIAL INFLAMMATORY REACTION INVOLVING WALLS OF ALVEOLI!!!
- alveolar septa are widened and edematous and usually have mononuclear inflammatory infiltrate of lymphocytes, macrophages, and sometimes plasma cells
- neutrophils in acute cases
- Alveoli may be free of exudate but in many, there is intra-alveolar proteinaceous material and cellular exudate
22
Q
Viral infections complicated by ARDS morphology
A
- pink hyaline membranes in alveolar walls
- Eradication of infection followed by reconstituting normal lung architecture
23
Q
Viral infection with superimposed bacterial infection morphology
A
- causes ulcerative bronchitis, bronchiolitis and bacterial pneumonia
- Herpes simplex, varicella, and adenovirus may be associated with necrosis of bronchial and alveolar epithelium and acute inflammation
24
Q
Clinical course of viral infections–viral community acquired pneumonia
A
- variable
- sometimes hidden as severe URI or chest colds
- cough may be absent; majority have fever, headache, muscle aches and leg pain
- edema and exudation causing mismatching of ventilation and blood flow and evoke symptoms out of proportion to scanty physical findings
- usually mild and resolve spontaneously but interstitial viral pneumonias can be epidemic and even small complications can lead to morbidity/mortality like in influenza epidemics
